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.     

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.     

Assessment of vitamin B-12, folate, and vitamin B-6 status and relation to sulfur amino acid metabolism in neonates

BACKGROUND: Total serum homocysteine (tHcy) has been used as an indicator of intracellular vitamin B-12, vitamin B-6, and folate status in adults, but data for neonates and infants are lacking. Vitamin B-12 deficiency may have fatal effects on neurologic development in infants; therefore, early diagnosis is crucial. OBJECTIVE: Our aim was to provide a reference range for tHcy in neonates and to explore the relation of tHcy to 1) serum vitamin concentrations, 2) the product of the transsulfuration pathway (cysteine), and 3) nutritional factors. DESIGN: tHcy, cysteine, folate, vitamin B-12, and vitamin B-6 were measured in 123 healthy, breast-fed neonates. The influence of nutrition (formula or human milk) on these variables was investigated in 60 infants. RESULTS: The mean (+/-SD) tHcy concentration was 7.8 +/- 3.1 micromol/L. tHcy showed a linear association with log vitamin B-12 (r = -0.64, P: < 0. 001), red blood cell folate (r = -0.33, P: < 0.001), and cysteine (r = 0.36, P: < 0.001). The strongest linear association was found between tHcy and the ratio of log cysteine to log vitamin B-12 (r = 0.71, P: < 0.0001). We found more neonates with probable tissue deficiencies of vitamin B-12 and folate on the basis of tHcy measurements than was expected from the analysis of serum vitamin concentrations alone (15.4% compared with 9.7%). Breast-fed infants had significantly lower vitamin B-12 concentrations and significantly higher serum tHcy and cysteine concentrations and ratios of log cysteine to log vitamin B-12 than did formula-fed infants (P: < 0.001). CONCLUSIONS: tHcy can be used as a functional indicator of vitamin B-12 and folate status in neonates. The ratio of cysteine to vitamin B-12 can be used as an additional index of impaired intracellular Hcy metabolism. tHcy and cysteine concentrations in infants are affected by nutritional factors.     

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.     

Vitamin B-12 deficiency is prevalent in 35- to 64-year-old Chinese adults

Low vitamin B-12 status alone, or in combination with low folate status, is related to neural tube defects (NTD) and hyperhomocysteinemia, a risk factor for atherosclerotic disease, but little is known about vitamin B-12 status in Chinese adults. In a cross-sectional study, we measured plasma vitamin B-12 in 2407 apparently healthy Chinese men and women, 35-64 y old, living in the south and the north of China. Plasma vitamin B-12 concentrations were lower among the northerners than the southerners (geometric means, 209 vs. 309 pmol/L, P < 0.001). Controlling for gender, age, season (spring and fall), and area (urban and rural) had little impact on the difference. We estimated that 11% of the southerners and 39% of the northerners had plasma vitamin B-12 concentrations <185 pmol/L, a level to define vitamin B-12 deficiency. Within each region, men had lower plasma vitamin B-12 concentrations and higher prevalence of vitamin B-12 deficiency than women (279 vs. 333 pmol/L and 15 vs. 8% in the south; 192 vs. 233 pmol/L and 47 vs. 34% in the north; P < 0.001 for all the differences). Low intakes of animal-based food, especially fish and dairy products, were significantly associated with vitamin B-12 deficiency. In the north, 59% of the participants were deficient in either folate (<6.8 nmol/L) or vitamin B-12, and 17% had deficiency in both. The corresponding rates were 16 and 1% in the southerners. To our knowledge, our findings provide the first evidence that vitamin B-12 deficiency is common in 35- to 64-y-old Chinese adults, especially in the north. Further studies are needed to evaluate the health effects and possible intervention strategies in areas where B-12 vitamin deficiency is common.     

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.     

B vitamins and plasma homocysteine concentrations in an urban and rural area of Costa Rica

