Lowering homocysteine with B vitamins has no effect on biomarkers of bone turnover in older persons: a 2-y randomized controlled trial

BACKGROUND: In recent prospective studies, higher homocysteine concentrations were shown to be a risk factor for osteoporotic fractures in older persons. Supplements containing folate and vitamins B-12 and B-6 lower homocysteine concentrations. OBJECTIVE: The objective of the study was to determine in healthy older persons whether lowering homocysteine with B vitamins affects plasma biomarkers of bone turnover. DESIGN: Healthy older persons (n = 276; aged >or=65 y) were randomly assigned to receive either a daily supplement containing folate (1 mg), vitamin B-12 (500 microg), and vitamin B-6 (10 mg) or a placebo for 2 y. Of these participants, we selected 135 with baseline homocysteine concentrations >15.0 micromol/L, and we measured serum bone-specific alkaline phosphatase, a marker of bone formation, and bone-derived collagen fragments, a marker of bone resorption, at baseline and 2 y later. RESULTS: At 2 y, plasma homocysteine concentrations were 5.2 mumol/L (95% CI: 3.9, 6.6 micromol/L; P < 0.001) lower in the vitamin than in the placebo group. No significant differences were found in either serum bone-specific alkaline phosphatase (-0.3 microg/L; 95% CI: -2.8, 2.1 microg/L; P = 0.79) or bone-derived collagen fragments (-0.0 microg/L; 95% CI: -0.1, 0.1 microg/L; P = 0.76) between the vitamin and placebo groups, respectively, with 2 y of supplementation. CONCLUSION: Supplementation with folate and vitamins B-6 and B-12 lowered plasma homocysteine but had no beneficial effect on bone turnover at the end of 2 y, as assessed by biomarkers of bone formation and resorption.     

Breakfast cereal fortified with folic acid, vitamin B-6, and vitamin B-12 increases vitamin concentrations and reduces homocysteine concentrations: a randomized trial

BACKGROUND: High homocysteine and low B vitamin concentrations have been linked to the risk of vascular disease, stroke, and dementia and are relatively common in older adults. OBJECTIVE: We assessed the effect of breakfast cereal fortified with folic acid, vitamin B-6, and vitamin B-12 on vitamin and homocysteine status. DESIGN: A randomized, double-blind trial was conducted in 189 volunteers aged 50-85 y. The subjects had no history of hypertension, anemia, asthma, cancer, or cardiovascular or digestive disease and did not regularly consume multiple or B vitamin supplements or highly fortified breakfast cereal. Subjects were randomly assigned to consume 1 cup (0.24 L) breakfast cereal fortified with 440 microg folic acid, 1.8 mg vitamin B-6, and 4.8 microg vitamin B-12 or placebo cereal for 12 wk. Blood was drawn at 0, 2, 12, and 14 wk. Methionine-loading tests were conducted at baseline and week 14. RESULTS: Final baseline-adjusted plasma homocysteine concentrations were significantly lower and B vitamin concentrations were significantly higher in the treatment group than in the placebo group (P < 0.001). The percentage of subjects with plasma folate concentrations < 11 nmol/L decreased from 2% to 0%, with vitamin B-12 concentrations < 185 pmol/L from 9% to 3%, with vitamin B-6 concentrations < 20 nmol/L from 6% to 2%, and with homocysteine concentrations > 10.4 micromol/L (women) or > 11.4 micromol/L (men) from 6.4% to 1.6%. The percentage of control subjects with values beyond these cutoff points remained nearly constant or increased. CONCLUSIONS: In this relatively healthy group of volunteers, consumption of 1 cup fortified breakfast cereal daily significantly increased B vitamin and decreased homocysteine concentrations, including post-methionine-load homocysteine concentrations.     

