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

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

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

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

B vitamin supplementation improves cognitive function in the middle aged and elderly with hyperhomocysteinemia

Objective: An intervention study was performed to determine if supplement containing folic acid, vitamin B₆, and vitamin B₁₂ could improve cognitive function and lower homocysteine in middle-aged and elderly patients with hyperhomocysteinemia.

Methods: One hundred and four participants with hyperhomocysteinemia were recruited in Tianjin, China, aged 55–94 years old. Fifty-seven individuals with hyperhomocysteinemia were included in the intervention group (vitamin B group, which received 800 µg/day of folate, with 10 mg of vitamin B₆ and 25 µg of vitamin B₁₂) and 47 patients in the placebo group. The endpoint was the improvement in cognitive function as evaluated by Basic Cognitive Aptitude Tests (BCATs). All parameters were measured before and after the treatment period of 14 weeks.

Results: The BCAT total score and four sub-tests scores (digit copy, Chinese character rotation, digital working memory, and recognition of meaningless figure) of BCAT at 14 weeks significantly increased only for the vitamin B group. Serum total homocysteine (tHcy) levels significantly decreased in the intervention group, while serum concentrations of folate, vitamin B₆, and vitamin B₁₂ significantly increased in the intervention group.

Conclusion: The results demonstrated that supplement containing folate, vitamin B₆, and vitamin B₁₂ in middle-aged and elderly patients with hyperhomocysteinemia could improve their cognitive function partly and reduce serum tHcy levels.     

待产女性血清维生素B12和叶酸水平的流行病学特征

目的 分析陕西省待产女性维生素B₁₂和叶酸水平及两者间关系的流行病学特征。方法 资料来源于2014年1月至2016年12月在6所三甲医院待产的健康孕妇,产前采集血样以测定维生素B₁₂和叶酸水平。采用分位数回归模型分析待产女性维生素B₁₂和叶酸水平间的关系。结果 共纳入1 277名待产女性,其血清维生素B₁₂的中位数为164.7 pg/ml,缺乏率为69.6%,血清叶酸的中位数为7.6 ng/ml,缺乏率为12.1%,单纯缺乏维生素B₁₂者占58.4%,单纯缺乏叶酸者占0.9%。农村待产女性维生素B₁₂和叶酸水平低于城市女性,维生素B₁₂和叶酸水平随年龄的增长而呈不同幅度增加,<25岁者维生素B₁₂和叶酸水平明显较低。叶酸缺乏者的维生素B₁₂水平比非缺乏者平均低37.62 pg/ml,分位数回归模型显示,在不同的维生素B₁₂分位点上,叶酸缺乏者的维生素B₁₂水平明显低于不缺乏者,且这种差异随着维生素B₁₂水平的升高而增大。结论 陕西省待产女性维生素B₁₂和叶酸缺乏症仍普遍存在,在妇幼保健实践中,叶酸增补的同时可能需重视维生素B₁₂补充。加大健康教育力度,重点提高农村和年轻女性对营养素补充重要性的认识,从而改善其维生素B₁₂和叶酸水平。     

Plasma 25-hydroxyvitamin D is positively associated with folate and vitamin B12 levels in adolescents

Vitamin D affects the absorption of folate in vitro, and perhaps of vitamin B₁₂ (B₁₂). However, epidemiological studies on the association of vitamin D with folate and B₁₂ are inconclusive. We hypothesized a positive association of plasma 25-hydroxyvitamin D [25(OH)D] with folate and B₁₂ levels in adolescents. This hypothesis was tested in a cross-sectional study of healthy adolescents (11–16 years old; n = 1416), selected from public middle schools from across Kuwait, using stratified multistage cluster random sampling. Plasma 25(OH)D was measured by LC–MS/MS. Serum B₁₂ and total folate in hemolyzed whole blood were analyzed with commercial kits; RBC and plasma folate were calculated from total folate. Data on potential confounders were collected from the parents and adolescents. In a univariable model, 25(OH)D as a continuous variable was positively associated with each of total, RBC, and plasma folate (P < .001). After adjusting for potential confounders, this association remained significant with total folate (β = 2.0, P < .001) and red blood cell folate (β = 1.8, P < .001), but not with plasma folate (β = 0.2, P = .34). A similar pattern of association was evident when 25(OH)D was fitted as categorical variable. Correlation between B₁₂ and 25(OH)D was weak but significant (ρ = 0.1, P < .001). 25(OH)D was positively associated with B₁₂ in both univariable and multivariable models (P < .001) when fitted as a categorical variable only. Simultaneous quantile regression confirmed these results. We conclude that plasma 25(OH)D is positively associated with folate and B₁₂ levels in adolescents. Properly designed large-scale randomized controlled trials are warranted to investigate the causal role of vitamin D in folate and B₁₂ absorption.     

