Updated on April 24, 2025

Article Summary:

• Glutathione limits oxidative stress, an underlying cause of decline in cognitive function.*
• Various studies highlight the role of glutathione in maintaining normal cognitive function and promoting neurological health.*
• Glutathione’s low absorption and bioavailability hinder its efficacy as a nutritional supplement. 
• Tesseract’s proprietary nutrient delivery nanotechnology enables optimal solubility of the ‘master antioxidant’ to help achieve its health-promoting benefits.  

Oxidative stress is an underlying cause of age-related cognitive function decline. It slowly builds up as a result of the aging process, exposure to chemical stressors, parasympathetic nervous system activation, and unrepaired stress damage. Antioxidants that help the brain cope with oxidative stress, such as glutathione, are, therefore, excellent candidates for helping to maintain cognitive function.*  

Because the level of glutathione depletes with aging, cognitive functions can be adversely impacted. Glutathione is involved in various metabolic processes, including regulating cellular division and differentiation, detoxification, immune cell function, and scavenging circulating reactive oxygen species (ROS).* Glutathione directly interferes with the oxidation of cellular proteins and limits oxidative stress.* Owing to the close relationship between cognitive function and oxidative stress, glutathione is a well-indicated candidate for helping to maintain cognitive function during aging.*   

This article explains the benefits of glutathione for brain health and how Tesseract’s glutathione formulation enables optimal absorption and bioavailability of the body’s ‘master antioxidant’.  

Exploring Glutathione for Brain Health

Extensive research has studied the role of glutathione in brain health. The following table highlights studies that have established the beneficial correlation between glutathione and neurological health.*

Glutathione for Brain Health*
Lower glutathione level and mild cognitive impairment: In a study assaying glutathione concentrations in the blood of individuals with mild cognitive impairment, all 25 participants with mild cognitive impairment had markedly lower glutathione levels than the study’s 53 control participants.1
Location and oxidation state of glutathione and mild cognitive impairment: A study found that increased ratios of oxidized glutathione to its unoxidized state in the anterior and cingulate cortices of the brain were associated with symptoms of mild losses of cognitive function.* Participants in the study who were diagnosed with mild cognitive impairment had 2.2 to 2.9 times as much oxidized glutathione in their brain as the healthy controls.2 A high concentration of oxidized glutathione in the brain can mean there is insufficient glutathione to remove the ROS that are circulating, indicating significant levels of cellular stress.
Glutathione supplementation to maintain normal cognitive function: Researchers studied whether glutathione infusion could rescue cells that had been artificially stressed by ROS and various other toxins in vitro. When glutathione molecules were infused into neurons exhibiting high levels of neuronal stress, their concentration of signaling molecules associated with cellular stress was reduced by 50 percent.3 This finding suggests that glutathione supplementation could be a viable option for helping to maintain normal cognitive function.*

Although glutathione supplementation presents a potentially promising method of maintaining healthy cognitive function, the compound is aggressively and rapidly metabolized by the liver, and dietary glutathione rarely makes it into the bloodstream to capture ROS. Highly bioavailable glutathione supplements contained in sophisticated delivery systems can traffic the molecule through the first pass of metabolism to increase its bioavailability.  

The Potential of Glutathione Supplementation

The most modern nutrient delivery systems incorporate nanotechnology that encapsulates glutathione in a sphere of fat molecules. After surviving first-pass metabolism, the glutathione supplement needs to find a way to cross the blood-brain barrier so it can scavenge ROS and benefit cognitive function.*

With the right glutathione supplement, the brain’s concentrations of glutathione can be sufficient to help maintain healthy cognitive function.* SafeCell®, developed by Tesseract Medical Research, is an innovative glutathione supplement that solves glutathione’s bioavailability and absorption challenges. 

SafeCell’s acetylated glutathione formula utilizes Tesseract’s proprietary CyLoc® – DexKey® nutrient delivery technology to achieve the benefits of glutathione for brain health.* The CyLoc® technology encases glutathione molecules for safe passage through the stomach, and the accompanying Dextrin® reactors release the active glutathione molecules at the desired point in the gastrointestinal tract to achieve their optimal absorption. 

References: 

¹Rinaldi P, et al. Neurobiology of Aging vol. 24,7 (2003):91591-9. doi:10.1016/s0197-4580(03)00031-9

²Duffy SL, et al. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association vol. 10,1 (2014):67-75. doi:10.1016/j.jalz.2013.01.005

³Lee M, et al. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology vol. 24,7 (2010):2533-2545. doi:10.1096/fj.09-149997

The cardiovascular system comprises the heart, arteries, veins, and capillaries and provides blood supply throughout the body. The parasympathetic and sympathetic nervous systems help the circulatory system respond to various stimuli to control the amount and velocity of blood carried through the vessels. 

Various factors, such as genetic conditions, infections, lifestyle, and aging, can impact the optimal functioning of the circulatory system. Circulatory dysfunction adversely affects the heart and blood vessels, restricts blood flow throughout the body, and can be the underlying cause of several cardiovascular conditions. 

In this post, we discuss the circulatory system, factors that affect its functions, how certain nutrients can support it, and why you should include the best circulation supplements in your diet to promote heart health. Use the links below to jump ahead to different topics on the page.

Circulatory System: An Overview	Risk Factors Affecting Circulatory Functions
Best Circulation Support Supplements: How They Promote Cardiovascular Health	Including an Advanced Circulation Supplement in Your Diet
FAQs: Frequently Asked Questions About Circulation Support Supplements

Cardiovascular System: An Overview

The cardiovascular system is categorized into two loops: 

• Systemic circulation: It allows oxygenated blood and nutrients to reach the rest of the body. 
• Pulmonary circulation: It allows the oxygenation of the blood. 

Let’s understand how the various components of the cardiovascular system work. 

• Heart: It pumps blood through the vessels directly into the arteries, particularly the aorta or the pulmonary artery. 

• Blood vessels: These include the arteries, veins, and capillaries. 

• Arteries: They carry blood away from the heart and are divided into large and small arteries. Large arteries receive the highest blood flow pressure and are, hence, thicker and more elastic. 

Smaller arteries, such as arterioles, have more smooth muscles for contraction and relaxation to regulate blood flow to different body parts. Arterioles face relatively smaller blood pressure and account for most of the resistance in the pulmonary circulation.  

• Veins: Veins transport blood back to the heart and contain valves to prevent the backflow of blood. 

• Capillaries: Capillaries branch off of arterioles and are a single-cell layer that exchanges nutrients, gases, and wastes with tissues and organs. 

Further, micro-circulation consists of a network of small blood vessels—arteries, arterioles, capillaries, venules, and veins. The micro-circulatory network, along with the interstitium and lymphatic vessels, helps maintain the homeostasis of tissues and the entire circulatory system. 

Risk Factors Affecting Cardiovascular Functions

Several risk factors can affect the optimal functioning of the cardiovascular system and accordingly increase the risks of adverse cardiovascular conditions. The following table highlights various risk factors that can compromise the cardiovascular system.

Risk Factors Affecting Cardiovascular Functions
Health conditions: Health conditions, such as high blood pressure and unhealthy cholesterol levels, pose risks to the circulatory system.  High blood pressure refers to the elevated pressure of the blood in arteries and other blood vessels. If not controlled, then it can damage the vital organs, including the heart, kidneys, and brain. Unhealthy blood cholesterol levels can cause narrowing of the arteries and decrease blood flow to other parts of the body. Various metabolic conditions, such as high blood glucose levels and unhealthy weight management, can also adversely affect the circulatory system.
Lifestyle: Eating a diet high in saturated fats, trans fats, cholesterol, and salt is linked to adverse heart conditions. Increased intake of alcohol and tobacco use raises blood pressure levels and has negative impacts on circulatory functions.  A sedentary lifestyle increases the chances of high blood pressure, high cholesterol levels, and high blood glucose levels, which, in turn, adversely affect cardiovascular functions.
Other factors: Factors such as genetics and family history, race and ethnicity, age, and gender also play a role in conditions that can adversely affect the circulatory system. When combined with unhealthy lifestyle choices, these factors elevate the risks of unhealthy cardiovascular conditions.

Best Circulation Support Supplements: How They Promote Cardiovascular Health

Your dietary choices significantly impact your cardiovascular system. Food sources that are high in sodium, sugar, unhealthy fats, and low in fiber can compromise venous function.¹ A balanced diet for circulatory health should consist of fruits and vegetables, fiber-rich foods, and foods that contain omega-3 fatty acids and vitamin E. Adequate hydration is also critical to maintaining cardiovascular health. 

A research study has highlighted that nutritional supplements, such as folate, omega-3 fatty acids, vitamin D, and calcium, are beneficial for achieving positive cardiovascular outcomes.² Furthermore, regular intake of probiotics enhances cardiovascular health by minimizing oxidative stress. 

The following table highlights several key nutrients that support circulation, the food sources that are rich in those nutrients, and their benefits. 

Best Circulation Support Supplements, Their Food Sources, and Benefits
The B Vitamin Family (B1, B6, B12, and Folic Acid)	B vitamins are water-soluble vitamins found in various foods, including fortified cereals, whole grains, lentils, bananas, liver, shellfish, and eggs. Vitamin B1 promotes better blood circulation through endothelium-dependent vasodilation — the widening of arteries and veins. Vitamins B6 and B12 minimize instances of blood clot formation in veins. Folic acid enhances endothelium-dependent vasodilation in the peripheral circulation.
Vitamin C	Citrus fruits, bell peppers, cherries, tomatoes, cruciferous vegetables, and white potatoes are rich sources of vitamin C. Vitamin C is an antioxidant that protects vascular vessels from the harmful effects of oxidative stress.
Vitamin E	Vitamin E, a fat-soluble vitamin, is contained in various fruits, vegetables, nuts, seeds, and cooking oils, including wheat germ oil, sunflower seeds, soybean oil, pumpkin, red bell peppers, spinach, and avocado. Vitamin E helps modulate multiple molecular mechanisms, limiting blood clot formation within veins and arteries and maintaining a natural inflammatory response in blood vessels.
Citrulline	Citrulline is an amino acid found in pumpkin, squash, cucumber, melons, and watermelon. Citrulline enhances L-arginine and nitric oxide (NO) levels, which increases blood flow and induces vasodilation.
Coenzyme Q10	CoQ10 is a fat-soluble compound synthesized in animal tissues. Food sources rich in CoQ10 include oily fish, organ meats, and whole grains. CoQ10 acts as an antioxidant to resist aging and the dysfunction caused by oxidative stress in vascular endothelial cells. CoQ10 supplementation helps alleviate various adverse health conditions associated with blood vessel dysfunction or insufficiencies.
Lipoic Acid	Vegetables like broccoli, spinach, Brussels sprouts, tomatoes, red meat, and organ meats are rich in the naturally occurring compound lipoic acid. Lipoic acid enhances endothelial function by increasing the bioavailability of endothelium-derived NO and functioning as an antioxidant by limiting oxidative stress and adverse inflammatory reactions.
Nattokinase	Is an enzyme released by bacteria during the fermentation of soybeans. The traditional Japanese meal of fermented soybeans is the richest source of nattokinase. Nattokinase supplementation helps limit hardening and narrowing of arteries, restricts the formation of blood clots, and lowers blood pressure.