High prevalence of hyperhomocysteinemia in Chinese adults is associated with low folate, vitamin B-12, and vitamin B-6 status

Elevated plasma total homocysteine (tHcy) concentrations are associated with lower folate, vitamin B-12, and vitamin B-6 status and are considered an independent risk factor for cardiovascular disease in developed countries, but data in developing countries are limited. We conducted a cross-sectional study to explore tHcy status and its association with plasma B vitamin status in 2471 Chinese men and women aged 35 to 64 y, living in the urban and rural areas of the northern and the southern regions of China. Blood samples were also collected in 2 seasons (spring and fall). The geometric mean plasma tHcy concentration was significantly higher in the north (adjusted geometric mean, 95% CI; 13.0 micromol/L, 12.6-13.3) than in the south (9.1, 8.9-9.4) after controlling for gender, area (urban and rural), age, and season (spring and fall). Twenty-eight percent of northerners and 7% of southerners had plasma tHcy concentrations>or=16.0 micromol/L, a level used to define hyperhomocysteinemia. Within each region, men had higher plasma tHcy concentrations than women (16.1 vs. 10.6 micromol/L in the north, and 10.7 vs. 7.9 micromol/L in the south) and 40% of the northern men had hyperhomocysteinemia. Generally, individuals living in the urban areas had 30% (95% CI, 1.0-1.6) greater odds of having high tHcy levels (>or=16 micromol/L) than those living in the rural areas. Low plasma concentrations of folate, vitamins B-12 and B-6, older age, being male, and living in urban areas were all independently associated with elevated tHcy, with low folate as the strongest determinant.     

Association between B vitamin intake and plasma homocysteine concentration in the general Dutch population aged 20-65 y

BACKGROUND: An elevated plasma total homocysteine (tHcy) concentration is associated with an increased risk of cardiovascular diseases. Folate, riboflavin, vitamin B-6, and vitamin B-12 are essential in homocysteine metabolism. OBJECTIVE: The objective was to describe the association between dietary intakes of folate, riboflavin, vitamin B-6, and vitamin B-12 and the nonfasting plasma tHcy concentration. DESIGN: A random sample of 2435 men and women aged 20-65 y from a population-based Dutch cohort examined in 1993-1996 was analyzed cross-sectionally. RESULTS: Univariately, intakes of all B vitamins were inversely related to the plasma tHcy concentration. In multivariate models, only folate intake remained inversely associated with the plasma tHcy concentration. Mean plasma tHcy concentrations (adjusted for intakes of riboflavin, vitamin B-6, vitamin B-12, and methionine and for age, smoking, and alcohol consumption) in men with low (first quintile: 161 microg/d) and high (fifth quintile: 254 microg/d) folate intakes were 15.4 and 13.2 micromol/L, respectively; in women, plasma tHcy concentrations were 13.7 and 12.4 micromol/L at folate intakes of 160 and 262 microg/d, respectively. In men, the difference in the mean plasma tHcy concentration between men with low and high folate intakes was greater in smokers than in nonsmokers (2.8 compared with 1.6 micromol/L) and greater in nondrinkers than in drinkers of >2 alcoholic drinks/d (3.5 compared with 1.4 micromol/L). In women, the association between folate intake and plasma tHcy was not modified by smoking or alcohol consumption. CONCLUSIONS: In this Dutch population, folate was the only B vitamin independently inversely associated with the plasma tHcy concentration. Changing dietary habits may substantially influence the plasma tHcy concentration in the general population.     

Lowering homocysteine with B vitamins has no effect on blood pressure in older adults

An elevated circulating homocysteine concentration is associated with the risk of cardiovascular disease. The mechanism by which an elevated homocysteine increases cardiovascular risk is unclear but may be mediated in part by elevating blood pressure. It is well established that supplements containing folate, vitamins B-12, and B-6 lower homocysteine concentrations. However, the effect of homocysteine-lowering vitamins on blood pressure has not been well studied. We sought to determine whether lowering homocysteine with B vitamins lowers blood pressure in healthy older people with elevated homocysteine concentrations. Two hundred seventy-six healthy older participants (> or = 65 y) with a homocysteine > or = 13 micromol/L were randomized to receive a daily supplement containing folate (1 mg), vitamin B-12 (500 microg), and vitamin B-6 (10 mg), or a placebo, for 2 y. Plasma homocysteine was lower in the Vitamins group than the Placebo group at both 1 [-4.3 micromol/L (95% CI; -4.9, -3.7)] and 2 y [-4.4 micromol/L (95% CI: -5.3, -3.6)]. Systolic and diastolic blood pressures as well as pulse pressure in the Vitamins group did not differ from the Placebo group over the duration of the trial. The mean differences in blood pressures, adjusted for baseline values, did not exceed 1 mm Hg. Supplemental B-vitamins lowered plasma homocysteine but had no effect on blood pressure in older people with elevated baseline homocysteine concentrations.     

