Effect of multivitamin supplementation on the homocysteine and methylmalonic acid blood concentrations in women over the age of 60 years

Summary Background Deficiency of folic acid, vitamin B₆ and/or vitamin B₁₂ can result in elevated total plasma homocysteine concentrations (tHcy), which are considered to be a risk factor for vascular disease. Studies have shown that supplementation of the three vitamins can lower tHcy even in subjects with tHcy in the normal range. Aim of the study The aim of this study was to evaluate the effect of a 6 month supplementation with vitamin B₆, B₁₂ and folate on the concentrations of total plasma homocysteine and serum methylmalonic acid (MMA) of elderly women. Methods The study was designed as a randomized placebo controlled doubleblind trial, and 220 healthy women (aged 60–91 years) were involved. The vitamin and mineral capsule contained pyridoxine (3.4 mg), folic acid (400 µg) and cobalamin (9 µg) in addition to other micronutrients. Blood concentrations of folate, cobalamin, tHcy, MMA and the activity coefficient of erythrocyte alpha-aspartic aminotransferase (alpha-EAST) were measured at baseline and after 6 months of supplementation. Dietary intake was evaluated at the beginning and the end of the intervention by two 3–day diet records. Results Median concentrations of serum cobalamin, serum folate and erythrocyte folate increased significantly and tHcy and alpha–EAST activity (indicative of improved status of vitamin B₆) coefficient decreased significantly in the supplemented group. Median MMA concentration of the supplemented group was significantly lower than that of the placebo group after the intervention. The vitamin supplementation had a greater decreasing effect on the tHcy concentration of volunteers with lower vitamin and higher tHcy initial concentrations. In a linear regression model, baseline tHcy, serum folate, age and alpha–EAST activity coefficient were significantly correlated with the change in tHcy. The change in MMA in the supplement group was significantly associated to the baseline MMA values. Conclusions Our results show that a 6 month supplementation including physiological dosages of B vitamins improves the status of these nutrients and reduces tHcy in presumed healthy elderly women.     

Three-month B vitamin supplementation in pre-school children affects folate status and homocysteine,but not cognitive performance

Background

Suboptimal vitamin B status might affect cognitive performance in early childhood. We tested the hypothesis that short-term supplementation with folic acid and selected B vitamins improves cognitive function in healthy children in a population with relatively low folate status.

Methods

We screened 1,002 kindergarten children for suboptimal folate status by assessing the total urinary para-aminobenzoylglutamate excretion. Two hundred and fifty low ranking subjects were recruited into a double blind, randomized, controlled trial to receive daily a sachet containing 220 μg folic acid, 1.1 mg vitamin B₂, 0.73 mg B₆, 1.2 μg B₁₂ and 130 mg calcium, or calcium only for 3 months. Primary outcomes were changes in verbal IQ, short-term memory and processing speed between baseline and study end. Secondary outcomes were urinary markers of folate and vitamin B₁₂ status, acetyl-para-aminobenzoylglutamate and methylmalonic acid, respectively, and, in a subgroup of 120 participants, blood folate and plasma homocysteine.

Results

Pre- and post-intervention cognitive measurements were completed by 115 children in the intervention and 122 in the control group. Compared to control, median blood folate increased by about 50 % (P for difference, P < 0.0001). Homocysteine decreased by 1.1 μmol/L compared to baseline, no change was seen in the control group (P for difference P < 0.0001) and acetyl-para-aminobenzoylglutamate was 4 nmol/mmol higher compared to control at the end of the intervention (P < 0.0001). We found no relevant differences between the groups for the cognitive measures.

Conclusion

Short-term improvement of folate and homocysteine status in healthy children does not appear to affect cognitive performance.     

High prevalence of hyperhomocysteinemia in chronic alcoholism: the importance of the thermolabile form of the enzyme methylenetetrahydrofolate reductase (MTHFR)