OBJECTIVE: We studied the association between total plasma homocysteine (tHcy) concentrations and folate, B(12), and B(6) status in the urban and rural areas of Costa Rica. Subjects and Methods: We determined plasma tHcy concentrations and assessed dietary folate, B(12) and B(6) intake by a food frequency questionnaire in 462 subjects selected by stratified random sampling in the urban and rural areas of Puriscal, Costa Rica. Plasma folate and vitamin B(12) concentrations were measured in women. RESULTS: THcy concentrations were higher (p < 0.01) in the rural compared with the urban area: 12.0 micro mol/L vs. 8.9 micro mol/L in men, and women 7.3 micro mol/L vs. 5.5 micro mol/L in women, respectively. The prevalence of hyperhomocysteinemia (greater than 15.0 micro mol/L) was twice as high in rural compared with urban men (19.8% vs. 10.8%, p = 0.06) and women (6.6% vs. 3.4%, p = 0.26). Most study subjects (98%) had folate intakes that were less than the recommended 400 micro g/day. In women, 31% of those living in the urban area and 40% of those in the rural area had plasma folate concentrations of less than 6.8 nmol/L, an indicator of folate deficiency. In women, age-adjusted mean tHcy concentrations ( micro mol/L) were higher in the lowest compared with highest quintiles for dietary vitamin B(6) (9.9 vs. 5.4, p < 0.05), B(12) (9.2 vs. 4.9, p < 0.01), and folate (7.0 vs. 5.7, p = 0.87). Similar results were found for plasma B(12) (9.9 vs. 5.4, p < 0.01) and folate (10.5 vs. 5.0, p < 0.0001). CONCLUSIONS: Residents of the rural area in Puriscal, Costa Rica have higher plasma concentrations of tHcy and lower intake of B vitamins, particularly in women. Because these characteristics are associated with high risk of cardiovascular disease, the efficacy of food fortification program in rural areas should be carefully addressed.     

Plasma homocysteine, folate and vitamin B(12) compared between rural Gambian and UK adults

The disease risk indicator plasma total homocysteine (tHcy) is influenced by genetic and environmental factors, including folate and vitamin B(12) status. Little is known about the determinants of tHcy in rural West Africa. We explored the hypothesis that tHcy in rural Gambian adults might vary between the sexes and physiological groups, and/or with folate and vitamin B(12) status. Comparisons were made with a British national survey. Non-pregnant Gambian women (n 158) had tHcy concentrations (geometric mean 9.0 micromol/l) similar to those of non-pregnant UK women (n 449; 9.4 micromol/l), whereas pregnant Gambian women (n 12) had significantly lower values (6.2 micromol/l). Gambian men (n 22) had significantly higher values (14.7 micromol/l) than British men (n 354; 10.8 micromol/l). Gambian lactating women and British men and women exhibited significant inverse relationships between log(e)(tHcy) and folate status; however, only the British subjects exhibited significant inverse relationships between loge(tHcy) and vitamin B(12) status. In the British sample, and in Gambian lactating women, folate and vitamin B(12) status variations together accounted for 20-25 % of the variation in log(e)(tHcy). Within the UK, black-skinned adults had folate and tHcy levels similar to those of their white-skinned counterparts, but significantly higher vitamin B(12) values. We conclude that, whereas folate and vitamin B(12) status are similar between British and rural Gambian populations, tHcy is higher in Gambian men and lower in pregnant Gambian women, and that serum vitamin B(12) values appear to be higher in black-skinned than white-skinned British subjects. Possible reasons are discussed.     

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.     

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.     

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.

     

Effect of age on plasma homocysteine concentrations in young and elderly subjects considering serum vitamin concentrations and different lifestyle factors

OBJECTIVES: The aim of this study was to investigate whether an increase in total homocysteine (tHcy) concentration with increasing age is due to diminishing serum concentrations of pyridoxal-5-phosphate (PLP), vitamin B-12, and folate. The possible influence of different lifestyle factors on tHcy concentration was considered. METHODS: Plasma tHcy, serum concentrations of pyridoxal-5-phosphate, vitamin B-12, and folate, intake of coffee and tea, alcohol, and methionine, as well as cigarette smoking, were determined in 252 elderly subjects (60-87 years old) of the longitudinal study on nutrition and health status in an aging population in Giessen (GISELA) and 99 young adults (20-34 years old) of the study on health and nutrition of young adults (GEJE). RESULTS: Mean plasma tHcy concentrations were significantly higher in elderly than in young female subjects (9.7 +/- 1.9 micromol/L vs. 9.0 +/- 1.6 micromol/L, p < 0.05), but there was no difference between elderly and young men (10.6 +/- 2.1 micromol/L vs. 10.7 +/- 2.6 micromol/L). No differences in tHcy were observed between young and elderly subjects after adjustment for serum concentrations of PLP, vitamin B-12, and folate. Multiple linear regression analysis revealed a significant influence of age only in elderly, but not in younger subjects. CONCLUSION: Higher tHcy concentrations in the elderly, in comparison to younger women, are due to lower serum concentrations of PLP, vitamin B-12, and folate, whereas within the age group of elderly subjects alone tHcy concentrations increase with age irrespective of serum vitamin concentrations.     

