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.     

Cognitive performance in relation to vitamin status in healthy elderly German women-the effect of 6-month multivitamin supplementation

BACKGROUND: Prior investigations have reported a link between poor status of antioxidants, folate, and cobalamin resulting in elevated total plasma homocysteine (tHcy) and methylmalonic acid (MMA) concentrations with an increased risk for reduced cognitive performance. The aim of the study was to evaluate the effect of a 6-month multivitamin supplementation on the cognitive performance of female seniors and to assess cognitive functioning in relation to vitamin status, tHcy, and MMA values at baseline. METHODS: The study was performed as a randomized placebo-controlled double-blind trial. 220 healthy, free-living women (aged 60-91 years) were included. Blood drawings and cognitive tests were performed at the Institute of Food Science of the University of Hanover, Germany. Vitamin and cognitive status have been evaluated prior to and 6 months after supplementation. Plasma ascorbic acid, serum concentrations of alpha-tocopherol, beta-carotene, and coenzyme Q10, serum and erythrocyte folate as well as serum cobalamin, serum MMA, and plasma tHcy concentrations were measured. Activity coefficient of erythrocyte alpha aspartic aminotransferase was used as functional index for vitamin B(6) status. The cognitive performance was assessed by the Symbol Search test, a subtest of the Wechsler Adult Intelligence Scale (WAIS-III) and the pattern-recognition test. Intelligence as assessed by the 'Kurztest für Allgemeine Intelligenz' (KAI) was a further variable. RESULTS: No significant differences in pattern-recognition and intelligence score were observed between vitamin and placebo group prior to and after multivitamin supplementation. In the Symbol Search test, the vitamin group exhibited better test results than the placebo group at both measure points. One-way ANOVA showed a marginally significant linear trend between the baseline tHcy concentration and the pattern-recognition score (P = 0.051) in the total sample. Multiple backward regression revealed only a significant influence of the school graduation on baseline cognitive function test results. A general linear model showed that the changes in cognitive function scores could not be explained by the type of treatment or blood parameters. CONCLUSIONS: Our data indicate that 6 months supplementation of physiological dosages of antioxidants and B vitamins have no effect on cognitive performance in presumedly healthy and well-nourished female seniors. An intervention period of only 6 months may be too short for improving cognitive performance in well-educated elderly women without dementia.     

Racial differences in prevalence of cobalamin and folate deficiencies in disabled elderly women.

BACKGROUND: Many previous investigations of cobalamin and folate status were performed in white populations. OBJECTIVE: Our objective was to determine whether there are racial differences in the prevalence of cobalamin and folate deficiency. DESIGN: The study was a cross-sectional comparison of baseline serum cobalamin, folate, methylmalonic acid (MMA), total homocysteine (tHcy), and creatinine concentrations, complete blood count, and vitamin supplementation in 550 white and 212 African American subjects from a cohort of physically disabled older women. RESULTS: The mean (+/-SD) serum MMA concentration was significantly higher in whites than in African Americans: 284 +/- 229 compared with 218 +/- 158 nmol/L (P = 0.0001). tHcy concentration was higher in African Americans than in whites: 12.4 +/- 7.0 compared with 10.9 +/- 4.6 micromol/L (P = 0.001). Serum cobalamin was lower in whites (P = 0.0002). Cobalamin deficiency (serum cobalamin <258 pmol/L and MMA >271 nmol/L) was more frequent in the white women (19% compared with 8%; P < 0.0003). Folate deficiency (serum folate <11.4 nmol/L, tHcy >13.9 micromol/L, and MMA <271 nmol/L) was more prevalent in African Americans than in whites (5% compared with 2%; P = 0.01). Multivitamin use was associated with lower tHcy but not with MMA concentrations. Regression models showed that age >85 y, African American race, serum creatinine >90 micromol/L, and high MMA concentration were all significantly correlated with higher tHcy. Creatinine > 90 micromol/L, white race, and folate concentration were positively associated with MMA concentration. CONCLUSIONS: Cobalamin deficiency with elevated serum MMA concentration is more prevalent in elderly white than in African American women and elevated serum tHcy and folate deficiency are more prevalent in elderly African American than in white women.     

