IngredientsThe flavan core is recognized in every single flavonoid structure. It consists of 15 carbon atoms which build two aromatic rings (commonly denoted as A and B) linked by a three-carbon chain. The flavan core consists of 15 carbon atoms that build two aromatic rings linked by a three-carbon chain. The connecting carbon chain is a part of a heterocyclic central ring (designated as C). Flavans are widely distributed in nature and result from a double reduction of a flavanone.
The flavonoid family includes more than 6,000 low-molecular-weight phenolic compounds, all derivatives of flavan. The main subgroups are flavones, flavonols, flavanones, flavanolols, flavan-3-ols, anthocyanins, isoflavones, and chalcones. In dietary supplement and nutritional science contexts, the term flavans most commonly refers specifically to the flavan-3-ol subclass — a group of particular nutritional and pharmacological interest.
Flavan-3-ols (sometimes referred to as flavanols) are a subgroup of flavonoids. They are derivatives of flavans, are structurally diverse, and include compounds such as catechins, epicatechin gallate, epigallocatechin gallate, proanthocyanidins, theaflavins, and thearubigins.
Flavanols consist of two aromatic rings connected through a three-carbon "bridge" that forms part of a six-member non-aromatic heterocyclic ring. The heterocyclic C-ring holds a hydroxyl unit at position 3, and so they are also called flavan-3-ols. The basic structure of flavan-3-ols also contains two hydroxyls on the aromatic A-ring, together with two ortho-grouped hydroxyls (a catechol group) at positions 3′ and 4′ of the B-ring. Flavanols possess two chiral carbons at positions 2 and 3 of the C-ring, and (+)-catechin and (−)-epicatechin are the most common optical isomers found in nature.
Flavanols are also referred to as flavan-3-ols, as the hydroxyl group is always bound to position 3 of the C ring. Unlike many flavonoids, there is no double bond between positions 2 and 3.
Flavan-3-ols, often referred to as flavanols, are the most complex class of the flavonoids because they range in size from simple monomers (catechin and its isomer epicatechin) to the oligomeric and polymeric proanthocyanidins, which are also known as condensed tannins. Proanthocyanidins can occur as polymers of up to 50 units, and when hydroxylated they can form gallocatechins or undergo esterification to form gallic acid.
The main monomeric forms are (+)-catechin, (−)-epicatechin, (+)-gallocatechin, (−)-epigallocatechin, (−)-epicatechin-3-O-gallate, and (−)-epigallocatechin-3-O-gallate. Oligomers or polymers of flavan-3-ols are known as proanthocyanidins, while polymers composed exclusively of epicatechin or catechin are named procyanidins.
Catechin was first isolated from the plant extract catechu, from which it derives its name. Epigallocatechin and gallocatechin contain an additional phenolic hydroxyl group when compared to epicatechin and catechin, respectively. Catechin gallates are gallic acid esters of the catechins; an example is epigallocatechin gallate, the most abundant catechin in tea.
The incorporation of an additional hydroxyl group at position 5′ of the B-ring provides a phenolic structure with three hydroxyls in ortho distribution, known as pyrogallol groups, which are present in gallocatechins.
EGCG amounts to more than 50% of the flavan-3-ol fraction in green tea extracts.
Many natural flavans are lipid-soluble and are prominent in the skin or peel of fruits and in the cutin of leaf surfaces. A number of flavans are phytoalexins, which impart fungi or insect resistance to the plant tissues.
The flavonoids are derived from phenylalanine and malonyl-coenzyme A in reactions catalyzed by polyketide synthase. Chain extension of 4-hydroxycinnamoyl-CoA with three molecules of malonyl-CoA gives initially a polyketide, which can be folded, allowing Claisen-like reactions to occur, generating aromatic rings. The biosynthesis of flavanols involves a cinnamoyl-CoA initiating unit, with chain extension using three molecules of malonyl-CoA, and is catalyzed by type III PKS enzyme.
Flavan-3-ols are abundant in teas derived from the tea plant Camellia sinensis, in particular green tea. Apart from tea, main sources in the human diet are chocolate, pome fruits, and berries and their products, such as juices or red wine. Their content in food is highly variable and affected by various factors, such as cultivar, processing and preparation.
