Adverse effects of obesity on overall health, quality of life, and related physical health metrics: A cross-sectional and longitudinal study from the All of Us Research Program. — CFSMEATLAS
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Adverse effects of obesity on overall health, quality of life, and related physical health metrics: A cross-sectional and longitudinal study from the All of Us Research Program.
Yao, Zhiqi, Tchang, Beverly G, Chae, Kacey et al. · Journal of internal medicine · 2025 · DOI
Quick Summary
This study looked at over 323,000 people in the United States to understand how obesity affects overall health and quality of life. Researchers found that people with higher body weight reported worse health, more pain, more fatigue, and greater difficulty with physical activity compared to people of normal weight. The effects were strongest in people with the most severe obesity, who were nearly 4 times more likely to report poor health and severe pain.
Why It Matters
This study is relevant to ME/CFS patients and researchers because it examines the relationship between obesity and fatigue, pain, and functional limitation—symptoms that overlap significantly with ME/CFS. Understanding how obesity influences these symptom domains may help clinicians and patients better characterize disease burden and distinguish between obesity-related fatigue versus ME/CFS-related fatigue in clinical practice.
Observed Findings
Among 323,640 participants, 9.5% had Class III obesity; 9.6% of those with Class III obesity reported poor overall health compared to 3.2% with normal weight.
In Class III obesity, 28.3% reported severe pain versus 13.2% in normal weight participants.
11.8% of Class III obese participants had prevalent insomnia compared to 8.4% in normal weight.
Class III obesity was associated with an odds ratio of 3.93 (95% CI 3.71-4.17) for severe pain and 3.13 (95% CI 2.98-3.29) for severely limited physical activity.
Class III obesity showed a hazard ratio of 2.83 (95% CI 2.36-3.40) for incident fibromyalgia.
Inferred Conclusions
Higher BMI categories show graded associations with worsening health metrics across self-reported overall health, pain, fatigue, and physical activity limitation.
Class III obesity confers substantially elevated risk for developing chronic pain syndrome, fibromyalgia, and insomnia compared to normal weight.
Obesity imposes a broad burden on multiple dimensions of well-being and health-related quality of life in the U.S. population.
Remaining Questions
Does the reported fatigue in obese participants meet clinical criteria for ME/CFS, or does it reflect fatigue from other causes (deconditioning, sleep disruption, metabolic dysfunction)?
What This Study Does Not Prove
This study does not prove that obesity causes ME/CFS or chronic fatigue syndrome; it only demonstrates statistical associations in a cross-sectional design. The study cannot establish causality or the direction of the relationship—it is possible that underlying illness (including undiagnosed ME/CFS) leads to weight gain rather than obesity causing fatigue. Additionally, the study's self-reported outcome measures were not validated against objective biomarkers or clinical assessment criteria specific to ME/CFS.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
What is the direction of causality between obesity and these outcomes—does obesity cause fatigue and pain, or do underlying conditions causing fatigue and pain lead to weight gain?
How much of the association between obesity and fatigue remains after controlling for sleep quality, physical inactivity, depression, and inflammatory markers?
Do weight loss interventions improve fatigue and pain severity in obese individuals with these comorbidities?