Safety of synthetic trans‐resveratrol as a novel food pursuant to Regulation (EC) No 258/97

Abstract

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked for an opinion on the safety of synthetic trans-resveratrol as a novel food with a purity of ≥99% (w/w). The Panel considers that the information provided on the composition and specifications of the novel food is sufficient. The applicant intends to market the novel food as a food supplement in capsule or tablet form at daily doses up to 150 mg/day. The Panel considers that resveratrol does not have a nutritionally relevant role in the human diet and that the consumption of the novel food is not nutritionally disadvantageous. In accordance with the EFSA Scientific opinion on genotoxicity testing strategies, the Panel considers that the negative in vivo genotoxicity assay is sufficient to rule out the concern based on the positive in vitro chromosomal aberration tests.Reduced body weight gain is seen consistently in animal studies. On the basis of the BMDL 05 of 344 mg/kg body weight (bw) per day derived from body weight data of female rats in a subchronic toxicity study and the intended intake of 150 mg/day, the margin of exposure is 172. For pregnant rats, it is below 62. Considering the weight of evidence, the Panel concludes that the intended intake level of 150 mg/day for adults does not raise safety concerns. The Panel notes that diarrhoea or other gastrointestinal symptoms were reported in four uncontrolled intervention studies at doses of 1 g resveratrol/day or higher. The Panel considers that the metabolite trans-resveratrol sulfate could inhibit CYP enzymes in humans and may interact with medicines which are mainly metabolised by CYP2C9. The Panel concludes that the novel food, synthetic trans-resveratrol, is safe under the proposed conditions of use.

Resveratrol, lunularin and dihydroresveratrol do not act as caloric restriction mimetics when administered intraperitoneally in mice

“…For example, the inhibitor of the cell-growth- and proliferation-regulating kinase mTOR rapamycin is an immunosuppressant and 2-deoxyglucose, which inhibits glycolysis, was cardiotoxic in rats when administered chronically 25,26 . In contrast, chronic resveratrol intake seems to be safe as stated by the European Food and Safety Authority 27 . However, not all studies observed a positive impact of resveratrol on lifespan and therefore do not support a role of resveratrol as putative CRM.…”

“…In 2016, the EFSA concluded that resveratrol supplements up to 150 mg/day were safe for human use 27 . Thus, we chose a dose of approximately 10 mg resveratrol (or equimolar bioacatives)/day *kg mouse.…”

In Contrast to Dietary Restriction, Application of Resveratrol in Mice Does not Alter Mouse Major Urinary Protein Expression

“…trial was carried out prior to the feeding trial. In a first attempt to study RSV-induced changes in mice that may benefit ageing-related parameters, middle-aged mice and a dose that, considering allometric scaling [36], would be considered safe [37], were used. Since RSV application did not change mouse phenotype at a moderate dose of supplementation in 14 month old mice [35], we chose a dietary application at an approx.…”

The Heme Oxygenase/Biliverdin Reductase System as Effector of the Neuroprotective Outcomes of Herb-Based Nutritional Supplements

“…It is worth mentioning the document released by the EFSA regarding the request by the European Commission on the safety of trans-resveratrol as a novel food (Efsa, 2016). In this document, the EFSA established that the 38 clinical studies provided in support of the claim do not lead to any conclusion about the efficacy of resveratrol, at doses up to 5 g/day for either acute (4 days) or chronic administration (4–12 weeks), in the treatment of metabolic diseases or cancer.…”