Resveratrol is famous because of a French Paradox discussion in the 1990s, when it was believed that French people who eat high-fat foods are not prone to cardiovascular disease because the red wine they often drink contains resveratrol
Since then, resveratrol has been continuously discovered for potential health benefits, including anti-aging, anti-diabetic, anti-cancer, anti-dementia…
What are the benefits of resveratrol in empirical medicine? Are there any side effects or contraindications? See text analysis for details.
What is resveratrol?
Resveratrol is an antiviral secreted by plants, which is present in more than 300 edible plants (common: grapes, blueberries, cranberries, peanuts, cocoa, etc.), used to fight trauma, bacteria, infection, ultraviolet rays and other external environmental stress, can be said to be the guardian saint of plants.
Resveratrol is a polyphenolic antioxidant that was first isolated from white hellebore by Takaoka in 1940.
Resveratrol is generally divided into cis and trans isomers, but trans is more stable (Trans-resveratrol is the most common in nature), and many effects are only seen in trans (such as regulating inflammatory pathways and anti-hyperplasia), so it has become the mainstream of current health ingredients and is also the main research target.
Most current supplements containing resveratrol are made from plant root extract from Polygonum cuspidatum.
What are the proven benefits of resveratrol?
1. Resveratrol is beneficial for blood pressure regulation
Hypertension is a chronic condition that can lead to a variety of health problems such as cardiovascular disease, myocardial infarction, stroke, retinopathy, and kidney failure.
It is estimated that about 1 billion people worldwide have high blood pressure, and by 2025, this number will reach 1.56 billion.
While medication and lifestyle changes, particularly diet management and exercise, are considered common strategies in this setting, adherence to these approaches is generally low.
A systematic literature review and meta-analysis (17 randomised controlled trials, 681 participants) noted that resveratrol had a favorable but non-significant effect on systolic, mean arterial and pulse blood pressure, while no effect on diastolic blood pressure was observed. Note 1
In addition, subgroup analysis showed that the relevant blood pressure improvement was most pronounced in patients with ≥ 300 mg per day or diabetes.
*Conclusion: Resveratrol may be helpful in blood pressure regulation, particularly in high-dose use (≥ 300 mg/day) and in patients with diabetes, but more studies are needed due to the heterogeneity of the included studies
2. Resveratrol is beneficial for memory and cognitive performance
Age-related cognitive decline, characterized by decreased functioning of mental processes such as attention regulation, memory ability, and processing speed, can be a significant burden on the individual as it is associated with reduced functional independence and quality of life.
The number of people over 60 is expected to double by 2050, and although ageing is an inevitable part, the rate of degradation varies widely between individuals, driven by modifiable lifestyle factors such as exercise, body mass index and dietary patterns.
A systematic literature review and meta-analysis (4 randomized controlled trials, 226 participants) noted that resveratrol supplementation had no significant effect on memory and cognitive performance (assessed by auditory language learning tests, including learning ability, delayed recall, memory, and recognition). Note 1
*Conclusion: To date, there is limited evidence that resveratrol supplementation is not significantly helpful for memory and cognitive performance, and more large, precisely designed trials are needed
3. Resveratrol is good for bone health
Osteoporosis is a bone disease characterized by osteopenia and microstructural changes that lead to bone fragility and an increased risk of fractures. The prevalence of osteoporosis steadily increases with age, and it is estimated that osteoporosis causes 1.5 million fractures in the United States each year.
According to the World Health Organization (WHO), osteoporosis is defined as bone density in the hip or spine at least 2.5 standard deviations below the average peak bone mass in young, healthy adults, as measured by a dual-energy X-ray bone densitometer (DXA).
A systematic literature review and meta-analysis (6 RCTs, 264 participants) noted that resveratrol supplementation significantly improved serum alkaline phosphatase (ALP) and bone alkaline phosphatase (BAP) values compared with placebo, but serum calcium, osteocalcin, Type I collagen c-terminal peptide (ICTP) and type I precollagen nitrogen-terminal pre-peptide (P1NP) did not show significant improvement. Note 2
The mechanism behind it may be related to resveratrol promoting osteoblast formation and differentiation, osteoblast-derived BAP-mediated, and antagonizing osteoclasts.
*Conclusion: Resveratrol may have a positive effect on improving bone health, but more studies are needed to support this due to the small sample size and heterogeneity between studies.
4. Resveratrol is beneficial to cardiovascular health
Cardiovascular disease, the leading cause of death from noncommunicable diseases and closely linked to lifestyles such as lack of exercise, smoking and unhealthy eating habits, is rising sharply worldwide
A sad statistic is that in the United States, one person dies from cardiovascular disease every 39 seconds, more people than cancer, so having appropriate strategies to manage cardiovascular health and its related conditions is necessary for any healthcare system.
A pooled analysis (21 randomized controlled trials with 681 overweight or obese participants) found that resveratrol supplementation significantly reduced total cholesterol, systolic blood pressure, and fasting blood sugar.