Alcoholism is related to malnutrition and low levels of several vitamins that take part in the metabolism of homocysteine. The objective of the study was to analyze the prevalence of hyperhomocysteinemia in patients with heavy alcohol intake and the factors on which it depends. Included in the study were 103 hospitalized heavy drinkers (i.e., patients with an intake of alcohol greater than 80 g per day). Serum homocysteine, folate, and vitamin B₁₂ levels, plasma vitamin B₆ levels, and CT677 polymorphisms of methylenetetrahydrofolate reductase (MTHFR) were determined. We also recorded the intensity of alcoholism, the status of nutrition, and the existence of liver cirrhosis. Determination of biochemical data was repeated after 15 days of withdrawal. Serum homocysteine levels were found to be significantly elevated, whereas serum folate and plasma B₆ levels were significantly decreased. Serum homocysteine levels were significantly higher in those heavy drinkers who showed the TT polymorphism of MTHFR, with a prevalence of hyperhomocysteinemia of 84.2% in the homozygote TT, 54.3% in the heterozygote CT, and 31.6% in the normal CC genotype. Serum homocysteine inversely correlated with serum folate, serum B₁₂, and plasma B₆ levels. We did not find any relation between serum homocysteine and intensity of alcoholism, nutritional status, or liver cirrhosis. Serum folate levels were significantly decreased in heavy drinkers, mainly depending on irregular feeding and malnutrition. After 15 days of withdrawal, serum homocysteine levels significantly decreased, whereas folate, B₁₂, and B₆ levels significantly increased. The conclusion is that heavy drinkers show a high prevalence of hyperhomocysteinemia related to low levels of folate, B₆, and B₁₂ and to the TT polymorphism of MTHFR. © 2001 Elsevier Science Inc. All rights reserved.     

The association between high plasma homocysteine levels and lower bone mineral density in Slovak women: the impact of vegetarian diet

Background  

A long-term vegetarian diet is generally poor in vitamin B group. The lack of vitamin B₁₂ together with vitamin B₆ and folate deficiency is closely related to homocysteine metabolism. Hyperhomocysteinemia was found to be associated with increased bone turnover markers and increased fracture risk. Thus, hyperhomocysteinemia, vitamin B₁₂ and folate deficiency may be regarded as novel risk factors for micronutrient deficiency-related osteoporosis.     

Intake of Folate,Vitamin B6 and Vitamin B12 and the Risk of CHD: The Japan Public Health Center-Based Prospective Study Cohort I

Objective: To investigate the association of dietary folate, vitamin B₆ (VB₆) and vitamin B₁₂ (VB₁₂) with the risk of coronary heart disease among middle-aged persons.

Methods: A total of 40,803 subjects aged 40–59 years living in the community who were free of prior diagnoses of cardiovascular disease and cancer and who completed a food frequency questionnaire were followed from 1990–1992 to the end of 2001 in the Japan Public Health Center-based Prospective Study.

Results: After 468,472 person-years of follow-up, 251 coronary heart disease incidents were documented. Coronary heart disease and definite myocardial infarction were inversely associated with dietary intake of folate, VB₆ and VB₁₂ after adjustment for age and sex, but the associations were attenuated after further adjustment for smoking, dietary and other cardiovascular risk factors. However, among non-multivitamin supplement users, multivariable hazard ratios (95% confidence intervals) in the highest vs. lowest quintiles of VB₆ intake were 0.60 (0.37–0.97) for total coronary heart disease and 0.52 (0.29–0.91) for definite myocardial infarction, and the inverse associations with VB₁₂ were marginally significant. The combination of below-median intake of three vitamins or of only B₆ conferred a twice excess risk of total coronary heart disease.

Conclusions: Dietary intake of VB₆ was associated with a reduced risk of coronary heart disease among middle-aged non-multivitamin supplement users. Dietary folate and VB₁₂ were also suggested to be protective factors for coronary heart disease.     

A critical evaluation of the relationship between serum vitamin B12, folate and total homocysteine with cognitive impairment in the elderly

