Oral Capsaicinoid Administration Alters the Plasma Endocannabinoidome and Fecal Microbiota of Reproductive-Aged Women Living with Overweight and Obesity

Abstract

Capsaicinoids, the pungent principles of chili peppers and prototypical activators of the transient receptor potential of the vanilloid type-1 (TRPV1) channel, which is a member of the expanded endocannabinoid system known as the endocannabinoidome (eCBome), counteract food intake and obesity. In this exploratory study, we examined the blood and stools from a subset of the participants in a cohort of reproductive-aged women with overweight/obesity who underwent a 12-week caloric restriction of 500 kcal/day with the administration of capsaicinoids (two capsules containing 100 mg of a capsicum annuum extract (CAE) each for a daily dose of 4 mg of capsaicinoids) or a placebo. Samples were collected immediately before and after the intervention, and plasma eCBome mediator levels (from 23 participants in total, 13 placebo and 10 CAE) and fecal microbiota taxa (from 15 participants in total, 9 placebo and 6 CAE) were profiled using LC–MS/MS and 16S metagenomic sequencing, respectively. CAE prevented the reduced caloric-intake-induced decrease in beneficial eCBome mediators, i.e., the TRPV1, GPR119 and/or PPARα agonists, N-oleoyl-ethanolamine, N-linoleoyl-ethanolamine and 2-oleoyl-glycerol, as well as the anti-inflammatory N-acyl-ethanolamines N-docosapentaenyl-ethanolamine and N-docosahexaenoyl-ethanolamine. CAE produced few but important alterations in the fecal microbiota, such as an increased relative abundance of the genus Flavonifractor, which is known to be inversely associated with obesity. Correlations between eCBome mediators and other potentially beneficial taxa were also observed, thus reinforcing the hypothesis of the existence of a link between the eCBome and the gut microbiome in obesity.

Capsaicin: A Potential Treatment to Improve Cerebrovascular Function and Cognition in Obesity and Ageing

“…Capsimax is a readily available capsaicin supplement containing 2% capsaicinoids [1.2–1.35% capsaicin, 0.6–0.8% dihydrocapsaicin, and 0.1–0.2% nordihydrocapsaicin]) from 15–25% Capsicum extract, 45–55% sucrose, and 30–35% cellulose gum coatings [ 148 ]. Capsimax prolongs release into the small intestine, which therefore overcomes pungency and related issues associated with direct chilli or capsaicin application [ 148 , 149 , 150 , 151 ]. OmniActive Health Technologies dissolution studies indicate a range of 60–75% of the total capsaicinoids content of Capsimax are released within four hours and are completely released beyond six hours post-ingestion [ 149 ].…”

“…A decrease in calorie consumption of 257 kcal per day and increased serum high-density lipoprotein (HDL) was reported in participants given 200 mg Capsimax, compared to 100 mg Capsimax or placebo at 12 weeks. Similarly, a 12-week study comparing 200 mg Capsimax or placebo alongside a calorie-restricted diet reported reductions in body weight, BMI, waist circumference, and fat mass in overweight and obese women of reproductive age [ 150 ]. This study reported a high dropout rate of 27%, which was due to the difficulties of compliance with the prescribed restrictive diet rather than side effects of the intervention.…”

“…This study reported a high dropout rate of 27%, which was due to the difficulties of compliance with the prescribed restrictive diet rather than side effects of the intervention. As restrictive diets can reduce adiposity [ 158 ], the outcomes found by Manca et al [ 150 ] could therefore be a result of the caloric restriction in this intervention, rather than Capsimax supplementation.…”

Recent advances in analysis of capsaicin and its effects on metabolic pathways by mass spectrometry

“…Frontiers in Nutrition 06 frontiersin.org 12 weeks while taking either capsaicin or a placebo (45). To evaluate the effects of the intervention, pre-and post-intervention blood and stool samples were subjected to LC-MS/MS, wherein the plasma levels of eCBome mediators and 16S metagenomic sequences in fecal microbiome taxa were analyzed.…”

Plant Secondary Metabolites Used for the Treatment of Diseases and Drug Development

“…A further study showed that the oral use of the capsaicinoids (the pungent principles of chilli peppers and prototypical activators of the transient receptor potential of the vanilloid type-1 channel administration) alters the plasma endocannabinoidome and faecal microbiota of reproductive-aged women living with overweight and obesity [3].…”