Elevated plasma homocysteine and low vitamin B-6 status in nonsupplementing older women with rheumatoid arthritis

OBJECTIVE: The purpose of this study was to determine if nonsupplementing older women (aged >or=55 years) with rheumatoid arthritis had higher plasma homocysteine and lower B-vitamin status compared to healthy controls. Elevated plasma homocysteine, a risk factor for cardiovascular disease, may help explain why individuals with rheumatoid arthritis have an increased risk of cardiovascular disease. METHODS: Older, free-living women were classified as rheumatoid arthritis (n=18) or healthy control (n=33). Participants were not using B-vitamin supplements. Fasting blood samples were measured for pyridoxal 5'phosphate (PLP) (the metabolically active coenzyme form of vitamin B-6), folate, red blood cell folate, vitamin B-12, transcobalamin II, homocysteine, C-reactive protein, and lipid concentrations. Participants completed 7-day weighed food records, the Stanford Health Assessment Questionnaire (HAQ), and a visual analog pain scale. RESULTS: PLP concentrations were lower in the rheumatoid arthritis vs healthy control participants (4.93+/-3.85 vs 11.35+/-7.11 ng/mL [20+/-16 vs 46+/-29 nmol/L]; P<0.01) whereas plasma homocysteine was higher in the rheumatoid arthritis group (1.63+/-0.74 vs 1.15+/-0.38 mg/L [12.1+/-5.5 vs 8.5+/-2.8 micromol/L]; P=0.02). Red blood cell folate concentrations were lower in the rheumatoid arthritis vs healthy control participants [414+/-141 vs 525+/-172 ng/mL [938+/-320 vs 1,190+/-390 nmol/L]; P=0.02). No significant differences were found for plasma folate, vitamin B-12, and transcobalamin II. An inverse correlation was found between PLP concentrations and the HAQ disability index (r=-0.37; P<0.01). A positive correlation was found between homocysteine concentrations and the HAQ disability index (r=0.36; P=0.01). Total cholesterol and low-density lipoprotein cholesterol levels were lower in the rheumatoid arthritis group (cholesterol 191+/-43 vs 218+/-33 mg/dL [4.95+/-1.11 vs 5.65+/-0.85 mmol/L]; P=0.02; low-density lipoprotein cholesterol 110+/-36 vs 137+/-29 mg/dL [2.85+/-0.93 vs 3.55+/-0.75 mmol/L]; P<0.01). No significant differences were seen between groups for protein (g/day), fat (g/day), cholesterol (mg/day), folate (microg/day), vitamin B-12 (microg/day), and vitamin B-6 (mg/day) dietary intakes. CONCLUSIONS: Poor vitamin B-6 status and elevated plasma homocysteine concentrations were seen in older women with rheumatoid arthritis compared to healthy controls and may contribute to their increased risk of cardiovascular disease.     

Low-dose vitamin B-6 effectively lowers fasting plasma homocysteine in healthy elderly persons who are folate and riboflavin replete

BACKGROUND: Current data suggest that physiologic doses of vitamin B-6 have no significant homocysteine-lowering effect. It is possible that an effect of vitamin B-6 was missed in previous trials because of a much greater effect of folic acid, vitamin B-12, or both. OBJECTIVE: The aim of this study was to investigate the effect of low-dose vitamin B-6 supplementation on fasting total homocysteine (tHcy) concentrations in healthy elderly persons who were made replete with folate and riboflavin. DESIGN: Twenty-two healthy elderly persons aged 63-80 y were supplemented with a low dose of vitamin B-6 (1.6 mg/d) for 12 wk in a randomized, double-blind, placebo-controlled trial after repletion with folic acid (400 microg/d for 6 wk) and riboflavin (1.6 mg/d for 18 wk); none of the subjects had a vitamin B-12 deficiency. RESULTS: Folic acid supplementation lowered fasting tHcy by 19.6% (P < 0.001). After folic acid supplementation, baseline tHcy concentrations ranged from 6.22 to 23.52 micromol/L and 10 subjects had suboptimal vitamin B-6 status (plasma pyridoxal-P < 20 nmol/L). Two-way analysis of variance showed that the significant improvement in vitamin B-6 status in response to vitamin B-6 supplementation (on the basis of both pyridoxal-P: and the erythrocyte aspartate aminotransferase activation coefficient) was reflected in a significant reduction in plasma tHcy of 7.5%. CONCLUSIONS: Low-dose vitamin B-6 effectively lowers fasting plasma tHcy in healthy subjects who are both folate and riboflavin replete. This suggests that any program aimed at the treatment or prevention of hyperhomocysteinemia should include vitamin B-6 supplementation.     

