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Safety and side effects of apple vinegar intake and its effect on metabolic parameters and body weight: a systematic review

• Published: 13 March 2020
• Volume 59 , pages 2273–2289, ( 2020 )

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• Tine Louise Launholt 1 ,
• Christina Blanner Kristiansen 2 &
• Peter Hjorth 3 , 4 , 5  

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Introduction

Apple vinegar (AV) has been proclaimed to have different health benefits, such as a weight loss, the ability to lower blood glucose levels, and reducing the risk of heart diseases. Studies on animals have demonstrated effects of AV consumption, deepening our knowledge of the beneficial effects and side effects.

The aims of this study were to evaluate the evidence of the effect of AV on metabolic parameters and body weight in humans, furthermore, to evaluate the safety and side effects of ingesting AV, and additionally to evaluate the evidence of the effect of AV on metabolic parameters, safety, and side effects of AV from studies performed on animals (mammals).

A systematic literature search was performed. The databases PubMed (MEDLINE), PsycInfo (Ebsco), CINAHL (Ebsco), and Embase (Ovid) were searched for relevant articles. Primary outcomes were glycated hemoglobin, postprandial glucose, and synonyms for blood glucose. Secondary outcomes were waist circumference, visceral fat, high-density lipoprotein, low-density lipoprotein, triglycerides, and total cholesterol. Studies performed on humans and animals were included. The included studies performed on humans were quality assessed for risk of bias using a version of the Cochrane Collaboration’s tool.

A total of 487 papers were identified in the literature search. Of these, 13 studies performed on humans and 12 studies performed on animals were included. There may be beneficial health effects from the consumption of AV. The risk of side effects when ingested in recommended quantities and in recommended ways seems inconsiderable.

Due to inadequate research of high quality, the evidence for the health effects of AV is insufficient. Therefore, more large-scale, long-term clinical studies with a low risk of bias are needed before definitive conclusions can be made.

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Nursing Education, UCL University College, Vejle, Denmark

Tine Louise Launholt

Psychiatric Department Odense – University Function, Mental Health Services, Region of Southern Denmark, Odense, Denmark

Christina Blanner Kristiansen

Department of Psychiatry, University of Southern Denmark, Vejle, Denmark

Peter Hjorth

Institute of Regional Health, University of Southern Denmark, Odense, Denmark

Centre for Psychiatric Nursing and Health Care Research, Region of Southern Denmark, Odense, Denmark

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All the authors have made substantial contributions to the conception and design of this study. PH and TL conducted the search and data extraction; PH and TL collected the data; and PH and TL analyzed the data and wrote the manuscript. All the authors read and approved the final content.

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Launholt, T.L., Kristiansen, C.B. & Hjorth, P. Safety and side effects of apple vinegar intake and its effect on metabolic parameters and body weight: a systematic review. Eur J Nutr 59 , 2273–2289 (2020). https://doi.org/10.1007/s00394-020-02214-3

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Received : 18 September 2019

Accepted : 26 February 2020

Published : 13 March 2020

Issue Date : September 2020

DOI : https://doi.org/10.1007/s00394-020-02214-3

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Authenticating apple cider vinegar's home remedy claims: antibacterial, antifungal, antiviral properties and cytotoxicity aspect

Affiliations.

• 1 a Department of Environmental Health Science , Konkuk University , Seoul , Korea.
• 2 b Department of Biotechnology , Indian Institute of Technology-Madras , Chennai , India.
• 3 c Department of Bioresources and Food Science , Konkuk University , Seoul , Republic of Korea.
• PMID: 29224370
• DOI: 10.1080/14786419.2017.1413567

These are the days when one would go online first seeking home remedies before seeing a doctor. Apple cider vinegar (ACV) is one such popular yet scientifically under-validated remedy. Our results prove the unequivocal antimicrobial activity of ACV to be true at full strength concentrations. However, the activity cannot be generalised because although strong antibacterial activity was observed at 25% concentrations, in terms of antifungal activity, yeasts, especially Candida were found to be less susceptible. The antimicrobial/antioxidant properties are ascertained to the total phenolic contents of ACV, as confirmed by our characterisation of the bioactive compounds and antioxidant activity. When checking for its cytotoxicity, ACV exhibited toxicity even at concentrations as low as 0.7%. These results indicate that there is no question of generalising the idea of ACV usage, instead more in vitro and in vivo validations are necessary in order to precisely weigh the pros and cons of ACV.

Keywords: Apple cider vinegar; anti-influenza; antibacterial; antifungal; home remedy.

• Acetic Acid / pharmacology*
• Anti-Bacterial Agents / pharmacology*
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• Antioxidants / pharmacology*
• Antiviral Agents / pharmacology*
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• Microbial Sensitivity Tests
• Anti-Bacterial Agents
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Is Apple Cider Vinegar Really a Cure-All?

It has been said to help with weight loss, blood sugar control, acne and more. But experts say the science is more nuanced.

By Alice Callahan

On TikTok , a man swirls a tablespoon of apple cider vinegar into a cup of water, drinks it and eats two slices of pizza. Then, he tests his blood sugar. “These are the best results of all,” he says, showing a much lower spike on a blood sugar graph than when he ate the pizza without the vinegar.

In other posts, TikTok users rave about apple cider vinegar’s remarkable ability to help them lose weight , settle their stomachs and — when applied to their skin — clear their acne and eczema .

Apple cider vinegar has been used as a home remedy for healing wounds, quelling coughs and soothing stomachaches for thousands of years, said Carol Johnston, a professor of nutrition at Arizona State University.

But while some of apple cider vinegar’s health claims have a little science behind them, Dr. Johnston said, many claims haven’t been studied at all. Here’s what we know about apple cider vinegar — and some important cautions to keep in mind if you try it.

How might apple cider vinegar benefit health?

Apple cider vinegar is made via fermentation, in which yeast and bacteria convert carbohydrates first into alcohol and then into acetic acid, which gives vinegar its pungent taste and odor and potentially, research suggests, its health benefits, Dr. Johnston said.

Social media proponents often recommend using unpasteurized and unfiltered versions, which contain a haze of bacteria and undigested carbohydrates called “the mother,” said Dr. Chris Damman, an associate professor of gastroenterology at the University of Washington School of Medicine. But there’s no evidence that these “raw” apple cider vinegars are healthier than regular ones, he said.

Vinegars made from apples and other fruits also contain compounds called polyphenols, which have antioxidant and anti-inflammatory properties and might contribute to their potential health benefits, he said.

What does the research suggest?

Blood sugar control.

In the early 2000s, Dr. Johnston, who had been studying how certain diets could help manage Type 2 diabetes, came across a study from 1988 showing that acetic acid could lower blood sugar spikes in rats after they were given a starch solution.

She was intrigued and decided to test the idea in people with Type 2 diabetes and insulin resistance .

Since then, Dr. Johnston and other researchers have found in small limited studies that drinking one to two tablespoons of apple cider or other types of vinegar mixed with water just before high-carbohydrate meals resulted in less drastic blood sugar spikes than meals without vinegar did.

Some studies suggest that vinegar may slow the movement of food through the digestive tract and interfere with certain enzymes that break carbohydrates down into simple sugars, resulting in lower blood sugar spikes.

But more research is needed to show that apple cider vinegar is safe and beneficial for long-term use, said Paul Gill, a researcher at Monash University in Australia.

Weight loss

Several small, short-term studies in adults who were classified as overweight or obese have found associations between apple cider vinegar and weight loss.

In a 2009 study of 155 adults in Japan, for instance, researchers found that those who drank two tablespoons of apple cider vinegar in water every day for three months lost about four pounds. And in one 2024 trial of 120 people aged 12 to 25 in Lebanon, researchers reported that those who took one tablespoon of apple cider vinegar with water each morning for three months lost an average of 15 pounds.

But the one study that tracked participants after they stopped taking apple cider vinegar found that, on average, they regained most of the weight within a month. And just as many studies on similar groups of people have found no links to weight loss.

Given the lack of robust data and the short time frames of the studies, Beth Czerwony, a dietitian at the Cleveland Clinic, said that she did not recommend that her patients use apple cider vinegar for weight loss.

If vinegar does indeed help people lose weight, it may do so by slowing digestion, which can make you feel fuller for longer, she said.

Animal research has also shown that acetic acid can reduce the accumulation of fat in certain tissues and may help increase the secretion of hormones that signal fullness. So while the evidence in humans is mixed, it’s plausible that vinegar could help with weight loss, Dr. Damman said.