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.     

Dietary pattern is associated with homocysteine and B vitamin status in an urban Chinese population

To identify existing dietary patterns and examine associations between these patterns and plasma homocysteine and B vitamin concentrations in an urban Chinese population living in Beijing (n = 119), dietary information was collected with a food frequency questionnaire designed for this population. Plasma homocysteine and B vitamin concentrations were examined. Food group variables, expressed as percentages of total energy intake, were entered into cluster analysis to define three distinct dietary pattern groups. The prevalence of high homocysteine (>11 micromol/L for women and 12 micromol/L for men), was 31.9%; of low folate (<6.8 nmol/L), 36.2%; of low vitamin B-12 (<221 pmol/L), 36.9%; and of low vitamin B-6 (<30 nmol/L), 16.0%. The three dietary patterns derived were defined by relatively greater intake of 1) fruit and milk, 2) red meat and 3) refined cereals. More than 40% of subjects in the refined cereals group had high plasma homocysteine and low plasma folate concentrations, and 67% had low plasma vitamin B-12 concentrations. Those following the refined cereals pattern were 4 and 5.2 times more likely to have high homocysteine and low vitamin B-12 concentrations, respectively, relative to the fruit and milk dietary pattern group (P < 0.01), after adjustment for potential confounders. High intake of refined cereals was associated with low B vitamin and high homocysteine concentrations, whereas the pattern high in fruit and milk was associated with the lowest homocysteine. Dietary patterns appear to play an important role in the micronutrient and homocysteine status of these Chinese adults.     

Effects of folate, vitamin B-12 and vitamin B-6 supplementation on methionine-induced hyperhomocysteinemia in rats

An excessive intake of dietary methionine increases plasma total homocysteine (tHcy, an independent risk factor for premature cardiovascular disease) by enhancing the synthesis of homocysteine. Information on the influence of excess dietary vitamins involved in homocysteine metabolism on the methionine-induced hyperhomocysteinemia is, however, limited. Thus, a six-week study was conducted to determine the influence of excess folic acid, vitamin B-12 and vitamin B-6 on the methionine-induced hyperhomocysteinemia in rats. Supplementation of the casein control diet with 10 and 20 g/kg L-Met increased plasma tHcy to 2.0 and 8.0 times control, respectively. The hyperhomocysteinemia caused by the addition of 10 g/kg L-Met to the control diet, was completely counteracted by extra folic acid or three vitamins combined (folic acid, 2 mg/kg; vitamin B-12, 25 μg/kg; plus vitamin B-6, 6 mg/kg) but the addition of extra vitamin B-12 or vitamin B-6 alone had no effect on plasma tHcy. Similarly, extra dietary folic acid or the three vitamins combined caused substantial reduction in plasma tHcy of rats fed the control diet supplemented with 20 g/kg L-Met but addition of vitamin B-12 or vitamin B-6 alone exacerbated plasma tHcy.     

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.     

Lowering plasma homocysteine concentrations of older men and women with folate, vitamin B-12, and vitamin B-6 does not affect the proportion of (n-3) long chain polyunsaturated fatty acids in plasma phosphatidylcholine

There is evidence to suggest that folate, homocysteine, or both affect the (n-3) long chain PUFA composition of tissues; however, this evidence is derived largely from experiments with animals and small observational studies in humans. Results from randomized controlled trials are needed. The objective of this study was to determine whether homocysteine lowering with a B vitamin supplement affects the proportion of (n-3) long-chain PUFA in plasma phosphatidylcholine. We conducted a double-blind, placebo-controlled, randomized clinical trial involving 253 participants, 65 y or older, with plasma homocysteine concentrations of at least 13 micromol/L. Participants in the vitamin group (n = 127) took a daily supplement containing 1000 microg folate, 500 microg vitamin B-12, and 10 mg vitamin B-6 for 2 y. The fatty acid composition of plasma phosphatidylcholine was measured at baseline and at 2 y. Plasma homocysteine concentrations during the course of the study were 4.4 micromol/L lower in the vitamin group than in the placebo group. The proportions of eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids in plasma phosphatidylcholine did not differ between the vitamin and placebo groups at 2 y; the mean differences after adjusting for baseline values and sex were -0.03 (99% CI: -0.22, 0.16), 0.03 (99% CI: -0.03, 0.09), and -0.02 (99% CI: -0.27, 0.24) mol%, respectively. Lowering plasma homocysteine concentrations of older men and women with folate, vitamin B-12, and vitamin B-6 had no effect on the proportion of (n-3) long-chain PUFA in plasma phosphatidylcholine.     

