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International Journal of Contemporary Hospitality Management

ISSN : 0959-6119

Article publication date: 26 May 2022

Issue publication date: 26 July 2022

Online food delivery (OFD) has witnessed momentous consumer adoption in the past few years, and COVID-19, if anything, is only accelerating its growth. This paper captures numerous intricate issues arising from the complex relationship among the stakeholders because of the enhanced scale of the OFD business. The purpose of this paper is to highlight publication trends in OFD and identify potential future research themes.

Design/methodology/approach

The authors conducted a tri-method study – systematic literature review, bibliometric and thematic content analysis – of 43 articles on OFD published in 24 journals from 2015 to 2021 (March). The authors used VOSviewer to perform citation analysis.

Systematic literature review of the existing OFD research resulted in six potential research themes. Further, thematic content analysis synthesized and categorized the literature into four knowledge clusters, namely, (i) digital mediation in OFD, (ii) dynamic OFD operations, (iii) OFD adoption by consumers and (iv) risk and trust issues in OFD. The authors also present the emerging trends in terms of the most influential articles, authors and journals.

Practical implications

This paper captures the different facets of interactions among various OFD stakeholders and highlights the intricate issues and challenges that require immediate attention from researchers and practitioners.

Originality/value

This is one of the few studies to synthesize OFD literature that sheds light on unexplored aspects of complex relationships among OFD stakeholders through four clusters and six research themes through a conceptual framework.

• Online food delivery
• Sharing economy
• Systematic literature review
• Bibliometric analysis
• Content analysis

Acknowledgements

The authors thank three anonymous reviewers, the guest editor, and the editor-in-chief for their critical and valuable comments in developing the manuscript in stages.

Shroff, A. , Shah, B.J. and Gajjar, H. (2022), "Online food delivery research: a systematic literature review", International Journal of Contemporary Hospitality Management , Vol. 34 No. 8, pp. 2852-2883. https://doi.org/10.1108/IJCHM-10-2021-1273

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Copyright © 2022, Emerald Publishing Limited

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• Open access
• Published: 16 July 2022

Investigating experiences of frequent online food delivery service use: a qualitative study in UK adults

• Matthew Keeble 1 ,
• Jean Adams 1 &
• Thomas Burgoine 1  

BMC Public Health volume  22 , Article number:  1365 ( 2022 ) Cite this article

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Food prepared out-of-home is typically energy-dense and nutrient-poor. This food can be purchased from multiple types of retailer, including restaurants and takeaway food outlets. Using online food delivery services to purchase food prepared out-of-home is increasing in popularity. This may lead to more frequent unhealthy food consumption, which is positively associated with poor diet and living with obesity. Understanding possible reasons for using online food delivery services might contribute to the development of future public health interventions, if deemed necessary. This knowledge would be best obtained by engaging with individuals who use online food delivery services as part of established routines. Therefore, we aimed to investigate customer experiences of using online food delivery services to understand their reasons for using them, including any advantages and drawbacks.

Methods and results

In 2020, we conducted telephone interviews with 22 adults living in the UK who had used online food delivery services on at least a monthly basis over the previous year. Through codebook thematic analysis, we generated five themes: ‘The importance of takeaway food’, ‘Less effort for more convenience’, ‘Saving money and reallocating time’, ‘Online food delivery service normalisation’ and ‘Maintained home food practices’. Two concepts were overarching throughout: ‘Place. Time. Situation.’ and ‘Perceived advantages outweigh recognised drawbacks’.

After considering each of the accessible food purchasing options within the context of their location and the time of day, participants typically selected online food delivery services. Participants reported that they did not use online food delivery services to purchase healthy food. Participants considered online food delivery service use to be a normal practice that involves little effort due to optimised purchasing processes. As a result, these services were seen to offer convenient access to food aligned with sociocultural expectations. Participants reported that this convenience was often an advantage but could be a drawback. Although participants were price-sensitive, they were willing to pay delivery fees for the opportunity to complete tasks whilst waiting for delivery. Furthermore, participants valued price-promotions and concluded that receiving them justified their online food delivery service use. Despite takeaway food consumption, participants considered home cooking to be irreplaceable.

Conclusions

Future public health interventions might seek to increase the healthiness of food available online whilst maintaining sociocultural values. Extending restrictions adopted in other food environments to online food delivery services could also be explored.

Peer Review reports

Purchasing food that is prepared out-of-home and served ready-to-consume is prevalent across the world [ 1 ]. The neighbourhood food environment includes all physically accessible food outlets where individuals can purchase and consume foods, including food prepared out-of-home (often referred to as ‘takeaway food’) [ 2 ]. An increased number of outlets selling this food in the neighbourhood food environment may have contributed to normalising its consumption [ 3 ]. Purchasing formats represent ways to buy takeaway food. Although the opportunity to purchase this food was once limited to visiting food outlets in person or placing orders directly with food outlets by phone, additional purchasing formats such as online food delivery services now exist [ 4 ]. Unlike physically accessing outlets in the neighbourhood food environment or contacting outlets by telephone before collection or delivery, online food delivery services exist within a digital food environment. On a single online platform, customers receive aggregated information about food outlets that will deliver to them based on their location. Customers then select a food outlet, and place and pay for their order. Orders are forwarded to food outlets where meals are prepared before being delivered to customers [ 5 ]. Online food delivery services have been available in the UK since around 2006. However, widespread internet and smartphone access has increased their use [ 6 ], with global online food delivery service revenue estimated at £2.9 billion in 2021 [ 7 ]. The COVID-19 pandemic may have accelerated and perpetuated market development [ 8 ].

Food sold by takeaway food outlets, and therefore available online, is typically nutrient-poor and served in portion sizes that exceed public health recommendations for energy content [ 9 , 10 ]. More frequent takeaway food consumption has been associated with poorer diet quality and elevated bodyweight over time [ 11 ]. Although it is currently unclear, using online food delivery services might lead to more frequent and higher overall takeaway food consumption. In turn, this could lead to increased risk of elevated bodyweight and associated comorbidities. Since an estimated 67% of men and 60% of women in the UK were already considered overweight or obese in 2019 [ 12 ], the possibility that using online food delivery services increases overall takeaway food consumption is a major public health concern, as recognised by the World Health Organization [ 4 , 13 , 14 ].

With respect to the neighbourhood food environment, food outlet accessibility (number) and proximity (distance to nearest), food availability (presence of variety), and attitudinal dimensions (acceptability) contribute to takeaway food purchasing practices [ 15 ]. Each of these domains apply to takeaway food access through online food delivery services. In 2019, the number of food outlets accessible through the leading online food delivery service in the UK ( Just Eat ) was 50% greater in the most deprived areas compared with the least deprived areas [ 16 ]. Furthermore, adults living in the UK with the highest number of food outlets accessible online had greater odds of any online delivery service use in the previous week compared to those with the lowest number [ 17 ]. To our knowledge, however, attitudinal dimensions of online food delivery service use have not been investigated in the public health literature. Given the complexity of takeaway food purchasing practices, there are likely to be unique and specific reasons for using online food delivery services. Understanding these reasons from the perspective of customers could contribute to more informed public health decision-making and intervention, which is important since public health interventions that include online food delivery services may be increasingly necessary as their growth in popularity continues worldwide [ 13 , 18 ].

In our study, we investigated experiences of using online food delivery services from the perspective of adults living in the UK who use them frequently. We aimed to understand their reasons for using these services, the possible advantages and drawbacks of doing so, and how they coexist with other food-related practices.

Between June and August 2020, we used semi-structured telephone interviews to study experiences of using online food delivery services from the perspective of adults living in the UK. We used the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist to guide the development and reporting of our study [ 19 ].

The University of Cambridge School of the Humanities and Social Sciences Research Ethics Committee provided ethical approval (Reference: 19/220).

Methodological orientation

We used a qualitative description methodological orientation to investigate our study aims. Qualitative description has been framed as less interpretative than other approaches [ 20 ]. However, it is theoretically and epistemologically flexible and can facilitate a rich description of perspectives [ 21 ], which matched our study aims.

Participants and recruitment

We used convenience sampling to recruit adults that used online food delivery services frequently. For the purpose of our study, we defined frequent customers as those who had used online food delivery services on at least a monthly basis over the previous year. We believed this level of use would make participants well-positioned to provide their experiences of using this purchasing format within established takeaway food purchasing practices. We also based participant recruitment on reported sociodemographic characteristics of online food delivery service customers [ 22 , 23 ]. As data collection progressed, we additionally considered level of education so that our sample included frequent customers who were less highly educated (see Table 1 ).

We used two social media platforms (Twitter and Reddit) to recruit participants. Participant recruitment through social media platforms can be fast and efficient [ 24 , 25 , 26 ]. If targeted advertising is not used (as in our study), participant recruitment in this way is also typically free. In our study, participant recruitment through social media was particularly appropriate, given that our aims were related to understanding experiences of using a digital purchasing format. Twitter users can publish and re-publish information, images, videos, and links to external sites. Reddit users can publish information, images and videos, and discuss topics within focused forums known as ‘Subreddits’. For Twitter, the primary researcher (MK) published recruitment materials using his personal account and relied on existing connections to re-publish them. For Reddit, MK created an alias account (he did not have a personal account at the time of our fieldwork) and published recruitment materials in Subreddits for cities in the UK with large populations according to the 2011 UK census, those related to online food delivery services, and those that discuss topics relevant to the UK [ 27 ]. See Additional file 1 (Box A1) for a complete list of Subreddits.

Recruitment materials asked interested individuals to contact MK by email. When contacted, MK responded by email with screening questions that asked about self-reported frequency of online food delivery service use over the past year, age, and level of education. When eligibility was confirmed, MK provided information about the study by email. This information included the study aims, details about researchers involved, the offer of a £20.00 electronic high street shopping voucher, and a formal invitation to participate. After five business days with no response to the invitation, MK sent a further email. After another five business days, we classified individuals that did not respond as ‘non-respondents’.

Data collection

Before data collection.

Before starting data collection, we planned to complete a maximum of 25 interviews. We did not target data saturation. Food purchasing and consumption are highly individual and influenced by previous experiences, cultural backgrounds, and preferences [ 28 ]. Therefore, we felt that it would be difficult to conclude data saturation was achieved based on the traditional conceptualisation of no new information being reported by participants [ 29 , 30 ]. Instead, we prioritised conceptual depth and information strength. This approach was aligned with the qualitative description methodological orientation of our study [ 30 ].

We wanted to investigate experiences of using online food delivery services from before the COVID-19 pandemic, when there were no restrictions on accessing multiple purchasing formats or consuming food on the premises. Therefore, we pre-specified that we would stop data collection if it became difficult for participants to refer to the time before March 2020, which is when pandemic related travel and food outlet access restrictions were first introduced in the UK. MK piloted an initial protocol with an eligible individual to confirm this would be possible, and made amendments based on their feedback.

Before starting data collection, MK reflected on his position as a population health researcher, and his previous training and experience in qualitative research [ 31 ]. MK also reflected on his own takeaway food consumption and previous use of online food delivery services. As of June 2020, MK consumed takeaway food infrequently and had previously placed one order with an online food delivery service. Although he was not a frequent customer according to our classification, MK was familiar with online food delivery services operating in the UK. MK concluded that despite having a broad understanding about why online food delivery services might be used, he could not use his own experiences to provide detailed reasons for favouring this purchasing format over alternative options.

Throughout data collection

MK completed one-off semi-structured telephone interviews with participants at a convenient time selected by them. At the start of the interview process, MK confirmed the rationale for the study, gave participants the opportunity to ask clarifying questions and asked them to provide verbal consent. MK used a topic guide that was developed based on a priori knowledge, pilot interview feedback and previous research related to takeaway food and online food delivery services [ 22 , 32 , 33 ]. MK amended the topic guide as data collection progressed so that points not initially considered could be discussed in future interviews. Interview questions focused on reasons for using online food delivery services, the perceived advantages and drawbacks of using these services, and how using them coexisted with other purchasing formats and food-related practices (see Box A2 in Additional file 1 for the final topic guide).

Although MK completed interviews during the COVID-19 pandemic, he did not ask questions related to this period of time, and prompted participants to think about the time before March 2020 so that pre-pandemic experiences could be discussed. MK digitally recorded interview audio and made field notes to track points for discussion within the interview.

After data collection

MK immediately reflected on topics discussed, data collection progress, possible links with existing theory, and the ability of participants to think about the time before the COVID-19 pandemic. We used these post-interview reflections to help inform our decision to stop data collection.

Data analysis

A professional company transcribed interview audio verbatim. Whilst listening to the corresponding audio, MK quality assured each transcript and anonymised it. Participants did not review their transcripts.

We used codebook thematic analysis. When using this analytic approach, researchers develop a codebook based on the final topic guide used during data collection and data familiarity that is achieved by reviewing collected data [ 34 , 35 ]. Codebook thematic analysis is aligned with qualitative description methodological orientations as it allows researchers to remain ‘close to the data’ and facilitates an understanding of a topic through the ‘spoken word’ of participants [ 36 ]. In practice, MK developed an initial codebook. MK, JA, and TB then reviewed three transcripts (a 10% sample). This number was manageable and allowed us to discuss a sample of collected data [ 37 ]. After discussion, MK refined the initial codebook to collapse codes that overlapped and to add new codes, which formed the final codebook. MK coded each transcript with the final codebook and reviewed reflections written after each interview. MK then studied the coded data to generate themes that were discussed and finalised with JA and TB. In the context of our study, themes summarise experiences of using online food delivery services from the perspective of participants. After discussion, we also identified that across the themes we generated, there were overarching concepts. For our study, concepts should be seen to offer an overall and consistent structure that capture the common and overlapping elements of each of the generated themes.

MK used NVivo (version 12) to manage the data and facilitate interpretation.

Participant and data overview

MK conducted interviews with 22 frequent online food delivery service customers between June and August 2020. Interviews lasted between 35 and 61 min. There were 12 male participants, 13 participants were aged between 20 and 29 years, and 15 had completed higher education. Since initial adoption, participants had typically used online food delivery services at least fortnightly but as often as daily, and during interviews they consistently referred to using the three most well-established online food delivery services operating in the UK ( Just Eat, Deliveroo, and Uber Eats ) (see Table 2 ).

During the 19 th interview, conducted in August 2020, it was difficult for the participant to think about the time before the onset of the COVID-19 pandemic in March 2020. MK completed three further interviews and then concluded that this difficulty was consistent so stopped data collection. We included data from all interviews in analyses. In addition to those who took part, three interviews were scheduled but cancelled by individuals without providing a reason, and there were nine non-respondents.

Summary and structure

We generated two concepts that were overarching throughout our data: ‘Place. Time. Situation.’ and ‘Perceived advantages outweigh recognised drawbacks’. Within these overarching concepts, we generated five themes: ‘The importance of takeaway food’, ‘Less effort for more convenience’, ‘Saving money and reallocating time’, ‘Online food delivery service normalisation’ and ‘Maintained home food practices’.

In the following sections, we present the findings for each of the overarching concepts, followed by each of the themes. Whilst we discuss each concept and theme in turn, all of their elements were present throughout the data and should be thought of as dynamic, overlapping, and non-hierarchical. For example, participants consistently reflected on features of online food delivery services within the context of their location at a specific time. The conclusion of this process dictated whether a feature was viewed as an advantage or a drawback, and in some cases whether an online food delivery service would be used. We provide examples of this comparison process at the end of our Results (Table 3 ).

Overarching concepts

Place. time. situation..

Participants described how their location and the time of day impacted their ability to access different types of food, including both ‘takeaway’ food and other types of food. When choosing one type of food over another, participants had a multi-factorial thought process that considered their food at home, immediate finances available for food, and the food already eaten that day.

Although data collection focused on takeaway food, participants were clear that this type of food was not always appropriate. As participant 10 (Female: 20–29 years) stated; “ I don’t always just go and get a takeaway; sometimes I’ll walk to the shop, get some food, and make something ”. This view was shared by participant 11 (Male 30–39 years); “ some days I’ll decide that it’s too expensive and I’ll either get something else direct from the restaurant or go to the supermarket and then make food ”.

Nonetheless, participants indicated that purchasing takeaway food was preferable in many situations. For example, when acting spontaneously, when meals had not been planned or if other types of food could not satisfy needs, then takeaway food was appropriate.

“ I think you’re more likely to get delivery and order online when it’s unplanned and you need a pick-me-up, or you need something quick, or you don’t have something and you’re really hungry .” Participant 15 (Male: 40-49 years)

When participants decided to purchase takeaway food, they recognised that their location and the time of day dictated the purchasing formats they could access and potentially use. Access to multiple purchasing formats created a second decision making process. Participants considered the cuisines they wanted, delivery times estimated by online food delivery services versus the time it would take to travel to a food outlet, the weather, their willingness to leave home, and previous experience with accessible food outlets. Alongside these influential factors, choosing one purchasing format over another was often based on what was most convenient.

“ If I’m out and about, on the way home and I’m passing via an outlet, then I’ll pick it up. If I’m at home and just kind of, don’t want to leave the house, then I’ll order via an app or online, just because it’s just convenient .” Participant 2 (Male: 20-29 years)

Despite having apparently decided how they would purchase takeaway food, participants stated that they could change their mind. In the case of online food delivery services, if estimated delivery times failed to meet expectations, this purchasing format would no longer be appropriate and another purchasing format or type of food would be selected. The need for food practices to align with other routines and schedules, and therefore meet expectations, was particularly clear when participant 8 (Female: 40–49 years) described that they used online food delivery services when they could “ relax on a Friday night with the whole evening free ”. However, if they do not have time to select a food outlet, place their order, and then wait for delivery they “ normally just have some spaghetti because that takes 10 min ”.

Participants also referred to online food delivery service marketing in their day-to-day environments, including branded food outlet signs and equipment used by delivery couriers. Participants stated that these things did not always trigger immediate use of online food delivery services, however, their omnipresence reminded them that these services were available.

“ I don’t know if I ever go onto Just Eat after seeing it advertised, I don’t think that’s ever directly led me to do it. But it certainly keeps it in your mind, it’s certainly at the forefront of your mind whenever you think of takeaway .” Participant 11 (Male: 30-39 years)

Perceived advantages outweigh recognised drawbacks

Throughout the data, participants recognised that a single online food delivery service feature could be an advantage or a drawback based on their location and the time of day. This was clearest when participant 2 (Male: 20–29 years) discussed the number of food outlets accessible online compared with those available through other purchasing formats. There was value in having access to “ 20, 30, 40 food outlets ” through online food delivery services as it meant more options, otherwise “ you’re more limited just by the virtue of where you are or what shops you’re passing ”. However, access to a greater number of food outlets was a drawback when it meant that making a selection was difficult. The constant comparison of advantages and drawbacks prompted MK to ask participants why they kept using online food delivery services. There was a consensus that features of these services were unique, mostly advantageous, and outweighed the instances where they were seen as drawbacks. Since participants continued to use online food delivery services to access unique features, this practice appears to be self-reinforcing, even if this means accepting that the same feature can sometimes be a drawback.

Participants favoured online food delivery services in many situations. Nevertheless, they acknowledged that if the overall balance between advantages and drawbacks changed then they would purchase takeaway food in other ways. This solution emphasises that takeaway food can often be accessed in multiple ways dependent on place and time. As it stands, participants anticipated that they would continue to use online food delivery services indefinitely.

“ I can’t see any reason why I would [stop using online food delivery services] , unless something went wrong with Just Eat, you know, the service had a massive problem, but at the moment I can’t see any reason why I would. ” Participant 16 (Male: 20-29 years)

Analytic themes

We now present each of the five themes generated from our analyses. As described, elements of each theme overlapped within the two overarching concepts presented above.

The importance of takeaway food

Participants emphasised that, ultimately, it was “ the food ” that they valued, and that directed them towards using online food delivery services.

“ It’s the food really, that leads me to use [online food delivery service] apps .” Participant 10 (Female: 20-29 years)

Participants reported that they did not use online food delivery services with the intent of purchasing healthy food. Participants told us that they expected takeaway food to be unhealthy and that online food delivery services facilitated access to this food. This perspective influenced the types of food that participants were willing to purchase through online food delivery services. For example, pizza (seen as unhealthy) was appropriate but a salad (seen as healthy) was not. Moreover, participants recognised that if they wanted to consume healthy food, they would most likely cook for themselves.

Participants stated that takeaway food had social, cultural, and behavioural value. For many, purchasing and consuming takeaway food at the end of the working week signified the start of the weekend, which was seen as a time for relaxation and celebration. This tradition was carried forward from childhood, with Friday night referred to as “ takeaway night ”. For participants, using an online food delivery service allowed them to maintain, yet digitalise, traditions.

“ It’s always a weekend thing, besides it being a convenient, really quick way of accessing food that is filling and tastes nice, for me, it marks the end of a work week .” Participant 4 (Female: 30-39 years)

Participants reported that in some situations consuming takeaway food as a group could be a way to socialise. This was especially the case during life transitions such as leaving home to start university.

“ When you move out you’re concentrating on making friends and getting a takeaway was quite an easy way for everyone to sit down around the table and socialise and to have drinks .” Participant 14 (Female: 20-29 years)

Participants did not value online food delivery services to the same extent that they did takeaway food. This perspective reinforced that online food delivery services were primarily used to satisfy takeaway food purchasing needs.

“ If Just Eat as an entity disappeared, or all online takeaways disappeared, I wouldn’t be upset […] it’s a luxury, it makes life easier .” Participant 9 (Male: 30-39 years)

Less effort for more convenience

Participants reported that it took little effort to use online food delivery services because they receive information about all food outlets that will deliver to them on a single platform. Additionally, participants valued the opportunity to save payment details, previous orders, and favourite food outlets for future use. Participants also informed us that they had a greater number of food outlets and a more diverse range of foods and cuisines to choose from compared with other purchasing formats. Due to the number of accessible food outlets, the selection process was not always fast. Nonetheless, participants indicated that online food delivery services make purchasing takeaway food easier and more convenient than other purchasing formats where information is less readily available.

“Y ou’ve got all of the different options laid out in front of you, it’s like one resource where everything is there and you can choose and make a decision, rather than having to pull out leaflets from a drawer or Google different takeaways in the area. It’s all there and it’s all uniform and it’s in one place .” Participant 3 (Female: 20-29 years) “ I can pick through a whole wide selection rather than being limited to the few takeaways down on my road or having to drive somewhere .” Participant 21 (Male: 20-29 years)

Participants emphasised that smartphone applications had been optimised to enhance this experience.

“ I guess it’s the convenience of just being able to open the app on my phone, and not have to go searching for menus or phone numbers and checking if places are open. So yeah, it’s the convenience .” Participant 15 (Male: 40-49 years) “ For me it’s just the ease of going on, clicking what you want, paying for it and it arriving. You don’t have to move, you don’t have to cook, you don’t have to think, it’s just there ready to go, someone’s doing the hard work for you .” Participant 1 (Female: 20-29 years)

However, greater convenience was not always advantageous. Some participants were concerned that convenient and easy access to takeaway food through online food delivery services might have negative consequences for health and other things.

“ It’s quite addictive in the way that it’s just so convenient to order. I’m not making stuff fresh at home, and I’m eating unhealthier .” Participant 21 (Male: 20-29 years) “ I think it adds to a general kind of laziness that is not good for people really. If you actually got up and went for a walk to go and get this food, at least there’s a slightly positive angle there .” Participant 17 (Male: 30-39 years) “ The convenience is not necessarily a positive thing, these apps can be abused because it’s so easy to access foods .” Participant 10 (Female: 20-29 years)

Saving money and reallocating time

Participants were price-sensitive and valued the opportunity to save money. When discussing financial aspects of online food delivery service use, participants referred to special offers they had received by email or through mobile device push notifications. Participants recognised that direct discounts (e.g. 10% off), free items (e.g. free appetizers on orders over £20.00), free delivery (e.g. on orders over £30.00), or time-limited price-promotions (e.g. 40% off all orders for the next three-hours) can justify takeaway food purchasing and online food delivery service use.

“ Getting a takeaway is always a treat, every time I do it I know I shouldn’t but then basically I’m convinced to treat myself, if there’s a discount I’m much more likely to do it because I don’t feel like it’s such a waste of money .” Participant 18 (Male: 20-29 years)

Participants recognised takeaway food as a distinct food category. Nevertheless, they appreciated that that they could use online food delivery services to purchase ‘restaurant food’. Since this food is usually accompanied by a complete dining experience that online food delivery services cannot replicate, participants expected to spend less on this food purchased online compared to when they dined inside a restaurant.

“ Some restaurants deliver through Deliveroo, [places] where you can sit down and have an experience, a dining experience, well that’s different […] you might go there for the dining experience .” Participant 4 (Female: 30-39 years) “ Sometimes I’m deterred from using Uber Eats because I noticed that the restaurants increase their prices if you buy it through them rather than directly […] I don’t want to pay over £10 for a takeaway dish, whereas I would pay that if I ate at a restaurant .” Participant 3 (Female: 20-29 years)

Although participants considered the price of food when deciding which outlet to order from, they traded money for time. Participants compared the time they would spend cooking or travelling to takeaway food outlets with the time taken to place orders through online food delivery services plus the tasks they could complete whilst waiting for meal delivery. Paying a delivery fee to have the opportunity to use time that would not have otherwise been available was acceptable.

“ Yeah, it costs money but at the same time we’re getting more time with the kids, and more time to do other stuff, so it’s absolutely fine as far as I’m concerned .” Participant 9 (Male: 30-39 years)

However, some participants were unsure about the appropriateness of paying to have food delivered as it might be unfair to delivery couriers.

“ I don’t feel like it’s necessarily right to make a delivery driver drive two minutes up the road just because I can’t be bothered to go and collect something that’s not very far away .” Participant 10 (Female: 20-29 years)

Online food delivery service normalisation

Participants had positive previous experiences of using online food delivery services. These experiences influenced future custom and contributed to an overall sense that using this purchasing format was now a normal part of living in a digital society. Some participants referred to watching television online to exemplify this point.