Green tea is a rich source of flavan-3-ols, principally epigallocatechin, epigallocatechin gallate, and epicatechin gallate. However, during fermentation of tea leaves the levels of catechins decline, and thus the main components of black tea are high-molecular-weight thearubigins, whose structures are derived from flavonoids. The catechins are widespread, but the main sources in the diet come from processed plant-foods such as tea, wine, and chocolate.
Flavanols are found abundantly in bananas, apples, blueberries, peaches, and pears. Barley and malt are considered good sources of proanthocyanidin (oligomers of flavan-3-ols), and act as major contributors to free radical scavenging activity. Out of nuts, hazelnuts and pecans are a rich source of proanthocyanidins, while roasted peanuts, almonds, pistachios, and cashews are a fair source of it. Dark chocolate, mint, rosemary, dill, and sage are also adequate sources of flavan-3-ols.
The predominant flavan-3-ols present in green tea leaves and their aqueous extracts include (−)-epicatechin (EC), (−)-epigallocatechin (EGC), (−)-epicatechin gallate (ECG), (−)-epigallocatechin gallate (EGCG), and (+)-catechin. Smaller amounts of other flavan-3-ols such as catechin gallate, gallocatechin, and gallocatechin gallate may also be present.
While cocoa beans (the seeds of Theobroma cacao) contain flavan-3-ols, these are susceptible to heat degradation during processing, causing the flavanol content in cocoa products, such as chocolate, to be relatively low. Modern science has learned that fermentation lowers the bitterness of roasted cocoa beans as well as their content of flavan-3-ols, while also creating more chocolate flavor when the beans are roasted.
Tea extracts are sold as dietary supplements labeled as tea catechins or tea polyphenols. Green tea extracts typically have higher levels of catechins, while black tea extracts have high levels of theaflavins and thearubigins.
Evidence from randomized controlled clinical trials indicates that the short- and long-term consumption of flavan-3-ols is beneficial on several health outcomes including cardiovascular, metabolic, cognitive, gut, and skin health. These health effects have led to the development of diverse flavan-3-ol-rich functional foods and nutraceuticals that address increasing consumer demand for nutritional interventions that are scientifically proven to support their health and wellbeing.
In natural sources, flavonoids may occur in free forms (aglycones), as glycosylated or acylated derivatives, and as oligomeric and polymeric structures such as the flavan-3-ol-derived condensed tannins (or proanthocyanidins). In contrast to many other flavonoids, flavan-3-ols do not generally exist as glycosides in plants.
The use of cacao, in its familiar food and beverage form, dates back about 3,800 years. Ancient fermenting pots and ceramic vessels showed traces of cacao and its active ingredient theobromine dating back to 1900 B.C. Around 1500 B.C., the Olmec began brewing, roasting, and grinding cacao beans for drinks and food, including gruel, and there is evidence that cacao may have been fermented and used as an alcoholic drink.
The use of cacao, in its familiar food and beverage form, dates back about 3,800 years. By the time of the discovery of America by Europeans, the Aztecs and Mayans had developed methods for drying, roasting, and grinding cacao beans for use in beverages and foods.
The Mayans used dozens of flavorings in their cacao preparations, from chillies to vanilla. Evidence from codices shows elaborate cacao recipes were produced also by the Aztec people (1300–1521). Aztec/Mexica cultures prepared multiple drinks involving chocolate along with other ingredients such as chilli, vanilla, ceiba seed, and flowers.
In native South and Central American cultures, cacao seeds were dried and then used to create drinking chocolate, which was often reserved for royalty, the priesthood, and aristocracy. Drinking chocolate played a role in religious ceremonies among the Olmecs, Toltecs, and Maya. Cocoa is an ancient fermented product made from the bean of the cacao tree, Theobroma cacao.
The use of green tea dates back to around 3000 BC in ancient China. Historical records, including the ancient medical text Shen Nong's Herbal Classic, demonstrate that the Chinese population was aware of tea's health-promoting and disease-preventative properties.
The concept of using tea was proposed for the first time by a Chinese King Shen Nung in 2737 BCE, when by chance some tea leaves were boiled in water. Green tea has been used in Traditional Chinese Medicine (TCM) for thousands of years as both a medicinal herb and a daily health tonic. Made from the leaves of the Camellia sinensis plant, green tea was first documented as a therapeutic substance in the Shennong Ben Cao Jing, a foundational TCM text attributed to the legendary emperor Shennong.