Vitamin B-12 metabolism in HIV-infected patients in the age of highly active antiretroviral therapy: role of homocysteine in assessing vitamin B-12 status

BACKGROUND: Before the advent of highly active antiretroviral therapy (HAART), 20% and 10% of HIV-infected patients had low vitamin B-12 and red blood cell folate (RBCF) concentrations, respectively. However, few patients had real vitamin B-12 deficiency. OBJECTIVE: We evaluated the prevalence of low vitamin B-12 and RBCF concentrations in HIV-infected patients receiving HAART and the usefulness of serum homocysteine (sHcy) for differentiating patients with deficiency from those with harmlessly low vitamin B-12. DESIGN: The prevalence of low vitamin B-12 and RBCF was evaluated in 126 HIV-infected patients receiving HAART. Moreover, sHcy concentrations were evaluated in 40 HIV-infected patients with low vitamin B-12 and in 37 HIV-infected patients with low RBCF and were compared with those in 128 HIV-infected patients with normal vitamin B-12 and RBCF. sHcy was used to monitor treatment with vitamin B-12 and folic acid in 28 patients (24 with low vitamin B-12 and RBCF and 4 with hyperhomocysteinemia but normal vitamin B-12 and RBCF). RESULTS: The prevalence of low vitamin B-12 was significantly lower in patients receiving HAART than in previously studied patients who did not receive HAART (8.7% compared with 27%). Nine of the 40 patients (22.5%) with low vitamin B-12 (< or = 200 pmol/L) had hyperhomocysteinemia (> 17.5 micromol homocysteine/L). Nineteen (51.4%) of the 37 patients with low RBCF (< or = 580 nmol/L, percentile 10) had hyperhomocysteinemia. Among the 9 patients with an RBCF concentration < or = 450 nmol/L (percentile 2.5), all had hyperhomocysteinemia. The treatment with vitamin B-12 and folic acid normalized sHcy concentrations. CONCLUSIONS: The prevalence of low vitamin B-12 decreased after the introduction of HAART. The study of sHcy is useful for detecting HIV-infected patients with low vitamin B-12 and real deficiency.     

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 (delta = 10.2%, p < 0.05). Mean plasma or erythrocyte folate decreased significantly (delta = 33.7%, p <0.05 and delta = -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 I 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 micromol/L. plasma tHcy was >14 micromol/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.     

Significant correlations of plasma homocysteine and serum methylmalonic acid with movement and cognitive performance in elderly subjects but no improvement from short-term vitamin therapy: a placebo-controlled randomized study

BACKGROUND: Deficiencies of vitamin B-12, folic acid, and vitamin B-6-as defined by laboratory measures-occur in 10-20% of elderly subjects. The clinical significance remains unresolved. OBJECTIVE: The objective was to explore any association between vitamin status and vitamin treatment and movement and cognitive performance in elderly subjects. DESIGN: Community-dwelling subjects (n = 209) with a median age of 76 y were randomly assigned to daily oral treatment with 0.5 mg cyanocobalamin, 0.8 mg folic acid, and 3 mg vitamin B-6 or placebo (double blind) for 4 mo. Movement and cognitive performance tests were performed before and after treatment. RESULTS: A high plasma total homocysteine (tHcy) concentration (> or =16 micromol/L) was found in 64% of men and in 45% of women, and a high serum methylmalonic acid (MMA) concentration (> or =0.34 micromol/L) was found in 11% of both sexes. Movement time, digit symbol, and block design (adjusted for age, sex, smoking, and creatinine) correlated independently with plasma tHcy (P < 0.01, < 0.05, and < 0.01, respectively); the simultaneity index and block design correlated with serum MMA (P < 0.05 for both). Vitamin therapy significantly decreased plasma tHcy (32%) and serum MMA (14%). No improvements were found in the movement or cognitive tests compared with placebo. Neither vitamin therapy nor changes in plasma tHcy, serum MMA, serum vitamin B-12, plasma folate, or whole-blood folate correlated with changes in movement or cognitive performance. CONCLUSIONS: High plasma tHcy and serum MMA were prevalent and correlated inversely with movement and cognitive performance. Oral B vitamin treatment normalized plasma tHcy and serum MMA concentrations but did not affect movement or cognitive performance. This might have been due to irreversible or vitamin-independent neurocognitive decline or to an insufficient dose or duration of vitamins.