The normalisation of using online food delivery services was particularly evident when MK prompted participants to think about the term ‘takeaway food’. Participants often referred to online food delivery services in the first instance and saw them as synonymous with takeaway food.

“ If you were to say ‘takeaway food’ I’d pull out my phone and I’d open one of the apps and say ‘okay, what should we order’, I wouldn’t say ‘oh let’s go to this road’, or ‘let’s go to that road’, I’d say ‘yeah, let’s look on the app’ .” Participant 21 (Male: 20-29 years)

For participants in our study, using online food delivery services replaced purchasing takeaway food in other ways. This perspective was linked to habitual takeaway food purchasing and sociocultural values. Participants rarely purchased takeaway food outside of set routines (for example only doing so at the weekend) because they did not think it was appropriate. As a result, participants reported that they had a limited number of opportunities to use multiple purchasing formats and thus increase their existing levels of consumption.

Maintained home food practices

Most participants were responsible for cooking at home, enjoyed doing so, and said they were competent at it. Nonetheless, cooking at home required personal effort and being “ lazy ” or “ tired ” or “ having nothing in the cupboards ” was used as a justification for using online food delivery services.

“ I cook, when I’m not using these apps I cook and prepare food for myself , it’s just on the odd occasion I might be feeling tired or want something different […] the rest of the time, I’m quite happy to cook .” Participant 10 (Female: 20-29 years)

Despite the apparent normalisation of using online food delivery services, participants did not feel that they would ever completely eliminate cooking at home. Most participants consumed home cooked food daily, whereas they consumed takeaway food less frequently. This contributed to the view that these two types of food were different. As a result, participants used online food delivery services to purchase food they could not or would not cook at home; for a break from normality, and as a “ cheat ” or “ treat ”.

Summary of findings

To our knowledge, this is the first published study in the public health literature to investigate experiences of using online food delivery services from the perspective of frequent customers.

Participants recognised that their location and the time of day meant that they could often access different types of food through multiple purchasing formats, at the same time. Participants stated that purchasing takeaway food was appropriate in many situations and typically favoured using online food delivery services. For many participants, using these services was now part of routines in their increasingly digital lives. As such, using online food delivery services appeared to be synonymous with takeaway food purchasing. This meant that participants expected food sold online to be unhealthy and that it was inappropriate to purchase healthy food in this manner. Participants consistently thought about how features of online food delivery services were an advantage or a drawback within the context of their location at any given point in time. This was a complex and dynamic thought process. Participants described how the advantages of these services were a strong enough reason to continue use, overcoming drawbacks such as the acknowledged unhealthfulness of takeaway food. Participants reported that using online food delivery services involved little effort as they were provided with food outlet information, menus, and payment facilities on one platform that had been optimised for use. Moreover, although the cost of food was an important consideration for participants, they were willing to pay a fee in exchange for the opportunity to complete tasks whilst waiting for meal preparation and delivery. Finally, using online food delivery services substituted purchasing takeaway food in other ways. Nevertheless, participants reported that cooking at home was a distinct food practice that occurred more frequently and was irreplaceable.

Interpretations

Participants described sociocultural values assigned to takeaway food. These values are proposed to develop from previous experiences [ 38 , 39 ]. For our participants, purchasing takeaway food at the weekend was a traditional routine that celebrated the end of the working week. In the past, this tradition might have meant visiting food outlets in the neighbourhood food environment. However, online food delivery services are now used and favoured. Since participants reported that it was takeaway food in and of itself that was a fundamental reason for seeking out online food delivery services, it is reasonable to conclude that sociocultural values linked to this food exist, and transfer, across purchasing formats.

Food purchasing has been recognised as situational and made in the context of place and time [ 40 , 41 ], with convenience reported as a consistent consideration [ 42 ]. Participants in our study reported that takeaway food was appropriate in many situations and acknowledged that it could often be accessed through multiple purchasing formats. Using one purchasing format over another came after considering multiple factors, including the level of effort required to find a suitable food outlet and place orders. As using online food delivery services took little effort, this purchasing format was often most convenient. However, participants were clear that although their decision had seemingly been made, it could be changed, especially if an online food delivery service feature that was supposedly an advantage became a drawback. For example, if estimated delivery times were too long or delivery fees were too high an alternative option would be considered. Our findings support that the decision about if and how to purchase takeaway food is dynamic and influenced by place and time [ 32 ].

Food access has previously been summarised within the domains of availability, accessibility, affordability, accommodation, and acceptability [ 15 ]. Although Caspi and colleagues described these domains in the context of physical food access, they are applicable to digital food environments. Broadly speaking, our research investigated the ‘acceptability’ of using online food delivery services, and participants made explicit reference to the domains of food ‘accessibility’ and ‘affordability’.

For example, participants told us that one particularly valuable aspect of using online food delivery services was the ability to access a greater number of food outlets compared with other purchasing formats. This finding speaks to our previous research that found a positive association between having the highest number of food outlets accessible online and any use of online food delivery services in the previous week amongst adults living in the UK [ 17 ]. The experiences of using online food delivery services reported in the current study support the possibility that having more food outlet choice contributes to the decision to adopt, and maintain, use of these services rather than necessarily increasing the frequency in which they are used. Other features of online food delivery services, such as having information about each of the accessible food outlets on one platform, likely amplify the perceived benefit of greater food outlet access. Notably, however, access to an increased number of food outlets was not always advantageous. This finding recognises a general awareness about the negative aspects of takeaway food consumption, previously captured from the perspectives of young adults in Australia and Canada [ 38 , 43 ].

Participants also discussed how the price of food influenced their use of online food delivery services. This reflects that food affordability is a fundamental purchasing consideration [ 32 ]. Beyond this, our findings provide insight into actions that food outlets registered to accept orders online might take to attract customers. Given that online food delivery service customers can often select from multiple food outlets at the same time, food outlets might aim to compete with one another by lowering the price of food sold or by introducing price-promotions in an attempt to capitalise on customer demand. Particularly in the case of the latter, participants acknowledged the importance of price-promotions. Previous evidence shows that price-promotions contribute to unhealthy food purchasing practices [ 44 , 45 ]. Access to price-promotions through online food delivery services has not been systematically documented. However, it is possible that their availability is positively associated with the number of food outlets accessible online. Since both price-promotions and the number of food outlets accessible online appear to influence online food delivery service use, the possibility of interaction between them is concerning for overall consumption of food prepared out-of-home, and subsequently, diet quality and health.

In some cases, participants reported that they used online food delivery services because they did not have time to cook at home. A number of tasks, including household chores, work, travel, and childcare, can limit the time available for, and take priority over, home cooking [ 46 ]. Using online food delivery services (and paying associated delivery fees) instead of cooking at home allowed participants in our study to complete non-food related tasks whilst waiting for meal preparation and delivery. Due to sociocultural values and perceived ‘rules’ about how frequently takeaway food 'should' be purchased, participants did not see online food delivery services as a complete replacement for cooking at home. Nevertheless, even partial replacement has implications for diet quality and health, especially since the food available and purchased online was acknowledged as unhealthy by participants in the current study.

Possible implications for public health and future research

Participants reported that using online food delivery services had mostly substituted, not supplemented, their use of other purchasing formats. Given the perspectives of participants in our study, an increasing number of food outlets could be registering to accept orders online to supply an apparent customer demand. Further research is required to understand the extent to which customer demand is driven by food outlet accessibility, and vice versa.

Participants in our study reported that despite using online food delivery services frequently, their overall takeaway food consumption had remained the same. We do not yet know if this perception would be reflected in objective assessment of takeaway food consumption. Further research that quantifies the use of multiple purchasing formats and takeaway food consumption over time is required to understand the potential public health implications as a result of using online food delivery services. Although evidence from Australia suggests that food sold through online food delivery services tends to be energy-dense and nutrient-poor [ 47 ], this has not been established in the UK, to our knowledge. Nor does it necessarily reflect the balance of what food is purchased. Objective assessment of the nutritional quality of foods available, and purchased, through online food delivery services in the UK could be the focus of future research. This evidence will help to better understand the extent to which public health concern is warranted.

With a few exceptions, food sold through online food delivery services is prepared in food outlets that are also physically accessible in the neighbourhood food environment [ 13 ]. From a public health perspective, this reinforces the intrinsic link between neighbourhood and digital food environments [ 48 ]. Therefore, public health interventions adopted in the neighbourhood food environment may also influence the digital food environment. For example, urban planning policies have been adopted to prevent new takeaway food outlets from opening in neighbourhoods [ 49 ]. By extension, this stops new food outlets from becoming accessible online. Other public health interventions that operate synergistically between physical and digital food environments might be increasingly required in the future. It will also be vital for any future interventions to consider how the geographical coverage of online food delivery services expands neighbourhood food outlet access [ 50 ], potentially undermining the effectiveness of interventions adopted in the neighbourhood food environment. Doing so would help address concerns that these services increase access to food prepared out-of-home [ 4 , 13 ]. Interventions of this nature could be particularly important in more deprived areas that have the highest number of accessible food outlets across multiple purchasing formats [ 16 , 51 ].

Participants recognised that online food delivery services provide access to takeaway food that was associated with being unhealthy. Participants were aware that they could purchase healthy food through online food delivery services, but this did not mean that they would . From a public health perspective, this finding indicates that the success of interventions intended to promote healthier takeaway food purchasing through online food delivery services might be limited by existing sociocultural values if they are not taken into consideration. A possible way to navigate this would be to improve the nutritional quality of food available online without necessarily making any changes salient. Interventions of this nature include healthier frying practices and reduced food packaging size [ 52 , 53 ]. Although these interventions were acceptable and feasible when implemented inside takeaway food outlets [ 54 ], further investigation is required to understand the extent to which they are appropriate in the context of online food delivery services. Changing the types of food available to purchase through online food delivery services could also lead to improved food access for those with limited kitchen facilities at home or limited mobility.

Public health interventions intended specifically for online food delivery services could also be developed. Potential approaches include preferential placement of healthy menu items, introducing calorie labelling and offering healthier food swaps. Embedding these approaches within existing online food delivery service infrastructures would allow implementation to be uniform [ 55 ], and their implementation could be optimised to enhance customer awareness and interaction. The potential success of approaches of this nature requires exploration. Nevertheless, in February 2022, the UK Behavioural Insights Team (formerly of the UK Government) published a protocol to investigate approaches to promoting the purchase of lower energy density foods through a simulated online food delivery service platform [ 56 ].

Price-promotions influenced and justified the use of online food delivery services. Legislation to restrict the use of volume-based price-promotions (e.g. buy-one-get-one-free, 50% extra free) on less healthy pre-packaged food sold both in-store and online were due to be introduced in England in October 2022 [ 57 ]. However, the introduction of this legislation has now been delayed. Although hot food served ready-to-consume was due to be excluded, given what is known about the impact of price-promotions on purchasing other food [ 58 ], and our participants’ description of the importance of price-promotions on their purchasing practices, extension of these restrictions to hot food served ready-to-consume might be warranted. Understanding how price-promotions influence food purchased from online food delivery services represents a first step to understand the need for future regulation.

Limitations

We recruited participants through two social media platforms, which means that our study sample was formed from a subset of all social media users. However, online recruitment was appropriate since we wanted to understand experiences of using a digital purchasing format. Moreover, the participants we recruited were mostly highly educated, potentially reflecting reported online food delivery service use amongst this socioeconomic group [ 22 , 23 ]. After 12 telephone interviews we acknowledged this and adjusted our recruitment strategy to ensure a more balanced sample with respect to level of education. Nevertheless, future research should explore the perspectives of frequent online food delivery service customers with lower levels of education, since it is possible that they have different reasons for using these services. Although we did not recruit infrequent online food delivery service customers or non-customers, they would not have been well-positioned to help us investigate our study aims. However, since we have described experiences of using online food delivery services from the perspective of frequent customers, future work should seek to understand perspectives of non-customers, customers who use them less frequently, and customers who use them for specific reasons.

As the first study in the public health literature to investigate frequent customer experiences of using online food delivery services, we chose a descriptive methodological orientation. Our descriptive approach meant that we did not investigate the underlying meaning of the language used by participants, however, this was not aligned with our aims. Furthermore, our descriptive methodological orientation allowed us to use codebook thematic analysis and include multiple researchers in analysis. Coding a 10% sample of interviews transcripts and discussing analytic themes would have been less appropriate with reflexive approaches to thematic analysis [ 34 , 35 , 59 ], but assisted with our interpretations.

We conducted fieldwork during the early stages of the COVID-19 pandemic, which might have altered the recent experiences of online food delivery service use and participant perspectives. However, MK asked participants to think about the time before the COVID-19 pandemic and reflected on their ability to do so. This reflexivity is in line with established practices regarding qualitative rigour [ 20 , 60 ], and allowed us to determine when it would be most appropriate to stop fieldwork. Nonetheless, we acknowledge the possibility that food-related practices have changed during the COVID-19 pandemic. As a result, it is possible that online food delivery services are now used for different reasons, both initially and over time, and by individuals with different sociodemographic characteristics than those in our study.

We used telephone interviews with frequent online food delivery service customers to investigate experiences of using this purchasing format. We found that the context of place and time influenced if and how takeaway food would be purchased. Online food delivery services were often seen as most appropriate. In part, this was due to the opportunity to access advantages not available through other purchasing formats, such as efficient and convenient ordering processes that had been optimised for customers. Fundamentally, however, online food delivery services provide access to takeaway food, which despite being acknowledged as unhealthy, has strong sociocultural value. There was a consistent awareness that some advantages of online food delivery services may also be drawbacks. Despite this, the drawbacks were not sufficiently negative to stop current or future online food delivery service use. Finally, price-promotions justified online food delivery service use and made this practice appealing. Public health interventions that seek to promote healthier food purchasing through online food delivery services may be increasingly warranted in the future. Approaches might include increasing the healthiness of the food available whilst maintaining sociocultural values and expectations, and extending restrictions on price-promotions to hot food prepared out-of-home.

Availability of data and materials

Processed and anonymised qualitative data from this study is available from the corresponding author upon reasonable request. Additional raw data related to this publication cannot be openly released; the raw data contains interview audio containing identifiable information.

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Matthew Keeble was funded by the National Institute for Health and Care Research (NIHR) School for Public Health Research (SPHR) [grant number PD_SPH_2015]. This work was supported by the Medical Research Council [grant number MC_UU_00006/7]. The views expressed are those of the authors and not necessarily those of any of the above named funders. The funders had no role in the design of the study, or collection, analysis and interpretation of the data, or in writing the manuscript. For the purpose of open access. the author has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising.

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Matthew Keeble: Conceptualization, Data curation, Formal analysis, Methodology, Writing – original draft, Writing – review & editing. Jean Adams: Conceptualization, Methodology, Supervision, Writing – review & editing. Thomas Burgoine: Conceptualization, Methodology, Supervision, Writing – review & editing. The author(s) read and approved the final manuscript.

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Box A1. Names of Subreddits used during participant recruitment. Box A2. Final telephone interview topic guide.

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Keeble, M., Adams, J. & Burgoine, T. Investigating experiences of frequent online food delivery service use: a qualitative study in UK adults. BMC Public Health 22 , 1365 (2022). https://doi.org/10.1186/s12889-022-13721-9

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How do you keep food delivery workers from being exploited, especially during a pandemic when they're so critical? Even once-Communist Russia is struggling with that question.

Mikhail rides his bicycle around Moscow for up to 12 hours a day with a large insulated pack on his back, even in the dead of winter, delivering food from restaurants to hungry consumers in their homes.

This is not your old-fashioned pizza delivery service. Mikhail is a front-line worker in one of the world’s fastest-growing industries.

The company he works for, the giant digital corporation Yandex, is often referred to as “Russia’s answer to Google.” Its main competitor, Delivery Club, is jointly owned by Russia’s largest state bank, Sberbank, and one of its biggest internet companies, Mail.Ru. On any given day, each company has an estimated 10,000 food delivery couriers schlepping around the city on bicycles, public transport, and sometimes their own cars.

Since the pandemic hit, with its attendant lockdowns, business has exploded. Formerly just a convenience, delivered food became a lifeline for struggling restaurants and customers isolated in their homes. There are no reliable figures, but some estimates say food deliveries have grown at least threefold. Thousands of young people laid off from jobs like store clerks, waiters, construction workers, and such, took up delivering food to make ends meet.

It has its advantages. “Nobody cares what your political opinions are, as long as you don’t bad-mouth the company. You can pretty much choose your own working hours, day or night. There’s a certain freedom that you feel,” says Mikhail. “There’s lots of work, as much as you want.”

From the moment he accepts an order, he is paid a fixed amount by time and distance to go to the designated restaurant, pick up the food, and deliver it to the customer. But if he is delayed for any reason he will be fined. If he switches off the GPS on his phone for more than half an hour, he will be docked a day’s wages. If he refuses to accept an order, he will be fined. Mikhail figures he works an average of 240 hours per month, for which he earns about $680.

What would he change, if he could?

“What we need,” says Mikhail, “is a union.”

The couriers are completely outside Russia’s official system of labor law. No official employment contract means no security, no benefits, and no means to redress grievances. It can be dangerous too: Last April a young courier in St. Petersburg died of a heart attack , allegedly brought on by exhaustion. So ironically in a country that spent 70 years under Communist Party rule, the couriers are having to reinvent combative trade unionism culture in Russia from the ground up to better their conditions.

“There are growing numbers of people who do this courier work permanently, for a living, and there are few other prospects for them in today’s economy,” says Kirill Ukraintsev, an activist journalist turned food-delivery union builder. “Russia’s inadequate labor legislation allows them to be classified as self-employed and thus frees the company from any responsibility for them. Although they are part of the fastest-growing and most profitable business, couriers are at the bottom of the labor pyramid. They are super-exploited. We want to change that.”

“Heroes of the pandemic”

The delivery phenomenon is not unique to Russia, of course. The same sorts of couriers can been seen in cities around the globe, especially since the beginning of the pandemic.

“This is a huge and rapidly expanding business. It’s a whole new world that’s being birthed by 21st-century technologies,” says Yevgeny Gontmakher, a social economist and former government adviser. “You see the traditional bank, Sberbank, teaming up with a digital company to create a whole ecosystem of new services, and reshaping the economic landscape as they go. The people driving this are mostly young, both the couriers and management of these new businesses, and they need to develop the people skills to keep it working. It’s not just in Russia; it’s a global phenomenon.”

And just like elsewhere in the world, the couriers have little in the way of work benefits or protection. That’s why, about six months ago, Mr. Ukraintsev decided he wanted to do more than just cover social conflicts and set out to build a union for the food delivery workers.

He’s since gathered about a hundred activists, including Mikhail, into an as-yet unrecognized Union of Couriers, and claims many more supporters. They have two key demands: the abolition of fines and the right of couriers to sign proper employment contracts like other workers. Mr. Ukraintsev is quite conversant in global developments, such as the passage of Proposition 22 in California, which secured some benefits for Uber and Lyft drivers – who are in an analogous position to food couriers – but denied them others.

They’ve had a few minor successes. The group staged a one-day wildcat strike in October, and even though the numbers of participating couriers was small, the action received a lot of positive coverage from a curious Moscow media. Managers of Delivery Club agreed to meet with the activists and promised to reduce some of the fines.

Earlier, several companies had funded the erection of the world’s first monument to food couriers , the “heroes of the pandemic,” in a Moscow commercial square.

An unsigned statement from Delivery Club, in response to questions from the Monitor, said that all outstanding complaints from couriers about payment delays and similar grievances have been dealt with, and “the service is now operating normally.”

Mr. Ukraintsev says he’s under no illusions that a bit of good press and nice corporate PR is going to change anything.

“This is going to be hard,” he says. “The new digital economy destroys all contacts between people. Each one works alone, and deals with the company mostly through his telephone, without any direct human contact. The workers are a shifting labor force, many of them migrant workers who lack even the protections of citizenship and fear being deported if they make waves. Our answer is to use the companies’ own digital methods, reaching out through social media, Telegram channels, and YouTube. But we’re also doing street protests and other more classical forms of outreach.”

“These food delivery workers need to be supported”

Boris Kagarlitsky, a veteran left-wing activist and professor at the Moscow School of Social and Economic Sciences, says that despite those early successes, the couriers are going to need solid political backing to achieve their main goal of being treated like regular workers.

“It’s easier to win some results in a growing industry. If they were fighting for a few scraps in a declining industry, their early efforts might have turned out quite differently,” he says. “But it’s pretty clear that public opinion was crucial to their early gains, and is going to be indispensable in their struggle going forward. These employers, whose services work at close quarters with the public every day, need to be concerned with positioning themselves in a positive PR light, so that’s a vulnerability.

“But more than that, these food delivery workers need to be supported by political forces that will press for laws to meet their needs. If we had a labor-friendly government in Russia, which we do not, it could impose regulations on the companies to register their workers as full employees. These couriers have some support from a few Moscow City Council members, mainly Communists, but no political party has yet taken their side.”

The official 30 million member Federation of Independent Trade Unions, which is aligned with the pro-Kremlin United Russia party, does not appear interested in helping. The much smaller, more recently created Confederation of Labor has extended legal assistance to the couriers, but does not seem in a position to do much more.

“We need to counter these new employer-centered ideas about ‘labor flexibility,’ and that can only happen through concerted political action, culminating in strong laws that permanently ground workers’ rights,” says Mr. Kagarlitsky. “We are very far from that right now, but this is just the beginning.”

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• Published: 26 March 2024

Predicting and improving complex beer flavor through machine learning

• Michiel Schreurs   ORCID: orcid.org/0000-0002-9449-5619 1 , 2 , 3   na1 ,
• Supinya Piampongsant 1 , 2 , 3   na1 ,
• Miguel Roncoroni   ORCID: orcid.org/0000-0001-7461-1427 1 , 2 , 3   na1 ,
• Lloyd Cool   ORCID: orcid.org/0000-0001-9936-3124 1 , 2 , 3 , 4 ,
• Beatriz Herrera-Malaver   ORCID: orcid.org/0000-0002-5096-9974 1 , 2 , 3 ,
• Christophe Vanderaa   ORCID: orcid.org/0000-0001-7443-5427 4 ,
• Florian A. Theßeling 1 , 2 , 3 ,
• Łukasz Kreft   ORCID: orcid.org/0000-0001-7620-4657 5 ,
• Alexander Botzki   ORCID: orcid.org/0000-0001-6691-4233 5 ,
• Philippe Malcorps 6 ,
• Luk Daenen 6 ,
• Tom Wenseleers   ORCID: orcid.org/0000-0002-1434-861X 4 &
• Kevin J. Verstrepen   ORCID: orcid.org/0000-0002-3077-6219 1 , 2 , 3  

Nature Communications volume  15 , Article number:  2368 ( 2024 ) Cite this article

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• Chemical engineering
• Gas chromatography
• Machine learning
• Metabolomics
• Taste receptors

The perception and appreciation of food flavor depends on many interacting chemical compounds and external factors, and therefore proves challenging to understand and predict. Here, we combine extensive chemical and sensory analyses of 250 different beers to train machine learning models that allow predicting flavor and consumer appreciation. For each beer, we measure over 200 chemical properties, perform quantitative descriptive sensory analysis with a trained tasting panel and map data from over 180,000 consumer reviews to train 10 different machine learning models. The best-performing algorithm, Gradient Boosting, yields models that significantly outperform predictions based on conventional statistics and accurately predict complex food features and consumer appreciation from chemical profiles. Model dissection allows identifying specific and unexpected compounds as drivers of beer flavor and appreciation. Adding these compounds results in variants of commercial alcoholic and non-alcoholic beers with improved consumer appreciation. Together, our study reveals how big data and machine learning uncover complex links between food chemistry, flavor and consumer perception, and lays the foundation to develop novel, tailored foods with superior flavors.

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Introduction

Predicting and understanding food perception and appreciation is one of the major challenges in food science. Accurate modeling of food flavor and appreciation could yield important opportunities for both producers and consumers, including quality control, product fingerprinting, counterfeit detection, spoilage detection, and the development of new products and product combinations (food pairing) 1 , 2 , 3 , 4 , 5 , 6 . Accurate models for flavor and consumer appreciation would contribute greatly to our scientific understanding of how humans perceive and appreciate flavor. Moreover, accurate predictive models would also facilitate and standardize existing food assessment methods and could supplement or replace assessments by trained and consumer tasting panels, which are variable, expensive and time-consuming 7 , 8 , 9 . Lastly, apart from providing objective, quantitative, accurate and contextual information that can help producers, models can also guide consumers in understanding their personal preferences 10 .

Despite the myriad of applications, predicting food flavor and appreciation from its chemical properties remains a largely elusive goal in sensory science, especially for complex food and beverages 11 , 12 . A key obstacle is the immense number of flavor-active chemicals underlying food flavor. Flavor compounds can vary widely in chemical structure and concentration, making them technically challenging and labor-intensive to quantify, even in the face of innovations in metabolomics, such as non-targeted metabolic fingerprinting 13 , 14 . Moreover, sensory analysis is perhaps even more complicated. Flavor perception is highly complex, resulting from hundreds of different molecules interacting at the physiochemical and sensorial level. Sensory perception is often non-linear, characterized by complex and concentration-dependent synergistic and antagonistic effects 15 , 16 , 17 , 18 , 19 , 20 , 21 that are further convoluted by the genetics, environment, culture and psychology of consumers 22 , 23 , 24 . Perceived flavor is therefore difficult to measure, with problems of sensitivity, accuracy, and reproducibility that can only be resolved by gathering sufficiently large datasets 25 . Trained tasting panels are considered the prime source of quality sensory data, but require meticulous training, are low throughput and high cost. Public databases containing consumer reviews of food products could provide a valuable alternative, especially for studying appreciation scores, which do not require formal training 25 . Public databases offer the advantage of amassing large amounts of data, increasing the statistical power to identify potential drivers of appreciation. However, public datasets suffer from biases, including a bias in the volunteers that contribute to the database, as well as confounding factors such as price, cult status and psychological conformity towards previous ratings of the product.

