Epicatechin Research

Impact of flavan-3-ols on blood pressure and endothelial function in diverse populations: a systematic review and meta-analysis of randomized controlled trials

Lagou V et al. • European journal of preventive cardiology (2025)

Flavan-3-ol-rich foods considerably reduce elevated BP and improve endothelial function independent of blood pressure supporting their use for cardiovascular prevention.

• Flavan-3-ol interventions included epicatechin, epigallocatechin-gallate, cocoa products, tea, grape extract, and apples delivering 586 mg (95% CI 510, 662) total flavan-3-ols.
• Interventions decreased office (-2.8 [95% CI -3.9, -1.7]/-2.0 [-2.6, -1.3] mmHg) and 24 h-ambulatory BP (-3.7 [-5.8, -1.6]/-2.6 [-4.5, -0.8] mmHg) after chronic repetitive consumption.
• Flow-mediated dilation increased after acute (+2.0% [1.6, 2.3]) and repetitive (+1.7% [1.3, 2.2]) consumption independent of BP.

Dietary flavonoid for preventing colorectal neoplasms

Jin H et al. • The Cochrane database of systematic reviews (2012)

There is insufficient and conflicting evidence regarding flavonoid intake and the prevention of colorectal neoplasms.

• A statistically significant reduced risk of CRC was found with high intake of epicatechin.
• There is insufficient and conflicting evidence regarding flavonoid intake and the prevention of colorectal neoplasms.
• It is difficult to determine flavonoid intake.

Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials

Hooper L et al. • The American journal of clinical nutrition (2012)

We found consistent acute and chronic benefits of chocolate or cocoa on FMD and previously unreported promising effects on insulin and HOMA-IR.

• Insulin resistance (HOMA-IR: -0.67; 95% CI: -0.98, -0.36) was improved by chocolate or cocoa due to significant reductions in serum insulin.
• Flow-mediated dilatation (FMD) improved after chronic (1.34%; 95% CI: 1.00%, 1.68%) and acute (3.19%; 95% CI: 2.04%, 4.33%) intakes.
• We found consistent acute and chronic benefits of chocolate or cocoa on FMD and previously unreported promising effects on insulin and HOMA-IR.

Biomarkers of (poly)phenol intake: a systematic review

Li Y et al. • Critical reviews in food science and nutrition (2025)

Further research is needed to enhance biomarker validity for precise dietary intake assessment in epidemiological studies.

• The most extensively validated biomarkers, SREM and PgVLM in 24-h urine, met five validation criteria.
• However, challenges remain, including limited specificity, short half-lives, inter-individual variability, and a lack of authentic chemical standards.
• Further research is needed to enhance biomarker validity for precise dietary intake assessment in epidemiological studies.

A Systematic Review Exploring the Phytochemical Composition and Anticancer Activities of Acacia catechu

Rana N et al. • Medical sciences (Basel, Switzerland) (2025)

However, further mechanistic investigations using pure compounds, along with preclinical and clinical trials, are essential to translate this potential into clinical applications.

• The plant has an abundance of phenolic compounds, including catechin, epicatechin, epigallocatechin-3-O-gallate, and epicatechin-3-O-gallate, which show strong anticancer activities.
• The anticancer potential of A. catechu is explained as it regulates several modulators like reactive oxygen species and cytokines, and downregulates oncogenic molecules like c-myc and various signaling pathways, such as c-Jun and NF-κB.
• Conclusions: Our findings suggest that A. catechu and its bioactive constituents have the potential for cancer prevention and therapy.

Neuroprotective Effects of Epicatechin against Oxidative Stress-Induced Cognitive Impairment: A Systematic Review and Meta-Analysis

Yoon YC et al. • Journal of agricultural and food chemistry (2025)

Collectively, the results highlight that epicatechin has the therapeutic potential for preventing or mitigating oxidative stress-related cognitive dysfunction.

• At the molecular level, epicatechin treatment increased the expression or activity of superoxide dismutase, catalase, and nuclear factor erythroid 2-related factor 2 and reduced the levels of nitric oxide, malondialdehyde, tumor necrosis factor-alpha, and interleukin-1 beta.
• These findings support the role of epicatechin in enhancing antioxidant defense and modulating neuroinflammation.
• Collectively, the results highlight that epicatechin has the therapeutic potential for preventing or mitigating oxidative stress-related cognitive dysfunction.

Effects of diet interventions, dietary supplements, and performance-enhancing substances on the performance of CrossFit-trained individuals: A systematic review of clinical studies

Dos Santos Quaresma MVL et al. • Nutrition (Burbank, Los Angeles County, Calif.) (2021)

All rights reserved.