Homocysteine and methylmalonic acid in diagnosis and risk assessment from infancy to adolescence

The concentration of total homocysteine (tHcy) in serum and plasma is elevated in both folate and cobalamin deficiencies, whereas methylmalonic acid (MMA) in serum, plasma, or urine is a specific marker of cobalamin function. The combined measurement of both metabolites is useful for the diagnosis and follow-up of these deficiency states. In addition, tHcy is elevated under various pathologic states (eg, renal failure), and hyperhomocysteinemia is associated with an increased risk of cardiovascular disease, cognitive dysfunction, and adverse pregnancy outcomes. The diagnostic utility of tHcy and MMA concentrations as markers of folate and cobalamin deficiencies in healthy and diseased children has been documented. This article briefly summarizes the biochemical background of tHcy and MMA and the associations of tHcy and MMA with various disease states and focuses on novel data obtained in infants, children, and adolescents, with emphasis on cobalamin status in infants. The utility of tHcy and MMA as indicators of cobalamin and folate deficiencies in adults can be extended to infants and older children. Furthermore, as in adults, tHcy is related to unhealthy lifestyle factors and is a risk factor for vascular disease. High MMA concentrations in newborns, occasionally denoted as benign methylmalonic aciduria, may reflect impaired cobalamin function.     

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.     

Plasma folate as marker of folate status in epidemiological studies: the European Investigation into Cancer and Nutrition (EPIC)-Potsdam study

Folate deficiency is often discussed as a potential risk factor for CVD and some cancers. Reliable assessment of folate status in large-scale epidemiological studies is therefore of major importance. The present study assessed the value of plasma folate (PF) compared with erythrocyte folate (EF) as a marker of folate status in 363 participants in the European Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort. EF and PF, total homocysteine (tHcy), pyridoxine, cobalamin, creatinine, total protein and packed cell volume were determined; glutamate carboxypeptidase (GCP) C1561T, reduced folate carrier (RFC) G80A and methylenetetrahydrofolate (MTHFR) C677T polymorphisms were analysed. Anthropometric measurements were taken and dietary intake was assessed with the EPIC-Potsdam food-frequency questionnaire. Comparison of EF and PF with factors that may modulate their concentrations was performed. Cross-classification of blood folates in quintile categories resulted in correct classification into the same or adjacent category of 75.5 % of all subjects. Age, BMI, pyridoxine and cobalamin, fruit and vegetable intake, and vitamin supplementation 24 h before blood draw were positively associated with EF and with PF. For tHcy an inverse association was found. Participants with the MTHFR 677TT genotype showed significantly elevated EF concentrations compared with those with 677CT genotype; EF and PF were more strongly correlated (r 0.78, P<0.0001) for participants with MTHFR 677TT genotype than for those with the 677CC or 677CT genotype. In summary, our present results indicate that plasma folate seems to be a suitable marker for assessment of folate status for use in large-scale epidemiological studies.     

Biochemical indexes of the B vitamins in cord serum are predicted by maternal B vitamin status

BACKGROUND: The concentration of total homocysteine (tHcy) is higher in newborns than in older children. Vitamin B-12 is the major determinant of tHcy in newborns. Maternal status of folate, vitamin B-12, and vitamin B-6 during pregnancy may affect the biochemical markers of these micronutrients in newborns. OBJECTIVE: Our objective was to study the relation between concentrations of the metabolites and B vitamins in maternal sera and concentrations in the umbilical venous blood of the corresponding newborns. DESIGN: We studied healthy pregnant women at the time of labor who were expecting healthy, full-term, appropriate-birth-weight babies. Samples were available from 82 mother-infant pairs. RESULTS: Concentrations of B vitamins were higher in cord samples than in maternal blood (folate, 2-fold; vitamin B-12, 1.5-fold; and vitamin B-6, 6-fold). Concentrations of cystathionine and methylmalonic acid (MMA) were also higher in the infants than in the mothers (x +/- SD: cystathionine, 462 +/- 189 and 343 +/- 143 nmol/L; MMA, 353 +/- 144 and 233 +/- 110 nmol/L). No significant differences in tHcy concentrations were observed between fetal and maternal samples. Concentrations of vitamin B-12 did not differ significantly between mothers of infants from different quartiles of cord MMA. Higher fetal MMA concentrations were related to higher maternal MMA and vitamin B-12 concentrations and lower fetal concentrations of vitamin B-12. Fetal concentrations of cystathionine were predicted by maternal cystathionine, gestational age, fetal vitamin B-6, and fetal tHcy. CONCLUSIONS: Maternal concentrations of the metabolic markers of B vitamins predict values in fetal blood at delivery. Fetal tHcy concentrations were low but were predicted by the vitamin status of the mother. The effect of increasing maternal intake of vitamins B-12 and B-6 during pregnancy on the fetal concentrations of the metabolites should be investigated.     

