analytical research labs hair test

• Analytical Research Labs (ARL)

ARL (Analytical Research Labs) offers a hair tissue mineral analysis, which is a screening test for evaluating the levels of 20 minerals and toxic metals in a hair sample. This analysis provides essential information related to nutrition and mineral ratios specific to an individual's current state of health. ARL is a reputable authority in the field of hair tissue mineral analysis, known for its experience and expertise in this area. The analysis is conducted by analyzing a sample of hair, making it a non-invasive and informative way to assess mineral imbalances and toxic metal exposure.

Popular test panels by Analytical Research Labs (ARL):

Hair tissue analysis [arl (analytical research labs)].

Providing a mineral blueprint of one's biochemistry, a hair tissue mineral analysis can provide pertinent information about one's metabolic rate, energy levels, and stage of stress. A hair tissue mineral analysis performed by Analytical Re

NUTRITIONAL ANALYTICS’ science

Lab certification, analytical research laboratories is government accredited with 45+ years’ experience. their specific procedures ensure accuracy of the hair test within 3%. in america, hair mineral analysis laboratories are inspected annually by the us dept of health and human services, health care financing administration, and the division of health standards and quality. an operating license is issued only if personnel and procedures meet their standards..

Sample Collection

Our collection method is simple, non-invasive and very easy to do at home. We only offer a collection method that meets the most rigorous standards for reliability, stability and validity.

How is the Hair Analyzed?

One of the most critical differences between analytical research labs and other commercial hair testing labs in the us and around the world are that they do not wash the hair with powerful solvents and detergents once the hair sample is collected. this critical difference is what sets them apart from all the other labs in operation. the reason for this is that the powerful detergents/solvents can wash out the water-soluble elements and skew their readings. this is critically important because these are the elements that control most of our metabolism..

THE RESEARCH

The chasm between what is in the clinical research and what the public knows about minerals and mineral balancing is vast. We want to bridge this gap so people can finally understand the power of mineral balancing. We have done this by curating a list of what we believe is some of the best research available out there from the different fields we draw upon. There are also multiple journals we recommend for people who wish to stay up to date on the latest research in the field of minerals and trace elements.

Disclaimer! All information on this website is only the opinion of the author and for educational purposes only. Nutritional balancing is a method to reduce stress on the body. It is not intended as diagnosis, treatment, prescription or cure for any health condition.

© nutritional analytics. all rights reserved 2020.

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Hair Tissue Mineral Analysis

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Hair Tissue Mineral Analysis is an indispensable tool in Nutritional Balancing. It allows us to construct corrective health programmes based, very specifically, on an individual’s biochemistry. As biochemistry develops, we can monitor change and adapt a programme accordingly, all at low cost and without any invasive procedures.

Contents and Quick Links

What is hair analysis?

Interpretation, using hair analysis, what is a metabolic pattern, why is hair analysis superior to blood tests, analytical research labs, the foundation of nutritional balancing.

This advanced screening test measures the levels of twenty-one minerals and toxic metals present in a sample of hair. Since the mineral content of your hair reflects the mineral content of your body tissue,   hair analysis provides us with a mineral blueprint of your cellular biochemistry.

Against popular belief, this does not mean that the total load of minerals and toxic metals in the body are measured .

No test can identify all of the mineral deficiencies, heavy metals and mineral excesses that exist deep in your tissues; within your bones, brain and organs, for example. Instead, a 2cm sample of hair cut close to the scalp reflects average cellular metabolic activity, over a three month period of time.

Metabolic   Activity – The chemical processes that take place in your body to keep you alive.

Sadly, the nature of hair analysis is rarely understood, and many will claim to be experts despite total incomprehension of this tool. Whilst a number of physicians are becoming aware of natural healing methods, they often apply them in a haphazard manner, which can make matters much worse.

Yet through correct interpretation of a hair analysis, it is possible to construct a metabolic picture of the body. This conveys the efficiency and efficacy of different metabolic patterns, influencing how you think, act, feel and heal. In other words, it demonstrates how your body is functioning and its ability to respond to stress. To our knowledge, no other simple test exists that can relay this crucial information.

Understanding these patterns makes it possible to assess the likelihood of many health conditions and to guide their correction. It enables bespoke design of nutritional programmes, determining which nutrients and foods are appropriate, and in what quantities. Because of its mathematical nature, hair analysis can determine food proportions with great accuracy, as well as specific supplement dosage.

Further to this, repeating hair analysis over time and comparing results with previous tests will demonstrate how well the body is progressing and what adjustments need be made to maintain optimal development.

In order to obtain this information, the understanding must go far beyond the identification of single mineral levels. We must recognise the relationships and interactions between minerals, communicated   clearly through mineral ratios and metabolic patterns.

A   metabolic pattern is a combination of mineral levels and/or mineral ratios .

A general rule is that metabolic patterns are the most important factors to consider when interpreting a hair analysis, followed by mineral ratios and finally, single mineral levels. The science of mineral balancing is almost always aimed at improving major metabolic patterns and not a single mineral.

By combining mineral levels, ratios and patterns on a hair analysis, we can assess the following in detail:

Oxidation patterns.   Dr. George Watson discovered that some people burn food at a faster rate than normal, and some at a slower rate. Knowing a person’s oxidation rate , as he called it, can help decide which foods are most needed, and which nutrients would be most helpful to restore balance. Giving the wrong nutrients can make your health problems worse. Hair analysis can be used to determine an individual’s oxidation rate with mathematical precision.

Autonomic nervous system patterns.   A properly performed hair analysis can assess many aspects of the functioning of the autonomic nervous system. This is a critical imbalance today in thousands of people and leads to hundreds of symptoms, from digestive disturbance and trouble eliminating toxic metals, to sleep disturbances, blood sugar problems and even cancers.

Energy patterns.   Having an adequate energy level is essential for health. All body activities, including healing, depend upon adequate energy synthesis. Hair analysis can be used to assess the efficiency of the body’s energy system and to recommend nutrients and foods that will assist in rebuilding that system.

Glandular, organ and tissue patterns.   Levels and ratios of tissue minerals relate to the activity of specific organs and glands. By calculating ratios on a hair analysis, the function of major glands and organs can be assessed, often long before abnormalities appear through x-rays and blood tests.

Dietary patterns.   Hair analysis can be used to quickly screen for hypoglycaemia and diabetes. Hair testing can usually guide a practitioner to correct Type 2 diabetes and some Type 1 diabetes without the need for most drugs. Mineral imbalances and chronic infections are often involved with these conditions.

Toxic metal patterns.   Toxic Metals are a serious problem today, contributing to many metabolic disorders and distressing symptoms including fatigue, infections, high blood pressure, heart disease, cancer, diabetes, dementia & Alzheimer’s. While routine blood tests cannot detect chronic heavy metal poisoning, Hair Tissue Mineral Analysis is one of the few methods approved by the Environmental Protection Agency for detecting toxic metals in the body.

Trend patterns. One of the most useful concepts in healthcare is the ability to identify disease trends before they occur, so that preventative action can be taken. Thirty or more disease trends can be identified from a correctly interpreted hair analysis.

Monitoring progress.   Symptom changes alone are not sufficient to determine whether a person is progressing on a healing programme. Hair analysis, however, can detect subtle changes in body chemistry, a wonderful benefit that enables careful monitoring of healing progress.