Although these nutrients can be obtained in the diet, nutritional supplements are also a suitable alternative for obtaining them to further support a healthy cardiovascular system.* 

Including An Advanced Circulation Support Supplement in Your Diet

NOX Flo SR^TM is an advanced cardiovascular health supplement developed by Tesseract Medical Research. It contains clinically validated rutinosides, Hesperidin 2S, and Diosmin citrus flavonoids, along with citrulline, Coenzyme Q10, and R-lipoic acid, for enhancing NO synthesis and NO-dependent endothelial function and vasodilation.* 

NattoGuard is an innovative circulation support supplement that contains nattokinase and two plant terpenes: borneol and trans-cinnamaldehyde. The hypoallergenic formulation has cardioprotective properties that optimize the functioning of the circulatory system.*   

The potent blend of nutrients in each of the above supplement formulations is powered by Tesseract’s proprietary CyLoc® —DexKey® nutrient delivery nanotechnology, which ensures optimal nutrient bioavailability and absorption. 

These groundbreaking circulation support supplements display unprecedented absorption of their active nutrients, which provides nutritional support to individuals experiencing compromised endothelial function and vascular insufficiencies.*

Frequently Asked Questions About Circulation Support Supplements

Here are some frequently asked questions (FAQs) about circulation support supplements. 

Can I take a circulation support supplement with prescribed medicines?

Although the health-promoting benefits of circulation support supplements are well-established, there is a potential for additive effects and a limited understanding of potential contraindications and side effects associated with taking them with prescription medications. Consult your healthcare provider before including a circulation support supplement in your diet or taking one with prescription medications. 

What should I look for when considering the best circulation support supplements?

The efficacy of a nutritional supplement depends on the active nutrients in the formulation and their having optimal absorption and bioavailability. When considering the best circulation support supplement, you should look for the desired ingredient as the active nutrient in the formulation and an advanced nutrient delivery technology that ensures the optimal absorption and bioavailability of the active ingredient.  

Citations: 

¹He J, Ma F, Yao J, et al. Ann Vasc Surg 2023;88:257-267. doi:10.1016/j.avsg.2022.06.015

²Khan SU, et al. Annals of Internal Medicine vol. 171,3 (2019):190-198. doi:10.7326/M19-0341

³Arora S, et al. Annals of Vascular Surgery vol. 20,5 (2006):653-658. doi:10.1007/s10016-006-9055-6

⁴Ren J, et al. Ecotoxicology and Environmental Safety vol. 241 (2022):113735. doi:10.1016/j.ecoenv.2022.113735

⁵Garg A, Lee JC-Y. Life (Basel, Switzerland) vol. 12,2 310. 18 Feb. 2022, doi:10.3390/life12020310

⁶Miyatake S, et al. Biochemistry and Biophysics Reports vol. 28 101149. 8 Oct. 2021, doi:10.1016/j.bbrep.2021.101149

⁷Zozina VI, et al. Current Cardiology Reviews vol. 14,3 (2018):164-174. doi:10.2174/1573403X14666180416115428

⁸Hajizadeh-Sharafabad F, Zahabi ES. Critical Reviews in Food Science and Nutrition vol. 62,11 (2022):2928-2941. doi:10.1080/10408398.2020.1861425

⁹Chen H, et al. Biomarker Insights vol. 13 1177271918785130. 5 Jul. 2018, doi:10.1177/1177271918785130

Updated April 15, 2025

Your skin is the largest organ in your body and needs high-quality nutritional support for optimal functioning and health. Quercetin, a natural antioxidant, protects skin health from damage caused by pollution, UV radiation, and other environmental stressors.* 

Get the answers to common queries about quercetin’s skin benefits, its potential health-promoting applications, its bioavailability and absorption challenges, and the best way to include quercetin in your diet. Use the links below to jump ahead to different topics on the page.

What Is Quercetin and Where Is It Found?	Potential Applications of Quercetin
What are Quercetin’s Skin Benefits?	Does Oral Ingestion of Quercetin Help?
Factors Affecting Quercetin’s Absorption in the body	Strategies To Enhance Quercetin’s Absorption
The Most Bioavailable Form of Quercetin	Why You Need a Quercetin Supplement
Different Types of Quercetin Formulations	FAQs: Frequently Asked Questions about Quercetin Supplements

What Is Quercetin and Where Is It Found?

Quercetin is a naturally occurring phytochemical, or flavonoid compound, found in fruits and vegetables. Quercetin and its derivatives have potent antioxidant properties that help regulate the body’s natural inflammatory response, translating to powerful positive bioactive effects on cell cycle progression and cellular signaling pathways.* 

Quercetin, mainly as Quercetin-3-O-glycoside, primarily serves as a natural pigment in fruits, vegetables, and flowers. Key dietary sources of quercetin include: 

• Apples
• Grapes
• Berries
• Cherries
• Citrus fruits
• Cruciferous vegetables
• Onions
• Kale
• Buckwheat
• Tomatoes
• Red wine
• Black tea

Quercetin concentrations can vary from one plant to another and even vary in different parts of the same plant. Onions, tea, and apples contain a significantly higher amount of quercetin.

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Potential Applications of Quercetin

Flavonoids like quercetin are more powerful antioxidants than vitamins C and E. As a potent antioxidant that supports the body’s natural inflammatory responses, quercetin extends beneficial effects by inhibiting kinases, oxidative damage, and cell cycle growth, and supporting neuronal survival.* The following table lists potential applications for quercetin:

System	Application
Cardiovascular Health*	Quercetin for Heart Health Support Quercetin vs CoQ10: Which to Choose
Kidney Health*	Quercetin for Kidney Health Support: Benefits
Immune Function*	Exploring Alternative Allergy Therapy: The Potential Benefits of Quercetin Quercetin’s Immune Support Properties
Gastrointestinal Health*	Does Quercetin Help Leaky Gut? Understanding The Science Behind An Innovative Treatment
Brain Health*	Research Supports Using A Quercetin Supplement to Benefit Alzheimer’s Disease Symptoms Does Quercetin Affect Sleep: FAQs Nutritional Support Supplements for Parkinson’s Disease: Considering Quercetin

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What are Quercetin’s Skin Health Benefits?

Evidence suggests that the oxidative stress caused by reactive oxygen and nitrogen species plays a critical role in the development of various adverse skin disorders.¹ The molecular characteristics of quercetin make it a potent scavenger of these reactive oxygen species (ROS) and reactive nitrogen species (RNS).* Quercetin’s ability to quench free radicals and support the skin’s cutaneous antioxidant defense system makes quercetin a preferred choice for extensive skin care applications.*

Quercetin helps maintain the body’s normal natural inflammatory responses by:  

• Inhibiting the release of histamine.* Histamine is a critical compound for immune responses and is released by basophils and mast cells, that can lead to the skin feel itchy and appear red, swollen, and patchy.² 
• Inhibiting the release of the proinflammatory cytokines and interleukin-4 (IL-4) and IL-13.* These signaling molecules are secreted by immune cells and trigger inflammatory responses.

The potential benefits quercetin offers for skin health can be condensed into two main functions: protection and restoration.*

Quercetin’s Skin Benefits*
Protection*	Restoration*
Quercetin enhances protection against skin damage caused by factors like UV radiation, toxic chemical contact, and histamines.*	Quercetin helps restore the skin’s barrier by supporting hydration and limiting transepidermal water loss* — the less water the skin passively evaporates, the higher the skin’s integrity levels.
Studies show that quercetin enhances protection against UV-mediated skin damage by directly inhibiting activities of protein kinase C delta (PKCδ) and Janus kinase 2 (JAK2), two key components of intracellular cell signaling pathways.*3	Lipids in the outermost epidermal layer are vital to maintaining the skin’s permeability barrier. When they are peroxidated, these lipids produce toxic effects in skin cells. Studies suggest quercetin’s role in reducing lipid peroxidation helps restore barrier functions to damaged skin.*4

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Does Oral Ingestion of Quercetin Help?

Although quercetin can be obtained in the diet from various fruits and vegetables, it has poor natural absorption in the body. 

Studies show that only one percent of quercetin is absorbed naturally when it is ingested orally.5

Quercetin’s low natural absorption, extensive metabolism, and rapid elimination from the body contribute to its low bioavailability in nutritional supplements.

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Factors Affecting Quercetin’s Absorption in the Body

Quercetin is primarily absorbed in the upper segment of the small intestine. Post-absorption, quercetin is metabolized in various organs, including the liver, small intestine, colon, and kidney, with the aid of biotransformation enzymes specific to the liver and small intestine. Finally, the kidney excretes quercetin and its metabolites in the urine.

Key factors affecting quercetin’s absorption in the body are:

• Poor aqueous solubility
• Instability in the physiological medium (stomach and intestine)
• Poor permeability
• Short biological half-life (resulting in rapid degradation)
• Extensive first-pass metabolism in the liver (resulting in extensive biotransformation)

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Strategies to Enhance Quercetin’s Absorption

Conventional approaches used to enhance quercetin’s absorption include consuming the better-absorbed glycosylated form of quercetin, consuming sources with higher quercetin content, and consuming quercetin with dietary components.   

