Erythrocyte trans fatty acid accumulation in elderly sarcopenic patients: biochemical evidence for oxidative stress-driven cis-trans isomerization of membrane lipids.

Free radical-mediated cis-trans isomerization of polyunsaturated fatty acids (FA) is well established in food chemistry, yet its occurrence as an endogenous biochemical process in oxidatively stressed human tissues remains poorly characterized. Sarcopenia, a geriatric syndrome defined by progressive loss of skeletal muscle mass and function, is associated with chronic oxidative stress. We hypothesized that this oxidative milieu drives in vivo cis-trans isomerization of erythrocyte membrane FA, generating trans isomers distinguishable from dietary exposure. A cross-sectional study was conducted in 160 subjects aged ≥65 years, classified as sarcopenic (n = 97) or non-sarcopenic (n = 63) by SARC-F questionnaire and handgrip strength. Erythrocyte FA profiles were determined by gas chromatography; plasma oxysterols were quantified by GC-MS. Specific trans isomers were markedly elevated in sarcopenic patients, especially C18:1 trans-11 (3.09-fold; p < 0.001) and the linoleic acid isomer C18:2 trans-9, cis-12 (2.66-fold; p < 0.001). Their cis counterparts were not significantly elevated. By contrast, two trans species that retain the cis-9 configuration, the ruminant dietary marker C18:2 cis-9, trans-11 (CLA) and the geometric isomer C18:2 cis-9, trans-12, were both paradoxically reduced (p = 0.007 and p < 0.001, respectively). Total trans FA correlated with non-enzymatic oxysterols 7-ketocholesterol (ρ = 0.49, p < 0.001),7α-hydroxycholesterol (ρ = 0.43, p = 0.003), and 7β-hydroxycholesterol (ρ = 0.49, p < 0.001), but not with enzymatically formed 24S-hydroxycholesterol. On multivariate analysis, total trans fatty acids remained independently associated with sarcopenia (OR 1.28; p = 0.018). These findings provide the first biochemical evidence that chronic oxidative stress in sarcopenic elderly patients drives endogenous cis-trans isomerization of membrane FA, challenging the notion that elevated trans FA represent a purely dietary phenomenon.