Effect of Folic Acid,Betaine, Vitamin B6, and Vitamin B12 on Homocysteine and Dimethylglycine Levels in Middle-Aged Men Drinking White Wine

Moderate regular consumption of alcoholic beverages is believed to protect against atherosclerosis but can also increase homocysteine or dimethylglycine, which are putative risk factors for atherosclerosis. We aimed (1) to investigate the effect of alcohol consumption on vitamins and several metabolites involved in one-carbon metabolism; and (2) to find the most effective way of decreasing homocysteine during moderate alcohol consumption. Methods: Male volunteers (n = 117) were randomly divided into five groups: the wine-only group (control, 375 mL of white wine daily for one month) and four groups combining wine consumption with one of the supplemented substances (folic acid, betaine, and vitamins B₁₂ or B₆). Significant lowering of homocysteine concentration after the drinking period was found in subjects with concurrent folate and betaine supplementation. Vitamin B₁₂ and vitamin B₆ supplementation did not lead to a statistically significant change in homocysteine. According to a multiple linear regression model, the homocysteine change in the wine-only group was mainly determined by the interaction between the higher baseline homocysteine concentration and the change in dimethylglycine levels. Folate and betaine can attenuate possible adverse effects of moderate alcohol consumption. Dimethylglycine should be interpreted together with data on alcohol consumption and homocysteine concentration.     

Urinary excretion of vitamin B1, B2, B6, niacin,pantothenic acid,folate, and vitamin C correlates with dietary intakes of free-living elderly,female Japanese

We hypothesized that 24-hour urinary excretion of water-soluble vitamins might correlate with their intake in free-living Japanese elderly females aged 70 to 84 years. We performed a cross-sectional study composed of 37 healthy, elderly, Japanese females living freely. All foods and the corresponding weights consumed for 4 consecutive days were recorded accurately. A 24-hour urine sample was collected on the fourth day, and the urinary content of water-soluble vitamins was measured. The urinary levels of all vitamins, except for B₁₂ (r = 0.01; P = .936), were correlated positively with the mean intake over the recent 4 days (vitamin B₁: r = 0.62; P < .001; vitamin B₂: r = 0.57; P < .001; vitamin B₆: r = 0.37; P < .005; niacin: r = 0.54; P < .001; niacin equivalents: r = 0.54; P < .001; pantothenic acid: r = 0.59; P < .001; folate: r = 0.55; P = .001; and vitamin C: r = 0.53; P < .001). Mean estimated intakes of water-soluble vitamins calculated using urinary concentrations and recovery rates showed 96% to 107% of their 3-day mean intake, except for vitamin B₁₂ (65%). We conclude that urinary levels of water-soluble vitamins, except for B₁₂, reflected their recent intake in free-living Japanese elderly females and could be used as a measure of their intake during the previous few days both for group means and for individual rankings within a group.     