Influence of methylenetetrahydrofolate reductase genotype, age, vitamin B-12, and folate status on plasma homocysteine in children

BACKGROUND: Several studies have examined the association of the methylenetetrahydrofolate reductase (MTHFR) genotype with plasma homocysteine in adults, but few studies have been performed in children. OBJECTIVE: We measured the concentrations of plasma total homocysteine, folate, and vitamin B-12 in a group of healthy fasting children and related these to MTHFR genotype. DESIGN: After the subjects fasted, blood samples were collected into EDTA-containing tubes. Plasma, red blood cells, and the buffy coat were immediately stored at -80 degrees C for biochemical and molecular analyses. Plasma total homocysteine was determined by HPLC. Folate and vitamin B-12 were measured by a double-labeled radioimmunoassay, and the genotypic analysis was performed by polymerase chain reaction amplification of genomic DNA extracted from blood leukocytes. RESULTS: Plasma homocysteine concentrations correlated negatively with folate and vitamin B-12(,) but positively with age (P: < 0. 0001). Whereas folate and vitamin B-12 accounted for 27% and 19% of the variation in homocysteine, respectively, age accounted for 48% of the variation. When the cohort was divided into older (>10 y) and younger (10 y. CONCLUSION: Our data show that in a healthy pediatric population, MTHFR genotype played a significant role in determining homocysteine concentrations in older (>10 y), nutritionally stressed children.     

Screening for vitamin B-12 and folate deficiency in older persons

BACKGROUND: Vitamin B-12 deficiency is usually accompanied by elevated concentrations of serum total homocysteine (tHcy) and methylmalonic acid (MMA). Folate deficiency also results in elevated tHcy. Measurement of these metabolites can be used to screen for functional vitamin B-12 or folate deficiency. OBJECTIVE: We assessed the prevalence of vitamin B-12 and folate deficiency in a population-based study (n = 1562) of older persons living in Oxford City, United Kingdom. DESIGN: We postulated that, as vitamin B-12 or folate concentrations declined from adequate to impaired levels, tHcy (or MMA) concentrations would increase. Individuals were classified as being at high risk of vitamin B-12 deficiency if they had low vitamin B-12 (< 150 pmol/L) or borderline vitamin B-12 (150-200 pmol/L) accompanied by elevated MMA (> 0.35 micromol/L) or tHcy (> 15.0 micromol/L). Individuals were classified as being at high risk of folate deficiency if they had low folate (< 5 nmol/L) or borderline folate (5-7 nmol/L) accompanied by elevated tHcy (> 15 micromol/L). RESULTS: Cutoffs of 15.0 micro mol/L for tHcy and 0.35 micro mol/L for MMA identified persons with normal or elevated concentrations. Among persons aged 65-74 and >or= 75 y, respectively, approximately 10% and 20% were at high risk of vitamin B-12 deficiency. About 10% and 20%, respectively, were also at high risk of folate deficiency. About 10% of persons with vitamin B-12 deficiency also had folate deficiency. CONCLUSION: Use of tHcy or MMA among older persons with borderline vitamin concentrations may identify those at high risk of vitamin B-12 deficiency who should be considered for treatment.     

Effect of vitamin B-6 deficiency on fasting plasma homocysteine concentrations.