Tamara Duker Freuman, a dietitian in New York City who specializes in digestive conditions, said that many of her patients remark that drinking apple cider vinegar before or after meals reduces their symptoms of acid reflux .

“I believe them,” she said. But, she noted, “hundreds of other patients with horrible reflux” have said that vinegar worsened their symptoms.

Unfortunately, there’s no good research on vinegar and digestive health, said Dr. Nitin K. Ahuja, a gastroenterologist at Penn Medicine.

People who use vinegar to treat reflux, which is commonly caused by stomach acid escaping into the esophagus, say that the acid from the vinegar prompts the stomach to produce less acid, Dr. Ahuja said. But, he added, there’s no supportive data, and “mechanistically, it doesn’t make sense” that adding acid to the stomach will somehow help to control it.

Studies performed in petri dishes suggest that apple cider vinegar can kill certain microbes , which could potentially create gut microbiome changes that might reduce bloating, Dr. Ahuja said. But again, he added, this has not been studied in humans.

If you have frequent or severe reflux symptoms, get treatment from a doctor, he said.

Skin conditions

Applying dilute apple cider vinegar to the skin has long been used as a home remedy for eczema, Dr. Lydia Luu, a dermatologist at the University of Virginia School of Medicine, said. And after several patients asked about such a treatment, she and her colleagues decided to test it.

In their 2019 study , the researchers asked 22 participants, half of whom had eczema, to soak one arm in tap water and one arm in dilute apple cider vinegar for 10 minutes per day for two weeks. Afterward, there were no differences between the participants’ skin in terms of its pH, microbes or its ability to retain moisture — all of which are typically altered in eczema. Sixteen of the study participants reported symptoms like mild burning or itching, mostly on the arm treated with vinegar; one developed severe itching, moderate burning and a small sore; and another developed a raised rash.

Apple cider vinegar “is not very helpful for eczema, unfortunately,” Dr. Luu said — and could make your symptoms worse.

Some of Dr. Luu’s patients “swear by” apple cider vinegar for wart removal, and TikTok is teeming with videos suggesting such a treatment for acne or dark spots or to remove skin tags . But there aren’t good studies about these uses, Dr. Luu said, and apple cider vinegar can cause chemical burns and skin scarring .

Is it safe to try?

Consuming apple cider vinegar, even when diluted, can interact with certain medications, including some drugs for diabetes and the heart, as well as diuretics. Apple cider vinegar may also lower blood potassium, which can be a problem for those who already have low levels, Ms. Czerwony said. So check with your doctor before trying it, she said.

The same advice goes for using apple cider vinegar on your skin, Dr. Luu said. A primary care doctor or dermatologist can likely recommend safer, more effective treatments.

If you want to use vinegar to control your blood sugar, Dr. Johnston suggested diluting one or two tablespoons of any type of vinegar into water and drinking, but don’t exceed two to four tablespoons in a day. Even when diluted, vinegar can erode tooth enamel , so she recommended drinking the vinegar with a straw.

If you drink it undiluted, you run the risk of corroding your esophagus lining too, Dr. Ahuja said.

“Don’t just shoot it,” Dr. Johnston added.

A safer and tastier approach, Dr. Damman suggested, is to use apple cider vinegar in your cooking. Mix it into a vinaigrette or sushi rice , pair with olive oil as a dip for bread, or incorporate it into a refreshing fizzy drink . If there are any health benefits to be reaped, he said, you’ll likely get them this way, too.

Alice Callahan is a Times reporter covering nutrition and health. She has a Ph.D. in nutrition from the University of California, Davis. More about Alice Callahan

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A Combination of Apple Vinegar Drink with Bacillus coagulans Ameliorates High Fat Diet-Induced Body Weight Gain, Insulin Resistance and Hepatic Steatosis

Raquel urtasun.

1 Biochemistry Area, Department of Health Science, Public University of Navarre, 31008 Pamplona, Spain; [email protected] (R.U.); [email protected] (M.A.); [email protected] (M.J.P.); [email protected] (M.O.)

Joana Díaz-Gómez

2 Ecovinal S.L., Pol. Ind Gobella, 1, 31589 Sartaguda, Spain; moc.lanivoce@zaidj (J.D.-G.); se.lanivoce@allinumg (G.M.)

Miriam Araña

María josé pajares.

3 Navarre’s Health Research Institute (IdiSNA), 31008 Pamplona, Spain

María Oneca

Paloma torre.

4 Nutrition and Bromatology area, Department of Natural Sciences, Public University of Navarre, 31006 Pamplona, Spain; se.arravanu@amolap

Maddalen Jiménez

5 Division of Hematological-Oncology, CIMA, University of Navarre, 31006 Pamplona, Spain; se.vanu@nazenemijm

Germán Munilla

Miguel barajas, ignacio encío.

Obesity is a worldwide epidemic characterized by excessive fat accumulation, associated with multiple comorbidities and complications. Emerging evidence points to gut microbiome as a driving force in the pathogenesis of obesity. Vinegar intake, a traditional remedy source of exogenous acetate, has been shown to improve glycemic control and to have anti-obesity effects. New functional foods may be developed by supplementing traditional food with probiotics. B. coagulans is a suitable choice because of its resistance to high temperatures. To analyze the possible synergic effect of Vinegar and B. coagulans against the metabolic alterations induced by a high fat diet (HFD), we fed twelve-week-old C57BL/6 mice with HFD for 5 weeks after 2 weeks of acclimation on a normal diet. Then, food intake, body weight, blood biochemical parameters, histology and liver inflammatory markers were analyzed. Although vinegar drink, either alone or supplemented with B. coagulans , reduced food intake, attenuated body weight gain and enhanced glucose tolerance, only the supplemented drink improved the lipid serum profile and prevented hepatic HFD-induced overexpression of CD36, IL-1β, IL-6, LXR and SREBP, thus reducing lipid deposition in the liver. The beneficial properties of the B. coagulans -supplemented vinegar appear to be mediated by a reduction in insulin and leptin circulating levels.

1. Introduction

The prevalence of obesity has increased worldwide in the last ~50 years, reaching epidemic proportions. Nowadays, it is one of the world’s greatest public health challenges because it comes associated with metabolic complications such as dyslipidemia and insulin resistance with a consequent risk of cardiovascular disease, non-alcoholic fatty liver disease (NAFLD) and other adverse health conditions [ 1 ]. Excess food intake, especially high-calorie diets, such as high-fat and high-sugar diets, is considered the greatest risk factor in the development of obesity [ 2 ]. In addition, over the last decade, different studies have been highlighting an increasingly more important role of the gut microbiota in the development of obesity. Many studies have reported differences in microbiota composition between obese and lean humans [ 3 , 4 ] and experimental studies have demonstrated that both short-and long-term dietary change can influence our microbiota by reducing bacterial diversity and modifying the microbial composition taxa [ 5 ]. However, potential mechanisms by which gut microbiota promote metabolic disorders and obesity are still not well understood. Normally, dietary polysaccharides that escape digestion in the small intestine are metabolized by the microbiota into short-chain fatty acids (SCFA) during fiber digestion. The most abundant SCFA are acetate, propionate and butyrate. Although some studies postulated that excess SCFA and bacterial genes related to polysaccharides metabolism presented in feces are associated with the obese phenotype [ 6 ], new evidence has also demonstrated that SCFA could also increase energy expenditure and anorexic hormone production and support a beneficial role for SCFA in carbohydrates and lipid metabolism, contributing to improved insulin sensitivity [ 7 ]. In addition, SCFA improve the gut health maintenance of intestinal barrier integrity, mucus production and protection against inflammation [ 7 ].

So far, obesity treatments such as exclusively calorie reduced intake and/or bariatric surgery modify the gut microbiota and are associated with health benefits. However, they have not been completed successfully in the long term. Both present restricted benefits, mostly because of complex and persevering hormonal response [ 8 ]. Consuming diets or foods with bioactive nutrients, such as fermented foods, has been proposed as an effective solution to improve the effectiveness of conventional treatments [ 9 , 10 ]. Some fermented foods are highly enriched in SCFA. Vinegar, widely used as a flavouring and preservative in aliments, is a fermented drink enriched in bioactive components such as acetic acid and polyphenolic compounds [ 11 ]. Besides, oral ingestion of vinegar increases circulation of acetate [ 12 ]. Multiple functional properties of the vinegar are well established, including antioxidant, anti-hyperglycaemia, anti-hypertension, anti-microbial, anti-thrombotic and even anti-cancer properties [ 13 ]. Moreover, in the last decades, vinegar has captured some interest for its beneficial effects on controlling body weight and visceral fat accumulation [ 11 , 14 , 15 ]. Mechanistically, acetate has been found to block fatty acid synthesis and reduce lipid content in liver and adipose tissue, improving obesity [ 16 , 17 ].

