Combination Of Folate Research Articles

Vitamin B12, Folate and Cognitive Function in Older Adults from Southern Brazil

Objective – To investigate if any combination of serum vitamin B12 and folate is superior to the use of separate vitamins for identify risk of probable cognitive deficit in older adults from southern Brazil. Methods -We analyzed data from the second wave (2013/14) of a population- and household-based survey. A total of 590 older adults (≥ 60 years) were included. Cognitive function was identified by the Mini-Mental State Examination (MMSE). The independent variables were serum levels of vitamin B12 and folate. The data were adjusted for age, education level, income, smoking status, alcohol intake, food intake, leisure-time physical activity, depression symptoms, chronic diseases, and body mass index. Results – High serum folate levels and their continuous increase were positively associated with cognition. The serum combination of vitamins most found in the study was the excess folate and normal for vitamin B12, but this combination was not associated with the cognitive function. Conclusion – The combination of folate and B12 is not high to any of them alone in associating with the probable or absence of cognitive deficit in older adults.

Effect of imbalance in folate and vitamin B12 in maternal/parental diet on global methylation and regulatory miRNAs

DNA methylation, a central component of the epigenetic network is altered in response to nutritional influences. In one-carbon cycle, folate acts as a one-carbon carrier and vitamin B12 acts as co-factor for the enzyme methionine synthase. Both folate and vitamin B12 are the important regulators of DNA methylation which play an important role in development in early life. Previous studies carried out in this regard have shown the individual effects of these vitamins but recently the focus has been to study the combined effects of both the vitamins during pregnancy. Therefore, this study was planned to elucidate the effect of the altered dietary ratio of folate and B12 on the expression of transporters, related miRNAs and DNA methylation in C57BL/6 mice. Female mice were fed diets with 9 combinations of folate and B12 for 4 weeks. They were mated and off-springs born (F1) were continued on the same diet for 6 weeks post-weaning. Maternal and fetal (F2) tissues were collected at day 20 of gestation. Deficient state of folate led to an increase in the expression of folate transporters in both F1 and F2 generations, however, B12 deficiency (BDFN) also led to an increase in the expression in both the generations. B12 transporters/proteins were found to be increased with B12 deficiency in F1 and F2 generations except for TC-II in the kidney which was found to be decreased in the F1 generation. miR-483 was found to be increased with all conditions of folate and B12 in both F1 and F2 generations, however, deficient conditions of B12 led to an increase in the expression of miR-221 in both F1 and F2 generations. The level of miR-133 was found to be increased in BDFN group in F1 generation however; in F2 generation the change in expression was tissue and sex-specific. Global DNA methylation was decreased with deficiency of both folate and B12 in maternal tissues (F1) but increased with folate deficiency in placenta (F1) and under all conditions in fetal tissues (F2). DNA methyltransferases were overall found to be increased with deficiency of folate and B12 in both F1 and F2 generations. Results suggest that the dietary ratio of folate and B12 resulted in altered expression of transporters, miRNAs, and genomic DNA methylation in association with DNMTs.

Effects of altered maternal folate and vitamin B12 on neurobehavioral outcomes in F1 male mice

Maternal folate and vitamin B12 status during pregnancy may influence development of central nervous system (CNS) in the offspring. Very little attention has been paid to understand the combined effects of both the vitamins during pregnancy. The present study was designed to evaluate the biochemical and behavioral outcomes following alterations in folate and vitamin B12 levels in C57BL/6 mice. The female mice were fed with different combinations of folate and vitamin B12 whereas; males were fed with normal diet for 4 weeks. The mice were mated and the pregnant mice received the same diets as before pregnancy. The F1 male mice were further continued on maternal diet for 6 weeks following neurobehavioral and biochemical assessment. The body weight of the F1 male mice was significantly decreased in the mice that received folate and vitamin B12 deficient diet. Altered cognitive functions were observed in the folate and B12 deficient F1 male mice as assessed by Morris water maze and novel object recognition tests. Spontaneous locomotor activity was decreased in F1 male mice fed with folate and B12 deficient diets. Elevated homocysteine levels and decreased hydrogen sulfide levels were also observed in the brain of F1 male mice on folate and B12 deficient diets. However, GSH and GSSG levels were increased in the brain of the animals supplemented with folate deficient diet with different combinations of B12. The study suggests that exposure of female mice to folate and vitamin B12 deficiency during pregnancy effects in-utero development of fetus, which further leads to behavioral anomalies in adult life and is sufficient to cause impaired cognitive behavior in the subsequent generation. Thus, elucidating the role and importance of maternal dietary folate and B12 ratio during pregnancy.

Lowering homocysteine and modifying nutritional status with folic acid and vitamin B12 in Indian patients of vascular disease

Hyperhomocysteinemia is more commonly associated with vascular disease in Indians than in the western populations. It is caused by genetic polymorphisms or dietary deficiencies of the B vitamins. We attempted to identify the association of hyperhomocysteinemia with vitamin B12 and folate in Indian patients of vascular disease. Homocysteine, vitamin B12 and folate levels were estimated in 100 controls and 100 patients of vascular disease. Homocysteine estimation was repeated in 73 patients on different vitamin supplements for 6 months. Homocysteine exhibited a significant negative correlation with B12 only in cerebrovascular disease and peripheral vascular diseasepatients, and with folate in coronary artery disease and cerebrovascular disease patients as well as controls. Single daily dose of folate was as effective as a combination of folate and cobalamin in reducing plasma homocysteine concentrations. Low levels of B12 contribute to the higher incidence of cerebrovascular disease and peripheral vascular disease, and low folate levels account for higher prevalence of hyperhomocysteinemia in coronary artery disease and cerebrovascular disease. Moreover, irrespective of the cause of hyperhomocysteinemia, folate is known to ameliorate it. Hence, large-scale corrective measures like food fortification or dietary supplementation with folate might benefit the Indian population and reduce the incidence and morbidity of vascular disease.

