Who Should Not Take Resveratrol

The plant origin of resveratrol creates the impression that it suits everyone. In reality, in concentrated form it is a biologically active substance that affects blood clotting, liver enzymes and, possibly, hormone receptors. Our editorial team explains who should give up the supplement or take it only after consulting a doctor.

Why a Supplement Has Contraindications

Resveratrol does not have an official package insert with an approved list of contraindications, as medicines do. Therefore, the list of risk groups is formed on the basis of three sources: the pharmacological properties of the substance, clinical studies with adverse events, and the assessments of regulators who determine for whom safety has not been established.

From a pharmacological point of view, resveratrol has at least three properties that create potential conflicts. It inhibits platelet aggregation under laboratory conditions (Pace-Asciak et al., 1995), changes the activity of cytochrome P450 enzymes in humans (Chow et al., 2010) and interacts with estrogen receptors in cell models (Gehm et al., 1997).

In its opinion on synthetic trans-resveratrol, EFSA recognized a dose of up to 150 mg per day as safe specifically for adults, and separately noted that pregnant and breastfeeding women are not the target group for such a product due to a lack of data. This is a typical approach of regulators to novel food products.

It is also worth distinguishing between dietary sources and supplements. Grapes, berries or peanuts contain microdoses of resveratrol, and there are no restrictions on consuming them within a normal diet. All the warnings below concern specifically concentrated capsules and powders.

Pregnancy, Breastfeeding, Children

During pregnancy, taking resveratrol supplements is not recommended. There are no controlled studies of safety for the fetus, and a substance that affects vascular tone, blood clotting and cellular signaling pathways could theoretically affect the development of the placenta and fetus. In such a situation the precautionary principle applies.

The same applies to the breastfeeding period. It is unknown in what amount resveratrol and its metabolites pass into breast milk and how they affect the infant. In the absence of data, most specialists advise refraining from any nonessential biologically active supplements.

Children and adolescents do not need resveratrol supplements. For them there are neither proven indications nor data on the safety of long-term intake. The effect on hormone receptors during puberty is an additional argument in favor of avoiding concentrated forms.

Women planning a pregnancy would be wise to stop taking it in advance and to discuss all supplements with a doctor at the planning stage.

People Taking Medications

The most numerous group for which resveratrol requires caution is people on ongoing drug therapy. In the study by Chow and colleagues (2010), taking 1 g per day for four weeks inhibited CYP3A4, CYP2C9 and CYP2D6 and induced CYP1A2. These enzymes are responsible for the metabolism of a significant portion of modern medicines.

Special attention goes to people with transplanted organs. Immunosuppressants have a narrow therapeutic window: even a moderate change in their concentration can lead either to toxicity or to rejection. For such patients, any new supplement must be coordinated with a transplant specialist.

People taking drugs with a narrow therapeutic range — some antiepileptic and antiarrhythmic agents — should also discuss resveratrol with a doctor. It is impossible to independently assess the risk of interaction in such cases.

It is important that most data on interactions were obtained at a dose of about 1 g. For doses of 100–250 mg the risk is probably lower, but "probably" is an insufficient basis for patients on critical therapy.

Diseases and Conditions That Require Caution

Blood clotting disorders.For people with hemophilia, thrombocytopenia, von Willebrand disease or a tendency to bleeding, resveratrol is not recommended. Its antiplatelet action, though moderate, can increase the risk of bleeding.

Planned surgeries and dental procedures.It is advisable to stop taking it at least two weeks before an intervention and to be sure to inform the surgeon and anesthesiologist. This is standard caution for supplements with antiplatelet action.

Hormone-dependent conditions.In laboratory models, resveratrol behaves as a mixed agonist-antagonist of estrogen receptors (Bowers et al., 2000). Its clinical significance is unknown, so for people with a history of breast, ovarian or uterine cancer, endometriosis or fibroids, intake is possible only after a doctor's decision.

Kidney diseases.In a phase II study of micronized resveratrol at a dose of 5 g per day in patients with myeloma, cases of acute kidney injury were recorded (Popat et al., 2013). Although this is a specific situation, people with chronic kidney disease would do better to avoid high doses.

Diseases of the liver and intestine.Resveratrol is actively metabolized in the liver, and the unabsorbed portion of the dose irritates the intestine. In the presence of chronic liver diseases, inflammatory bowel diseases or irritable bowel syndrome, the decision to take it should be made together with a doctor.

A Self-Check Before Starting

Before buying resveratrol, our editorial team suggests honestly answering a few questions. If the answer to even one of them is "yes," intake should be discussed with a doctor rather than decided on your own.

• Do you take any prescription drugs on an ongoing basis?
• Do you have a tendency to bleeding, bruising or a blood disease?
• Are you planning surgery or a dental procedure within the next month?
• Do you have, or have you had, hormone-dependent diseases?
• Do you have chronic diseases of the kidneys, liver or intestine?
• Are you pregnant, planning a pregnancy or breastfeeding?

Athletes who strive for maximum adaptation to endurance training should take into account the data of Gliemann and colleagues (2013) on a possible weakening of training effects. This is not a contraindication in the medical sense, but an argument to weigh the advisability of taking it.

If there are no warnings, this does not mean the supplement is necessarily needed. The value of resveratrol for a healthy person remains a subject of debate, and the decision to take it should be made consciously rather than under the influence of advertising.

While taking it, pay attention to unusual bruising, bleeding gums, persistent digestive disorders or a rash. If they appear, stop taking it and see a doctor.

Editorial Conclusions

Concentrated resveratrol is not suitable for pregnant or breastfeeding women, children, people with blood clotting disorders, or patients on immunosuppressants.

Taking anticoagulants, antiplatelet agents, statins and other drugs metabolized via CYP enzymes, as well as hormone-dependent conditions and kidney or liver diseases, require mandatory coordination with a doctor.

For healthy adults without ongoing therapy, moderate doses are usually well tolerated, but even here intake should be stopped before surgeries and if unusual symptoms appear.

We also recommend reading our materials about the side effects of resveratrol, about how to take it, and about what it can be combined with.

References

1. Chow HHS, Garland LL, Hsu CH, et al. Resveratrol modulates drug- and carcinogen-metabolizing enzymes in a healthy volunteer study. Cancer Prev Res. 2010;3(9):1168–1175.
2. Pace-Asciak CR, Hahn S, Diamandis EP, Soleas G, Goldberg DM. The red wine phenolics trans-resveratrol and quercetin block human platelet aggregation and eicosanoid synthesis: implications for protection against coronary heart disease. Clin Chim Acta. 1995;235(2):207–219.
3. Gehm BD, McAndrews JM, Chien PY, Jameson JL. Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. Proc Natl Acad Sci USA. 1997;94(25):14138–14143.
4. Bowers JL, Tyulmenkov VV, Jernigan SC, Klinge CM. Resveratrol acts as a mixed agonist/antagonist for estrogen receptors alpha and beta. Endocrinology. 2000;141(10):3657–3667.
5. Popat R, Plesner T, Davies F, et al. A phase 2 study of SRT501 (resveratrol) with bortezomib for patients with relapsed and or refractory multiple myeloma. Br J Haematol. 2013;160(5):714–717.
6. Gliemann L, Schmidt JF, Olesen J, et al. Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men. J Physiol. 2013;591(20):5047–5059.
7. EFSA Panel on Dietetic Products, Nutrition and Allergies. Safety of synthetic trans-resveratrol as a novel food pursuant to Regulation (EC) No 258/97. EFSA J. 2016;14(1):4368.