Dietary intake of live microbes is inversely associated with fatigue and modified by serum folate among adults aged 40 years or more.

Abstract

To investigate the independent associations between dietary live-microbe intake, as well as circulating levels of folate metabolites, and fatigue, and to examine their interaction as a potential biological pathway underlying fatigue in aging adults. Cross-sectional analysis of adults aged ≥40 years participating in the National Health and Nutrition Examination Survey 2011-2023. Fatigue was assessed using the Patient Health Questionnaire fatigue item and categorized as none/low versus moderate/severe. Dietary intake of live-microbe foods was derived from two 24-h recalls and classified as low, medium, or high. Total serum concentrations folate and its metabolites, including 5-methyltetrahydrofolate, were quantified. Survey-weighted logistic regression, adjusted for sociodemographic, dietary, and clinical covariates, estimated main effects and interactions between the effects of 5-methyltetrahydrofolate and of live-microbe intake; sensitivity analyses additionally adjusted for depressive symptoms and sleep disturbance. Moderate/severe fatigue was reported by 16.3% of 14,376 participants and 15.0% reported no intake of live-microbe foods. High versus low live-microbe intake was associated with lower odds of moderate/severe fatigue (odds ratio [OR] 0.60; 95% confidence interval [CI] 0.46-0.79). Higher serum 5-methyltetrahydrofolate levels were also associated with lower odds of moderate/severe fatigue (OR 0.85; 95% CI 0.73-0.98). In stratified analyses, high live-microbe intake corresponded to 38-65% lower odds of moderate/severe fatigue only among adults with higher levels of 5-methyltetrahydrofolate, with no significant associations among those with lower levels. Intake of microbe-rich foods and higher levels of circulating 5-methyltetrahydrofolate are both associated with lower levels of fatigue in midlife and older adults, and folate sufficiency appears to potentiate the fatigue-reducing benefits of live-microbe foods, supporting a nutrient-microbe pathway relevant to healthy aging.