Dietary source of vitamin B12 intake and vitamin B12 status in female elderly Koreans aged 85 and older living in rural area

Recently, we found and analyzed vitamin B₁₂ in some Korean traditional plant foods which had not reported, yet. This study was to investigate vitamin B₁₂ intake and its dietary sources and the vitamin B₁₂ status in the very old elderly Koreans. We measured serum vitamin B₁₂ level and estimated the amounts of vitamin B₁₂ intake from different dietary sources in female elderly Koreans aged 85 and over who had consumed a relatively low animal traditional diet for the whole life. The average age of the subjects (n = 127) was 98.0 years (85-108 years). The assessment on energy and nutrient intake involved a one-day 24-hour recall, and serum vitamin B₁₂ concentration was measured by radioimmunoassay. Overall diet pattern was not different between the 85-99 yr-old group and centenarians, except centenarians were taking more dairy product. The average ratio of plant food to animal food consumption was 87.5:12.5 in weight. The average vitamin B₁₂ intake of our subjects was 3.2 µg/day, and 52.7% of subjects consumed under estimated average requirement, 2.0 µg/day. On dietary source, 67.3% of dietary vitamin B₁₂ was from meat, eggs and fishes and 30.6% was from plant foods, such as soybean-fermented foods, seaweeds, and kimchi. The average serum vitamin B₁₂ concentration was 450.5 pg/mL, and low serum vitamin B₁₂ (< 200 pg/mL) was found in 9.6% of subjects. Dietary vitamin B₁₂ intake was significantly lower in subjects with low serum vitamin B₁₂ (0.79 µg/day) than those with normal serum vitamin B₁₂ (3.47 µg/day). There were no significant difference in vitamin B₁₂ intake and its dietary sources and serum vitamin B₁₂ level between the 85-99 yr-old group and centenarians. In conclusion, several plant-origin foods including seaweed, soybean-fermented foods, and kimchi, may contribute significantly to good vitamin B₁₂ status in very old elderly Koreans.     

Relative and biomarker-based validity of a food frequency questionnaire that measures the intakes of vitamin B12, folate, iron, and zinc in young women

Folate, vitamin B₁₂, iron, and zinc are particularly important nutrients for women of childbearing age. We tested the hypothesis that an electronic, 235-item, semiquantitative food frequency questionnaire (FFQ) is a valid measure of dietary intake when compared with repeat dietary 24-hour recalls. Biomarkers of folate, vitamin B₁₂, iron, and zinc were determined because their measurement errors are unrelated to errors in dietary questionnaires. Female adults (N = 256) aged 18 to 35 years completed the FFQ, and a representative subset (n = 53) completed repeat dietary 24-hour recalls. The FFQ estimates (mean ± SD) were 315 ± 132 μg for folate, 3.1 ± 2.1 μg for vitamin B₁₂, 15.4 ± 5.6 mg for iron, and 15.1 ± 6.4 mg for zinc. The percentage of women classified within the same ±1 quartile for energy intake by the 2 methods was 77.3%. There was moderate agreement between the 2 dietary methods, and no systematic bias was noted for energy, folate, vitamin B₁₂, and zinc. The deattenuated energy-adjusted correlation coefficients ranged from 0.41 (dietary folate equivalents) to 0.60 (folate). Significant correlations between biomarker and nutrient intakes were found for folate (r = 0.37, P < .01) and vitamin B₁₂ (r = 0.27, P < .01). The electronic FFQ developed in the present study is a relatively valid tool that was able to adequately assess and rank individuals according to their nutrient intakes.     

Prevalence of nutrient deficiencies in bariatric patients

ObjectiveThe aims of this study were to determine the prevalence of nutrient deficiencies in patients who present for bariatric surgery, assess nutritional status after surgery, and compare these with preoperative levels.MethodsA retrospective study was conducted to identify preoperative and 1-year postoperative nutrition deficiencies in patients undergoing bariatric surgery. The screening included serum ferritin, vitamin D, vitamin B₁₂, homocysteine, folate, red blood cell folate, and hemoglobin. Results were available for 232 patients preoperatively and 149 patients postoperatively. Two-tailed χ² tests and paired-sample t tests were used.ResultsPreoperatively, vitamin D deficiency was noted at 57%. The prevalence of abnormalities 1 year after roux-en-Y gastric bypass was higher compared with preoperative levels (P < .05). After surgery, anemia was detected in 17%, elevated homocysteine levels (women only) in 29%, low ferritin in 15%, low vitamin B₁₂ in 11%, and low RBC folate in 12%. Mean hemoglobin, ferritin, and RBC folate levels deteriorated significantly but remained well within normal ranges. The prevalence of vitamin D deficiencies decreased, but not significantly. In sleeve gastrectomy patients, mean ferritin levels decreased (P < .05), without any patient developing a deficiency.ConclusionVitamin D deficiency is common among morbidly obese patients seeking bariatric surgery. Because the prevalence of micronutrient deficiencies persists or worsens postoperatively, routine nutrition screening, recommendation of appropriate supplements, and monitoring adherence are imperative in this population.     

