Grundler · Nutrients 2024 · prospective observational cohort study · n=1610

Long-Term Fasting-Induced Ketosis in 1610 Subjects: Metabolic Regulation and Safety.

Cited 24 times in the scientific literature.

Level 4 - case-series / case-control

Uncontrolled prospective observational cohort study without a non-fasting comparator group.

PubMed 38931204 · doi:10.3390/nu16121849 · record verified 2026-08-31

What was done

Daily variations in fasting ketonemia and ketonuria were monitored in a cohort of 1,610 subjects fasting for 4 to 21 days according to the Buchinger Wilhelmi program. Participants received minimal caloric supplementation of approximately 75 to 250 kcal per day (consisting of daily fruit juice, vegetable soup, and honey), and the intensity of ketosis was evaluated alongside metabolic changes and participant characteristics.

What was found

Ketonuria appeared in more than 95% of participants from day 4 onwards. Subjects who consumed only vegetable soup without fruit juice or honey had lower caloric intake (72 kcal vs. 236 kcal) and lower carbohydrate intake (15.6 g vs. 56.5 g), resulting in more intense ketonuria. High ketonuria occurred predominantly in younger males with higher body weight, lower baseline HDL-C, and lower baseline urea. These individuals exhibited greater decreases in blood glucose, glycated hemoglobin, body weight, and waist circumference, alongside a larger increase in blood uric acid concentration. Ketosis never reached pathological levels.

Why it matters

This study shows that prolonged fasting with low-calorie supplementation consistently triggers physiological ketosis without causing pathological ketoacidosis. It demonstrates that modest carbohydrate supplementation modulates ketosis intensity rather than suppressing it.

Limits

The study was single-arm and lacked a non-fasting or strictly water-only control group. Exact numerical values, ranges, and statistical variance for ketone concentrations, blood glucose, and uric acid were not reported in the abstract. Participants were enrolled in a structured, specialized clinic program, which limits generalizability to unsupervised settings.

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