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.     

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.     

Holo-transcobalamin is an indicator of vitamin B-12 absorption in healthy adults with adequate vitamin B-12 status

BACKGROUND: It has been hypothesized that the response of holo-transcobalamin (holo-TC) to oral vitamin B-12 may be used to assess absorption. To develop a reliable clinical absorption test that uses holo-TC, it is necessary to determine the optimal timeline for vitamin B-12 administration and postdose assessment. OBJECTIVE: The objective of this study was to assess the magnitude and patterns of change in the postabsorption response of holo-TC to oral vitamin B-12. DESIGN: Adult (18-49 y) male and female participants (n = 21) with normal vitamin B-12 status were given three 9-mug doses of vitamin B-12 at 6-h intervals beginning early morning (baseline) on day 1. Blood was drawn at 17 timed intervals over the course of 3 d for the analysis of holo-TC and other indicators of vitamin B-12 status. RESULTS: Mean holo-TC increased significantly (P < 0.001) from baseline at 6 h (11%) and 24 h (50%). TC saturation increased significantly (P < 0.001) from baseline at 12.5 h (33%) and 24 h (50%). The mean cobalamin concentration changed significantly (P < 0.001) from baseline at 24 h (15%) and 48 h (14%). The ratio of holo-TC to cobalamin increased significantly (P < 0.001) at 24 h (32%). CONCLUSIONS: The greatest increase in holo-TC was observed 24 h after ingestion of three 9-mug doses of vitamin B-12. Our results indicate that a vitamin B-12 absorption test based on measurement of holo-TC after administration of three 9-mug doses of vitamin B-12 should run for 24 h.     

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.     

Transcobalamin 776C->G polymorphism negatively affects vitamin B-12 metabolism

BACKGROUND: A common genetic polymorphism [transcobalamin (TC) 776C-->G] may affect the function of transcobalamin, the protein required for vitamin B-12 cellular uptake and metabolism. Remethylation of homocysteine is dependent on the production of 5-methyltetrahydrofolate and adequate vitamin B-12 for the methionine synthase reaction. OBJECTIVES: The objectives were to assess the influence of the TC 776C--> G polymorphism on concentrations of the transcobalamin-vitamin B-12 complex (holo-TC) and to determine the combined effects of the TC 776C-->G and methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphisms and vitamin B-12 status on homocysteine concentrations. DESIGN: Healthy, nonpregnant women (n = 359; aged 20-30 y) were screened to determine plasma vitamin B-12, serum holo-TC, and plasma homocysteine concentrations and TC 776C-->G and MTHFR 677C-->T genotypes. RESULTS: The serum holo-TC concentration for women with the variant TC 776 GG genotype was significantly different (P = 0.0213) from that for subjects with the CC genotype (74 +/- 37 and 87 +/- 33 pmol/L, respectively). An inverse relation was observed between plasma homocysteine concentrations and both serum holo-TC (P G polymorphism negatively affects the serum holo-TC concentration and provide additional evidence that vitamin B-12 status modulates the homocysteine concentration in this population.     

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.     

Long-term ovo-lacto vegetarian diet impairs vitamin B-12 status in pregnant women

A well-planned vegetarian diet has been stated to be adequate during pregnancy. The aim of the present study was to compare serum vitamin B-12 and homocysteine concentrations in pregnant women (n = 109) consuming vegetarian and Western diets and to evaluate the adequacy of current dietary reference intakes of vitamin B-12 for these women. Pregnant women adhering to vegetarian diets for at least 3 y, with subgroups of ovo-lacto vegetarians (OLVs; n = 27), low-meat eaters (LME, n = 43), and women eating an average Western diet (control group, n = 39), were recruited. Dietary vitamin B-12 intake, serum vitamin B-12, and plasma total homocysteine (tHcy) concentrations were measured in wk 9-12, 20-22, and 36-38 of pregnancy. During pregnancy serum vitamin B-12 concentrations of ovo-lacto vegetarians (P < 0.001) and low-meat eaters (P = 0.050) were lower than those of the control group. We observed the combination of low serum vitamin B-12 concentrations and elevated plasma tHcy in 22% of ovo-lacto vegetarians, in 10% of low-meat eaters, and in 3% of controls (P = 0.003). In OLVs, serum vitamin B-12 predicted 60% of the plasma tHcy variation (P < 0.001), but in LMEs and controls only <10% (NS). Serum vitamin B-12 concentrations increased and plasma tHcy decreased sharply with increasing dietary intake of vitamin B-12 toward a cutoff point of 3 mug/d. Pregnant women consuming a long-term predominantly vegetarian diet have an increased risk of vitamin B-12 deficiency. Current recommended dietary intakes urgently need reevaluation.     