• Differences in Glycosylation. The glycosyl group’s presence in quercetin’s molecular structure enhances its water solubility and increases the absorption of quercetin glycosides. For example, the body absorbs quercetin glucosides found in onions or shallots more readily than its rutinosides — the major quercetin glycoside in tea. 

• Food Matrix of Quercetin Consumption. Certain foods, like onions, asparagus, and berries, have relatively higher natural concentrations of quercetin than other sources.  

• Co-Administration of Dietary Components. The intake of quercetin with dietary fat can increase its absorption, likely by micellarization in the small intestine.⁶

The ideal strategy for enhancing quercetin’s bioavailability is to protect its integrity in the upper gastrointestinal tract and release it in the colon with prolonged sustained release.

Novel Formulations

Alternative delivery systems, including nanoformulations, help overcome bioavailability-related issues in quercetin supplements. Nutritional supplements formulated at the nanoparticle level achieve a larger surface area compared to their typical raw material counterparts.  They can be customized for targeted delivery of quercetin molecules while protecting their integrity against metabolizing enzymes and other physiological conditions. Nanoparticles also enable a controlled release of quercetin molecules at the desired point in the intestinal tract.  

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The Most Bioavailable Form of Quercetin

The solubility of different forms of quercetin varies. Quercetin aglycones or glycosides in apples, tea, and red wine have lower solubility compared to quercetin glucosides from onions, which appear to have the highest absorption rate.

Quercetin glucoside — the naturally occurring form of quercetin — displays an estimated absorption rate of 3%-17% per 100 mg of ingested quercetin.7

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Why You Need A Quercetin Supplement

Because of its low water solubility, unformulated quercetin ranks low in terms of health-promoting benefits. Although dietary sources support the body with lower concentrations of quercetin, consuming a higher concentration can require taking quercetin in nutritional supplement form. Strategies like structural transformation, absorption enhancers, carrier complexes, and nanotechnology help develop highly bioavailable quercetin supplement formulations for benefits including:

• Better absorption 
• Minimized frequency and amount of quercetin intake

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Different Types of Quercetin Formulations

Various formulations of quercetin offer multiple delivery modes, including:

• Oral ingestion: Common types of oral nutritional supplements include tablet, capsule, and powder forms. 

• Topical application: Liposomal formulations with lipid-based nanoparticles that encapsulate quercetin molecules enhance the topical delivery of quercetin in the form of ointments, gels, and sprays.  

• Intravenous injection: Injectable formulations of water-soluble quercetin are used to address a wide range of pathological conditions. 

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FAQs: Frequently Asked Questions about Quercetin Supplements

Are there side effects to taking a quercetin supplement?

Quercetin intake as a nutritional supplement at one gram daily³ is considered safe; adverse side effects from quercetin supplementation have rarely been reported. However, the clinical results of long-term quercetin use at levels at or above one gram daily for longer than 12 weeks are yet to be determined.

Can I take a quercetin supplement with a prescription medicine?

It is always recommended to consult a healthcare provider before including a quercetin nutritional supplement in your diet or taking one with a prescription medicine.  

How do I determine the efficacy of a quercetin supplement formulation?

The desired efficacy of a quercetin supplement formulation lies in enhanced bioavailability and absorption of the active nutrient molecules. Tesseract Medical Research’s QuerciSorb Immuphore SR^®, an innovative quercetin supplement complex, contains four ingredients — quercetin, zinc, vitamin C, and vitamin D — to support the immune system’s optimal functioning, which includes healthy skin.*

Tesseract’s proprietary CyLoc^® – DexKey^® technology is a revolutionary nanomolecular nutrient delivery system that enhances the absorption of quercetin molecules by releasing them at the desired point in the intestinal tract. The unprecedented levels of absorption and bioavailability in each quercetin molecule enable micro-dosing of this formulation to achieve quercetin’s skin benefits.*

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References:

¹Byamba D, et al. Annals of Dermatology vol. 22,3 (2010):269-278. doi:10.5021/ad.2010.22.3.269

²Weng Z, et al. PloS One vol. 7,3 (2012):e33805. doi:10.1371/journal.pone.0033805

³Shin EJ, et al. International Journal of Molecular Sciences vol. 20,21 5262. 23 Oct. 2019, doi:10.3390/ijms20215262

⁴Maramaldi, et al. Clinical, Cosmetic and Investigational Dermatology vol. 9 55-62. 26 Feb. 2016, doi:10.2147/CCID.S98890

⁵Gugler R, et al. European Journal of Clinical Pharmacology vol. 9,2-3 (1975):229-234. doi:10.1007/BF00614022

⁶Guo Y, et al. Molecular Nutrition & Food Research vol. 57,5 (2013):896-905. doi:10.1002/mnfr.201200619

⁷Li Y, et al. Nutrients vol. 8,3 167. 15 Mar. 2016, doi:10.3390/nu8030167

Updated April 10, 2025

Hangovers are an all-too-common consequence of both social drinking and binge drinking, and no definitive remedy exists to cure them. Do hangover pills work? Although several products claim to cure hangovers, there is no substantial evidence for their efficacy. 

Glutathione is a ‘master antioxidant’ that strengthens immune function, helps maintain a normal inflammatory response, and enables the body to compensate for cellular stress.* Glutathione also plays a key role in detoxification processes in the liver,  the organ that works overtime during a hangover. Glutathione’s pharmacological properties make it a potent supplement to address a hangover. 

This post discusses the anatomy of a hangover, how glutathione can address a hangover, and why you should include an advanced glutathione supplement in your diet if you do drink. Use the links below to jump ahead to different topics on the page. 

The Anatomy of A Hangover	Do Hangover Pills Work?
Addressing Hangovers by Targeting Oxidative Stress	How does Glutathione Address Hangover?
Frequently Asked Questions About Glutathione Supplements

The Anatomy of a Hangover

Let’s understand the physiological basis of a hangover. Although a hangover is commonly thought of as simply the body’s reaction to excessive alcohol consumption, the medical basis of a hangover is more nuanced because of the multiple ways in which drinking alcohol affects the body. 

The symptoms of hangovers are diverse and can include:

• Low mood
• Thirst
• Fatigue
• Muscle cramping
• Generalized pain
• Headache
• Nausea
• Anxiety
• Diarrhea
• Inflammation

The spectrum of hangover symptoms spans different organ systems. Hangovers have at least four separate pathologies:

• Disruption of sleep
• A buildup of toxic metabolic byproducts, such as acetaldehyde
• Dehydration
• Immune function activation and suppression

A review of hangover research concluded that alcohol’s effect on immune function is the largest contributor to hangover severity and incidence.¹ However, that doesn’t mean treating immune function alone is sufficient to minimize a hangover; each pathology produces a different subset of hangover symptoms, and there is no simple way to address all of them at once. 

Do Hangover Pills Work?

Do hangover pills work? There is no definite answer. The best way to prevent a hangover is to consume alcohol in moderation and ensure adequate hydration when drinking. As people age, their ability to process alcohol decreases, leading to an uptick in unexpected hangovers and individuals seeking hangover remedies, including hangover pills. The following table highlights various hangover remedies. 

Common Remedies for Hangover
Traditional remedies. Conventional home remedies, such as vinegar, fenugreek, thyme, ginger, pear cactus, red ginseng, and asparagus, are often used to alleviate hangover symptoms.
Over-the-counter medications.  Non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics (pain relievers) are preferred to address headaches associated with hangovers. However, formulations containing acetaminophen should be avoided because when it is consumed contemporaneously with alcohol it is toxic to the liver.
Nutrient supplementation and electrolyte mixtures. These products are designed to replenish the vitamins, minerals, and electrolytes lost during metabolic alcohol clearance. Such products aim to reduce the impact of dehydration while providing the body with precursor chemicals needed to continue clearing toxic byproducts.

Addressing Hangovers by Targeting Oxidative Stress

The most promising hangover therapies seek to augment the body’s ability to compensate for cellular stress. Rather than simply providing pain relief or restoring lost nutrients, these therapies improve the ability of the immune system to function in the wake of overindulgence in alcohol. Strengthening the immune system is critical because hangover-associated inflammation is a result of immune dysregulation caused by oxidative stress.Significantly, oxidative stress has recently been implicated as one of the primary mechanisms of the immunologic pathology of hangovers.² In general terms, oxidative stress is a process by which free radicals bond to critical enzymes and cellular molecules, thus preventing them from performing their intended purpose and causing damage. New therapies, such as glutathione supplementation, address hangover pathology by limiting oxidative stress.

How Does Glutathione Address Hangover?

Glutathione is a molecule produced by the body that protects cells from oxidative stress by bonding to free radicals with great efficiency, thus preventing damage to cellular machinery.* 

In a study evaluating the physiopathological state of alcohol hangovers in the brain cortex of animal models, it was found that glutathione-related enzymes were most affected in nerve terminals.³ When mice were artificially induced to have the conditions of a hangover, the researchers found that 17.5 percent more free radicals were present in their blood than in healthy controls, indicating high levels of oxidative stress. In contrast, glutathione concentrations were found to be 43 percent lower than in controls, and the activity of certain critical enzymes was 40 percent lower. 

As oxidative stress increased with the severity of the hangover, the glutathione level of the mice became further depleted. As glutathione levels decreased, the free radicals more easily damaged enzymes, reducing their activity and causing harm to the mice. This harm included a 57-percent increase in the incidence of enzymes responsible for recycling neurotransmitters, suggesting broadly detrimental and wide-ranging mood disturbances. The results of the study imply that a glutathione shortage is a large part of the problem when it comes to the molecular basis of a hangover.

There has also been a randomized double-blind placebo-controlled crossover clinical trial that demonstrated that glutathione supplementation significantly lowered serum acetaldehyde concentrations after alcohol consumption.⁴ Although it did not significantly affect serum alcohol levels, the reduction in acetaldehyde is crucial, as it is a major contributor to hangover symptoms.⁴

The following table highlights several studies exploring the effects of glutathione on alcohol metabolism. 