Potential sources of exogenous acetate include vinegar as well as the supplementation of acetogenic fiber and probiotics or lactic acid bacteria [ 18 ]. Among lactic acid bacteria, Bifidobacterium and Lactobacillus are the most studied and used probiotic microorganisms [ 19 ]. However, these microorganisms cannot survive heat treatment. Bacillus spores can survive severe processing conditions as well as tolerate and resist against the harsh conditions found in the gastrointestinal tract [ 20 ]. Although the use of probiotic strains of Bacillus is still recent, emerging studies have described the health benefits associated with their ingestion [ 20 , 21 ]. For instance, probiotic strains of Bacillus were shown to provide protective effects against high fat diet-induced metabolic disorders in mice [ 22 ] and anti-obesity effects [ 23 ]. However, relatively few studies have examined the possible synergistic effect between fermented foods and a specific Bacillus species. B. coagulans GBI-30 is a lactic producing, spore forming, bacteria with GRAS (generally recognized as safe) status [ 20 ]. Authorized for human usage, the strain, that transiently colonizes the intestine without the need for frequent consumption, has already been proven to have beneficial effects in a variety of disorders, including irritable bowel syndrome, colitis, rheumatoid arthritis, and common viral infections of the respiratory tract [ 24 ].

For this reason, the aim of this study was to investigate whether the combination of B. coagulans GBI-30 with a heat-processed organic drink that contains apple cider vinegar, will be useful to prevent the development of obesity and its metabolic alterations such as insulin resistance and fatty liver in a mouse model of diet-induced obesity.

2. Materials and Methods

2.1. organic vinegar drink and probiotic strain.

The organic vinegar drink was elaborated by Ecovinal S.L. (Sartaguda, Spain) and contains 5% organic raw apple cider, unfiltered vinegar and fruit juices. The vinegar dose used in our animal study was equivalent to the concentration of one tablespoon of vinegar diluted in 300 mL. This concentration was selected based on previous animal studies considered as low dose [ 25 , 26 ] and the recommended amount in human studies (1 tablespoon of vinegar per day) [ 27 ]. The complete nutritional analysis is shown in Table 1 . After heat-treatment, the vinegar drinks were stored at room temperature until used. An organic drink of equal calorie content and formulation to apple vinegar drink without vinegar (Vehicle) was also produced by Ecovinal S.L. (Sartaguda, Spain) for the experimental animal procedure.

Nutritional analysis of organic apple vinegar drink.

Freeze-dried spores of B. coagulans GBI-30 6086, kindly provided by Ganeden Inc. (Mayfield Heights, OH, USA) were added to vinegar drinks in order to achieve 10 9 –10 10 spores per serving of the drink product (200 mL), i.e., approximately 10 7 –10 8 spores/mL. This dose was selected based on two different rat studies that showed increased fecal SCFA [ 28 ] and no metabolic homeostasis affectation [ 20 ].

2.2. Animal and Experimental Design

Eight-week-old male C57BL/6J mice were purchased from Charles River Laboratories. Mice were maintained in a temperature (22 to 28 °C) and humidity-controlled room on a 12-h light/12-h dark cycle with free access to food and drink during all of the study. In order to study the effect of vinegar and B. coagulans in a diet-induced obesity mice model, mice at the age of 12 weeks and at an average weight of 26.0 g, were randomly assigned into 5 groups ( n = 6 mice per group). Each group had free access to one of the following beverages:

(1) Water, (2) Organic drink without vinegar (Vehicle), (3) Vehicle with B. coagulans GBI-30 6086 (Vehicle_Bc), (4) Apple vinegar drink (Vinegar), (5) Apple vinegar drink supplemented with B. coagulans GBI-30 6086. (Vinegar_Bc). The different groups were acclimatized for 2 weeks with a normal standard pellet diet (ND).

Then, group 1 remained on the ND while the other groups were fed with a High fat diet (HFD) (60% Kcal from fat Teklad Diet TD.06414, Envigo, Madison, WI, USA) for 5 additional weeks, as shown in the experimental design ( Figure 1 ).

Animal groups and experimental design used in the study. HFD: High fat diet, ND: Normal rodent diet.

During the experimental study, food and drink intake were recorded 2 times per week and body weight was measured weekly. Drink was changed every 3 days to minimize contamination. At the end of the experimental period (7 weeks), animals were sacrificed by cervical dislocation after overnight fasting. All animal procedures were approved by the Institutional Committee on Care and Use of Laboratory Animals (CEEA, University of Navarra, Protocol number: 028-18).

2.3. Fasting Blood Glucose and Tolerance Test

Animals were fasted overnight, with free access to water prior to the test, and blood samples were obtained from the tip of the tail vein. Glucose concentrations were monitored using a pre-calibrated glucometer (Accu-chek Aviva, Roche, Basel, Switzerland). Fasting blood glucose (FBG) was recorded once a week.

In order to perform a glucose tolerance test (GTT), mice were fasted overnight, and 2 g/kg body weight of glucose was injected intraperitoneally. Measurement of blood glucose levels were performed at 0, 20, 40, 60, 90, and 120 min after glucose injection by collection of tail blood samples. The area under the curve (AUC) was assessed for each group from 0 to 120 min post glucose injection. The Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), a widely used index for the assessment of insulin resistance [ 29 ], was calculated by the formula: HOMA-IR = serum C-peptide (nmol L −1 ) * serum glucose (mmol L −1 )/22.5.

2.4. Serum Biochemical Analysis

Mice were fasted overnight before retro-orbital blood was drawn. Serum was obtained from blood samples after centrifugation for 15 min at 2200 × g at 4 °C. Supernatant was collected and stored at −20 °C. Fasting serum cholesterol and triglycerides (TG) were determined using direct enzymatic colorimetric assays (Sigma-Aldrich, St. Louis, MO, USA). Total Free fatty acid (FFA) serum levels were quantified by means of a colorimetric assay using a commercial kit (Sigma-Aldrich, St. Louis, MO, USA).

2.5. C-Peptide, GLP-1 and Leptin Analysis

Serum C-peptide was assayed by sandwich ELISA method using an Ultra-Sensitive Mouse C-peptide ELISA kit (Abyntek Biopharma, Derio, Spain). GLP-1 levels in serum were determined using an ELISA kit (Sigma-Aldrich, St. Louis, MO, USA). Leptin levels were quantified using an enzyme-linked immunosorbent assay ELISA kit (Sigma-Aldrich, St. Louis, MO, USA).

2.6. Quantitative Real-Time PCR (RT-qPCR)

Total RNA was extracted from the livers of mice using a RNeasy Mini kit (Qiagen, Germantown, MD, USA). Then, cDNA synthesis (RT) was performed with RT Premix (Invitrogen, Carlsbad, CA, USA). Quantitative real-time PCR (qPCR) were achieved using IQ SYBR green (Bio-Rad, Hercules, CA, USA), in a CFX Connect TM Real-time system (Bio-Rad, Hercules, CA, USA) according to the manufacturer’s instructions. The primer pairs used are listed in Table 2 . The mRNA levels were calculated as a ratio, using the 2 −∆∆ C T method, for comparing the relative mRNA expression levels between different groups in the qPCR. All qPCRs were performed in triplicate and RPLPO gene was used to normalize gene expression.

Primer sequence for qPCR.

Gene full names. RPLPO: Ribosomal protein P0; LXR: Liver X receptor; CD36: Cluster of differentiation 36; PPARα: Peroxisome proliferator.activated receptor; SREBP: sterol regulatory element-binding protein; FASN: Fatty acid synthase; IL-1β: Interleukin 1 beta; IL-6: Interleukin 6; CPT-1: Carnitine palmitoyltransferase; ACC: Acetyl-CoA-carboxylase.

2.7. Liver Histology and Morphometry

Tissue samples obtained from necropsy were fixed in 10% formalin for 24 h. The tissues were dehydrated, paraffin-embedded and processed for hematoxylin and eosin (H&E) staining. Digital images (ten per liver section) were acquired randomly with a 40× objective using a digital camera coupled to a conventional microscope (Olympus CH, Shinjuku, Japan).

The morphometric estimation of hepatic steatosis was analyzed with ImageJ software using digital images obtained and data expressed as a percentage of the area occupied by lipid droplets. For the quantification of the macrovesicular steatosis, two different observers, who were blinded for the treatment applied to each animal, individually examined the images and visually determined the percentage of hepatocytes containing macrovesicular lipid droplets. Macrovesicular steatosis was defined as lipid droplets larger than the cell nucleus.

