Macronutrient Composition and Depressive Symptoms Among Working-Age Participants in a US National Health Survey: An Isocaloric Substitution Analysis.

BACKGROUND: Depressive symptoms are common among working-age adults, and diet may be a modifiable correlate. Macronutrient composition has been linked to depressive symptoms, but usually one macronutrient at a time, and the few analyses of exchanges between them were confined to restricted populations. Protein, fat, and carbohydrate together account for almost all dietary energy, so a higher share of one implies a lower share of another. This study aimed to identify which exchange of energy between protein, fat, and carbohydrate, if any, is associated with depressive symptoms in working-age adults. METHODS: In a cross-sectional analysis of the National Health and Nutrition Examination Survey from August 2021 to August 2023, we analysed 2,125 participants aged 20-64 years with two complete 24-hour dietary recalls. Depressive symptoms were defined as a Patient Health Questionnaire-9 score of 10 or higher. Protein, fat, and carbohydrate were expressed as percentages of macronutrient-derived energy, summing to 100%. Logistic regression estimated odds ratios (ORs) across quartiles, and leave-one-out models estimated isocaloric substitution of 5% of macronutrient energy, adjusted for demographic, socioeconomic, and lifestyle factors and body mass index. Models were repeated by sex and employment status. Unweighted analyses were primary. RESULTS: Depressive symptoms were present in 277 participants (13.0%). The OR for the highest versus lowest quartile was 0.42 (95% CI: 0.28-0.63; P for trend < 0.001) for protein and 1.81 (1.24-2.65) for carbohydrate; fat showed no association. Replacing 5% of macronutrient energy from carbohydrate with protein was associated with lower odds (OR: 0.70, 0.59-0.84; survey-weighted: 0.76, 0.61-0.95), as was the same exchange from fat to protein (0.74, 0.60-0.90; survey-weighted: 0.78, 0.58-1.05), whereas exchanging carbohydrate for fat was not. Substitution estimates were similar by sex and among participants who were currently working (0.73, 0.58-0.92) and those who were not. CONCLUSIONS: Among working-age adults, replacing carbohydrate or fat with protein was associated with lower odds of depressive symptoms. The design is cross-sectional, and prospective confirmation is needed.