Resveratrol

What is Resveratrol ?

Resveratrol was first discovered in the 1940s. Resveratrol is a natural chemical compound found naturally in red grape skins, grape juice, peanuts, mulberries, and some Japanese herbs (Japanese knotweed). It seems the roots of Japanese knotweed has abundant resveratrol. In the recent years, this compound received renewed interest as several findings implicated resveratrol could increase cell survival and slow aging in yeast (and later in mice) by activating a “longevity” gene known as SIRT1 capable of mimicking the effects of calorie restriction, and regulating longevity in lower organisms. But the dose of resveratrol administered in experiments is always much higher than you’d normally consume in a daily diet. You would need to drink a hundred to a thousand glasses of red wine to equal the doses that improve health in mice ³⁾.

Given the worldwide increase in age-related metabolic diseases and obesity, resveratrol supplement has been promoted as a treatment for many conditions — including aging. The first real interest in this compound came when in 1992 resveratrol was postulated to explain some of the cardio-protective effects of red wine ⁴⁾. Five years later, in 1997, Jang and colleagues reported resveratrol to work as a chemo-preventive agent, by the ability to inhibit carcinogenesis at multiple stages in lab mice ⁵⁾. Meanwhile, anti-inflammatory and anti-oxidant properties were identified for resveratrol ⁶⁾, ⁷⁾.

Resveratrol supplements have not been well studied in people. We don’t really know what benefits and risks they might have. We also don’t know if resveratrol is necessarily more important than some of the other natural substances in wine.

Nonetheless, resveratrol has become a popular supplement. People use it for many different conditions. Some take resveratrol supplements to try to prevent or treat serious diseases, like cancer or heart disease. Others hope that they will slow the aging process. For now, these uses are unsupported by evidence.

Resveratrol and weight loss, what is the evidence ?

The anti-obesity effects of resveratrol shown in lab mice are not transposed into an efficient therapy of human obesity ⁸⁾. Recent peer-reviewed human clinical trials did not show the ability of resveratrol as a weight loss compound.

Resveratrol supplements appeared to aid those with the stiffest blood vessels in small study ⁹⁾

The antioxidant resveratrol — found in red wine, peanuts and berries — might improve the health of blood vessels in people with type 2 diabetes, a small study suggests.

Some preliminary evidence also suggests that resveratrol in humans may have anti-inflammatory effects, prevent cancer, diminish arterial stiffness, and improve endothelial reactivity in older women ¹⁰⁾, ¹¹⁾, ¹²⁾.

The study ¹³⁾, ¹⁴⁾ found that resveratrol supplements lessened artery stiffness in some people with type 2 diabetes. Stiffening of the arteries, called arteriosclerosis, raises the risk of heart attack and stroke. As you age, your arteries stiffen, which can lead to an increased risk of heart disease. In people with type 2 diabetes and obesity, this process starts earlier and can have more severe consequences.

The body’s largest artery is the aorta, which carries blood from the heart toward the rest of the body. For the study, the researchers measured the aortic thickness of 57 patients with type 2 diabetes (age 56 and obese, on average). The investigators also conducted tests to measure blood-vessel health.

Some patients were given resveratrol supplements, while the others were given a placebo. Overall, the study found a trend toward less aortic stiffness in participants taking resveratrol supplements, but it wasn’t statistically significant.

However, in a subset of 23 patients who had an exceptionally stiff aorta at the start of the study, 100-milligram (mg) daily doses of resveratrol for two weeks reduced stiffness nearly 5 percent. That regimen was followed by 300-mg doses over two weeks, which decreased stiffness by 9 percent, the researchers said.

Aortic stiffness increased among those taking a placebo for four weeks, the researchers found.

In treatment with resveratrol among people with diabetes, there was a trend toward improvement in the stiffness. And in people with higher stiffness there was more of a benefit.

“While the research suggests there might be ways to improve blood vessel abnormalities in people with type 2 diabetes, it’s too soon to recommend resveratrol for that purpose”, said the lead researcher Dr. Naomi Hamburg. She is chief of the vascular biology section at Boston University School of Medicine. The author added that a longer study is needed to look at whether resveratrol is going to reduce heart attacks and stroke. However, Hamburg pointed out that the doses of resveratrol used in the study were much greater than exists in a glass of red wine, a major dietary source of the antioxidant.

For now, the overall recommendation is to have a diet that’s rich in fruits and vegetables.

In animal studies, resveratrol has been shown to activate a “longetivity” gene (SIRT1) that appears to delay aging and development of several diseases ¹⁵⁾, ¹⁶⁾.

To see if the same thing would happen in humans, the same researchers took samples from the blood-vessel linings of seven patients and looked at SIRT1 activity. They found that gene activity increased slightly after resveratrol supplementation. This doesn’t prove that reservatrol activates the longevity gene, only that there was an association.

This study shows that a natural antioxidant in these foods can reverse age-related changes in the arteries.

Impressively, the effect was seen after just a few weeks of treatment. Who knows what more prolonged antioxidant treatment could do to the arteries and other organs. Many people obtain resveratrol in their daily diet.