Glutathione and Alcohol Metabolism
The combination of cysteine and glutathione limits ethanol-induced hangover. In a study evaluating the protective effects of cysteine and glutathione against ethanol-induced hangover and liver damage in mice, it was found that the co-supplementation alleviated the hangover symptoms and limited the alcohol-induced oxidative stress by regulating the Nrf2 signaling pathway.5
Glutathione enhances alcohol metabolism.* Glutathione has been found to address hangover behavior patterns, including locomotor activity.6 Additionally, it increased the activity of alcohol dehydrogenase and aldehyde dehydrogenase to enhance alcohol metabolism.* Glutathione also enhances the expression of antioxidant enzymes to aid the hepatic breakdown of alcohol.*

Research indicates that glutathione could be an effective hangover therapy by: 

• Limiting oxidative stress caused by excessive consumption of alcohol.* A glutathione supplement could improve the body’s ability to cope with oxidative stress at a minimum.* 

• Limiting gastrointestinal distress involved in a hangover.* Limiting the oxidative stress caused by a hangover could also limit inflammation.* This could potentially address some of the gastrointestinal distress associated with hangover, allowing intestinal cells to function optimally, which in turn, could simultaneously enhance mood.* 

A glutathione supplement can act as a safe, effective, and easily accessible alternative to traditional hangover pills. For acute hangovers, glutathione administered intravenously acts faster compared to oral glutathione supplements. 

Recently, glutathione supplements have been formulated using nutrient delivery nanotechnology that addresses the metabolic challenges that impact the efficacy of the ‘master antioxidant’. Such formulations enhance the bioavailability of glutathione to better address hangover symptoms and achieve positive outcomes. 

FAQs: Frequently Asked Questions About Glutathione Supplements

Is it safe to take a glutathione supplement for a prolonged period?

Limited data exist on the safety and efficacy of prolonged glutathione supplementation. Because glutathione supplementation in high doses might cause toxicity, consult a healthcare provider before including a glutathione supplement in your diet for long periods.   

Can I take a glutathione supplement with a prescription medicine?

Limited data exists on the potential contraindications of glutathione with prescription medicines. Consult your healthcare provider before taking a glutathione supplement with a prescription medicine.   

How do you determine the efficacy of a glutathione supplement formulation?

Enhanced bioavailability and absorption of glutathione are critical indicators of a supplement formulation’s efficacy. 

Tesseract Medical Research’s SafeCell® is an innovative, hypoallergenic S-Acetyl-Glutathione complex formulated for optimal bioavailability and absorption. Tesseract’s proprietary CyLoc® – DexKey® nutrient delivery nanotechnology encases each glutathione molecule, protecting it from early degradation during transit through the stomach. The accompanying DexKey® reactors enable targeted delivery of the active ingredient molecules for enhanced absorption. The result is unprecedented absorption of glutathione in lesser amounts than previously required to support liver health.*

Finally, answering the question, do hangover pills work? There is no definite answer. While glutathione is sometimes included in hangover remedies due to its role in supporting liver detoxification, it should not be considered merely a “hangover pill”. Glutatione plays a much broader role as the body’s “master antioxidant” by supporting liver function, cellular health,and overall physiological balance. 

References: 

¹Penning R, et al. The pathology of alcohol hangover. Current Drug Abuse Reviews vol. 3,2 (2010): 68-75. doi:10.2174/1874473711003020068

²van de Loo, AJAE, et al. The inflammatory fesponse to alcohol consumption and its role in the pathology of alcohol hangover.” Journal of Clinical Medicine vol. 9,7 2081. 2 Jul. 2020, doi:10.3390/jcm9072081

³Karadayian AG, et al. Free radical production and antioxidant status in brain cortex non-synaptic mitochondria and synaptosomes at alcohol hangover onset. Free Radical Biology & Medicine vol. 108 (2017):692-703. doi:10.1016/j.freeradbiomed.2017.04.344

⁴Song G, et al. Effects of GSH on Alcohol Metabolism and Hangover Improvement in Humans: A Randomized Double-Blind Placebo-Controlled Crossover Clinical Trial. Nutrients. 2024;16(19):3262. Published 2024 Sep 26. doi:10.3390/nu16193262

⁵Kim H, et al. Combination of cysteine and glutathione prevents ethanol-induced hangover and liver damage by modulation of Nrf2 signaling in HepG2 cells and mice. Antioxidants (Basel, Switzerland) vol. 12,10 1885. 20 Oct. 2023, doi:10.3390/antiox12101885

⁶Lee H-Y, et al. Glutathione’s role in liver metabolism and hangover symptom relief: Dysregulation of protein S-slutathionylation and antioxidant enzymes. Biomolecules & Therapeutics vol. 33,1 (2025):117-128. doi:10.4062/biomolther.2024.182

Article Summary:

• Glutathione is a poorly absorbed molecule, and research is underway to determine the best way to take it as a nutritional supplement. 
• This ‘master antioxidant’ is rapidly degraded naturally in the small intestine, followed by its elimination from the body. 
• Tesseract’s SafeCell® is an innovative S-Acetyl-Glutathione complex that enables unprecedented absorption of glutathione.

Glutathione, referred to as “the master detoxifier”, is an essential antioxidant present in every cell of the body. It plays a critical role in: 

• Scavenging free radicals
• Supporting nutrient metabolism
• Maintaining necessary cellular activities, such as protein synthesis, cell signaling, and immune regulation

However, several factors can lead to reduced levels of glutathione in the body, such as: 

• Advancing age
• Poor lifestyle choices
• Pathologies that can compromise the body’s antioxidant defenses 

Unfortunately, dietary intake of glutathione-rich foods may not be sufficient to maintain optimal levels. For this reason, glutathione supplementation may be necessary to adequately support various health functions in the body.

But can glutathione be effectively taken as a nutritional supplement? Are there potential side effects? What is the recommended daily intake of glutathione? This article answers frequently asked questions about glutathione supplementation.  

What is the Most Effective Way to Take Glutathione?

Glutathione is commercially available in various delivery forms: 

• Oral supplement (Let’s not use these three in this list – we should say “oral sprays, and capsules”)
• Intravenous (IV) drip
• Intranasal drops or spray
• Nebulized glutathione

Each of these delivery forms has its advantages and limitations, but oral supplementation remains a widely used and accessible option for most practitioners and patients. 

The most common forms of oral glutathione supplements are powders, tablets, and capsules. 

Notably, oral glutathione supplements have not been considered the most effective in terms of absorption. Co-supplementation of glutathione with other nutrients can enhance its solubility. For example, one clinical study showed that taking glutathione along with vitamin C can enhance glutathione’s concentration in the blood.*¹

Recent research suggests that oral glutathione formulations in liposomal or sublingual forms might be more bioavailable. 

What is the Recommended Daily Intake of Glutathione?

The recommended daily oral intake of glutathione is 500mg—1,000 mg. In a balanced diet, fruits and vegetables can contribute up to 50 percent of the recommended intake, while meat consumption typically contributes less than 25 percent.

When is it the Best Time to Take Glutathione?

A glutathione supplement is usually best taken before or after breakfast or dinner. Consult with your healthcare provider to determine the right time to take one.  

What are Glutathione’s Absorption Challenges? 

Glutathione is naturally a difficult-to-absorb molecule; therefore, its health-promoting benefits can be significantly limited due to its poor natural bioavailability and absorption. The following are the common absorption challenges of glutathione:

Common Absorption Challenges of Glutathione
Rapid degradation in the intestine: In the small intestine, glutathione is rapidly broken down by the enzyme gamma-glutamyl transpeptidase (GGT), which dilutes glutathione and lowers its level in the blood.
Elimination of circulating glutathione: Glutathione conjugates formed in the liver are excreted intact in bile or converted into water-soluble by-products that are excreted in the urine.

What is the Average Amount of Glutathione Present in a Nutritional Supplement?

Glutathione supplements generally contain between 150 mg and 1,000 mg of glutathione. Consult your healthcare provider to determine the right amount of daily glutathione your body needs to support the targeted health functions.

Are There Side Effects of Glutathione Supplementation?

The safety profile of glutathione supplements is well established, with only minimal side effects reported, such as: 

• Mild stomach upset
• Abdominal cramps
• Bloating

There is limited safety data on prolonged usage of glutathione beyond two months and above 500 mg daily intake. And, if pregnant or breastfeeding, always consult your healthcare provider before including a daily glutathione supplement in your diet.   

Are There Innovative Glutathione Supplement Formulations for Enhanced Bioavailability?

Various innovative approaches have been explored to enhance glutathione’s absorption and bioavailability, including: 

• Using nutrient delivery nanotechnology: Nanostructured nutrient delivery systems enable the encapsulation of glutathione molecules in lipid carriers, thereby enhancing its absorption.

• Formulating supplements with an acetylated form of glutathione: Glutathione supplement formulations that contain the highly stable S-Acetyl-Glutathione are more readily absorbed. 

Tesseract Medical Research’s SafeCell® is an S-Acetyl-Glutathione complex that utilizes Tesseract’s proprietary CyLoc® – DexKey® nutrient delivery technology. This nanomolecular nutrient delivery technology addresses the natural bioavailability challenge of glutathione by enabling the unprecedented absorption of billions of glutathione molecules at the optimal point in the intestinal tract — one molecule at a time. This technology unlocks the significant health-promoting potential of this ‘master antioxidant’ molecule to optimally support your health and wellness goals.* 

Citation
¹Johnston CS, Meyer CG, Srilakshmi JC. Am J Clin Nutr 1993 Jul;58(1):103-105. doi: 10.1093/ajcn/58.1.103. PMID: 8317379.

Updated on April 3, 2025

Social media touts berberine as ‘nature’s Ozempic’ and a quick weight-loss solution but what exactly is it? Berberine is bioactive compound derived from plants, such as barberry, Oregon grape, and golden seal, and has a long history of usage in Ayurvedic and Chinese medicine. Although the health-promoting benefits of berberine are well-established, its role as a weight management aid is still being investigated. 

This post explains the benefits of adding berberine to your weight management program, why you should consider berberine as a supplement to promote endocrine health, and how Tesseract’s proprietary berberine supplement formulation overcomes berberine’s bioavailability challenges. Use the links below to jump ahead to different topics on the page. 

Berberine for Weight Management: Misinformation or Fact?	How Does Berberine Promote Glucose Metabolism?
How Berberine Indirectly Supports Weight Management	Is It Safe to Take Berberine for Weight Management?
An Advanced Berberine Supplement Formulation for Weight Management	Frequently Asked Questions About Berberine Supplements

Berberine for Weight Management: Misinformation or Fact?