Classical multivariate statistics and machine learning methods have been used to predict flavor of specific compounds by, for example, linking structural properties of a compound to its potential biological activities or linking concentrations of specific compounds to sensory profiles 1 , 26 . Importantly, most previous studies focused on predicting organoleptic properties of single compounds (often based on their chemical structure) 27 , 28 , 29 , 30 , 31 , 32 , 33 , thus ignoring the fact that these compounds are present in a complex matrix in food or beverages and excluding complex interactions between compounds. Moreover, the classical statistics commonly used in sensory science 34 , 35 , 36 , 37 , 38 , 39 require a large sample size and sufficient variance amongst predictors to create accurate models. They are not fit for studying an extensive set of hundreds of interacting flavor compounds, since they are sensitive to outliers, have a high tendency to overfit and are less suited for non-linear and discontinuous relationships 40 .

In this study, we combine extensive chemical analyses and sensory data of a set of different commercial beers with machine learning approaches to develop models that predict taste, smell, mouthfeel and appreciation from compound concentrations. Beer is particularly suited to model the relationship between chemistry, flavor and appreciation. First, beer is a complex product, consisting of thousands of flavor compounds that partake in complex sensory interactions 41 , 42 , 43 . This chemical diversity arises from the raw materials (malt, yeast, hops, water and spices) and biochemical conversions during the brewing process (kilning, mashing, boiling, fermentation, maturation and aging) 44 , 45 . Second, the advent of the internet saw beer consumers embrace online review platforms, such as RateBeer (ZX Ventures, Anheuser-Busch InBev SA/NV) and BeerAdvocate (Next Glass, inc.). In this way, the beer community provides massive data sets of beer flavor and appreciation scores, creating extraordinarily large sensory databases to complement the analyses of our professional sensory panel. Specifically, we characterize over 200 chemical properties of 250 commercial beers, spread across 22 beer styles, and link these to the descriptive sensory profiling data of a 16-person in-house trained tasting panel and data acquired from over 180,000 public consumer reviews. These unique and extensive datasets enable us to train a suite of machine learning models to predict flavor and appreciation from a beer’s chemical profile. Dissection of the best-performing models allows us to pinpoint specific compounds as potential drivers of beer flavor and appreciation. Follow-up experiments confirm the importance of these compounds and ultimately allow us to significantly improve the flavor and appreciation of selected commercial beers. Together, our study represents a significant step towards understanding complex flavors and reinforces the value of machine learning to develop and refine complex foods. In this way, it represents a stepping stone for further computer-aided food engineering applications 46 .

To generate a comprehensive dataset on beer flavor, we selected 250 commercial Belgian beers across 22 different beer styles (Supplementary Fig.  S1 ). Beers with ≤ 4.2% alcohol by volume (ABV) were classified as non-alcoholic and low-alcoholic. Blonds and Tripels constitute a significant portion of the dataset (12.4% and 11.2%, respectively) reflecting their presence on the Belgian beer market and the heterogeneity of beers within these styles. By contrast, lager beers are less diverse and dominated by a handful of brands. Rare styles such as Brut or Faro make up only a small fraction of the dataset (2% and 1%, respectively) because fewer of these beers are produced and because they are dominated by distinct characteristics in terms of flavor and chemical composition.

Extensive analysis identifies relationships between chemical compounds in beer

For each beer, we measured 226 different chemical properties, including common brewing parameters such as alcohol content, iso-alpha acids, pH, sugar concentration 47 , and over 200 flavor compounds (Methods, Supplementary Table  S1 ). A large portion (37.2%) are terpenoids arising from hopping, responsible for herbal and fruity flavors 16 , 48 . A second major category are yeast metabolites, such as esters and alcohols, that result in fruity and solvent notes 48 , 49 , 50 . Other measured compounds are primarily derived from malt, or other microbes such as non- Saccharomyces yeasts and bacteria (‘wild flora’). Compounds that arise from spices or staling are labeled under ‘Others’. Five attributes (caloric value, total acids and total ester, hop aroma and sulfur compounds) are calculated from multiple individually measured compounds.

As a first step in identifying relationships between chemical properties, we determined correlations between the concentrations of the compounds (Fig.  1 , upper panel, Supplementary Data  1 and 2 , and Supplementary Fig.  S2 . For the sake of clarity, only a subset of the measured compounds is shown in Fig.  1 ). Compounds of the same origin typically show a positive correlation, while absence of correlation hints at parameters varying independently. For example, the hop aroma compounds citronellol, and alpha-terpineol show moderate correlations with each other (Spearman’s rho=0.39 and 0.57), but not with the bittering hop component iso-alpha acids (Spearman’s rho=0.16 and −0.07). This illustrates how brewers can independently modify hop aroma and bitterness by selecting hop varieties and dosage time. If hops are added early in the boiling phase, chemical conversions increase bitterness while aromas evaporate, conversely, late addition of hops preserves aroma but limits bitterness 51 . Similarly, hop-derived iso-alpha acids show a strong anti-correlation with lactic acid and acetic acid, likely reflecting growth inhibition of lactic acid and acetic acid bacteria, or the consequent use of fewer hops in sour beer styles, such as West Flanders ales and Fruit beers, that rely on these bacteria for their distinct flavors 52 . Finally, yeast-derived esters (ethyl acetate, ethyl decanoate, ethyl hexanoate, ethyl octanoate) and alcohols (ethanol, isoamyl alcohol, isobutanol, and glycerol), correlate with Spearman coefficients above 0.5, suggesting that these secondary metabolites are correlated with the yeast genetic background and/or fermentation parameters and may be difficult to influence individually, although the choice of yeast strain may offer some control 53 .

Spearman rank correlations are shown. Descriptors are grouped according to their origin (malt (blue), hops (green), yeast (red), wild flora (yellow), Others (black)), and sensory aspect (aroma, taste, palate, and overall appreciation). Please note that for the chemical compounds, for the sake of clarity, only a subset of the total number of measured compounds is shown, with an emphasis on the key compounds for each source. For more details, see the main text and Methods section. Chemical data can be found in Supplementary Data  1 , correlations between all chemical compounds are depicted in Supplementary Fig.  S2 and correlation values can be found in Supplementary Data  2 . See Supplementary Data  4 for sensory panel assessments and Supplementary Data  5 for correlation values between all sensory descriptors.

Interestingly, different beer styles show distinct patterns for some flavor compounds (Supplementary Fig.  S3 ). These observations agree with expectations for key beer styles, and serve as a control for our measurements. For instance, Stouts generally show high values for color (darker), while hoppy beers contain elevated levels of iso-alpha acids, compounds associated with bitter hop taste. Acetic and lactic acid are not prevalent in most beers, with notable exceptions such as Kriek, Lambic, Faro, West Flanders ales and Flanders Old Brown, which use acid-producing bacteria ( Lactobacillus and Pediococcus ) or unconventional yeast ( Brettanomyces ) 54 , 55 . Glycerol, ethanol and esters show similar distributions across all beer styles, reflecting their common origin as products of yeast metabolism during fermentation 45 , 53 . Finally, low/no-alcohol beers contain low concentrations of glycerol and esters. This is in line with the production process for most of the low/no-alcohol beers in our dataset, which are produced through limiting fermentation or by stripping away alcohol via evaporation or dialysis, with both methods having the unintended side-effect of reducing the amount of flavor compounds in the final beer 56 , 57 .

Besides expected associations, our data also reveals less trivial associations between beer styles and specific parameters. For example, geraniol and citronellol, two monoterpenoids responsible for citrus, floral and rose flavors and characteristic of Citra hops, are found in relatively high amounts in Christmas, Saison, and Brett/co-fermented beers, where they may originate from terpenoid-rich spices such as coriander seeds instead of hops 58 .

Tasting panel assessments reveal sensorial relationships in beer

To assess the sensory profile of each beer, a trained tasting panel evaluated each of the 250 beers for 50 sensory attributes, including different hop, malt and yeast flavors, off-flavors and spices. Panelists used a tasting sheet (Supplementary Data  3 ) to score the different attributes. Panel consistency was evaluated by repeating 12 samples across different sessions and performing ANOVA. In 95% of cases no significant difference was found across sessions ( p  > 0.05), indicating good panel consistency (Supplementary Table  S2 ).

Aroma and taste perception reported by the trained panel are often linked (Fig.  1 , bottom left panel and Supplementary Data  4 and 5 ), with high correlations between hops aroma and taste (Spearman’s rho=0.83). Bitter taste was found to correlate with hop aroma and taste in general (Spearman’s rho=0.80 and 0.69), and particularly with “grassy” noble hops (Spearman’s rho=0.75). Barnyard flavor, most often associated with sour beers, is identified together with stale hops (Spearman’s rho=0.97) that are used in these beers. Lactic and acetic acid, which often co-occur, are correlated (Spearman’s rho=0.66). Interestingly, sweetness and bitterness are anti-correlated (Spearman’s rho = −0.48), confirming the hypothesis that they mask each other 59 , 60 . Beer body is highly correlated with alcohol (Spearman’s rho = 0.79), and overall appreciation is found to correlate with multiple aspects that describe beer mouthfeel (alcohol, carbonation; Spearman’s rho= 0.32, 0.39), as well as with hop and ester aroma intensity (Spearman’s rho=0.39 and 0.35).

Similar to the chemical analyses, sensorial analyses confirmed typical features of specific beer styles (Supplementary Fig.  S4 ). For example, sour beers (Faro, Flanders Old Brown, Fruit beer, Kriek, Lambic, West Flanders ale) were rated acidic, with flavors of both acetic and lactic acid. Hoppy beers were found to be bitter and showed hop-associated aromas like citrus and tropical fruit. Malt taste is most detected among scotch, stout/porters, and strong ales, while low/no-alcohol beers, which often have a reputation for being ‘worty’ (reminiscent of unfermented, sweet malt extract) appear in the middle. Unsurprisingly, hop aromas are most strongly detected among hoppy beers. Like its chemical counterpart (Supplementary Fig.  S3 ), acidity shows a right-skewed distribution, with the most acidic beers being Krieks, Lambics, and West Flanders ales.

Tasting panel assessments of specific flavors correlate with chemical composition

We find that the concentrations of several chemical compounds strongly correlate with specific aroma or taste, as evaluated by the tasting panel (Fig.  2 , Supplementary Fig.  S5 , Supplementary Data  6 ). In some cases, these correlations confirm expectations and serve as a useful control for data quality. For example, iso-alpha acids, the bittering compounds in hops, strongly correlate with bitterness (Spearman’s rho=0.68), while ethanol and glycerol correlate with tasters’ perceptions of alcohol and body, the mouthfeel sensation of fullness (Spearman’s rho=0.82/0.62 and 0.72/0.57 respectively) and darker color from roasted malts is a good indication of malt perception (Spearman’s rho=0.54).

Heatmap colors indicate Spearman’s Rho. Axes are organized according to sensory categories (aroma, taste, mouthfeel, overall), chemical categories and chemical sources in beer (malt (blue), hops (green), yeast (red), wild flora (yellow), Others (black)). See Supplementary Data  6 for all correlation values.

Interestingly, for some relationships between chemical compounds and perceived flavor, correlations are weaker than expected. For example, the rose-smelling phenethyl acetate only weakly correlates with floral aroma. This hints at more complex relationships and interactions between compounds and suggests a need for a more complex model than simple correlations. Lastly, we uncovered unexpected correlations. For instance, the esters ethyl decanoate and ethyl octanoate appear to correlate slightly with hop perception and bitterness, possibly due to their fruity flavor. Iron is anti-correlated with hop aromas and bitterness, most likely because it is also anti-correlated with iso-alpha acids. This could be a sign of metal chelation of hop acids 61 , given that our analyses measure unbound hop acids and total iron content, or could result from the higher iron content in dark and Fruit beers, which typically have less hoppy and bitter flavors 62 .

Public consumer reviews complement expert panel data

To complement and expand the sensory data of our trained tasting panel, we collected 180,000 reviews of our 250 beers from the online consumer review platform RateBeer. This provided numerical scores for beer appearance, aroma, taste, palate, overall quality as well as the average overall score.

Public datasets are known to suffer from biases, such as price, cult status and psychological conformity towards previous ratings of a product. For example, prices correlate with appreciation scores for these online consumer reviews (rho=0.49, Supplementary Fig.  S6 ), but not for our trained tasting panel (rho=0.19). This suggests that prices affect consumer appreciation, which has been reported in wine 63 , while blind tastings are unaffected. Moreover, we observe that some beer styles, like lagers and non-alcoholic beers, generally receive lower scores, reflecting that online reviewers are mostly beer aficionados with a preference for specialty beers over lager beers. In general, we find a modest correlation between our trained panel’s overall appreciation score and the online consumer appreciation scores (Fig.  3 , rho=0.29). Apart from the aforementioned biases in the online datasets, serving temperature, sample freshness and surroundings, which are all tightly controlled during the tasting panel sessions, can vary tremendously across online consumers and can further contribute to (among others, appreciation) differences between the two categories of tasters. Importantly, in contrast to the overall appreciation scores, for many sensory aspects the results from the professional panel correlated well with results obtained from RateBeer reviews. Correlations were highest for features that are relatively easy to recognize even for untrained tasters, like bitterness, sweetness, alcohol and malt aroma (Fig.  3 and below).

RateBeer text mining results can be found in Supplementary Data  7 . Rho values shown are Spearman correlation values, with asterisks indicating significant correlations ( p  < 0.05, two-sided). All p values were smaller than 0.001, except for Esters aroma (0.0553), Esters taste (0.3275), Esters aroma—banana (0.0019), Coriander (0.0508) and Diacetyl (0.0134).

Besides collecting consumer appreciation from these online reviews, we developed automated text analysis tools to gather additional data from review texts (Supplementary Data  7 ). Processing review texts on the RateBeer database yielded comparable results to the scores given by the trained panel for many common sensory aspects, including acidity, bitterness, sweetness, alcohol, malt, and hop tastes (Fig.  3 ). This is in line with what would be expected, since these attributes require less training for accurate assessment and are less influenced by environmental factors such as temperature, serving glass and odors in the environment. Consumer reviews also correlate well with our trained panel for 4-vinyl guaiacol, a compound associated with a very characteristic aroma. By contrast, correlations for more specific aromas like ester, coriander or diacetyl are underrepresented in the online reviews, underscoring the importance of using a trained tasting panel and standardized tasting sheets with explicit factors to be scored for evaluating specific aspects of a beer. Taken together, our results suggest that public reviews are trustworthy for some, but not all, flavor features and can complement or substitute taste panel data for these sensory aspects.

Models can predict beer sensory profiles from chemical data

The rich datasets of chemical analyses, tasting panel assessments and public reviews gathered in the first part of this study provided us with a unique opportunity to develop predictive models that link chemical data to sensorial features. Given the complexity of beer flavor, basic statistical tools such as correlations or linear regression may not always be the most suitable for making accurate predictions. Instead, we applied different machine learning models that can model both simple linear and complex interactive relationships. Specifically, we constructed a set of regression models to predict (a) trained panel scores for beer flavor and quality and (b) public reviews’ appreciation scores from beer chemical profiles. We trained and tested 10 different models (Methods), 3 linear regression-based models (simple linear regression with first-order interactions (LR), lasso regression with first-order interactions (Lasso), partial least squares regressor (PLSR)), 5 decision tree models (AdaBoost regressor (ABR), extra trees (ET), gradient boosting regressor (GBR), random forest (RF) and XGBoost regressor (XGBR)), 1 support vector regression (SVR), and 1 artificial neural network (ANN) model.

To compare the performance of our machine learning models, the dataset was randomly split into a training and test set, stratified by beer style. After a model was trained on data in the training set, its performance was evaluated on its ability to predict the test dataset obtained from multi-output models (based on the coefficient of determination, see Methods). Additionally, individual-attribute models were ranked per descriptor and the average rank was calculated, as proposed by Korneva et al. 64 . Importantly, both ways of evaluating the models’ performance agreed in general. Performance of the different models varied (Table  1 ). It should be noted that all models perform better at predicting RateBeer results than results from our trained tasting panel. One reason could be that sensory data is inherently variable, and this variability is averaged out with the large number of public reviews from RateBeer. Additionally, all tree-based models perform better at predicting taste than aroma. Linear models (LR) performed particularly poorly, with negative R 2 values, due to severe overfitting (training set R 2  = 1). Overfitting is a common issue in linear models with many parameters and limited samples, especially with interaction terms further amplifying the number of parameters. L1 regularization (Lasso) successfully overcomes this overfitting, out-competing multiple tree-based models on the RateBeer dataset. Similarly, the dimensionality reduction of PLSR avoids overfitting and improves performance, to some extent. Still, tree-based models (ABR, ET, GBR, RF and XGBR) show the best performance, out-competing the linear models (LR, Lasso, PLSR) commonly used in sensory science 65 .

GBR models showed the best overall performance in predicting sensory responses from chemical information, with R 2 values up to 0.75 depending on the predicted sensory feature (Supplementary Table  S4 ). The GBR models predict consumer appreciation (RateBeer) better than our trained panel’s appreciation (R 2 value of 0.67 compared to R 2 value of 0.09) (Supplementary Table  S3 and Supplementary Table  S4 ). ANN models showed intermediate performance, likely because neural networks typically perform best with larger datasets 66 . The SVR shows intermediate performance, mostly due to the weak predictions of specific attributes that lower the overall performance (Supplementary Table  S4 ).

Model dissection identifies specific, unexpected compounds as drivers of consumer appreciation

Next, we leveraged our models to infer important contributors to sensory perception and consumer appreciation. Consumer preference is a crucial sensory aspects, because a product that shows low consumer appreciation scores often does not succeed commercially 25 . Additionally, the requirement for a large number of representative evaluators makes consumer trials one of the more costly and time-consuming aspects of product development. Hence, a model for predicting chemical drivers of overall appreciation would be a welcome addition to the available toolbox for food development and optimization.

Since GBR models on our RateBeer dataset showed the best overall performance, we focused on these models. Specifically, we used two approaches to identify important contributors. First, rankings of the most important predictors for each sensorial trait in the GBR models were obtained based on impurity-based feature importance (mean decrease in impurity). High-ranked parameters were hypothesized to be either the true causal chemical properties underlying the trait, to correlate with the actual causal properties, or to take part in sensory interactions affecting the trait 67 (Fig.  4A ). In a second approach, we used SHAP 68 to determine which parameters contributed most to the model for making predictions of consumer appreciation (Fig.  4B ). SHAP calculates parameter contributions to model predictions on a per-sample basis, which can be aggregated into an importance score.

A The impurity-based feature importance (mean deviance in impurity, MDI) calculated from the Gradient Boosting Regression (GBR) model predicting RateBeer appreciation scores. The top 15 highest ranked chemical properties are shown. B SHAP summary plot for the top 15 parameters contributing to our GBR model. Each point on the graph represents a sample from our dataset. The color represents the concentration of that parameter, with bluer colors representing low values and redder colors representing higher values. Greater absolute values on the horizontal axis indicate a higher impact of the parameter on the prediction of the model. C Spearman correlations between the 15 most important chemical properties and consumer overall appreciation. Numbers indicate the Spearman Rho correlation coefficient, and the rank of this correlation compared to all other correlations. The top 15 important compounds were determined using SHAP (panel B).

Both approaches identified ethyl acetate as the most predictive parameter for beer appreciation (Fig.  4 ). Ethyl acetate is the most abundant ester in beer with a typical ‘fruity’, ‘solvent’ and ‘alcoholic’ flavor, but is often considered less important than other esters like isoamyl acetate. The second most important parameter identified by SHAP is ethanol, the most abundant beer compound after water. Apart from directly contributing to beer flavor and mouthfeel, ethanol drastically influences the physical properties of beer, dictating how easily volatile compounds escape the beer matrix to contribute to beer aroma 69 . Importantly, it should also be noted that the importance of ethanol for appreciation is likely inflated by the very low appreciation scores of non-alcoholic beers (Supplementary Fig.  S4 ). Despite not often being considered a driver of beer appreciation, protein level also ranks highly in both approaches, possibly due to its effect on mouthfeel and body 70 . Lactic acid, which contributes to the tart taste of sour beers, is the fourth most important parameter identified by SHAP, possibly due to the generally high appreciation of sour beers in our dataset.

Interestingly, some of the most important predictive parameters for our model are not well-established as beer flavors or are even commonly regarded as being negative for beer quality. For example, our models identify methanethiol and ethyl phenyl acetate, an ester commonly linked to beer staling 71 , as a key factor contributing to beer appreciation. Although there is no doubt that high concentrations of these compounds are considered unpleasant, the positive effects of modest concentrations are not yet known 72 , 73 .

To compare our approach to conventional statistics, we evaluated how well the 15 most important SHAP-derived parameters correlate with consumer appreciation (Fig.  4C ). Interestingly, only 6 of the properties derived by SHAP rank amongst the top 15 most correlated parameters. For some chemical compounds, the correlations are so low that they would have likely been considered unimportant. For example, lactic acid, the fourth most important parameter, shows a bimodal distribution for appreciation, with sour beers forming a separate cluster, that is missed entirely by the Spearman correlation. Additionally, the correlation plots reveal outliers, emphasizing the need for robust analysis tools. Together, this highlights the need for alternative models, like the Gradient Boosting model, that better grasp the complexity of (beer) flavor.

Finally, to observe the relationships between these chemical properties and their predicted targets, partial dependence plots were constructed for the six most important predictors of consumer appreciation 74 , 75 , 76 (Supplementary Fig.  S7 ). One-way partial dependence plots show how a change in concentration affects the predicted appreciation. These plots reveal an important limitation of our models: appreciation predictions remain constant at ever-increasing concentrations. This implies that once a threshold concentration is reached, further increasing the concentration does not affect appreciation. This is false, as it is well-documented that certain compounds become unpleasant at high concentrations, including ethyl acetate (‘nail polish’) 77 and methanethiol (‘sulfury’ and ‘rotten cabbage’) 78 . The inability of our models to grasp that flavor compounds have optimal levels, above which they become negative, is a consequence of working with commercial beer brands where (off-)flavors are rarely too high to negatively impact the product. The two-way partial dependence plots show how changing the concentration of two compounds influences predicted appreciation, visualizing their interactions (Supplementary Fig.  S7 ). In our case, the top 5 parameters are dominated by additive or synergistic interactions, with high concentrations for both compounds resulting in the highest predicted appreciation.

To assess the robustness of our best-performing models and model predictions, we performed 100 iterations of the GBR, RF and ET models. In general, all iterations of the models yielded similar performance (Supplementary Fig.  S8 ). Moreover, the main predictors (including the top predictors ethanol and ethyl acetate) remained virtually the same, especially for GBR and RF. For the iterations of the ET model, we did observe more variation in the top predictors, which is likely a consequence of the model’s inherent random architecture in combination with co-correlations between certain predictors. However, even in this case, several of the top predictors (ethanol and ethyl acetate) remain unchanged, although their rank in importance changes (Supplementary Fig.  S8 ).

Next, we investigated if a combination of RateBeer and trained panel data into one consolidated dataset would lead to stronger models, under the hypothesis that such a model would suffer less from bias in the datasets. A GBR model was trained to predict appreciation on the combined dataset. This model underperformed compared to the RateBeer model, both in the native case and when including a dataset identifier (R 2  = 0.67, 0.26 and 0.42 respectively). For the latter, the dataset identifier is the most important feature (Supplementary Fig.  S9 ), while most of the feature importance remains unchanged, with ethyl acetate and ethanol ranking highest, like in the original model trained only on RateBeer data. It seems that the large variation in the panel dataset introduces noise, weakening the models’ performances and reliability. In addition, it seems reasonable to assume that both datasets are fundamentally different, with the panel dataset obtained by blind tastings by a trained professional panel.

Lastly, we evaluated whether beer style identifiers would further enhance the model’s performance. A GBR model was trained with parameters that explicitly encoded the styles of the samples. This did not improve model performance (R2 = 0.66 with style information vs R2 = 0.67). The most important chemical features are consistent with the model trained without style information (eg. ethanol and ethyl acetate), and with the exception of the most preferred (strong ale) and least preferred (low/no-alcohol) styles, none of the styles were among the most important features (Supplementary Fig.  S9 , Supplementary Table  S5 and S6 ). This is likely due to a combination of style-specific chemical signatures, such as iso-alpha acids and lactic acid, that implicitly convey style information to the original models, as well as the low number of samples belonging to some styles, making it difficult for the model to learn style-specific patterns. Moreover, beer styles are not rigorously defined, with some styles overlapping in features and some beers being misattributed to a specific style, all of which leads to more noise in models that use style parameters.

Model validation

To test if our predictive models give insight into beer appreciation, we set up experiments aimed at improving existing commercial beers. We specifically selected overall appreciation as the trait to be examined because of its complexity and commercial relevance. Beer flavor comprises a complex bouquet rather than single aromas and tastes 53 . Hence, adding a single compound to the extent that a difference is noticeable may lead to an unbalanced, artificial flavor. Therefore, we evaluated the effect of combinations of compounds. Because Blond beers represent the most extensive style in our dataset, we selected a beer from this style as the starting material for these experiments (Beer 64 in Supplementary Data  1 ).