2.8. Triglyceride Liver Content

First, liver tissue was homogenized in a 5% Nonidet P40 solution. After heating the samples to 100 °C in a water bath for 5 min, they were cooled to room temperature. Triglyceride content in the liver extracts was then determined using a Triglyceride Quantification Kit (Sigma-Aldrich, MO, USA). Obtained values were normalized with protein liver content.

2.9. Statistical Analysis

Data were expressed as the mean ± standard deviation (SD). Statistical analysis was performed using GraphPad Prism version 8 (GraphPad, La Jolla, CA, USA). The statistical analysis of body weight evolution and glucose tolerance test were performed by two-way repeated measures ANOVA followed by Bonferroni post hoc test. For all other data, one-way analysis of variance ANOVA or Kruskal–Wallis test followed by Tukey’s multiple comparison test was performed. The Student’s t or Mann–Whitney U test was used for the two groups’ comparisons. p values < 0.05 were considered as statistically significant.

3.1. Vinegar Drink Either Alone or in Combination with B. coagulans Attenuated High Caloric Diet-Induced Weight Gain

In this study, we examined the effect of an Apple vinegar drink, either alone or in combination with B. coagulans , in mice fed with a HFD. For this purpose, male C57BL/6 mice were divided into five groups (six mice per group) with free access to the above described drinks of equal calorie content, except for the ND group (water control group) ( Figure 1 ). During the entire HFD feeding period, mice body weight was significantly higher in every HFD group than in the ND group ( Figure 2 A). Though increased, total body weight at the end of the experimental procedure showed lower increments in the HFD+Vinegar and HFD+Vinegar_Bc groups than in the non-vinegar obese mice group (HFD+Vehicle) ( p < 0.05). This significant attenuation of total body weight was already observed from week 5 of the experimental design ( Figure 2 A). In accordance with this result, an increase in body weight gain in mice fed with HFD ( p < 0.001) was observed at the end of the experimental period ( Figure 2 B), and a significant reduction in this increase was observed in the HFD+Vehicle_Bc, HFD+Vinegar, HFD+Vinegar_Bc groups when compared to their corresponding control obese mice (HFD+Vehicle) ( p < 0.05 for all except p < 0.01 for HD+Vinegar_Bc) ( Figure 2 B).

Effect of the different drinks on body weight, weight gain, food and calorie intake in HFD-induced obese mice. ( A ) Changes in body weight during the animal experimental study, ( B ) Differences in body weight gain between groups, ( C ) Daily energy intake calculated by converting the amount of food and drink consumed into calories, ( D ) Differences in food intake (g/mouse/day) between groups, ( E ) Metabolic or food efficiency ratio represented as the body weight gain relative to energy intake. Abbreviations. ND: Normal diet; HFD: High fat diet; ND+Water: Normal diet plus water; HFD+Vehicle: High fat diet plus vehicle (non-vinegar), HFD+Vehicle_Bc: High fat diet plus vehicle and B. coagulans ; HFD+Vinegar: High fat diet plus vinegar; HFD+Vinegar_Bc: High fat diet plus vinegar and B. coagulans. Data are expressed as mean ± SD. * p   <  0.05, ** p   <  0.01, *** p   <  0.001 vs. ND group, # p   <  0.05, ## p   <  0.01 ### p   <  0.001 vs. HFD+Vehicle. ( n = 6 mice per group).

Mean energy intake was estimated by converting the amount of food and drink consumed into calories using the information provided by the Tekland diet manufacturer (Envigo, Madison, WI, USA) and the calorie content of the vinegar drink ( Table 1 ). As shown in Figure 2 C, daily energy intake was higher in HFD mice than in the ND mice ( p < 0.001). However, this increase was significantly smaller in HFD+Vehicle_Bc, HFD+Vinegar and HFD+Vinegar_Bc groups than in the HFD+Vehicle group ( p < 0.05, p < 0.05, p < 0.01, respectively). This result may be attributable to a reduction in mice food intake, as the daily food consumption (grams) in HFD+Vehicle_Bc, HFD+Vinegar and HFD+Vinegar_Bc was lower than in the HFD+Vehicle and ND groups ( p < 0.05, p < 0.05, p < 0.001, respectively) ( Figure 2 D). However, there were no significant differences between HFD groups in drink intake (not shown), nor in the metabolic efficiency ratio (body weight gain relative to mean energy intake) among the HFD groups ( Figure 2 E).

3.2. Vinegar Drink Either Alone or in Combination with B. coagulans Improves Glycemic and Glucose Tolerance

To explore the effect of vinegar ± B. coagulans on glucose homeostasis, basal serum glucose was measured at several time points during the experimental procedure, and a GTT was performed at the end of the experiment. No significant changes were detected in serum glucose level among the groups before week 4 of the experimental study. However, at week 4 all HFD groups displayed higher basal glucose levels than the ND group ( p < 0.001 for HFD+Vehicle, HFD+Vehicle_Bc and HFD+Vinegar_Bc groups, p < 0.05 for HFD+Vinegar) ( Figure 3 A). Interestingly, after seven weeks only the HFD+Vehicle and HFD+Vehicle_Bc exhibited higher fasting glucose levels than the ND group ( p < 0.01). Moreover, significantly smaller fasting blood glucose levels were found in the HFD+Vinegar and HFD+Vinegar_Bc mice than in the HFD+Vehicle group ( p < 0.05) ( Figure 3 A).

Vinegar and B. coagulans improved glucose homeostasis. ( A ) Fasting blood glucose measured at several time points during the experimental procedure, ( B ) Blood glucose levels in response to glucose tolerance test at week 7, ( C ) Effect on area under the curve (AUC). Abbreviations. ND: Normal diet; HFD: High fat diet; ND+Water: Normal diet plus water; HFD+Vehicle: High fat diet plus vehicle (non-vinegar), HFD+Vehicle_Bc: High fat diet plus vehicle and B. coagulans ; HFD+Vinegar: High fat diet plus vinegar; HFD+Vinegar_Bc: High fat diet plus vinegar and B. coagulans. Data are expressed as mean ± SD. * p < 0.05, ** p < 0.01, *** p < 0.001 vs. ND, # p < 0.05, ## p < 0.01 vs. HFD+Vehicle group. ( n = 6 mice per group).

In regard to the GTT performed at week 7, as expected, basal serum glucose concentration was higher in the HFD+Vehicle and HFD+Vehicle_Bc mice than in the ND group ( p < 0.01). In contrast, the basal glucose concentration in HFD+Vinegar and HFD+Vinegar_Bc group was lower than in the HFD+Vehicle group ( p < 0.05) ( Figure 3 B). Peak levels of glucose were reached in every group 20 min after the intraperitoneal administration of glucose. Glucose levels remained higher in the HFD+Vehicle mice than in the ND mice 40, 60, 90 and 120 min after injection ( p < 0.001) ( Figure 3 B).

In contrast, glucose levels in the HFD+Vinegar and HFD+Vinegar_Bc groups decreased faster from minute 60 to 120, normalizing their values compared to HFD+Vehicle ( p < 0.01). A trend towards normalization was also observed in the HFD+Vehicle_Bc mice, though in this case the decrease did not reach statistical significance ( Figure 3 B). Besides, the area under the curve (AUC) was greater in all HFD mice than in the ND mice ( p < 0.001 for HFD+Vehicle, and p < 0.01 for the rest of HFD groups) ( Figure 3 C), indicating impaired glucose tolerance. However, HFD+Vehicle_Bc, HFD+Vinegar and HFD+Vinegar_Bc presented smaller AUC than the HFD+Vehicle mice ( p < 0.05, p < 0.01, p < 0.01, respectively), pointing to a better glucose tolerance for mice in these groups than for those in the HFD control group ( Figure 3 C).

3.3. Vinegar Drink Together with B. coagulans Attenuates Dislipidemia in Obese Mice

To assess the effect of vinegar ± B. coagulans on lipid profile in mice fed HFD, triglycerides, cholesterol and free fatty acids (FFA) levels were determined in serum. After 5 weeks of HFD feeding, a significant increase in serum triglyceride levels was quantified in HFD+Vehicle and HFD+Vinegar groups compared to the ND group ( p < 0.05), thus suggesting the onset of dyslipidemia by HFD feeding ( Figure 4 A). As shown in the figure, supplementation of HFD with Vinegar and B. coagulans prevented this increase (HFD+Vinegar_Bc vs. HFD+Vehicle: p < 0.05).