Misinformation about berberine has led to its popularity as an alternative to prescription medications for weight management. But this misinformation about berberine poses risks of its overconsumption or contraindications with prescription medications for weight management, which can result in adverse side effects.    

Let’s examine some of the misinformation that surrounds this potent phytochemical. 

Misinformation: Berberine is an appetite suppressant. 

Fact: There is no conclusive evidence that establishes berberine as a appetite suppressant. Berberine is an antioxidant, its primary mechanism of action is to help maintain normal inflammatory responses in cells.* However, because berberine also promotes normal glucose metabolism and lipid metabolism, it can indirectly promote healthy weight management.*    

Misinformation: Berberine is a weight loss agent. 

Fact: Berberine does moderate the intestinal absorption of glucose and limits exercise-induced exhaustion and muscle damage, and these effects translate to healthy weight management. More research is required to explore berberine’s role as a weight loss agent. As an antioxidant, berberine can limit oxidative stress post-exercise and lower muscle soreness and physical stress to counter exercise-induced exhaustion.*¹ Berberine can also enhance skeletal muscle mass and exert cardioprotective effects.*² These benefits of berberine enhance physical endurance, which indirectly supports weight management.*

How Does Berberine Promote Glucose Metabolism?

Poor weight management is characterized by abnormal glucose metabolism, which leads to reduced glucose disposal in adipose tissues. Unhealthy weight gain often leads to elevated levels of blood sugar, lipids (fats), and insulin, as well as insulin resistance. 

Several studies have investigated berberine’s ability to promote glucose metabolism, and thereby contribute to healthy weight management,* although the exact mechanism of berberine’s action on glucose metabolism is not fully understood. The following table highlights studies that have explored berberine’s role in promoting glucose and lipid metabolism.* 

Berberine and Glucose Homeostasis
Promoting Insulin Secretion and Addressing Insulin Resistance*	As an antioxidant, berberine protects the insulin-producing cells in the pancreas.* It promotes insulin secretion and reduces insulin resistance through various cellular signal transduction pathways, such as the cyclic adenosine monophosphate (cAMP) pathway.*3
Stimulating Glucose Breakdown*	Berberine-induced activation of signaling pathways stimulates the breakdown of glucose into pyruvic acid, thereby releasing energy.*4
Inhibiting Glucose Synthesis from Non-carbohydrate Components*	Berberine regulates mitochondria-related pathways, which inhibits glucose synthesis from non-carbohydrate components in liver cells.*5
Limiting Digestion of Carbohydrates in the Intestine*	By limiting carbohydrate digestion in the intestine, berberine inhibits intestinal absorption of glucose.*6
Promoting Lipid Metabolism*	Insulin is integral to lipid metabolism because it promotes cholesterol biosynthesis and uptake.* Berberine is a known activator of adenosine monophosphate-activated protein kinase (AMPK), which contributes to fatty acid oxidation and limits lipid accumulation, particularly that of low-density lipoprotein cholesterol (LDL-C).*7

How Does Berberine Promote Glucose Metabolism?

Although the direct effects of berberine on weight management are still unclear, berberine does influence several mechanisms that indirectly promote weight management. The following are some of the pathways that berberine influences to support weight management. 

• Promoting a healthy gut microbiota.* The gut microbiota regulates metabolism, appetite, and the hormonal and immune systems that affect body weight. Berberine promotes a balanced and healthy gut microbiota, particularly enhancing the growth of short-chain fatty acid (SCFA) producing bacteria.*⁸   

• Displaying glucose support properties.* As discussed above, berberine helps maintain normal blood glucose and lipid levels, enhances insulin secretion, and attenuates glucose tolerance and insulin resistance.*⁹ The combined effects of berberine on maintaining normal glucose homeostasis promotes healthy weight management.*

• Limiting differentiation of adipocytes.* Adipose tissue plays a crucial role in whole-body energy metabolism; it’s divided into white and brown adipose tissue. White adipose tissue is a key energy reservoir for other organs; whereas, brown adipose tissue accumulates lipids for cold-induced adaptive thermogenesis. Depending on nutritional changes, adipose tissues can undergo dynamic remodeling at an accelerated pace, which is considered one of the underlying causes of weight gain. 

Berberine promotes the distribution of brown adipose tissue and thermogenesis, and adipose tissue remodeling.*¹⁰  

Is It Safe to Take Berberine for Weight Management?

The short-term safety profile of berberine is well-established, although there is limited data about its effects on pregnant or breastfeeding women. Berberine can cause mild or infrequent side effects or potential contraindications when taken with certain prescription medications. The following table highlights some of the common side effects of berberine supplements: 

Berberine’s Side Effects
Gastrointestinal side effects include constipation, diarrhea, flatulence, and stomach pain.
Potential risk of low glucose level with prolonged intake of a high-dose berberine supplement.
Potential contraindications with drugs that are metabolized via CYP enzymes.

The side effects of berberine supplements depend on the delivery route (type of formulation) and the duration of intake. Therefore, it is always recommended to consult your healthcare provider before including a berberine supplement in your diet or taking one with a prescription medication. 

An Advanced Berberine Supplement Formulation for Weight Management

Unformulated berberine poses three key challenges that can adversely impact its efficacy:

• Intolerable taste: Berberine has an intensely bitter taste. Berberine hydrochloride, the most common ingredient of commercially available berberine supplements, has high aqueous solubility, making it difficult to mask its taste.  

• Intake in high amounts: Consuming a high amount of berberine to compensate for its low bioavailability can result in adverse gastrointestinal events, such as upset stomach, cramping, and diarrhea.  

• Poor absorption: Poor absorption means your body does not experience the desired beneficial effects of berberine. 

Most commercially available berberine nutritional supplements contain 400-500 mg of berberine per capsule, with berberine hydrochloride being the primary ingredient. Berberine supplements are usually in the form of tablets, capsules, and fluid extracts.  

Compared to unformulated berberine, novel berberine supplement formulations use innovative approaches, such as nanotechnology, to enhance berberine’s palatability and bioavailability to achieve its health-promoting benefits. However, the safety and efficacy of berberine varies greatly depending on the type of formulation.

Frequently Asked Questions About Berberine Supplements for Weight Management

Here are frequently asked questions (FAQs) about using berberine for weight management:

Can I take berberine for weight management? 

Berberine can promote healthy weight management,* but it should not be considered as a supplement to achieve quick weight loss. Consult your healthcare provider before including a berberine supplement in your weight management program.  

Are there side effects to taking a berberine for weight management?

Clinical studies have established that berberine is safe and well-tolerated for short-term use. However, as mentioned earlier, side effects such as flatulence, nausea, constipation, and diarrhea can occur.  

Can I take a berberine supplement with a prescription medicine?

Berberine may cause potential contraindications with prescription medications. Always consult with your healthcare provider before including a berberine supplement in your diet or taking it with a prescription medicine for weight management.   

How do I determine the efficacy of a berberine supplement for weight management?

The efficacy of a berberine supplement lies in enhanced palatability, bioavailability, and absorption of the berberine molecules. Tesseract Medical Research’s BerberActiv®, an innovative, hypoallergenic berberine supplement formulation, achieves optimal absorption of berberine while enhancing its palatability to achieve user compliance.    

Tesseract’s proprietary CyLoc^® – DexKey^® nutrient delivery nanotechnology ensures unprecedented absorption of berberine molecules in the intestinal tract — one molecule at a time to maximize berberine’s benefits. The CyLoc® matrix encases each berberine molecule in its smart delivery system and masks berberine’s bitter taste. The DexKey® reactors release each berberine molecule at the desired point in the intestinal tract to achieve maximum absorption. Enhanced absorption enables micro-dosing — the ingestion of a lesser amount of berberine to achieve the desired powerful and rapid physiological response.  

With better delivery of berberine to the body’s tissues, BerberActiv® supports healthy blood glucose metabolism and lipid metabolism, optimal gastrointestinal and cardiovascular health, healthy weight management, and normal inflammatory and immune responses.*    

References: 

¹Chen L, et al. vol. 13 4561-4569. 23 Nov. 2020, doi:10.2147/DMSO.S275301

²Wang YW, et al. Zhonghua xin xue guan bing za zhi vol. 47,8 (2019): 647-652. doi:10.3760/cma.j.issn.0253-3758.2019.08.010

^3,4,7,Cao C,  Su M. Effects of berberine on glucose-lipid metabolism, inflammatory factors and insulin resistance in patients with metabolic syndrome. Experimental and Therapeutic Medicine vol. 17,4 (2019): 3009-3014. doi:10.3892/etm.2019.7295

^5,6Yin J, et al. Berberine improves glucose metabolism through induction of glycolysis. American Journal of Physiology. Endocrinology and Metabolism vol. 294,1 (2008):E148-E156. doi:10.1152/ajpendo.00211.2007

⁸Zhang L, et al. Effects of berberine on the gastrointestinal microbiota.” Frontiers in Cellular and Infection Microbiology vol. 10 588517. 19 Feb. 2021, doi:10.3389/fcimb.2020.588517

⁹Utami AR, et al. Berberine and its study as an antidiabetic compound. Biology vol. 12,7 973. 8 Jul. 2023, doi:10.3390/biology12070973

¹⁰Xu Y, et al. Berberine modulates deacetylation of PPARγ to promote adipose tissue remodeling and thermogenesis via AMPK/SIRT1 pathway.” International Journal of Biological Sciences vol. 17,12 3173-3187. 25 Jul. 2021, doi:10.7150/ijbs.62556

Updated on April 1, 2025

Are you struggling to manage your weight? Do you feel like no matter what you do, it’s still difficult to meet your health goals? Successful weight management efforts are critical to limiting the cardiovascular risks associated with being overweight, as well as addressing related metabolic, pulmonary, and gastrointestinal conditions. However, many of us are unable to balance our food intake and activity levels due to a variety of both individual and broader reasons. Underlying metabolic conditions further make popular weight management strategies ineffective while medications for weight management often carry the risk of potential side effects. So, is there a natural compound with minimal side effects that can be included in the diet to support weight management efforts?   

Research suggests that curcumin is a promising, natural bioactive compound that displays multiple mechanisms of action that beneficially affect cellular biochemical and physiological regulation. The health-promoting benefits of curcumin can address metabolic conditions and the associated unintended weight gain. This post discusses the correlation between gut microbiota and metabolism, the role of curcumin in weight management, and why you should include an advanced curcumin supplement in your diet. Use the links below to jump ahead to different topics on the page. 