In the first set of experiments, we adjusted the concentrations of compounds that made up the most important predictors of overall appreciation (ethyl acetate, ethanol, lactic acid, ethyl phenyl acetate) together with correlated compounds (ethyl hexanoate, isoamyl acetate, glycerol), bringing them up to 95 th percentile ethanol-normalized concentrations (Methods) within the Blond group (‘Spiked’ concentration in Fig.  5A ). Compared to controls, the spiked beers were found to have significantly improved overall appreciation among trained panelists, with panelist noting increased intensity of ester flavors, sweetness, alcohol, and body fullness (Fig.  5B ). To disentangle the contribution of ethanol to these results, a second experiment was performed without the addition of ethanol. This resulted in a similar outcome, including increased perception of alcohol and overall appreciation.

Adding the top chemical compounds, identified as best predictors of appreciation by our model, into poorly appreciated beers results in increased appreciation from our trained panel. Results of sensory tests between base beers and those spiked with compounds identified as the best predictors by the model. A Blond and Non/Low-alcohol (0.0% ABV) base beers were brought up to 95th-percentile ethanol-normalized concentrations within each style. B For each sensory attribute, tasters indicated the more intense sample and selected the sample they preferred. The numbers above the bars correspond to the p values that indicate significant changes in perceived flavor (two-sided binomial test: alpha 0.05, n  = 20 or 13).

In a last experiment, we tested whether using the model’s predictions can boost the appreciation of a non-alcoholic beer (beer 223 in Supplementary Data  1 ). Again, the addition of a mixture of predicted compounds (omitting ethanol, in this case) resulted in a significant increase in appreciation, body, ester flavor and sweetness.

Predicting flavor and consumer appreciation from chemical composition is one of the ultimate goals of sensory science. A reliable, systematic and unbiased way to link chemical profiles to flavor and food appreciation would be a significant asset to the food and beverage industry. Such tools would substantially aid in quality control and recipe development, offer an efficient and cost-effective alternative to pilot studies and consumer trials and would ultimately allow food manufacturers to produce superior, tailor-made products that better meet the demands of specific consumer groups more efficiently.

A limited set of studies have previously tried, to varying degrees of success, to predict beer flavor and beer popularity based on (a limited set of) chemical compounds and flavors 79 , 80 . Current sensitive, high-throughput technologies allow measuring an unprecedented number of chemical compounds and properties in a large set of samples, yielding a dataset that can train models that help close the gaps between chemistry and flavor, even for a complex natural product like beer. To our knowledge, no previous research gathered data at this scale (250 samples, 226 chemical parameters, 50 sensory attributes and 5 consumer scores) to disentangle and validate the chemical aspects driving beer preference using various machine-learning techniques. We find that modern machine learning models outperform conventional statistical tools, such as correlations and linear models, and can successfully predict flavor appreciation from chemical composition. This could be attributed to the natural incorporation of interactions and non-linear or discontinuous effects in machine learning models, which are not easily grasped by the linear model architecture. While linear models and partial least squares regression represent the most widespread statistical approaches in sensory science, in part because they allow interpretation 65 , 81 , 82 , modern machine learning methods allow for building better predictive models while preserving the possibility to dissect and exploit the underlying patterns. Of the 10 different models we trained, tree-based models, such as our best performing GBR, showed the best overall performance in predicting sensory responses from chemical information, outcompeting artificial neural networks. This agrees with previous reports for models trained on tabular data 83 . Our results are in line with the findings of Colantonio et al. who also identified the gradient boosting architecture as performing best at predicting appreciation and flavor (of tomatoes and blueberries, in their specific study) 26 . Importantly, besides our larger experimental scale, we were able to directly confirm our models’ predictions in vivo.

Our study confirms that flavor compound concentration does not always correlate with perception, suggesting complex interactions that are often missed by more conventional statistics and simple models. Specifically, we find that tree-based algorithms may perform best in developing models that link complex food chemistry with aroma. Furthermore, we show that massive datasets of untrained consumer reviews provide a valuable source of data, that can complement or even replace trained tasting panels, especially for appreciation and basic flavors, such as sweetness and bitterness. This holds despite biases that are known to occur in such datasets, such as price or conformity bias. Moreover, GBR models predict taste better than aroma. This is likely because taste (e.g. bitterness) often directly relates to the corresponding chemical measurements (e.g., iso-alpha acids), whereas such a link is less clear for aromas, which often result from the interplay between multiple volatile compounds. We also find that our models are best at predicting acidity and alcohol, likely because there is a direct relation between the measured chemical compounds (acids and ethanol) and the corresponding perceived sensorial attribute (acidity and alcohol), and because even untrained consumers are generally able to recognize these flavors and aromas.

The predictions of our final models, trained on review data, hold even for blind tastings with small groups of trained tasters, as demonstrated by our ability to validate specific compounds as drivers of beer flavor and appreciation. Since adding a single compound to the extent of a noticeable difference may result in an unbalanced flavor profile, we specifically tested our identified key drivers as a combination of compounds. While this approach does not allow us to validate if a particular single compound would affect flavor and/or appreciation, our experiments do show that this combination of compounds increases consumer appreciation.

It is important to stress that, while it represents an important step forward, our approach still has several major limitations. A key weakness of the GBR model architecture is that amongst co-correlating variables, the largest main effect is consistently preferred for model building. As a result, co-correlating variables often have artificially low importance scores, both for impurity and SHAP-based methods, like we observed in the comparison to the more randomized Extra Trees models. This implies that chemicals identified as key drivers of a specific sensory feature by GBR might not be the true causative compounds, but rather co-correlate with the actual causative chemical. For example, the high importance of ethyl acetate could be (partially) attributed to the total ester content, ethanol or ethyl hexanoate (rho=0.77, rho=0.72 and rho=0.68), while ethyl phenylacetate could hide the importance of prenyl isobutyrate and ethyl benzoate (rho=0.77 and rho=0.76). Expanding our GBR model to include beer style as a parameter did not yield additional power or insight. This is likely due to style-specific chemical signatures, such as iso-alpha acids and lactic acid, that implicitly convey style information to the original model, as well as the smaller sample size per style, limiting the power to uncover style-specific patterns. This can be partly attributed to the curse of dimensionality, where the high number of parameters results in the models mainly incorporating single parameter effects, rather than complex interactions such as style-dependent effects 67 . A larger number of samples may overcome some of these limitations and offer more insight into style-specific effects. On the other hand, beer style is not a rigid scientific classification, and beers within one style often differ a lot, which further complicates the analysis of style as a model factor.

Our study is limited to beers from Belgian breweries. Although these beers cover a large portion of the beer styles available globally, some beer styles and consumer patterns may be missing, while other features might be overrepresented. For example, many Belgian ales exhibit yeast-driven flavor profiles, which is reflected in the chemical drivers of appreciation discovered by this study. In future work, expanding the scope to include diverse markets and beer styles could lead to the identification of even more drivers of appreciation and better models for special niche products that were not present in our beer set.

In addition to inherent limitations of GBR models, there are also some limitations associated with studying food aroma. Even if our chemical analyses measured most of the known aroma compounds, the total number of flavor compounds in complex foods like beer is still larger than the subset we were able to measure in this study. For example, hop-derived thiols, that influence flavor at very low concentrations, are notoriously difficult to measure in a high-throughput experiment. Moreover, consumer perception remains subjective and prone to biases that are difficult to avoid. It is also important to stress that the models are still immature and that more extensive datasets will be crucial for developing more complete models in the future. Besides more samples and parameters, our dataset does not include any demographic information about the tasters. Including such data could lead to better models that grasp external factors like age and culture. Another limitation is that our set of beers consists of high-quality end-products and lacks beers that are unfit for sale, which limits the current model in accurately predicting products that are appreciated very badly. Finally, while models could be readily applied in quality control, their use in sensory science and product development is restrained by their inability to discern causal relationships. Given that the models cannot distinguish compounds that genuinely drive consumer perception from those that merely correlate, validation experiments are essential to identify true causative compounds.

Despite the inherent limitations, dissection of our models enabled us to pinpoint specific molecules as potential drivers of beer aroma and consumer appreciation, including compounds that were unexpected and would not have been identified using standard approaches. Important drivers of beer appreciation uncovered by our models include protein levels, ethyl acetate, ethyl phenyl acetate and lactic acid. Currently, many brewers already use lactic acid to acidify their brewing water and ensure optimal pH for enzymatic activity during the mashing process. Our results suggest that adding lactic acid can also improve beer appreciation, although its individual effect remains to be tested. Interestingly, ethanol appears to be unnecessary to improve beer appreciation, both for blond beer and alcohol-free beer. Given the growing consumer interest in alcohol-free beer, with a predicted annual market growth of >7% 84 , it is relevant for brewers to know what compounds can further increase consumer appreciation of these beers. Hence, our model may readily provide avenues to further improve the flavor and consumer appreciation of both alcoholic and non-alcoholic beers, which is generally considered one of the key challenges for future beer production.

Whereas we see a direct implementation of our results for the development of superior alcohol-free beverages and other food products, our study can also serve as a stepping stone for the development of novel alcohol-containing beverages. We want to echo the growing body of scientific evidence for the negative effects of alcohol consumption, both on the individual level by the mutagenic, teratogenic and carcinogenic effects of ethanol 85 , 86 , as well as the burden on society caused by alcohol abuse and addiction. We encourage the use of our results for the production of healthier, tastier products, including novel and improved beverages with lower alcohol contents. Furthermore, we strongly discourage the use of these technologies to improve the appreciation or addictive properties of harmful substances.

The present work demonstrates that despite some important remaining hurdles, combining the latest developments in chemical analyses, sensory analysis and modern machine learning methods offers exciting avenues for food chemistry and engineering. Soon, these tools may provide solutions in quality control and recipe development, as well as new approaches to sensory science and flavor research.

Beer selection

250 commercial Belgian beers were selected to cover the broad diversity of beer styles and corresponding diversity in chemical composition and aroma. See Supplementary Fig.  S1 .

Chemical dataset

Sample preparation.

Beers within their expiration date were purchased from commercial retailers. Samples were prepared in biological duplicates at room temperature, unless explicitly stated otherwise. Bottle pressure was measured with a manual pressure device (Steinfurth Mess-Systeme GmbH) and used to calculate CO 2 concentration. The beer was poured through two filter papers (Macherey-Nagel, 500713032 MN 713 ¼) to remove carbon dioxide and prevent spontaneous foaming. Samples were then prepared for measurements by targeted Headspace-Gas Chromatography-Flame Ionization Detector/Flame Photometric Detector (HS-GC-FID/FPD), Headspace-Solid Phase Microextraction-Gas Chromatography-Mass Spectrometry (HS-SPME-GC-MS), colorimetric analysis, enzymatic analysis, Near-Infrared (NIR) analysis, as described in the sections below. The mean values of biological duplicates are reported for each compound.

HS-GC-FID/FPD

HS-GC-FID/FPD (Shimadzu GC 2010 Plus) was used to measure higher alcohols, acetaldehyde, esters, 4-vinyl guaicol, and sulfur compounds. Each measurement comprised 5 ml of sample pipetted into a 20 ml glass vial containing 1.75 g NaCl (VWR, 27810.295). 100 µl of 2-heptanol (Sigma-Aldrich, H3003) (internal standard) solution in ethanol (Fisher Chemical, E/0650DF/C17) was added for a final concentration of 2.44 mg/L. Samples were flushed with nitrogen for 10 s, sealed with a silicone septum, stored at −80 °C and analyzed in batches of 20.

The GC was equipped with a DB-WAXetr column (length, 30 m; internal diameter, 0.32 mm; layer thickness, 0.50 µm; Agilent Technologies, Santa Clara, CA, USA) to the FID and an HP-5 column (length, 30 m; internal diameter, 0.25 mm; layer thickness, 0.25 µm; Agilent Technologies, Santa Clara, CA, USA) to the FPD. N 2 was used as the carrier gas. Samples were incubated for 20 min at 70 °C in the headspace autosampler (Flow rate, 35 cm/s; Injection volume, 1000 µL; Injection mode, split; Combi PAL autosampler, CTC analytics, Switzerland). The injector, FID and FPD temperatures were kept at 250 °C. The GC oven temperature was first held at 50 °C for 5 min and then allowed to rise to 80 °C at a rate of 5 °C/min, followed by a second ramp of 4 °C/min until 200 °C kept for 3 min and a final ramp of (4 °C/min) until 230 °C for 1 min. Results were analyzed with the GCSolution software version 2.4 (Shimadzu, Kyoto, Japan). The GC was calibrated with a 5% EtOH solution (VWR International) containing the volatiles under study (Supplementary Table  S7 ).

HS-SPME-GC-MS

HS-SPME-GC-MS (Shimadzu GCMS-QP-2010 Ultra) was used to measure additional volatile compounds, mainly comprising terpenoids and esters. Samples were analyzed by HS-SPME using a triphase DVB/Carboxen/PDMS 50/30 μm SPME fiber (Supelco Co., Bellefonte, PA, USA) followed by gas chromatography (Thermo Fisher Scientific Trace 1300 series, USA) coupled to a mass spectrometer (Thermo Fisher Scientific ISQ series MS) equipped with a TriPlus RSH autosampler. 5 ml of degassed beer sample was placed in 20 ml vials containing 1.75 g NaCl (VWR, 27810.295). 5 µl internal standard mix was added, containing 2-heptanol (1 g/L) (Sigma-Aldrich, H3003), 4-fluorobenzaldehyde (1 g/L) (Sigma-Aldrich, 128376), 2,3-hexanedione (1 g/L) (Sigma-Aldrich, 144169) and guaiacol (1 g/L) (Sigma-Aldrich, W253200) in ethanol (Fisher Chemical, E/0650DF/C17). Each sample was incubated at 60 °C in the autosampler oven with constant agitation. After 5 min equilibration, the SPME fiber was exposed to the sample headspace for 30 min. The compounds trapped on the fiber were thermally desorbed in the injection port of the chromatograph by heating the fiber for 15 min at 270 °C.

The GC-MS was equipped with a low polarity RXi-5Sil MS column (length, 20 m; internal diameter, 0.18 mm; layer thickness, 0.18 µm; Restek, Bellefonte, PA, USA). Injection was performed in splitless mode at 320 °C, a split flow of 9 ml/min, a purge flow of 5 ml/min and an open valve time of 3 min. To obtain a pulsed injection, a programmed gas flow was used whereby the helium gas flow was set at 2.7 mL/min for 0.1 min, followed by a decrease in flow of 20 ml/min to the normal 0.9 mL/min. The temperature was first held at 30 °C for 3 min and then allowed to rise to 80 °C at a rate of 7 °C/min, followed by a second ramp of 2 °C/min till 125 °C and a final ramp of 8 °C/min with a final temperature of 270 °C.

Mass acquisition range was 33 to 550 amu at a scan rate of 5 scans/s. Electron impact ionization energy was 70 eV. The interface and ion source were kept at 275 °C and 250 °C, respectively. A mix of linear n-alkanes (from C7 to C40, Supelco Co.) was injected into the GC-MS under identical conditions to serve as external retention index markers. Identification and quantification of the compounds were performed using an in-house developed R script as described in Goelen et al. and Reher et al. 87 , 88 (for package information, see Supplementary Table  S8 ). Briefly, chromatograms were analyzed using AMDIS (v2.71) 89 to separate overlapping peaks and obtain pure compound spectra. The NIST MS Search software (v2.0 g) in combination with the NIST2017, FFNSC3 and Adams4 libraries were used to manually identify the empirical spectra, taking into account the expected retention time. After background subtraction and correcting for retention time shifts between samples run on different days based on alkane ladders, compound elution profiles were extracted and integrated using a file with 284 target compounds of interest, which were either recovered in our identified AMDIS list of spectra or were known to occur in beer. Compound elution profiles were estimated for every peak in every chromatogram over a time-restricted window using weighted non-negative least square analysis after which peak areas were integrated 87 , 88 . Batch effect correction was performed by normalizing against the most stable internal standard compound, 4-fluorobenzaldehyde. Out of all 284 target compounds that were analyzed, 167 were visually judged to have reliable elution profiles and were used for final analysis.

Discrete photometric and enzymatic analysis

Discrete photometric and enzymatic analysis (Thermo Scientific TM Gallery TM Plus Beermaster Discrete Analyzer) was used to measure acetic acid, ammonia, beta-glucan, iso-alpha acids, color, sugars, glycerol, iron, pH, protein, and sulfite. 2 ml of sample volume was used for the analyses. Information regarding the reagents and standard solutions used for analyses and calibrations is included in Supplementary Table  S7 and Supplementary Table  S9 .

NIR analyses

NIR analysis (Anton Paar Alcolyzer Beer ME System) was used to measure ethanol. Measurements comprised 50 ml of sample, and a 10% EtOH solution was used for calibration.

Correlation calculations

Pairwise Spearman Rank correlations were calculated between all chemical properties.

Sensory dataset

Trained panel.

Our trained tasting panel consisted of volunteers who gave prior verbal informed consent. All compounds used for the validation experiment were of food-grade quality. The tasting sessions were approved by the Social and Societal Ethics Committee of the KU Leuven (G-2022-5677-R2(MAR)). All online reviewers agreed to the Terms and Conditions of the RateBeer website.

Sensory analysis was performed according to the American Society of Brewing Chemists (ASBC) Sensory Analysis Methods 90 . 30 volunteers were screened through a series of triangle tests. The sixteen most sensitive and consistent tasters were retained as taste panel members. The resulting panel was diverse in age [22–42, mean: 29], sex [56% male] and nationality [7 different countries]. The panel developed a consensus vocabulary to describe beer aroma, taste and mouthfeel. Panelists were trained to identify and score 50 different attributes, using a 7-point scale to rate attributes’ intensity. The scoring sheet is included as Supplementary Data  3 . Sensory assessments took place between 10–12 a.m. The beers were served in black-colored glasses. Per session, between 5 and 12 beers of the same style were tasted at 12 °C to 16 °C. Two reference beers were added to each set and indicated as ‘Reference 1 & 2’, allowing panel members to calibrate their ratings. Not all panelists were present at every tasting. Scores were scaled by standard deviation and mean-centered per taster. Values are represented as z-scores and clustered by Euclidean distance. Pairwise Spearman correlations were calculated between taste and aroma sensory attributes. Panel consistency was evaluated by repeating samples on different sessions and performing ANOVA to identify differences, using the ‘stats’ package (v4.2.2) in R (for package information, see Supplementary Table  S8 ).

Online reviews from a public database

The ‘scrapy’ package in Python (v3.6) (for package information, see Supplementary Table  S8 ). was used to collect 232,288 online reviews (mean=922, min=6, max=5343) from RateBeer, an online beer review database. Each review entry comprised 5 numerical scores (appearance, aroma, taste, palate and overall quality) and an optional review text. The total number of reviews per reviewer was collected separately. Numerical scores were scaled and centered per rater, and mean scores were calculated per beer.

For the review texts, the language was estimated using the packages ‘langdetect’ and ‘langid’ in Python. Reviews that were classified as English by both packages were kept. Reviewers with fewer than 100 entries overall were discarded. 181,025 reviews from >6000 reviewers from >40 countries remained. Text processing was done using the ‘nltk’ package in Python. Texts were corrected for slang and misspellings; proper nouns and rare words that are relevant to the beer context were specified and kept as-is (‘Chimay’,’Lambic’, etc.). A dictionary of semantically similar sensorial terms, for example ‘floral’ and ‘flower’, was created and collapsed together into one term. Words were stemmed and lemmatized to avoid identifying words such as ‘acid’ and ‘acidity’ as separate terms. Numbers and punctuation were removed.

Sentences from up to 50 randomly chosen reviews per beer were manually categorized according to the aspect of beer they describe (appearance, aroma, taste, palate, overall quality—not to be confused with the 5 numerical scores described above) or flagged as irrelevant if they contained no useful information. If a beer contained fewer than 50 reviews, all reviews were manually classified. This labeled data set was used to train a model that classified the rest of the sentences for all beers 91 . Sentences describing taste and aroma were extracted, and term frequency–inverse document frequency (TFIDF) was implemented to calculate enrichment scores for sensorial words per beer.

The sex of the tasting subject was not considered when building our sensory database. Instead, results from different panelists were averaged, both for our trained panel (56% male, 44% female) and the RateBeer reviews (70% male, 30% female for RateBeer as a whole).

Beer price collection and processing

Beer prices were collected from the following stores: Colruyt, Delhaize, Total Wine, BeerHawk, The Belgian Beer Shop, The Belgian Shop, and Beer of Belgium. Where applicable, prices were converted to Euros and normalized per liter. Spearman correlations were calculated between these prices and mean overall appreciation scores from RateBeer and the taste panel, respectively.

Pairwise Spearman Rank correlations were calculated between all sensory properties.

Machine learning models

Predictive modeling of sensory profiles from chemical data.

Regression models were constructed to predict (a) trained panel scores for beer flavors and quality from beer chemical profiles and (b) public reviews’ appreciation scores from beer chemical profiles. Z-scores were used to represent sensory attributes in both data sets. Chemical properties with log-normal distributions (Shapiro-Wilk test, p  <  0.05 ) were log-transformed. Missing chemical measurements (0.1% of all data) were replaced with mean values per attribute. Observations from 250 beers were randomly separated into a training set (70%, 175 beers) and a test set (30%, 75 beers), stratified per beer style. Chemical measurements (p = 231) were normalized based on the training set average and standard deviation. In total, three linear regression-based models: linear regression with first-order interaction terms (LR), lasso regression with first-order interaction terms (Lasso) and partial least squares regression (PLSR); five decision tree models, Adaboost regressor (ABR), Extra Trees (ET), Gradient Boosting regressor (GBR), Random Forest (RF) and XGBoost regressor (XGBR); one support vector machine model (SVR) and one artificial neural network model (ANN) were trained. The models were implemented using the ‘scikit-learn’ package (v1.2.2) and ‘xgboost’ package (v1.7.3) in Python (v3.9.16). Models were trained, and hyperparameters optimized, using five-fold cross-validated grid search with the coefficient of determination (R 2 ) as the evaluation metric. The ANN (scikit-learn’s MLPRegressor) was optimized using Bayesian Tree-Structured Parzen Estimator optimization with the ‘Optuna’ Python package (v3.2.0). Individual models were trained per attribute, and a multi-output model was trained on all attributes simultaneously.

Model dissection

GBR was found to outperform other methods, resulting in models with the highest average R 2 values in both trained panel and public review data sets. Impurity-based rankings of the most important predictors for each predicted sensorial trait were obtained using the ‘scikit-learn’ package. To observe the relationships between these chemical properties and their predicted targets, partial dependence plots (PDP) were constructed for the six most important predictors of consumer appreciation 74 , 75 .

The ‘SHAP’ package in Python (v0.41.0) was implemented to provide an alternative ranking of predictor importance and to visualize the predictors’ effects as a function of their concentration 68 .

Validation of causal chemical properties

To validate the effects of the most important model features on predicted sensory attributes, beers were spiked with the chemical compounds identified by the models and descriptive sensory analyses were carried out according to the American Society of Brewing Chemists (ASBC) protocol 90 .

Compound spiking was done 30 min before tasting. Compounds were spiked into fresh beer bottles, that were immediately resealed and inverted three times. Fresh bottles of beer were opened for the same duration, resealed, and inverted thrice, to serve as controls. Pairs of spiked samples and controls were served simultaneously, chilled and in dark glasses as outlined in the Trained panel section above. Tasters were instructed to select the glass with the higher flavor intensity for each attribute (directional difference test 92 ) and to select the glass they prefer.

The final concentration after spiking was equal to the within-style average, after normalizing by ethanol concentration. This was done to ensure balanced flavor profiles in the final spiked beer. The same methods were applied to improve a non-alcoholic beer. Compounds were the following: ethyl acetate (Merck KGaA, W241415), ethyl hexanoate (Merck KGaA, W243906), isoamyl acetate (Merck KGaA, W205508), phenethyl acetate (Merck KGaA, W285706), ethanol (96%, Colruyt), glycerol (Merck KGaA, W252506), lactic acid (Merck KGaA, 261106).

Significant differences in preference or perceived intensity were determined by performing the two-sided binomial test on each attribute.

Reporting summary

Further information on research design is available in the  Nature Portfolio Reporting Summary linked to this article.

Data availability

The data that support the findings of this work are available in the Supplementary Data files and have been deposited to Zenodo under accession code 10653704 93 . The RateBeer scores data are under restricted access, they are not publicly available as they are property of RateBeer (ZX Ventures, USA). Access can be obtained from the authors upon reasonable request and with permission of RateBeer (ZX Ventures, USA).  Source data are provided with this paper.

Code availability

The code for training the machine learning models, analyzing the models, and generating the figures has been deposited to Zenodo under accession code 10653704 93 .

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Acknowledgements

We thank all lab members for their discussions and thank all tasting panel members for their contributions. Special thanks go out to Dr. Karin Voordeckers for her tremendous help in proofreading and improving the manuscript. M.S. was supported by a Baillet-Latour fellowship, L.C. acknowledges financial support from KU Leuven (C16/17/006), F.A.T. was supported by a PhD fellowship from FWO (1S08821N). Research in the lab of K.J.V. is supported by KU Leuven, FWO, VIB, VLAIO and the Brewing Science Serves Health Fund. Research in the lab of T.W. is supported by FWO (G.0A51.15) and KU Leuven (C16/17/006).

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These authors contributed equally: Michiel Schreurs, Supinya Piampongsant, Miguel Roncoroni.

