Christen and colleagues found that daily supplementation with 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12 for seven years reduced homocysteine levels by 18% in 300 women with three or more risk factors for coronary heart disease but did not affect other cardiovascular inflammatory biomarkers.24 Another study by Kataria and colleagues demonstrated that daily supplementation of 2 mg of folic acid, 25 mg of vitamin B6, and 0.5 mg of vitamin B12 resulted in an 11% reduction in risk of vascular death among 8,513 stroke patients but had no effect on cardiovascular risk.25 In addition, treatment for four weeks with oral doses of 1.8 g/day of N-acetylcysteine, a precursor to the antioxidant glutathione, has been found to lower blood homocysteine levels by reducing cellular oxidation, but has not consistently reduced the risk of cardiac events in cardiovascular patients.26,27 The reasons for the lack of protective effects of folic acid, vitamin B6, and vitamin B12 on inflammatory biomarkers and risk of CVD are unclear

Inhibition of 5-reductase activity in late pregnancy decreases gestational length and fecundity and impairs object memory and central progestogen milieu of juvenile rat offspring
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This reduced effectiveness may stem from the progressive nature of type 2 diabetes itself, incorrect dosing or administration, lifestyle changes, or the natural evolution of your condition
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