Background Serum homocysteine increases with age and is also considered a marker for low serum vitamin B₁₂ and folate. Furthermore, raised serum total homocysteine has been associated with atrophic changes in the brain. An association between serum vitamin B₁₂/folate and cognitive impairment would be of considerable public health importance in view of the increasing numbers of elderly people. Aim To systematically review published studies on the relationship between serum vitamin B₁₂, folate and total homocysteine and cognitive function in the elderly. Design and data sources A systematic review was undertaken of published evidence in English, examining the association between low serum vitamin B₁₂/folate and raised total homocysteine with cognitive impairment (as indicated by low scores on neuropsychological testing) in subjects aged over 60 years. Sixteen electronic databases and cited articles were searched. Of 383 potential articles, six fulfilled the eligibility criteria: three case control and three cohort studies were identified. ‘The Cochrane Non‐Randomized Studies Methods Group’ guidelines were used for assessment and extraction of data from these studies. Results All three case control studies found that serum total homocysteine was significantly higher in cases when compared with controls, and there was wide variation for both serum vitamin B₁₂ and folate in both groups of participants. The relationship of serum folate and vitamin B₁₂ status with cognitive impairment was heterogeneous and one case control study reported decreasing cognitive scores with increasing serum vitamin B₁₂. In the cohort studies, although serum total homocysteine could predict the rate of decline in neuropsychological testing, the overall odds ratio/relative risk (RR) of developing cognitive impairment in relation to levels of serum B₁₂ and serum folate were not significant. Although one study reported a significant RR of developing Alzheimer's disease when both serum folate and B₁₂ levels were low. One cohort study reported an increased prevalence of Alzheimer's type dementia in subjects who had normal serum vitamin B₁₂ at baseline. Conclusion Serum total homocysteine is negatively correlated with neuropsychological tests scores. But the evidence does not support a correlation between serum vitamin B₁₂ or folate and cognitive impairment in people aged over 60 years. Hence, there is little evidence to justify treating cognitive impairment with vitamin B₁₂ or folate supplementation. This is consistent with the findings from recent systematic reviews of randomized double‐blind trials, which have not found any evidence of potential benefit of vitamin supplementation. Further research is required in order to establish whether raised serum total homocysteine is a cause or consequence of disease.     

Factors affecting the distribution of folate forms in the serum of elderly German adults

Purpose

We investigated the roles of age, vitamin B₁₂ markers, and the 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism as determinants of folate forms in serum.

Methods

We measured the serum concentrations of (6S)-5-CH₃–H₄folate, (6S)-H₄folate, (6S)-5-HCO–H₄folate, (6R)-5,10-CH⁺–H₄folate, and folic acid in 146 non-supplemented older participants (median age 74 years). The concentrations of total vitamin B₁₂, holotranscobalamin (holoTC), methylmalonic acid (MMA), and total homocysteine (tHcy) were also measured.

Results

Elevated metabolites (MMA > 271 nmol/L and tHcy > 12.0 μmol/L) were found in 24.0 and 63.0 % of the participants, respectively. We found a significant age-dependent decrease (participants with a median age of 87 years compared with participants with a median age of 60 years) in the sum of serum folate levels, the (6S)-5-CH₃–H₄folate concentration, and the (6S)-5-CH₃–H₄folate proportion. In addition, participants with elevated metabolite levels were older, had lower concentrations of the sum of folates and (6S)-5-CH₃–H₄folate, and had higher concentrations of (6S)-5-CHO–H₄folate and creatinine but had a comparable holoTC/total vitamin B₁₂ ratio. No association was found between the MTHFR C677T genotype and serum folate forms.

Conclusion

Low serum (6S)-5-CH₃–H₄folate concentrations and the proportion of (6S)-5-CH₃–H₄folate (percentage of the sum of folate forms) are related to older age and elevated MMA and tHcy levels.     

Homocysteine levels and cognitive function scores measured with MMSE and BCAT of middle-aged and elderly subjects in Tianjin City

Objective

China is proceeding into the aging society. There are near 6 million elderly suffering senile dementia, while cognitive impairment is an important clinical feature in dementia. The factors involved in cognitive dysfunction in the middle-aged and the elderly persons were investigated.

Design

Cross-sectional study.

Setting

Community dwellers and nursing home residents in Tianjin, China.

Subjects

Total of 662 subjects(284 men and 378 women) aged 55–93.

Methods

A designed questionnaire was used to collect their demographic data, information of disease and medication, and life style. Mini-mental state examination (MMSE) and Basic Cognitive Aptitude Tests (BCAT) software were applied to evaluate their cognitive function. Serum total homocysteine (tHcy) level was quantified by enzyme conversion method. A multiple linear stepwise regression analysis was applied to find the influencing factors of cognitive function.

Results

The average serum tHcy concentrations was 15.95±7.29 μmol/L, while the prevalence of hyperhomocysteinemia (HHE) was 45.4%. The average serum tHcy level and prevalence of HHE were higher in men than those in women after ruling out the age differences. The mean MMSE and BCAT scores were 26.74±2.71 and 50.26±18.84 respectively. The BCAT score was negatively correlated with age and positively correlated with education. Multiple linear stepwise regression equations showed that the P value was less than 0.001, the BCAT regression equation showed that the R2=0.453. Serum tHcy concentration was negatively correlated with total scores of BCAT, digit copy, Chinese character comparison, mental arithmetic, Chinese character rotation and recall answer of mental arithmetic test. Total scores of BCAT were negatively correlated with education, inhabitancy, serum tHcy concentration and age. In addition, Chinese character rotation was correlated with tea consumption. Remembrance and recognition of dual words and nonsense figures was correlated with income level.

