A Novel Genetic Risk Factor Linking Choline to Skeletal Muscle Fragility

Earlier controlled feeding studies have demonstrated that men with the common MTHFD1 variant 1958A have a much higher choline requirement than men without it (Kohlmeier et al., PNAS 2005). With choline intakes below their needs, creatine kinase (CK) activity increased greatly in some of these men as a sign of muscle dysfunction. We wanted to know whether physically active and fit men with elevated CK activity were more likely to carry the MTHFD1 1958A allele associated with increased choline requirement.CK activities were measured in 145 Caucasian men prior to their entry in a physically challenging officer candidates’ training course and related to their MTHFD1 1958 genotypes. Genotype distribution (25 AA, 82 AG, 38 GG) indicated Hardy‐Weinberg equilibrium. Following our previous practice, we used the 90th percentile to distinguish between normal and high CK values. Men with high CK levels were much more likely to have one or two A alleles than men normal levels (odds ratio 6.03, p=0.04). The attributable risk for exceeding the 90th percentile related to the presence of an MTHFD1 1958 A allele was 81%.Whether the men with signs of muscle damage were choline‐deficient is not known. Nonetheless, the more common presence of the A allele suggests that men with a high CK activity are more likely to be choline deficient. Higher choline intake may help them maintain muscle integrity during times with high‐intensity exercise.