Stress patterns.   A superb capacity of hair analysis is its potential to assess stress within the body. Through correct interpretation, it is possible to uncover some twenty to thirty stress response patterns and determine the body’s current stage of stress. This type of analysis and interpretation is based on the stress theory of disease, first put forth by Hans Selye, MD some 60 years ago, yet still widely ignored in the medical profession. It is extremely useful, helping to reverse many types of pathology that do not respond well to other methods of care, be that traditional medical care or holistic healthcare.

Psychological and emotional patterns.   Biochemical imbalances can contribute to many mental and emotional conditions. Hair analysis is outstanding in that it allows us to predict, explain and propose nutritional solutions for these complaints. Common conditions include anxiety, depression, hyperactivity, phobias, insomnia, panic attacks, ADD, ADHD, autism, schizophrenia, dementia, violence, bipolar disorder and more.

Movement patterns.   These are related to a person’s lifestyle and current activities; their life path and movement or progress through life. They can be extremely helpful in counselling a person, promoting understanding of both physical and emotional illness.

Whilst blood tests will always be valuable in determining a number of parameters, they are incapable of providing the information that one can interpret from a Hair Tissue Mineral Analysis. The reasons for this are:

Mineral levels in the blood are ten times less than they are in the tissues, making measurement more difficult.

The body maintains blood levels within very narrow parameters at the expense of cellular health. This means that problems will not show up in the blood until they have reached a critical stage of development, perhaps years after their potential detection through hair analysis.

Blood tests are subject to daily fluctuations due to foods eaten the previous day, emotional states and so on. Hair analysis is not affected by such rapid changes and therefore provides a more dependable, long-term metabolic blueprint.

Toxic metals are easier to detect in the hair than in the blood. They are not found in high concentrations in the blood, unless the test is performed immediately after an acute exposure. Most toxic metals accumulate in the soft tissues , including the hair, as the body works to move them to locations where they will do less damage.

To ensure accuracy in hair analysis, it is imperative that samples are NOT washed at the laboratory and   that their interpretation is in line with Dr. Paul Eck’s methodology.

At Hair Diagnostics, all Hair Tissue Mineral Analyses are performed by Analytical Research Labs, Inc. (ARL) in the USA. This is the laboratory that Dr. Eck established himself, in 1974, and one of only two laboratories in the world that do not wash hair samples for testing. Washing hair samples at the laboratory has been shown to dramatically reduce test reliability.

As one of the most respected and experienced leaders in the Hair Tissue Mineral Analysis field, ARL has been setting professional standards for hair testing and interpretation laboratories for decades. As pioneers in the field of Hair Tissue Mineral Analysis interpretation , ARL was the first laboratory to integrate the factors of stress, oxidation types, mineral relationships, homeostatic states and natural healing principles into this science. It was the first laboratory to recognise the importance of hair mineral ratios, to determine oxidation rates and to identify and correlate more than thirty metabolic disease trends using hair analysis.

Interpretations of mineral levels and ratios are measured against an ideal standard of health at ARL, rather than a vast average range, as used by other laboratories working in hair analysis. ARL continues to lead the field of Hair Tissue Mineral Analysis today.

Please note: Provided sufficient hair is available for a second sample, ARL will automatically retest any reading that falls outside of expected ranges.

Thanks to Hair Tissue Mineral Analysis, every aspect of a Nutritional Balancing programme can be tailored to the individual. This includes diet plans, supplementation, detox protocols and lifestyle recommendations. Find out more about the programme…

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Hair Diagnostics 2a Maiden Lane Stamford PE9 2AZ UK [email protected]

Introduction to the Hair Mineral Analysis Test and Heavy Metals Test

Discover what mineral imbalance is at the root of your symptoms and preventing you from regaining your vitality and health…

If you are interested in optimising your weight, energy, mental or emotional health, skin, hair, digestion, thyroid or adrenal health etc OR you are not responding to supplements, other health protocols, blood tests not showing WHY you have health issues or symptoms — this simple hair test can tell you what’s really happening AT THE CELLULAR LEVEL where energy is created.

You will be tested for 20 ESSENTIAL MINERALS AND HEAVY METALS and these will be analysed for levels, ratios and stress patterns. You will get the full analysis based on the work of Dr Paul Eck of Analytical Research Labs, the additional discoveries of Dr Lawrence Wilson – and the many years of clinical experience of an HTMA Practitioner and Nutritional Consultant.

For speed we now send everything via email. 

• You will receive hair test instructions and forms. 
• You will need to print your forms. 
• You will need to supply 2 envelopes: one for your sample and one for the sample envelope and form. 
• Once the lab has received your sample it takes about 1.5 weeks to process and then a few days for the analysis when we receive your chart. 
• Your programme, analysis, diet, supplement and detox suggestions will be emailed to you. For this incredible price you also get unlimited email support for any questions, advice etc.
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Hair Tissue Mineral Analysis – Analytical Research Labs

US$ 160.00 – US$ 200.00

Hair tissue mineral analysis (Analytical Research Labs, U.S.A.) reveals your metabolic profile, mineral imbalances, heavy metal toxicity and possibly reasons for symptoms.

Hair can be sampled at home and sent directly to the lab. Once ordered, easy to follow instructions and forms will be emailed to you.

Note: If you have previously performed a hair test with ARL, please let us know in the comments section during check out. We will prepare a retest report with comparison analysis.

Description

Additional information.

• You can refer to samples of the various reports in the “Additional Information” tab.
• Hair analysis chart indicating levels for 15 major minerals, 6 major toxins and 6 mineral ratios.
• Expert analysis and tailored nutritional balancing program from a practitioner. This will include practitioner comments and an interpretation of your hair mineral patterns. These can help you better understand your physical and psychological symptoms. The expert analysis also contains recommendations for diet, supplements, detoxification procedures and lifestyle that are optimal for your health condition.
• 30 minutes consultation call and 4 months email support included.
• A thorough interpretative report that lists trends and provides a detailed explanation of the results.
• In the case of a retest, a comparison analysis is included to explain what changes have taken place in your biochemistry since the previous test.
• Have a look at our sample lab report .
• Lab Report + Expert Analysis  includes all of the reports and services described above.
• The lab report   is a computer generated report containing standard analysis on hair mineral levels and ratios, as well as basic recommendations for diet, supplements and lifestyle.
• Expert analysis   is prepared by a nutritional balancing practitioner based on the latest research and findings. The report includes analysis of hair mineral levels and ratios, and describes hair mineral patterns that are not included in the lab report. Expert analysis also includes a customised nutritional balancing program covering diet, supplements, detoxification procedures and lifestyle.
• Our nutritional balancing programs are based on methodologies developed from 45 years of research to help you improve and regain health and vitality.
• All reports are sent in soft copy via email.
• Once you have ordered, instructions and forms will be emailed to you providing guidelines on how to take the hair sample and how to send the sample to the lab.
• The process usually takes 2 to 3 weeks depending on the time it takes for your hair sample to reach the lab.
• You are eligible for 20% off supplements from Endo-met when ordered as my client.

View Sample Hair Analysis Chart

View Sample HTMA Expert Analysis

View Sample Hair Analysis Lab Report

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Using Hair Analysis to Improve Health Through Nutrition!