Conclusions

Hyperhomocysteinemia is associated with cognitive impairment in the middle-aged and the elderly persons in Tianjin. The BCAT scores could well represent the detailed cognitive function in elderly and negatively correlate with age, but positively correlated with education level. Serum tHcy concentration was negatively correlated with total BCAT scores..     

Interplay of vitamin D,vitamin B12, homocysteine and bone mineral density in postmenopausal females

ABSTRACT

Osteoporosis is most common age related, multifactorial disease. The aim of the researchers were to discover the association between serum homocysteine, vitamin D, vitamin B₁₂ and bone mineral density in postmenopausal non-osteoporotic and osteoporotic females. In this cross- sectional study, 156 postmenopausal females between 50–70 years of age were recruited and divided into two groups, non-osteoporotic (n = 52) and osteoporotic (n = 104). There was significant negative correlation of homocysteine with vitamin D and B₁₂ in postmenopausal non-osteoporotic and homocysteine with vitamin B₁₂ in postmenopausal osteoporotic females. Serum homocysteine levels were predicted by vitamin D in postmenopausal non-osteoporotic and vitamin B₁₂ in postmenopausal osteoporotic females.     

Hyperhomocysteinemia and vitamin B-12 deficiency in elderly using Title IIIc nutrition services

BACKGROUND: The effect of the folate food fortification program on the prevalence of hyperhomocysteinemia in the older population with coexisting vitamin B-12 deficiency is not known. OBJECTIVE: The objective was to determine the prevalence of hyperhomocysteinemia and vitamin B-12 deficiency in elderly who were using Title IIIc nutrition services, after folate food fortification in the United States. DESIGN: Demographic, nutritional, cognitive, routine diagnostic, and serum methylmalonic acid (MMA) and total homocysteine (tHcy) tests were performed in a convenience sample of 103 elderly enrolled in nutrition service programs in rural northeast Georgia. A subgroup (n = 27) was treated with vitamin B-12, 2.5 mg, and a multivitamin with 400 micro g folic acid, 2 mg vitamin B-6, and 27 mg ferrous fumarate. RESULTS: The total cohort included 103 participants (+/- SD age: 76.4 +/- 8.1; 80% female; 68% white, 32% African American). Vitamin B-12 deficiency (serum vitamin B-12 < 258 pmol/L and MMA > 271 nmol/L) was present in 23%. Mean serum folate was high, 39.3 nmol/L, and no subject had serum folate < 6.8 nmol/L. Mean tHcy was 17.6 +/- 7.2 micro mol/L in vitamin B-12-deficient subjects and 10.8 +/- 3.6 micro mol/L in those who were nondeficient. Determinants of high tHcy were vitamin B-12 deficiency, high serum creatinine, and low red blood cell folate. Those with vitamin B-12 deficiency were more likely to have poor cognition (58% compared with 20%, P < 0.001) and anemia (38% compared with 18%, P = 0.042). High-dose oral B-12 therapy lowered mean MMA and tHcy by 49% and 32%, respectively. CONCLUSION: Vitamin B-12 deficiency was prevalent and was associated with poor cognition, anemia, and hyperhomocysteinemia.     

Folate Status Worsens in Recently Institutionalized Elderly People without Evidence of Functional Deterioration

Objective: To follow folate status, hematological and cognitive changes during the first year of institutionalization among elderly subjects.

Design: Prospective study.

Setting: Long-stay unit of the Dijon University Geriatric Hospital.

Subjects: Twenty women and four men older than 65 years admitted consecutively.

Main outcome measures: Folate and vitamin B-6 dietary intake was evaluated by a five-day record on admission (day 1 or d 1), at day 45 (d 45), day 90 (d 90), day 135 (d 135), day 180 (d 180), day 360 (d 360). Circulating levels of folate, vitamin B-6, total homocysteine (tHcy), blood counts and cognitive performance were determined in parallel.

