High HDL-C Linked to Increased Risk of Low Muscle Mass in Older Men: Study Reveals

The investigation involved 1,995 adults aged 50 and above, aiming to explore the connection between HDL-C levels and chest CT-defined muscle mass. Researchers measured the muscle area of the erector spinae at the T12 vertebral level and analyzed how HDL-C levels corresponded with low muscle mass, a key indicator of sarcopenia.

The study led to the following findings:

• Higher HDL-C levels were consistently linked to reduced muscle area in older adults.
• The association was stronger in men (β = -3.16) compared to the overall group (β = -1.91).
• There was no statistically significant association between HDL-C levels and muscle area in women.
• Elevated HDL-C levels more than doubled the risk of low muscle mass in the entire cohort (OR = 2.28).
• In older men, the risk of low muscle mass was three times higher with increased HDL-C levels (OR = 3.28).
• The sex-specific differences suggest a stronger adverse effect of high HDL-C on muscle health in men than in women.

The researchers employed multivariate logistic regression and restricted cubic spline (RCS) models to validate these findings, both confirming a linear relationship between HDL-C levels and the risk of low muscle mass. These results suggest that HDL-C, traditionally associated with cardiovascular benefits, may also play a role in age-related muscle health, though not necessarily a protective one.

Despite the compelling data, the study acknowledges some limitations. The observational nature of the research does not allow for causal conclusions. Additionally, functional assessments like grip strength, which are important in diagnosing sarcopenia, were not included. The findings are also limited to a Chinese population, and further studies across diverse ethnic groups are necessary to broaden applicability.

Moreover, since the study participants were drawn from individuals undergoing CT scans for lung cancer screening, the possibility of selection bias cannot be ruled out. Lifestyle factors like diet and exercise, which could influence both HDL-C and muscle mass, were also not accounted for.

The authors concluded, "The findings present HDL-C as a potentially useful biomarker for identifying older individuals, particularly men, who are at increased risk of muscle loss. Further research is needed to understand the mechanisms behind this association and whether interventions targeting HDL-C could aid in sarcopenia prevention or management."

Reference:

Zhang W, Liu Y, Zhang Y, Zhang D, Wang J and Chen X (2025) Associations between high-density lipoprotein cholesterol levels and computed tomography-defined low muscle mass in older adults and sex-related differences. Front. Endocrinol. 16:1600431. doi: 10.3389/fendo.2025.1600431