The Connection Between the Gut Microbiota and Metabolism	How Curcumin Promotes Gut Microbiota
Curcumin for Weight Management	Bioavailability and Absorption of Curcumin
An Advanced Curcumin Supplement Formulation for Weight Management	Frequently Asked Questions About Curcumin Supplements

The Connection Between the Gut Microbiota and Metabolism

A healthy gut microbiota is an essential part of maintaining the body’s metabolism and energy balance. A healthy gut microbiota also plays a key role in maintaining immune and metabolic homeostasis and providing protection against pathogens. An imbalance in the gut microbiota can adversely affect the metabolic, immune, and endocrine systems, as well as energy homeostasis and lipid metabolism, all of which can result in weight gain. 

Furthermore, the relative lack of diversity in the gut microbiota can disturb the structure and function of the gut’s intestinal barrier, which can cause metabolites and microbes to enter the bloodstream and cause adverse inflammatory responses. This, in turn, may lead to several undesirable metabolic pathways to be over-activated, leading to¹: 

• Increased energy extraction from food: Through the activation of the G-protein coupled receptors (GPCR), the cell surface proteins are involved in signal transmission and increased production of short-chain fatty acids (SCFA). 

• Increased fat storage and activation of the endocannabinoid system: Through the activation of the endocannabinoid system and decreasing the levels of lipoprotein lipase. Low levels of the lipoprotein lipase, a fasting-induced adipose factor FIAF (a regulator of lipid metabolism) results in increased fat storage. 

• Inhibited fat utilization in muscles. Through the inhibition of the activity of protein kinase activated by AMP-activated protein kinase.     

Beneficial gut bacteria, such as Lactobacillus, Bifidobacterium, and Akkermansia, are traditional probiotics that play an important role in balancing the human intestinal microecology. Supplementation with Akkermansia muciniphilia has been found to enhance metabolic parameters and promote weight loss.²

How Curcumin Promotes Gut Microbiota

Curcumin, the polyphenolic active ingredient in turmeric, is an antioxidant known to exert beneficial health effects through multiple mechanisms and biochemical targets.* Curcumin limits oxidative stress and maintains normal inflammatory responses in cells by downregulating the secretions of the pro-inflammatory cytokines, such as the interleukins or TNF-α.*

Research indicates that curcumin can directly regulate the intestinal microflora.* The reciprocal interaction between curcumin and the gut microbiota involves two different phenomena: 

• The regulation of the intestinal microflora by curcumin 
• The biotransformation of curcumin by the intestinal microbiota 

Oral intake of curcumin leads to its distribution throughout the intestines, where it benefits the gut microbiota through microbial richness, diversity, and composition.* In diet-induced obese animal models, curcumin supplementation exerted protective metabolic effects by downregulating adverse immune responses in adipose tissues, mediated by alterations in the composition of gut microbiota and the metabolism of curcumin into curcumin-o-glucuronide.³

Curcumin promotes a healthy gut microbiota through: 

• Promoting beneficial bacterial strains*
• Enhancing intestinal barrier functions*
• Positively altering microbial diversity and composition*
• Counteracting the expression of pro-inflammatory cytokines*

Curcumin for Weight Management

Curcumin is a safe, natural, and well-tolerated botanical compound. A growing body of evidence suggests that curcumin can be an effective weight management aid. The following table highlights how curcumin exerts its beneficial effects in weight management.

Curcumin for Weight Management
Increases energy expenditure.* The gut microbiota comprises regulators of bile acid metabolism, lipid absorption, lipid synthesis, and energy metabolism. Research indicates a correlation between gut microbiota and energy metabolism. In high-fat diet-induced obese mice, curcumin enhanced insulin sensitivity and energy expenditure.*4
Limits the expression of inflammatory cytokines in adipose tissues.* Oxidative stress leads to adverse immune responses in adipose tissues, which stimulates adipocyte differentiation and promotes lipogenesis. As an antioxidant, curcumin scavenges reactive oxygen species (ROS) and inhibits the activation of NF-κB (nuclear factor-κB) signaling pathways in adipose tissues.*5
Inhibits adipogenesis.* Adipocytes are key cellular components of adipose tissue and play a significant role in lipid homeostasis and energy balance. Curcumin interferes with or constrains several stages of adipocyte differentiation.*6
Regulates lipid metabolism.* Lipid metabolism involves the synthesis, storage, and degradation of fatty acids, triglycerides, and cholesterol. 5’-AMP-activated protein kinase (AMPK) is a regulator of the lipid synthesis pathways and causes the oxidation of fatty acids in the liver to inhibit cholesterol synthesis. Peroxisome proliferator-activated receptor α (PPARα) also influences fatty acid oxidation and cholesterol breakdown during lipid metabolism. Curcumin beneficially causes AMPK and PPARα activation to limit lipid accumulation.*7

Bioavailability and Absorption of Curcumin

Curcumin has naturally low bioavailability and absorption, which hinders its efficacy in weight management. Curcumin’s chemical instability and water insolubility result in its rapid metabolism in the gastrointestinal tract and systemic elimination from the body. The bioavailability and absorption of free curcumin are reflected in:  

• Free curcumin versus curcumin metabolites: Curcumin is largely metabolized in the liver and the intestines, and the gut microbiota. The large intestine’s enzymes metabolize curcumin in two phases. Notably, it is curcumin metabolites that are detected in the blood, while the amount of free curcumin after oral intake is insignificant or barely detectable. 

• Biotransformation of curcumin and composition of gut microbiota: Curcumin is further transformed through the interaction of enzymes produced by the gut microbiota in the colon. The composition of the gut microflora results in differences in the biotransformation of curcumin consumed in a regular diet.  

Most orally consumed curcumin is eliminated from the body after only minimal systemic absorption. As a result, advanced delivery systems, such as nano-delivery, are often used to improve curcumin’s absorption and efficacy.

An Advanced Curcumin Supplement Formulation for Weight Management

The following table highlights the key features you should consider when selecting an advanced curcumin supplement to support your weight management efforts: 

Key Features of An Advanced Curcumin Supplement for Weight Management
Palatability: Most curcumin formulations fail to mask the taste of curcumin, which hinders user compliance. An advanced curcumin supplement formulation should be well-tolerated to promote oral ingestion.
Absorption: An advanced supplement formulation should utilize novel nutrient delivery systems for targeted delivery of curcumin for optimal absorption.
Bioavailability: An advanced supplement formulation should contain the most bioavailable form of curcumin for optimal solubility to achieve curcumin’s benefits for supporting weight management efforts.

TetraCumin^® is an advanced supplement formulation developed by Tesseract Medical Research, and is considered one of the best curcumin supplements for supporting weight management.* TetraCumin contains tetrahydrocurcumin and utilizes Tesseract’s proprietary CyLoc^® – DexKey^® technology — a revolutionary nutrient delivery system that enhances the palatability of the tetrahydrocurcumin molecules, maximizes their absorption and bioavailability, and enables their micro-dosing. 

Tesseract’s CyLoc® technology encases each tetrahydrocurcumin molecule in a dextrin fiber delivery cage to mask its unpleasant taste while maintaining its molecular integrity during transit through the stomach. The accompanying DexKey® reactors release the tetrahydrocurcumin molecules at the desired point in the intestinal tract, allowing for their optimal absorption and bioavailability.

Frequently Asked Questions About Curcumin Supplements for Weight Management

The following are frequently asked questions about the usage, safety, and efficacy of utilizing a curcumin nutritional supplement to support weight management:

Does a curcumin supplement for weight management work? 

Unlike unformulated curcumin, a nutritional supplement formulated with a highly absorbable and bioavailable form of curcumin, such as tetrahydrocurcumin, achieves maximum absorption. The enhanced absorption and bioavailability of curcumin in an advanced formulation can achieve curcumin’s benefits for supporting weight management. 

Are there side effects to taking a curcumin supplement?

Curcuminoids are approved as ‘Generally Recognized as Safe’ (GRAS) by the U.S. Food and Drug Administration and are widely used as a food additive. Curcumin is well-tolerated and safe, up to doses between 4,000 – 8,000 mg daily for 3 months, although doses of 500 mg – 2,000 mg are typically recommended for routine supplementation.  

Can I take a curcumin supplement with a prescription medicine?

Although curcumin’s safety profile is well-established, consult with your healthcare practitioner before taking it for weight management or taking it with a prescription medicine. 

References: 

¹Khan MJ, et al. Role of gut microbiota in the aetiology of obesity: Proposed mechanisms and review of the literature. Journal of Obesity vol. 2016 (2016): 7353642. doi:10.1155/2016/7353642

²Depommier C, et al. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nature Medicine vol. 25,7 (2019):1096-1103. doi:10.1038/s41591-019-0495-2

³Islam T, et al. Curcumin reduces adipose tissue inflammation and alters gut microbiota in diet-induced obese male mice.” Molecular Nutrition & Food Research vol. 65,22 (2021):e2100274. doi:10.1002/mnfr.202100274

⁴Zou T, et al. Curcumin improves insulin sensitivity and increases energy expenditure in high-fat-diet-induced obese mice associated with activation of FNDC5/irisin. Nutrition (Burbank, Los Angeles County, Calif.) vol. 90 (2021): 111263. doi:10.1016/j.nut.2021.111263

⁵Pérez-Torres I, et al. Oxidative stress, plant natural antioxidants, and obesity.” International Journal of Molecular Sciences vol. 22,4 1786. 11 Feb. 2021, doi:10.3390/ijms22041786

⁶Mohamed GA, et al. Natural anti-obesity agents. Bulletin of Faculty of Pharmacy, Cairo University 52.2 (2014):269-284.

⁷Rahmani S, et al. Treatment of non-alcoholic fatty liver disease with curcumin: A randomized placebo-controlled trial.” Phytotherapy Research : PTR vol. 30,9 (2016):1540-1548. doi:10.1002/ptr.5659

Updated 3/27/2025

Article Summary:

• Curcumin interacts with various molecular targets in the body, such as NF-κB, which indicates its role in supporting musculoskeletal and joint health.*
• The efficacy of curcumin supplements depends on the bioavailability and absorption of the active ingredients.
• Tetrahydrocurcumin—a bioactive metabolite of curcumin—is more bioavailable, which makes Tesseract’s joint supplement formulation easily absorbable in the body.

