Muscle mass, BMI, and mortality among adults in the United States: A population-based cohort study

Abstract

Background: The level of body-mass index (BMI) associated with the lowest risk of death remains unclear. Although differences in muscle mass limit the utility of BMI as a measure of adiposity, no study has directly examined the effect of muscle mass on the BMI-mortality relationship.

Methods: Body composition was measured by dual-energy x-ray absorptiometry in 11,687 participants of the National Health and Nutrition Examination Survey 1999-2004. Low muscle mass was defined using sex-specific thresholds of the appendicular skeletal muscle mass index (ASMI). Proportional hazards models were created to model associations with all-cause mortality.

Results: At any level of BMI ≥22, participants with low muscle mass had higher body fat percentage (%TBF), an increased likelihood of diabetes, and higher adjusted mortality than other participants. Increases in %TBF manifested as 30-40% smaller changes in BMI than were observed in participants with preserved muscle mass. Excluding participants with low muscle mass or adjustment for ASMI attenuated the risk associated with low BMI, magnified the risk associated with high BMI, and shifted downward the level of BMI associated with the lowest risk of death. Higher ASMI was independently associated with lower mortality. Effects were similar in never-smokers and ever-smokers. Additional adjustment for waist circumference eliminated the risk associated with higher BMI. Results were unchanged after excluding unintentional weight loss, chronic illness, early mortality, and participants performing muscle-strengthening exercises or recommended levels of physical activity.

Conclusions: Muscle mass mediates associations of BMI with adiposity and mortality and is inversely associated with the risk of death. After accounting for muscle mass, the BMI associated with the greatest survival shifts downward toward the normal range. These results provide a concrete explanation for the obesity paradox.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. BMI versus total body fat percentage based on muscle mass status and age.

Graphs show scatter plots of BMI and total body fat percentage and fitted b-splines based on muscle mass status for women (Panel A) and men (Panel B), and based on age

Fig 2. Risk of all-cause mortality by BMI category and muscle mass status.

Bars indicate prevalence of low muscle mass in each BMI category. One participant with BMI >35 (38 kg/m2) had low muscle mass and was grouped with participants with BMI 30-<35 kg/m2 for statistical analysis. Models adjusted for age, sex, race/ethnicity, smoking status, physical activity level, and education. Error bars represent 95% confidence intervals.

Fig 3. The risk of death according to BMI for the full cohort (upper panel) and for participants with preserved muscle mass (lower panel).

Mortality modeled as a restricted cubic spline and models adjusted for age, sex, race/ethnicity, smoking status, physical activity level, and education. The shaded area represents the 95% confidence interval.

Fig 4. Association of BMI with all-cause mortality without and with adjustment for appendicular skeletal muscle mass index for the full cohort.

Models adjusted for age, sex, race/ethnicity, smoking status, physical activity level, and education. Error bars represent 95% confidence intervals.

Fig 5. Association of BMI with all-cause mortality without and with adjustment for appendicular skeletal muscle mass index after stratification by smoking status.

Models adjusted for age, sex, race/ethnicity, smoking status, physical activity level, and education. Error bars represent 95% confidence intervals.

Fig 6. Association of BMI with all-cause mortality without and with adjustment for appendicular skeletal muscle mass index and waist circumference.

Models adjusted for age, sex, race/ethnicity, smoking status, physical activity level, and education. Error bars represent 95% confidence intervals.

Fig 7. Risk of mortality by BMI category and muscle mass status, without and with adjustment for waist circumference.

Y-axis truncated for clarity (see S6 Fig for untruncated y-axis). Models adjusted for age, sex, race/ethnicity, smoking status, physical activity level, and education. Error bars represent 95% confidence intervals.