In TCM pharmacology, green tea is classified as a "bitter and sweet, cool" herb. This means it is believed to clear heat, resolve dampness, promote alertness, and support digestion. Modern pharmacological research has identified specific compounds in green tea — including catechins, L-theanine, and caffeine — that correspond to many of these traditional therapeutic claims.
When tea arrived in Japan in the 8th century via Chinese Buddhist monks, it carried its medicinal reputation. The Zen monk Eisai (1141–1215) wrote Kissa Yojoki ("Drinking Tea for Health"), one of Japan's earliest texts on tea.
Green tea is very popular because of its marked health benefits comprising its anticancer, antioxidant, and antimicrobial activities, as well as its effectiveness in reducing body weight. It was recognized by Chinese people as an effective traditional drink required for the prophylaxis against many health ailments.
Catechin was first isolated from the plant extract catechu, from which it derives its name. Acacia catechu, commonly known as catechu or black cutch, has long been used in Ayurvedic and South Asian traditional medicine. Historically, it has been consumed as a treatment of mild diarrhea and applied to the mouth as a gum strengthener. There is some evidence that it helps maintain gut balance and freshens breath.
The flavan-3-ol class encompasses a spectrum of structurally related compounds, each with its own biochemical profile:
Flavan-3-ols occur usually as aglycone monomers, oligomers, or esterified with gallic acid to form gallocatechin and epigallocatechin.
Flavonoids are small molecules produced de novo by plants as secondary metabolites. These chemical compounds have a broad spectrum of established health-promoting effects. They are due to their antioxidative, anti-inflammatory, anti-mutagenic, and anti-carcinogenic properties coupled with their capacity to modulate key cellular enzyme functions.
The biological activities of flavonoids are dependent upon their chemical structures, which in turn rely on their structural class, level of hydroxylation, substitution pattern, connection position, existence of a C2=C3 double bond, and level of polymerization.
The modulatory effects of polyphenols on vasodilation and vascular tone via the nitric oxide (NO) signaling pathway have been well established. They can interact with signaling pathways involving kinases such as phosphatidylinositol 3-kinase (PI3K)/Akt and eNOS, leading to an increase in NO production.
The exact mechanisms behind improvements in vascular outcomes likely include the enhanced bioavailability of endothelial-derived nitric oxide, decreasing superoxide-mediated nitric oxide breakdown, and improvement in serum lipids.
Monomeric flavan-3-ols are taken up and metabolized upon uptake in the small intestine, mainly by O-methylation and glucuronidation, and then further metabolized by the liver. The colonic microbiome also has a role in the metabolism of flavan-3-ols, which are catabolized to smaller compounds.
Phenyl-γ-valerolactones and phenylvaleric acids could contribute to the preventive effects attributed to flavan-3-ols on cardiovascular diseases through hypotensive properties and by attenuating the monocyte adhesion to endothelial cells that are involved in the development of atherosclerosis.
Direct interactions between flavan-3-ols and the gut microbiome are likely to alter host immune and inflammatory status as well as microbiome diversity.
The antidiabetic effects of various microbial metabolites from flavan-3-ols have been investigated from different perspectives, and the involved mechanisms are apparently not only related to their antioxidant properties, but also to their ability to modulate different signaling pathways.
Catechin and its isomer epicatechin inhibit prostaglandin endoperoxide synthase with an IC50 value of 40 μM. Five flavan-3-ol derivatives, including (+)-catechin and gallocatechin, isolated from plant species, exhibit equal to or weaker inhibitory activity against COX-2 relative to COX-1, with IC50 values ranging from 3.3 μM to 138 μM.
The bioavailability of flavan-3-ols depends on the food matrix, type of compound, and their stereochemical configuration. While monomeric flavan-3-ols are readily taken up, oligomeric forms are not absorbed. Most data for human metabolism of flavan-3-ols are available for monomeric compounds, especially epicatechin.
The degree of polymerization influences bioavailability: generally, monomeric flavan-3-ols can be absorbed in the small intestine, while structures with a higher polymerization degree are metabolized by the intestinal microbiota.
The bioavailability of cocoa flavanols is very low and their bioactivity in vivo seems to be greatly mediated by the derived phenolic metabolites formed by intestinal microbiota.
Studies have reported a poor bioavailability of flavonoid compounds in humans, which presents a major challenge for determining their optimal dosage, recommended intake, and, consequently, their therapeutic application.