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VIB—KU Leuven Center for Microbiology, Gaston Geenslaan 1, B-3001, Leuven, Belgium

Michiel Schreurs, Supinya Piampongsant, Miguel Roncoroni, Lloyd Cool, Beatriz Herrera-Malaver, Florian A. Theßeling & Kevin J. Verstrepen

CMPG Laboratory of Genetics and Genomics, KU Leuven, Gaston Geenslaan 1, B-3001, Leuven, Belgium

Leuven Institute for Beer Research (LIBR), Gaston Geenslaan 1, B-3001, Leuven, Belgium

Laboratory of Socioecology and Social Evolution, KU Leuven, Naamsestraat 59, B-3000, Leuven, Belgium

Lloyd Cool, Christophe Vanderaa & Tom Wenseleers

VIB Bioinformatics Core, VIB, Rijvisschestraat 120, B-9052, Ghent, Belgium

Łukasz Kreft & Alexander Botzki

AB InBev SA/NV, Brouwerijplein 1, B-3000, Leuven, Belgium

Philippe Malcorps & Luk Daenen

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Contributions

S.P., M.S. and K.J.V. conceived the experiments. S.P., M.S. and K.J.V. designed the experiments. S.P., M.S., M.R., B.H. and F.A.T. performed the experiments. S.P., M.S., L.C., C.V., L.K., A.B., P.M., L.D., T.W. and K.J.V. contributed analysis ideas. S.P., M.S., L.C., C.V., T.W. and K.J.V. analyzed the data. All authors contributed to writing the manuscript.

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Correspondence to Kevin J. Verstrepen .

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Schreurs, M., Piampongsant, S., Roncoroni, M. et al. Predicting and improving complex beer flavor through machine learning. Nat Commun 15 , 2368 (2024). https://doi.org/10.1038/s41467-024-46346-0

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Encapsulation is a drug or food ingredient loaded-delivery system that entraps active components, protecting them from decomposition/degradation throughout the processing and storage stages and facilitates their delivery to the target tissue/organ, improving their bioactivities. The application of this technology is expanding gradually from pharmaceuticals to the food industry, since dietary bioactive ingredients, including polyphenols, are susceptible to environmental and/or gastrointestinal conditions. Polyphenols are the largest group of plants' secondary metabolites, with a wide range of biological effects. Literature data have indicated their potential in the prevention of several disorders and pathologies, ranging from simpler allergic conditions to more complex metabolic syndrome and cardiovascular and neurodegenerative diseases. Despite the promising health effects in preclinical studies, the clinical use of dietary polyphenols is still very limited due to their low bioaccessibility and/or bioavailability. Encapsulation can be successfully employed in the development of polyphenol-based functional foods, which may improve their bioaccessibility and/or bioavailability. Moreover, encapsulation can also aid in the targeted delivery of polyphenols and may prevent any possible adverse events. For the encapsulation of bioactive ingredients, several techniques are applied such as emulsion phase separation, emulsification/internal gelation, film formation, spray drying, spray-bed-drying, fluid-bed coating, spray-chilling, spray-cooling, and melt injection. The present review aims to throw light on the existing literature highlighting the possibility and clinical benefits of encapsulated polyphenols in health and disease. However, the clinical data is still very scarce and randomized clinical trials are needed before any conclusion is drawn.

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Introduction

Polyphenols are one of the largest groups of plant secondary metabolites, containing benzene rings with hydroxyl (OH) moieties, and are categorized into flavonoids and non-flavonoids. Flavonoids share a common carbon skeleton of diphenyl propane, two benzene rings (rings A and B) joined by a linear three-carbon chain. The central three-carbon chain forms a closed pyran ring (ring C) with A benzene ring. Depending on the oxidation state of the central pyran ring and substitution patterns, flavonoids can be subdivided into flavones, isoflavones, flavonols, flavan-3-ols, flavanones, and anthocyanidins. Non-flavonoid polyphenols can be subdivided into benzoic acid derivatives, cinnamic acid derivatives, stilbenes, lignans, and curcuminoids (Ullah et al. 2020 ). Polyphenols are potent antioxidants abundantly found in the human diet including fruits, vegetables, and beverages. Flavonoids account for two-thirds of the total polyphenols intake while phenolic acids account for the remaining one-third. The flavonoids most abundantly found in the human diet include flavanols (especially catechins and proanthocyanidins), anthocyanins, and their oxidation products (Han et al. 2007 ). Dietary polyphenols may modulate numerous signalling pathways at cellular and molecular levels, resulting in protecting individuals against oxidative stress and inflammation, which are at the basis of many chronic degenerative disease developments. They play a beneficial role as cardioprotective, antidiabetic, antimicrobial, antiplatelet, antiasthma, neuroprotective, anxiolytic and antidepressant, and anticarcinogenic agents, to name a few (Daglia 2012 ; Khan et al. 2018 , 2019 ; Ullah et al. 2022 ). The global market of polyphenols is considerably increasing with 1.68 billion dollars reported in 2022 (Grand View Research 2023 ).

Despite the wide range of reported health effects, the use of polyphenols in food supplements and functional foods has not been optimally realized because of their poor oral bioaccessibility and bioavailability, which derive from their physiochemical properties (i.e., limited liberation from the food matrix (Moelants et al. 2012 ), poor solubility in gastrointestinal fluids (Porter et al. 2007 ; Pouton and Porter 2008 ), low permeability across the epithelial cells (Martinez and Amidon 2002 ; Actis-Goretta et al. 2013 ), and/or molecular transformations in the gastrointestinal tract (Barros and Junior 2019 ). The low bioaccessibility and bioavailability of polyphenols not only depend on the intrinsic properties of phenolic compounds (i.e., anthocyanins) but also the food matrix effect, the presence of specific transporters, and so on. Polyphenols also interact with gut microbiota strains in the colon, leading to deep modification of molecules. In addition, the low stability of dietary polyphenols to denaturing conditions such as pH, enzymes, heat, light, and oxygen further limits the utilization of polyphenols as functional ingredients. Depending on the aforementioned factors, the amount of polyphenols that can reach the intestine, be absorbed, and be distributed at the tissue level varies greatly, being often very low, affecting the exerted beneficial effects on human health (Yang et al. 2008 ; Cao et al. 2021 ). The bioavailability of dietary polyphenols may also be affected by the interaction with other dietary components such as carbohydrates, proteins, fats, dietary fibers, and alcohol. For instance, different fat contents increase the oral absorption of flavonoids while cellular uptake of polyphenol metabolites may be affected by the plasma proteins binding. Their affinity with plasma albumin may also increase the plasma half-life (i.e., epigallocatechin gallate) and in some cases slow their elimination from the body (i.e., quercetin) and thus increase the likelihood of their side effects (Pandareesh et al. 2015 ). Food processing (juicing of fruits or homogenization of vegetables), nanoformulations, encapsulation, enzymatic treatments (enhanced bioavailability of isoflavones by enzymatic hydrolysis of nonfermented soy drink with β-glucosidase), food-based fermentation (to break down the complex polyphenols into simpler ones) are some of the technological and biotechnological processes employed to improve the bioavailability of polyphenols (Polia et al. 2022 ).

Encapsulation techniques (known since the 1970s) consist of the entrapping of active ingredients within wall materials, where the active agent can be called core, payload, or internal phase while the wall material can be called coating, carrier material, matrix, capsule, or external phase. The external phase is designed to protect the active agents from deteriorating factors (El-Kader and Abu Hashish 2020 ). These technologies have relevance for the pharmaceutical sector and are also of significant interest to the food industry (Nedovic et al. 2011 ). Many encapsulation techniques are currently used to encapsulate bioactive agents, including emulsion phase separation, emulsification/internal gelation, film formation, spray drying, spray-bed-drying, fluid-bed coating, spray-chilling, spray-cooling or melt injection (Nedovic et al. 2011 ; Bartosz and Irene 2016 ). In recent years, the food industry started to require the protection of functional food components that are generally more susceptible to environmental and/or gastrointestinal conditions (for instance, polyphenols) and thus, encapsulation could be employed as one of the effective protective approaches that may improve the bioavailability and bioactivities of polyphenols. In addition, these techniques can also be used to improve the delivery of active components as well as their controlled release over a prolonged period (Lesmes and McClements 2009 ).

This review aims to show the latest progress in the clinical efficacy of encapsulated phenolic compounds in terms of their therapeutic properties. In order to collect data in this study, several specialized databases, such as Web of Science, Scopus, TRIP database, PubMed/MedLine, and Google Scholar were used for extensive literature surveys. The research was conducted using specific terms related to the topic of the current paper, including “Phenolic compounds”, “Plant extracts”, “Flavonoids”, “Flavones”, “Flavanols”, “Flavonols”, “Flavanones”, “Isoflavones”, “Anthocyanins”, “Non-flavonoids”, “Therapeutic properties”, “Biological activity”, “Encapsulation”, “Spray drying”, “Lignans”, “Tannins”, “Hydroxycinnamic acids”, “Hydroxybenzoic acids”, “Freeze drying”, Extrusion”, “Emulsification”, “Coacervation”, “Molecular inclusion”, “Ionic gelation”, “Clinical trials”, “Pre-clinical trials”, “Drug Delivery”. The research included articles covering the periods of 2011 and 2023 to provide sufficient data by the current papers. The selected papers were manually screened to exclude duplications, non-English communications, and topics that are not relevant to the scope of this investigation. We also excluded editorials, letters, conference abstracts, and uncontrolled observations. The remaining publications were grouped as clinical and non-clinical studies, and subsequently classified according to the class of the phenolic compound by indicating the encapsulation techniques that were applied. Study selection was performed by three independent reviewers. The major outputs of the selected papers were evaluated, and clinical and pre-clinical studies on encapsulated phenolic compounds were presented in tables.

Encapsulation of phenolic compounds and novel delivery methods

Currently, the encapsulation of polyphenolic compounds is gaining much more importance in recent years. There are excellent published reviews discussing the encapsulation of phenolic compounds (Fang and Bhandari 2010 ; Cavalcanti et al. 2011 ; Munin and Edwards-Lévy 2011 ). The encapsulation could be defined as an active compound or mixture coated with a polymer to protect them against any other effects, and that allows a controlled release of the bioactive compounds at specific sites (Dias et al. 2017 ). The encapsulation could cover bad odor and taste and contribute to better appearance and physical properties of the products (Naczk and Shahidi 2006 ). The encapsulation efficiency is influenced by various factors, including the use of coating and active material and interactions between components (Jyothi et al. 2010 ). Due to their low bioavailability properties, the controlled release of active material is very important for phenolic compounds.

The phenolic compounds have low bioavailability, and this may be due to several factors because they will pass via multiple membranes, which are exposed by various pathways. The phenolic acid class has low absorption, water solubility, and a high metabolism rate, thus leading to low bioavailability. This problem could be overcome via a controlled release in the targeted cells. This method is an approach of targeted delivery and requires safeguarding the active material while passing via the digestive tract, which accounts for the drug being delivered at the site of action, where it can be absorbed and produce its beneficial effects. Therefore, taking these into consideration, the encapsulation technique could be an interesting concept. The encapsulation process requires the use of different coating materials, which could increase the bioavailability of the active material. Previous reports showed that most information on the bioavailability of encapsulated phenolic compounds regarded quercetin, catechins, anthocyanins, etc. (Grgić et al. 2020 ).

The capsules can be further divided, i.e. if the size of the capsule is less than 1 µm, they are termed nano-capsules and if it is 3–800 µm they are termed microcapsules (del Rio et al. 2013 ; Ezhilarasi et al. 2013 ). There are many encapsulation methods that are suitable for the development of food ingredients. Several factors account for choosing the encapsulation technique (i.e., compound or mixture to be encapsulated, properties of the capsules such as morphology and their size). Therefore, encapsulation efficiency should be developed by considering these parameters. The different types of encapsulation techniques are discussed in Fig.  1 .

Different encapsulation techniques and coating materials used to increase the bioavailability of polyphenolic compounds

Encapsulation by spray-drying The spray-drying technique is a commonly used method, as it has many advantages, which are low cost, easy scale-up, and better final product features (González-Barrio et al. 2010 ; Ezhilarasi et al. 2013 ). The principle of the spray-drying technique is the preparation of the wall material by mixing the components, which are passed through a nozzle or spinning wheel in a hot chamber, where the mixture is atomized. The mixture in contact with hot air evaporates the solvent and solidifies the active material. Therefore, the resulting mixture is in the form of powder, which is collected at the bottom of the instrument (Fang and Bhandari 2010 ). The spray-drying technique is a suitable technique for encapsulating many compounds or active materials and could provide support to the encapsulated material and help to increase its shelf life. This technique has a disadvantage as it has a limited number of wall materials (Fang and Bhandari 2010 ; Pillai et al. 2012 ).

Encapsulation by freeze-drying (Lyophilization) This technique works by freezing the active materials to form ice, which is further transferred to vacuum chambers. Further, it creates a porous material to provide a good final powdered product (Fang and Bhandari 2010 ). This technique is simple, especially for the encapsulation of aromas and volatile oils, which are sensitive to high temperatures. The major disadvantage of this technique is that it takes a long time to remove water and has high economic and energy costs (Pillai et al. 2012 ; Ishwarya et al. 2015 ; Vulić et al. 2019 ).

Encapsulation by extrusion In this process, the solution containing the polymer with the material is passed via a nozzle by a gel solution (Joye and McClements 2014 ). In this technique, the syringes are used as nozzles as an extrusion method to be used in the laboratory; for this purpose, the sodium alginate is used as a wall material, and the capsules are formed in a calcium chloride solution (Munin and Edwards-Lévy 2011 ). One important aspect to be noted is the capsule size, which depends on the diameter of the syringe used and the flow rate at which it is released (Joye and McClements 2014 ). The extrusion technique has many advantages, i.e., it is a very simple method to carry out in the laboratory, the end capsule will have a high shelf life, and the most important advantage is that it can encapsulate both hydrophilic and hydrophobic compounds. One of the major disadvantages is that the scale-up method is not easy and is expensive (Jia et al. 2016 ).

Encapsulation by emulsification Emulsification is a technique that involves two immiscible liquids such as water and oil, in which one of the two liquids is added in the form of droplets (Fang and Bhandari 2010 ). This technique requires an emulsifier for proper stabilization. In this method, the encapsulated bioactive compounds after the emulsification process can either be powder or liquid at the final stage (Fang and Bhandari 2010 ). This technique is divided into nano and double emulsions, where this encapsulation is mainly suitable for oil-soluble compounds such as sterols, and dietary fats (Fang and Bhandari 2010 ; Jia et al. 2016 ).

Encapsulation by coacervation The encapsulation method by coacervation is defined as the separation of polyelectrolyte phases and the formation of coacervate from solution and core material (Ezhilarasi et al. 2013 ). The determination of coacervation type depends on the number of polymers used. For instance, if one polymer is used, the technique is simple, whereas if multiple polymers are used the technique is more complex. The cross-linking agents, chemicals, and enzymes can be used to enhance the firmness and stability of wall material (Fang and Bhandari 2010 ; Ezhilarasi et al. 2013 ; Jia et al. 2016 ). The formation of coacervates is attained by electrostatic interactions of the cross-linking agent, and these agents must be strong and, at the same time must not be too large to prevent precipitation (Oancea et al. 2018 ). It is an important method with high efficiency of the encapsulated core material with a controlled release. The disadvantages of this technique are that the capsules obtained by this technique are not stable, and the cost of the procedure is very expensive (Fang and Bhandari 2010 ; Munin and Edwards-Lévy 2011 ).

Encapsulation by molecular inclusion The principle involved in this method is the polar molecules get bonded to the polar molecules via hydrogen, and Van der Waals bonding and electrostatic interactions. This technique contains a hydrophilic exterior and a hydrophobic interior, which is completely suitable for encapsulating polar molecules, and the most commonly used material is cyclodextrins (Fernandes et al. 2013 ; Mishra 2015 ).

Encapsulation by ionic gelation Ionic gelation is one of the simple encapsulation techniques, where the active material is encapsulated using microbeads with a biopolymer. The most commonly used gel in this system is calcium alginate gel. The active material is suspended in a polymer solution and this mixture is passed using a syringe, spraying or vibrating nozzle, atomizing disk, and jet cutter (Mishra 2015 ).

Clinical studies on encapsulated phenolics

The biological effects of polyphenols on the body may vary depending on their bioavailability. Direct evidence of the bioavailability of these compounds was observed by measuring their amount in plasma and urine after oral ingestion of foodstuffs with certain concentrations of these compounds or the pure compound whose effect is desired to be studied (Scalbert and Williamson 2000 ). It is noted that polyphenols have low bioavailability due to many internal and external factors, such as their low stability in the gastrointestinal environment, chemical structure, molecular weight, low hydrosolubility, and rapid elimination (Conte et al. 2016 ). Polyphenol's bioaccessibility might change easily due to its characteristic properties. To overcome this, different delivery systems may be used. The selection of the encapsulation process and the wall material prevents the degradation of polyphenols in the gastrointestinal environment but also controls their release in the target medium (Garavand et al. 2021 ). Clinical studies are essential to understand the effects of foods or food polyphenols on human health. Although the results of preclinical studies are promising, clinical studies in the literature about encapsulated phenolic compounds are still limited.

Plant extracts

Limited clinical studies are using encapsulated phenolic components with different encapsulation techniques that investigate the therapeutic efficiency of plant-extract-containing capsules (Table  1 ). A study by Christman et al. ( 2019 ) investigated the effects of peanut skin extract in human subjects on oral glucose tolerance. The encapsulation process of peanut skin phenolics was performed using a spray drying method with maltodextrin (10.5% (w/w)) as a coating agent. In a cross-over randomized trial conducted on 15 healthy subjects (7 males and 8 females) with five treatments on different days in randomized order, each participant carried out 5 different experimental treatments. These treatments have been performed for oral glucose tolerance tests using 5 different substances including 50-g glucose solution (GS) as a reference; GS + 12 mg of vegi-capsulated maltodextrin as placebo; GS + 120 mg of vegi-capsulated maltodextrin-encapsulated peanut skin extract as treatment; GS + 28 g of unfortified coated peanuts; GS + 28 g of chilli lime coated peanuts fortified with peanut skin extract. According to the study, the peanut skin extract treated with the glucose reference caused a significantly ( p  < 0.05) lower peak blood glucose response at 45 min, indicating that it was successful in lowering the glycemic response. However, there was no difference in the glycemic response area under the curve between any treatments using the tolerance test. Additionally, research has demonstrated that peanut skin extracts can reduce the postprandial glucose spike that results from taking a glucose load. According to the findings, encapsulated peanut skin extract that is high in phenols is a promising compound for human mechanisms. To evaluate the effectiveness of 2% encapsulated activated grape seed extract (E-AGSE) essence on human skin, a 4-week, 31-subject sensitive-skin cosmetic trial was conducted (Tao et al. 2021 ). The 2% E-AGSE essence formulation (containing 0.02% AGSE) was given to the subjects, who were advised to apply it in the morning and evening and refrain from using any other skincare products on their faces for the first week before and for the length of the study. In this clinical trial, an improvement in anti-aging, hydration, and brightness endpoints was seen by using E-AGSE. It was demonstrated that E-AGSE's in vitro action translates to human subjects, with topically administered 2% E-AGSE Essence being well tolerated and effective in increasing skin brightness and hydration while minimizing the appearance of wrinkles in humans. It was revealed that E-AGSE in vitro activity translates to human subjects, with topically applied 2% E-AGSE essence being well tolerated and effective in increasing skin brightness and hydration as well as minimizing the appearance of wrinkles.

There are various studies based on animal studies employing encapsulated plant-based extracts for assessing their health effects (Table  2 ). Encapsulating the bioactive agents in the liposome delivery system could improve solubility and stability, prevent unwanted interactions with other molecules, and enhance the bioactivity of these natural components. There are several studies of that nanoliposome delivery system used to investigate the health-promoting potentials of phenolic-rich fractions of Rheum ribes extract (Shamansoori et al. 2022 ) and Alcea rosea leaves extract (Hassirian et al. 2022 ) in the mice infected by enteropathogenic Escherichia coli (O157:H7) and phenolic rich fractions of Artemisia aucheri 's areal parts (Mehdizadeh et al. 2022 ) and Achillea millefolium extract (Nateghi et al. 2022 ) in the mice infected by enteropathogenic Campylobacter jejuni . In these studies, mice were administered 10 mg/kg b.w./day encapsulated and nonencapsulated phenolic-rich fractions of plant extract for 28 days, and mice were challenged with food-borne pathogens on day 21. As a result, both the non-encapsulated phenolic-rich fractions of plant extracts and the nanoliposome-encapsulated phenolic-rich fractions showed health-promoting activity. Additionally, the nanoliposomes played a critical role against the infections more potential due to the enhancement in solubility, bioavailability, and absorption of phenolic compounds as compared with the nonencapsulated ones in improving the health parameters in mice. In another study, a phenolic-rich fraction of Ferula gummosa leaf using a spray-drying technique was fabricated to investigate the potential phytobiotic effect against Campylobacter jejuni infection in mice (Kamelan Kafi et al. 2022 ). Treatment mice groups were administered 150 mg or 300 mg phenolic compounds per/kg b.w. with a normal diet for 4 weeks and infected on day 21. The results indicated that fabricated phytobiotic could potentially enhance the growth parameters, liver enzymes, and lipid peroxidation, improve the ileum's morphometric parameters, and inhibit the ileal population of Campylobacter jejuni.

Acute toxicity of encapsulated green coffee fruit extracts using spray drying method (Faria et al. 2020 ), polyherbal formulation (PHF) rich in natural polyphenolic compounds using the freeze-drying method (Hussain et al. 2018 ) and Moringa oleifera leaf polyphenols using thin-layer hydration method (Wanjiru et al. 2022 ) were investigated using animal models for 14 days. The study by Faria et al. ( 2020 ) used 100, 500, 1000, 2500, and 5000 mg/kg of body weight of encapsulated green coffee fruit extracts and there was not any adverse effect on both female or male mice for 14 days of oral single dosage until 1000 mg/kg b.w. In this study, considering a 60 kg adult body weight, a human equivalent dose could be estimated at 189 mg/kg b.w./day or 11.34 g/day for encapsulated green coffee fruit extracts and results indicated that encapsulated green coffee fruit extracts could be safe for daily consumption. Similarly, in the study of Hussain et al. ( 2018 ) it was showed that 2000 mg/kg encapsulated polyherbal formulation ( Chlorophytum borivilianum , Astragalus membranaceus , Eurycoma longifolia roots and Hygrophila spinosa T. Anders seeds (1:1:1:1) phenolics) had no toxic effects and mortality and indicated that microencapsulated products of polyherbal extract were regarded as safe for consumption. Also, the study of Wanjiru et al. ( 2022 ) indicated the safety of Moringa oleifera polyphenol-loaded phytosomes at a dose below 2000 mg/kg. Besides, Sambucus nigra L. extracts-based nanoformulations were studied in the context of its anti-inflammatory effect of 1.0 mg/kg b.w. administration on rat paw edema triggered by carrageenan. PLGA ((poly(lactide- co -glycolide)) and PCL (poly-ɛ-caprolactone) based nanoformulations were prepared using the emulsification/solvent diffusion method and solvent-displacement method, respectively. PLGA nanoparticles showed the greatest inhibitory effect on the extract, with a 23% inhibition rate compared to the free extract gel formulation. In addition, the encapsulation of the extract in PLGA nanoparticles was more effective than in PCL nanoparticles. PLGA nanoparticles exhibited potent anti-inflammatory effects in vivo, with an average inhibition rate of 61% against edema when applied as topical. Results suggested higher efficacy using a delivery system when compared to the extract in free form (Mota et al. 2020 ).

Rutin (Fig.  2 a) is one of the well-known flavones. Despite the many benefits of rutin, the topical application of this compound is limited due to its physical properties. The ethosome delivery system was used in the study of Cristiano et al. ( 2021 ) to improve the transport of this compound through the skin and to increase its pharmacological effects. Optimum formulation of ethosomes and free rutin which contains 2.7 mg/mL rutin were administered by 10 healthy human volunteers. The ethosomes optimized in the study both improved the anti-inflammatory activity of the rutin and ensured that its safe profile on human volunteers was observed.

Chemical structures of flavones. a Rutin, b luteolin, c chrysin, d apigenin

Animal preclinical studies have been performed to examine the promising health potential effect of rutin, delivery systems using the thin film hydration method (Amjadi et al. 2021 ) and oil-in-water microemulsion technique (Pandian et al. 2020 ). In a study by Amjadi et al. ( 2021 ), rutin-loaded nanophytosomes containing 25 mg rutin/kg per day were used to investigate the therapeutic potency in streptozotocin-induced diabetic rats for 4 weeks. The study showed that rutin-loaded nanophytosomes administration for 4 weeks was more effective than the control group, also this increased the antioxidant defenses in the diabetic rats more than free rutin. Additionally, treatment with rutin-loaded nanophytosomes regulated weight loss and food intake. In conclusion, this study showed that rutin-loaded nanophytosomes were more effective than free-form to take advantage of their therapeutic potential, particularly to attenuate diabetic complications. In another study, rutin-loaded solid lipid nanoparticles were used to examine the effect of the blood–brain barrier in the rat (Pandian et al. 2020 ). Rutin-loaded solid lipid nanoparticles were prepared using the oil-in-water microemulsion technique. In vivo biodistribution study using rutin-loaded solid liquid nanoparticles and free rutin were done through lateral tail vein injection at the dose of 10 μg/kg b.w. daily for 5 days. After 54 h of injection, the presence and biodistribution of rutin-loaded solid-lipid nanoparticles were detected in the brain, heart, kidney, liver, lung, and spleen as 15.23, 8.68, 4.78, 5.04, 0.92, and 11.52%, respectively. But free rutin did not reach the brain because of its rapid hepatic first-pass metabolism and macromolecular size. Consequently, solid lipid nanoparticle formulation is a promising delivery system for rutin to reach the target tumors across the blood–brain barrier.