However, a recent phase 2 study of SRT501, a micronized oral formulation of resveratrol that activates SIRT1, in multiple myeloma patients was halted early owing to a high level of adverse effects and renal failure ¹⁷⁾.

Another cloud: a company called Sirtris Pharmaceuticals, which was established to develop drugs from resveratrol, pulled the plug on the program in 2010 when a clinical trial showed that one of these drugs might be linked to kidney damage ¹⁸⁾.

Resveratrol and Anti-aging and Anti-cancer ¹⁹⁾

Resveratrol is being examined in at least 110 clinical trials on: age-related macular degeneration, aging, Alzheimer’s disease (AD), cancer including, (colon, follicular lymphoma, liver cancer, multiple myeloma (MM) and neuroendocrine tumors), cardiovascular problems including, (diastolic heart failure, hypertensive heart disease, cerebral blood flow, heart failure, heart failure with preserved ejection fraction), chronic renal insufficiency, cellulite, cognitive disorders, dyslipidemia, diabetes, diabetic nephropathy, endometriosis, eye diseases, Friedreich Ataxia, Huntington disease, memory, metabolic disorders, mood disorders, polycystic ovary syndrome (PCOS), seasonal allergic rhinitis, nonalcoholic fatty liver disease, peripheral arterial disease, obesity, schizophrenia, sedentary lifestyle, sports concussion, and other disorders.

In summary ²⁰⁾, the anti-aging, anti-cancer, anti-neurological effects of resveratrol have been examined in many different diseases and environments. While there have been many beneficial effects postulated to be induced by consumption of resveratrol, the concentrations required to obtain those health benefits may be high. Although, there probably are many beneficial health effects of consumption of products rich in resveratrol. A good, well-balanced diet may prevent certain diseases from occurring ²¹⁾.

In another study published online by JAMA Internal Medicine on May 12, 2014 ²²⁾, researchers report that dietary resveratrol did not affect health, longevity in the population study. The study participants were men and women, 65 years or older, who participated in the Invecchiare in Chianti, “Aging in the Chianti Area” (InCHIANTI) Study, conducted in 2 small towns in Tuscany, Italy.  Resveratrol levels achieved with a Western diet did not have a substantial influence on health status and mortality risk of the population in this study.

Results are based on data collected from 1998 to 2009, as part of the Invecchiare in Chianti Study (“Aging in the Chianti Region”). The team of scientists from America and Italy, including NIA Scientific Director Dr. Luigi Ferrucci, found that resveratrol in the diet was not associated with a reduced incidence of cardiovascular disease, cancer, and inflammation, nor was it associated with longevity.

In the paper ²³⁾, researchers note the interest in resveratrol supplementation in the U.S. and elsewhere, and they caution against use of such supplements based on animal data thus far. The paper states there is “limited and conflicting human clinical data demonstrating any metabolic benefits of resveratrol, and there is no data concerning its safety in high doses or for long-term supplementation in older people, who often have multiple comorbidities for which they are taking multiple medications.”

The study authors suggest that more research with a larger group of participants is needed to determine whether resveratrol could have benefits in people, especially those who are overweight with health issues like diabetes.

Natural Medicines Comprehensive Database rates effectiveness based on scientific evidence.

Insufficient evidence to rate effectiveness of Resveratrol for:

• Acne. Early evidence shows that applying a gel containing resveratrol to the face might reduce the severity of acne.
• Lung disease (chronic obstructive pulmonary disease, COPD). Early research suggests that taking a combination product containing resveratrol, vitamin C, zinc, and flavonoids slightly reduces coughing and mucus production in people with COPD.
• Diabetes. Some research suggests that taking 5 mg of resveratrol twice daily for 4 weeks does not affect insulin levels in people with diabetes. However, other evidence shows that taking a specific product that contains resveratrol (Biofort) daily for 3 months reduces blood sugar, blood pressure and fat levels in the blood.
• “Hardening of the arteries” (atherosclerosis).
• High cholesterol.
• Preventing cancer.
• Other conditions.

More evidence is needed to rate resveratrol for these uses.

How much resveratrol should you take ?

Resveratrol is an unproven treatment and there is no standard dose.

Given the lack of evidence about their safety, resveratrol supplements are not recommended for children or for women who are pregnant or breastfeeding.

Taking resveratrol supplements comes with some risks ²⁴⁾, because no one knows

• the safe, effective dose for humans
• how long-term use will affect us for better or for worse.

That makes taking a resveratrol supplement a bit of an experiment—sort of like the tests on lab mice. A big difference is that mice have researchers assessing their response to resveratrol, but we don’t. If you take a resveratrol supplement, or plan to, let your doctor know so you both can be alert for any possible harms.

If you believe that resveratrol will help you live longer and healthier, get it from food or wine, not by choking down resveratrol pills. Why ? Eating red grapes, blueberries, and pistachios, or having a glass of your favorite red wine, are pleasurable ways to take in resveratrol. Plus you get all the other healthful plant products that come with the resveratrol.