Profile IV – Retest – Comprehensive Nutrition (ARL)

Analytical research labs inc. profile iv.

The Profile IV (Retest) is a P rogress Test and C omparison Analysis . Included is a complete retesting of your mineral levels to check what changes have taken place in your biochemistry since the previous test. Modifications to the food and supplement program are suggested where there has been significant progress.

Because food and supplement recommendations are quite specific, it is stressed that progress tests be done 12 weeks after the initial analysis.

Our Profile IV Hair Analysis by Analytical Research Labs Inc. includes:

• A comprehensive interpretation, in layman terms, (usually 26 pages)
• Stage of stress
• Organs and systems patterns
• Metabolic patterns and trends
• Electrolyte patterns
• Digestion patterns
• Recommendations for foods and supplements
• Program support – Up to 1-hour complementary phone Consultation (included in US orders only) to review results and includes any additional questions while following the program

Note:  Supplements from Endo-met Laboratories (ARL) are purchased separately. Tests not available to New York residents. For accuracy, we prefer untreated scalp hair. See  FAQ’s .

Profile IV – Retest – Analytical Research Labs Inc.

Only $164.00 (U.S. only – NO International Orders!)

Order your Hair Analysis today!

Commonly tested elements:

Nutritional Elements:  Calcium, Magnesium, Sodium, Potassium, Iron, Copper, Manganese, Zinc, Chromium, Selenium, Phosphorus

Toxic Elements:  Arsenic, Mercury, Cadmium, Lead, Aluminum

Additional Elements: Cobalt, Molybdenum, Lithium, Nickel

Significant Mineral Ratios:  Calcium/Magnesium, Calcium/Potassium, Sodium/Magnesium, Sodium/Potassium, Zinc/Copper, Calcium/Phosphorous

View a  Sample Report  from Analytical Research Labs Inc.

The content and laboratory services provided on this site are for educational and informational purposes only and not intended to diagnose, treat, prevent, or cure disease.

How to interpret Hair Analysis Results?

• Post published: January 25, 2022

Are you confused with understanding your Hair Mineral Analysis?

You might have thought you found a deal on a Hair Analysis test but now that you have your results you don’t understand them.  Many companies don’t offer any further information or a consultation.  If they do, it may cost more than the lab fee leaving you frustrated.  No one wants to be stuck in the same place as where you were before they took the test, much less even more confused!

• Not sure if the levels or ratios are good, bad, or perfect?
• Not sure what diet it dictates for your oxidation rate known as metabolism rate?
• Still unsure which exact supplements your biochemistry needs for corrections?
• Left where you started, unclear on your health status or what your next step should be?

What can a Hair Analysis Test show?

Your hair sample is a soft tissue biopsy showing which minerals need to be balanced to help your body in correcting many symptoms.  They may stem from hormone imbalance, incorrect supplementation, diet or environmental toxins and SO much more. Let’s find the root cause to reverse engineer the issues for cellular correction.  I will look at your current test to determine specific markers.

We will go over your:

• mineral deficiencies or excesses
• heavy metal toxicities
• protein synthesis or catabolism
• cellular sugar storage
• thyroid function
• adrenal health
• cell membrane strength or weakness

and more while I answer any questions you may have about your needs.

Hair Analysis results are like a detailed short film in comparison to an exact moment snapshot of your blood test.  Your blood will borrow from your cells like a savings account to maintain balance (homeostatis) but once your cells are empty there are no loans to recover.  The hair is dead but the information deposited is the key to correcting deeper issues.

Who can help you read your Hair Mineral Analysis results?

Me!  For over a decade I have used my expertise to help clients with exact steps to eating the right diet, taking the supplements their body needs, and coaching through detox symptoms when they arise in the healing process.

My basic Hair Analysis service includes supplement recommendations and an explanation of what each of them does for your body. I also review the results on a phone call or zoom to explain your results.  Since you have some lab results, you won’t have to redo it to understand it.

Each lab has values that are a bit different, but I can equate your numbers as closely as possible to Analytical Research Labs ranges for comparison. After we review your results we can retest 3-4 months later to see what positive improvements your changes have been made to get better clarity and focus on deeper corrections.

What is the best laboratory to use for a Hair Mineral Analysis Test?

I use Analytical Research Laboratories, Inc. (ARL)  .  Let me explain why.

Several factors combine to make our Hair Tissue Mineral Analysis the best in the industry!

We are one of only two laboratories that do not wash the hair at the laboratory. Washing hair samples at the laboratory has been shown to erratically wash out the water-soluble elements. This creates much less accurate results. In a 2001 study in the Journal of the AMA (Seidel, S. et al., Assessment of Commercial Laboratories Performing Hair Mineral Analysis, JAMA, 285(1) Jan 3:67-72.) the two laboratories that did not wash the hair, of which we were one, showed superb reliability.

We use technologically advanced testing instruments, including the Perkin Elmer Elan 9000 ICP Mass Spectrometer. This gives you the most accurate Hair Analysis results so you can make corrections.

We are proud of our laboratory quality control procedures. These include known controls which are tested at the beginning, middle and end of every batch of hair samples to insure the accuracy of the results.

We automatically retest any reading that is out of a normally expected range, provided sufficient hair is available for a second sample.

Hair Analysis results are printed on an easy-to-read graph, unlike many of the other laboratories. This is a great benefit for both practitioners and their clients as well. The printed graph includes the mineral results, major mineral ratios and the oxidation type.  We offer the only complete individualized test interpretation by the method developed by the late Dr. Paul C. Eck, our founder.

What line of professional supplements are recommended?

Unlike any other dietary supplement company, we offer a specifically formulated line of mineral and vitamin supplements designed to match the biochemical individuality of our users.  Our ability to recognize which minerals and vitamins are either compatible or detrimental to each other permits us to make nutritional supplement recommendations which are exceedingly accurate and effective.

ARL has a continuous program of research to revise and improve our formulas assuring the most advanced products available today.  They closely monitor the most authoritative sources of information to stay informed of the latest dietary and nutritional concepts.  We combine this knowledge with our own work in the field to take advantage of the highest quality methods, procedures and ingredients that will assure maximum biological and metabolic effectiveness of our product line.

If you have already done a test but need help understanding it, I’m here to help you without having to pay for another lab fee.

Why is a Hair Analysis interpretation necessary?

Without an expert to guide you with your analysis you will be left unclear about your next step. If you supplement with a mineral that is low you could be contributing toward toxicity as well as adding to the toxicity. Knowing what other minerals or heavy metals are affecting an imbalance is key. Correction must be done within the body as a whole, not just troubleshooting one symptom or level at a time.

Why do I need an expert to help me understand my Hair Analysis Results?

Because you need a Nutritional Consultant that specializes in Hair Mineral Analysis to understand the nuances of reading the results, answer your specific questions, and to help you understand what your next step is in your health journey.  Isn’t that why you did a hair test in the first place?

Let’s take the mystery out of your Hair Test today, LET’S CHAT about your health goals!

Read more on understanding mineral levels on a Hair Analysis and learning if you are a slow or fast oxidizer .

Copyright Scientific Nutrition, LLC 2022

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ARL Lab Profile

Laboratory services provided by arl, profile i - laboratory mineral assay.

This profile represents the basic Multi-Element Laboratory Assay reporting the patient test results for macro and micro minerals, toxic metals and significant ratios. A chart is provided that identifies the patient/client information and graphically illustrates the test results. There is no interpretation provided with this profile.