Results: From d 1 to d 360, mean folate and vitamin B-6 intakes remained below the French RDA and mean folate intakes decreased significantly (Δ = ?10.2%, p <0.05). Mean plasma or erythrocyte folate decreased significantly (Δ = ?33.7%, p <0.05 and Δ = ?30.2%, p <0.001, respectively) from d 1 to d 360; no significant change was observed for the other blood parameters. The incidence of folate deficiency increased (8% vs. 37% for plasma folate <6.8 nmol/L and 8% vs. 17% for erythrocyte folate <340 nmol/L) from d 1 to d 360. Mean plasma pyridoxal 5′-phosphate (PLP) remained <20 nmol/L during the one-year follow-up. There was no difference between genders for plasma tHcy. Although mean plasma tHcy was <14 μmol/L, plasma tHcy was >14 μmol/L in about one-third of the subjects. At each period, 50% or more subjects were anemic (Hct <35% in women and Hct <40% in men), but the anemia was normocytic (MCV <100 fL). Subjects had a moderate dementia at admission, and no change was observed during the study.

Conclusions: Subjects were already vitamin B-6 deficient at admission. Folate status was impaired during the study. Low vitamin intakes were the main cause of vitamin B-6 deficiency and folate status deterioration. Hematology and mental status capacity were not aggravated by folate status deterioration. Plasma tHcy didn’t appear to be an earlier predictor of folate deficiency.     

Oral vitamin B12 supplementation reduces plasma total homocysteine concentration in women in India

People in India have a high prevalence of low vitamin B12 status and high plasma total homocysteine (tHcy) concentrations. In a proof of principle trial, we studied the effect of oral vitamin B12 (500 microg) and/or 100 g cooked green leafy vegetables (GLV) every alternate day in a 2x2 factorial design over a 6-week period. Forty-two non-pregnant vegetarian women (age 20-50 years) were randomly allocated to four study groups. Clinical measurements were made at the beginning and at the end of the study, and blood samples were collected before, and 2 and 6 weeks after commencement of intervention. Forty women completed the trial. Twenty-six women had low vitamin B12 status (<150 pmol/L) and 24 had hyperhomocysteinemia (>15 micromol/L). GLV supplementation did not alter plasma folate or tHcy. Vitamin B12 supplementation increased plasma vitamin B12 concentration (125 to 215 pmol/L, p <0.05) and reduced tHcy concentration (18.0 to 13.0 micromol/L, p <0.05) within first 2 weeks, both of which remained stable for the next 4 weeks. Plasma vitamin B12 and tHcy concentrations did not change in those who did not receive vitamin B12, and there was no change in plasma folate concentration in any of the groups. Blood haemoglobin concentration increased marginally within first two weeks in those women who received vitamin B12 (by 3 g/L, p <0.05) and the number of women with macrocytosis decreased from 2 to zero. There was no change in vibration sensory threshold during the period of the study. High-dose per oral vitamin B12 supplementation significantly reduced plasma tHcy within 2 weeks but did not achieve normal plasma tHcy concentration even after 6 weeks. People in India have a high prevalence of low vitamin B12 status and high plasma total homocysteine (tHcy) concentrations.     

Correlations between folate, B12, homocysteine levels, and radiological markers of neuropathology in elderly post-stroke patients

OBJECTIVE: To investigate serum levels of folate, B12, and total homocysteine (tHcy) in elderly post-stroke patients, and the possible correlations with radiological markers of neuropathology. DESIGN: Cross-sectional study. SETTING: Department of Neurology, Cardinal Tien Hospital. SUBJECTS: Eighty-nine elderly post-stroke patients were enrolled for dietary assessment and blood tests. Neuroradiological assessment was done in 62 of these patients. MAIN OUTCOME MEASURES: Dietary folate and vitamin B12 intakes were evaluated by a 24-h recall system using a semi-quantitative questionnaire. Circulating levels of folate, B12, and tHcy were measured. Magnetic resonance imaging (MRI) or computed tomography (CT) was used for evaluation of brain lesions including infarction and atrophy. RESULTS: Mean folate and B12 intakes of these post-stroke patients were 69% and 261% of the recommended dietary allowances (RDA), respectively. Inadequate folate levels, defined as serum folate < 6 ng/mL, was noted in 68% of these patients. Hyperhomocysteinemia levels (tHcy >or=15 micromol/L) were observed in 48%. According to tertiles of serum tHcy and folate levels, the rate of brain atrophy, but not brain infarctions, are significantly associated with elevated tHcy (P = 0.0126) and decreased folate levels (P = 0.0273). After adjustments for age, sex, disease status, brain infarctions and carotid stenosis, the odds ratio of brain atrophy was 9.8 (95% CI: 1.7-56.4, P = 0.0101) in the hyperhomocysteinemia group and 9.6 (95% CI: 1.1-81.3, P = 0.0377) in the low folate group (serum folate < 3.0 ng/mL) compared with the group with normal tHcy and folate levels. No significant association was noted between vitamin B12 levels and brain lesions. CONCLUSIONS: Our data shows that folate deficiency and hyperhomocysteinemia are prevalent in elderly post-stroke patients. These two conditions are strongly and independently associated with the development of brain atrophy.     

