FOLATE, VITAMIN-B12, HOMOCYSTEINE STATUS AND DNA-DAMAGE IN YOUNG AUSTRALIAN ADULTS

We performed a cross-sectional study (n = 49 males, 57 females) and a randomized double-blind placebo-controlled dietary intervention study (rt = 31/32 per group) to determine the effect of folate and vitamin B 12 (B12) on DNA damage (micronucleus formation;and DNA methylation) an d plasma homocysteine (HC) in young Australian adults aged 18-32 years . None of the volunteers were folate deficient (i.e. red blood cell fo late <136 nmol/l) and only 4.4% (all females) were vitamin B12 deficie nt (i,e, serum vitamin B12 <150 pmol/l), The cross-sectional study sho wed that (i) the frequency of micronucleated cells (MNCs) was positive ly correlated with plasma HC in males (R = 0.293, P < 0.05) and (ii) i n females MNC frequency was negatively correlated with serum vitamin B 12 (R -0.359, P < 0.01) but (iii) there was no significant correlation between micronucleus index and folate status. The results also showed that the level of unmethylated CpG (DNA) was not significantly relate d to vitamin B12 or folate status. The dietary intervention involved s upplementation with 3.5x the recommended dietary intake (RDI) of folat e and vitamin B12 in wheat bran cereal for three months followed by te n times the RDI of these vitamins via tablets for a further three mont hs. In the supplemented group, MNC frequency was significantly reduced during the intervention by 25.4% in those subjects with initial MNC f requency in the high 50th percentile but there was no change in those subjects in the low 50th percentile for initial MNC frequency. The red uction in MNC frequency was significantly correlated with serum vitami n B12 (R = -0.49, P < 0.0005) and plasma HC (R = 0.39, P < 0.006), but was not significantly related to red blood cell folate, DNA methylati on status was not altered in the supplemented group. The greatest decr ease in plasma HC (by 37%) during the intervention was observed in tho se subjects in the supplemented group with initial plasma HC in the hi gh 50th percentile, and correlated significantly with increases in red blood cell folate (R = -0.64, P < 0.0001) but not with serum vitamin B12, The results from this study suggest that (i) MNC frequency is min imized when plasma HC is below 7.5 mu mol/l and serum vitamin B12 is a bove 300 pmol/l and (ii) dietary supplement intake of 700 mu g folic a cid and 7 mu g vitamin B12 is sufficient to minimize MNC frequency and plasma HC, Thus, it appears that elevated plasma HC, a risk factor fo r cardiovascular disease, may also be a risk factor for chromosome dam age.