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.     

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.     

Determinants of plasma total homocysteine concentration in the Framingham Offspring cohort

BACKGROUND: Established determinants of fasting total homocysteine (tHcy) concentration include folate and vitamin B-12 status, serum creatinine concentration, and renal function. OBJECTIVE: Our objective was to examine the relation between known and suspected determinants of fasting plasma tHcy in a population-based cohort. DESIGN: We examined the relations between fasting plasma tHcy concentrations and nutritional and other health factors in 1960 men and women, aged 28-82 y, from the fifth examination cycle of the Framingham Offspring Study between 1991 and 1994, before the implementation of folic acid fortification. RESULTS: Geometric mean tHcy was 11% higher in men than in women and 23% higher in persons aged > or = 65 y than in persons aged < 45 y (P < 0.001). tHcy was associated with plasma folate, vitamin B-12, and pyridoxal phosphate (P for trend < 0.001). Dietary folate, vitamin B-6, and riboflavin were associated with tHcy among non-supplement users (P for trend < 0.01). The tHcy concentrations of persons who used vitamin B supplements were 18% lower than those of persons who did not (P < 0.001). tHcy was positively associated with alcohol intake (P for trend = 0.004), caffeine intake (P for trend < 0.001), serum creatinine (P for trend < 0.001), number of cigarettes smoked (P for trend < 0.001), and antihypertensive medication use (P < 0.001). CONCLUSIONS: Our study confirmed, in a population-based setting, the importance of the known determinants of fasting tHcy and suggested that other dietary and lifestyle factors, including vitamin B-6, riboflavin, alcohol, and caffeine intakes as well as smoking and hypertension, influence circulating tHcy concentrations.     

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.     

Plasma Total Homocysteine Level in Association With Folate,Pyridoxine, and Cobalamin Status Among Iranian Primary Breast Cancer Patients

Recently the elevated plasma total homocysteine (tHcy) concentration has been concerned as the secondary feature of tumoral proliferation and enhances the likelihood of thrombogenesis in cancer patients. The objective of this study was to determine the associations between folate, cobalamin, and pyridoxine with fasting plasma tHcy concentration in breast cancer (BC) patients. The intake levels of nutrients were assessed using a validated food frequency questionnaire in 141 newly diagnosed BC patients. The plasma tHcy and pyridoxal-5-phosphate were measured using high performance liquid chromatography with fluorescence detector. Plasma tHcy levels were observed to be significantly higher among BC participants with Stage III where the plasma concentrations of folate was also comparatively less (P < 0.05) than other stages. Dietary pyridoxine was even being consumed less at this stage (P < 0.05). The plasma, dietary, and residual variables of folate were inversely correlated with plasma tHcy concentration (P < 0.05). Dietary cobalamin was also associated negatively with tHcy (P < 0.05). The odds ratio of comparing the highest tertile of plasma cobalamin (>394 pmol/l) and folate (>11.4 ng/ml) vs. the lowest categories were associated with reduced odds of high tHcy occurrence with 0.20 (95% confidence interval: 0.04–0.98) and 0.14 (95% confidence interval: 0.03–0.64), respectively. In conclusion, nutrition-related methyl-group insufficiency could lead to imbalance in tHcy metabolism, as a possible cancer marker.     

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.     

Risk of persistent cobalamin deficiency in adolescents fed a macrobiotic diet in early life

BACKGROUND: Cobalamin deficiency has been described in children consuming macrobiotic diets. OBJECTIVE: We investigated whether moderate consumption of animal products is sufficient for achieving normal cobalamin function in 73 adolescents who had received a macrobiotic diet until 6 y of age and had then switched to a lactovegetarian, lactoovovegetarian, or omnivorous diet (macrobiotic adolescents). DESIGN: Hematologic indexes and serum concentrations of methylmalonic acid (MMA), total homocysteine (tHcy), and folate were measured. Current consumption frequency of animal products and cobalamin intake from dairy products were assessed by questionnaire. Data from 94 age-matched adolescents who received an omnivorous diet from birth were used as a reference. RESULTS: Serum cobalamin concentrations were significantly lower and concentrations of MMA and folate and mean corpuscular volume (MCV) were significantly higher in macrobiotic adolescents than in control adolescents: of macrobiotic adolescents, 21% had abnormal MMA concentrations (>0.41 micromol/L), 37% had abnormal cobalamin concentrations (<218 pmol/L), 10% had abnormal tHcy concentrations (> 12.8 micromol/L), and 15% had abnormal MCV (> 89 fL). In macrobiotic adolescents, dairy products (200 g milk or yogurt and 22 g cheese/d) supplied on average 0.95 microg cobalamin/d; additionally, these adolescents consumed fish, meat, or chicken 2-3 times/wk. In girls, meat consumption contributed more to cobalamin status than the consumption of dairy products, whereas in boys these food groups were equally important. CONCLUSIONS: A substantial number of the formerly strict macrobiotic adolescents still had impaired cobalamin function. Thus, moderate consumption of animal products is not sufficient for restoring normal cobalamin status in subjects with inadequate cobalamin intake during the early years of life.     

