Substrate utilization during short-term fasting in older men and women

Older people are prone to involuntary fasting, but systematic assessment of their mobilization and oxidation of the three macronutrients during fasting has not been previously reported. Because of changes in body composition and metabolic regulatory pathways with aging, older people might have different kinetics of utilization of macronutrient stores during fasting than younger people. We measured body composition by dual-energy X-ray absorptiometry and studied the effects of a 36-h fast on protein mobilization, lipolysis, glucose output, and protein, fat, and carbohydrate oxidation in 10 older (60-81 yr) and 10 younger (18-35 yr) healthy adults. A 36-h fast induced a pronounced shift toward fat oxidation: in the postabsorptive state, fat oxidation averaged 52%-55% of resting energy expenditure (REE) and increased to 63%-68% after fasting, with corresponding decreases in carbohydrate oxidation. Protein oxidation decreased with fasting but still contributed 16%-18% of REE in older participants. For several metabolic variables (respiratory exchange ratio, glucose <i>R</i><sub>a</sub>, glycerol <i>R</i><sub>a</sub>, urea <i>R</i><sub>a</sub>, urea excretion, and percent of REE from carbohydrate and fat), we observed significant age × fasting interactions (<i>P</i> < 0.01). Younger adults exhibited larger decreases in glucose <i>R</i><sub>a</sub> and greater increases in markers of protein turnover (leucine <i>R</i><sub>a</sub>, urea production) and lipolysis, whereas older adults showed blunted glucose and leucine responses but maintained substantial protein oxidation. These age-related differences suggest that older adults rely relatively more on ongoing protein catabolism during short-term fasting, which may contribute to vulnerability to muscle loss during illness or prolonged inadequate intake.<b>NEW & NOTEWORTHY</b> A 36-h fast had a profound effect on substrate utilization in older women and men. In the postabsorptive state, fat oxidation averaged 52%-55% of REE. After a 36-h fast, fat oxidation increased to 63%-68%, with corresponding decreases in carbohydrate oxidation. The continued reliance on protein oxidation (16%-18% of REE) with fasting may be an important factor in the muscle loss seen in older adults with chronically inadequate food intake and impaired physical activity.

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Journal
American Journal of Physiology-Endocrinology and Metabolism
Published
2026-02-04
DOI
https://doi.org/10.1152/ajpendo.00530.2025
Primary Topic
Muscle metabolism and nutrition
Type
article
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article

Substrate utilization during short-term fasting in older men and women

Naomi K. Fukagawa, San Wang, Rita H. Tsay, Danya Zhang
American Journal of Physiology-Endocrinology and Metabolism
Muscle metabolism and nutrition
article

Substrate utilization during short-term fasting in older men and women

Naomi K. Fukagawa, San Wang, Rita H. Tsay, Danya Zhang
article en

Abstract

Older people are prone to involuntary fasting, but systematic assessment of their mobilization and oxidation of the three macronutrients during fasting has not been previously reported. Because of changes in body composition and metabolic regulatory pathways with aging, older people might have different kinetics of utilization of macronutrient stores during fasting than younger people. We measured body composition by dual-energy X-ray absorptiometry and studied the effects of a 36-h fast on protein mobilization, lipolysis, glucose output, and protein, fat, and carbohydrate oxidation in 10 older (60-81 yr) and 10 younger (18-35 yr) healthy adults. A 36-h fast induced a pronounced shift toward fat oxidation: in the postabsorptive state, fat oxidation averaged 52%-55% of resting energy expenditure (REE) and increased to 63%-68% after fasting, with corresponding decreases in carbohydrate oxidation. Protein oxidation decreased with fasting but still contributed 16%-18% of REE in older participants. For several metabolic variables (respiratory exchange ratio, glucose <i>R</i><sub>a</sub>, glycerol <i>R</i><sub>a</sub>, urea <i>R</i><sub>a</sub>, urea excretion, and percent of REE from carbohydrate and fat), we observed significant age × fasting interactions (<i>P</i> < 0.01). Younger adults exhibited larger decreases in glucose <i>R</i><sub>a</sub> and greater increases in markers of protein turnover (leucine <i>R</i><sub>a</sub>, urea production) and lipolysis, whereas older adults showed blunted glucose and leucine responses but maintained substantial protein oxidation. These age-related differences suggest that older adults rely relatively more on ongoing protein catabolism during short-term fasting, which may contribute to vulnerability to muscle loss during illness or prolonged inadequate intake.<b>NEW & NOTEWORTHY</b> A 36-h fast had a profound effect on substrate utilization in older women and men. In the postabsorptive state, fat oxidation averaged 52%-55% of REE. After a 36-h fast, fat oxidation increased to 63%-68%, with corresponding decreases in carbohydrate oxidation. The continued reliance on protein oxidation (16%-18% of REE) with fasting may be an important factor in the muscle loss seen in older adults with chronically inadequate food intake and impaired physical activity.

American Journal of Physiology-Endocrinology and MetabolismVol. 330(3)
Massachusetts Institute of Technology (US)
Openalex Percentile: Top 70%
Muscle metabolism and nutrition
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