Biomarkers of vitamin B-12 status in NHANES: a roundtable summary

A roundtable to discuss the measurement of vitamin B-12 (cobalamin) status biomarkers in NHANES took place in July 2010. NHANES stopped measuring vitamin B-12-related biomarkers after 2006. The roundtable reviewed 3 biomarkers of vitamin B-12 status used in past NHANES--serum vitamin B-12, methylmalonic acid (MMA), and total homocysteine (tHcy)--and discussed the potential utility of measuring holotranscobalamin (holoTC) for future NHANES. The roundtable focused on public health considerations and the quality of the measurement procedures and reference methods and materials that past NHANES used or that are available for future NHANES. Roundtable members supported reinstating vitamin B-12 status measures in NHANES. They noted evolving concerns and uncertainties regarding whether subclinical (mild, asymptomatic) vitamin B-12 deficiency is a public health concern. They identified the need for evidence from clinical trials to address causal relations between subclinical vitamin B-12 deficiency and adverse health outcomes as well as appropriate cutoffs for interpreting vitamin B-12-related biomarkers. They agreed that problems with sensitivity and specificity of individual biomarkers underscore the need for including at least one biomarker of circulating vitamin B-12 (serum vitamin B-12 or holoTC) and one functional biomarker (MMA or tHcy) in NHANES. The inclusion of both serum vitamin B-12 and plasma MMA, which have been associated with cognitive dysfunction and anemia in NHANES and in other population-based studies, was preferable to provide continuity with past NHANES. Reliable measurement procedures are available, and National Institute of Standards and Technology reference materials are available or in development for serum vitamin B-12 and MMA.     

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.     

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.     

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.     

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.     

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.     

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.     

B vitamin status and concentrations of homocysteine and methylmalonic acid in elderly German women

BACKGROUND: Prior investigations found that elderly persons are at higher risk than are younger persons for B vitamin deficiency, which leads to elevated plasma total homocysteine (tHcy) concentrations that are associated with an increased risk for certain diseases such as coronary artery disease. To date, published data have shown decreased vitamin status and elevated tHcy among the elderly. OBJECTIVE: We evaluated the dietary intake and the blood status of various B vitamins and tHcy and methylmalonic acid (MMA) concentrations in 178 younger (60-70-y-old) female seniors. DESIGN: Dietary intake was assessed with a 3-d diet record. Thiamine, riboflavin, and vitamin B-6 activity coefficients of erythrocyte transketolase (EC 2.2.1.1), erythrocyte glutathione reductase (EC 1.6.4.2), and erythrocyte alpha-aspartic aminotransferase (EC 2.6.1.1) were used as functional indexes for the status of the 3 vitamins, respectively. Concentrations of serum and red blood cell folate, serum cobalamin and MMA, and plasma tHcy were measured. RESULTS: Indexes of thiamine, pyridoxine, and cobalamin indicated insufficient status in one-third of the women, whereas tHcy and MMA concentrations were elevated in 17.4% and 9.6% of the women, respectively. An association between vitamin intake and vitamin concentration in the blood was found only for folate. The mean tHcy concentration in subjects in the lowest quartile of serum folate concentration was 23% higher than that in subjects in the highest quartile. There was no association between riboflavin and tHcy concentrations. MMA was positively correlated with age and inversely correlated with serum cobalamin concentration. CONCLUSIONS: Even in younger, well-educated, female seniors, the prevalence of low B vitamin status and elevated plasma tHcy concentration is high. Thiamine, pyridoxine, folate, and cobalamin supplementation should be considered.     