B-vitamins and homocysteine in Spanish institutionalized elderly

BACKGROUND: Hyperhomocysteinemia is an accepted risk factor for cardiovascular disease, and possibly also for cognitive impairment and dementia. It has also been proposed as a marker for the status of the B vitamins, which participate in the metabolism of homocysteine. Therefore, especially in the elderly, it is important to know the prevalence of high homocysteine (tHcy) levels and the influence that B vitamins have on them. MATERIAL AND METHODS: 218 elderly of both sexes, aged 60-105, living in an elderly home in Granada (Spain), were screened for serum folate, red blood cell (RBC) folate, serum cobalamin (B12) (Abbott, IMx), holotranscobalamin II (Holo-TC II) (HoloTC RIA, Axis-Shield), methylmalonic acid (MMA) (MS-GC), total pyridoxine (B6) (HPLC), and total homocysteine (tHcy) (Abbott, IMx). RESULTS: Hyperhomocysteinemia (tHcy >12 pmol/L) was detected in 80.7%. Serum folate deficiency was severe (< or =4 ng/mL) in 19.3% and moderate (4-7 ng/mL) in 43.1%. In 14.2% of the elderly RBC folate was < or =175 ng/mL, and in 61.0% it was between 175-400 ng/mL. Vitamin B12, measured in serum (< or =200 pg/mL), was deficient in 15.8%, but if measured as Holo-TC II (< or =45 pmol/L), deficiency ranged up to 39.1%. MMA was high (> or =300 nmol/L) in 45.6%. Vitamin B6 (< 20 nmol/L) was low only in one person. In order to identify the factors that could predict tHcy levels, a multiple regression analysis was performed. Best results corresponded to the combination of log serum folate and log Holo-TC II, which gave values of R > 0.5. If analyzed independently, the highest correlation was with log serum folate (r = -0.290), followed by RBC folate (r = -0.263), Holo-TC II (r = -0.228), log B12 (r = -0.175), and log B6 (r = -0.078). CONCLUSION: There is a high prevalence of vitamin B deficiency and hyperhomocysteinemia in the studied population. Our data confirm the influence of these vitamins, especially folate, on tHcy levels, but hyperhomocysteinemia cannot be used as the only diagnostic criterion to detect subclinical vitamin deficiency in elderly people, especially to detect vitamin B12 deficiency.     

Dietary intake of B-vitamins in mothers born a child with a congenital heart defect

Background Periconceptional use of multivitamins reduces the risk of a child with a congenital heart defect (CHD). Data on the impact of maternal diet, however, are lacking. Aim of the study We investigated the association between the maternal dietary intake of B-vitamins and having a child with a CHD. Methods A case-control study was performed in 192 mothers of a child with a CHD and 216 mothers of a healthy child. Mothers filled out food frequency questionnaires covering the current dietary intake, and general questionnaires at 17 months after the index-pregnancy. Maternal blood samples were taken to determine B-vitamin and plasma total homocysteine (tHcy) concentrations as nutritional biomarkers. Pregnant and lactating mothers and those with another diet compared with the preconceptional period were excluded for analysis. Case-mothers and controls were compared using the Mann-Whitney U test and logistic regression. Results The dietary intake of macronutrients and B-vitamins was comparable between both groups, but all mothers had a substantially lower median folate intake (cases 161 μg, controls 175 μg) than the Dutch recommended dietary allowance of 300 μg. Within the case-group, the intake of proteins and vitamin B₆ and the concentrations of serum vitamin B₁₂ and folate were significantly lower in hyperhomocysteinemics (tHcy ≥ 14.5 μmol/l) than in normohomocysteinemics. The maternal educational level was positively associated with B-vitamin intake, except for vitamin B₁₂ in controls. Low educated case-mothers showed a significantly lower median vitamin B₁₂ intake than controls (2.8 μg and 3.8 μg, P = 0.01). The CHD risk doubled if vitamin B₁₂ intake in these mothers reduced by 50% (OR 2.0; 95% CI: 1.1–3.5). Conclusions A diet low in vitamin B₁₂ is associated with an increased risk of a child with a CHD, especially in low educated women. A disbalance in the maternal intake of proteins and low folate intake may play a role as well, but needs further investigation. As hyperhomocysteinemia is a strong risk factor for adult cardiovascular disease, these data may imply that the hyperhomocysteinemic mothers and their children should be targeted for nutritional interventions.     