The catabolism of homocysteine through cystathionine synthesis requires pyridoxal-5'-phosphate, thus the effect of vitamin B-6 deficiency on plasma homocysteine concentrations was evaluated. Total fasting plasma homocysteine concentrations were measured in 11 elderly subjects aged 64.4 +/- 1.7 y (mean +/- SE) who consumed a vitamin B-6-deficient diet for less than or equal to 20 d. Only 1 of the 11 subjects was found to have elevated homocysteine concentrations even though all subjects exhibited high urinary xanthurenic acid concentrations after a tryptophan load, a measure indicative of vitamin B-6 deficiency. In a supporting study, fasting plasma homocysteine concentrations were measured in 3- and 23-mo-old rats fed vitamin B-6-deficient diets and were compared with those of vitamin B-6-replete, pair-fed controls. There was no difference in homocysteine concentrations between deficient and pair-fed animals after 6 wk of the dietary regimen for either age group; after 9 wk a modest elevation was observed in the 3-mo-old deficient rats whereas no difference was observed for the 23-mo-old rats. It is concluded that fasting plasma homocysteine concentrations are not initially elevated in vitamin B-6 deficiency and therefore fasting plasma homocysteine concentrations are not a good indicator of vitamin B-6 status.     

Plasma homocysteine, but not folate or vitamin B-12, predicts mortality in older people in the United Kingdom

There is uncertainty about the importance of plasma levels of homocysteine, vitamin B-12, and folate for all-cause and cardiovascular disease (CVD) mortality in older people. We examined the associations between plasma levels of folate, vitamin B-12, and homocysteine, and all-cause and CVD mortality among community-dwelling adults aged > or = 75 y living in the United Kingdom. In a population-based prospective cohort study, 853 men and women aged > or = 75 y were examined in 1995-98 as part of the Medical Research Council Trial of Assessment and Management of Older People in the Community. During a median follow-up of 7.6 y (5528 person-years of follow-up), 429 individuals (50.3%) died, including 185 from CVD. Individuals with plasma homocysteine levels in the top one-third compared with the bottom one-third had a 2-fold higher risk of all-cause mortality (hazard ratio, 2.20; 95% CI, 1.76, 2.75; P < 0.001) and CVD mortality (hazard ratio, 1.96; 95% CI, 1.39, 2.78; P < 0.001) after adjustment for age, sex, and other covariates. There was no association of plasma folate or vitamin B-12 levels with mortality. Our results extend previously reported associations of homocysteine with mortality, and the absence of associations of folate and vitamin B-12 with mortality, to the older population.     

Vitamin E, vitamin B-6, vitamin B-12, and folate status of gastric bypass surgery patients

The vitamin E, vitamin B-6, vitamin B-12, and folate status of 22 gastric bypass subjects aged 23 to 60 years was evaluated before surgery and at 6 and 12 months after surgery. Before surgery, 77% of subjects had adequate plasma vitamin E levels; 36%, adequate plasma pyridoxal phosphate levels; 100%, adequate plasma vitamin B-12 levels; and 45%, adequate plasma folate levels. The food intake of all subjects was sharply reduced after surgery. After surgery, subjects were classified into three vitamin supplement groups on the basis of average daily vitamin supplement intake. Subjects taking higher levels of supplements containing the vitamins in question had significantly higher plasma concentrations of the vitamins than those taking low or moderate levels. The mean plasma vitamin values in the moderate supplement group were indicative of adequate status for all vitamins, but plasma vitamin B-12 levels at 12 months post-surgery were significantly lower than pre-surgery levels. In the low supplement group, mean plasma vitamin levels were in or near marginal or deficient ranges. The majority of subjects consuming supplements of vitamin E, vitamin B-6, and folate near the US RDA maintained normal vitamin status. Subjects taking more than 100 micrograms vitamin B-12 daily had adequate vitamin B-12 status. Significant correlations (r = .67 to .94) were observed between vitamin supplement levels and the respective plasma vitamin concentrations.     