Profile II - Laboratory Mineral Assay and Comprehensive Interpretation

This profile includes the complete Multi-Element Laboratory Assay provided in Profile I, plus a thorough interpretation that reviews significant mineral levels and ratios and provides pertinent information related to the patient's metabolic rate, energy levels, autonomic balance, basic dietary guidelines and a complete dietary supplement program designed to assist in balancing body chemistry.

Profile III - Laboratory Mineral Assay and Supplement Recommendations

This profile includes the complete Multi-Element Laboratory Assay provided in Profile I, plus a complete dietary supplement program designed to assist in balancing body chemistry.

Profile IV- Laboratory Mineral Assay and Progress/Comparison Interpretation

This profile includes the complete Multi-Element Laboratory Assay provided in Profile I, plus a thorough 12-15 page interpretation that evaluates any significant changes in the patient's biochemistry. A detailed comparison of current mineral levels and ratios with previous test results, modifications to the dietary supplement program.

Profile V - Personalized Transition Dietary Plan

This profile provides a personalized transition dietary plan based entirely upon the results of your hair tissue mineral analysis. This 22-25 page report includes three complete transition diets, menu plans and a wealth of information covering food preparation, eating habits, modifying one's habits, cooking, shopping and other valuable information. This profile may be ordered as an addition to any of the other profiles.

Hair Analysis: Why We Use Analytical Research Labs

Posted by Eileen Durfee on 22nd Mar 2015

Get your  Hair Analysis test and Nutritional Balancing program to determine the toxic metals and mineral imbalances in your body! This will help guide a corrective program customized to enhance your health. This is the most affordable and reliable method for precise results that will lead the way to a healthier life.  All of the Hair Analysis tests purchased through us are processed by  Analytical Research Labs and reviewed by  Dr. Lawrence Wilson . 

Why we recommend Analytical Research Labs

There are several factors that contribute to why Analytical Research Labs is the most  recommended for processing Hair Analysis tests:

• They do not wash the hair samples at the lab

For the most complete analysis, it is necessary that the hair  is not washed in the lab before testing. The results can vary when the washing agents and chemicals remove natural minerals from the hair. 

• Dr. Eck’s ideal ratios and levels are used

Analytical Research Labs provides a full Hair Analysis test interpretation based on Dr. Paul Eck's methods. This includes information about energy levels, carbohydrate tolerance, autonomic balance, metabolic trends, diet guidelines, metabolic rate, sugar tolerance, immune system, glandular activity, and a customized supplement program.

• Personalized Dr. Wilson program

All Hair Analysis tests processed with Analytical Research Labs include a Dr. Wilson created and customized program based on your personal lifestyle and diet to provide the most successful and accurate outcome.

A criticism may be made that other research labs point out more toxic elements than Analytical Research Labs. However, ARL does not review more toxic metals than are necessary to help create a corrective program. They analyze and report only the essential information in order to keep the costs low and lead the way with the most accurate Nutritional Balancing Science program possible.

Purchase your Hair Analysis test from Wellness Shopping Online today for the best results and a personalized plan to help improve your health and future!

This material is for educational purposes only The preceding statements have not been evaluated by the Food and Drug Administration This information is not intended to diagnose, treat, cure or prevent any disease.

• #Dr. Lawrence Wilson
• #Dr. Wilson and associates
• #Hair Analysis
• #Hair Analysis kit
• #Hair Analysis lab report
• #Nutritional Balancing Science
• #www.drlwilson.com

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A Review on Saliva-Based Health Diagnostics: Biomarker Selection and Future Directions

Swati kumari.

1 Department of Restorative Dentistry, College of Dentistry, University of Illinois at Chicago, Chicago, IL USA

Mesk Samara

Remya ampadi ramachandran.

2 Department of Biomedical Engineering, University of Illinois at Chicago, Chicago, IL USA

Haritha George

3 Department of Biological and Chemical Sciences, Illinois Institute of Technology, Chicago, IL USA

Russell P. Pesavento

4 Department of Oral Biology, College of Dentistry, University of Illinois at Chicago, Chicago, IL USA

Mathew T. Mathew

Associated data.

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

The human body has a unique way of saying when something is wrong with it. The molecules in the body fluids can be helpful in the early detection of diseases by enabling health and preventing disease progression. These biomarkers enabling better healthcare are becoming an extensive area of research interest. Biosensors that detect these biomarkers are becoming the future, especially Point Of Care (POC) biosensors that remove the need to be physically present in the hospital. Detection of complex and systemic diseases using biosensors has a long way to go. Saliva-based biosensors are gaining attention among body fluids due to their non-invasive collection and ability to detect periodontal disease and identify systemic diseases. The possibility of saliva-based diagnostic biosensors has gained much publicity, with companies sending home kits for ancestry prediction. Saliva-based testing for covid 19 has revealed effective clinical use and relevance of the economic collection. Based on universal biomarkers, the detection of systemic diseases is a booming research arena. Lots of research on saliva-based biosensors is available, but it still poses challenges and limitations as POC devices. This review paper talks about the relevance of saliva and its usefulness as a biosensor. Also, it has recommendations that need to be considered to enable it as a possible diagnostic tool.

Graphical Abstract

Introduction

Any disease deviates from healthy well-being, and early disease detection is critical for proper treatment and eradication. Saliva-based diagnosis has drawn significant attention due to its ease of collection, cost-effectiveness, accessible storage, and non-invasiveness. Other body fluids like blood and urine routinely used for disease diagnosis have associated collection issues. Saliva has biocomponents that could be used as potential biomarkers. Hence, saliva as a diagnostic tool will add to the diagnostic arsenal, providing critical information about oral and systemic health. The Salivary biomarkers range in different omic realms, from proteomics to metabolomics to transcriptomics. Considering its various possibilities, this review explores several studies in saliva-related diagnostics and its correlation with systemic diseases, highlighting its potential as a diagnostic specimen.

Saliva is a crucial human body fluid that protects the oral cavity from infections [ 1 ]. It acts as a lubricant that protects teeth and regulates the enzymatic activity in the mouth. Research shows a salivary flow reduction can indicate dental caries risk [ 2 ]. The salivary biofilm covers the tooth surface [ 3 ], naturally protecting the tooth against decay and erosion.

The major and minor salivary glands secrete saliva, which flows through the ducts and reaches the mouth [ 4 ]. The significant glands include the parotid gland, submandibular gland, and sublingual gland (Fig.  1 ), and are the combination of mucous and serous cells that aid in the secretion of saliva. Mucous cells are columnar; they secrete thick and viscous saliva, while serous cells are triangular and secrete thin, watery saliva [ 5 ] (Fig.  2 ). Serous cells are found to be smaller, with an oval-shaped nucleus; mucous cells are much larger and have a paler color. Humans produce nearly 600 mL of saliva daily, essentially composed of 99% water and containing sodium, potassium, and chloride electrolytes. The salivary composition depends on the diet or nutrient intake. The presence of genetic material in the saliva of the person aids in many genomic applications, including forensic evidence [ 6 ]. Saliva contains proteins such as amylases and immunoglobulin, which break down starch and other substances that aid digestion [ 7 ]. Additionally, it contains antimicrobial factors that retain the health of oral microbiota and substances like urea and ammonia [ 8 ]. Collectively, these components in saliva make it a powerful and valuable diagnostic tool.