Luteolin (Fig.  2 b) is a hydrophobic compound and has poor biocompatibility, which leads to low bioavailability. To overcome this problem, in a study, integrated lecithin–bile salt nanovesicle system, called bilosomes, was used to deliver luteolin for enhancing the UV-induced skin damage in rats (Abbas et al. 2022 ). A thin film hydration method was used to prepare the nanovesicles. Skin irritation and UVB exposure tests were performed in rats using 50 mg/kg daily luteolin bilosomes compared with untreated, control, free form of luteolin and blank groups. The in vitro test showed that bilosomes resulted in 3.67-fold higher skin accumulation of luteolin compared to free luteolin suspension. In another study, Wu et al. ( 2018 ) fabricated a liposome delivery system by thin film hydration method used to determine the effect of luteolin in antitumor efficacy on colorectal carcinoma. This study showed that the liposome delivery system was found to be more efficient in the inhibition of tumor growth activity in the mouse tumor model of colorectal carcinoma compared to free luteolin. Wu et al. ( 2019 ) used folic acid-modified poly(ethylene glycol)-poly(ecaprolactone) (Fa-PEG-PCL) nano-micelle was used to deliver luteolin for glioma treatment. The nano-micelles of luteolin were fabricated using the self-assembly method. Rats were administered 50 mg/kg free luteolin, luteolin nanoparticles, and luteolin/Fa-PEG-PCL microparticles. The Fa-PEG-PCL delivery system improves the sustaining of the drug release and pharmacokinetic characteristics of luteolin. In this study, in vivo model of intracranial tumors and subcutaneous tumors in GL261 glioma mice showed that glioma was inhibited by 42.7%, 59.5%, and 81.2% with free luteolin, luteolin nanoparticles, and luteolin/Fa-PEG-PCL microparticles, respectively. In conclusion, this study indicated that luteolin/Fa-PEG-PCL microparticles may be used for treatment and chemoprevention.

Chrysin (Fig.  2 c) has low solubility and poor bioavailability. To overcome these problems of chrysin, methoxy poly(ethylene glycol)-β-polycaprolactone nanoparticles were fabricated using the oil-in-water technique (Kim et al. 2017a ). Free chrysin (50 mg/kg) was administered once a day, 5 times weekly for 3 weeks, and 5 mg/kg chrysin nanoparticle was administered every 2 days, 3 times weekly for 3 weeks. Although, the free chrysin administration amount was higher than chrysin nanoparticles, encapsulated one delayed tumor growth to the same extent as chrysin, enhanced the therapeutic efficacy in vivo in mice, and offered a beneficial formulation for chemotherapy.

Apigenin (Fig.  2 d), which is commonly found in fruits, vegetables, tea, chamomile, and wheat sprouts (Shukla and Gupta 2010 ), has some limitations in clinical potential due to its poor aqueous solubility, and rapid metabolism. In a study, an optimized formulation of phospholipid phytosome for delivering the apigenin was fabricated to investigate the in vivo antioxidant potential (Telange et al. 2017 ). The phytosomes exhibited antioxidant potential by significantly ( p  < 0.05) decreasing the levels of lipid peroxidase and increasing the levels of superoxide dismutase, glutathione, and catalase. According to the results, phytosomes can be used to enhance the solubility, oral bioavailability, and pharmacological properties of phytoconstituents that have low solubility.

Catechin (C), epicatechin (EC), epigallocatechin (EGC), and epigallocatechin-3-gallate (EGCG) are the four main compounds of green tea (Fig.  3 ). Tea catechins have low bioavailability, which is mainly due to their poor stability and low gastrointestinal absorption. In the gastrointestinal tract, most catechins are metabolized, degraded, and catabolized before they can be absorbed in the small intestine, which leads to low uptake in the blood and low distribution into the organs (Rashidinejad et al. 2021 ). The use of encapsulation techniques can overcome these properties of flavanols and increase their bioavailability. However, the articles related to the investigation of the carrier systems of flavanols in clinical studies are still limited.

Chemical structures of flavanols. a Catechin, b epicatechin, c epigallocatechin, d epigallocatechin-3-gallate

Chitosan microparticles were used to reduce the physical limitations of catechin in green tea extract for decreasing catechin degradation and improving its skin permeation (Wisuitiprot et al. 2022 ). A split-face, double-blind, randomized placebo-controlled clinical study was conducted to detect the effect of green tea extract-loaded chitosan microparticles (GTP) on facial skin. GTPs were prepared using the water-in-silicone emulsion technique. The participants were subjected to a cream containing 1% (w/w) GTP, which includes 0.018% total catechins or 0.006% EGCG, on one side of their face and a placebo cream on the other side for 8 weeks. This clinical study showed that after applying emulsion incorporated with GTP, skin elasticity significantly ( p  < 0.05) progressed within 1 month and the fine wrinkles decreased within 2 months compared to baseline. Also, a significant ( p  < 0.05) increase in whole facial skin elasticity was determined after applying both GTP and placebo cream from baseline. As the reason for the increased elasticity in the skin, it is indicated that it is due to the moisture provided by the oil-in-water emulsion. Compared to placebo cream, it has been reported that the reason for the increased skin elasticity in the skin area where GTP cream is applied is because of the catechins contained in green tea extract protecting and stabilizing the skin collagen from degradation. Additionally, the cream containing GTP improved the melanin index within the sixth week after application. In conclusion, this study indicated that GTPs are a promising active ingredient in cosmetics and dermatological products for reducing wrinkles and lightening the skin.

In a study by Lazzeroni et al. ( 2017 ), a lecithin formulation of a caffeine-free green tea catechin extract called Greenselect Phytosome (GSP) was used to investigate the tissue distribution, effect on cell proliferation and circulating biomarkers in breast cancer patients of EGCG. GSP (300 mg), a soy lecithin delivery system that contains 44.9 mg of EGCG and 65.12 mg of catechins, was administrated by twelve early breast cancer patients daily for 4 weeks before surgery. Due to repeated administration of phytosome, total EGCG concentrations were accessed between 17 and 121 ng/mL in plasma and were detectible in all tumor tissue samples. In this research, it was proposed that adding lecithin to the formulation could enhance the absorption of EGCG without compromising safety. It was found that oral intake of GSP leads to increased bioavailability of EGCG in the body and EGCG may accumulate in breast tumor tissue. The presence of EGCG in breast cancer tissue was found to have antiproliferative effects, meaning it may inhibit the growth and spread of cancer cells. These findings suggest that the use of GSP, potentially in combination with lecithin, may have potential as a therapeutic agent for breast cancer and other breast-related conditions. The effect of encapsulation techniques on the bioavailability of flavanones has not been observed in the mentioned clinical studies. Although clinical studies examining the delivery systems of flavanones are limited, there are in vivo studies in the literature showing the positive effects of delivery systems on animals.

The wound healing potential of a hybrid fibrous patch containing epigallocatechin 3-gallate loaded chitosan nanoparticle within enzymatically crosslinked polyvinyl alcohol/collagen (PVA-Tyr/Col/NCs-EGCG) was investigated using rats (Bairagi et al. 2018 ). This study showed that the percentage of wound healing of the rat skin treated with untreated (control), sterile paraffin gas (standard of care), and PVA-Tyr/Col/NCs-EGCG was 62 ± 3.5%, 79 ± 3.2%, and 96 ± 3.7% after 14 days, respectively. As a result of the study, the group treated with the PVA-Tyr/Col/NCs-EGCG combination had a significantly ( p  < 0.05) higher average wound closure rate compared to other groups in time intervals. In conclusion, the histological analysis of the hybrid fibrous patch suggests that it may be suitable for utilization as a skin substitute to repair injured skin. In a study by Peng et al. ( 2018 ), tea polyphenols (TP) entrapped within polysorbate 80 and corn oil nanoemulsion (a dose of 112 mg/kg) by oil in water (O/W) nanoemulsion method was administrated to twelve male Sprague–Dawley rats. According to the results, compared to TP aqueous solution, the total amount of absorbed catechins which includes EGCG and EGC was significantly ( p  < 0.001) higher. The nanoemulsion delivery system provided a higher amount of absorbed EGCG content as 28.6% compared to the TP solution. However, the amount of EGCG absorbed from the TP aqueous solution was found to be significantly ( p  < 0.05) less than the maximum amount of EGCG absorbed from the nanoemulsion. It has been stated that encapsulated EGCG molecules may have a different release model than those in an aqueous solution. In conclusion, it was stated that the nanoemulsion carrier system used in the study improved the oral bioavailability of EGCG and EGC catechins and facilitated the controlled release of tea catechins. In a study by Sinsinwar and Vadivel ( 2021 ), the anti-infective potential of catechin-in-cyclodextrin-in phospholipid liposome (CCPL) was investigated in the Methicillin-resistant Staphylococcus aureus mediated surgical site infection model using Balb/c mice. Mice were administered different doses of CCPL as 4, 8, and 16 mg/kg b.w. and for 7 days. According to the results, a significant ( p  < 0.05) dose-dependent improvement was observed, a significant ( p  < 0.0001) decrease in the number of bacteria occurred, and it was noted that enhanced epithelization and inflammation were significantly prevented in skin samples. This study showed that this delivery method of catechin could be taken into consideration to mitigate mediated surgical site infection after clinical trials.

Overall, these studies suggest that encapsulation techniques offer the possibility of enhancing the bioavailability of flavanols and their therapeutic effects. Several applications, ranging from skincare to cancer treatment and infection prevention, demonstrate the versatility and potential of these innovative delivery systems for improving flavanol efficacy in a number of clinical settings.

The main limitations of flavonols (Fig.  4 ) such as quercetin, myricetin, fisetin, and kaempferol are their low water solubility, low stability depending on environmental conditions, and low bioavailability. Due to these properties, there is a limitation in the beneficial effects of these compounds, and require a high level of dosage for consumption. As a result of the low solubility of the compound in water, it is necessary to take it into the body in a solution to increase its absorption from the gastrointestinal system. There are limited published clinical studies investigating the effect of the delivery system for flavonols, such as quercetin (Riva et al. 2019 ) and fisetin (Krishnakumar et al. 2022 ).

Chemical structures of flavonols. a Quercetin, b myricetin, c fisetin, d kaempferol

There are several clinical studies to investigate the effects of quercetin which are ongoing and have no results yet. In a study, the therapeutic efficacy of quercetin and quercetin-encapsulated poly-ethylene glycol-poly lactide-co-glycolic acid (PLGA-PEG) nanoparticles, using the oil-in-water (O/W) single emulsion solvent evaporation method, on tongue squamous cell carcinoma cell line will be studied (ClinicalTrials.gov Identifier: NCT05456022). Another clinical study, which is a phase II clinical trial, was aimed to investigate the effect of Dasatinib, quercetin phytosome ( Sophora japonica concentrate (leaf)/phosphatidylcholine complex from sunflower), and fisetin capsules on senescent cell load and bone resorption markers and to increase bone formation markers in elderly women (ClinicalTrials.gov Identifier: NCT04313634). Also, there are 2 different clinical studies that focused on the effect of quercetin phytosome on COVID-19 disease (ClinicalTrials.gov Identifier: NCT04578158 and NCT04861298).

Knowledge of the clinical effects of flavonols on the human body plays a very important role in determining the encapsulation techniques and carrier systems to be used. Phytosomes can be used as a carrier system to improve solubility, and bioavailability as well as to protect the encapsulated bioactive compounds against external stimuli, for instance, enzymes, light, temperature, and pH variations (Semalty et al. 2010 ; Gang et al. 2012 ; Kuo and Tsao 2017 ). Riva et al. ( 2019 ) examined the solubility of a food-grade lecithin-based formulation of quercetin, which is called Quercetin Phytosome®, in simulated gastrointestinal fluids and oral absorption in healthy volunteers. Randomized crossover pharmacokinetic clinical study included one of 250 mg film-coated quercetin, one of 250 mg film-coated tablet of Quercetin Phytosome, and two of 250 mg film-coated tablets (500 mg) of Quercetin Phytosome. Blood samples have been collected before treatment and during administration for 24 h. According to the data obtained from the study, it was noted that the solubility and absorption of quercetin increased with the use of quercetin phytosome instead of individual quercetin, and therefore an improvement in the bioavailability of quercetin was observed. In a study by Chalet et al. ( 2018 ), quercetin and its phase-II metabolites were observed in human intestinal duodenal fluids after ingestion, from 15 min to 4 h after 500 mg quercetin capsule consumption. According to the results, quercetin phase-II metabolites were detected in the intraluminal environment which indicates the fast formation of metabolites in the intestinal wall and reflux in the lumen. In another study, the efficacy of targeting protein disulfide isomerase with isoquercetin to diminish hypercoagulability in cancer patients has been investigated (Zwicker et al. 2019 ). Phase II trial with 2 different treatments including 500 mg and 1000 mg isoquercetin capsules has been monitored in plasma samples for 56 days. According to the results of the study, daily administration of 1000 mg isoquercetin decreased D-dimer plasma concentration and increased protein disulfide isomerase inhibitory activity in plasma. D-dimer levels have not been reduced with the administration of the lower dose of quercetin (500 mg). Consequently, the results of this study showed that isoquercetin targets extracellular protein disulfide isomerase and enhances markers of coagulation in advanced cancer patients.

The clinical application of fisetin is limited due to its low water solubility and low bioavailability. Thus, Krishnakumar et al. ( 2022 ) developed a self-emulsifying water-dispersible formulation using green technology to overcome these problems. Novel formulation of food-grade fisetin prepared by using sunflower lecithin, sunflower oil, and fenugreek galactomannans, following a gel-phase thin-film dispersion of fisetin micelles into galactomannan hydrogel matrix and subsequent evaporation. A single-dose, randomized, comparative, double-blinded cross-over design was carried out including 1000 mg of fisetin formulation (FF-20, contained 192 mg fisetin) and unformulated fisetin (UF). Blood samples were collected after 12 h of oral ingestion (the washout period was 10 days between 2 treatments). According to the study, the plasma concentration of fisetin during FF-20 administration was 26.9-fold higher than that of UF. Also, the maximum plasma concentration of FF-20 (238.2 ng/mL) was 23 times greater when compared to UF (9.97 ng/mL). Additionally, the conversion amount of fisetin to geraldol, which is the active metabolite of fisetin, has been reduced by encapsulation. Encapsulation of fisetin has a protective effect on environmental factors such as low pH conditions and intestinal biotransformation as well as lead to better absorption for self-emulsified nanomicelle and higher bioavailability.

Animal preclinical studies have been performed to examine the promising potential health effects of quercetin, using the ionic gelation method followed by lyophilization (Baksi et al. 2018 ), desolvation procedure followed by spray drying (Peñalva et al. 2019 ), and coacervation (Peñalva et al. 2019 ); kaempferol using quasi-emulsion solvent diffusion technique (Kazmi et al. 2021 ), nanoliposomes (Haeri et al. 2022 ); myricetin using thin-film hydration (Hou et al. 2019 ), single-step precipitation (Liu et al. 2022 ), hot melt emulsification technique followed by ultrasonication (Halder et al. 2022 ); fisetin using coacervation technique (Kadari et al. 2017 ). In a study conducted by Peñalva et al. ( 2019 ), the bioavailability of quercetin prepared by coacervation was found to be about 9 times higher than its free form. The oral bioavailability of fisetin was also increased using poly-lactide-co-glycolic acid nanoparticles as a complex of hydroxyl propyl beta-cyclodextrin as a delivery system in mice (Kadari et al. 2017 ). In another study, kaempferol nanoparticles have shown a higher protective effect against oxidative stress-induced liver injury than the control (Kazmi et al. 2021 ).

Clinical studies investigating the effects of encapsulation techniques on flavonols are still emerging, with limited published data. Animal studies using a variety of encapsulation methods have consistently demonstrated the improved bioavailability and therapeutic efficacy for quercetin, kaempferol, myricetin, and fisetin. Regardless of the encapsulation method used, such as ionic gelation, quasi-emulsion solvent diffusion, nanoliposomes, or coacervation, these studies have demonstrated the potential of encapsulation in enhancing flavonol health benefits. Overall, encapsulation techniques have emerged as essential tools for overcoming the limitations of flavonols, despite the challenges. Encapsulation seems to have the potential to enhance therapeutic outcomes in ongoing clinical trials and preclinical studies.

Naringenin (NG; Fig.  5 a) which is a naturally occurring flavanone has various pharmacological activities (Verhoeyen et al. 2002 ). Naringenin has poor bioavailability and permeability due to its low aqueous solubility during oral administration (Hsiu et al. 2002 ; Yen et al. 2009 ). To overcome this problem and cover the bioactive material, different types of encapsulation methods can be used. Although there have been several clinical studies that have shown that flavanones are beneficial for health (Galluzzi et al. 2022 ; Murugesan et al. 2020 ; Naeini et al. 2021 ; Namkhah et al. 2021 ; Rebello et al. 2019 ), there is no clinical study that investigates the effect of encapsulation techniques on flavanone delivery in the human body. However, the encapsulation techniques may have the potential to improve the transport of flavanones in the body as it has been stated in several pre-clinical studies. Different coating materials and encapsulation techniques can use to increase bioavailability. Rebaudioside nanomicelles were prepared using a thin-film hydration technique to encapsulate the hesperidin (Fig.  5 b) (Wang et al. 2021 ). The concentration of plasma drug level and tissue distribution of hesperidin in rats were increased by encapsulation, additionally better antitumor activity was observed when compared to free hesperidin. In another study, dipotassium glycyrrhizinate was used as a micelle nanocarrier to encapsulate the hesperidin into an ophthalmic solution (Zhang et al. 2021 ). Encapsulated hesperidin was prepared using the solvent evaporation method. Ocular irritation and corneal penetration tests were done in rabbits using 4.5 mg/mL ophthalmic solution with free and encapsulated hesperidin. In conclusion, a new ophthalmic solution formulation for hesperidin was developed. Furthermore, encapsulation of naringenin with liposomes containing phospholipid, cholesterol, sodium cholate, and isopropyl myristate was done using the thin-film hydration method (Wang et al. 2017 ). The relative bioavailability of encapsulated naringenin administered to mice increased approximately 13.44 times. As a result, there was a significant ( p  < 0.05) improvement in the solubility and oral bioavailability of naringenin due to the liposomal formulation. These results showed that the encapsulation techniques and coating material are critical points for the bioavailability of flavanones and various clinical studies should be peformed.

Chemical structures of flavanones. a Naringenin, b hesperidin

Isoflavones

There has been limited knowledge about the clinical studies of encapsulated isoflavones and several animal studies examined the therapeutic effects of encapsulated genistein (Kaundal et al. 2019 ; Han et al. 2021 ; Hou et al. 2021 ; Yang et al. 2021 ). Genistein (Fig.  6 ) is a well-known isoflavone, but its poor solubility and low oral bioavailability require the use of carrier systems to overcome these limitations. Although there are no clinical studies, there are in vitro and in vivo studies examining genistein with promising results (Kaundal et al. 2019 ; Han et al. 2021 ; Hou et al. 2021 ; Yang et al. 2021 ).

Chemical structure of genistein

Kaundal et al. ( 2019 ) fabricated indocyanine green-tagged, genistein-containing casein nanoformulations (ICG-Gen@CasNPs) that exhibit enhanced cellular uptake in a three-dimensional raft culture model and human glioblastoma monolayer. According to this study, ICG-Gen@CasNPs strongly accumulated in the brain after crossing the blood–brain barrier, demonstrating the system's great biocompatibility, and demonstrating the lack of any nonspecific toxicity in vivo. When compared to the control group, in vivo toxicology revealed negligible toxicity in the heart, kidney, liver, spleen, and brain tissues, indicating low toxicity and good biocompatibility with ICG-Gen@CasNPs. Han et al. ( 2021 ) constructed a macrophage membrane-coated solid lipid nanoparticles that attached rabies virus glycoprotein molecules to the surface of the membrane to deliver the genistein for the treatment of Alzheimer's disease in mice. The solvent injection method was used to prepare the solid liquid nanoparticles. Mice were administered 5 mg/kg genistein by tail vein injection. By combining the synergies of macrophage membranes, rabies virus glycoprotein, and triphenylphosphine cation, the Genistein encapsulated drug delivery system demonstrated the most beneficial results in reducing the symptoms of Alzheimer’s disease in vivo. According to the results obtained from this study, it has been stated that biomimetic nanosystems designed to delay the progression of Alzheimer’s disease may be promising therapeutic candidates. In another study, a dipotassium glycyrrhizinate (DG) based micelle ophthalmic solution encapsulating genistein (Gen) was fabricated (Hou et al. 2021 ). Ocular tolerance evaluation (50 μL/drop of DG-Gen ophthalmic solution was instilled topically into the rabbits’ eyes 13 times at 30-min intervals), corneal penetration test (5 μL/drop, × 4 drops, 10-min intervals) and corneal epithelial wound healing (micelle formulation containing DG 75 mg/mL and Gen 5 mg/mL) were performed in rabbits. These findings demonstrated that HMGB1 signaling is a potential target for regulation in the treatment of diabetic keratopathy and that a novel DG-micelle formulation containing active substances such as genistein could block HMGB1 signaling in a coordinated manner to promote diabetic corneal, and nerve wound healing. Yang et al. ( 2021 ) used 1,4-butanediol diglycidyl ether to crosslink chitosan and graft thioglycolic acid onto the chitosan chain. The fabricated mucoadhesive chitosan demonstrated excellent mucoadhesive properties. The produced chitosan hydrogel (CT-G) with genistein did not exhibit any systemic toxicity in vivo. The released genistein is an estrogen analog that maintains the moisture condition of the vaginal tract to reduce the symptoms of vaginal atrophy. After receiving estradiol treatment, the thickness recovered, while the CT-G-treated group successfully recovered the mucosal thickness to around 54% of the control group to treat vaginal atrophy. In conclusion, the fabricated CT-G was a safe hydrogel that could be administered intravaginally or locally to treat vaginal atrophy and maintain a steady release for at least three days. Further animal and clinical research should be conducted to understand the therapeutic effect of genistein and other isoflavones.

Anthocyanins

Among the natural polyphenols, anthocyanidins and their glycosides, in other words, anthocyanins, has gained special attention due to their remarkable biological activities such as anticancer (Wang and Stoner 2008 ), antidiabetic (Les et al. 2021 ), antioxidant (Filaferro et al. 2022 ), anti-inflammatory, antimutagenic (Gerardi et al. 2016 ) effects both in vitro and in vivo. They have been shown to possess cardiovascular and neurological protection (Chen et al. 2022 ; Dong et al. 2022 ), improve cognitive performance (Ahles et al. 2021 ), attenuate memory deficit (Pacheco et al. 2018 ) and they can be widely used in the formulations of foods and beverages, pharmaceutic and cosmetic products (Brudzyńska et al. 2021 ; Abdo et al. 2022 ; Câmara et al. 2022 ; Echegaray et al. 2022 ).

However, poor absorption, rapid metabolism, and excretion of anthocyanins limit their biological activities after ingestion (el Mohsen et al. 2006 ). Furthermore, these molecules are highly susceptible to external factors such as physicochemical factors (light, heat, oxygen, metal ions, SO 2 , ascorbic acid, pH change), gastrointestinal digestion (digestive enzymes, pH change throughout the gastrointestinal tract, proteins) (Hocine et al. 2018 ). Therefore, they are notably sensitive, unstable, and prone to degradation which makes their incorporation into food and medical products a challenging task. At this point, the development of novel delivery systems via encapsulating these molecules seems to be an efficient way to overcome these drawbacks and improve their stability, bioaccessibility, bioavailability, and bioactivity.

The encapsulation of anthocyanins from different sources has been widely performed and investigated at in vitro conditions (Limsitthichaikoon et al. 2020 ; Sun et al. 2021 ; Catalkaya et al. 2022 ; Wang et al. 2022b ). In vivo studies, especially those with human studies, focusing on the application of anthocyanins in encapsulated forms are still scarce. There are only a few studies employing anthocyanins in nanocarriers for nano delivery.

Damrongrungruang et al. ( 2021 ) reported that anthocyanin complex niosome gel containing anthocyanins from purple waxy corn and blue butterfly pea petals improved the healing time of oral wounds, decreased the pain from oral wounds and improved the participants’ quality of life higher than the other treatments in the study which is a randomized, block, placebo-controlled, double-blind clinical trial with 60 volunteers.

There are various studies based on animal studies employing encapsulated anthocyanins for assessing their health effects. Cyanidin-3-glucoside (Fig.  7 ) loaded cross-linked chitosan nanoparticles obtained by ionic gelation method were utilized for the treatment of UVB-induced epidermal damage in mice models. It was observed that nano-encapsulated cyanidin-3-glucoside was more effective in the treatment of damage than cyanidin-3-glucoside alone at the same concentration. Also, with the nano-Cyanidin-3-glucoside treatment, biomarkers of DNA damage, oxidative stress, and regulatory pathways for apoptosis, including caspases and members of the B-cell lymphoma/leukemia-2 were regulated in a good way (Liu et al. 2018 ). Similarly, cross-linked chitosan nanoparticles loaded with black carrot anthocyanin extract were administered to male Wistar albino rats at 600 mg/kg body weight to evaluate their gastro-protective effect on ethanol-HCl induced ulcer. The results revealed that consumption of anthocyanin-loaded chitosan nanoparticles induced the expression of anti-inflammatory cytokines and suppression of pro-inflammatory cytokines showing the gastro-protective effect of nano-encapsulated anthocyanins. No hemorrhage, necrosis, or erosion was detected in the anthocyanin-loaded chitosan nanoparticles group whereas mild symptoms were observed in the anthocyanin and empty chitosan nanoparticles group (Raman et al. 2022 ).

