Fasting-Mimicking Diet Reduces Trimethylamine N-Oxide Levels and Improves Serum Biochemical Parameters in Healthy Volunteers.

Eduards Sevostjanovs,Maija Dambrova,Sabine Upmale-Engela,Melita Videja,Ilze Konrade,Edgars Liepinsh

doi:10.3390/nu14051093

Eduards Sevostjanovs, Maija Dambrova + Show 4 more

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https://doi.org/10.3390/nu14051093

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Abstract

Elevated plasma levels of trimethylamine N-oxide (TMAO) have been proposed as a diet-derived biomarker of cardiometabolic disease risk. Caloric restriction is the most common dietary intervention used to improve cardiometabolic health; however, novel trends suggest a fasting-mimicking diet (FMD) as a more feasible alternative. FMD is a variation of intermittent fasting, based on caloric restriction and limitation of protein sources of animal origin, applied in daily cycles during a 5-day period. As TMAO is intensively produced by gut microbiota after the consumption of animal-derived products, we aim to investigate whether a 5-day FMD affects plasma TMAO levels and markers of metabolic health. To investigate whether an increase in vegetable intake possesses similar effects on TMAO levels and metabolic parameters, healthy volunteers (n = 24) were subjected to a 5-day FMD and 19 volunteers served as a reference group (VEG). This group of volunteers consumed an additional four servings of vegetables per day, but otherwise stayed on their usual diet. FMD resulted in a twofold decrease in plasma TMAO levels, which was not evident in the volunteers from the VEG group. Moreover, FMD led to a weight loss of 2.8 ± 0.2 kg and a subsequent reduction in BMI compared to baseline. The FMD group exhibited a significant elevation in plasma ketone bodies (14-fold compared to baseline) and a decrease in IGF-1 levels by 37 ± 8 ng/mL. Since fasting glucose and C-peptide levels decreased, all volunteers in the FMD group showed improved insulin sensitivity and a decreased HOMA-IR index. In contrast, in the VEG group, only a slight reduction in plasma levels of fasting glucose and triglycerides was noted. In conclusion, we show that FMD is a viable strategy to reduce plasma levels of TMAO by limiting caloric intake and animal-derived protein consumption. The reduction in the level of TMAO could be an additional benefit of FMD, leading to a reduced risk of cardiometabolic diseases.

Highlights

In 8 out of 19 volunteers, we observed a reduction in plasma trimethylamine N-oxide (TMAO) levels after the dietary intervention; 11 volunteers experienced an increase in plasma TMAO levels
We demonstrate that 5 days of fasting-mimicking diet (FMD) is a viable dietary strategy to reduce plasma levels of TMAO, which is a diet-derived cardiovascular and metabolic disease risk biomarker
Our data suggest that the reduction in TMAO and improvement in the parameters that characterize glucose metabolism and the general metabolic state in healthy volunteers are attributed to intermittent energy restriction and the limitation of animal-derived protein consumption rather than increased vegetable intake

Summary

Introduction

Despite the well-known relationship between unhealthy dietary patterns and an increased risk of cardiovascular and metabolic diseases, research continuously tries to identify novel diet-derived culprits that are responsible for the molecular mechanisms that cause the detrimental health effects. One study that attempted to link dietary choices and cardiometabolic health identified that the gut microbiota metabolite trimethylamine N-oxide (TMAO) is associated with a higher incidence of adverse cardiovascular outcomes [1]. In turn, have added to this knowledge by identifying a TMAO plasma concentration of 6.18 μmol/L as a major adverse cardiovascular event risk threshold [10]. T2D patients with elevated plasma levels of TMAO are more susceptible to major adverse cardiovascular events, such as myocardial infarction, hospitalization for heart failure and unstable angina [13]

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