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Side Effects of Resveratrol

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Resveratrol is generally considered beneficial and protective of health. At this point, not enough clinical studies report on its harmful effects. The tolerability depends on the dose, varying gut microbiota, health status, and bioavailability of resveratrol. However, it has been linked to certain unfavorable side effects in a limited number of instances.

Dosage Dependency of Resveratrol

Resveratrol has a direct correlation with cell apoptosis. Resveratrol serves as an anti-apoptotic drug at low doses, protecting the heart by enhancing cell survival proteins. At greater doses, however, resveratrol acts as a pro-apoptotic chemical, inducing apoptosis in cancer cells via a “death signal.” Additionally, at larger dosages, resveratrol has the ability to inhibit the development of pre-existing tumors. Thus, resveratrol may be extremely beneficial in sustaining human health at low doses, yet at large doses, resveratrol can be toxic to healthy cells but has the power to destroy cancer cells.

Oxidizing Agent 

Research suggests that it may act as a pro-oxidizing agent in the body. Rather of consistently slowing or preventing the cell damage caused by free radicals, resveratrol may demonstrate pro-oxidant characteristics, resulting in cellular DNA damage and oxidative stress.

Small Vs Large Doses.

In general, if a person consumes resveratrol in small doses over a short period of time, they will not suffer any negative effects. However, with daily dosages of 2.5 g or more, the following adverse effects may occur:

One participant in a 2016 study got fever and cytopenia (low blood cell count) when consuming 1.5 g resveratrol per day for 6 months.

When taken orally: Resveratrol is commonly found in modest levels in foods. When used orally in quantities of up to 1500 mg daily for up to three months, resveratrol supplements may be safe. For 2-6 months, higher dosages of up to 2000-3000 mg daily have been used successfully. These greater dosages, however, are more likely to induce gastrointestinal trouble.

Skin Application: Resveratrol may be safe to take for up to 30 days.

Nasal Spray: Resveratrol is possibly safe when used for up to 4 weeks.

POSSIBLE RISKS OF RESVERATROL

Pregnancy and Lactation. 

When consumed in the proportions found in some foods, resveratrol is most likely safe. However, the source of resveratrol is critical during pregnancy and breastfeeding. Resveratrol can be found in grape skins, grape juice, wine, and a variety of other foods. When pregnant or breastfeeding, wine should not be consumed as a source of resveratrol and must be avoided.

Blood Disorders and Surgery.

In those with bleeding problems, resveratrol may decrease blood coagulation and increase the risk of bleeding. It also has been linked to an increase in the risk of bleeding during and after surgery. So it is advised to stop using resveratrol at least two weeks before surgery.

Estrogen Related Conditions.

Resveratrol has the potential to mimic estrogen. If anyone has a disease that might be exacerbated by estrogen exposure like breast cancer, uterine cancer, ovarian cancer, endometriosis, or uterine fibroids, they avoid using resveratrol. Women having a history of estrogen-sensitive malignancies, such as breast, ovarian, and uterine cancers, should avoid resveratrol supplements until more is known about its estrogenic effect in humans.

Interactions With Medications. 

Resveratrol has been found interacting with below drugs and effecting their efficacy. A dosage of 1000 mg / 1 g per day or above was reported to inhibit cytochrome P450 thus leading to interactions with many other drugs.

  • Carbamazepine: The effects of resveratrol pretreatment on carbamazepine pharmacokinetics and CYP3A4 enzyme activity were investigated in 12 healthy males. It raised peak drug concentration (46.2%), area under the curve (37.1%), and half-life (22.8%) compared to control, and decreased apparent oral clearance (33.1%), apparent volume of distribution (33.1%) of carbamazepine (compared to control) (by 19.3 percent ). The Cmax and AUC parent ratios of carbamazepine metabolites were similarly reduced.
  • Anticoagulants/Antiplatelet Drugs: Resveratrol may help blood clot more slowly. When used with drugs that decrease blood coagulation, resveratrol may increase the risk of bruising and bleeding.
  • Medications changed by the liver (Cytochrome P450 1A1 (CYP1A1) substrates): CYP enzymes are phase I biotransformation enzymes involved in the metabolism of endogenous substances and medicinal drugs. The most common CYP isoform in the human liver and intestines is CYP3A4, which is responsible for half of all medications sold in the US. Resveratrol may alter the rate at which these drugs are metabolized by the liver. This may alter the efficacy and safety of these drugs.
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