Chemical structure of cyanidin-3- O -glucoside

A functional drink made of anthocyanin-loaded niosomes was tested for its potential antidiabetic activity on diet-induced obese mice. Feeding of mice with a high-fat diet along with metformin as a positive control (200 µg/mL), empty niosomes as a negative control (100 µg/mL), anthocyanin solution (280 µg/mL) or anthocyanin loaded niosomes (160 µg/mL) was evaluated after four weeks. According to the findings, fasting glucose levels and insulin levels as well as intolerance to glucose and insulin were decreased only in the group treated with anthocyanin-loaded niosomes. On the other hand, encapsulated anthocyanin treatment for four weeks resulted in a significant reduction in animal weights ( p  < 0.05) collectively showing that anthocyanin-loaded niosomes ameliorated metabolic abnormalities related to obesity (Colorado et al. 2020 ). In another study, black carrot anthocyanins encapsulated in chitosan nanoparticles have been shown to present in vivo antioxidant activity after daily administration to the male albino Wistar rats at 600 mg/kg body weight by increasing the serum superoxide dismutase and catalase enzyme activities (Chatterjee et al. 2021 ). Anthocyanins loaded into poly(ethylene glycol)-gold nanoparticles have been shown to pass the blood–brain barrier in test animals. These nano-encapsulated molecules reduced Aß 1-42 -induced neurodegeneration and inflammation in mouse brains by inhibiting NF-kB/JNK/GSK3β signalling pathways (Kim et al. 2017b ). In a study, researchers investigated the potential anticancer effect of exosomal anthocyanidins isolated from bilberry extract. Five mg/kg body weight of exosomal anthocyanins, 10 mg/kg body weight free anthocyanins or vehicle were administered to female athymic nude (nu/nu) mice having human lung tumor to follow its antitumor effect. As a result, although exoanthocyanidins were given to the mice at a one-half concentration of the free anthocyanidins, they caused a significant decrease in the tumor volume ( p  < 0.01) while the tumor growth inhibition was insignificant in the free anthocyanidin treatment group compared to the vehicle group (Munagala et al. 2017 ). The biological effects of nanoencapsulated anthocyanins were also tested in a fish model. In a study, tilapia fish were fed with 0.5 or 1 mg/g body weight nano-encapsulated pelargonidin in poly-lactide-co-glycolide for 7 days and intoxicated by a pesticide cypermethrin at the end of one-week administration. The results revealed that 0.5 mg/g body weight nano-encapsulated pelargonidin supplementation showed a protective effect on pesticide intoxication as it decreased the % cell cytotoxicity in cypermethrin intoxicated fishes, oxidative stress biomarkers modulated (cypermethrin-induced lipid peroxidase levels decreased, and superoxide dismutase activity increased, catalase activity decreased compared to cypermethrin treated group).

While in vitro studies have provided valuable insights, the scarcity of human studies employing encapsulated anthocyanins still need further exploration in clinical settings. However, insights from animal studies suggest the potential of nanoencapsulated anthocyanins in ameliorating various health conditions, including epidermal damage, neurodegeneration, cancer, etc.

Non-flavonoids

Lignans polyphenolic compounds with phytoestrogenic properties are derived from phenylalanine in plants. After their ingestion, these compounds are metabolized by the gut microbiota to mammalian lignans enterolactone (ENL), enterodiol (END), etc. (Wcislo and Szarlej-Wcislo 2014 ). Lignans represent different biological activities such as antioxidant (Wang et al. 2018 ), estrogenic and anti-estrogenic (Lee et al. 2005 ; Kartika et al. 2020 ), and hepatoprotective (Eweda et al. 2020 ) activities as well as they are involved in hormone metabolism and availability (Wu et al. 2006 ), affect gene expression and/or enzyme activity (Ide et al. 2009 ). Additionally, according to previous human studies, they have been associated with a lower risk of several diseases such as colorectal cancer (Johnsen et al. 2010 ), breast cancer (Cotterchio et al. 2008 ), prostate cancer (Hedelin et al. 2006 ), cardiovascular disease (Zhang et al. 2008 ). Post-menopausal symptoms have also been shown to be ameliorated by dietary lignans (Lemay et al. 2002 ). Since these functions are mostly associated with END and ENL, the metabolism of dietary lignans by the gut microbiota may have the utmost importance for these biological activities to be exhibited.

The health-beneficial effects of lignans may be enhanced by encapsulating them. Ni et al. ( 2019 ) conducted meta-analyses on the association between podophyllotoxin nanogel and condyloma acuminatum. The meta-analysis contained 13 randomized controlled trials in which 1716 patients were examined. The overall results of the studies showed that podophyllotoxin nanogel significantly ( p  < 0.00001) improved the cure rate, reduced the medication time and recurrence rate, and decreased the side effects such as edema, erosion, and pain. Also, it decreased the risk of HPV infection in patients.

Although there are not many human studies on encapsulated lignans, several animal studies investigated the association between encapsulated lignans and diseases. In a study, in vivo anti-tumor effect of podophyllotoxin loaded in layered double hydroxides nanoparticles (PPT-LDH). The in vivo tests showed that PPT-LDH delivery was more efficient and the toxicity of podophyllotoxin on animals was lower in its nano-encapsulated form compared to the free form. Also, PPT-LDH showed notable therapeutic effects by decreasing the tumor volume higher than free podophyllotoxin or control treatment (Qin et al. 2010 ).

(−)-Hinokinin-loaded poly( d , l -lactide- co -glycolide) microparticles were tested on experimental mice for treatment of Chagas disease. According to the results, feeding animals with 40 mg/kg (−)-Hinokinin equivalent microparticles showed a trypanocidal effect since significantly decreased parasitemia in mice ( p  < 0.05) (Saraiva et al. 2010 ). In another study, colchicine mesoporous silica nanoparticles/hydrogel composite-loaded cotton patches were investigated for their protective effect on osteoarthritis. When the rats were treated with transdermal patches with a drug dose of 5 mg/kg/daily for 21 days, locomotor activity and blood glutathione levels in osteoarthritis-bearing rats were improved and TNF-α, COX-2, nitric oxide, and malondialdehyde levels were notably decreased (Mohamed et al. 2020 ). Anti-inflammatory and anti-melanoma properties of encapsulated colchicine in rats were also investigated by recent studies. It was shown that colchicine-loaded calcium carbonate nanoparticles (at a dose of 2 mg/kg) attenuated acute myocardial infarction injury by its anti-inflammatory effect (Wang et al. 2022a ) whereas colchicine-loaded polyvinyl alcohol-chitosan nanofibers showed a significant ( p  < 0.001) increase in skin deposition after topical application and exhibited anti-melanoma effect (Morad et al. 2021 ).

In summary, the encapsulation of lignans emerges as a promising strategy to enhance their health-beneficial effects. Recent studies showed that encapsulation not only improves the therapeutic efficacy of lignans but also minimizes the side effects. While human studies on encapsulated lignans are limited, animal studies provide evidence on the efficacy of nano-encapsulation in various health conditions. In summary, encapsulated lignans have great potential for advancing therapeutic interventions, despite the fact that they are still in their early stages of exploration.

Tannins are water-soluble highly complex polyphenolic compounds found in plants that have the ability to precipitate proteins, inhibit digestive enzymes, and restrict the utilization of vitamins and minerals. They are usually classified into three groups: hydrolyzable tannins that include gallotannins, and ellagitannins; condensed tannins (proanthocyanidins) and complex tannins (Khanbabaee and van Ree 2001 ). They are regarded as a double-edged sword as they may promote health or affect inversely. They have been shown to have negative health effects such as hepatotoxic, anti-nutritional, and carcinogenic activities as well as positive health effects such as antimutagenic, anticarcinogenic, antimicrobial, anti-AIDS, immunomodulation activities (Chung et al. 1998 ).

There is very limited data on the health effects of these substances in encapsulated forms. In a study, proanthocyanidin-standardized cranberry juice or encapsulated cranberry powder was evaluated in terms of their suppression ability on Helicobacter pylori infection in terms of dose–response effect at second and eighth weeks in a randomized, double-blind, placebo-controlled clinical trial on 522 H. pylori- positive adults. The results showed that H. pylori infection may be suppressed after the consumption of proanthocyanidin-standardized juice twice a day. However, encapsulated cranberry powder showed no effect on H. pylori infection at both time points (Li et al. 2021 ). In another study, proanthocyanidin-standardized whole cranberry powder (containing 14.5 mg/g proanthocyanidins) was assessed for its efficacy on urinary tract infections in a total of 60 female participants in a randomized, double-blind, controlled, and dose-dependent clinical study. Low-dose (500 mg/day) or high-dose (1000 mg/day) supplementation of encapsulated cranberry proanthocyanidins for 90 days resulted in a reduction of Escherichia coli counts in urine samples as well as symptoms of urinary tract infections when they are compared to the control group. Thus, both doses of encapsulated cranberry proanthocyanidins were recommended as a complementary to antibiotic prophylactic therapy against recurrent urinary tract infections (Sengupta et al. 2011 ).

Additionally, some in vivo studies tested the biological activities of these compounds on animals. In a study, tannic acid encapsulated in the polylactic acid-10R5-polylactic acid copolymer was found to have an inhibiting effect on the colorectal tumor in mice when it was given at 10 mg/kg dosage. Also, the nano-capsule improved the quality of life and increased the lifespan of cancer-bearing mice (Ren et al. 2019 ). Microencapsulated condensed tannins were used for the treatment of hyperglycemia in male Sprague Dawley rats. Firstly, condensed tannins extracted from red type III sorghum bran were microencapsulated in kafirin protein which is also isolated from sorghum. After that, the rats were fed with microparticles corresponding to 116 mg tannins/kg body weight, and their oral starch tolerance and serum insulin were tested. According to the results, microencapsulated tannins led to inhibition of amylases, limitation in starch digestion, and decrease in the glucose concentration available for absorption thus decreasing blood glucose levels. Due to lower blood glucose levels after microencapsulated tannins treatment insulin secretion was not affected (Links et al. 2016 ).

As these findings provide preliminary insight into the potential benefits of encapsulated tannins, further research, particularly in human clinical trials, is necessary to determine their broader health effects, optimal dosages, and potential complementary therapeutic applications.

Hydroxycinnamic acids

To reveal the therapeutic properties of encapsulated hydroxycinnamic acids (Fig.  8 ), plenty of studies have been conducted by using different delivery systems for ferulic acid (Thakkar et al. 2015 ; Bairagi et al. 2018 ; Panwar et al. 2018 ; Hsu et al. 2019 ; Dhayanandamoorthy et al. 2020 ; Rezaeiroshan et al. 2020 ; Pueknang and Saewan 2022 ; Tabassum et al. 2023 ), sinapic acid (Balagangadharan et al. 2019 ; Chandika et al. 2022 ), coumaric acid (Neog and Rasool 2018 ; Venkatesan et al. 2022 ; Wang et al. 2022c ), caffeic acid (Subbarayan et al. 2020 ; Kamath et al. 2022 ; Vyawahare et al. 2022 ), chlorogenic acid (Ye et al. 2021 ) and rosemarinic acid (Lee et al. 2008 ). However, there is limited clinical investigations carried out to understand the therapeutic potential of encapsulated hydroxycinnamic acids.

Chemical structures of hydroxycinnamic acid derivatives. a Ferulic acid, b sinapic acid, c p -coumaric acid, d caffeic acid, e chlorogenic acid, f rosemarinic acid

Ferulic acid (4-hydroxy-3-methoxy-cinnamic acid) is one of the most abundant phenolic acids found in plants such as rice, wheat, fruits, and vegetables. Although ferulic acid has numerous beneficial effects (Thakkar et al. 2015 ; Bairagi et al. 2018 ; Panwar et al. 2018 ; Hsu et al. 2019 ; Dhayanandamoorthy et al. 2020 ; Rezaeiroshan et al. 2020 ; Pueknang and Saewan 2022 ; Tabassum et al. 2023 ), there are some limitations due to its low water solubility and reduced bioavailability. Therefore, different types of methods were developed to remove these barriers. For instance; one study conducted by Pueknang and Saewan ( 2022 ) demonstrated the anti-aging effect of free ferulic acid or encapsulated ferulic acid-containing creams that there was no skin irritation on the upper arm of volunteers after 30 min and 24 h of the treatment. Moreover, encapsulated ferulic acid-containing creams exhibited a higher skin-lightening effect at 4 weeks and there were 11.4 and 5.7% decreases in the melanin content of volunteers after the use of encapsulated ferulic acid and native ferulic acid-containing creams, respectively. Regarding the anti-aging effect, after-4 weeks, the increase in gross elasticity by 11.3 and 7.8%, net elasticity by 13.8 and 6.9%, and the portion of the elasticity by 14.5 and 7.2% were determined for encapsulated and free ferulic acid containing creams, respectively.

In addition to this study, there have been many in vivo (pre-clinical) investigations on the therapeutic properties of encapsulated hydroxycinnamic acids. In a study conducted by Panwar et al. ( 2018 ), the anti-diabetic properties of native ferulic acid and ferulic acid as nanoparticles were compared. Nanoparticles were obtained by cross-linking of ferulic acid (1 mg/mL) and chitosan (1%) and then, rats were treated with those compounds, separately, at a dose of 10 mg/kg body weight. Results of the oral glucose tolerance test indicated higher blood glucose levels in diabetic groups in comparison to that of animals administrated with native or encapsulated ferulic acid. In detail, there was a remarkable reduction in the glucose levels of the animals treated with ferulic acid nanoparticles rather than animals treated with native ferulic acid or reference drug glibenclamide. Besides, the reduction in the body weight of the animals was detected as 7.43, 2.82, and 2.05% for the diabetic control group, the native ferulic acid applied group, and encapsulated ferulic acid applied group, respectively. While there was a body weight loss in diabetic animals due to the degradation of structural proteins, there was no change in the body weight of control animals.

In another research, the wound healing potential of ferulic acid loaded poly(lactic- co -glycolic acid) nanoparticles and ferulic acid loaded poly(lactic- co -glycolic acid) based hydrogels were investigated using rats with Diabetes Mellitus (Bairagi et al. 2018 ). It was reported that there was a significant ( p  < 0.001) decrease in blood glucose levels of oral ferulic acid-loaded polymeric nanoparticles treated as well as oral and topical ferulic acid-loaded polymeric nanoparticles treated groups in comparison to the control group on the 14th day of the experiment. Similar results were gained for the wound healing properties of those compounds that size of the wound diminished significantly ( p  < 0.01) after 8 days of the oral or oral and topical ferulic acid-loaded nanoparticle as well as topical ferulic acid-loaded nanoparticle-based hydrogel applications.

In the case of the hepatoprotective effect of ferulic acid, liposomes (Hsu et al. 2019 ) and β-cyclodextrin inclusion complexes (Tabassum et al. 2023 ) have been developed. After injection of ferulic acid-containing liposomes into rats, hepatic marker enzymes including AST and ALT were determined in blood serum. Based on the findings, serum AST and ALT levels were decreased from 500 IU/L and 200 IU/L to 325 IU/L and 140 IU/L at 0.025 µmol/kg ferulic acid concentration, respectively. Furthermore, serum AST and ALT levels were found to be similar to that of the control group (without liver injury) at 0.025 µmol/kg ferulic acid concentration (Hsu et al. 2019 ). These outcomes were in line with those obtained by (Tabassum et al. 2023 ) that the initial AST, ALT, SOD, and MDA levels were obtained as 227 U/L, 105.4 U/L, 37.4 U/mg, and 22.5 nmol/100 mg, respectively, in animals with liver injury. On the other hand, they were reduced to 186.7 U/L, 84.3 U/L, 43.4 U/mg, and 17.8 nmol/100 mg for ferulic acid application as well as 134.2 U/L, 66.5 U/L, 55.6 U/mg and 15.3 nmol/100 mg for ferulic acid-β-cyclodextrin inclusion complexes treatment, respectively.

Ferulic acid within niosomes was studied in the context of its anti-inflammatory effect on rat paw edema triggered by carrageenan. An overview of the outcomes indicated about 21.4% inhibition in edema by ferulic acid containing niosomal gel, indicating better penetration of niosomal gel to the skin in comparison to conventional gel (Rezaeiroshan et al. 2020 ).

Asthma, which is responsible for sudden deaths in severe conditions, was also been evaluated in a study carried out by Dhayanandamoorthy et al. ( 2020 ). In this study, ferulic acid and ferulic acid entrapped within chitosan nanoparticles (at 66 mg/m 3 ferulic acid equivalent) by ionic gelation technique were administrated to mice. According to the results, a significant ( p  < 0.001) reduction of response to methacholine was obtained with the application of ferulic acid-loaded nanoparticles rather than untreated and ferulic acid-treated groups.

Considering the chemopreventive effect of this phenolic compound against pancreatic cancer, ferulic acid-loaded chitosan-based solid-lipid nanoparticles were used for the assessment (Thakkar et al. 2015 ). These results were in line with the previous ones that nanoparticles with ferulic acid did not cause any side effects like weight loss. Besides, while the tumor volume of control mice was recorded as 2576 mm 3 , it was detected as 2235 mm 3 and 1424 mm 3 for ferulic acid-loaded nanoparticles and a combination of aspirin + ferulic acid-loaded nanoparticles.

Sinapic acid (4-hydroxy-3,5-dimethoxy cinnamic acid) is another phenolic acid that has low aqueous solubility properties. To exhibit plenty of health benefits, different attempts have been performed to improve its delivery (Balagangadharan et al. 2019 ). Chandika et al. ( 2022 ) enriched the wound healing dressing by using chitooligosaccharides/sinapic acid-loaded hydrogel. Indeed, the wounds treated with this hydrogel contracted significantly (35.3%) when compared to the control (48.8%) on day 7 post-surgery. On day 14 post-surgery, wounds treated with sinapic acid-containing hydrogel contracted up to 5.8%, whereas it was found as 10.2% for the blank control group. Based on the results, hydrogel incorporated with sinapic acid showed a great healing effect same to that of commercial wound dressing, indicating great water absorption of this hydrogel that facilitates cell migration and proliferation. Besides, the calvarial bone regeneration potential of chitosan-based sinapic acid-loaded nanoparticles was assessed 4th weeks after the surgery of the rats (Balagangadharan et al. 2019 ). According to the outcomes, differentiation of osteoblast was reported to be at maximal for sinapic acid-loaded fiber treatment, while there was only a small amount of bone generation for control or chitosan-based fibers without sinapic acid.

p -Coumaric acid (4-hydroxycinnamic acid) is another isomer of hydroxycinnamic acids that has various pharmacological benefits. Coumaric acid-loaded polymeric nano or micro-particles have been fabricated for controlled and targeted drug delivery. The Anticancer potential (Wang et al. 2022c ) and anti-diabetic effect (Venkatesan et al. 2022 ) of coumaric acid-containing nanoparticles produced by the nanoprecipitation method were analyzed. According to the results, coumaric acid-loaded nanoparticles treatment (5 mg/kg) had an inhibitory effect in CT26 tumor-bearing mice, while the tumor in the control (without drug) group grew up aggressively (Wang et al. 2022c ). Similarly, coumaric acid-loaded nanoparticles application (80 mg/kg) prevented the body weight loss (230.2 g), ameliorated kidney weight (1.90 g) and kidney hypertrophy index (0.82%) as well as controlled plasma insulin level (~ 100 mg/dL) and insulin concentration (~ 12 µU/mL). On the other hand, 162.4 g body weight, 2.38 g kidney weight, 1.46% kidney hypertrophy index, ~ 325 mg/dL plasma insulin level, and ~ 7 µU/mL insulin concentration were recorded for diabetic rats (Venkatesan et al. 2022 ).

Regarding the therapeutic potential of encapsulated caffeic acid (3, 4-hydroxycinnamic acid), several types of research have been reported (Subbarayan et al. 2020 ; Kamath et al. 2022 ; Vyawahare et al. 2022 ). Kamath et al. ( 2022 ) generated caffeic acid-loaded nanostructured lipid carriers-based cream for the operation of inflammation in rats by topical treatment. In detail, 0.5% caffeic acid was found to be the most effective treatment with 51.18% inhibition of paw edema, in comparison to that of 1.0% caffeic acid (42.24% inhibition) and 1.5% caffeic acid (46.25% inhibition) after 2 h. On the other hand, 0.5% caffeic acid loaded nanostructured lipid carrier-based cream exhibited 26.57% inhibition at the same duration, suggested to be a promising treatment of this formulation for delivering the caffeic acid for a longer period. In another study carried out by Vyawahare et al. ( 2022 ), it was indicated that the body weight of rats with arthritis decreased significantly during 21 d, while the group of rats treated with caffeic acid-loaded nanomicelles restored body weight. Moreover, the paw diameter of rats, as an indicator of the disease severity, was reduced significantly ( p  < 0.001) in the caffeic acid-loaded nanomicelles applied group due to declined swelling, rather than in the untreated group. In addition to the anti-inflammatory effect of caffeic acid-loaded delivery systems, the role of caffeic acid hydrogel in rats with spinal cord injury was also analyzed. Results indicated the caffeic acid hydrogels + human gingival stem cell application as a promising scaffold by triggering the progress in transplants, more than caffeic acid hydrogels alone (Subbarayan et al. 2020 ).

In the case of chlorogenic acid, self-microemulsifying drug delivery systems were produced for targeted drug delivery for patients with mesenteric lymph nodes (Ye et al. 2021 ). It was shown that self-microemulsifying drug delivery systems promote chlorogenic acid transepithelial transportation and led to accumulation within mesenteric lymph nodes by the pathway of lymphatic transport. Besides, chlorogenic acid-loaded self-microemulsifying delivery systems prevented tumor growth in orthotopic G422 glioma model mice. The antitumor effect of chlorogenic acid-loaded self-microemulsifying delivery systems (35 mg/kg) was found to be higher than that of free chlorogenic acid (20 mg/kg).

Rosmarinic acid was also investigated clinically in subjects with atopic dermatitis in terms of erythema, edema, oozing, excoriations, chenification, and dryness (Lee et al. 2008 ). Rosemarinic acid-containing emulsion-based cream was topically applied to the elbow flexures of patients two times a day. Patients' skin conditions were assessed during 2 months of the treatment. Results from this study indicated diminished transepidermal water loss at 8 weeks when compared to the beginning of the treatment. Moreover, erythema (0.53), edema (0.53), and oozing (0.32) items were detected to be statistically different for the cream with rosmarinic acid rather than only cream treatment (0.63, 0.68, and 0.32, respectively) at the end of 2 months.

Overall, encapsulated hydroxycinnamic acids exhibit diverse and promising health effects. From dermatological applications to potential treatments for diabetes, cancer, and inflammatory conditions, these compounds have a wide range of applications. Although preclinical studies have provided valuable insights, further clinical studies are needed in order to validate these findings.

Hydroxybenzoic acids

Up to date, a wide variety of studies have been carried out to understand the bioactive properties of hydroxybenzoic acid derivatives (Fig.  9 ), including 4-hydroxybenzoic, gallic (3,4,5-trihydroxybenzoic acid), protocatechuic (3,4-dihydroxy), vanillic (3-methoxy-4-hydroxy), ellagic, syringic (4-hydroxy-3, 5-dimethoxybenzoic acid) (Tomás-Barberán and Clifford 2000 ; Jiang et al. 2022 ). On the other hand, the literature is lack of clinical investigations about encapsulated or free hydroxybenzoic acids.

Chemical structures of hydroxybenzoic acid derivatives. a 4-hydroxybenzoic acid, b gallic acid, c protocatechuic acid, d vanillic acid, e ellagic acid, f syringic acid

Although there are no clinical studies on encapsulated protocatechuic acid, there are several researches that indicate the potential use of non-encapsulated protocatechuic acid by clinical analyses in terms of its wound healing (Jalali et al. 2020 ) as well as insulin responsiveness modulator and anti-inflammation properties (Ormazabal et al. 2018 ).

While the impact of herbal supplement combined with non-encapsulated gallic acid on the weight loss of the healthy subjects has been determined by a clinical trial (Roberts et al. 2007 ), anticandidal ( Candida albicans ) and antiinflammatory potential (Teodoro et al. 2017 ) as well as wound healing effects (Altan et al. 2020 ) of gallic acid-loaded drug delivery systems have been investigated by in vivo analysis. According to the results of pre-clinical studies, there was no remarkable decrease in invasion scores of gallic acid loaded hydroxypropyl-β-cyclodextrin complex treated rat groups when compared to the control group (without gallic acid). However, similar to the positive control of nystatin treatment, gallic acid loaded hydroxypropyl-β-cyclodextrin complex could also diminish the inflammatory response in the mucosae.

To investigate the therapeutic potential of ellagic acid, drug delivery systems using emulsion–diffusion–evaporation (Mady and Shaker 2017 ), self-microemulsion (Zheng et al. 2019 ) and liposomes (Najafi et al. 2019 ) were formed. In the pre-clinical studies, it was demonstrated that MDA content in the liver reduced, whereas SOD and GSH levels were enhanced significantly ( p  < 0.05) for ellagic acid-loaded self-microemulsion treatment in mice in comparison to that of control (without drug) or free ellagic acid applications (Zheng et al. 2019 ). Similar trends were also obtained by Najafi et al. ( 2019 ) that monitored the efficiency of ellagic acid-loaded liposomes on the quality of post-thawed sperm. 1 mM ellagic acid-loaded liposome treatment enhanced the motility (71.3%), membrane functionality (70.5%), viability (77.5%), mitochondrial activity (70.7%) rather than rest of the ellagic acid concentrations in liposomes and control group (without drug).