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.     

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.     

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.     

Plasma vitamin B-12 concentrations relate to intake source in the Framingham Offspring study

BACKGROUND: Low vitamin B-12 status is prevalent among the elderly, but few studies have examined the association between vitamin B-12 status and intake. OBJECTIVE: We hypothesized that vitamin B-12 concentrations vary according to intake source. DESIGN: Plasma concentrations and dietary intakes were assessed cross-sectionally for 2999 subjects in the Framingham Offspring Study. The prevalence of vitamin B-12 concentrations <148, 185, and 258 pmol/L was examined by age group (26-49, 50-64, and 65-83 y), supplement use, and the following food intake sources: fortified breakfast cereal, dairy products, and meat. RESULTS: Thirty-nine percent of subjects had plasma vitamin B-12 concentrations <258 pmol/L, 17% had concentrations <185 pmol/L, and 9% had concentrations <148 pmol/L, with little difference between age groups. Supplement users were significantly less likely than non-supplement-users to have concentrations <185 pmol/L (8% compared with 20%, respectively). Among non-supplement-users, there were significant differences between those who consumed fortified cereal >4 times/wk (12%) and those who consumed no fortified cereal (23%) and between those in the highest and those in the lowest tertile of dairy intake (13% compared with 24%, respectively), but no significant differences by meat tertile. Regression of plasma vitamin B-12 on log of intake, by source, yielded significant slopes for each contributor adjusted for the others. For the total group, b = 40.6 for vitamin B-12 from vitamin supplements. Among non-supplement-users, b = 56.4 for dairy products, 35.2 for cereal, and 16.7 for meat. Only the meat slope differed significantly from the others. CONCLUSIONS: In contrast with previous reports, plasma vitamin B-12 concentrations were associated with vitamin B-12 intake. Use of supplements, fortified cereal, and milk appears to protect against lower concentrations. Further research is needed to investigate possible differences in bioavailability.     

Very low oral doses of vitamin B-12 increase serum concentrations in elderly subjects with food-bound vitamin B-12 malabsorption

The BOSSANOVA study, a randomized double-blind trial, was designed to test the ability of very low oral doses of vitamin B-12 to increase the serum vitamin B-12 concentration in elderly subjects with food-bound vitamin B-12 malabsorption, and to determine whether there was a dose response. We also aimed to quantitatively assess the most efficient dose to be added to flour in addition to folic acid (flour cofortification with vitamin B-12 and folic acid). Sixty-seven patients were randomly assigned to 1 of 6 groups receiving various daily oral doses of vitamin B-12 (i.e., 2.5, 5, 10, 20, 40, or 80 microg/d) for 30 d. The dose-response was tested for different biological variables using a mixed model, taking into account the variable's initial value (between-subject effect), a linear log-dose effect, and a linear log (dosextime) interaction, where time was d 15 or d 30. We planned to determine the amount of oral vitamin B-12 that would increase the serum vitamin B-12 concentration by 37 pmol/L (50 ng/L). Significant between-subject effects were found for serum vitamin B-12, plasma homocysteine, and methylmalonic acid concentrations, but a log-dose effect was found only for vitamin B-12 (P<0.001). The slope of the line tended to be higher (P=0.07) at d 30 than at d 15. For a mean serum vitamin B-12 increase of 37 pmol/L, a dose of 5.9 (95% CI, 0.9-12.1) microg/d was needed. We concluded that very low oral doses of vitamin B-12 increased serum vitamin B-12 concentrations in elderly subjects with subclinical vitamin B-12 deficiency, following a log-dose pattern. Our results could be beneficial in the design of a public health program for safe flour cofortification with folic acid.