Serum lipid profile in HFD-fed mice supplemented with vinegar and non-vinegar drinks ± B. coagulans for 5 weeks. ( A ) Concentration of serum Triglycerides (TG), ( B ) Serum total cholesterol, ( C ) and serum free fatty acids (FFA) on mice fed ND or HFD, respectively. Abbreviations. ND: Normal diet; HFD: High fat diet; ND+Water: Normal diet plus water; HFD+Vehicle: High fat diet plus vehicle (non-vinegar), HFD+Vehicle_Bc: High fat diet plus vehicle and B. coagulans ; HFD+Vinegar: High fat diet plus vinegar; HFD+Vinegar_Bc: High fat diet plus vinegar and B. coagulans. Values are expressed as the mean ± SD. * p < 0.05, *** p < 0.001 vs. ND, # p < 0.05 vs. HFD+Vehicle group. ( n = 6 mice per group).

In this dyslipidemic condition, cholesterol levels were significantly higher in all HFD groups (HFD+Vehicle, HFD+Vehicle_Bc, HFD+Vinegar, HFD+Vinegar_Bc) than in the ND group ( p < 0.001 for HFD+Vehicle and p < 0.05 for the rest of the HFD groups). Only the HFD+Vinegar_Bc group significantly ameliorated cholesterol levels compared to the HFD+Vehicle group ( p < 0.05) ( Figure 4 B). In addition, there were no significant differences in fasting serum FFA between the HFD+Vehicle, HFD+Vehicle_Bc, HFD+Vinegar and ND groups. However, a significant reduction was found in FFA serum concentration of the HFD+Vinegar_Bc when comparing it to the control group ( p < 0.05) ( Figure 4 C).

3.4. Vinegar Supplemented with B. coagulans Ameliorated Fat Liver Accumulation: Histological Assessment of the Liver

Photomicrographs of liver tissue for all animal experimental groups are shown in ( Figure 5 A). At the end of the animal study, the liver tissue of mice fed with ND presented a normal architecture of hepatocytes, with no appearance of lipid droplet deposition ( Figure 5 A). In contrast, HFD-fed mice showed fat droplet deposition consisting of mixed microvesicular and macrovesicular steatosis, while vinegar and B. coagulans , alone or in combination, remarkably suppressed vacuole formation and lipid accumulation in hepatocytes ( Figure 5 A). The histopathological quantification showed a higher degree of macrovesicular steatosis in HFD+Vehicle mice than in the ND group ( p < 0.01) ( Figure 5 B). Interestingly, vinegar drink, B. coagulans and the combination of both exhibited less macrovesicular deposition, though a statistically significant change was observed only in the HFD+Vehicle_Bc group ( p < 0.05) ( Figure 5 B). The quantification of liver micro and macrovesicular steatosis yielded a higher number of vesicles in the HFD+Vehicle group than in the ND ( p < 0.05) ( Figure 5 C). For the rest of the HFD groups, no significant differences in micro and macrovesicular steatosis with the ND group were found ( Figure 5 C). Consistent with this histological and morphological observation, hepatic TG accumulation appeared to be higher in mice fed with HFD compared to ND ( p < 0.01 for HFD+Vehicle, and p < 0.05 for the rest of the HFD groups) ( Figure 5 D). Supplementation of HFD with vinegar, B. coagulans , or their combination did not significantly counteract hepatic TG accumulation, although a trend towards a decrease was observed in every case. In summary, our results showed that vinegar, and B. coagulans alone or in combination, may reduce fat liver accumulation induced by the HFD and improve liver steatosis.

Effect of vinegar and B. coagulans on hepatic histology and TG liver accumulation in HFD-induced obese mice. ( A ) Representative images of H&E-stained liver sections from different animal experimental groups are shown (40 × magnification), ( B ) Percentage of macrovesicular steatosis, ( C ) Percentage of hepatic steatosis ( D ) and hepatic TG content on mice fed ND or HFD, respectively. Scale bar: 50 µm. Abbreviations. ND: Normal diet; HFD: High fat diet; ND+Water: Normal diet plus water; HFD+Vehicle: High fat diet plus vehicle (non-vinegar), HFD+Vehicle_Bc: High fat diet plus vehicle and B. coagulans ; HFD+Vinegar: High fat diet plus vinegar; HFD+Vinegar_Bc: High fat diet plus vinegar and B. coagulans. Values are expressed as the mean ± SD. * p < 0.05, ** p < 0.01 vs. ND, # p < 0.05 vs. HFD+Vehicle group. ( n = 6 mice per group).

3.5. Vinegar Drink Together with B. coagulans Ameliorates the Expression of Altered Lipid Metabolism-Related and Pro-Inflammatory Genes in the Livers of High Fat Diet Mice

Fatty liver occurs when fat accumulation is caused by impaired fatty acid oxidation along with increased lipid synthesis. To understand the molecular mechanisms underlying the protective effect observed in the liver for the vinegar drink supplemented with B . coagulans , we next evaluated the expression in liver tissue of lipid metabolism-related genes, such as lipogenic genes, fatty acid synthesis genes or fatty acid oxidation genes ( Figure 6 ). As shown in the Figure, at the end of the experimental study we found a significant increase in the expression of the adipogenesis-related gene CD36 in the liver of mice fed with HFD+Vehicle compared to mice fed with ND ( p < 0.01). Figure 6 A also shows that supplementation of HFD with either vinegar, B. coagulans or both prevented HFD from inducing long chain fatty acid receptor CD36 expression ( p < 0.05 compared to HFD+Vehicle), thereby attenuating fatty acid uptake in the liver. Similar results were found when looking for LXR sensor of cholesterol metabolism and lipid biosynthesis expression: LXR mRNA expression was higher in the HFD+Vehicle, HFD+Vehicle_Bc and HFD+Vinegar groups than in the ND group ( p < 0.01). However, supplementation of HFD with Vinegar + B. coagulans prevented induction of LXR by HFD (HFD+Vinegar_Bc vs. HFD+Vehicle: p < 0.01) and maintained normal LXR expression levels.

Effect of vinegar ± B. coagulans on mRNA levels of hepatic genes. ( A , B ) Effect of vinegar ± B. coagulans on mRNA levels of several genes involved in hepatic lipogenesis and β-oxidation, ( C ) Effect of vinegar ± B. coagulans on mRNA expression levels of pro-inflammatory cytokines in the liver. Total RNA extracted from the liver was reverse transcribed, and each gene expression was quantified by real-time PCR using gen-specific primers. All genes were normalized to expression of RPLPO. The relative expression level of each gene was calculated as the fold change from the triplicates in each group using the 2 −ΔΔ C t method. The y-axis represents the relative expression of the studied genes. Gene full names. RPLPO: Ribosomal protein P0; LXR: Liver X receptor; CD36: Cluster of differentiation 36; PPARα: Peroxisome proliferator activated receptor; SREBP: sterol regulatory element-binding protein; FASN: Fatty acid synthase; IL-1β: Interleukin 1 beta; IL-6: Interleukin 6; CPT-1: Carnitine palmitoyltransferase; ACC: Acetyl-CoA-carboxylase. Abbreviations. ND: Normal diet; HFD: High fat diet; ND+Water: Normal diet plus water; HFD+Vehicle: High fat diet plus vehicle (non-vinegar), HFD+Vehicle_Bc: High fat diet plus vehicle and B. coagulans ; HFD+Vinegar: High fat diet plus vinegar; HFD+Vinegar_Bc: High fat diet plus vinegar and B. coagulans. Data are expressed as mean ± SD. * p < 0.05, ** p < 0.01 vs. control, # p < 0.05, ## p < 0.01 vs. HFD+Vehicle group. ( n = 6 mice per group).

Plasma fatty acid taken up by the liver is further augmented by increased hepatic de novo lipogenesis. LXR directly regulates the expression of genes involved in fatty acid synthesis including SREBP, a master regulator of fatty acid synthesis. Thus, not surprisingly, HFD feeding induced a significant upregulation of SREBP in mice fed with HFD+Vehicle (HFD+Vehicle vs. ND: p < 0.01) ( Figure 6 B). Upregulation was attenuated by both vinegar and B. coagulans , though only reached statistical significance when the two were present (HFD+Vinegar_Bc vs. HFD+Vehicle: p < 0.01) ( Figure 6 B).

Regulation of de novo lipogenesis occurs too by the regulation of various key enzymatic activities, including FAS and ACC among others. Analysis of the hepatic expression of these genes revealed no statistically significant differences in ACC expression among groups ( Figure 6 B). However, HFD feeding increased FAS expression (HFD+Vehicle vs. ND: p < 0.05). In this case, neither vinegar nor B. coagulans supplementation led to a significant attenuation of HFD-induced FAS expression ( Figure 6 B).