Clinical trials have shown that supplementation with flavan-3-ols, mostly derived from cocoa products, significantly reduces blood pressure and improves endothelial function. Studies on catechins from green tea demonstrated better results when involving healthy individuals.
Compared to a low-flavan-3-ol group, the high-flavan-3-ol group showed an increase in flow-mediated dilation (FMD) chronically (over 12 weeks) by 1.6% (p < 0.01) and a reduction in diastolic blood pressure by 1.6 mmHg and mean arterial blood pressure by 1.2 mmHg (p < 0.05), independent of exercise.
Another double-blind, crossover RCT, involving 16 patients with coronary artery disease (mean age 64 years) receiving a dietary high-flavan-3-ol intervention (providing 750 mg flavan-3-ols) and a low-flavan-3-ol intervention for 30 days, showed an improvement in brachial artery FMD by 4.6% (p < 0.05) and a reduction in systolic blood pressure (−4.2 ± 2.7 mmHg; p = 0.013) in the treated group compared to the control group.
Additionally, flavan-3-ols have also been shown to reduce arterial stiffness.
A randomized, double-blind, placebo-controlled, 2-by-2 factorial trial of cocoa extract supplementation and multivitamins for prevention of CVD and cancer was conducted among 21,442 US adults (12,666 women aged ≥65 years and 8,776 men aged ≥60 years), free of major CVD and recently diagnosed cancer.
Participants were randomly assigned to a cocoa extract supplement (500 mg/day flavanols, including 80 mg (−)-epicatechins) or placebo. The primary outcome was a composite of confirmed incident total cardiovascular events, including myocardial infarction, stroke, coronary revascularization, cardiovascular death, carotid artery disease, peripheral artery surgery, and unstable angina.
During a median follow-up of 3.6 years, 410 participants taking cocoa extract and 456 taking placebo had confirmed total cardiovascular events (HR: 0.90; 95% CI: 0.78, 1.02; p = 0.11). For secondary endpoints, HRs were 0.73 (95% CI: 0.54, 0.98) for CVD death, 0.87 (95% CI: 0.66, 1.16) for MI, 0.91 (95% CI: 0.70, 1.17) for stroke, 0.95 (95% CI: 0.77, 1.17) for coronary revascularization, and 0.89 (95% CI: 0.77, 1.03) for all-cause mortality.
Per-protocol analyses censoring follow-up at nonadherence supported a lower risk of total cardiovascular events (HR: 0.85; 95% CI: 0.72, 0.99). There were no safety concerns. Cocoa extract supplementation did not significantly reduce total cardiovascular events among older adults but reduced CVD death by 27%.
Evidence strength assessment: This was among the largest and most rigorous RCTs conducted on any dietary bioactive compound. While the primary composite endpoint did not reach statistical significance, the significant reduction in CVD mortality is noteworthy. The trial supports but does not definitively confirm flavan-3-ols as a cardiovascular intervention in supplement form.
The Expert Panel found moderate evidence supporting cardiometabolic protection resulting from flavan-3-ol intake, and proposed the first dietary recommendation for a bioactive food compound. Moderate evidence supporting cardiometabolic protection resulting from flavan-3-ol intake in the range of 400–600 mg/day was supported in the literature.
Increasing consumption of dietary flavan-3-ols can help improve blood pressure, cholesterol concentrations, and blood sugar. Strength of evidence was strongest for some biomarkers (i.e., systolic blood pressure, total cholesterol, HDL cholesterol, and insulin/glucose dynamics). It should be noted that this is a food-based guideline and not a recommendation for flavan-3-ol supplements.
Guideline recommendation for a plant bioactive such as flavan-3-ols is a departure from previous recommendations because it is not based on deficiencies but rather improvement in health outcomes.
Epidemiological studies showed an association between higher flavan-3-ol intake and a lower risk of CVD and mortality.
In a large cohort study, participants in the highest tertile of flavan-3-ol intake exhibited a 33% lower risk of all-cause mortality compared to those in the lowest tertile (HR = 0.67, 95% CI: 0.49–0.92). For monomers, hazard ratios ranged from 0.55 for higher levels of epigallocatechin to 0.71 for higher levels of gallocatechin. Kaplan–Meier curves indicated significant differences in survival status across dietary flavan-3-ol intake groups. However, no association was found between flavan-3-ol intake and cardiovascular mortality risk.