In addition, subgroup analysis showed that the associated lowering of total cholesterol, systolic blood pressure, diastolic blood pressure, glucose, and insulin was most pronounced in subjects who consumed higher doses of resveratrol (daily dose≥300 mg). Note 3
*Conclusion: For overweight or obese people, resveratrol supplementation may have a positive effect on cardiovascular health, but more research is needed to confirm its clinical benefits
5. Resveratrol improves hyperlipidemia
Hyperlipidemia (also known as hyperlipidemia) can be roughly divided into elevated cholesterol, elevated triglycerides or both, and is one of the components of metabolic syndrome, closely related to obesity, type 2 diabetes, hypertension, coronary heart disease and stroke.
The cause of hyperlipidemia may be genetic, environmental, or both.
In general, genetic syndromes are characterized by very high cholesterol levels (> 300 mg/dL) and triglycerides (>500 mg/dL), cutaneous xanthelasma, family history, or lack of expected response to the maximum therapeutic dose of lipid-lowering agents.
A systematic literature review and meta-analysis (21 randomized controlled trials with 949 adults) noted that resveratrol did not significantly improve lipid-related values (e.g., total cholesterol, high-LDL cholesterol, and triglycerides). Note 4
*Conclusion: Up to now, oral resveratrol has no obvious effect on improving hyperlipidemia
6. Resveratrol helps with weight loss
According to multiple epidemiological studies, obesity has been identified as a major causative agent of a variety of diseases, such as: cancer (breast, endometrial, ovarian, colon, esophageal, kidney, pancreatic, prostate), type 2 diabetes, hypertension, stroke, coronary heart disease, congestive heart failure, asthma, chronic back pain, osteoarthritis, pulmonary embolism, gallbladder disease.
Therefore, weight loss is not only for the pursuit of perfect posture, but also to be healthier.
A systematic literature review and meta-analysis (28 randomized controlled trials, 1,514 participants) noted that Oral resveratrol (median dose: 300 mg, median duration 12 weeks) was associated with weight (WMD: -0.51 kg), body mass index (BMI, WMD: -0.17 kg m2), and waist circumference (WMD: -0.79 cm), but no significant improvement in fat mass. Note 5
In addition, subgroup-analysis further found that the relevant effect of reducing body weight and body mass index was especially at a daily dose of <500 mg, long-term intervention (≥ 3 months) and obese patients.
*Conclusion: Oral resveratrol may have a positive effect on weight loss, but more randomized controlled trials are needed
7. Resveratrol regulates blood sugar and is beneficial to diabetics
Type 2 diabetes is a common multifactorial genetic syndrome that is determined by several different genes and environmental factors. It currently affects 150 million people worldwide, and rates are increasing rapidly due to secondary factors such as obesity, high blood pressure and sedentary lifestyles.
If one parent has type 2 diabetes, the offspring have a 35% risk of developing type 2 diabetes; If both parents have type 2 diabetes, the risk of developing type 2 diabetes increases to 70%.
A systematic literature review and meta-analysis (9 RCTs, 283 participants) suggested that resveratrol supplementation improved fasting blood glucose (-0.29 mmol/l), insulin resistance index, and insulin level (-0.64 U/mL) in people with diabetes. Note 6
In addition, subgroup analysis showed that resveratrol doses greater than 100 mg daily were most effective in reducing fasting blood glucose.
The mechanism behind resveratrol may be related to resveratrol-activated “histone deacetylase SIRT1” and “AMP-activated protein kinase”.
*Conclusion: For type 2 diabetes, resveratrol may have a positive effect on glycemic control, but the limited size of small samples and possible bias still require further confirmation from large randomized controlled trials
8. Resveratrol improves non-alcoholic fatty liver
Non-alcoholic fatty liver disease is a group of diseases (excluding alcohol consumption, viral infections or other special causes) caused by excessive fat accumulation (more than 5% of liver weight), including nonalcoholic steatohepatitis, liver fibrosis and portal hypertension cirrhosis.
It is estimated that about one-third of the total population of the Western world and Asia currently suffers from the disease, and symptoms may include right upper quadrant pain, tiredness, hepatosplenomegaly, etc. Although changing lifestyle, limiting calorie intake and losing weight can help the disease positively, it is often difficult for most people to achieve.
Resveratrol is considered a lifesaver against fatty liver because of its anti-inflammatory, antioxidant and calorie-like effects.
A systematic literature review and meta-analysis (including 4 clinical trials, 158 participants) pointed out that resveratrol did not have any positive effect on liver fibrosis and fatty liver-related disease parameters (e.g., AST, ALT), that is, the evidence was still insufficient. Note 7
*Conclusion: To date, resveratrol has not been found to have a positive effect on non-alcoholic fatty liver disease
9. Resveratrol fights cancer
Cancer remains the top 10 cause of death in most countries, with 1.6 million new cases diagnosed each year in the United States, and the incidence increases with age.
Radiation and chemotherapy are the most common cancer treatment options, but cancer cells are resistant to anticancer drugs and often result in unsatisfactory results.