• These outcomes may have been obtained due to methodological limitations such as small sample size, lack of control over influencing variables, short period of exercise intervention.
• Despite the popularity and growing evidence about CF, little is known about the relationship between performance-enhancing substances or dietary interventions and CF performance.
• Given the lack of scientific evidence, new studies with potential ergogenic supplements, a better methodological model, and practical application are required.Copyright © 2020 Elsevier Inc.

New Trends to Treat Muscular Atrophy: A Systematic Review of Epicatechin

German IJS et al. • Nutrients (2024)

However, there is no protocol standardization or enough clinical evidence to draw more specific conclusions on its therapeutic implementation.

• Epicatechin showed positive effects on follistatin and on the stimulation of factors related to the myogenic actions (MyoD, Myf5, and myogenin).
• Furthermore, the literature also showed that epicatechin can interfere with mitochondrias' biosynthesis in muscle fibers, stimulation of the signaling pathways of AKT/mTOR protein production, and amelioration of skeletal musculature performance, particularly when combined with physical exercise.
• Epicatechin can, for these reasons, exhibit clinical applicability due to the beneficial results under conditions that negatively affect the skeletal musculature.

The Effects of Flavonoids on Skeletal Muscle Mass, Muscle Function, and Physical Performance in Individuals with Sarcopenia: A Systematic Review of Randomized Controlled Trials

Wu C et al. • Nutrients (2023)

Flavonoids may have a great potential to treat sarcopenia.

• Skeletal muscle mass significantly increased in three studies, muscle strength significantly elevated in two studies, and physical performance significantly improved in two studies.
• RCTs evaluated the main outcomes of tea catechins, epicatechin, and isoflavones intervention.
• The majority of studies (five in six) found at least one of the main outcomes is elevated by flavonoids intervention.

Revisiting the bioavailability of flavan-3-ols in humans: A systematic review and comprehensive data analysis

Di Pede G et al. • Molecular aspects of medicine (2023)

Published by Elsevier Ltd.

• They contributed to the bioavailability of flavan-3-ols for over 20%.
• Mean bioavailability for flavan-3-ols was moderate (31 ± 23%, n bioavailability values = 20), and it seems to be scarcely affected by the amount of ingested compounds.
• This highlights the need to better clarify the metabolic yield with which monomer flavan-3-ols and proanthocyanidins are metabolized in humans.

Prevention from radiation damage by natural products

Fischer N et al. • Phytomedicine : international journal of phytotherapy and phytopharmacology (2018)

Some secondary metabolites from plants reveal radioprotective features against cellular damage caused by irradiation.

• Some secondary metabolites from plants reveal radioprotective features against cellular damage caused by irradiation.
• These results warrant further analysis to develop phytochemicals as radioprotectors for clinical use.
• Further research warranted to confirm findings

Dietary Plants for the Prevention and Management of Kidney Stones: Preclinical and Clinical Evidence and Molecular Mechanisms

Nirumand MC et al. • International journal of molecular sciences (2018)

Further investigations are required to confirm the safety and efficacy of these compounds.

• The main underlying mechanisms of these dietary plants and their isolated phytonutrients in the management of urolithiasis include diuretic, antispasmodic, and antioxidant activity, as well as an inhibitory effect on crystallization, nucleation, and aggregation of crystals.
• The results as presented in this review demonstrate the promising role of dietary plants and phytophenols in the prevention and management of kidney stones.
• Further investigations are required to confirm the safety and efficacy of these compounds.

Effect of an (-)-Epicatechin Intake on Cardiometabolic Parameters-A Systematic Review of Randomized Controlled Trials

Dicks L et al. • Nutrients (2022)

Unbiased RCTs on the impact of an EC intake are needed, which should also investigate the additive or synergistic effects of EC with other cocoa ingredients.

• For most trials, some concerns exist for overall RoB.
• Thus, EC intake may improve endothelial function in healthy young adults.
• For further parameters (mostly secondary outcomes), it remains unclear if EC has no effect or if this was not detectable.

Effects of Cocoa-Derived Polyphenols on Cognitive Function in Humans. Systematic Review and Analysis of Methodological Aspects

Barrera-Reyes PK et al. • Plant foods for human nutrition (Dordrecht, Netherlands) (2020)

However, the available evidence is very diverse and future studies may address the identified sources of variation to strengthen current evidence on this promising field.

• Memory (n = 5) and executive function (n = 4) showed the most significant effects with medium and large effect sizes after intake of intermediate doses of cocoa flavanols (500-750 mg/day).
• Effects on cognitive function were observed after consumption of 50 mg/day of (-)-epicatechin and in studies using a component-matched placebo and cocoa as the polyphenol vehicle given to healthy adults (18-50 years).
• Overall, this set of studies suggest a positive effect of cocoa polyphenols on memory and executive function.

