Effect of 1 year B and D vitamin supplementation on LINE-1 repetitive element methylation in older subjects

BACKGROUND: Disturbed DNA methylation is causally related to chronic diseases like cancer and atherosclerosis. B vitamins are cofactors required for methyl group synthesis and may therefore affect DNA methylation. Vitamin D has epigenetic effects. We tested if B and D vitamin supplementation has an effect on genomic long interspersed nuclear element-1 (LINE-1) methylation and the metabolites S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH). METHODS: Fifty subjects (median age 68.0 years) were supplemented with a daily oral dose of B vitamins (500 µg folic acid, 500 µg vitamin B12 and 50 mg vitamin B6), 1200 IU vitamin D and 456 mg calcium. Fasting blood samples were collected before and after 1 year of supplementation. LINE-1 methylation was determined in genomic DNA from blood cells as a surrogate for whole genome methylation. In addition, SAM, SAH and total homocysteine (tHcy) were measured in plasma samples. RESULTS: Plasma homocysteine decreased significantly after supplementation (12.8 vs. 9.1 µmol/L; p<0.05), whereas SAM, SAH, the SAM/SAH ratio and LINE-1 methylation did not change significantly. LINE-1 methylation was not significantly correlated with SAH, homocysteine or B vitamins. CONCLUSIONS: Long-term vitamin B supplementation had no effect on LINE-1 methylation in blood cells nor on plasma levels of SAM and SAH. Vitamin B and D supplementation seems to have no effect on DNA methylation, especially in cases where no severe deficiency exists.