Conclusion and future prospects

Dietary polyphenols are considered as effective and safe in the treatment and prevention of a wide range of chronic diseases (i.e. diabetes, obesity, cardiovascular diseases, neurological disorders, and some forms of cancers). Though polyphenols have shown a potential role in combating several pathologies at the cellular and molecular levels through the modulation of many signalling pathways, their low bioaccessibility and bioavailability, and their interaction with other nutrients and/or drugs remain the main concerns and challenges for clinicians. These issues can be successfully overcome by formulating encapsulated polyphenols, as evident by the results reported in several in vitro and in vivo studies. Encapsulation prevents the degradation of polyphenols in the gastrointestinal tract and promotes the targeted release of the active agent. The gradual advancement in the development and design of encapsulation carriers increases the application prospects of polyphenols as functional food ingredients. With the enhanced pursuit of food functionalization, some special dietary foods designed with polyphenols as their main bioactive are widely appreciated and have received pertinent safety certifications. Rutin, luteolin, chrysin, apigenin, catechins, quercetin, fisetin, naringenin, tannins, hydroxycinnamic acids, and hydroxybenzoic acids have been successfully encapsulated using different techniques, showing considerable health effects in human subjects. However, encapsulated formulations of certain dietary polyphenols with functional properties and excellent biological activities are yet to be tested in clinical trials, which continues to pose limitations on their use in functional food development. Thus, robust and randomized clinical trials to extensively assess the encapsulated polyphenols in the management of various diseases are highly encouraged before any conclusion is drawn. In addition, some other critical factors that need to be considered while developing polyphenol loaded-delivery systems include the molecular features of phenolic compounds (i.e., molecular weight, solubility, polarity, stability, and melting point), the storage and processing conditions (i.e., ionic strength, pH, and temperature), and flavor and shelf-life of the end product. Based on the therapeutic potential of phenolic compounds in clinical and pre-clinical trials, encapsulation techniques, including liposomes, emulsions and spray drying have been gaining great attention. On the other hand, selection of the appropriate carrier agents, the ratio between carrier and active compound as well as the concerns about toxicity, side effects and safety for each type of phenolic compound should be taken into consideration. More clinical data is required to elucidate their biocompatibility and safety, long-term effects, and interactions with other medications. Additionally, encapsulated polyphenols can be costly to produce, and their scalability is another concern. This may limit the availability of encapsulated polyphenols as a therapeutic option for resource-constrained healthcare systems, especially if the cost of production is prohibitively high. Finally, regulatory approval and standardization may be the other challenging issues for encapsulated polyphenols.

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Gulay Ozkan, Tuğçe Ceyhan, Gizem Çatalkaya & Esra Capanoglu

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Published on 8.4.2024 in Vol 26 (2024)

Longitudinal Monitoring of Clinician-Patient Video Visits During the Peak of the COVID-19 Pandemic: Adoption and Sustained Challenges in an Integrated Health Care Delivery System

Authors of this article:

Original Paper

• Jessica A Palakshappa 1, 2 , MD, MS   ; 
• Erica R Hale 1, 2 , MS   ; 
• Joshua D Brown 1 , PhD   ; 
• Carol A Kittel 2 , MA   ; 
• Emily Dressler 2 , PhD   ; 
• Gary E Rosenthal 1, 2 , MD   ; 
• Sarah L Cutrona 3, 4 , MD, MPH   ; 
• Kristie L Foley 2 , MS, PhD   ; 
• Emily R Haines 2 , PhD   ; 
• Thomas K Houston II 1, 2 , MD, MPH  

1 Atrium Health Wake Forest Baptist, Winston Salem, NC, United States

2 Wake Forest University School of Medicine, Winston Salem, NC, United States

3 Department of Population and Quantitative Health Sciences, University of Massachusetts Chan Medical School, Worcester, MA, United States

4 Center for Healthcare Organization and Implementation Research, Veterans Affairs Bedford Healthcare System, Bedford, MA, United States

Corresponding Author:

Jessica A Palakshappa, MD, MS

Wake Forest University School of Medicine

1 Medical Center Blvd

Winston Salem, NC, 27157

United States

Phone: 1 336 716 8465

Email: [email protected]

Background: Numerous prior opinion papers, administrative electronic health record data studies, and cross-sectional surveys of telehealth during the pandemic have been published, but none have combined assessments of video visit success monitoring with longitudinal assessments of perceived challenges to the rapid adoption of video visits during the pandemic.

Objective: This study aims to quantify (1) the use of video visits (compared with in-person and telephone visits) over time during the pandemic, (2) video visit successful connection rates, and (3) changes in perceived video visit challenges.

Methods: A web-based survey was developed for the dual purpose of monitoring and improving video visit implementation in our health care system during the COVID-19 pandemic. The survey included questions regarding rates of in-person, telephone, and video visits for clinician-patient encounters; the rate of successful connection for video visits; and perceived challenges to video visits (eg, software, hardware, bandwidth, and technology literacy). The survey was distributed via email to physicians, advanced practice professionals, and clinicians in May 2020. The survey was repeated in March 2021. Differences between the 2020 and 2021 responses were adjusted for within-respondent correlation across surveys and tested using generalized estimating equations.

Results: A total of 1126 surveys were completed (511 surveys in 2020 and 615 surveys in 2021). In 2020, only 21.7% (73/336) of clinicians reported no difficulty connecting with patients during video visits and 28.6% (93/325) of clinicians reported no difficulty in 2021. The distribution of the percentage of successfully connected video visits (“Over the past two weeks of scheduled visits, what percentage did you successfully connect with patients by video?”) was not significantly different between 2020 and 2021 ( P =.74). Challenges in conducting video visits persisted over time. Poor connectivity was the most common challenge reported by clinicians. This response increased over time, with 30.5% (156/511) selecting it as a challenge in 2020 and 37.1% (228/615) in 2021 ( P =.01). Patients not having access to their electronic health record portals was also a commonly reported challenge (109/511, 21.3% in 2020 and 137/615, 22.3% in 2021, P =.73).

Conclusions: During the pandemic, our health care delivery system rapidly adopted synchronous patient-clinician communication using video visits. As experience with video visits increased, the reported failure rate did not significantly decline, and clinicians continued to report challenges related to general network connectivity and patient access to technology.

Introduction

Interest in telehealth from policy makers, health care providers, patients, and families continues to grow [ 1 ], including newer modalities such as video visits [ 2 ]. Video visits refer to clinician-patient communication that includes real time video and audio assessment of the patient when the clinician is in a different location. Video visits have the potential to improve efficiency for clinicians and to improve access for patients, particularly those who reside in rural areas or with transportation barriers [ 3 ]. The technology to support video visits has existed for decades; however, only a small minority of clinicians used this form of telehealth in their practices [ 4 ] prior to the COVID-19 pandemic. There are multiple reasons why telehealth adoption was slow despite its potential benefits including changing cost and reimbursement policies, federal and state licensing laws, incompatible electronic health records, and gaps in internet access in certain areas.

The COVID-19 pandemic and subsequent public health emergency led to fundamental shifts in how health care was delivered in the United States, including the rapid adoption of telehealth services. Before the public health emergency, approximately 13,000 fee-for-service Medicare beneficiaries received telehealth services in a week and that number increased to nearly 1.7 million beneficiaries by the last week of April 2020 [ 5 ]. While the need to avoid in-person contact fueled the initial rapid rise, regulations and restrictions were temporarily lifted during this time facilitating its use. Clinicians were also paid for telehealth services at the same rate as in-person medical services. Several studies have reported on the rapid uptake of telehealth, including video visits, in this context [ 6 - 8 ]. However, few reports have explored rates of success and failure of video visits over time. The challenges clinicians face in conducting video visits have also not been explored. Understanding these challenges will be important for improving and expanding the reach of telehealth services after the pandemic has ended.

In the context of the rapidly increasing use of telehealth to conduct video visits, and consistent with the sociotechnical model’s [ 9 ] emphasis on monitoring the implementation of health information technology in complex adaptive health care systems, our health care delivery system initiated a series of brief assessments of video visit adoption. The research objective of this report is to summarize the findings of the video visit monitoring including (1) the use of video visits (compared with in-person and telephone visits) over time during the pandemic, (2) video visit successful connection rates, and (3) changes in perceived video visit challenges. With patient and clinician skills and experience with video visits increasing over time, our primary hypothesis was that clinicians’ perceived challenges to completing video visits (eg, software, hardware, bandwidth, and technology literacy) would decline over time.

Study Design

The design was a longitudinal series of 2 cross-sectional assessments (2020 and 2021). In summary, for the dual purpose of monitoring and improving telehealth implementation in our health care delivery system, institutional leaders developed a brief web-based survey regarding the use of video visits and challenges. The survey was initially distributed in 2020. Given the ongoing public health emergency and the need to re-evaluate telehealth use, the survey was repeated in 2021. Institutional leaders encouraged clinicians to complete the survey, communicating encouragement via emails and announcements at in-person faculty and departmental meetings.

Ethical Considerations

As the brief assessments were distributed by the clinical system as part of ongoing quality improvement, the project was approved as an research protocol as exempt from human participants approval by the Wake Forest University School of Medicine Institutional Review Board (IRB00077473). The survey did not collect identifying information from the participants.

Survey Development

Published in 2010 by Sittig and Singh [ 9 ], the sociotechnical model of health information technology was the first to fully emphasize the importance of system monitoring in implementation frameworks. Key aspects of monitoring, including measuring how the technology is being used by clinicians and whether implementation outcomes are being achieved, were considered when developing the survey. The survey was developed with a literature search, expert review, and iterative pilot-testing (see Multimedia Appendix 1 ). The final survey included 12 questions related to rates of in-person, telephone, and video for clinician-patient encounters; the rate of successful connection for video visits; and perceived challenges to video visits (eg, software, hardware, bandwidth, and technology literacy).

Study Population

The study population included all outpatient clinicians practicing across the health care delivery system; we excluded clinicians without direct patient care responsibilities. The system includes 5 hospitals and over 350 primary care and specialty clinics that provide care to over 2 million persons annually. The brief assessment was distributed to clinicians in 2020 and 2021 (1937 clinicians and 2843 clinicians, respectively).

Survey Distribution and Data Collection

As we are an integrated health care delivery system, we had access to the contact details of all providers. Our group practice clinical operations executive committee facilitated the survey distribution by requesting that each department chair and clinical service line director send an email to their team of providers to notify them of the survey and encourage completion. Surveys were collected and managed using REDCap (Research Electronic Data Capture), a secure, web-based app designed to support data capture [ 10 , 11 ]. A unique survey link was distributed via email to each clinician in May 2020 and March 2021. The system sent up to 2 reminder emails if the recipient had not yet completed the survey.

Statistical Analysis

To take full advantage of the data collected, we first analyzed the results as 2 cross-sectional surveys. In this primary analysis, we included all respondents in each year. We recognize that a subset of clinicians also responded in both years. Thus, as a secondary analysis, we analyzed the data limited to the longitudinal cohort who participated in both years. First, summary statistics are presented as count (frequency) for categorical variables and mean (SD) or median (IQR) for continuous variables as appropriate. Generalized estimating equations were then used to model frequency distributions of in-person, telephone, and video visits, and patient and clinician challenges. These logit models were adjusted for within-respondent correlation across surveys via an exchangeable correlation structure. P values of .05 were considered statistically significant. P values for multiple comparisons in frequency distributions of in-person, telephone, and video visits between physicians, advanced practice professionals (APPs), and other clinicians were adjusted via the Tukey-Kramer method to control for type I errors with a corrected P value <.05 deemed statistically significant [ 12 ]. All statistical analyses were performed with R (version 4.2.1; R Core Team) [ 13 ].

We recognize that a subset of clinicians responded in both years. Thus, as a secondary analysis, we analyzed the data limited to the longitudinal cohort who participated in both surveys. For the secondary analysis, matched pairs analyses were performed as were performed in the entire sample with only those responses from clinicians that completed both surveys.

Surveillance Participation and Participant Characteristics

In 2020, 1937 surveys were sent and 511 responses were received (response rate 26.4%). In 2021, 2843 surveys were sent and 615 responses were received (response rate 21.6%). In both years, over 55% of the respondents were physicians from a wide range of clinical specialties. About half of the clinicians who completed the survey in 2020 also completed it in 2021 ( Table 1 ).

a n=511 responses in 2020 and n=615 responses in 2021.

b n=300 responses in 2020 and n=353 responses in 2021.

Health Care Delivery by In-Person and Telephone

To place the volume of telehealth in context, we first asked about the number of in-person encounters completed over the past 2 weeks ( Table 2 ). The distribution of responses differed between 2020 and 2021 ( P <.001). Modeled probabilities show fewer respondents reported zero (22.2% vs 4.9%) or 1 to 10 (33.5% vs 11.5%) in-person visits in 2021 as compared with 2020. The volume of in-person visits increased over time ( Table 2 ). Further, the majority of respondents (399/509, 78.4%) reported at least 1 telephone visit in 2020 and 65.7% (369/562) in 2021 although the distribution of responses differed from 2020 to 2021 ( P <.001).

a Differences in frequency distributions between 2020 and 2021 tested via generalized estimating equation modeling; P value adjusted using Tukey-Kramer method to control for type I errors.

Health Care Delivery by Video Visits

Many health care providers were engaged in virtual care, with 65.9% (336/510) health care providers reporting video visit encounters in 2020 and 57.6% (325/564) health care providers reporting video visit encounters in 2021 ( Table 2 ) although the distribution of responses again changed from 2020 to 2021 ( P <.001). Compared with 2020, fewer 2021 respondents reported 11-25 (18.6% vs 6.7%), 26-50 (5.9% vs 2.8%), or over 50 (2.4% vs 2%) visits.

Secondary analyses were robust to missing data and showed that the results (distributions of in-person, phone, and video visits) did not change when limiting the data to only respondents who participated in both surveys.

Comparing Health Care Delivery by Physicians, APPs, and Others

We also compared health care delivery modality by type of clinician (physicians, APPs, or others). Patterns of health care delivery reported in the overall sample were similar in the physician, APP, and other subgroups. There were no significant differences between physicians and APPs in the number of patient encounters that were completed as in-person, telephone visits, or video visits in 2020 or 2021.

Perceived Challenges to Patient-Clinician Connection Using Video Visits

The use of video visits came with challenges. In 2020, only 21.7% (73/336) of clinicians reported no difficulty connecting with patients during video visits and 28.6% (93/325) of clinicians reported no difficulty in 2021 ( Figure 1 ). The distribution of the percentage of successfully connected video visits (“Over the past two weeks of scheduled visits, what percentage did you successfully connect with patients by video?”) was not significantly different between 2020 and 2021 ( P =.74, Figure 1 ). There was also no significant difference between physicians and APPs in the rate of successful video connection with patients in either year.

Clinicians were asked about the challenges in successfully completing video visits (see Table 3 ). The most commonly reported challenge was poor connectivity. This response increased over time with 30.5% (156/511) selecting it as a challenge in 2020 and 37.1% (228/615) selecting it as a challenge in 2021 ( P =.01). Patients not having access to their electronic health record portals was also a commonly reported challenge (109/511, 21.3% in 2020 and 137/615, 22.3% in 2021; P =.73).

a P value adjusted using the Tukey-Kramer method to control for type I errors.

b For some clinical video visits, a prerequisite was that patients needed to have registered with the patient portal.

Principal Findings

Although telehealth technology was available in our health care delivery system prior to the COVID-19 pandemic, it saw only limited use for providing synchronous care to patients prior to the pandemic. Inconsistent reimbursement for services, restrictions on the physical location of patients and clinicians during telehealth, and rules about types of visits that were acceptable for telehealth services all contributed to its limited use [ 14 , 15 ]. With the pandemic, and consistent with other reports, our health care delivery system rapidly expanded the provision of clinical care by way of video visits. Later in the pandemic, in-person visits did increase, but the use of video visits remained well above prepandemic levels.

Overall, there has been a shift toward a more positive sentiment about telehealth and telemedicine since the start of the pandemic. A scoping review by Doraiswamy et al [ 16 ] reported 543 telehealth-related papers (mostly opinions, commentaries, and perspectives; 61%) published across 331 different journals from January to June 2020. Most of these new reports had a “celebratory” or favorable sentiment about the use of telehealth. The scope of the increase in telehealth during the public health emergency likely contributed to this sentiment though concerns about patient and clinician connection, the lack of physical examinations, and cost-effectiveness were still noted by some. Although our providers reported benefits for clinical video telehealth beyond audio-only calls for patient-provider visits, failure to connect using clinical video visits was common.

While reports have documented challenges with clinical video telehealth [ 17 ], few have monitored these challenges over time. During the pandemic, as our health care delivery system’s experience with video visits grew, clinicians did not report a meaningful reduction in connection failure rate. The most frequently reported challenges were general network connectivity and those related to the digital divide (eg, patient lack of internet access, needed software, or internet-connected cameras). Gaps in access to technology and the internet for telehealth may impact some patient groups more than others. For example, older age, rural residence, dual Medicare and Medicaid enrollment, and non-Hispanic Black or Hispanic race or ethnicity have been shown to be associated with a lower probability of technology ownership, access to the internet, and use of the internet for communication in cancer survivors [ 18 ]. Further, over 10% of clinicians also reported that they experienced software or hardware challenges (eg, limited availability of internet cameras at a clinical location). Expanding telehealth will require ongoing investments in technology for clinicians. New workflows to support successful connection during video visits and follow-up processes may also be needed.

Our video visit monitoring results were shared with clinical operations leadership. In response to the sustained challenges noted, we initiated a new video visit program to provide patient support prior to scheduled video visits. Our technology navigators are a specially trained, centralized team and are directed to reach out to vulnerable patients and families to facilitate video visit access. A new electronic health record dashboard identified patients with (1) a scheduled video visit and (2) 1 or more risk factors (eg, lack of a prior successful video visit and lack of patient portal access). We further prioritized patients older than 65 years and those living in rural areas. Technology navigators reached out by telephone to contact these at-risk patients to assess their technology access (eg, internet, software, webcam, or smartphone), technology literacy and perceived competence, and availability of at-home support from family and friends. The technology navigators then troubleshoot any challenges noted by the patients and offer to conduct a “practice” video visit. Evaluation of this program is ongoing. In 2022-2023, the navigators contacted 1266 patients at high risk for video visit failure. Among those contacted, 515 requested and were provided assistance. With previsit support from the navigators, the patient-provider scheduled video visit completion rate was 84% as compared with a 60% completion rate among those patients who did not receive support.

Limitations of our video visit surveillance analysis include that the data were collected across 1 health care delivery system with an integrated electronic health care record system. The perceptions and challenges may be different in a smaller health care system and in those with different health care record systems. The survey measured only clinician-reported telehealth use and success rates which may be limited by recall. As with all surveys, our results may be biased as only about one-quarter of the sample responded. It is possible that respondents experienced more challenges conducting video visits than those who did not respond. Further, not all clinicians longitudinally completed both the 2020 and 2021 surveys—due both to response rates and providers leaving and entering the health care system. Thus, changes over time may represent differences in the underlying sample. For example, new clinicians may have been more or less familiar with conducting video visits.

Conclusions

Recent reviews have noted the need for more evidence related to telehealth’s implementation, effectiveness, and health equity in telehealth access [ 16 , 19 , 20 ]. Although internet and smartphone access has increased over the last decade (with older adults being one of the fastest-growing subgroups of new adoption), our longitudinal video visit surveillance reveals that the digital divide is still a significant barrier to video visit access.

Although Healthy People 2030 (a set of national objectives to improve health and well-being) includes developmental and research objectives related to patient portals and increasing the use of telehealth to improve access to health services [ 21 ], some social determinants of health taxonomies do not include technology access. If telehealth is increasingly an important component of health care access, then technology access (eg, internet, smartphone, patient portal, and connected hardware, such as internet-connected video) should be considered a social determinant of health [ 22 ]. A comprehensive solution to overcoming the digital divide has not yet been achieved. However, some partial solutions include directly providing technology to patients, providing detailed instructions, and support services (eg, our technology navigator program), and engaging trusted caregivers (family and friends) who may be able to assist patients [ 23 - 27 ].

Acknowledgments

The project was supported through the National Cancer Institute Cancer Moonshot initiative—iDAPT: Implementation and Informatics–Developing Adaptable Processes and Technologies for Cancer Control (P50 CA244693); the Wake Forest Clinical and Translational Science Award (5UL1TR001420); and also a career development award to JAP (1K23AG073529).

Conflicts of Interest

None declared.

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Abbreviations

Edited by G Eysenbach, T Leung; submitted 26.10.23; peer-reviewed by K Moulaei; comments to author 19.12.23; revised version received 24.01.24; accepted 09.03.24; published 08.04.24.

©Jessica A Palakshappa, Erica R Hale, Joshua D Brown, Carol A Kittel, Emily Dressler, Gary E Rosenthal, Sarah L Cutrona, Kristie L Foley, Emily R Haines, Thomas K Houston II. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 08.04.2024.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in the Journal of Medical Internet Research, is properly cited. The complete bibliographic information, a link to the original publication on https://www.jmir.org/, as well as this copyright and license information must be included.

Home » Russian Food » Getting hungry at midnight? Here are 24 hour food delivery in Russia

Getting hungry at midnight? Here are 24 hour food delivery in Russia

• Post author By Yulie
• Post date December 17, 2018
• No Comments on Getting hungry at midnight? Here are 24 hour food delivery in Russia

24-hour food delivery in Russia

The food delivery is another online service that continues to show steady growth and even provide 24 hours services. The benefit of working together from both restaurant and delivery services has welcome many fans and subscribers. The combination of network, resources and, expertise is the latest trend of business in Russia. Here are some reputable and well-known food delivery in Russia.

1. Grow Food

The company at first offers food delivery to athletes on a subscription basis. Then more various customer start ordering their long list of healthy dishes. Their service available both in Moscow and Saint Petersburg, which expansion plan to Krasnodar, Kazan, and Yekaterinburg and other Russian cities. Grow Food delivery home cook meals with the highlight of Russian vegan food . Therefore, you can set assure this company delivers fresh and great food.

2. Food Panda

Food Panda is a combination of companies Russia’s leading food delivery service with over 2,500 restaurants in Russia. Moreover, It also plans to reach 50 countries in the future. The food delivery service works together with many restaurants. You have wide range choices from an inexpensive restaurant , Halal restaurant , or even late-night restaurants. Therefore, you can easily ask them to bring your favorite dish from your favorite restaurant.

3. ChefMarket

The Moscow-based food delivery offers a trial delivery without subscription for a weekly delivery of fresh ingredients with recipes for your dinners. It brings you fresh ingredients to cook yourself. Moreover, it gives customer freedom to arrange their own menu.

The difference of this delivery compared to other food delivery is their weight lost menu. The food that helps you lose weight  is put together by the best chef working together with weight loss expert. This course is a collaboration with French nutritionist doctor Pierre Dukan. The ingredients and recipes claim to lose 5 kg extra weight per month on average.

It is easy to get high-quality restaurant meals to your doorstep in 45 minutes or less. Foodfox reinvents food ordering by working closely with best restaurants and providing fast, transparent and reliable delivery. This food delivery started delivering in Moscow city and expanded its delivery services coverage over time. Their services also come with an online website and Foodfox app on iPhone or Android.

5. ZakaZaka

There are over than 2,600 connected restaurants and 126,000 orders in this 24 hours service food delivery. ZakaZaka claims to be the second player in the Russian food delivery market. Their services also include a mobile app that makes it easier for anyone to order. Especially if you want to eat but don’t want to go out. It is a solution for a late night dinner at home with restaurant menus.

6. Ginza Delivery

This food delivery service tries to win costumers over with lots of promotional ads. There are points to redeem from registration to their apps or website. In addition, there are much bonus with extra discounts for many various kinds of orders. They provide various food in collaboration with popular restaurants in the area. Moreover, this delivery service also provides gifts and flowers delivery. Moreover, beside delivery foo,d they also deliver groceries like vegetables, fruits, and other products. Their service is 24 hours a day around the clock.

7. Yandex.Eat

Yandex is one of Russian famous shopping online service  and their expansion business into food delivery services called Yandex.Eats. It connects hungry consumers with restaurants with an easy efficient method for receiving food delivery from nearby restaurants within 30-35 minutes. Like other food delivery apps in Russia, Yandex.Eats has an easy-to-navigate app, available in 24 Russian cities with 6500+ restaurant options. The most important feature is their 24 hours service to serves all day and night long.

In addition to their long list of features, is the concept of the ‘Dark Kitchens’ where several partner restaurants share space to prepare food for delivery by Y.Eats. The bright yellow branding food service filled the streets of Moscow, with the delivery team cruising all around the city on scooters.

8. Munchery

This food delivery specializes in Russian dishes. It is a great way to have a taste of true Russia flavors with their authentic natural ingredient and spices. It claims to serve delicious, all-natural, chef-crafted food, precisely where and when you want it. Therefore, you can expect around the clock service with the best result. It literally tries to serve various mealtimes, take-out, home cooking variety as their specialty.

9. Pizzasushiwok

The very first food delivery is the worldwide pizza delivery. You can’t miss out a chance to try out this Italian famous dish in Russia. One of the most popular websites and food delivery in Moscow is Pizzasushiwok. As the name suggests, it’s a classic Russian combo of Japanese and pizza. Apparently, among the  most likable things for Russian people have is both of these dishes. The site gives great food delivery option with easy payment methods. Moreover, delivery is free in the Moscow area for orders over certain amounts.

10. Yakitoriya

This Asian based food delivery service offers good-quality Asian food and fusion. Their English-language website makes it easier for foreign traveler in Russia to make an order and use their websites. Their best famous dish is sushi which is the number one popular order for customers. It is an option among other food available to bring right in front of your doorstep.

Moscow now has a whole service for meeting the need for easy shopping, whether its clothes, books or the basic need as meals and snacks. There are online websites and food delivery that allow you to order and pay either online or by cash after your food arrives at your front door. Moreover, many of these services are available not only in Russia but also in English. It is another reason for traveling to Russia and never worry about what to eat and where.

That late night craving is an easy problem by using these numerous food delivery service available in most big cities in Russia. They have many great features, English spoken officers and apps to cater to the need of foreign traveler. Do the proper search, have detailed info on the food and your place of stay to ensure a fast deliverance. Moreover, ordering during rush hour, it is wise to place orders in up to an hour and a half in advance.

• Tags 24 hours food delivery , food delivery , russia , russian foods

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