Inulin Supplementation Does Not Reduce Plasma Trimethylamine N-Oxide Concentrations in Individuals at Risk for Type 2 Diabetes

Abstract

Trimethylamine N-oxide (TMAO) is associated with type 2 diabetes (T2DM) and increased risk of adverse cardiovascular events. Prebiotic supplementation has been purported to reduce TMAO production, but whether prebiotics reduce fasting or postprandial TMAO levels is unclear. Sedentary, overweight/obese adults at risk for T2DM (n = 18) were randomized to consume a standardized diet (55% carbohydrate, 30% fat) with 10 g/day of either an inulin supplement or maltodextrin placebo for 6 weeks. Blood samples were obtained in the fasting state and hourly during a 4-h high-fat challenge meal (820 kcal; 25% carbohydrate, 63% fat; 317.4 mg choline, 62.5 mg betaine, 8.1 mg l-carnitine) before and after the diet. Plasma TMAO and trimethylamine (TMA) moieties (choline, l-carnitine, betaine, and γ-butyrobetaine) were measured using isocratic ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). There were no differences in fasting or postprandial TMAO or TMA moieties between the inulin and placebo groups at baseline (all p > 0.05). There were no significant changes in fasting or postprandial plasma TMAO or TMA moiety concentrations following inulin or placebo. These findings suggest that inulin supplementation for 6 weeks did not reduce fasting or postprandial TMAO in individuals at risk for T2DM. Future studies are needed to identify efficacious interventions that reduce plasma TMAO concentrations.

A Mediterranean diet does not alter plasma trimethylamineN-oxide concentrations in healthy adults at risk for colon cancer

“…The present study population was unique compared to other studies that examined Mediterranean dietary patterns and TMAO concentration in that the population was based in North America. Additionally, the subjects were at increased risk for colon cancer but were otherwise healthy 16,22,38 . The dietary intervention was not associated with reductions in serum TMAO concentration despite elevated fasting concentrations at baseline compared with another study from our group looking at younger adults with lower baseline TMAO concentration 38 .…”

“…Current research is underway to evaluate dietary strategies to reduce TMAO concentration by influencing TMA release by the gut microbiome 7,12,13 . However, previous studies from our group have shown that traditional approaches to modulating the composition and function of the microbiome (prebiotics and probiotics), as well as short-term flavonoid intervention 14 , failed to reduce circulating TMAO concentrations 15,16 . A choline analog (3,3,-dimethylbutanol) has emerged as an effective inhibitor of choline metabolism and subsequent TMAO production in rodents 8 , but this compound is currently not approved for human use.…”

“…TMAO, L-carnitine, choline, betaine and γ-butyrobetaine were measured as described previously [14][15][16]38 with minor modifications. The serum aliquots used for the present analyses of TMAO and related compounds were prepared from fasting blood samples obtained in EDTA tubes and stored at −80˚C.…”

Role of Gut Microbiota-Generated Short-Chain Fatty Acids in Metabolic and Cardiovascular Health

“…Recent evidence from animal studies suggest that soluble dietary fibre reduces TMA and TMAO metabolism by 40.6 and 62.6%, respectively, which was associated with increased SCFA production and reduced serum lipids and cholesterol [ 63 ]. In contrast, inulin supplementation in humans had no effect on fasting or post-prandial TMAO levels [ 64 ], indicating the challenges in translating findings from animals to humans and the complexity of the role of different dietary fibres on microbial activity.…”

Nutritional Strategies in Prediabetes: A Scoping Review of Recent Evidence

“…The effects of inulin [ 70 ], chromium [ 97 ], galacto-oligosaccharides [ 39 ] and betaine [ 73 ] supplementation were reported by one study each. None reported any significant positive metabolic effect nor decrement in diabetic risk factors.…”