Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials

Objective: To determine the size of reduction in homocysteine concentrations produced by dietary supplementation with folic acid and with vitamins B-12 or B-6.

Dose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials

Background: Dietary supplementation with B vitamins that lower blood homocysteine concentrations is expected to reduce cardiovascular disease risk, but there has been uncertainty about the optimum regimen to use for this purpose.

A rapid dietary assessment tool to determine intake of folate was developed and validated

Background and Objective: Estimates of dietary folate intake are currently of considerable interest, but no rapid tools are available to assess dietary intake of folate that are well suited to everyday health promotion activities, We developed and tested the reliability and validity of two prototypes of a rapid dietary assessment tool (a folate intake tool, FIT) to determine dietary intake of folate. Study Design and Setting: Five hundred and sixty eight men and women aged 33-93 years from Perth, Western Australia. Completed one of the two prototypes of the tool and gave a fasting blood sample for measurement of serum folate. A subset (n - 277) of participants completed the same tool on a second occasion 3-6 weeks later. Results: The Pearson correlations (r) between folate score from the tool and serum folate were moderately high for both prototypes (FIT-A r = 0.54-, FIT-B r = 0.49). The folate scores for the two prototypes were similar on repeat testing and correlated strongly (FIT-A r = 0.75; FIT-B r = 0.68). Conclusions: The rapid dietary assessment tool described here, FIT, provides a valid and reliable measurement of dietary intake of folate for both men and women. (c) 2005 Elsevier Inc. All rights reserved.

Red clover (Trifolium pratense) isoflavones and serum homocysteine in premenopausal women : a pilot study

Background: There is limited information on the effect of isoflavones on homocysteine concentrations, a risk factor for a number of chronic diseases. Methods: Twenty-three premenopausal women participated in a double-blind, randomized, parallel study for four menstrual cycles. Subjects consumed either placebo or purified red clover (Trifolium pratense) isoflavone (86mg/day) tablets. Blood samples were collected weekly during cycles 1, 3, and 4 for determination of serum folate and total homocysteine concentrations. Dietary intake was monitored monthly. Results: Concentrations of folate and homocysteine in serum did not change significantly in either group, and there were no significant differences observed between the follicular and luteal phases of the menstrual cycle. The participants' dietary records indicated that nutrient intake was constant, and compliance was confirmed by analysis of urinary isoflavone concentrations and tablet counts in returned containers. Conclusions: These results suggest that in the absence of any dietary modification, supplementation with purified isoflavones that are predominantly methoxylated has no effect on serum homocysteine or folate in premenopausal women.

Plasma Homocysteine Is Not Subject to Seasonal Variation.

Background: Studies investigating the relationship between plasma total homocysteine (tHcy) and vascular disease usually rely on a single measurement. Little information is available, however, on the seasonal variability of plasma tHcy. The aim of this study was to investigate the seasonal variation in fasting plasma tHcy and related B-vitamin intake and status in a group of people who did not consume fortified foods or take B-vitamin supplements. Methods: In this longitudinal study, a group of 22 healthy people were followed for 1 year. A fasting blood sample and dietary information were collected from each individual every 3 months, i.e., at the end of each season. Results: There was no significant seasonal variation in plasma tHcy or in B-vitamin intake or status with the exception of red cell folate (significantly lower in spring compared with autumn or winter) and serum folate (significantly lower in spring compared with the other seasons). Although the between-person variation in plasma tHcy was high (47%), the within-person variation was low (11%). This low variation, combined with the low methodologic imprecision of 3.8%, yielded a high reliability coefficient for plasma tHcy (0.97). Conclusions: Although there was a small seasonal variation in folate status, there was no corresponding seasonal variation in plasma tHcy. The high reliability coefficient for plasma tHcy suggests that a single measurement is reflective of an individual’s average plasma tHcy concentration, thus indicating its usefulness as a potential predictor of disease. This, however, needs to be confirmed in different subgroups of the population.

Homocysteine and B-group vitamins in renal transplant patients

Increased plasma homocysteine is an independent risk factor for cardiovascular disease. We have investigated homocysteine and B-group vitamin levels in renal transplant patients. Fasting blood was collected from 55 renal transplant recipients with good renal function and 32 age/sex matched control subjects. Total homocysteine was increased in transplant recipients in comparison to controls (10.9+/-1.5 vs. 6.7+/-1.3 micromol/l, P < 0.001). There was no difference in homocysteine between patients receiving cyclosporin (n = 39, homocysteine 11.0+/-1.5 micromol/l) and patients receiving prednisolone + azathioprine (n = 16, 10.8+/-1.6 micromol/l, mean+/-S.D.), although there was a significant correlation between homocysteine and serum cyclosporin concentration in the sub-group of patients receiving that immunosuppressive regimen (r = 0.42, P < 0.05). Levels of B-group vitamins were similar in patients and controls. Plasma homocysteine is increased in renal transplant recipients even in the presence of minor degrees of renal impairment and normal levels of B-group vitamins.

