Pilot Study of Novel Intermittent Fasting Effects on Metabolomic and Trimethylamine -oxide Changes During 24-hour Water-Only Fasting in the FEELGOOD Trial.

Nutrients. 2019;11(2)

Plain language summary

Intermittent fasting – the practice of significantly cutting food intake on a number of days and eating normally on others – has been connected with numerous health benefits such as weight loss, reduced risk of heart disease and Type 2 diabetes, longer life span and improved quality of life. This randomised, cross over trial of 30 healthy individuals sought to evaluate the effects of fasting on Trimethylamine N-oxide (TMAO) levels, a substance produced in humans by intestinal bacteria and associated with heart disease in humans. 74 other metabolites were also measured. Subjects were randomised to a ‘fasting first’ group, with water-only intake for 24 hours, followed by 24 hours of eating freely, or an ‘eating first’ group, before crossing over. Measurements were made at baseline, at the end of the fasting day and at the end of the eating day. The authors found that TMAO levels decreased on the fasting day compared to the eating day. These levels returned to pre-fasting levels within 24 hours. 30 of the other 74 metabolic markers, including some amino acids and fatty acids, achieved significant changes between fasting and eating days. The authors suggest that consistent and repeated episodes of intermittent fasting may lead to improved health and reduced risk of heart disease and diabetes. Nutrition Practitioners may wish to consider intermittent fasting when working with clients with these conditions.


undefined: Intermittent fasting (IF) has been connected with health benefits such as weight loss, lower risk of coronary artery disease (CAD) and diabetes, increased longevity, and improved quality of life. However, the mechanisms of these IF benefits in humans require further investigation. This study sought to elucidate some of these mechanisms through secondary analyses of the Fasting and ExprEssion of Longevity Genes during fOOD abstinence (FEELGOOD) trial, in which apparently healthy participants were randomized in a Latin square design to a 24-h water-only fast and a 24-h ad libitum fed day. Two pathways were investigated, with trimethylamine -oxide (TMAO) levels measured due to their association with elevated risk of CAD, along with conductance of a broad panel of metabolic analytes. Measurements were made at baseline, at the end of the fasting day, and at the end of the fed day. A fasting mean of 14.3 ng in TMAO was found versus the baseline mean of 27.1 ng with = 0.019, although TMAO levels returned to baseline on refeeding. Further, acute alterations in levels of proline, tyrosine, galactitol, and urea plasma levels were observed along with changes in 24 other metabolites during the fasting period. These acute changes reveal short-term mechanisms which, with consistent repeated episodes of IF, may lead to improved health and reduced risk of CAD and diabetes.

Lifestyle medicine

Patient Centred Factors : Mediators/Intermittent fasting
Environmental Inputs : Diet ; Microorganisms
Personal Lifestyle Factors : Nutrition
Functional Laboratory Testing : Blood
Bioactive Substances : Trimethylamine N-oxide ; TMAO ; Proline ; Tyrosine ; Galactitol ; Urea

Methodological quality

Allocation concealment : Not applicable


Nutrition Evidence keywords : Water fasting ; Heart disease ; Calorie restriction