Diagram shows the three salivary glands and their locations

Diagram shows the types of acinar cells in salivary glands

The main focus of this review is to summarize the existing studies that use salivary biomarkers and identify salivary biomarkers for various systemic diseases. This review has three specific objectives (a) to summarize the literature in terms of different kinds of salivary biomarkers, especially those associated with systemic diseases; (b) to examine the relationship with periodontitis and also the advantage of oral/salivary biosensors; (c) to look at the change in the field after the covid pandemic.

Method of Review

This review was based on salivary biocomponent presence, which could be used as biomarkers for early detection and diagnosis of oral health and the potential association with oral and systemic diseases. The principle question, which is the focus of this review, is, “Is there any change in salivary biocomponents which could be used in diagnostic/biosensor development”. Electronic databases such as PubMed, Scholar, Science Direct, NIH, MDPI, Web of Science, and other websites such as Wiley online library, RSC Publishing, and Google Scholar were considered for this review focusing only on the available literature. Figure  3 illustrates the article selection method adopted to conduct this review. No limits on dates were placed on the database search. The search query included saliva, systemic diseases, salivary bio components, and serum.

Flowchart representing the article selection method

Saliva as a Potential Biofluid for Biosensing

Saliva: the primary function.

Saliva can act as a buffer in the oral cavity to prevent pathogens from infecting the cavity, and it neutralizes the acids produced by highly acidic food consumed [ 9 ]. This prevents enamel from degradation and protects the teeth. For example, consuming fermented carbohydrates in cookies, soda, and candy can lead to decreased oral pH, and salivary peptides are released to increase the pH of the saliva to maintain the normal oral pH [ 10 ]. Ammonia and urea in saliva also increase pH, allowing the buffer system to function effectively. The ability to analyze normal vs. abnormal levels of urea and other substances in saliva opens the door for various biosensor development, where specific biosensors can test for various salivary biomarkers and categorize them as normal versus abnormal. As a result of this analysis, abnormal signs or increased/decreased levels of crucial enzymes or biomarkers can be used to diagnose possible disease or infection detection.

Other functions of saliva include rinsing, solubilizing food substances, bacterial clearance, lubricating soft tissues, bolus formation, swallowing, speech, and facilitation of mastication; all related to its fluid characteristics and specific components. In addition, saliva components contribute to mucosal coating, digestion, and antibacterial defense [ 11 ].

Properties of Saliva

Saliva is a hypotonic solution that contains water, electrolytes, mucus, and enzymes. Approximately 90% of saliva is secreted from major salivary glands such as parotid, submandibular, and sublingual. Elements of non-salivary origin include gingival crevicular fluid (GCF), expectorated bronchial and nasal secretions, serum and blood derivatives from oral wounds, bacteria and bacterial products, viruses, and fungi desquamated epithelial cells, other cellular components, and food debris [ 12 ].

Human saliva mirrors the body's health and well-being. More than 20% of proteins in the blood are also found in saliva, making saliva an invasive option for detecting biomarkers that correlate with the disease state. Saliva has numerous advantages over blood as a diagnostic fluid, allowing for a non-invasive, simple, and safe sample collection. Its composition reflects the state of health and illness in a body, and it can potentially be a diagnostic medium for systemic diseases. Saliva can be considered as gland-specific saliva or whole saliva. Evaluations of the secretions from the individual salivary glands help detect gland-specific pathology, i.e., infection and obstruction. However, the whole saliva is most frequently studied with analysis for systemic disorders.

Salivary Constituents

An average person can produce 600 mL of saliva per day. Saliva contains 99% water and one percent organic molecules such as salivary amylase, mucopolysaccharide, mucin, and lysozymes, and some inorganic matter such as sodium, potassium, calcium chloride, and thiocyanate ions. Various bio-components are also found in saliva, including protein and related molecules, nucleic acid components, and endogenous and exogenous metabolites[ 13 ]. Examples of biocomponents detectable in saliva [ 14 – 16 ] are summarized in Table ​ Table1 1 .

Examples of biocomponents detectable in saliva

Advantages of Salivary Test

The main advantage of this non-invasive technique is that patients with needle usage restrictions, such as children, aged, and hemophiliac patients, can do the sample collection and test for biomarkers. Also, unlike blood, saliva can be self-collected, and unlike urine, saliva can be collected at any time. These are the necessary conditions that point-of-care testing (POCT) must meet to make on-site testing possible anywhere at home or the workplace. Furthermore, it can be beneficial for mass screening tests and continuous monitoring. Table ​ Table2 2 shows various approaches to diagnosing systemic diseases and body conditions using salivary biomarkers with the possibility of being used as diagnostic methodologies even in a clinical setting.

Summary of various approaches to diagnosing systemic diseases and body conditions using salivary biomarkers

Sample Collection

Saliva can be collected in two methods: unstimulated and stimulated saliva. Unstimulated saliva is produced consistently within the oral cavity and is present in the mouth. The second type is stimulated saliva, collected using chewing gum or a flavor drop into the oral cavity. The activated taste buds respond to the brain and increase the secretion of saliva in larger quantities [ 8 ]. Previous research exposes that stimulated saliva expressed more than three times the number of biomolecules than unstimulated saliva [ 17 ]. Stimulated saliva contributes to most daily secretions, whereas unstimulated saliva covers the oral tissue and acts as a lubricant [ 18 ].

A Lashley cup can be used to collect oral fluids via suction from a specific gland. Cotton swabs can also be used but may cause unwanted bias. Various saliva-collecting devices are manufactured by companies like Salimetrics® v (State College, PA, USA), DNAGenotek (Kanata, ON, Canada), and Oasis Diagnostics® Corporation (Vancouver, WA, USA). These devices revolutionized collecting saliva and its transportation methods without contamination [ 16 ]. However, draining, spitting, and suctioning are standard approaches [ 19 ]. Regardless of the method used, the subject should clean the oral cavity with water to avoid contamination before collection.

Biosensor Selections

Biosensors are an exciting addition to the world of nanomedicine and technology. They allow patients and healthcare providers to monitor disease progressions and treatment efficiency [ 20 ]. Biosensors can detect various indicators of diseases in fluids, such as blood, saliva, and urine. Additionally, biosensors allow patients to understand their illnesses and their betterment over time. The development of biosensors allows patients to have an affordable alternative to doctors' appointments and reduce the need for stressful medical bills and inefficient circumstances. Such devices are considered to be “point-of-care”. This means they play a vital role in detecting diseases early on and surveilling any crucial data to provide patients with early treatments and prevent disease progression (Tables ​ (Tables3 3 and ​ and4 4 ).

