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Background and objectives Human susceptibility to chronic non-communicable disease may be explained, in part, by mismatches between our evolved biology and contemporary environmental conditions. Disease-induced fatigue may function to reduce physical activity during acute infection, thereby making more energy available to mount an effective immune response. However, fatigue in the context of chronic disease may be maladaptive because long-term reductions in physical activity increase risks of disease progression and the acquisition of additional morbidities. Here we test whether cumulative chronic morbidity is associated with subjective fatigue. Methodology We constructed a cumulative chronic morbidity score using self-reported diagnoses and algorithm-based assessments, and a subjective fatigue score based on four questionnaire items using cross-sectional survey data from the Study on global AGEing and adult health (SAGE), which features large samples of adults from six countries (China, Ghana, India, Mexico, Russia, South Africa). Results In a mixed-effects linear model with participants nested in countries (N = 32,455), greater cumulative chronic morbidity is associated with greater subjective fatigue (β = 0.34, SE = 0.005, P &amp;lt; 2e−16). This association replicates within each country and is robust to adjustment for key sociodemographic and physical covariates (sex, age, household wealth, physical function score, habitual physical activity, BMI, BMI2). Conclusions and implications Fatigue is a common but perhaps maladaptive neuropsychological response to chronic morbidity. Disease-induced fatigue may mediate a self-perpetuating cycle, in which chronic morbidity reduces physical activity, and less physical activity increases cumulative chronic morbidity. Longitudinal research is needed to test whether chronic morbidity, fatigue, and physical activity form a cyclical feedback loop. LAY SUMMARY Fatigue during acute illness may promote recovery, but persistent fatigue in the context of chronic disease may make matters worse. We present evidence from six countries that more chronic disease is associated with more fatigue. This fatigue may reduce physical activity, which increases risks of acquiring additional chronic health problems.

Greater chronic morbidity is associated with greater fatigue in six countries