Clinical and Dietary Determinants of Ketosis During Long-Term Fasting in 1610 Subjects

OBJECTIVES: The health-promoting effects of fasting are increasingly documented. Long-term fasting according to the Buchinger Wilhelmi program (200 kcal/day, approximately 30 grams of carbohydrates) elicits various health-improving effects. The metabolic switch from glucose to fat oxidation is associated with an elevation in urine ketone concentrations (ketonuria). We hypothesised that inter-individual differences in ketonuria are due to variations in daily intake of carbohydrate facultative supplements. We further hypothesised that changes in ketonuria are linked to the beneficial effects of therapeutic fasting on an individual basis, and that these could be predicted from a person's demographic data and metabolic status before they entered the fasting program. METHODS: We evaluated daily variations in carbohydrate intake and ketonuria in a group of 1610 subjects during a 4 to 21-day fasting period. Ketosis was estimated non-invasively in urine with Ketostix strips. Unsupervised hierarchical clustering of ketonuria was used to stratify patients as subgroups. Random Forest classification was performed using R package Caret. Differences in the effects of fasting between the different subgroups were model-predicted estimated marginal means. RESULTS: Ketonuria was less intense in individuals who consumed honey and/or juice, which corresponded to a daily carbohydrate intake of approximately 30 grams. Participants with high ketonuria were younger, had lower blood urea concentrations, and lower HDL levels, before they entered the fasting program. Subjects excreting the largest amounts of ketones in their urine had a larger decrease in blood glucose levels, glycated haemoglobin (HbA1c) levels, body weight and waist circumference, and a larger increase in blood uric acid concentrations, in the group of patients. CONCLUSIONS: We showed that even a low level carbohydrate intake influences ketonuria during long-term fasting. The course of ketonuria could be predicted based on a patient's characteristics before they entered the fasting program. Individuals with the most intense ketonuria presented the most pronounced metabolic changes during long-term fasting. Altogether, our study paves the way to the establishment of personalised long-term fasting strategies. FUNDING SOURCES: This study was funded by Amplius GmbH, Überlingen, Germany.