A population study of the influence of beer consumption on folate and homocysteine concentrations

OBJECTIVE: Mild hyperhomocysteinemia is a significant and independent risk factor for vascular diseases. Blood total homocysteine concentration (tHcy) is considered to be the product of an interaction between genetic and nutritional factors notably intake of folate, vitamin B12 and pyridoxine. The aim of the study was to determine whether regular intake of beer containing large amount of folate and other vitamins influences the tHcy blood concentrations. DESIGN: Cross-sectional population-based survey. SETTING: Adult population, residents of Pilsen (Czech Republic) and vicinity. SUBJECTS: Population series included 292 males and 251 females aged 35-65 y, mean age 53.4 y. All subjects were examined by a standard protocol for clinical, anthropometrical and laboratory estimations. MAIN OUTCOME MEASURES: tHcy was measured by high-pressure liquid chromatography with fluorescent detection, blood folate and B12 levels immunochemically using commercial kits. RESULTS: Beer intake was associated with blood folate and vitamin B12 concentrations positively and with tHcy concentration negatively. By categories of beer intake, subjects with intake of 1 l daily or more had significantly lower tHcy and higher folate concentrations than those reporting lower daily beer intake. CONCLUSION: Moderate beer consumption may help to maintain the tHcy levels in the normal range due to high folate content. Folate from beer may thus contribute to the protective effect of alcohol consumption on cardiovascular disease in population with generally low folate intake from other nutrients. SPONSORSHIP: Supported by grant 301/00/P089 Grant Agency of Czech Republic and Internal Grant Agency of the Ministry of Health.     

Alterations of Homocysteine Serum Levels during Alcohol Withdrawal Are Influenced by Folate and Riboflavin: Results from the German Investigation on Neurobiology in Alcoholism (GINA)

Aims: Various studies have shown that plasma homocysteine (HCY) serum levels are elevated in actively drinking alcohol-dependent patients a during alcohol withdrawal, while rapidly declining during abstinence. Hyperhomocysteinemia has been associated not only with blood alcohol concentration (BAC), but also with deficiency of different B-vitamins, particularly folate, pyridoxine and cobalamin. Methods: Our study included 168 inpatients (110 men, 58 women) after admission for detoxification treatment. BAC, folate, cobalamin, pyridoxine, thiamine and riboflavin were obtained on admission (Day 1). HCY was assessed on Days 1, 7 and 11. Results: HCY levels significantly declined during withdrawal. General linear models and linear regression analysis showed an influence of BAC, folate and riboflavin on the HCY levels on admission as well as on HCY changes occurring during alcohol withdrawal. No significant influence was found for thiamine, cobalamin and pyridoxine. Conclusions: These findings show that not only BAC and plasma folate levels, but also plasma levels of riboflavin influence HCY plasma levels in alcohol-dependent patients.     

The B-vitamins in malnutrition with alcoholism. A model of intervitamin relationships.