Several studies have shown that PPARα expression is activated by fatty acids. This is especially important during fasting, when plasma FFAs and the flux of fatty acids through the liver increase dramatically [ 30 ]. Accordingly, in our experimental study HFD feeding induced a significant upregulation of PPARα compared to ND ( p < 0.05), and in consonance with the reduction in FFA serum concentration described above, HFD-induced PPARα upregulation was prevented by HFD+Vinegar_Bc (HFD+Vinegar_Bc vs. HFD+Vehicle: p < 0.05) ( Figure 6 B). Besides, HFD feeding impaired the fatty acid oxidation pathway as pointed out by the slight decrease observed in mRNA abundance of CPT1 in HFD-fed mice, which was restored in HFD+Vehicle_Bc and HFD+Vinegar, although this last result did not reach statistical significance ( Figure 6 B).

Obesity is closely associated with an increased risk of NAFLD that includes a disease spectrum that ranges from steatosis or isolated fatty liver to non-alcoholic steatohepatitis (NASH), a more aggressive form that can progress to fibrosis, cirrhosis and hepatocarcinoma [ 31 ]. Numerous studies have reported complex interactions between obesity, hepatic steatosis and chronic inflammation. In addition, adipose tissue dysfunction and the hepatic inflammatory response have an important role in the transition from isolated fatty liver or steatosis to NASH. To examine whether vinegar drink ± B. coagulans improved liver inflammation in HFD-fed mice, the amount of mRNA of pro-inflammatory cytokines in the liver was determined. As shown in Figure 6 C, HFD feeding induced a significant up-regulation of IL-1β and IL-6 mRNA (HFD+Vehicle vs. ND: p < 0.001 and p < 0.05, respectively). Supplementation of HFD with either vinegar, B. coagulans or both prevented Il-1β upregulation (HFD+Vehicle_Bc vs. HFD+Vehicle, p < 0.05, HFD+Vinegar vs. HFD+Vehicle: p < 0.01, and HFD+Vinegar_Bc vs. HFD+Vehicle: p < 0.01) in the liver ( Figure 6 C). Similarly, liver mRNA expression of IL-6 was significantly reduced in HFD+Vinegar and HFD+Vinegar_Bc mice, compared with HFD+Vehicle mice ( p < 0.001 and p < 0.05, respectively) ( Figure 6 C).

3.6. Effect of Vinegar Drink and B. coagulans on Leptin, GLP-1 and Insulin Levels in Serum

Emerging evidence has shown an important role of the microbiota–gut–brain axis in the control of food intake by the hypothalamus and in insulin and leptin signaling in the contribution to evolution of obesity [ 32 ]. As mentioned before, mice fed with a HFD supplemented with vinegar ± B. coagulans gained less weight and had reduced food intake than non-vinegar HFD-fed mice. For this reason, we explored whether vinegar ± B. coagulans improved the response to anorexigenic hormones such as leptin, insulin and glucagon-like peptide 1 (GLP-1) in serum of HFD-fed mice.

Apart from the well-known effect of fasting GLP-1 as an anorexic hormone able to reduce appetite and food intake [ 33 ], growing evidence has suggested that the reduction in plasma GLP-1 levels is related to disorders of glucose homeostasis [ 34 ]. In addition, recent studies have demonstrated that fasting circulating SCFA (acetate) are related to insulin sensitivity, lipolysis and fasting GLP-1 concentration in human blood [ 35 ]. To understand whether the mechanism underlying the effect of vinegar and B. coagulans to inhibit food intake and improve glucose homeostasis, could be related to the production of this anorexic hormone, fasting serum GLP-1 levels were explored. Figure 7 A shows that mice receiving HFD had reduced serum fasting GLP-1 concentration than ND mice ( p < 0.05). Neither vinegar nor B. coagulans supplementation counterparted this effect. However, no significant differences in fasting serum GLP-1 level were detected between the HFD+Vinegar_Bc and ND mice ( Figure 7 A).

Effect of vinegar ± B. coagulans on GLP-1, Leptin and C-peptide in serum. ( A ) Fasting serum GLP-1, ( B ) Fasting serum leptin, ( C ) Fasting C-peptide levels, ( D ) Insulin sensibility estimated using average HOMA-IR in each group calculated from fasting serum glucose and fasting serum C-peptide concentrations with the formula: serum C-peptide (nmol L −1 ) * serum glucose (mmol L −1 )/22.5. Abbreviations. ND: Normal diet; HFD: High fat diet; ND+Water: Normal diet plus water; HFD+Vehicle: High fat diet plus vehicle (non-vinegar), HFD+Vehicle_Bc: High fat diet plus vehicle and B. coagulans ; HFD+Vinegar: High fat diet plus vinegar; HFD+Vinegar_Bc: High fat diet plus vinegar and B. coagulans Data are expressed as mean ± SD. * p   <  0.05, ** p   <  0.01, *** p   <  0.001 vs. ND group, # p   <  0.05, ### p   <  0.001 vs. HFD+Vehicle. ( n = 6 mice per group).

As shown in Figure 7 B, HFD mice exhibited significantly higher levels of leptin in serum than ND mice ( p < 0.001 for HFD+Vehicle and HFD+Vinegar, p < 0.05 for the rest of the HFD groups), indicating leptin resistance in HFD-fed mice. Supplementation of HFD with either vinegar, B. coagulans or both decreased leptin serum levels (HFD+Vehicle_Bc vs. HFD+Vehicle: p < 0.001, HFD+Vinegar vs. HFD+Vehicle: p < 0.05, and HFD+Vinegar_Bc vs. HFD+Vehicle: p < 0.001), suggesting that the administration of vinegar ± B. coagulans to HFD mice improved leptin sensibility as evidenced by reduced food intake.

As shown before, the mean values of AUC obtained during GTT were greater in HFD-fed mice, thus indicating insulin resistance. In accordance with this, fasting serum C-peptide levels were elevated in HFD mice compared to ND mice ( p < 0.001 for HFD+Vehicle, p < 0.01 for HFD+Vehicle_Bc and p < 0.05 for HFD+Vinegar and HFD+Vinegar_Bc) ( Figure 7 C). Supplementation of HFD with vinegar attenuated elevation (HFD+Vinegar and HFD+Vinegar_Bc groups vs HFD+Vehicle: p < 0.05). These results partially correlated with the insulin resistance index based in C-peptide (HOMA-IR) that showed a significant increase in all HFD-fed groups when compared to the ND mice ( p < 0.01 for HFD+Vehicle and p < 0.05 for the rest of HFD groups). However, the resistance index was not restored by vinegar, B. coagulans , or their combination, although a trend towards a decrease was observed in every case ( Figure 7 D).

4. Discussion

Obesity is a prevalent health issue worldwide [ 36 , 37 ]. Associated with modernization, it affects physical activity and food habits. Consuming high fat diets has been identified as the main important reason for the increased risk of developing obesity [ 2 ]. Initially, apart from genetics and environmental factors, obesity was only attributed to a prolonged imbalance between energy intake and energy expenditure [ 38 ]. Nowadays, numerous studies in mice and humans have also shown that obesity is associated with changes in the diversity and abundance of the microbiota [ 5 , 6 ]. In addition, growing evidence has demonstrated that the microbiota may impact body weight gain and adiposity through a network of interconnected pathways, such as energy harvest and production of microbial metabolites, inflammatory response, and effects on the gut–brain axis. SCFA metabolites participate in this complex signaling [ 7 ].

Fermented foods, especially vinegars produced for different fruits, have long being consumed worldwide to obtain different health benefits, including body weight control [ 11 ]. Vinegar is considered a dietary source of acetate, due to its ingestion acetate levels in plasma increasing rapidly [ 39 ]. Nowadays, new functional foods are increasing their popularity due to their wide-range and long-term benefits [ 40 ]. Specially, people are interested in weight loss shifting away from “magic pills” and traditional weight loss programs to more natural and healthier alternatives. In line with this idea, the purpose of this study was to explore the role of a new functional drink, obtained from an organic apple vinegar beverage inoculated with the spore-forming B. coagulans as a probiotic in diet-induced obese mice.