Influence of vitamin intake and MTHFR polymorphism on the levels of DNA damage in tobacco farmers

Background: Genetic damage may occur spontaneously under normal metabolic circumstances, inadequate intake of nutrients, and excessive exposure to environmental mutagens. Objectives: To evaluate the influence of the intake of micronutrients vitamin B₁₂, vitamin B₆, and folate and of the polymorphism methylenetetrahydrofolate reductase (MTHFR) C677T on the induction of DNA damage in tobacco farmers. Methods: The study involved 66 men and 44 women engaged in tobacco cultivation in the region of Venâncio Aires (Rio Grande do Sul state, Brazil). Peripheral blood samples were collected to analyze DNA damage using the Comet assay, the micronucleus (MN) test and MTHFR C677T polymorphism. Dietary intake was evaluated based on the mean values obtained from three 24-h diet recall questionnaires, and nutrient intake data were computerized and estimated in the Food Processor SQL 10.9 program. The statistical tests used to generate the stated results were Kruskal–Wallis test, Exact Fisher’s test, and multivariate linear regression analysis. Results: DNA damage was significantly higher in individuals who had an inadequate intake of folate, vitamin B₁₂, and vitamin B₆ (P < 0.01) assessed by Comet assay. In relation to MN test results, buccal cells showed MN frequency higher in individuals with inadequate intake of vitamin B₆ (P < 0.01). No difference was observed in MN lymphocytes frequency. No significant association was detected between MTHFR C677T polymorphism and DNA damage in tobacco farmers. Conclusion: Our results suggest that folate, vitamin B₁₂, and vitamin B₆ deficiency may be associated with genotoxic effect in individuals exposed to pesticides.     

Plasma total homocysteine,folate, and vitamin B12 status in Korean adults

Elevated plasma total homocysteine (tHcy) levels have been established as a risk factor for occlusive cardiovascular disease. Also known is that plasma folate and vitamin B12 influence homocysteine metabolism as cosubstrate and cofactor, respectively. However, not much information is available describing plasma tHcy levels and their relationship to plasma folate and vitamin B12 status in Koreans. We measured the plasma levels of tHcy, folate, and vitamin B12 in 195 adults (99 males, 96 females; 23-72 y old in the lower middle class). The mean plasma tHcy levels of males, 11.18 +/- 3.88 micromol/L, was significantly higher (p < 0.001) than that of females, 9.20 +/- 2.65 micromol/L. The distribution of tHcy levels of males showed a wide range, 3-50 micromol/L, with a long tail toward higher values. Thus the incidence of hyperhomocysteinemia (> or = 5 micromol/L) in males, 10.1%, was significantly higher (< 0.02) than the 2.1% in females. As age increased, plasma tHcy levels tended to be higher in females. Therefore, sex differences in plasma tHcy levels disappeared in subjects over fifty. On the other hand, both plasma folate (6.47 +/- 3.06 vs 7.96 +/- 3.55 ng/mL, p < 0.01) and vitamin B12 levels (537.0 +/- 222.0 vs. 664.1 +/- 309.8 ng/mL, p < 0.01) were significantly lower in males than in females. A plasma folate deficiency (< 3.0 ng/mL) was found in 6.1% of males and 2.1% of females. And a vitamin B12 deficiency (< 150 pg/mL) was detected in 2.0% and 1.0%, respectively. Plasma tHcy levels were related with inversely plasma concentrations of folate (r = -0.37249, p < 0.001) as well as vitamin B12 (r = -0.22560, p < 0.01) in both sexes. Plasma levels of tHcy and the prevalence of hyperhomocysteinemia in Korean adults are similar to findings in the West. Our results indicate that male adults may be in worse condition for cardiovascular disease (CVD) than females. And improving folate and vitamin B12 status may reduce plasma tHcy level, which may be more important in males.     