1. The B-vitamin status of fifty-nine patients, mainly from the lower socio-economic classes in Bombay, with a history of chronic malnutrition, and of alcoholism of 1-5-20 years' duration, was studied before and during treatment, and in relation to their clinical, especially neurological, condition. These patients were divided into two neurological categories: (I) those with peripheral neuropathy (mainly sensory and distal) alone, (2) those with mental changes (mainly confusion and disorientation) also. Both categories frequently showed pellagrous pigmentation and mucocutaneous signs of B-vitamin deficiency. 2. Thiamin and erythrocyte transketolase (EC 2.2.1.1) activity, riboflavin, nicotinic acid, pantothenic acid, total and pyridoxal fraction of vitamin B6, folate and total vitamin B12 were estimated in the blood and the cerebrospinal fluid (CSF) of these patients, and also in the blood of sixty-nine control subjects and in the CSF of some of them. The concentrations of all the vitamins, except vitamin B12, were highly significantly lower in the blood of patients of category I compared to the controls, and erythrocyte transketolase activity and pyridoxal concentration in patients of category 2 were significantly lower than those of category I patients. Blood pantothenic acid and folate concentrations were reduced less consistently. 3. Serum vitamin B12 concentration was significantly increased (though within normal range) in the patients compared to the control group, probably because of the moderate hepatic insufficiency (as assessed by liver function tests) in the former. 4. The concentrations of thiamin, riboflavin, nicotinic acid and total vitamin B6 were also highly significantly lower in the CSF in patients of category I compared with controls. Furthermore, thiamin, nicotinic acid and total vitamin B6 concentrations were significantly lower in patients of category 2 than those of category I patients, indicating that CSF levels reflect better the neurological status of these patients. 5. There was a moderate increase in the blood concentration of all the vitamins tested, after a relatively poor hospital diet alone. There was a concurrent increase in the blood levels of thiamin, riboflavin, nicotinic acid and pantothenic acid after parenteral treatment with either thiamin or nicotinic acid. The administration of pyridoxine resulted in a significant increase in the blood levels of riboflavin and the pyridoxal fraction of vitamin B6.     

Dietary predictors of plasma total homocysteine in the Hordaland Homocysteine Study

Established dietary predictors of plasma total homocysteine (tHcy) include folate, riboflavin, and vitamins B6 and B12, while information is scarce regarding other dietary components. The aim of this study was to examine the relation between a variety of food groups, food items and nutrients, and plasma tHcy in a large population-based study. The study population included 5812 men and women aged 47-49 and 71-74 years who completed a 169-item FFQ. tHcy was examined across quartiles of dietary components by multiple linear regression analyses adjusting for age, sex, energy intake, various risk factors for elevated tHcy, as well as for dietary and plasma B-vitamins. Among 4578 non-users of vitamin supplements, intake of vegetables, fruits, cereals, eggs, fish and milk, as well as chicken and non-processed meats were inversely associated with tHcy level. The estimated mean difference in tHcy per increasing quartile of intake ranged from - 0.11 (95 % CI - 0.21, - 0.01) micromol/l for milk to - 0.32 (95 % CI - 0.42, - 0.22) micromol/l for vegetables. Positive associations were found for sweets and cakes. Whole-grain bread was significantly inversely related to tHcy only after additional adjustment for dietary and plasma B-vitamins. The nutrients folate, vitamin B6, B12, and riboflavin were inversely related to tHcy. Complex carbohydrates were inversely, and fat positively associated with tHcy, also after adjustment for dietary and plasma B-vitamins. In conclusion, food items rich in B-vitamins and with a low content of fat and sugar were related to lower tHcy levels. Eggs, chicken, non-processed meat, fish and milk were inversely associated with tHcy.     

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.     

Association of folate intake and serum homocysteine in elderly persons according to vitamin supplementation and alcohol use

BACKGROUND: The serum total homocysteine concentration (tHcy), an indicator of folate status and a possible risk factor for vascular disease, is elevated with impaired renal function and poor vitamin B-12 status, which are common in the elderly. OBJECTIVE: Our objective was to determine the association between tHcy, folate intake, alcohol consumption, and other lifestyle factors in elderly persons. DESIGN: This cross-sectional study used linear regression to model changes in tHcy. Subjects were 278 men and women aged 66-94 y studied in 1993. RESULTS: Total folate intake was negatively associated with tHcy in models adjusted for age, sex, serum creatinine, and serum albumin. We found an interaction between food folate intake and supplement use. Food folate intake had an inverse dose-response relation with tHcy that was limited to nonusers of supplements. Predicted tHcy was 1.5 micromol/L lower in users of supplements containing folate and vitamin B-12 than in nonusers and was independent of food folate intake. We found a positive dose-response relation of coffee and tea intake with tHcy, a positive association for alcohol intake of > or = 60 drinks/mo compared with low intake, and an interaction of alcohol use with folate intake and supplement use. Compared with alcohol users, nonusers had higher predicted tHcy and a lower inverse dose-response relation of food folate intake with tHcy. CONCLUSIONS: The inverse association between folate intake and tHcy was strongest among nonusers of supplements and among alcohol drinkers. Identifying modifiable factors related to tHcy, a possible risk factor for vascular disease, is especially important in elderly persons.