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Neurodegenerative diseases are the diseases of the central nervous system with various aetiology and symptoms. Dementia, Alzheimer's disease (AD), Parkinson's disease (PD) and autism are some examples of neurodegenerative diseases. Hyperhomocysteinemia (Hhcy) is considered to be an independent risk factor for numerous pathological conditions under neurodegenerative diseases. Along with genetic factors that are the prime cause of homocysteine (Hcy) imbalance, the nutritional and hormonal factors are also contributing to high Hcy levels in the body. Numerous clinical and epidemiological data confirm the direct correlation of Hcy levels in the body and generation of different types of central nervous system disorders, cardiovascular diseases, cancer and others. Till now, it is difficult to say whether homocysteine is the cause of the disease or whether it is one of the impacts of the diseases. However, Hhcy is a surrogate marker of vitamin B deficiency and is a neurotoxic agent. This Mini Review will give an overview of how far research has gone into understanding the homocysteine imbalance with prognostic, causative and preventive measures in treating neurodegenerative diseases., (© 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Background: Hyperhomocysteinemia (hyper-Hcy) is an important and reversible cardiovascular disease risk factor. We examined the prevalence of hyper-Hcy, plasma folate levels, and dietary folate intake in adolescents and young adults who had undergone kidney transplantation during childhood to assess the necessity for managing dietary folate., Methods: This cross-sectional study was performed in 89 kidney transplant recipients (age at kidney transplantation: 12.6 ± 4.1 years; age during study: 21.2 ± 5.5 years). Hyper-Hcy and plasma folate deficiency were defined as plasma homocysteine (Hcy) >15 nmol/ml and plasma folate <3.0 ng/ml, respectively., Results: Of the patients, 60 (67.4 %) had hyper-Hcy and 14 (15.7 %) had plasma folate deficiency. Plasma homocysteine levels correlated negatively with estimated glomerular filtration rate (eGFR; r = -0.565, p < 0.01) and plasma folate levels (r = -0.434, p < 0.01). For determinants of plasma homocysteine levels, a priori selected variables included kind of calcineurin inhibitor, age at kidney transplantation, pretransplant duration of dialysis, time since transplantation, age at examination, eGFR, and plasma folate. Stepwise multiple linear regression analysis revealed eGFR and plasma folate levels as significant independent variables influencing plasma homocysteine levels. Dietary folate intake in 11 of 16 patients (66.8 %) with eGFR ≥ 60 ml/min/1.73 m(2) was below the recommended dietary allowance for Japanese., Conclusions: The prevalence of hyper-Hcy and plasma folate deficiency, as well as the low dietary folate intake, suggest that dietary management of folate is necessary for adolescents and young adults who have undergone kidney transplantation during childhood.

Background/objectives: Unlike most Western populations, MTHFR 677T is a rare allele and a risk factor for a variety of disorders in India. What kind of nutritional (environmental) and/or genetic factors could contribute to the genetic risk is not known. To assess the incidence of hyperhomocysteinemia and its correlation with the polymorphism in homocysteine (Hcy)-pathway genes and associated cofactors in the native populations of eastern India., Subjects/methods: Healthy population from four eastern states of India. Genotyping of SNPs, HPLC and chemiluminescence-based assay for homocysteine, vitamin B12 and folic acid., Results: Approximately 30% of the population has hyperhomocysteinemia (>15 μmol/lit; hypHcy) with varying frequencies in the four states from where samples were collected (n=1426). Polymorphisms of MTR and CBS do not affect hypHcy. 677T and 1298C alleles of MTHFR and G80 RFC-1 show association with hypHcy. In contrast, RFC-1 80AA is protective even in presence of 677T MTHFR. Addition of each mutant allele has an additive effect on Hcy level. Vitamin B12 (cofactor in methionine synthesis) clearly modulates the genotypic effect on Hcy level. Although frequency of individuals with low folic acid is ≈11, 49% of the population is vitamin B12 deficient (<220 pg/lit) and has a significant negative correlation with Hcy. Individuals with optimum vitamin B12 and folic acid generally have low Hcy, even in risk genotypes., Conclusions: One of the plausible reasons for susceptibility of individuals with MTHFR C677T in the studied population to various disorders is the high frequency of hyperhomocysteinemia and vitamin B12 deficiency in the 'healthy population'. Apparently, supplementation of vitamin B(12) to this health-impoverished community may help lessen the risk of several multifactorial disorders.

Mild to moderate hyperhomocysteinemia has been recognized as an independent risk factor for coronary heart diseases, neurodegenerative diseases, osteoporosis, and pregnancy complications. Low intakes and decreased absorption of the B-vitamins are the most common causes of hyperhomocysteinemia, which is very prevalent in elderly people. The current review summarizes results from epidemiological studies and presents possible pathological mechanisms of hyperhomocysteinemia. In addition, the current study is a critical evaluation of results from several intervention studies that have been initiated for primary or secondary prevention of coronary and degenerative diseases. Lowering the risk of stroke is currently the most impressive effect of homocysteine-lowering-treatment and underlines the causal relationship. Available data is not sufficient for a final conclusion about the effectiveness of homocysteine-lowering in patients with coronary vascular diseases. Current recommendations stress the importance of measurement of plasma concentrations of homocysteine in patients with multiple risk factors. This allow early intervention with B-vitamins.

Elevated plasma homocysteine level is a risk factor for atherosclerotic disease. Plasma homocysteine levels are influenced by genetic, physiological and lifestyle factors. Among the lifestyle factors, diet plays a significant role. Dietary intakes of folate, vitamins B12, B6 and B2 have been reported to be inversely related to plasma homocysteine concentration. Prevalence of subclinical deficiencies of these vitamins is high in Indian population. Folate status is the major determinant of plasma homocysteine level and there is a strong inverse correlationship between plasma homocysteine level and serum or erythrocyte folate levels. A combination therapy with B vitamins--folate, vitamins B12 and B6 is an effective means to reduce elevated homocysteine levels in general people and in patients with myocardial infarction. To maintain low plasma homocysteine concentration, people should be advised to increase their consumption of pulses, eggs, green leafy vegetables and fruits which are rich in B vitamins.