Folic acid and diseases - supplement it or not? / Ácido fólico e doenças - suplementá-lo ou não?

SUMMARY Introduction: folic acid is a water soluble vitamin, which is synthetically-produced and found in fortified foods and supplements. Folate is found naturally in plants, such as the dark green leafy vegetables. Folate is not synthesizedde novo by humans, therefore the daily requirements are met from the dietary intake of folic acid supplements or food rich in this vitamin. Folate deficiency could lead to numerous common health problems. Hyperhomocysteinemia and the possibility of malignancy developments are the long term consequences of this deficit albeit contradictory findings on these claims. Methods: the articles included in this review focused on recent updated evidence-based reports and meta-analyses on the associations of the serum folate/folic acid and the various diseases found globally. Results: the benefit of folic acid supplementation in the pre-conception period for the prevention of neural tube defects (NTDs) was well established and it was suggested that counseling sessions should be given to women with previous pregnancies affected by NTDs. However, supplementation of folic acid and its medicinal effects in the treatment of other diseases were contradictory and unclear. Conclusion: more detailed investigations into the health benefits of folic acid are needed before it could be recommended for supplementation, treatment or prevention of some of the diseases discussed in this review.

RESUMO Introdução: ácido fólico é uma vitamina solúvel em água produzida sinteticamente e encontrada em alimentos e suplementos enriquecidos. O folato é encontrado naturalmente em plantas, como vegetais folhosos verde-escuros. O folato não é sintetizado de novo por seres humanos; portanto, as necessidades diárias são satisfeitas a partir da ingestão de suplementos de ácido fólico ou alimentos ricos nessa vitamina. A deficiência de folato pode levar a inúmeros problemas de saúde comuns. Hiper-homocisteinemia e a possibilidade de desenvolver malignidades são as consequências a longo prazo desse déficit, ainda que os resultados sejam contraditórios sobre essas afirmações. Métodos: os artigos incluídos nesta revisão tratam de relatórios recentes atualizados com base em provas e metanálises sobre a associação entre o folato/ácido fólico e várias doenças encontradas globalmente. Resultados: o benefício da suplementação de ácido fólico no período de pré-concepção para a prevenção de defeitos do tubo neural (DTN) foi bem estabelecido e foi sugerido que sessões de aconselhamento devem ser providas às mulheres com gravidezes anteriores afetadas por DTN. No entanto, os benefícios da suplementação de ácido fólico e os efeitos medicinais no tratamento de outras doenças são contraditórios e pouco claros. Conclusão: investigações mais detalhadas sobre os benefícios do ácido fólico são necessárias antes que a suplementação seja recomendada para tratamento ou prevenção de algumas das doenças discutidas nesta revisão.

Different doses of oral folic acid for homocysteine-lowering therapy in patients on hemodialysis a randomized controlled trial

We compared the effect of higher and lower doses of folic acid compared to our routine daily dose on plasma homocysteine levels, in our hemodialysis patients. Eighty patients on hemodialysis receiving oral folic acid, 10 mg/d, were randomized to receive folic acid at either doses of 5 mg/d [group 1] or 15 mg/d [group 2] for 2 months. Plasma levels of total homocysteine were measured before and after the study period. Hyperhomocysteinemia was seen in 75 patients [93.8%] before, and in 37 patients of group 1 [92.5%] and 39 of group 2 [97.5%] after the study period. In group 1, a nonsignificant decrease occurred in plasma homocysteine level [29.67 +/- 12.26 micro mol/L to 27.78 +/- 9.94 micro mol/L, P = .30], while in group 2, there was a significant decrease in homocysteine level [32.40 +/- 9.76 micro mol/L to 29.58 +/- 9.62 micro mol/L, P = .01]. Changes in homocysteine level correlated with its baseline level [r = -0.42, P < .001]. In both groups, significant reductions in homocysteine level were seen mostly in those patients with high baseline homocysteines. Routine folic acid supplementation of 10 mg/d could not normalize plasma homocysteine levels in most of our patients. Increasing folic acid dose made a statistically significant but clinically trivial decrease in homocysteine levels, and could not normalize homocysteine level in most patients. Patients with a higher baseline homocysteine level achieved a greater reduction, which may be explained by primary noncompliance of some patient. Further investigation of folic acid dosage is suggested

Hyperhomocysteinemia and bone mineral density: a case - control study

To find out whether homocysteine has a direct effect on bone or it is an innocent bystander? The study was designed to investigate probable role of homocysteine on bone mineral density [BMD]. This a case-control study wherein, 30 patients with at Least one densitometry criterion of osteoporosis in femoral neck or Lumbar spine were enrolled as the case group along with another 30 normal subjects with normal BMD, as the control group. The patients of the two groups were matched for their ages and sex. In all eligible patients BMD was measured by DEXA and fasting serum homocysteine level were measured by Enzyme Immunoassay Kit. The mean of serum level of homocysteine were 11.67 +/- 4.38 and 11.97 +/- 3.09 imol/l in control and case groups respectively. The difference between two groups was not significant [P=0.761]. Serum homocysteine level and BMC of various areas in case and control groups had no significant correlation [lumbar spine in control group [r= 0.025, p=0.9], lumbar spine in case group [r=0.071, p=0.716], femoral neck in control group [r=0.276, p=0.147], femoral neck in case group [r=0.001, p=0.998fl. Despite numerous studies about direct effect of homocysteine on increase of osteoporotic fracture risk, our study did not show a correlation between serum Level of homocysteine and BMD. Due to multiplicity of factors affecting bone density, final conclusions need extensive investigations with attention to other confounding factors

Hyperhomocysteinaemia & folic acid supplementation in patients with high risk of coronary artery disease.