Curcumin is a naturally occurring compound derived from the turmeric plant. Curcumin has a wide range of beneficial pharmacological and physiological activities.* The health-promoting potential of curcumin has been extensively researched to determine how it promotes a healthy immune response and a healthy gastrointestinal environment, as well as supporting cardiovascular health, optimal lipid profiles, and musculoskeletal system.* 

Currently, curcumin is widely used as in ingredient in joint support supplements. It is important to understand how joint support supplements work to ensure you choose the right supplement formulation.

How Does Curcumin Support Joint Jealth? 

The following table highlights how curcumin’s natural properties support joint health. 

Curcumin’s Effect on Joint Health
Curcumin binds with several molecular targets and directly regulates their activities or indirectly regulates their functions.* Among curcumin’s molecular targets, some, like NF-κB, are involved in bone remodeling, which suggests curcumin’s beneficial in supporting musculoskeletal and joint health.*1
Curcumin’s antioxidant properties help maintain the body’s natural inflammatory responses.* As a potent antioxidant, curcumin promotes a healthy inflammatory response to non-chronic musculoskeletal and joint discomfort.*

How Much Curcumin Should I Take to Maintain Optimal Joint Health?

The Allowable Daily Intake (ADI) value of curcumin is 0-3 mg/kg per body weight.
Source: European Food Safety Authority

In clinical trials studying the impact of curcumin on joint health, adult participants received between 100-400 mg/day. It should be noted that there is no standard suggested daily use of curcumin for supporting joint health.

Are Curcumin Supplements Effective for Joint Health?

The efficacy of a curcumin supplement for joint health depends on the bioavailability of the active ingredient and how well the body absorbs it. Although curcumin holds immense beneficial potential, its clinical application is hampered by its naturally low solubility, which can lead to poor absorption and rapid metabolism, followed by rapid clearance from the body, resulting in its poor bioavailability to the plasma and tissues. 

Several strategies are used to enhance curcumin’s bioavailability in nutritional supplement formulations, including:

• Using optimal bioavailable forms of curcumin, such as Tetrahydrocurcumin  
• Combining curcumin with piperine, a bioactive compound derived from black pepper 
• Mixing turmeric powder and turmeric essential oil
• Developing curcumin nanoformulations

A clinical trial studying the effect of curcumin supplementation on post-exercise muscle soreness demonstrated beneficial changes in inflammatory cytokine profiles—the signaling proteins that help regulate the body’s inflammatory response.*² This suggests that supplementation with a more bioavailable form of curcumin translates to faster recovery from, and enhanced functional capacity during, exercise sessions.*    

Are there side effects of curcumin supplements? 

Although several clinical studies have established curcumin’s efficacy and safety, ingesting higher amounts of curcumin can be associated with certain adverse health effects. In dose escalation studies evaluating the safety of ingesting high amounts of curcumin (500-12,000 mg daily), some volunteers experienced diarrhea, nausea, headache, rash, and yellow stool.³ To avoid these potential adverse effects, individuals should consult with their healthcare practitioner to determine the appropriate amount of daily curcumin intake for their needs.     

How Do I Select the Right Curcumin Supplement for Joint Health? 

When it comes to selecting the right curcumin supplement for joint health, there are two key factors for consideration. 

• Palatability: First generation curcumin supplements faced challenges with user compliance due to the inability to mask curcumin’s unpleasant taste.

• Efficacy: Curcumin’s naturally poor absorption and bioavailability required users to take a significant amount of a curcumin supplement to experience its health-promoting benefits.

Tesseract Medical Research has developed TetraCumin^® — a proprietary joint supplement formulation that contains tetrahydrocurcumin for supporting musculoskeletal and joint health.* Tetrahydrocurcumin, a primary metabolite of curcumin, displays similar health-promoting activities to those of curcumin but is more stable.* The increased stability of tetrahydrocurcumin makes it more bioavailable in tissue and plasma and significantly more effective than curcumin. Thus, tetrahydrocurcumin avoids the pitfalls of the older manufacturing processes of curcumin supplements. 

Tesseract’s TetraCumin has overcome curcumin’s bioavailability challenges with our revolutionary CyLoc^® – DexKey^® nutrient delivery system, which significantly enhances the bioavailability of tetrahydrocurcumin, ensuring its timely absorption at the targeted point in the intestinal tract. 
Tesseract’s CyLoc® technology encases each tetrahydrocurcumin molecule to maintain its integrity and mask the unpalatable taste and smell. The DexKey^® technology accompanying each CyLoc^® molecule ensures targeted delivery of the molecules at the desired release point within the intestinal tract. The result is the optimal absorption and effectiveness of each tetrahydrocurcumin molecule, making them a bioavailable reality.

References:

¹Zhou H, et al. The targets of curcumin. Current Drug Targets vol. 12,3 (2011):332-347. doi:10.2174/138945011794815356

²McFarlin BK, et al. Reduced inflammatory and muscle damage biomarkers following oral supplementation with bioavailable curcumin. BBA Clinical vol. 5 72-8. 18 Feb. 2016, doi:10.1016/j.bbacli.2016.02.003

³Lao CD, et al. Dose escalation of a curcuminoid formulation. BMC Complementary and Alternative Medicine vol. 6 10. 17 Mar. 2006, doi:10.1186/1472-6882-6-10

Article Summary:

• Glutathione is a key antioxidant found in high concentrations in the liver, where it scavenges harmful free radicals and facilitates their safe degradation.*
• This ‘master antioxidant’ supports many other bodily functions, including nutrient metabolism, vitamin C and E regeneration, and regulation of cellular events.* 
• Optimum glutathione absorption in the gastrointestinal tract is a major challenge associated with the oral intake of glutathione nutritional supplements. 

Oxidative stress is an umbrella term that refers to the processes in the body when oxidants (the molecules that are harmful to tissues and organs) outnumber the body’s antioxidants. Glutathione is the body’s most abundant non-protein compound in organic tissues that acts like an “antioxidant superhero”. Although it is naturally produced by the body, glutathione’s level can decrease with age, poor diet, lifestyle changes, and other negative factors, thereby potentially contributing to adverse health effects. 

Below, we discuss how glutathione’s detoxification activity occurs in the liver to support your body’s optimal functioning,* and why you should include a glutathione supplement in your diet.    

Glutathione and Detoxification — How This Master Antioxidant Supports Your Body

Let’s understand why liver detox happens and the critical role antioxidants play in shielding liver cells from free radicals. 

The Role of Antioxidants in Detox 

Oxidative stress results from an overabundance of reactive oxygen species (ROS) — or free radicals — in cells and tissues. While having ROS is an important physiological necessity to drive the body to produce energy in the Citric Acid Cycle, increased ROS production or an excess of ROS can adversely affects important cellular structures like lipids, proteins, and nucleic acids, eventually leading to various impaired cellular functions. Enzymatic and non-enzymatic antioxidant molecules, like glutathione, are part of the body’s natural cellular defense system that protects cells and tissues from ROS-induced damage.

Glutathione’s Role in Detoxification in the Liver 

The liver’s main detoxification function is to filter the blood, and metabolize and remove harmful substances from our bodies. To mitigate the effects of these substances, there is a high concentration of glutathione in the liver that serves as a protective barrier. Glutathione detox in the liver works through:

• Regulating detoxification pathways. Glutathione and glutathione-related enzymes, including glutathione S-transferase (GST), glutathione peroxidase (GPx), and glutathione reductase, help regulate the liver’s complex detoxification pathways.* 
• Scavenging free radicals. Instead of letting free radicals adversely react with the body’s cellular machinery, glutathione molecules ‘scavenge’ these harmful free radicals and help neutralize them in Phase I liver metabolism.* 
• Safely degrading free radicals. During oxidative stress, the liver exports oxidized glutathione molecules into bile¹ to safely degrade free radicals for elimination via stool.* In Phase II liver metabolism, glutathione molecules join the activated intermediates produced during Phase I to make them water-soluble for easier excretion by the kidneys in urine.* 

The following table highlights the beneficial effects of glutathione for liver detoxification support.

Beneficial Effects of Glutathione Detox in the Liver
Direct neutralization of Persistent Organic Pollutants (POPs) and other oxidative chemicals.*
Excretion of heavy metals, like mercury, lead, and arsenic, from cells.*
Excretion of POPs and other heavy metals from the body.*
Metabolism and excretion of drug metabolites from the body.*

How Glutathione Helps Your Body to Function Optimally* 

The glutathione molecule holds immense potential for promoting the optimal functioning of the body.* Let’s review some of the ways the body’s ‘master antioxidant’ supports various functions.

How Glutathione Supports Various Functions
Antioxidant defense.* The primary role of glutathione is to directly scavenge various oxygen and nitrogen oxidants, detoxify hydrogen and lipid peroxides, and prevent the oxidation of biomolecules.*
Regulation of cellular events.* Glutathione regulates various cellular events, including cell proliferation and cell death, gene expression, protein and DNA synthesis, and immune responses.*
Regeneration of vitamins C and E.* Glutathione protects cells from oxidants through recycling vitamins C and E,* which are powerful antioxidants themselves.
Nutrient metabolism.* Glutathione plays a beneficial role in regulating glucose, lipid, and amino acid metabolism in the body.*

A clinical trial³ studying the long-term effectiveness of oral glutathione supplementation concluded that daily consumption of a glutathione supplement increases the body’s level of glutathione. Owing to the critical role of this master antioxidant in promoting liver health, glutathione is widely used as a supplement in oral, topical, intravenous, intranasal, and nebulized forms.     

Benefits of Including an Oral Glutathione Supplement in Your Diet

Although oral glutathione has been shown to be well absorbed in laboratory animal models, the efficacy of oral glutathione supplements for human use has been limited due to the challenge of determining its absorption in the gastrointestinal tract.  

