Resveratrol

Assessment and Plan: Resveratrol

• Resveratrol has promising potential health benefits against cancer, heart disease, and nervous system deterioration but there is not enough research-based evidence to ensure either the benefits or safety in humans. Resveratrol supplements may be a dangerous due to the lack of regulation, unknown effective dose, and lack of standardization.

• There have been several promising potential benefits of resveratrol on various cancers in in-vitro and in animal studies requiring research for confirmation in humans.

• Oral administration of resveratrol to animals was found to reduce tumor formation in animal models of colon cancer (2).

• An in-vitro study showed that resveratrol inhibited the growth of multiple myeloma cells regardless of sensitivity or resistance to conventional chemotherapy agents (3).

• Cecchinato, V. et al found that resveratrol encouraged apoptosis (cell death) in acute lymphoblastic leukemia cells by inhibiting the survival signaling pathways, and increased production of pro-apoptotic proteins (4).

• Lu R et al found that resveratrol inhibited growth of estrogen receptor-positive breast cancer cells in vitro resulting in the inhibition of human breast cancer cell growth (5).

• Zhou HB, et al found that resveratrol suppressed the growth of esophageal cancer cells by inducing apoptosis (cell death) in a dose and time dependent way (6).

• Resveratrol was found to possess several potential benefits for heart health in in-vitro and in animal studies requiring more research for confirmation in humans.

• Fukuda, S et al found that resveratrol promoted angiogenesis (growth of new blood vessels) from pre-existing vessels of an ischemic heart (restriction in blood supply to tissues) in a rat model of myocardial infarction (MI) (7).

• Resveratrol at a dose of 2.5 or 5 mg/kg improved post-ischemic ventricular recovery, reduced myocardial infarct size, and reduced cardiomyocyte cell compared to the control group, but doses at 25 or 50 mg/kg had multiple harmful heart effects (8).

• Sato et al. demonstrated that an ethanol-free red wine extract and trans-resveratrol are cardio-protective against ischemia (restriction in blood supply to tissues) by functioning as a strong antioxidant (9). These findings support the benefits of red wine on heart health which may be a much safer way of obtaining the benefit of resveratrol rather than resveratrol supplements due to safety concerns of lack of regulation, unknown effective dose, and lack of standardization.

• Resveratrol (and red wine) also provides cardio-protection by mechanism of the inhibition of platelet aggregation (10). This may result in lower risk of thrombosis in atherosclerotic coronary arteries.

• Resveratrol enhanced longevity in mice but there is no reliable research yet available on lifespan enhancement by resveratrol in humans. A study conducted on middle-aged mice on high-calorie diets found that resveratrol improved insulin function, increased mitochondria, improved motor function, minimized ill effects of a high-calorie diet, produced the effects of calorie restriction, and extended the lifespan of middle-aged mice (12).

• Resveratrol may help prevent neuronal loss in patients multiple sclerosis (MS), but more research is needed. Researchers used extremely high doses of resveratrol in mice which reduced damage to axons of nerve cells (11). The doses used in the study are extremely unsafe in humans but a lower dose may be a potential therapy for MS in the future. As noted above, high doses were associated with detrimental cardiac effects (8).

• Resveratrol and COPD: Researchers believe that resveratrol may be an effective future treatment option for COPD by reducing the release of interleukins significantly (16), but more research is needed.

• Resveratrol adverse reactions, interactions:

• Resveratrol-treated rabbits had an increase in atherosclerotic lesions compared to a control group (13). This suggests that resveratrol results in atherosclerotic development, rather than protecting against it.

• Resveratrol had no adverse effects at a dose of 300 mg per kilogram but had multiple toxicities at doses of 3000 mg per kilogram including elevated BUN, creatinine, alkaline phosphatase, alanine aminotransferase, total bilirubin, and albumin; reduced hemoglobin, hematocrit, and red cell counts; and increased white cell counts, renal (kidney) lesions, increased liver weights among females, reduced body weight gain with 1000 mg per kilogram (females only), and elevated white blood cell count with 1000 mg per kilogram (males only) (14).

• Juan, et al found that trans-resveratrol given to rats at a dose of 20 mg orally per kilogram did not result in toxic adverse events (15).

• Platelet aggregation in hypercholesterolemic rabbits was inhibited both by resveratrol at a dose of 4 mg per kilogram, and with Chinese red wine was given with or without alcohol at 4 ml/kg/day (9). Therefore resveratrol may result in an increased risk of bleeding in patients with bleeding disorders or in patients taking warfarin, Coumadin, heparin, aspirin, and non-steroidal anti-inflammatory medications.