BACKGROUND & OBJECTIVES: Many traditional independent risk factors such as diabetes mellitus, hypertension, hypercholesterolaemia, smoking, male sex, old age, etc., contribute to the development of coronary artery disease (CAD). Hyperhomocysteinaemia is an independent risk factor of CAD but the role of plasma homocysteine (Hcy) in high risk patients (> or = 3 risk factors) is not known. We investigated the role of plasma Hcy, folic acid, vitamin B12 in patients with high risk (> or = 3 risk factors) of CAD and effects of supplementation of folic acid in the patients with hyperhomocysteinaemia. METHODS: The plasma Hcy levels in 152 patients with > or = 3 risk factors of CAD and 136 patients with 1-2 risk factors and 48 individuals with no risk factors were measured using high performance liquid chromatography (HPLC) with fluorescence detection. Plasma folic acid and vitamin B12 levels were also measured in these patients with immunoassays. The patients with hyperhomocysteinaemia were treated with 5 mg of folic acid for 8 wk, and plasma levels of Hcy were measured after treatment. RESULTS: The plasma Hcy level was significantly higher in the patients with > or = 3 risk factors of CAD than in those with 1-2 risk factors and controls. The plasma levels of folic acid and vitamin B12 were significantly lower in the patients with > or = 3 risk factors of CAD compared to those with 1-2 risk factors and controls. The Hcy levels in the patients with > or = 3 risk factors of CAD significantly reduced by 33.5 per cent after 8 wk folic acid administration. INTERPRETATION & CONCLUSION: Plasma Hcy level was elevated significantly in patients with > or = 3 risk factors of CAD. Hyperhomocysteinaemia appears to play an important role in the pathogenesis of CAD. Folic acid supplementation may be useful in reducing plasma Hcy level in high risk patients with hyperhomocysteinaemia.

Hyperhomocyst(e)inemia in chronic stable renal transplant patients

PURPOSE: Hyperhomocyst(e)inaemia is an important risk factor for atherosclerosis, which is currently a major cause of death in renal transplant patients. The aim of this study was to assess the influence of immunosuppressive therapy on homocyst(e)inemia in renal transplant recipients. METHODS: Total serum homocysteine (by high performance liquid chromatography), creatinine, lipid profile, folic acid (by radioimmunoassay-RIA) and vitamin B12 (by RIA) concentrations were measured in 3 groups. Group I patients (n=20) were under treatment with cyclosporine, azathioprine, and prednisone; group II (n=9) were under treatment with azathioprine and prednisone; and group III (n=7) were composed of renal graft donors for groups I and II. Creatinine, estimated creatinine clearance, cyclosporine trough level, lipid profile, folic acid, and vitamin B12 concentrations and clinical characteristics of patients were assessed with the aim of ascertaining determinants of hyperhomocyst(e)inemia. RESULTS: Patient ages were 48.8 ñ 15.1 yr (group I), 43.3 ñ 11.3 yr (group II); and 46.5 ñ 14.8 yr (group III). Mean serum homocyst(e)ine (tHcy) concentrations were 18.07 ñ 8.29 mmol/l in renal transplant recipients; 16.55 ñ 5.6 mmol/l and 21.44 ñ 12.1 mmol/l respectively for group I (with cyclosporine) and group II (without cyclosporine) (NS). In renal donors, tHcy was significantly lower (9.07 ñ 3.06 mmol/l; group I + group II vs. group III, p<0.008). There was an unadjusted correlation (p<0.10) between age (r=0.427; p<0.005) body weight (r=0.412; p<0.05), serum creatinine (r=0.427; p<0.05), estimated creatinine clearance (r=0.316; p<0.10), and tHcy in renal recipients (group I +II). Independent regressors (r2=0.46) identified in the multiple regression model were age (coefficient= 0.253; p=0.009) and serum creatinine (coefficient=8.07; p=0.045). We found no cases of hyperhomocyst(e)inemia in the control group. In contrast, 38 per cent of renal recipients had hyperhomocyst(e)inemia: 7 cases (35 per cent) on cyclosporine and 4 (45 per cent) without cyclosporine, based on serum normal levels. CONCLUSIONS: Renal transplant recipients frequently have hyperhomocyst(e)inemia. Hyperhomocyst(e)inemia in renal transplant patients is independent of the scheme of immunosuppression they are taking. The older the patients are and the higher are their serum creatinine levels, the more susceptible they are to hyperhomocyst(e)inemia following renal transplantation

Homocysteine, a new cardiovascular risk factors

Homocystinuria is a rare inherited metabolic disease transmitted as an autosomal recessive trait. Arterial and venous thromboembolic events are frequent and life-threatening complications in homocystinuric patient. It has been suggested that mild homocysteinemia could be a risk factor for vascular disease. Homocysteine can promote lipid peroxidation and damage vascular endothelial cells. Moreover, homocysteine interferes with natural anticoagulant system and the fibrinolytic system. Homocysteinemia should be known in patients with premature vascular disease, especially in subjects with no risk factors. Folic acid, vitamin B6 can lower homocysteine levels