B. coagulans is an ideal choice to develop functional foods because of its resistance to high temperatures. Although, there are still few studies showing the effect of B. coagulans on microbiota, several beneficial effects have been reported. Recently, it has been published that the administration of B. coagulans to rats resulted in a drastic increase in acetate and butyrate in rat feces, with a relatively higher level of total SCFA compared to untreated control rats [ 28 ]. In the present study, we found that both vinegar drink alone and vinegar drink supplemented with B. coagulans improved glucose tolerance and prevented body weight gain in a mice model of HFD-induced obesity. It is worth noting that we also found a protective effect on lipid profile, decreased expression of genes involved in lipogenesis, and a reduction in macrovesicular hepatic steatosis only when the organic drink was supplemented with both vinegar and B. coagulans . The ability of B. coagulans to increase intestinal acetate and butyrate concentrations [ 28 ], thus improving the effect of vinegar, is a likely explanation for this finding.

In the search for the mechanism involved in the control of weight gain, the impact of vinegar and B. coagulans on plasma leptin, insulin and Glucagon-like peptide 1 (GLP-1) was explored. GLP-1 is known for its glucoregulatory and appetite-suppressing effects, playing an important role in the regulation of food intake and insulin secretion [ 41 ]. Several studies have demonstrated that high fat diets impair the secretory function of GLP-1-producing cells [ 42 , 43 ]. More concretely, a reduction in GLP-1 expression was observed in diet-induced obese mice characterized by mitochondrial stress in colon enterocytes [ 44 ]. By contrast, in enteroendocrine L-cells, SCFA increase GLP-1 expression and secretion by activation of GRP43, mainly by the effect of dietary fibers [ 45 ]. According to these observations, we detected a reduction in fasting serum GLP-1 in HFD-induced obese mice. Interestingly, fasting serum GLP-1 levels were not reduced in HFD+Vinegar_Bc-induced obese mice, which suggests that GLP-1 regulation of appetite is involved in the effect of vinegar and B. coagulans on food intake and body weight. Thus, B. coagulans -derived SCFA, likely acetate, may contribute to the vinegar activity in the regulation of GLP-1 in vivo, although this needs further investigation.

Leptin is mainly produced by adipocytes, and serum HFD-induced levels of leptin correlate with adipocyte fat storage [ 46 ]. Acting in hypothalamic centers, major roles of leptin are the regulation of food intake and increasing energy expenditure. Leptin resistance occurs in response to high fat diets. In obesity, circulating levels of leptin rise, although its ability to reduce food intake and to increase energy expenditure diminishes; hyperleptinaemia and inflammation have been postulated as causative mechanisms [ 47 ]. Using different mouse models, Koch et al. demonstrated: first, that 6-weeks treatment of obese wild type mice with a leptin neutralizing antibody drives a 10% reduction in food intake; second, that hyperleptinaemia is a driving force of metabolic disorders; third, that a partial restoration of leptin levels in plasma leads to improved leptin sensibility and insulin sensitivity, and reduces weight gain and hepatic steatosis [ 48 ]. Recently, the same authors reported that preserving lower leptin levels in an obesogenic environment is highly beneficial for obesity and diabetes control. In this last study, partial leptin deficiency led to a better leptin sensibility in HFD mice, as assessed by an overall reduced food intake [ 49 ]. In concordance with these studies, in this work we found that a vinegar drink, either alone or supplemented with B. coagulans , partially reduced circulating leptin levels, improved glucose tolerance, decreased C-peptide levels in serum, and improved the insulin sensitivity index in HFD-induced obese mice. Normally, lower body weight and better glucose tolerance correlate positively, both in animal models and in human clinical studies. For this reason, we speculate that the observed beneficial effects obtained with vinegar and B. coagulans , such as improved glucose tolerance and even reduced fatty liver, could be in part explained by its ability to restore leptin sensibility, thus reducing food intake and body weight gain.

Fatty liver disease is associated with insulin resistance and obesity and may be considered as the hepatic manifestation of metabolic syndrome. While the physiopathology of the non-alcoholic fatty liver disease (NAFLD) is not fully understood, steatosis is considered as a key initial event. Lipotoxicity, insulin resistance and inflammation are essential players in the progression towards a non-alcoholic liver steatohepatitis (NASH), the more aggressive form of NAFLD [ 50 ]. Obesity-associated chronic inflammation is known to be responsible for the impaired insulin response. However, the role of pro-inflammatory cytokines in NAFLD is still unclear, although several studies have demonstrated that TNFα, IL-1β and IL-6 are important mediators in the development of NAFLD. In addition to their expected role as pro-inflammatory cytokines in inflammation, they promote steatosis, inflammation and fibrosis. For instance, IL-1β can stimulate the production of TNFα and IL-6, and increases the accumulation of triglycerides and cholesterol [ 51 ]. In the present work, we found that vinegar supplemented with B. coagulans improved the lipid profile and suppressed hepatic steatosis induced by HFD in mice. This protective effect seems to be mediated by a reduction in the hepatic expression of CD36, a protein involved in fatty acid uptake. Disruption of hepatic CD36 has been shown to reduce both lipid content and free fatty acid uptake in the liver of HFD-fed mice, and also to protect against associated systemic inflammation and insulin resistance [ 52 ]. According to these results, we also found that vinegar, B. coagulans and their combination suppressed the HFD-induced overexpression of IL-1β and IL-6 inflammatory cytokines in the liver. They also reduced HFD-induced overexpression of SREBP and LXR transcription factors. LXR is a nuclear receptor that controls lipid metabolism by regulating the expression of SREBP and other genes involved in hepatic lipogenesis in NAFLD [ 53 ]. In the liver, SREBP is involved in the biogenesis of cholesterol, fatty acids and triglycerides; it also has a role in the pathogenesis of NAFDL and NASH [ 54 ]. Activated by downstream signaling, SREBP increases FAS mRNA expression, which collaborates in fatty acids synthesis. Down-regulation of SREBP expression is thus a likely explanation for the reduction in both fat accumulation in the liver and cholesterol and triglycerides levels in serum observed in the HFD+Vinegar_Bc mice. Additionally, activation of LXR has also been described to have anti-inflammatory effects in steatosis [ 55 , 56 ]. Therefore, the reduction in LXR expression could reflect the effect of vinegar and B. coagulans on systemic inflammation. All together, these results are consistent with the alleviated liver hepatic fat accumulation induced by vinegar and B. coagulans in our mice model of diet-induced obesity

In the context of NAFLD, hepatic steatosis can be stimulated via increased fatty acid uptake, increased de novo lipogenesis and failed fatty acid oxidation. In the present work, we did not find a clear modulation of the hepatic expression of the lipogenic genes FAS and ACC by vinegar and B. coagulans. In contrast, our data show that vinegar and B. coagulans, independently, tended to enhance hepatic oxidation since they prevent the HFD-induced down-regulation of CPT1. Surprisingly, the expression of PPARα, a gene known to promote fatty acid oxidation, was increased in every HFD-fed group except for the HFD+Vinegar_Bc mice. Since hepatic fasting has been shown to induce PPARα expression [ 57 ] and considering that we collected liver hepatic tissue after an eight-hour fast, our animal experimental procedure could be the reason for this result. For this reason, further experiments are needed to better characterize the action of vinegar and B. coagulans on the beta-oxidation pathway in the liver.

5. Conclusions

In summary, our study demonstrates that a new functional organic drink containing apple cider vinegar reduced food intake, attenuated body weight gain and enhanced glucose tolerance. Moreover, when supplemented with B. coagulans at a concentration of approximately 10 7 –10 8 spores/mL, the drink also improved the lipid serum profile and prevented hepatic steatosis induced by HFD in mice. This protective effect was mediated by a reduction in the hepatic expression of CD36, IL-1β, IL-6, LXR and SREBP, which alleviated fat accumulation in the liver. The ability of the vinegar drink to partly restore leptin and insulin sensibilities could explain its beneficial effects. Further experiments are needed to confirm whether B. coagulans -derived SCFA contribute or not to the vinegar activity.

Author Contributions

Conceptualization, G.M., M.B. and I.E.; methodology, R.U., J.D.-G., M.O., M.J.P., M.J., M.A.; investigation and formal analysis, R.U., J.D.-G., P.T., M.J.P. and M.A.; writing—original draft preparation, R.U., M.B. and I.E.; writing—review and editing, R.U., M.J.P., M.A., M.B. and I.E.; supervision, G.M., P.T., M.B. and I.E.; funding acquisition, G.M., I.E. and M.B. All authors have read and agreed to the published version of the manuscript.

This research was funded by grant from Department of Economic Development, Navarre Government [Modalidad: “Transferencia del Conocimiento”, References: 0011-1365-2018-000111 (UPNA) and 0011-1365-2018-000170 (ECOVINAL, S.L.U.)].