Heavy coffee consumption and plasma homocysteine: a randomized controlled trial in healthy volunteers

BACKGROUND: An elevated plasma concentration of total homocysteine is considered to be a strong risk factor for cardiovascular disease. Heavy coffee drinking has been related to high homocysteine concentrations in epidemiologic studies and in one experiment in which healthy subjects drank unfiltered, boiled coffee. OBJECTIVE: Our goal was to determine whether daily consumption of paper-filtered coffee raises plasma concentrations of total homocysteine in healthy subjects. DESIGN: Twenty-six volunteers (18-53 y of age) consumed 1 L/d of paper-filtered coffee brewed with 70 g regular ground beans or no coffee for 4 wk each in a randomized, crossover design. RESULTS: The mean (+/-SD) plasma concentration of total homocysteine in fasting blood was 8.1 +/- 1.8 micromol/L after abstention from coffee and 9.6 +/- 2.9 micromol/L after 3-4 wk of coffee drinking, a difference of 1.5 micromol/L (95% CI: 0.9, 2.1 micromol/L) or 18% (P: < 0.001). Coffee increased homocysteine concentrations in 24 of 26 individuals. Circulating concentrations of vitamin B-6, vitamin B-12, and folate were unaffected. CONCLUSION: Drinking large quantities of paper-filtered coffee raises fasting plasma concentrations of total homocysteine in healthy individuals.     

Vitamin B-12 status is inversely associated with plasma homocysteine in young women with C677T and/or A1298C methylenetetrahydrofolate reductase polymorphisms

Methylenetetrahydrofolate reductase (MTHFR) polymorphisms may negatively influence one-carbon metabolism and increase health risks in women of reproductive age. The effect of MTHFR single nucleotide polymorphisms at bp 677 and/or 1298 and differences in folate and vitamin B-12 status on plasma homocysteine concentration in women of reproductive age (20-30 y; n = 186) were investigated. From the multivariate regression model, homozygotes (n = 23) for the C677T MTHFR variant had plasma homocysteine concentrations that were higher (P < 0.05) than those observed in the other 5 genotype groups, including those who were heterozygous for both variants (677CT/1298AC; n = 32). Plasma homocysteine was negatively associated with plasma vitamin B-12 concentration (P = 0.015) and serum folate (P = 0.049), with the degree of correlation between plasma vitamin B-12 and homocysteine concentrations dependent on MTHFR genotype. The C677T and A1298C MTHFR polymorphisms were significant predictors (P < 0.05) of plasma homocysteine when regression analysis was used to model plasma homocysteine concentration as a function of genotype, supplement use, serum folate and plasma vitamin B-12 concentration. Plasma homocysteine decreased as vitamin B-12 concentration increased (P = 0.0005) in individuals who were heterozygous for both the C677T and A1298C variants with nonsignificant trends (P = 0.114-0.128) in individuals homozygous for either the C677T or A1298C variants. In contrast, within the group of individuals with the wild-type genotype for both the C677T and A1298C MTHFR variants, homocysteine was not associated with changes in plasma vitamin B-12 concentrations. These data suggest that enhancing vitamin B-12 status may significantly decrease homocysteine in young women with C677T and/or A1298C MTHFR polymorphisms, even when vitamin B-12 concentrations are within the normal range.     

Folate and colorectal neoplasia: relation between plasma and dietary markers of folate and adenoma recurrence

BACKGROUND: The results of epidemiologic studies indicate that higher intakes or blood concentrations of folate are associated with a lower risk of colorectal neoplasia; however, only one study assessed the role of homocysteine. OBJECTIVE: We assessed the relation between biochemical and dietary markers of folate status and colorectal adenoma recurrence. DESIGN: Analyses were conducted in 1014 men and women aged 40-80 y who had undergone removal of all colorectal polyps. Diet and supplement use were ascertained through a food-frequency questionnaire administered at study entry. Blood collected at baseline was used to measure plasma folate and homocysteine concentrations. Unconditional logistic regression was used to assess the odds of recurrence associated with the intakes of folate, methionine, and vitamins B-6 and B-12 and with plasma folate and homocysteine. RESULTS: Relative to subjects in the highest quartile of plasma homocysteine, those in the lowest quartile had an odds ratio (OR) of adenoma recurrence of 0.69 (95% CI: 0.47, 1.02; P for trend = 0.02) after adjustment for confounding factors. Lower odds of recurrence were shown for higher plasma folate (OR: 0.66; 95% CI: 0.46, 0.97) and higher total intakes (dietary plus supplemental) of folate (OR: 0.61; 0.42, 0.89) and vitamin B-6 (OR: 0.65; 0.45, 0.94). Slightly weaker and nonsignificant associations were shown for dietary folate, methionine, and total vitamin B-12. CONCLUSIONS: A lower recurrence of colorectal adenomas was shown in subjects with higher intakes and plasma concentrations of folate. Additional markers involved in folate metabolism, including lower homocysteine and higher vitamin B-6 intake, were also associated with lower odds of recurrence.     