Through a systematic, evidence-based approach, evidence mapping on flavan-3-ol intake and CVD outcomes demonstrated sufficient data relating to flavan-3-ol intake and biomarkers and clinical outcomes of CVD and diabetes. The current evidence base highlights the distribution of available data, which both supports the development of future systematic reviews and identifies the research need for future long-term RCTs.
The association between flavonoid consumption and risk for type 2 diabetes mellitus has been examined in a large European multicenter, nested case-control study — the "EPIC-InterAct" project — that included 16,835 diabetes-free participants and 12,043 diabetics. In this study, participants in the highest quintile of total flavonoid intake (>608.1 mg/day) had a 10% lower risk of diabetes than those in the lowest quintile (<178.2 mg/day). Specifically, the risk of diabetes was inversely correlated with the intake of flavan-3-ols (monomers and dimers only) and flavonols.
Recent meta-analyses of randomized controlled trials have examined the possible health effects of green tea flavan-3-ol monomers (catechins) on glucose metabolism and have provided conflicting results. A meta-analysis of seven trials in pre-diabetic and diabetic patients found no effect of green tea or green tea extracts on fasting plasma glucose, fasting serum insulin, or measures of glycemic control. Conversely, another meta-analysis of 17 trials in pre-diabetic, diabetic, or overweight/obese subjects found that administration of green tea extracts for 4 to 16 weeks improved fasting plasma glucose and HbA1c level. The effect on fasting glucose was observed only with high doses of catechins (≥457 mg/day) and when the confounding effect of caffeine was removed.
Evidence strength assessment: Meta-analyses on glycemic outcomes are mixed. Epidemiological data suggest a protective association with type 2 diabetes, but clinical trial evidence is inconsistent and appears dose-dependent and population-dependent. High-quality, long-duration RCTs are needed.
The hypothesis that dietary flavanols might improve cognitive function in subjects with mild cognitive impairment was tested in a double-blind, parallel arm study in 90 elderly individuals with mild cognitive impairment randomized to consume once daily for 8 weeks a drink containing approximately 990 mg (high flavanols), approximately 520 mg (intermediate flavanols), or approximately 45 mg (low flavanols) of cocoa flavanols per day. Cognitive function was assessed by Mini Mental State Examination, Trail Making Test A and B, and verbal fluency test.
Interestingly, the improvement of cognitive performance was associated with a reduction in insulin resistance, suggesting a possible influential role of glucose metabolism in modulating cognitive function in these subjects.
In the Cocoa, Cognition, and Aging (CoCoA) study, daily consumption of cocoa flavanols for 8 weeks improved cognitive performance in a group of cognitively intact older adults, without major adverse effects. Furthermore, cocoa flavanol consumption significantly improved blood pressure and several metabolic markers.
One study reported reductions in cardiovascular risk markers (systolic and diastolic blood pressure, total and LDL-cholesterol, insulin resistance), and these changes were proposed to partly contribute to ameliorate cognitive performance in those who consumed the flavan-3-ol-rich cocoa drink. The data could be replicated in cognitively healthy older people (ages 61–85 years), suggesting that cocoa flavan-3-ols might enhance some aspects of cognitive function during healthy aging.
Evidence strength assessment: Clinical evidence for cognitive benefits is encouraging but limited to relatively small trials, primarily using cocoa-derived flavan-3-ols. Several trials indicate performance improvements on processing speed, executive function, and working memory in older adults. Evidence is preliminary and requires replication in larger, longer trials.
Scientific evidence has strongly shown that regular intake of dietary flavonoids in efficacious amounts reduces the risk of oxidative stress- and chronic inflammation-mediated pathogenesis of human diseases such as cardiovascular disease, certain cancers, and neurological disorders.
Green tea catechins have been marketed and studied as weight management compounds, particularly for their thermogenic and fat-oxidation properties. Green tea supplements are often taken for weight loss because of catechin's expected fat-burning effect. However, evidence from meta-analyses is modest, and results vary depending on dose, caffeine co-administration, and population studied. No specific meta-analysis results for weight outcomes could be verified from authoritative sources within the scope of this review; claims in this area should be treated as preliminary.
A search on the PubMed database using the keywords "dietary flavonoids + human health" returned more than 570 results from randomized controlled trials (RCTs), systematic reviews, and meta-analyses of RCTs that are related to the consumption and use of dietary flavonoids and their diverse health benefits for humans.