Conflicts of Interest

Germán Munilla (head) and Joana Díaz-Gómez (Research Department) work at Ecovinal S.L., the company that elaborated the organic vinegar drink. The other authors declare that no conflicts of interest exist.

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May 04, 2024

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Apple Cider Vinegar Market to Reach $1.82 Billion by 2030, Says Allied Market Research

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6 Healthy Vinegar Uses That Put Apple Cider Vinegar to Shame

The underestimated vinegar.

A pple cider vinegar is touted for its various health benefits , but people may forget that other types of vinegar can offer perks, too. For instance, white vinegar can be good for your body as well.

Here are some of the benefits (and risks) of using white vinegar for consumption, cooking, cleaning and disinfection.

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What is white vinegar?

White vinegar, or distilled white vinegar, is a clear solution of acetic acid and water . The earliest known use of vinegar dates to more than 10,000 years ago.

In general, vinegar is made with a two-step process of fermentation.

First, yeast ferments the sugars or carbohydrates in foods like potatoes, grains, or fruit and converts them to alcohol . Then, acetic acid bacteria ( Acetobacter ) converts the alcohol to acetic acid during the fermentation process.

Most white vinegar is made by the fermentation of grain alcohol, or ethanol.

The result is diluted into a solution that is sold in just about any store for general all-purpose use like cleaning, and even cooking.

But not all vinegar is created equal. The difference between cleaning vinegar and distilled white vinegar is their level of acidity.

White vinegar has 5% acidity, and cleaning vinegar has 6% Although it's only a one percent difference, cleaning vinegar is much stronger white vinegar —20% stronger—and is not intended for consumption.

Another clue is that you can also find the distilled white vinegar in the condiment aisle, but the cleaning vinegar will be with other cleaners in general stores.

Although it's OK to use distilled white vinegar for cleaning, the same isn't true for using cleaning vinegar in recipes. Remember, that extra acidity means it is not safe for consumption.

Home Cleaning Tips Straight From the CDC

White vinegar vs. apple cider vinegar

Other than their color, there are a few differences between white and apple cider vinegar.

Apple cider is contains anywhere from 5-6% acetic acid. It comes from crushed, fermented apples.

White vinegar, however, contains 4-7% acetic acid and is from the fermentation of grain alcohol.

Can You Drink Apple Cider Vinegar While Fasting?

Healthy vinegar uses to try

Although there's arguably a bit more research on apple cider vinegar , there are plenty of uses for white vinegar, too. Here's what the current, limited research says about the health benefits and uses of vinegar.

Promote weight loss

A 2015 review in the Journal of the Academy of Nutrition and Dietetics suggests that weight loss might be a secondary effect of consuming vinegar. While the evidence is mixed as to the benefits for people with diabetes, it's safe when used in reasonable amounts to flavor food, according to the report.

Vinegar consumption could increase fullness by slowing the rate at which the stomach empties, leading to reduced calorie intake.

In one study in Bioscience, Biotechnology, and Biochemistry, people who were overweight consumed vinegar over a 12-week period. They found that the people who consumed a beverage containing either one or two tablespoons of vinegar had slightly lower body weight, BMI, visceral fat area, waist circumference, and serum triglyceride levels at the end of the study than those who consumed the same drink without the added vinegar. (They drank half of it at breakfast, and the rest at dinner.)

The difference was about 2 to 4 pounds and 0.4 to 0.7 BMI points between the groups, according to the report.

While there are potential weight management benefits to white vinegar, studies are limited, conflicting, and mostly animal-based. Because of this, more research is needed, according to Malina Malkani, a registered dietitian nutritionist and author.

"However, if it's an ingredient people enjoy, including vinegar in moderation in meals and snacks is a great way to incorporate it into the diet while possibly reaping some of the potential health benefits," she says.

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Help control blood sugar

Malkani notes that the same is true of the research on blood sugar and vinegar.

One meta-analysis (a combination of studies) in Diabetes Research and Clinical Practice looked at the effect of vinegar intake on post-meal glucose response . They found that those who consumed vinegar compared to those who did not had lower blood sugar and glucose, which suggests it might be a tool for improving glycemic control or managing diabetes.  

This is likely because of the acetic acid in vinegars, according to a 2016 paper in Comprehensive Reviews in Food Science and Food Safety.  The acid regulates the concentration of blood glucose by improving insulin sensitivity and promoting glycogen production.

In a small study of eight men with pre-diabetes in the European Journal of Clinical Nutrition,  the researchers found that vinegar ingestion before a meal also had a positive impact on insulin resistance, although it didn't seem to lower blood sugar.

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In the study, the men consumed about three tablespoons of a vinegar and water mixture or the same amount of plain water directly before eating a meal.

In a report in the Journal of Diabetes and Endocrinology, researchers looked at 60 people with type 2 diabetes. Half of the people added about a tablespoon of white vinegar to their middle meal each day for a month while the other half added water as a placebo.

Those taking vinegar saw a decrease in fasting blood sugar and lowered HbA1c, an indicator of blood glucose.

9 Surprising Foods That Can Wreak Havoc on Your Blood Sugar

Treat wounds and sores

Vinegar contains antimicrobial properties, meaning it's great for treating everything from nail fungus and warts to skin infections, according to reports in the Journal of Infection and Public Health and PLoS One .

For example, a one-to-one mixture of white vinegar and rubbing alcohol can be used as a treatment for swimmer's ear , an infection of the outer ear, according to an American Academy of Pediatrics news report.

One small study of 100 people in the Indian Journal of Plastic Surgery suggests that a one percent acetic acid solution (vinegar) may accelerate wound healing because of its ability to combat a wide range of bacteria and fungi.

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Research in the Journal of Applied Microbiology found that a cleaning solution of tea tree oil, club soda, and vinegar is better at cleaning ceramics than bleach.

You can even use vinegar as part of an alternative toothbrush cleaning solution, too.

A study in Scientific World Journal looked at two-hundred eighty toothbrushes to find out the best disinfectants . The researchers found that white vinegar was best at killing Streptococcus mutans bacteria, a cause of tooth decay. (The toothbrush goes in the solution; it is not for drinking or swishing in the mouth).

And an article in the World Journal of Dentistry suggests using a combination of white vinegar and table salt to swish your toothbrush in before letting it air dry.

Note that you should not brush your teeth with this solution, but rather just use it to cleanse your brush. The strong acidity level may damage tooth enamel. (More on this below)

Here’s Why Your Stress Is Ruining Your Dental Health, Says a Dentist

Clean produce

"White vinegar works well as a cleaning agent for fruits and vegetables because of its ability to inhibit food-borne pathogens," Malkani says. "Produce can be spritzed with a vinegar and water solution, then rinsed with water before eating."

The ideal ratio is one part vinegar to four cups of water.

This Is the Best Way to Clean Pesticides Off Your Fruit, According to Science

Cook and pickle

Malkani says that you can also use white vinegar as an ingredient for salad dressings, sauces, and marinades. And adding it to a marinade helps tenderize meat.

"It provides a bright flavor and the perception of a salty taste which can help facilitate lower sodium meals, as it contains no sodium and negligible calories," she says.

Some people like to use vinegar with pickling seasonings and water to pickle vegetables and fruits, or along with baking soda in baked goods as a leavening agent, Malkani adds.

Other fun ways to cook with white vinegar are:

• Adding a tablespoon to a cup of milk as a quick buttermilk alternative.
• Add a splash of vinegar to simmering water when poaching eggs, so the whites don't separate.
• You can even add a teaspoon to rice cooking water for fluffier rice.

Vinegar can harm tooth enamel and has other risks

Make sure to dilute the vinegar if you are drinking it instead of cooking with it.

When highly acidic liquids like white vinegar are consumed often, and especially when they are sipped frequently or swished in the mouth, they can lead to tooth erosion , according to Malkani.

"When consumed frequently and in large volumes, white vinegar may also cause inflammation, irritation, and damage to the mouth, throat, and digestive system as a result of its high acidity, so moderation is key," she says.

The best way to consume white vinegar is as an add-on or ingredient for pickling or baked goods. A little goes a long way.

Other research in the Journal of the Academy of Nutrition and Dietetics suggests potential adverse effects, like low blood sugar and low potassium levels, when certain blood sugar and heart medications are supplemented with vinegar .

If you are dealing with health issues like diabetes, the bottom line is to consider these vinegar uses as supplemental—not first-line defenses. And always speak with a health care professional before adding supplements to your diet.

For more wellness updates,  follow The Healthy on  Facebook ,  Instagram , and  Twitter .  Keep reading:

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