Response of red blood cell folate to intervention: implications for folate recommendations for the prevention of neural tube defects

Committees worldwide have set almost identical folate recommendations for the prevention of the first occurrence of neural tube defects (NTDs). We evaluate these recommendations by reviewing the results of intervention studies that examined the response of red blood cell folate to altered folate intake. Three options are suggested to achieve the extra 400 mu g folic acid/d being recommended by the official committees: increased intake of folate-rich foods, dietary folic acid supplementation, and folic acid fortification of food. A significant increase in foods naturally rich in folates was shown to be a relatively ineffective means of increasing red blood cell folate status in women compared with equivalent intakes of folic acid-fortified food, presumably because the synthetic form of the vitamin is more stable and more bioavailable. Although folic acid supplements are highly effective in optimizing folate status, supplementation is not an effective strategy for the primary prevention of NTDs because of poor compliance. Thus, food fortification is seen by many as the only option likely to succeed. Mandatory folic acid fortification of grain products was introduced recently in the United States at a level projected to provide an additional mean intake of 100 mu g folic acid/d, but some feel that this policy does not go far enough. A recent clinical trial predicted that the additional intake of folic acid in the United States will reduce NTDs by >20%, whereas 200 mu g/d would be highly protective and is the dose also shown to be optimal in lowering plasma homocysteine, with possible benefits in preventing cardiovascular disease. Thus, an amount lower than the current target of an extra 400 mu g/d may be sufficient to increase red blood cell folate to concentrations associated with the lowest risk of NTDs, but further investigation is warranted to establish the optimal amount.

Plasma total homocysteine and carotid intima-media thickness in type 1 diabetes: A prospective study

Objective: Plasma total homocysteine (tHcy) has been positively associated with carotid intima-media thickness (IMT) in non-diabetic populations and in a few cross-sectional studies of diabetic patients. We investigated cross-sectional and prospective associations of a single measure of tHcy with common and internal carotid IMT over a 6-year period in type 1 diabetes. Research design and methods: tHcy levels were measured once, in plasma obtained in 1997–1999 from patients (n = 599) in the Epidemiology of Diabetes Interventions and Complications (EDIC) study, the observational follow-up of the Diabetes Control and Complications Trial (DCCT). Common and internal carotid IMT were determined twice, in EDIC “Year 6” (1998–2000) and “Year 12” (2004–2006), using B-mode ultra-sonography. Results: After adjustment, plasma tHcy [median (interquartile range): 6.2 (5.1, 7.5) μmol/L] was significantly correlated with age, diastolic blood pressure, renal dysfunction, and smoking (all p < 0.05). In an unadjusted model only, increasing quartiles of tHcy correlated with common and internal carotid IMT, again at both EDIC time-points (p < 0.01). However, multivariate logistic regression revealed no significant associations between increasing quartiles of tHcy and the 6-year change in common and internal carotid IMT (highest vs. lowest quintile) when adjusted for conventional risk factors. Conclusions: In a type 1 diabetes cohort from the EDIC study, plasma tHcy measured in samples drawn in 1997–1999 was associated with measures of common and internal carotid IMT measured both one and seven years later, but not with IMT progression between the two time-points. The data do not support routine measurement of tHcy in people with Type 1 diabetes.

Association of serum homocysteine with major depressive disorder: results from a large population-based study.

BACKGROUND: Studies on the association between homocysteine levels and depression have shown conflicting results. To examine the association between serum total homocysteine (tHcy) levels and major depressive disorder (MDD) in a large community sample with an extended age range. METHODS: A total of 3392 men and women aged 35-66 years participating in the CoLaus study and its psychiatric arm (PsyCoLaus) were included in the analyses. High tHcy measured from fasting blood samples was defined as a concentration ≥15μmol/L. MDD was assessed using the semi-structured Diagnostic Interview for Genetics Studies. RESULTS: In multivariate analyses, elevated tHcy levels were associated with greater odds of meeting the diagnostic criteria for lifetime MDD among men (OR=1.71; 95% CI, 1.18-2.50). This was particularly the case for remitted MDD. Among women, there was no significant association between tHcy levels and MDD and the association tended to be in the opposite direction (OR=0.61; 95% CI, 0.34-1.08). CONCLUSIONS: In this large population-based study, elevated tHcy concentrations are associated with lifetime MDD and particularly with remitted MDD among men.

Serum homocysteine and physical exercise in patients with Parkinson's disease

Background: Hyperhomocysteinemia is a major risk factor for cerebral and peripheral vascular diseases, as well as cortical and hippocampal injury, including an increased risk of dementia and cognitive impairment. Elevated serum homocysteine (Hcy) concentrations are common in patients with Parkinson's disease (PD) who have been treated with levodopa; however, physical exercises can help reduce Hcy concentrations. The aim of the present study was to compare serum Hcy levels in patients with PD who partook in regular physical exercises, sedentary PD patients, and healthy controls.Methods: Sixty individuals were enrolled in the present study across three groups: (i) 17 patients who did not partake of any type of exercise; (ii) 24 PD patients who exercised regularly; and (iii) 19 healthy individuals who did not exercise regularly. All participants were evaluated by Hoehn and Yahr scale, the Unified Parkinson's Disease Rating Scale (UPDRS) and Schwab and England scale (measure daily functionality). The serum levels of Hcy were analyzed by blood samples collected of each participant. An analysis of variance and a Tukey's post hoc test were applied to compare and to verify differences between groups. Pearson's correlation and stepwise multiple regression analyses were used to consider the association between several variables.Results: Mean plasma Hcy concentrations in individuals who exercised regularly were similar to those in the healthy controls and significantly lower than those in the group that did not exercise at all (P = 0.000). In addition, patients who did not exercise were receiving significantly higher doses of levodopa than those patients who exercised regularly (P = 0.001). A positive relationship between levodopa dose and Hcy concentrations (R(2) = 0.27; P = 0.03) was observed in patients who did not exercise, but not in those patients who exercised regularly (R(2) = 0.023; P = 0.15).Conclusions: The results of the present study suggest that, even with regular levodopa therapy, Hcy concentrations in PD patients who exercise regularly are significantly lower than in patients who do not exercise and are similar Hcy concentrations in healthy controls.