Changes in lifestyle and plasma total homocysteine: the Hordaland Homocysteine Study

BACKGROUND: Elevated plasma concentrations of total homocysteine (tHcy) are a risk factor for cardiovascular disease. tHcy is a marker of folate and cobalamin deficiencies and is also related to several lifestyle factors. OBJECTIVE: We examined whether changes in lifestyle influence tHcy over time. DESIGN: A population-based, prospective study was conducted in 7031 subjects from western Norway who constituted 2 age groups (41-42 and 65-67 y) at baseline (1992-1993). The subjects were reinvestigated in 1997-1999 ( follow-up: 6 y). RESULTS: During follow-up, median tHcy concentrations decreased 0.10 (25th and 75th percentiles: -1.24, 1.00) micromol/L in the younger subjects and increased 0.39 (25th and 75th percentiles: -0.99, 1.79) micromol/L in the older subjects. Changes in plasma vitamin status and vitamin supplement use were the strongest determinants of changes in tHcy over time. Each unit increase in plasma folate (nmol/L) and vitamin B-12 (pmol/L) was associated with reductions in tHcy concentrations of 0.2 and 0.1 micromol/L, respectively. Among the younger and older age groups, those who started to take vitamin supplements during follow-up had significant reductions in tHcy concentrations of 0.42 (95% CI: -0.65, -0.20) and 0.41 (-0.78, -0.03) micromol/L, respectively. In the younger subjects who quit smoking, tHcy concentrations decreased 0.54 (-0.91, -0.16) micromol/L. Weight changes were inversely related to tHcy. Both baseline history of cardiovascular disease or hypertension and cardiovascular events during follow-up were significantly associated with changes in tHcy. CONCLUSIONS: Changes in lifestyle factors over time influence tHcy concentrations. These changes are modest when compared with the strong associations between tHcy and lifestyle factors in cross-sectional studies.     

Children of Latino immigrants, 4-8 years, in rural Nebraska are adequate in vitamin B-6

Plasma concentrations of B-6 vitamers and homocysteine as well as erythrocyte alanine aminotransferase activity coefficients and vitamin B-6 (dietary + supplement) intakes of apparently healthy young Latino children of immigrant parents living in rural Nebraska were determined and differences determined by gender. Thirty-five Latino children (16 males and 19 females), aged 4-8 years, were included in the study. Nutrient intake information was obtained from the children's parents utilizing two nonconsecutive 24-hour food recalls. No differences were observed by gender with regard to vitamin B-6 intakes, plasma concentrations of B-6 vitamers and homocysteine, and erythrocyte alanine aminotransferase activity coefficients. The intakes of all children met the Recommended Dietary Allowance for vitamin B-6. Plasma pyridoxal 5'-phosphate concentrations, plasma homocysteine concentrations, and erythrocyte alanine aminotransferase activity coefficients of the children were (mean +/- SD) 83.71 +/- 37.35 nmol/L, 6.81 +/- 1.63 micromol/L, and 1.08 +/- 0.06, respectively. All the Latino children of immigrant parents in this study had values indicative of adequate vitamin B-6 status.     

Effect of oral vitamin B-12 with or without folic acid on cognitive function in older people with mild vitamin B-12 deficiency: a randomized, placebo-controlled trial

