**10. Effects of diet, renal disease on homocysteine – Other diseases**

Kai et al did not assess dietary indices. Prior studies have all found that low vitamin B12 and or folic acid are related to hyperhomocysteinaemia (D'Angelo et al, 1997; Clarke et al, 2003; Kluijtmans et al, 2003). Seemungal et al estimated dietary intake of vitamins using the food frequency questionnaire and found no relation to plasma HCY values but Fimognari et al estimated serum vitamin B12and folic acid levels directly. The Fimognari et al study also attempted to determine if there was a role for co-morbidities in the elevation of HCY in COPD. Thus they attempted to control for those factors known to be associated with hyperhomocysteinaemia such as vascular disease, renal disease and diabetes (Dominguez et al, 2010; Austen et al 2003). When they controlled for these factors in a multivariate analysis in the COPD patients only, they found that the best predictors of high HCY were low serum folic acid, vitamin B12 and triglycerides. This has been supported by further work from the Andersson et al group (Andersson et al, 2007)

Fimognari et al did not measure vitamin B6 levels. Further these multivariate analysis, did not include the normal subjects therefore did not include COPD as a factor even though a prior analysis of all subjects in the Fimognari et al study had shown a relationship between both presence of COPD as well as FEV1% and HCY. It is therefore not clear whether a repeat analysis using all subjects in the study with COPD and FEV1% as independent variables would have yielded significant relationships with three B vitamins.