Prevalence and predictors of anemia in a population of North Indian children

ObjectiveAnemia is an important health concern worldwide, particularly in poor populations such as in India. The objective of this study was to determine the prevalence and predictors of anemia and iron status.MethodsOne thousand children ages 6 to 30 mo were included in a study undertaken in low- to middle-income neighborhoods in New Delhi, India. Children of Tigri and Dakshinpuri were identified through a community survey. Plasma concentrations of hemoglobin (Hb), soluble transferrin receptor (sTfR), folate, vitamin B₁₂, and total homocysteine (tHcy) were measured. Predictors for plasma Hb concentration were identified in multiple linear regression models and considered significant if P-value <0.05.ResultsThe prevalence of anemia (Hb concentration <11 g/dL) was 69.6% (n = 696) whereas the prevalence of iron deficiency (elevated sTfR i.e., >4.7 nmol/L) was 31% (n = 309). The main predictors for Hb concentration were plasma concentrations of sTfR (standardized beta coefficient [β], −0.49; P < 0.001), folate (β, 0.15; P < 0.001), vitamin B₁₂ (β, 0.10; P < 0.001), tHcy (β, −0.11; P < 0.001) among the biomarkers. Length-for-age Z score (β, 0.08; P = 0.002) and family income (β, 0.06; P = 0.027) also predicted Hb concentration.ConclusionAnemia was common in this population. Iron, folate, and vitamin B₁₂ status were important predictors for plasma Hb concentration. Improving the status of these nutrients might reduce the burden of childhood anemia in India.     

Folic acid and vitamin B12 supplementation lowers plasma homocysteine but has no effect on serum bone turnover markers in elderly women: a randomized,double-blind,placebo-controlled trial

An elevated homocysteine level is a newly recognized risk factor for osteoporosis. Older individuals may have elevated homocysteine levels due to inadequate folate intake and/or lower absorption of vitamin B₁₂. The aim of this study was to determine whether there is an impact of folic acid and vitamin B₁₂ supplementation on homocysteine levels and, subsequently, on bone turnover markers in older women with mildly to moderately elevated homocysteine levels. It is hypothesized that supplementation with folic acid and vitamin B₁₂ will improve homocysteine levels and, in turn, positively modify bone turnover markers in this population. This randomized, double-blind, placebo-controlled trial included 31 women (65 to 93 years) with homocysteine levels greater than 10 μmol/L. Participants were randomly assigned to receive either a daily folic acid (800 μg) and vitamin B₁₂ (1000 μg) (n = 17) or a matching placebo (n = 14) for 4 months. The results showed significantly lower homocysteine concentrations in the vitamin group compared to the placebo group (10.6 vs 18.5 μmol/L, P = .007). No significant difference in serum alkaline phosphatase or C-terminal cross-linking telopeptide of type I collagen was found between the vitamin and placebo groups before or after supplementation. The use of folic acid and vitamin B₁₂ as a dietary supplement to improve homocysteine levels could be beneficial for older women, but additional research must be conducted in a larger population and for a longer period to determine if there is an impact of supplementation on bone turnover markers or other indicators of bone health.     

Hyperhomocysteinemia is associated with vitamin B-12 deficiency: A cross-sectional study in a rural,elderly population of Shanxi China

Objectives

To report the association of lifestyle factors and plasma vitamin B-12 with hyperhomocysteinemia in a large sample of men and women living in a region of China where there is an increased risk of NTDs.

Design

Community-based, cross-sectional study of Lvliang City, Shanxi Province, China.

Setting

Hyperhomocysteinemia is an independent risk factor for cardiovascular disease (CVD) and a sensitive marker of vitamin B-12 and folate deficiency.

Participants

A total of 2355 (1044 men and 1311 women) participants born before 1 January 1958 (≥55 years of age) and living in Lvliang City for at least 2 months a year were included.

Measurements

The participants were assessed regarding demographic characteristics, height, weight, as well as having a physical examination and blood sampling for serum cholesterol, total homocysteine (tHcy), folate, and vitamin B12 levels.

Results

The median (25th–75th percentile) tHcy concentration was 21.5 (15.8–33.6) µmol/L in men and 18.0 (13.4–24.8) µmol/L in women. The overall prevalence of hyperhomocysteinemia (tHcy ≥15 µmol/L) was 72.6% (84.3% in men and 63.2% in women), inversely correlated with folate (r=–0.230, P=0.006) and vitamin B-12 (r=–0.540, P<0.001), and positively correlated with uric acid (r=0.054, P<0.001). Vitamin B-12 and folate deficiency, older age, and male gender were associated with elevated tHcy; with vitamin B-12 deficiency being the strongest.

Conclusions

Plasma tHcy concentration and hyperhomocysteinemia were significantly higher in this population than in previously studied populations. Vitamin B-12 and folate supplementation, concomitant lifestyle changes such as smoking cessation, and lipid-lowering treatments may help to decrease plasma tHcy concentrations and reduce the CVD risk in this population.