Beneficial and cautionary outcomes of resveratrol supplementation in pregnant nonhuman primates

Abstract

Resveratrol has been proposed as a potential therapeutic to improve metabolic health during pregnancy, yet little is known about the fetal effects of this maternal dietary supplement. We hypothesized that when administered to pregnant nonhuman primates (NHPs), resveratrol would increase uterine blood flow and mitigate the harmful consequences of maternal Western-style diet (WSD) consumption. NHPs were fed a WSD (36% fat) supplemented with 0.37% resveratrol throughout pregnancy. Outcomes were compared with cohorts fed WSD alone and control chow (14% fat) to distinguish between WSD and resveratrol-specific effects in these animals. In the early third trimester, uterine blood flow was measured by Doppler ultrasound before fetal delivery and tissue collection. Resveratrol resulted in 30% maternal weight loss and improved glucose tolerance, increased uterine artery volume blood flow, and decreased placental inflammation and liver triglyceride deposition. In addition, fetal pancreatic mass was enlarged by 42%, with a 12-fold increase in proliferation by Ki67 immunohistochemistry. These results demonstrate that resveratrol use during pregnancy yields improvements in maternal and placental phenotype with beneficial effects in the fetal liver but an unexplained and concerning alteration in fetal pancreatic development, which strongly cautions against the use of resveratrol by pregnant women.

Impact of maternal nutrition in pregnancy and lactation on offspring gut microbial composition and function

“…67 Furthermore, work in a non-human primate model has demonstrated that placental inflammation is increased with a maternal high fat diet. 71,72 Intriguingly, work in this same model has provided early evidence that the offspring microbiome is altered in association with maternal diet. 39 In this study, dams were either provided a high-fat diet or a control diet prior and during pregnancy and lactation.…”

Consumption of a Western-style diet during pregnancy impairs offspring islet vascularization in a Japanese macaque model

“…Although human studies have not yet assessed the safety or efficacy of resveratrol treatment during pregnancy in women consuming a WSD, our group demonstrated recently in our NHP model of WSD consumption during pregnancy that supplementation improved placental blood flow, consistent with its role in enhancing vascular function (52). However, this was accompanied by a concerning increase in total pancreas mass and proliferation and an elevation in the ␤-cell/␣-cell ratio (52). In this study, resveratrol supplementation during pregnancy resulted in a significant increase in islet vascularization, consistent with its known vasodillatory effect.…”

Resveratrol and its oligomers: modulation of sphingolipid metabolism and signaling in disease

“…Very recently, resveratrol administered to nonhuman primates was found to exhibit several health benefits as observed from rodent studies. However, an abnormal developmental effect was found in fetal pancreas, arguing against the use of resveratrol in pregnant woman (Roberts et al 2014). Resveratrol might also interact with other dietary supplements or drugs as it inhibits human cytochrome P450 (CYP) enzymes (Baur and Sinclair 2006).…”