Heterogeneity among reviewed trials related to differences in health status of the target population and characteristics of exposure, including differences in doses, supplement composition, and trial duration, may at least partially explain discrepancies among explored studies. Limitations also comprise potential interactions, including accumulating, synergistic, and antagonistic effects with other supplement components as well as food matrix components. The variations in actual exposure to flavan-3-ol metabolites related to differences in gut microbiota composition cannot be ruled out.
Flavan-3-ols are consumed through food sources and as concentrated dietary supplements. The following dosages are as stated in cited sources:
Supplement forms available commercially include standardized green tea extracts (typically standardized to a percentage of total catechins or EGCG), cocoa extract capsules, and proanthocyanidin-rich grape seed extracts. Tea extracts are sold as dietary supplements labeled as tea catechins or tea polyphenols.
Catechins, in particular epigallocatechin gallate, in green tea extract can be hepatotoxic. Health Canada and EFSA have advised for caution, recommending intake from supplements should not exceed 800 milligrams (mg) per day.
Consecutive cases of liver damage seemingly caused by excessive consumption of green tea supplements have been reported, and this has become a safety concern. As a result, the green tea extract Exolise was withdrawn from the market in France and Spain in 2003.
On the basis of a review in which more than 200 cases involving green tea products were examined, the affixing of a hazard label to green tea-containing preparations was considered by the US Pharmacopeia (USP) Dietary Supplement Information Expert Committee. Out of a total of 216 cases, 27 reports of liver damage were considered possible and likely caused by GTE-induced toxicity.
The literature supports a potential relationship between high-dose green tea extract consumption and transient changes in serum liver enzymes. Rare (<5%) and transient liver transaminase elevations have been documented. Hepatotoxicity tended to show a temporal relationship between green tea extract consumption and effect onset, with green tea extract-induced toxicity mainly manifesting after roughly 3–4 months of consumption.
The incidence and severity of hepatotoxicity increased when green tea extract or EGCG was administered under fasted conditions, while exposure to green tea under fed conditions appears to alleviate such risk.
Oketch-Rabah et al. suggested that repeated oral administration of GTE, particularly during periods of fasting, increased the bioavailability but also the toxicity of catechins.
Research suggests that people should not go on a diet while consuming EGCG for weight loss; otherwise the risk of liver injury will be significantly increased. This discovery provides new evidence for understanding the "drug-host" interaction hypothesis of drug hepatotoxicity and provides experimental reference for clinical safe use of green tea-related dietary supplements.
Numerous in vitro drug interaction studies have investigated the inhibitory activity of flavonoids on various cytochrome P450 monooxygenase (CYP) enzymes. For example, Li et al. reported a structure-dependent inhibition of CYP3A4 by some flavonoids.
Flavonoids can also affect drug transporters (so-called "efflux pumps") involved in the cell uptake and the extrusion of drugs and, therefore, can alter the metabolism and the absorption of drugs. In in vitro studies, flavonoids exhibited inhibitory effects on proteins which confer resistance to various conventional drugs.
Despite all the in vitro evidence, more definitive results from clinical research are needed to confirm these observations and determine the clinical significance of drug–flavonoid interactions.
Data on the effects of catechins in humans are scarce, which is partly due to their low stability and oral bioavailability. Furthermore, catechins may also participate in pharmacokinetic interactions when co-administered with certain drugs such as anticancer agents.
Recent studies have shown how polyphenol oxidase-rich foods such as bananas dramatically influenced the bioavailability of flavan-3-ols when consumed together, and there is evidence for an increase in bioavailability and efficacy of flavan-3-ols when methylxanthines were present.
The bioavailability of flavan-3-ols can be affected by nutrient–nutrient interactions with foods containing polyphenol oxidase.
In the large COSMOS trial, there were no safety concerns among participants consuming 500 mg flavanols/day over a median of 3.6 years, suggesting that this dose level is well-tolerated in the general older adult population. These interventions have shown favorable results in prior research studies and are well-tolerated and safe at doses studied in the trial.
Safety is an important consideration that must be assessed through meticulous and extensive quality control testing, especially since supplements are not subject to the same stringent regulations as pharmaceuticals. Human studies (e.g., randomized controlled trials) are required in order to provide clinical and scientific evidence regarding the safe and efficacious dose ranges for these products.
Health conditions that Flavans may help support.
Body systems that Flavans may help support.
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