Summary of literature reviews on oral biosensors

Clinical Need for Biosensors

A fully developed biosensor will generally consist of a bioreceptor, which recognizes the substance of interest [ 20 ] (Fig.  4 ). It will also contain a substance transducer to convert the biomarker into a viable number or readable graph. For example, viruses, such as COVID-19, can also be detected through saliva. This allows highly contagious diseases to be detected quickly [ 21 ]. This allows easy and quick data processing and communication between patients, clinics, and doctors from their homes. Figure  4 a) is a representation of a potential app that can be developed to connect with a transducer and used to send important data to healthcare professionals; Fig.  4 b) shows a sample disposable transducer test strip that can be used with the collected saliva in a test tube which offers a non-invasive testing possibility.

a Diagram shows a potential app that can be developed to connect with a transducer and send important data to healthcare professionals, b Diagram shows a sample test tube that will include the easily obtained saliva sample and the disposable transducer strip

Cobalt metal diagnostic devices are currently used for glucose quantification [ 22 ]. This diagnostic device, the cobalt metal framework, monitors glucose levels in patients. It is paper-based, which makes it cheap and effective, and disposable. However, this device requires blood as a sample medium instead of saliva, which could risk infection if mishandled and make it less accessible. Figure  5 is a schematic of the commonly used three biomarkers in the collected saliva with a transducer used for it.

Diagram shows an example of a transducer and the three main biomarkers to be tested

Salivary Biomarkers

Various biomarkers are present in saliva, and some are identified through infrared spectroscopy. Cells proliferate much faster, and therefore, cancers can metastasize quickly. Apart from monitoring periodontal diseases [ 23 , 24 ], saliva has been used to identify systemic inflammations and screening purposes in epidemiological studies [ 25 ], revealing its possibility as a diagnostic tool. The presence of cancer-detection biomolecules leads researchers to believe that biomarkers in saliva can indicate cancers and provide options for early detection[ 26 ].

Gingival Crevicular Fluid (GCF) GCF

Gingival crevicular fluid (GCF) is a fluid secreted by the gums, specifically at the line where the gums and the teeth meet. GCF is unique because it is considerably low in quantity in a healthy oral cavity and spikes higher when a patient has gum disease or infection. GCF is also non-invasive, and its concentration can indicate disease [ 27 ]. The composition of GCF is unique due to its electrolytes, albumins, globulins, lipoproteins, and other components. GCF has shown its ability to detect anti-HIV antibodies [ 28 ], which enables its use as a diagnostic marker in HIV-positive patients.

Microbiome as a Biomarker

A typical example of bacteria in the saliva is Streptococcus Gordonii, which is found in periodontal environments and causes bone loss and inflammation [ 29 ] . Additionally, S. Gordonii can enter the blood circulatory system and cause life-threatening diseases such as endocarditis. It can affect the formation of healthy biofilm protective layers, thereby increasing the risk of dental caries [ 30 ]. With the overwhelming use of Ti-based dental implants, the Ti-based biosensors are crucial as they can provide information about peri-implantitis and bacterial disintegration upon antibacterial or antimicrobial agents.

Alpha-Amylase as Biomarker

Alpha-amylase plays a significant role in odor, flavor, and oral texture [ 31 ], it also monitors stress levels [ 32 ]. Although alpha-amylase is only found in small amounts in saliva, it still significantly influences the oral cavity.

Urea as Biomarker

Levels of urea in saliva can provide insight into chronic kidney disease [ 33 ] and renal failure. Salivary urea and bicarbonate act as a buffer, and their levels can vary based on salivary gland stimulation [ 34 ]. Providing patients with a biosensor will allow them to better understand their condition through a simple smartphone app. Additionally, they can seek medical help if normal urea levels are shifted and remain aware of their bodily functions, further preventing emergencies. The presence of urea in saliva makes saliva a test sample facilitating easy, point-of-care feasibility using optical or electrochemical biosensors.

Cancer Biomarkers

With oral cancer being one of the top cancers in the world, controlling its cell cycle and early detection is a crucial step to prevent it from spreading [ 35 ]. Generally, detecting oral cancer can take a long period, is expensive, and is invasive for the patient. Collecting a sample and analyzing it directly through a biosensor allows painless detection, is time efficient, and does not require the presence of a trained expert. Serum and plasma are often used to detect biomarkers, specifically for monitoring diseases and their progression.

Diagnosis of Systemic Diseases Using Saliva

Some systemic diseases may affect the composition of salivary biomarkers presence. These characteristic changes may contribute to the diagnosis and early detection of these diseases .

Metabolic Diseases—Heart Diseases, Diabetes, and Liver Diseases

Cardiovascular diseases.

Cardiovascular diseases are reported as one of the leading causes of death annually by the World Health Organization (WHO) . Human saliva plays a significant diagnostic role in the detection of cardiovascular diseases by examining the salivary biomarkers, e.g., C-reactive proteins (CRP) [ 36 ], Cardiac troponin (cTn) [ 37 ], and Creatine phosphokinase [ 38 ] and NT-ProBNP [ 39 ]. Table ​ Table5 5 summarizes various Salivary Biomarkers in Cardiovascular diseases. Activation of MMP-8 plays a vital role in the pathogenesis of coronary artery diseases. It causes infarction growth, tissue repair, and cardiac remodeling [ 40 ]. MMP-8 and its tissue inhibitor TIMP-1(tissue inhibitor of matrix metalloproteinase-1) concentration are associated with ischemia and infarction [ 41 ]. The ratio of MMP-8/TIMP-1 reflects the progression of cardiovascular diseases in serum [ 42 ]. The additional enzyme involved is Lysozyme, which is present in saliva and other secretions such as mucus and tears [ 43 ].

Summary of various salivary biomarkers in cardiovascular diseases

Literature reports the compatibility between a biomarker of saliva and blood for the diagnosis of Acute Myocardial Infarction (AMI). Serum biomarkers for Acute Myocardial Infarction were Troponin 1, B-type natriuretic peptide, and creatine kinase. In saliva, C-reactive protein (CRP) was found as a biomarker that is the most predictive biomarker of AMI. AMI was diagnosed with 80.0% sensitivity and 100% specificity. This finding shows the potential of salivary biomarkers combined with ECG as an additional diagnostic method for AMI patients [ 44 ].

Diabetes Mellitus

Diabetes is another common systemic disease in the world and developing rapidly due to dietary habits, genetics, and other systemic disease-related complications. In addition, patients with diabetes have higher glucose and alpha-hydroxybutyrate levels and significant changes in carbohydrate, lipid, and oxidative stress levels. The relation between HbA1c and Salivary glucose concentrations in patients with diabetes is reported, indicating blood glucose levels could be easily monitored by the saliva in patients with diabetes mellitus [ 45 ]. MMP-8 levels are also elevated in patients who have diabetes [ 43 ]. It can be used as a salivary biomarker; however, further studies are needed to diagnose diabetes. Table ​ Table6 6 shows various Salivary Biomarkers found for diabetes in different research experiments.

Summary of various salivary biomarkers found for diabetes

Liver Diseases

Hepatocellular Carcinoma (HCC) is one of the deadliest types of cancer that causes a large number of deaths around the world. Early detection of HCC is complicated. Salivary long non-coding RNA-PCDH9-13:1(salivary lnc-PCDH9-13:1) is a specific biomarker for the diagnosis of early HCC [ 46 ]. HCC tissue, by necrosis and apoptosis, secretes lncRna in blood, and then through the salivary gland blood supply, it goes to saliva. Alpha-fetoprotein-L3 is also a promising salivary biomarker of HCC [ 47 ]. Hepatitis B and C virus infections commonly cause chronic liver diseases and liver cirrhosis. The natural history of hepatitis B and C virus infection can remain latent without manifesting symptoms. Most patients are asymptomatic, unaware of existing illnesses, and prone to disease progression and transmission. Additionally, some infected people remain undiagnosed due to their unwillingness to provide a blood sample. HBV and HCV infections are monitored mainly by blood and serological test. Interestingly, reports have indicated that HBV and HCV DNAS, viral antigens, and antibodies also exist in infected person’s saliva and correlate significantly with blood samples [ 48 ]. These findings show the potential role of saliva as a non-invasive diagnostic method for HBV and HCV infection. A commercially available test that can rapidly identify HCV antibodies in saliva using an Enzyme Immunoassay (EIA) was also developed [ 49 ]. The result obtained by this test is almost similar to that of serum immunoassay. It is widely available in Europe; however, waiting for approval by the FDA in the United States. Once approved, this could impact the early detection and management of HCV infections [ 50 ]. Table ​ Table7 7 summarizes salivary biomarkers found in the literature for liver diseases.