BACKGROUND: Vitamin B-12 deficiency is associated with cognitive impairment in older people. However, evidence from randomized trials of the effects of vitamin B-12 supplementation on cognitive function is limited and inconclusive. OBJECTIVE: The objective was to investigate whether daily supplementation with high doses of oral vitamin B-12 alone or in combination with folic acid has any beneficial effects on cognitive function in persons aged >/=70 y with mild vitamin B-12 deficiency. DESIGN: In a double-blind, placebo-controlled trial, 195 subjects were randomly assigned to receive 1000 microg vitamin B-12, 1000 microg vitamin B-12 + 400 microg folic acid, or placebo for 24 wk. Vitamin B-12 status was assessed on the basis of methylmalonic acid, total homocysteine (tHcy), and holotranscobalamin (holoTC) concentrations before and after 12 and 24 wk of treatment. Cognitive function was assessed before and after 24 wk of treatment with the use of an extensive neuropsychologic test battery that included the domains of attention, construction, sensomotor speed, memory, and executive function. RESULTS: Vitamin B-12 status did not change significantly after treatment in the placebo group; however, oral vitamin B-12 supplementation corrected mild vitamin B-12 deficiency. Vitamin B-12 + folic acid supplementation increased red blood cell folate concentrations and decreased tHcy concentrations by 36%. Improvement in memory function was greater in the placebo group than in the group who received vitamin B-12 alone (P = 0.0036). Neither supplementation with vitamin B-12 alone nor that in combination with folic acid was accompanied by any improvement in other cognitive domains. CONCLUSION: Oral supplementation with vitamin B-12 alone or in combination with folic acid for 24 wk does not improve cognitive function.     

Multivitamin/mineral supplementation improves plasma B-vitamin status and homocysteine concentration in healthy older adults consuming a folate-fortified diet

Elevated homocysteine has been identified as an independent risk factor for cardiovascular and cerebrovascular disease. Although multivitamin use has been associated with low plasma homocysteine concentrations in several observational studies, no clinical trials have been conducted using multivitamin/mineral supplements to lower homocysteine. We determined whether a multivitamin/mineral supplement formulated at about 100% Daily Value will further lower homocysteine concentration and improve B-vitamin status in healthy older adults already consuming a diet fortified with folic acid. In this randomized, double-blind, placebo-controlled trial, 80 free-living men and women aged 50-87 y with total plasma homocysteine concentrations of > or =8 micromol/L received either a multivitamin/mineral supplement or placebo for 56 d while consuming their usual diet. After the 8-wk treatment, subjects taking the supplement had significantly higher B-vitamin status and lower homocysteine concentration than controls (P: < 0.01). Plasma folate, pyridoxal phosphate (PLP) and vitamin B-12 concentrations were increased 41.6, 36.5 and 13.8%, respectively, in the supplemented group, whereas no changes were observed in the placebo group. The mean homocysteine concentration decreased 9.6% in the supplemented group (P: < 0.001) and was unaffected in the placebo group. There were no significant changes in dietary intake during the intervention. Multivitamin/mineral supplementation can improve B-vitamin status and reduce plasma homocysteine concentration in older adults already consuming a folate-fortified diet.     

Low vitamin B-12 status and risk of cognitive decline in older adults

BACKGROUND: Elevated total homocysteine (tHcy) concentrations have been associated with cognitive impairment, but it is unclear whether low vitamin B-12 or folate status is responsible for cognitive decline. OBJECTIVE: We examined the associations of cognitive decline with vitamin B-12 and folate status in a longitudinal cohort study performed from 1993 to 2003 in Oxford, United Kingdom. DESIGN: Cognitive function was assessed with the Mini-Mental State Examination on >/=3 occasions during 10 y and related to serum concentrations of vitamin B-12, holotranscobalamin (holoTC), tHcy, methylmalonic acid (MMA), and folate with the use of linear mixed models in 1648 participants who provided blood in 1995. RESULTS: Cognitive function declined abruptly at younger ages in some participants but remained intact in others until very old age. In multivariate regression analyses after adjustment for established risk factors, concentrations of holoTC (a marker of reduced vitamin B-12 status), tHcy, and MMA predicted cognitive decline, but folate did not. A doubling in holoTC concentrations (from 50 to 100 pmol/L) was associated with a 30% slower rate of cognitive decline (-0.137 to -0.083), whereas a doubling in tHcy (from 10 to 20 micromol/L) or MMA (from 0.25 to 0.50 micromol/L) was associated with >50% more rapid cognitive decline (-0.090 to -0.169) and (-0.104 to -0.169), respectively. After adjustment for all vitamin markers simultaneously, the associations of cognitive decline with holoTC and MMA remained significant. CONCLUSIONS: Low vitamin B-12 status was associated with more rapid cognitive decline. Randomized trials are required to determine the relevance of vitamin B-12 supplementation for prevention of dementia.