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Purified Resveratrol

Also known as: Resveratrol, RSV, 3,5,4'-trihydroxy-trans-stilbene

Overview

Resveratrol is a naturally occurring polyphenolic compound found in various plants, including grapes, red wine, berries, and peanuts. It is widely used as a dietary supplement due to its purported antioxidant, anti-inflammatory, and cardiometabolic properties. Research on purified resveratrol supplementation is extensive, with numerous randomized controlled trials (RCTs) and meta-analyses exploring its effects on human health. Key characteristics include its ability to scavenge free radicals and modulate various cellular pathways involved in metabolism and inflammation. While its primary use is for general health and anti-aging, significant research focuses on its potential benefits for glucose and lipid metabolism. It is available in various forms, with purified resveratrol being the subject of much of the clinical research.

Benefits

Resveratrol demonstrates moderate evidence for several health benefits, particularly in metabolic health. A meta-analysis of 25 RCTs involving 1,171 participants showed that resveratrol significantly reduced hemoglobin A1c (HbA1c) by a standardized mean difference (SMD) of −0.48, indicating improved long-term blood glucose control, especially beneficial for obese and diabetic patients. This same analysis also reported modest but significant reductions in total cholesterol (SMD = −0.15) and LDL cholesterol (SMD = −0.42), with a slight increase in HDL cholesterol (SMD = 0.16). Additionally, resveratrol supplementation was found to significantly reduce waist circumference (SMD = −0.36), suggesting potential benefits for central obesity. While some studies indicate improvements in liver enzymes for individuals with liver disorders, a broader meta-analysis found no overall significant effect on liver enzymes in the general population. Evidence for improvements in cardiovascular risk markers like C-reactive protein (CRP), blood pressure, and overall cholesterol levels is inconsistent or limited across studies, with some systematic reviews finding no significant effects.

How it works

Resveratrol primarily exerts its effects through its potent antioxidant properties, neutralizing free radicals and reducing oxidative stress. It modulates several key signaling pathways involved in inflammation, glucose metabolism, and lipid regulation. A significant mechanism involves the activation of sirtuin 1 (SIRT1), a protein linked to cellular longevity and metabolic regulation, and AMP-activated protein kinase (AMPK), which plays a crucial role in energy homeostasis. Resveratrol also influences lipid metabolism by modulating LDL receptor expression and promoting cholesterol efflux. Despite these mechanisms, its oral bioavailability is relatively low due to rapid metabolism and conjugation in the body, which can limit its systemic effects.

Side effects

Resveratrol supplementation is generally considered safe at typical doses used in clinical trials, which are often up to 1,000 mg/day. Common side effects are rare and usually mild, primarily involving gastrointestinal discomfort. However, caution is advised with higher doses, specifically exceeding 1,000 mg/day, as these have been associated with an increase in liver alkaline phosphatase levels, particularly in older adults. While no major drug interactions or contraindications have been consistently reported in randomized controlled trials, individuals with pre-existing liver disorders may benefit from resveratrol but should be monitored closely. Due to its potential effects on blood glucose and lipids, individuals on medications for diabetes or dyslipidemia should consult a healthcare professional before starting supplementation. Pregnant or breastfeeding women and children should avoid resveratrol due to insufficient safety data.

Dosage

Effective doses of resveratrol in clinical trials vary widely, ranging from as low as 8 mg/day to as high as 1,500 mg/day. Significant metabolic effects, particularly concerning glucose and lipid parameters, have typically been observed at doses between 100 mg/day and 500 mg/day. Doses exceeding 1,000 mg/day may pose safety concerns, such as increased liver alkaline phosphatase, and do not consistently demonstrate superior efficacy. There is no established consensus on the optimal timing for administration, and the formulation (e.g., purified resveratrol versus plant extracts) can influence bioavailability. While co-administration with bioavailability enhancers like piperine is being investigated, it is not yet a standard recommendation. It is advisable to start with lower doses and gradually increase if needed, under professional guidance, especially given the wide range of effective doses and potential for dose-dependent side effects.

FAQs

Does resveratrol improve cardiovascular health?

Evidence for improvements in cholesterol and blood pressure is inconsistent. Some studies show modest lipid changes, but overall, no significant effects on C-reactive protein (CRP) or blood pressure have been consistently found in moderate to high-quality RCTs.

Is resveratrol effective for diabetes?

Yes, meta-analyses indicate significant reductions in HbA1c and waist circumference, supporting benefits in glucose metabolism for diabetic and obese individuals. It can help improve long-term blood sugar control.

Are there safety concerns with resveratrol?

Resveratrol is generally safe at moderate doses (up to 1,000 mg/day). However, caution is advised at higher doses, especially in older adults or those with pre-existing liver conditions, due to potential increases in liver enzymes.

How long does it take to see effects from resveratrol?

Most randomized controlled trials demonstrating metabolic improvements lasted between 2 and 12 months. Consistent use over several months is typically required to observe potential benefits.

Research Sources

https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2022.795980/full – This systematic review and meta-analysis of 25 RCTs (1,171 participants) found that resveratrol significantly reduced HbA1c, waist circumference, total cholesterol, and LDL cholesterol, with a modest increase in HDL, particularly in obese and diabetic populations. Despite high heterogeneity, the study suggests benefits for glucose and lipid metabolism.
http://evidence.nihr.ac.uk/alert/resveratrol-supplements-do-not-improve-cardiovascular-risk-markers/ – This systematic review of 10 RCTs (600 participants) concluded that resveratrol had no statistically significant effect on key cardiovascular risk markers such as C-reactive protein (CRP), cholesterol, or blood pressure. The findings suggest limited impact on these specific markers.
https://pubmed.ncbi.nlm.nih.gov/36642444/ – This systematic review and meta-analysis of 37 RCTs investigated resveratrol's effect on liver biomarkers. It found no overall significant effect in the general population but noted improvements in ALT and glutamyl transferase in patients with liver disorders and younger adults. High doses (>1,000 mg/day) were associated with increased alkaline phosphatase.
https://academic.oup.com/nutritionreviews/article/71/12/822/1833632?login=true – This systematic review and meta-analysis of 7 RCTs (282 subjects) found no significant effect of resveratrol supplementation on plasma lipid levels. The study highlights inconsistent findings regarding resveratrol's impact on lipids, possibly due to small sample sizes and older studies.
https://pubmed.ncbi.nlm.nih.gov/35431994/ – This is likely a duplicate or related entry to the first source (Zhou et al., 2022) given the similar publication details and findings related to HbA1c and metabolic parameters. It reinforces the evidence for resveratrol's positive effects on glucose and lipid metabolism in specific populations.