Dose-response relationship between cocoa flavanols and human endothelial function: a systematic review and meta-analysis of randomized trials

Sun Y et al. • Food & function (2019)

This meta-analysis provides evidence that cocoa flavanols could significantly improve endothelial function, with an optimal effect observed with 710 mg total flavanols, 95 mg (-)-epicatechin or 25 mg (+)-catechin.

• A significant improvement of FMD by 1.17% (95% CI: 0.76% to 1.57%) was calculated, with strong evidence of a non-linear association (inverted U-shape) between cocoa flavanols and FMD.
• This meta-analysis provides evidence that cocoa flavanols could significantly improve endothelial function, with an optimal effect observed with 710 mg total flavanols, 95 mg (-)-epicatechin or 25 mg (+)-catechin.
• However, there was substantial variation in the results that could not be explained by the characteristics that we explored, and there were significant risk-of-bias concerns with a large majority of the studies.

Pharmacological Aspects and Potential Use of Phloretin: A Systemic Review

Mariadoss AVA et al. • Mini reviews in medicinal chemistry (2019)

Despite a multitude of clinical studies, new efforts are needed in clinical research to determine the complete therapeutic potential of phloretin.Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

• Fruits such as apples contain a variety of phytochemicals, including (+)-catechin and (-)-epicatechin, phlorizin, phloretin quercetin, cyanidin-3-Ogalactoside, chlorogenic acid, and p-coumaric acid, all of which are strong antioxidants.
• Phloretin, a natural phenolic compound, is a dihydrochalcone, which is present in the apple.
• It exhibits a wide variety of activities such as antioxidative, anti-inflammatory, anti-microbial, anti-allergic, anticarcinogenic, anti-thrombotic, and hepatoprotective, besides being involved in the activation of apoptotic associated gene expression and signal transduction in molecular pathways.

Relative impact of flavonoid composition, dose and structure on vascular function: a systematic review of randomised controlled trials of flavonoid-rich food products

Kay CD et al. • Molecular nutrition & food research (2012)

The present analysis suggests that flavonoid bioactivity does not follow a classical linear dose-response association and this may have important biological implications.

• Meta-analyses of combined flavonoid subclasses showed significant improvements in FMD (chronic, 0.73% (0.17, 1.30) 14 RCTs; acute, 2.33% (1.58, 3.08) 18 RCTs) and blood pressures (systolic, -1.46 mmHg (-2.38, -0.53) 63 RCTs; diastolic, -1.25 mmHg (-1.82, -0.67) 63 RCTs).
• The present analysis suggests that flavonoid bioactivity does not follow a classical linear dose-response association and this may have important biological implications.
• Further research warranted to confirm findings

Effects of daily multivitamin-multimineral and cocoa extract supplementation on epigenetic aging clocks in the COSMOS randomized clinical trial

Li S et al. • Nature medicine (2026)

• MVM had a stronger effect on PCGrimAge among those with accelerated biological aging at baseline (-0.236 [-0.380 to -0.091]) compared with those with normal or decelerated biological aging (-0.013 [-0.130 to 0.104]; P = 0.018 for interaction).
• Cocoa extract did not have an effect on the five epigenetic clocks tested.

Beyond Taste: The Impact of Chocolate on Cardiovascular and Steatotic Liver Disease Risk Factors

Tomaru JM et al. • Nutrients (2026)

Further large-scale, long-term trials are needed to confirm these beneficial effects and to standardize the dosage and formulation of cocoa flavanols.

• These findings suggest a potential role for cocoa flavanol-rich dark chocolate in cardiometabolic health; however, the evidence remains preliminary and is limited by heterogeneous study designs, small sample sizes, and short intervention durations.
• Despite these limitations, current evidence supports the inclusion of moderate dark chocolate consumption as a possible adjunct strategy to mitigate cardiometabolic and hepatic metabolic risks.
• Further large-scale, long-term trials are needed to confirm these beneficial effects and to standardize the dosage and formulation of cocoa flavanols.

Cocoa Flavanol Supplementation and Risk of Age-Related Macular Degeneration: An Ancillary Study of the COSMOS Randomized Clinical Trial

Christen WG et al. • JAMA ophthalmology (2025)

In this ancillary study of the COSMOS randomized clinical trial, cocoa extract supplementation for a median period of 3.6 years among older women and men had no effect overall on occurrence of AMD.

• Mean (SD) participant age was 72.1 (6.6) years, and 12 666 participants (59.1%) were female.
• During a median (IQR) period of 3.6 (3.2-4.2) years of treatment and follow-up, 344 participants (1.6%) experienced a confirmed AMD event (316 incident AMD, 28 progression to advanced AMD).
• For the primary composite end point, there were 159 cases (1.5%) in the cocoa extract group and 185 cases (1.7%) in the placebo group (hazard ratio [HR], 0.87; 95% CI, 0.71-1.08; P = .21).