To address the challenge of glutathione absorption in the body, Tesseract Medical Research has formulated SafeCell^® — an acetylated form of oral glutathione. Coupled with Tesseract’s revolutionary CyLoc^® – DexKey^® delivery system, Tesseract’s SafeCell formulation is developed for superior absorption and efficacy to better achieve the benefits of glutathione detox.* Tesseract’s unique nutrient delivery system directly releases each molecule of acetyl glutathione into the intestinal tract — billions of molecules at a time — one by one. SafeCell^’‘s enhanced efficacy supports the optimal functioning of other antioxidants, down-regulating oxidative stress and up-regulating natural detoxification pathways.*    

References:

¹https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2596047/pdf/yjbm00117-0089.pdf Accessed 31 March 2023

²Chen Y, Yang Y, Miller ML, et al. Hepatology. 2007 May;45(5):1118-1128. doi: 10.1002/hep.21635.

³Richie JP Jr., Nichenametla S, Neidig W, et al. Randomized Eur J Nutr. 2015 Mar;54(2):251-263. doi: 10.1007/s00394-014-0706-z. Epub 2014 May 5. PMID: 24791752.

Children diagnosed with autism spectrum disorder (ASD) frequently experience abdominal pain, constipation, vomiting, and diarrhea. In recent years, growing evidence suggests that autism spectrum disorder (ASD) is closely associated with gastrointestinal health. Research indicates that the bacterial populations of the gut microbiome can influence gastrointestinal and neurobehavioral ASD symptoms.  

Although there is no cure for ASD, various medications, diets, supplements, and therapies can help manage its symptoms. Owing to the strong connection between the gut microbiome and ASD, interventions aimed at normalizing the gut microbiome might help manage ASD symptoms. 

This post explains how autism is linked to gut bacteria, how a mother’s gut bacteria can affect a child’s risk of ASD, and why one should consider butyric acid supplementation to help manage ASD symptoms. Use the links below to jump ahead to different topics on the page. 

Gut-Brain Connection in Autism Spectrum Disorder

The gut contains millions of nerve cells that form an extensive network called the enteric nervous system (ENS), also known as the ‘second brain.’ The ENS and the central nervous system (CNS), mainly connected through the vagus nerve, form the gut-brain axis. 

The bi-directional communication between our gut and brain through the ENS, CNS, hormones, neurotransmitters, and immune responses greatly influences neurological and gastrointestinal health. For example, as much as 90 percent of neurotransmitters, such as serotonin, are produced in the gut and influence our emotions by regulating the gut-brain axis.      

The human gut microbiome consists of trillions of bacterial cells primarily involved in beneficial activities such as producing metabolites, transporting them, and maintaining gut homeostasis. However, various pathogenic microbes, like Clostridium bolteae, can adversely affect the gut, resulting in unwanted gastrointestinal conditions. Interestingly, Clostridium bacteria in the colon is associated with a higher risk and severity of ASD, potentially due to mechanisms involving gut-brain interactions and neurotoxic metabolite production.¹ 

How Autism Is Linked to Gut Bacteria

Several pilot studies on the gastrointestinal bacterial composition in ASD reveal that the gut microbiota composition is distinctive in ASD children. A high acidic pH level in their stools indicates an imbalance in the microbiota that can lead to downstream adverse effects on the gastrointestinal and nervous systems through the gut-brain axis.  

The following table highlights several studies indicating how autism is linked to gut bacteria.

Links Between Autism and Gut Bacteria
An increased presence of pathogenic bacteria in gut microbiota of ASD children: A clinical study found that children with ASD had a higher abundance of specific gut microbiomes, such as Firmicutes and Proteobacteria, than their neurotypical siblings.2 The Lactobacillaceae family was more abundant in ASD children, while the Bifidobacterium and Prevotella genera showed lower quantities. In short, more pathogenic genera and species were present in the gut microbiota of ASD children.
Distinct and less diverse gut microbial compositions in ASD children: In a study highlighting systemic changes in gut microbiome associated with autism and related gastrointestinal problems, lower levels of bacteria in the Prevotella and Coprococcus genera and the unclassified Veillonellaceae bacterial group were found in individuals with autism.3 Interestingly, the presence of autistic symptoms, rather than the severity of gastrointestinal symptoms, was associated with a less diverse gut microbiome.

These studies indicate how the presence of pathogenic and less diverse gut microbial composition might elicit adverse neurobehavioral symptoms via the gut-brain connection.

In addition, ASD symptoms are associated with higher levels of intestinal permeability and defects in the gastrointestinal barrier.⁴ A higher level of intestinal permeability can result in toxins and the by-products produced by pathogenic bacteria traveling through the gut-brain axis, which can then disrupt chemical balances in the brain and exacerbate ASD symptoms. 

How Short-Chain Fatty Acids Alter Gut Microbiome

Multiple short-chain fatty acids (SCFAs) in the large intestine are produced from the fermentation of carbohydrates, such as dietary fibers, by the gut’s microbiota. SCFAs can cross the blood-brain barrier and affect CNS functions, such as regulating oxidative stress and neuronal cell death, and maintaining normal inflammatory responses in nerve cells. The primary short-chain fatty acids (SCFAs) in the large intestine are:

• Acetic acid 
• Propionic acid 
• Butyric acid

Studies show altered gut compositions in children with ASD, characterized by elevated levels of SCFAs, particularly propionic acid. Excess propionic acid that crosses the blood-brain barrier sets the stage for a toxic environment that can result in cognitive and motor impairments. It has been observed that the greater the gastrointestinal disturbance in autistic children, the greater the risk of behavioral problems, language impairment, and irritability.  

Although the exact mechanism of SCFAs’ influence on the CNS is still unclear, research indicates that SCFAs do modify neurological processes at the molecular level and thus have the potential to affect behavior. 

Evidence for the role of SCFAs in influencing CNS functions highlights their role in influencing the gut-brain axis and their fluctuating levels. 

Does a Mother’s Gut Bacteria Affect A Child’s Risk for Autism?

Animal studies indicate that variations in maternal gut microbiota might increase the risk of ASD in children. The maternal gut microbiota is associated with neurodevelopmental abnormalities in mouse offspring. Further studies highlight a strong genetic influence on the development of autism. 

In a pilot study examining the relationship between the gut microbiome profiles of children with ASD and their mothers, researchers observed a striking correlation between the microbiomes of the mother-child pairs.⁵ However, because the mothers of children with ASD were neurotypical, they presented variations in their bacterial biomarkers. Compared to their mothers, children with ASD harbor unique bacterial biomarkers, such as increased amounts of the pathogenic genera Alcaligenaceae, Clostridium, Haemophilus, and Wautersiella.

Interestingly, emerging studies have also indicated that both genetic and epigenetic factors in paternal sperm also play a significant role in the development of ASD in children. 

Nutritional Supplements that Promote Gut Health and Help Manage ASD Symptoms

Both preliminary research and anecdotal evidence indicate that probiotics, prebiotics, and dietary changes can be effective in addressing the symptoms of autism. The following table highlights several key dietary nutrients that can beneficially address ASD symptoms. 

Key Dietary Nutrients for Managing the Symptoms of Autism
Vitamin D3: A vitamin D deficiency during pregnancy and early childhood can significantly impact the developing brain and result in adverse neuropathologies, including ASD. Vitamin D is a key dietary nutrient for promoting healthy neurodevelopment and minimizing oxidative stress.
Vitamin B12: Vitamin B12 plays a significant role in inhibiting the toxicity of nitrous oxide (N2O), an air pollutant considered to be a risk factor for ASD.
Omega-3 fatty acids: EPA and DHA are two omega-3 fatty acids that are critical for normal brain structure and function. They are substrates for the production of the lipid-based signaling molecules necessary for cellular communication and immune regulation.
Probiotics and digestive enzymes: Nutritional supplements of probiotics and digestive enzymes help restore normal gut microbiota and limit the gut’s production and absorption of toxins.
Butyric acid: Butyric acid is an intracellular signaling molecule and immunoregulator. Studies indicate that it benefits gene expression in ASD.
Folinic acid: Supplementation with this reduced form of folate helps stabilize cerebrospinal fluid folate concentrations, which can improve the neurological symptoms associated with ASD.

Butyric Acid Supplementation for ASD-Affected Children

The link between autism, gut bacteria, and gut health is well-established. As a key energy substrate for colon cells, butyric acid enhances mitochondrial function in cell lines in male children with autism.⁶  

For all children with ASD, butyric acid supplementation can enhance gut health by up-regulating the beneficial activity of the white blood cells in the colon, thereby generating a more normal inflammatory response. Butyric acid might also serve as a critical metabolite to help rescue energy metabolism in ASD-affected individuals. 

AuRx^® is a stabilized butyric acid complex developed by Tesseract Medical Research to provide specific nutritional support for children with ASD. This hypoallergenic formulation, delivered in a palatable-tasting powder, enables the maximum absorption and bioavailability of butyric acid molecules through the proprietary CyLoc^® – DexKey^® nutrient delivery nanotechnology. Tesseract’s gold-standard medical food is intended to counter the gut-brain nutrient imbalance experienced by children with ASD. 

References

¹Rosenfeld CS. Microbiome disturbances and Autism Spectrum Disorders.” Drug Metabolism and Disposition: The Biological Fate of Chemicals vol. 43,10 (2015):1557-1571. doi:10.1124/dmd.115.063826

²Abuljadayel D, et al. Gut microbiota of children with autism spectrum disorder and healthy siblings: A comparative study. Experimental and Therapeutic Medicine vol. 28,5 430. 16 Sep. 2024, doi:10.3892/etm.2024.12719

³Kang D-W, et al. Reduced incidence of Prevotella and other fermenters in intestinal microflora of autistic children. PloS One vol. 8,7 e68322. 3 Jul. 2013, doi:10.1371/journal.pone.0068322

⁴Li Q, et al. The gut microbiota and Autism Spectrum Disorders.” Frontiers in Cellular Neuroscience vol. 11 120. 28 Apr. 2017, doi:10.3389/fncel.2017.00120

⁵​​Li N, et al. Correlation of gut microbiome between ASD children and mothers and potential biomarkers for risk assessment.” Genomics, Proteomics & Bioinformatics vol. 17,1 (2019):26-38. doi:10.1016/j.gpb.2019.01.002

⁶Rose S, et al. Butyrate enhances mitochondrial function during oxidative stress in cell lines from boys with autism. Translational Psychiatry vol. 8,1 42. 2 Feb. 2018, doi:10.1038/s41398-017-0089-z