Homocysteine lowering therapy

Effect of homocysteine-lowering therapy with folic acid, vitamin B12. and vitamin B6 on clinical outcome after coronary angioplasty. 

Homocysteine-lowering therapy and restenosis after coronary angioplasty... 

Schnyder G, et al. Effect of homocysteine-lowering therapy on restenosis after percutaneous coronary intervention for narrowings in small coronary arteries. Am J Cardiol 2003 91 (10) 1265-1269. 

Schnyder G, Rofifi M, Flammer Y, Pin R, Hess OM. Effect of Homocysteine-Lowering Therapy With Folic Acid, Vitamin B12, and Vitamin B6 on Clinical Outcome After Percutaneous Coronary Intervention The Swiss Heart Study A Randomized Controlled Trial. JAMA 2002 288 973-979. 

Schnyder G, Roffi M, Flammer Y, Pin R, Hess OM. 2002. Effect of homocysteine lowering therapy with folic acid, vitamin B(12), and vitamin B(6) on clinical outcome after percutaneous coronary intervention the Swiss Heart Study a randomized controlled trial. JAMA 288 973-979. 

Hyperhomocysteinemia also has been implicated as a risk factor for other complications of pregnancy, including intrauterine growth retardation, eclampsia, birth defects other than neural tube defects, and premature separation of the placenta from the wall of the uterus. It is not yet known, however, whether treatment with folic acid or other homocysteine-lowering therapies will protect pregnant women from these complications. 

Homocysteine-lowering therapy is lifesaving for patients with severe hyperhomocysteinemia due to CBS deficiency. Approximately 50% of patients respond to treatment with pharmacological doses (100 to 800 mg daily) of pyridox-ine (a form of vitamin B6). Adjunctive therapy may include betaine (2 to 6 g daily), folic acid (5 to 10 mg daily), or cobalamin (0.05 to 1.0 mg daily), or methionine restriction. Long-term homocysteine-lowering therapy substantially decreases cardiovascular risk in these patients. 

Saposnik, G., Ray, J.G., Sheridan, P., McQueen, M., and Lonn, E., 2009. Homocysteine-lowering therapy and stroke risk, severity, and disability additional findings from the HOPE 2 trial. Stroke. 40 1365-1372. 

Thambyrajah, J., Landray, M.J., Jones, H.J., McGlynn, F.J., Wheeler, D.C., and Townend, J.N., 2001. A randomized double-blind placebo-controlled trial of the effect of homocysteine-lowering therapy with folic acid on endothelial function in patients with coronary artery disease. Journal of the American College of Cardiology. 37 1858-1863. 

Since homocysteine-lowering therapy, which activates the remethylation pathway, accelerates the transmethylation reaction (Koyama et at. 2010) (Figure 47.6, Table 47.1, the clinical assessment of homocysteine-lowering therapy may have to include examinations of wide-ranging factors (dementia, prevalence of cancer, etc.) as listed above (i-viii). 

Therefore, discussion of whether or not homocysteine-lowering therapy reduces ADMA is complicated and this may be one of the reasons why a direct... 

Supplementation with the antioxidant vitamins ascorbic acid (250 mg) and mixed natural tocopherols (50 IU on alternate days) may be beneficial. Higher doses may vitiate the impact of lipid lowering therapy. Other naturally occurring antioxidants such as resveratrol, 3-catechin, selenium, and various carotenoids found in a variety of fruits and vegetables may provide additional antioxidant defense. Homocysteine, which initiates proatherogenic changes in endothelium, can be reduced in many patients by restriction of total protein intake to the amount required for amino acid replacement. Daily supplementation with up to 2 mg of folic acid plus other B vitamins is also recommended. 

The results of these three large trials are consistent and lead to the conclusion that there is no clinical benefit from vitamin supplementation in patients with cardiovascular disease (CVD). 4s suggested by Loscalzo (69), the results indicate that either homocysteine is not a important atherogenic determinant or the vitamin therapy might have other adverse effects that offset its homocysteine-lowering effects, such as cell proliferation through synthesis of thymidine, hypermethylation of DNA, or increased methylation potential leading to elevated levels of ADMA. 

VITATOPS Trial Study Group, 2002. The VITATOPS (Vitamins to Prevent Stroke) Trial rationale and design of an international, large, simple, randomised trial of homocysteine-lowering multivitamin therapy in patients with recent transient ischaemic attack or stroke. Cerebrovascular Diseases. 13. 120-126. 

The difference between the outcome of the Swiss Heart Study and that of FACIT illustrates how difficult it is to explain the results in terms of the biological effects of vitamin therapy. The positive results of the Swiss Heart Study seem to confirm the classical homocysteine hypothesis, which holds that homocysteine is an important atherosclerotic determinant and that lowering of homocysteine with vitamin therapy might reduce the rates of cardiovascular events. However, it is more difficult to explain the results of FACIT by an adverse effect of low plasma homocysteine, and consequently, a less simplistic perspective on the methionine-homocysteine metabolism and the multiple effects of folate, B6, and B 2 is needed. 

Tice JA, Ross E, Coxson PG, et al. Cost-effectiveness of vitamin therapy to lower plasma homocysteine levels for the prevention of coronary heart disease. JAMA 2001 286 936-943. 

Nutrition Compared with immunosuppressive therapy based on ciclosporin, glucocorticoids, and mycophenolate, a regimen based on everolimus resulted in significantly lower serum homocysteine concentrations in renal transplant recipients [42 ]. 

Metabolism In a prospective controlled study in 74 patients taking isotretinoin for cystic acne, blood concentrations of homocysteine, vitamin B12, and folate were assessed before and after 45 days of isotretinoin therapy [39 ]. The control group consisted of 80 individuals. Homocysteine concentrations were significantly higher in those who took isotretinoin. The vitamins were unaffected, but serum lipids and liver enzymes increased significantly. These effects may have been due to inhibition of cystathionine-beta-synthase, an enzyme required for the metabolism of homocysteine by either the drug or liver dysfunction. Daily supplementation with vitamin B12 and folate can lower plasma concentrations of homocysteine, and the authors therefore recommended the use of these vitamins in patients taking isotretinoin. 

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