The effect of oral folic acid on glutathione, glycaemia and lipids in Type 2 diabetes.

Plasma homocysteine is an established risk factor for vascular disease and precursor of the anti-oxidant glutathione. This study was designed to investigate the relationship of changes in homocysteine (Hcy) induced by oral folate to glutathione and measures of glycaemia and lipid metabolism in Type 2 diabetes (T2DM). Twenty-seven patients (26 male, 1 female, aged 48-68 years) with T2DM and microalbuminuria were treated with folic acid 10 mg daily for 3 months. During the study, diastolic blood pressure (p=0.04), HbA1c (p=0.04), serum triglycerides (p=0.04) and serum total/HDL-cholesterol ratio (p=0.004) all increased and serum HDL-cholesterol fell (p=0.006). The increased red cell folate correlated with a reduction in microalbuminuria (p=0.001). Overall, plasma glutathione increased (p=0.016) despite reduction in its precursor Hcy (p<0.001). Change in glutathione correlated inversely with change in HbA1c (p<0.02), total cholesterol (p=0.003) and triglycerides (p<0.02) and positively with HDL-cholesterol (p=0.033). Increase in glutathione correlated with levels of vitamin B6 (p<0.05). Metformin treatment protected against the rise in blood pressure (BP) (p=0.02), independently of changes in plasma glutathione. In summary, oral folic acid supplementation in T2DM reduced plasma Hcy and increased glutathione levels. HbA1c, triglycerides and HDL-cholesterol deteriorated during the trial: their levels correlated inversely with changes in glutathione. The increase in glutathione may depend on an adequate supply of B6, as changes in glutathione correlated with vitamin B6 levels. Reduced Hcy and increased glutathione may both mediate improvement in vascular function and outcome. Some aspects of the response to folate may be different in patients on metformin.

Hip fracture patients may be vitamin B6 deficient. Controlled study of serum pyridoxal-5'-phosphate.

Deficiency of vitamin B6 in rats may result in defective bone formation, possibly due to decreased activity of the enzyme ornithine decarboxylase which requires pyridoxal-5'-phosphate (PLP) as a co-factor and is responsible for production of intracellular putrescine, a metabolic regulator. We studied 3 groups of patients (62 fit ambulant out-patients, 21 elective arthroplasty patients, and 20 hip fracture patients) and assayed their PLP status by high performance liquid chromatography. The reference range derived from the out-patients was 13-106 nmol/L. 3 of the arthroplasty group and 10 of the fracture group had serum PLP concentrations less than 13 nmol/L (P < 0.01). We conclude that PLP may be an etiologic factor in hip fracture by virtue of its role in the activity of a key regulatory protein.