Summary of various salivary biomarkers found for liver diseases

Inflammatory Disease—Rheumatoid Arthritis

Rheumatoid arthritis causes joint pain and damage throughout the body, as it is a chronic inflammatory disease. In rheumatoid arthritis, the body attacks its tissue; in severe cases, it may destroy internal organs. Because of pain and swelling IL-1beta, MMP-8, and TNF-alpha increase in inflamed joints and serum. It is anticipated that rheumatoid arthritis increases the risk of periodontal diseases. MMP-8 is elevated in saliva in patients with rheumatoid arthritis, and its increased level causes periodontal inflammation [ 51 ]. Several studies have suggested a strong association between rheumatoid arthritis and periodontal diseases. IL-1beta level in the saliva is high in rheumatoid arthritis compared to patients with periodontal disease [ 52 ]. Rheumatoid arthritis patients receiving anti-TNF-alpha antibody therapy have lower IL-1beta and TNF-alpha levels in saliva. Table ​ Table8 8 summarizes salivary biomarkers found for Rheumatoid arthritis during the current review .

Summary of salivary biomarkers found for Rheumatoid arthritis

Malignant Tumors—Breast Cancer and Cystic Fibrosis

Breast cancer.

Breast cancer, besides skin cancer, is the most common type of cancer in females. Mammography, the most generic method used to detect breast cancer, has a few limitations, such as overdiagnosis and false positives. It fails for small, early-stage tumors, dense breast tissue, and women under 40. The most crucial aspect of saving a patient is the early detection of breast cancer. There are several challenges and concerns in the early detection of breast cancer, including the risk of disease transfer through serum-based breast cancer screening. To address these challenges, a handy and self-screening saliva-based biosensor was developed by Sania Arif et al. [ 53 ] by using salivary autoantibodies ATP6AP1 [ 76 ]. Lately, detecting Human Epidermal Receptor-2 (HER2) levels in saliva has also been suggested to diagnose breast cancer [ 54 ]. Cancer antigen 15-3 (CA 15-3) is a protein that is produced by normal breast cells. In many people with cancerous breast tumors, there is an increased production of CA 15-3.

The salivary level of CA 15-3 is 50% higher in an infected person than in a healthy person or those with benign tumor cases. Therefore, it has been suggested to use CA 15-3 for the early detection of breast cancer [ 55 ]. Tumor protein p53 regulates cell division by keeping cells from growing and proliferating too fast or uncontrolled. Salivary levels of p53 are reported less in breast cancer patients than in healthy individuals [ 56 ]. Salivary autoantibodies against both HER2 and MUC-1 have been reported for the early detection of breast cancer [ 57 ]. Milk-derived peptides proline and valine are suggested as potential salivary biomarkers for detecting early and advanced stages of breast cancer [ 58 ]. Table ​ Table9 9 indicates various salivary biomarkers found for breast cancer.

Summary of various salivary biomarkers found for breast cancer

Cystic Fibrosis

Cystic Fibrosis (CF) is a genetically transmitted disease among children and young adults. It occurs due to defective electrolyte transport in epithelial cells and viscous mucus secretions from glands and epithelia [ 59 ]. The organs most affected in CF are (a) sweat glands, which produce a secretion with elevated concentrations of sodium and chloride; (b) the lungs, which develop the chronic obstructive pulmonary disease; (c) the pancreas, resulting in pancreatic insufficiency [ 60 ]. DNA analysis is not considered for CF diagnosis due to mutations in the CF gene. At the same time, the diagnosis is derived from the characteristic clinical signs and symptoms and elevated sweat chloride values analysis.

CF patients contain increased calcium levels [ 61 – 63 ]. Elevated levels of calcium and proteins in submandibular saliva resulted in a calcium-protein aggregation which caused turbidity of saliva [ 64 ]. The elevated calcium and phosphate levels in the saliva of children diagnosed with CF may explain why these children demonstrate a higher occurrence or formation of calculus than healthy controls [ 65 ]. The effect of alteration in the salivary compositions is also seen in the lipid profile of cystic fibrotic patients, which is markedly changed compared to healthy subjects [ 66 ]. The submandibular gland saliva of cystic fibrosis patients contains 66% more lipid per 100 ml saliva than that of a healthy subject. The salivary fatty acid profile can be a good indicator of the early detection of tumorigenesis processes and cardiovascular diseases, which are influenced by dietary intake [ 67 ]. Table ​ Table9 9 shows the summary of salivary biomarkers found for cystic fibrosis. Saliva-based CF disease diagnosis might take a long way to reach the bedside from the bench.

Infectious Diseases

Human Immunodeficiency Virus (HIV) causes AIDS and weakens the body's ability to fight infection. This virus can be transmitted through contact with infected blood, semen, and vaginal fluids. Today, strict antiretroviral therapy can slow down the disease progression and complications. Both HIV and anti-HIV antibodies can be detected in saliva [ 68 ], which provides an alternative method to detect HIV antibodies apart from blood. In 1980, oral fluid was collected with the particular collecting device "OraSure" for the saliva HIV antibody test [ 69 ]. OraSure is commercially available in the United States and can be used to diagnose HIV. Additionally, rapidly screening HIV-1 and HIV-2 via saliva-based enzyme-linked immunosorbent assay (ELISA) in 20 min also eliminates the necessity for blood tests [ 70 ]. Since it is widely accessible after the approval of the FDA, the over-the-counterpoint of care ELISA kit makes HIV tests not only easy but also private [ 71 ]. Currently, 25% of HIV-positive individuals are unaware of their infection and responsible for most new cases annually. The point-of-care testing kit provided a means to assess their HIV status and possibly reduce HIV infections. Furthermore, it may enhance long-term survival rates by facilitating retroviral therapy's early initiation. Secretory Leukocyte Protease Inhibitor enzyme (SLPI) present in saliva shows antiretroviral therapy and prevents HIV-1 infection for 3 weeks after infection; however, human plasma and synovial fluid cannot inhibit HIV-1 infectivity [ 64 ].

Diagnosis of HIV with saliva is safe over blood, as saliva collection is painless, non-invasive with minimal or no risk of infection, inexpensive, simple, and rapid. Furthermore, viral transmission via saliva is unlikely as the infectious virus is rarely isolated from saliva [ 72 ]. Saliva collection also simplifies the diagnostic process in special populations for whom blood drawing is challenging. This population can be individuals with compromised venous access (e.g., injecting drug users), patients with hemophilia, and children. Studies have demonstrated that HIV infection diagnosis based on a specific salivary antibody is equivalent to a serum-based diagnosis. And, therefore, applicable for both clinical use and epidemiological surveillance [ 73 ]. In conclusion, the collection and analysis of saliva offer a simple, safe, well-tolerated, and accurate method for diagnosing HIV infection.