Stroke prevention - B vitamins

In a nutshellThe association between elevated Hcy, the B vitamins linked to it, and stroke incidence and severity appears strong.So far, a dozen RCTs, (almost all in patients with significant atherosclerosis), have tried to prevent stroke by reducing Hcy through various combinations of folate, B12and B6. In only one trial did this clearly succeed.

Neurologists’ Evaluation and Treatment of Hyperhomocysteinemia in Stroke Patients

Observational study data have suggested that neurologists preferentially selected younger patients with generally few traditional stroke risk factors for homocysteine testing. The aim of this study was to corroborate observational data by assessing neurologists' reported practices for the detection and treatment of hyperhomocysteinemia in patients with acute ischemic stroke. All academic neurology faculty (n = 49), trainees (neurology residents/fellows, n = 53), and a random sample of community-based neurologists (n = 66) throughout North Carolina were surveyed regarding their homocysteine testing and treatment practices. Nine neurologists were ineligible because they had either retired or moved out of state. A total of 93 of the remaining 159 surveys (58.5%) were completed (response rates: faculty, 74%; trainees, 47%; community-based neurologists, 56%). Patients age < 50 years (n = 52; 63%) and the absence of traditional stroke risk factors (n = 57; 70%) were the most common factors cited as prompting homocysteine testing. The homocysteine level threshold for treatment varied independently by practice type (faculty: median, 14 mumol/L; range, 6-16 mumol/L; trainees: median, 14.5 mumol/L; range, 10-20 mumol/L; community-based: median, 10.4 mumol/L; range, 7-15 mumol/L; P = .01), the number of stroke patients evaluated during a typical week (Spearman's r = .32; P = .034), and year of training completion (Spearman's r = .41; P = .003). About half (51%) treat elevated homocysteine with a combination of folate, vitamin B(12), and vitamin B(6). Consistent with observational data, the majority of the neurologists surveyed report that they select young stroke patients who lack traditional stroke risk factors for homocysteine testing. Thresholds for treatment varied between community-based and academic neurologists and correlated with the physicians' stroke patient volume.

Homocysteine, B-vitamin supplementation, and stroke prevention: from observational to interventional trials

Homocysteine is an amino acid, the metabolism of which is linked to that of several vitamins-especially folic acid, B6, and B12. A high concentration of homocysteine in the plasma is linked to vascular disease, including stroke. Concentrations of homocysteine can be inexpensively and safely lowered by treatment with a combination of folate, vitamin B12, and vitamin B6. However, whether the association between high plasma concentrations of homocysteine and vascular disease is causal is unclear. Two studies have assessed the relation between dietary or supplementary B vitamin intake on the risk of stroke. In a prospective observational study of 43?732 healthy men, there was an inverse relation between dietary folate intake and the risk of ischaemic stroke. The Vitamin Intervention for Stroke Prevention study (VISP) was the first large-scale randomised interventional study that investigated the lowering of homocysteine concentrations with B vitamins in patients with ischaemic stroke. There was an association between baseline homocysteine concentrations and vascular risk in this trial. Plasma concentrations of homocysteine were only modestly reduced by high-dose versus low-dose formulation, and there was no treatment effect on recurrent stroke, coronary events, or deaths. Limitations of VISP included that only patients with mild increases in baseline homocysteine concentrations were studied, only modest reductions of homocysteine concentrations were achieved, and follow up was short. In addition, fortification of food with folate and treatment of low vitamin-B12 concentrations may have masked the effect of treatment on stroke risk. WHAT NEXT?: When exposure can be safely assigned at random, as in the case of B-vitamin therapy, randomised trials should be the standard proof to determine the effect of therapy. The results of the first randomised clinical trial of B vitamins for secondary prevention of stroke were neutral. Larger trials with longer follow-up, selection of patients with higher plasma concentrations of homocysteine, and systematic assessment of cognitive functions and dementia are needed. In the meantime, homocysteine-lowering treatment that is cheap and well-tolerated should be considered a rational approach in patients at high risk of stroke and high concentrations of homocysteine.

Statistical Interaction Model for Exchangeability of Food Folates in a Rat Growth Bioassay

The comparative value of several sources of dietary folate in promoting growth of folate-depleted rats was determined in a folate depletion-repletion rat growth bioassay. Folate-depleted rats were fed an amino acid-based diet supplemented with 11 different concentrations of folate (227, 272, 317, 363, 408, 454, 499, 544, 590, 635 and 680 nmol/kg) from each of 12 different sources of folate (folic acid, fried beef liver, cooked pinto beans individually, or as 1/3, 1/1, or 3/1 combinations of folate from the folic acid/beans, folic acid/beef liver and beans/beef liver) for a total of 132 treatments. Growth response to folic acid and bean folate was linear, whereas that to beef liver folate was distinctly nonlinear, beef liver folate being more potent at lower dietary concentrations but less potent at higher concentrations compared with folic acid and bean folate. Folic acid and bean folate were equivalent to and exchangeable with one another in promoting growth. Beef liver folate and folic acid/bean folate had an interactive effect in promoting growth. The nature of the interaction was antagonistic in that the presence of folic acid and/or bean folate reduced the efficacy of beef liver folate and vice versa. Beef liver folate is not exchangeable with either folic acid or bean folate. We conclude that food folates generally are not exchangeable and do interact adversely. A statistical interaction model that predicted the growth-promoting effect of several sources of dietary folate was developed and validated.