Clin Nutr, 2023, Dec;42(12):2328-2337. doi: 10.1016/j.clnu.2023.09.027.

The associations of erythrocyte membrane polyunsaturated fatty acids with skeletal muscle loss: A prospective cohort study.

Su M Zhang X Hu W et al.

Background & aims: Polyunsaturated fatty acids (PUFAs) may play a vital role in maintaining skeletal
muscle mass in the aged population. This study investigated the longitudinal relationship between the
concentrations of erythrocyte membrane PUFAs and age-related changes in skeletal muscle mass over
an average 6.5 years of follow-up in a Chinese middle-aged and older adult population. Methods: A total
of 1494 participants aged 57.4 ± 4.7 years were included in this study. Skeletal muscle mass was
determined using dual-energy X-ray absorptiometry. Per year percent changes in the skeletal muscle
index (Δ% SMI), appendicular skeletal muscle index (Δ% ASMI), and total body lean mass index (Δ%
TBLMI) from baseline were calculated. Concentrations of total and individual cis-n-3 and cis-n-6 PUFAs of
the erythrocyte membrane were determined using gas-liquid chromatography. Results: Fully adjusted
linear regression models showed that per unit increases in the concentrations of C18:2 n-6, C20:4 n-6,
C22:4 n-6, and total n-6 PUFAs resulted in increases of 0.022%-0.155 % in the Δ% SMI (P for linearity:
<0.001-0.006). Restricted cubic spline analysis revealed an inverted U-shaped relationship between the
concentrations of C20:2 n-6, C22:5 n-3, C22:6 n-3, and total n-3 PUFAs and the Δ% SMI (P for non-
linearity: <0.001-0.036). In addition, an inverted U-shaped curve was also detected for the relationships
of the linoleic acid/α-linolenic acid ratio (P for non-linearity = 0.010) and n-6/n-3 PUFA ratio (P for non-
linearity = 0.013) with the Δ% SMI, with the Δ% SMI peaking at respective ratios of 124.96 and 3.69.
Similar associations were revealed by the Bayesian kernel machine regression model. No interaction
effect was detected between the individual PUFAs for the Δ% SMI in the bivariate exposure-response
analysis. Overall, similar results were observed for the Δ% ASMI and Δ% TBLMI. Conclusions: The
associations between different individual PUFAs and age-related muscle loss in middle-aged and older
adults may be different. Our results suggest that high concentrations of erythrocyte membrane n-6
PUFAs may be correlated with less skeletal muscle mass loss, whereas extremely high concentrations of
n-3 PUFAs may be correlated with more muscle loss.

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