A systematic review pointed out that according to available in vitro and in vivo studies, resveratrol can promote apoptosis, anti-proliferation and anti-inflammation effects on cancer cells, and can be used as a sensitizer for anticancer drugs to enhance the effectiveness of anti-cancer treatment. Note 8
*Summary: Although resveratrol has shown good anti-cancer effects in many in vitro and in vivo experiments, there is still a lack of large-scale human trials, so its dosage, efficacy and safety have yet to be confirmed
10. Resveratrol is beneficial for age-related macular degeneration
Choroidal neovascularization is the most complex complication (wet lesion) of age-related macular degeneration, and these new abnormal blood vessels often lead to macular edema, retinal pigment epithelial cell degeneration and even retinal detachment, and if left untreated, can lead to blindness.
Vascular endothelial growth factor VEGF inhibitors are currently the main therapies used in the treatment of wet macular degeneration, which can slow down abnormal angiogenesis and visual degeneration.
In a preliminary study, resveratrol inhibited vascular endothelial growth factor VEGF, slowed choroidal neovascularization (caused by inflammatory hormone TGF-β or tissue hypoxia), and may improve the disease process of macular degeneration. Note 9
In addition, other small studies have found that resveratrol (after 1 hour of use) helps increase choroidal thickness (increases blood flow, slows the chance of macular degeneration) (compared to placebo). Note 10
*Conclusion: To date, no studies have directly confirmed the relationship between resveratrol and age-related macular degeneration, so further confirmation is needed
11. Resveratrol prolongs animal life
So far, the scientific community believes that the most effective way to extend human life is through calorie restriction, which is to limit daily calorie intake by 20 to 40 percent under nutritionally balanced conditions.
Diverse species with calorie restriction have also been shown to significantly extend lifespans (up to 60%) in many studies, and although long-term studies in humans have not yet been released, preliminary evidence is certain that the results should be consistent.
In a 6-month human study, following a calorie-restricted diet reduced a variety of life-related values, including insulin levels, body temperature, and DNA damage, and helped reduce the incidence of metabolic syndrome, cardiovascular disease, and cancer. Note 11
In some studies, resveratrol has found that the effect of disease resistance and life extension mechanism is similar to calorie restriction (which activates the sirtuin 1 longevity gene). Note 12
Therefore, in an animal-controlled study (both groups were fed high-calorie foods), mice consuming resveratrol significantly improved survival and reduced mortality by 31% (in addition to increased insulin sensitivity, hypoglycemia, increased mitochondrial capacity, improved mobility, etc.) Note 13
*Conclusion: The longevity extension effect of resveratrol in humans is inconclusive, so it still needs to be confirmed by more large-scale and precisely designed studies in the future
12. Resveratrol is beneficial for ulcerative colitis
Ulcerative colitis is a kind of inflammatory bowel disease, the main clinical symptoms are hemorrhagic diarrhea, abdominal cramps and other symptoms, is a chronic inflammation caused by immune dysfunction (intestinal mucosa is the main affected site), and patients also have a high incidence of bowel cancer.
At present, it is believed that oxidative stress and free radicals play an important role in the cause and exacerbation of diseases, and resveratrol has become the target of many studies because of its excellent scavenging ability of reactive oxygen species.
A double-blind controlled study (6 weeks in 56 patients with mild to moderate ulcerative colitis) found that taking resveratrol (500 mg daily) not only helped reduce the concentration of malondialdehyde (MDA, a product of free radical attack, higher oxidative stress) but also increased the body’s total antioxidant capacity and superoxide dismutase (SOD, a type of antioxidant) concentration. Note 14
In addition, resveratrol-treated groups also had significant improvements in disease activity and quality of life (compared to placebo-controlled groups).
What are the side effects of resveratrol?
Resveratrol is still an emerging health ingredient, and so far, there are few large human trials, so the exact effective dose and safety concerns (side effects) have not been established.
In a human study (29 days), large doses of resveratrol between 2.5 g and 5.0 g daily were found to produce mild gastrointestinal symptoms (including nausea, flatulence, abdominal discomfort, and diarrhoea) (symptoms occurred 2 to 4 days after initiation and half an hour to 1 hour after ingestion). Note 15
Safety precautions
1. Do not use by pregnant women, nursing mothers, children, liver and kidney dysfunction (due to unknown safety)
2. May have anticoagulant effect, so do not take with related anticoagulant drugs, antiplatelet drugs, non-steroidal anti-inflammatory drugs (NSAIDs), common drug name: aspirin , clopidogrel, diclofenac, ibuprofen, naproxen, dalteparin (dalteparin sodium), enoxaparin, heparin, warfarin. Note 17
3. Resveratrol may interfere with enzymes in the liver related to metabolizing drugs (such as cytochrome P450, CYP1A2), which in turn affects the effects of many common drugs and may cause unknown risks for drug users, so it should be avoided in combination with drugs or herbs, or consult a qualified doctor or pharmacist before use.
4. May have mild estrogenic activity (found in animal studies, not confirmed by human studies) (Note 16), for safety reasons, those with estrogen-sensitive diseases (such as breast, ovarian, uterine cancer, endometriosis, or uterine fibroids) should avoid taking it
5. Stop using resveratrol at least 2 weeks before surgery (due to possible anticoagulant effect)