Additionally, saliva-based diagnoses are not only limited to HIV infection. It also plays a significant role in diagnosing infectious diseases such as Malaria, dengue, Ebola, Mycobacterium tuberculosis, and Herpes Simplex virus. The malaria level of IgG antibodies Plasmodium falciparum antigen is present in saliva and strongly correlates with the plasma level [ 74 ]. Using saliva as a medium for point-of-care screening will improve early disease state management by identifying the source of infection at an early stage.

Relationship Between Peridontitis and Systemic Diseases

A positive correlation is found between alpha-2 macroglobulin and HbA1c, demonstrating that alpha-2-macroglobulin in saliva could reflect the glycemic control in patients with Type-2 diabetes mellitus [ 64 ], whereas the concentration of salivary melatonin decreases in Type-2 diabetes and periodontitis patients. This indicates that salivary melatonin is essential in the pathogenesis of diabetes and periodontal diseases and can be used as a biomarker in diagnosing and treating these two diseases [ 65 ].

Periodontal therapy can collaborate with systemic rheumatoid therapy to improve rheumatoid arthritis conditions [ 74 ]. After periodontal therapy in rheumatoid arthritis patients, Disease activity score 28 (DAS28) decreases significantly, showing that periodontal therapy can be used in association with RA systemic therapy. Structural damage resulting from chronic inflammation is the primary cause of loss of function and pain seen in the progression of rheumatoid arthritis and periodontal diseases. Also, the porphyromonas gingivalis periodontal pathogen is associated with the production of Anti-citrullinated proteins antibodies (ACPA) in Rheumatoid arthritis patients (Fig.  6 ) [ 75 ]. However, further studies should be established to verify this link between rheumatoid arthritis and periodontal diseases [ 75 ]. Several studies reported severe periodontal symptoms in rheumatoid arthritis patients. Therefore, paying attention to the oral cavity of rheumatoid arthritis patients and referring them for regular dental checkups might positively impact the management and treatment of rheumatoid arthritis.

Common risk factors and pathogen in the pathogenesis of rheumatoid arthritis and periodontitis

Advantages of Oral Biosensors

Oral biosensor research reported so far confirms its feasibility to assess health and reports disease states as viable numbers or signals based on biomarkers present in the specimen used, such as the whole saliva. An essential aspect of this approach is its non-invasive needleless nature, easy collection, and availability.

A biosensor capable of detecting oral cancer from saliva samples facilitates one of the historical goals of cancer research. With the help of salivary biomarkers, a non-invasive oral cancer diagnostic strategy is established, with minimum expense, ease to use, and a home-based routine testing possibility [ 76 , 77 ]. Existing biosensor studies are grouped under tables representing their general (Table ​ (Table3) 3 ) and clinical (Table ​ (Table4) 4 ) perspectives.

Current Status and Future Direction

The biosensor as a diagnostic tool has been used for decades to diagnose, treat, and prevent countless diseases. When observing the usage of biosensors during a pandemic, their meaning takes on a new level. After the COVID-19 pandemic began in late 2019, salivary biosensors have become the primary tool to detect the virus and begin the process of spread prevention and treatment [ 78 ].

Comparing these tests shows that these biosensors can efficiently analyze a common denominator, saliva. Saliva is being used as an easy communication path between both clinics and marketing companies to provide a wide range of services. Due to its easy accessibility and inexpensive extraction, it is increasingly becoming a popular medium for scientists to use for viruses, ancestry, and other disease biomarkers that indicate severe or fatal diseases.

In an experiment with the saliva and serum sample of 250 individuals with a prior history of cardiovascular diseases, salivary levels of CRP, prostaglandin E2 (PGE2), leukotriene B4 (LTB4), matrix metalloproteinase 9 (MMP9), creatinine, and lysozyme were measured. A significant correlation identified between salivary and serum CRP levels among patients with ischemic heart disease (IHD) confirms that saliva can be used as an alternative means for the evaluation of cardiovascular risk [ 79 ]

Saliva contains several biomarkers that play an important role in determining systemic diseases. Salivary biomarkers such as C-reactive protein, Myeloperoxidase, MMP-9, salivary glucose, IL-1, salivary proteins, TNF-alpha, can be used to diagnose various systemic diseases; however, further studies are required to confirm the significance of these biomarkers. A panel of biomarkers can be used to screen and assess systemic disease risk. As our knowledge of salivary biomarkers expands, the potential applications, interconnection, and common biomarkers for oral and systemic disease diagnosis will also grow. Table ​ Table10 10 summarizes various salivary biosensors used for various systemic diseases. In the future, there are rich possibilities that salivary diagnostics can be used as an effective tool for saving lives and preserving those already saved.

Summary of various salivary biosensors for systemic disease detection

Saliva-based diagnostics seems to be an important tool for regularly screening larger populations. However, further technology development and identification of robust and discriminatory sets of salivary biomarkers are required to apply saliva as a diagnostic tool in day-to-day practice. Saliva is non-invasive, easy to handle, and with the possibility of self-collection fluid—these characteristics are critical in a pandemic scenario, enabling less exposure to healthcare professionals.

Conclusions

This review paper highlights the need for saliva-based biosensors that can benefit patients and healthcare providers. It also reveals the importance of developing a system that can function based on salivary biomarkers for each systemic disease detection. From a healthcare professional's perspective, using a biosensor will allow faster results that do not always require a medical appointment. The data transferred from patient to doctor can be discussed and sent to multiple healthcare professionals, allowing for various opinions on the data analyzed by that biosensor. They would also allow cost-effective strategies to track patients and their disease progression and real-time monitoring. The development of whole saliva-based biosensors will be challenging due to the variation in the dietary habits of individuals. However, it will provide an efficient resource that can lower the risks of the progression of oral diseases and early prediction of other systemic diseases. Advances in machine learning and ultra-sensitive detector modalities will overcome big data issues and lower concentrations. AI and machine learning can help find relationships, nullifying variabilities like age, race, and food habits [ 80 ]. This knowledge will contribute to a better understanding and correlation between systemic and oral health. The main findings of this review are:

• Saliva can be an alternative biological diagnostic fluid.
• Non-invasive saliva collection facilitates a home-based diagnosis approach; however, more studies should be in place to incorporate saliva-based diagnostics into daily use.
• While several questions remain open, the potential advantages of salivary analysis for diagnosing systemic disease suggest that further studies are warranted.
• Saliva-based diagnosis is gaining attention after the covid pandemic, with oral health as an indicator of overall health, and dentists will have greater involvement in identifying non-oral or systemic diseases apart from their routine responsibilities.

Acknowledgements

The authors would like to acknowledge the financial support of NIH Funding 1 R01 DE031832-01, and Blazer foundation, Rockford, IL, USA.

Author Contributions

SS and MS-literature review, RAR-Manuscript editing. SG-Organize the tables and editing, HG- Editing, RW-Editing and review, RPP-Editing and supervising, MM-Editing supervising.

Data Availability

Declarations.

There is no competing interest between authors on this submitted work.

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