Nutritional supplementation of hop rho iso-alpha acids, berberine, vitamin D3, and vitamin K1 produces a favorable bone biomarker profile supporting healthy bone metabolism in postmenopausal women with metabolic syndrome

Metabolic syndrome poses additional risk for postmenopausal women who are already at risk for osteoporosis. We hypothesized that a nutritional supplement containing anti-inflammatory phytochemicals and essential bone nutrients would produce a favorable bone biomarker profile in postmenopausal women with metabolic syndrome. In this 14-week, randomized trial, 51 women were instructed to consume a modified Mediterranean-style, low-glycemic-load diet and to engage in aerobic exercise. Those in the intervention arm (n = 25) additionally received 200 mg hop rho iso-alpha acids, 100 mg berberine sulfate trihydrate, 500 IU vitamin D₃, and 500 μg vitamin K₁ twice daily. Forty-five women completed the study. Baseline nutrient intake did not differ between arms. Compared with baseline, the intervention arm exhibited an approximate 25% mean decrease (P < .001) in serum osteocalcin (indicative of bone turnover), whereas the placebo arm exhibited a 21% increase (P = .003). Serum 25-hydroxyvitamin D increased 23% (P = .001) in the intervention arm and decreased 12% (P = .03) in the placebo arm. The between-arm differences for osteocalcin and 25-hydroxyvitamin D were statistically significant. Serum insulin-like growth factor I was statistically increased in both arms, but the between-arm differences were not statistically significant. Subanalysis showed that among those in the highest tertile of baseline insulin-like growth factor I, the intervention arm exhibited a significant increase in amino-terminal propeptide of type I collagen, whereas the placebo arm showed a significant decrease at 14 weeks. Treatment with rho iso-alpha acids, berberine, vitamin D₃, and vitamin K₁ produced a more favorable bone biomarker profile indicative of healthy bone metabolism in postmenopausal women with metabolic syndrome.     

Calcium,vitamin D,milk consumption,and hip fractures: a prospective study among postmenopausal women

BACKGROUND: Short trials of calcium supplementation show that it reduces loss of bone density in postmenopausal women; longer observational studies do not generally find a lower risk of hip fracture with higher-calcium diets. Fewer studies have focused on vitamin D in preventing postmenopausal osteoporosis or fractures. OBJECTIVE: We assessed relations between postmenopausal hip fracture risk and calcium, vitamin D, and milk consumption. DESIGN: In an 18-y prospective analysis in 72 337 postmenopausal women, dietary intake and nutritional supplement use were assessed at baseline in 1980 and updated several times during follow-up. We identified 603 incident hip fractures resulting from low or moderate trauma. Relative risks (RRs) from proportional hazards models were controlled for other dietary and nondietary factors. RESULTS: Women consuming > or = 12.5 microg vitamin D/d from food plus supplements had a 37% lower risk of hip fracture (RR = 0.63; 95% CI: 0.42, 0.94) than did women consuming < 3.5 microg/d. Total calcium intake was not associated with hip fracture risk (RR = 0.96; 95% CI: 0.68, 1.34 for > or = 1200 compared with < 600 mg/d). Milk consumption was also not associated with a lower risk of hip fracture (P for trend = 0.21). CONCLUSIONS: An adequate vitamin D intake is associated with a lower risk of osteoporotic hip fractures in postmenopausal women. Neither milk nor a high-calcium diet appears to reduce risk. Because women commonly consume less than the recommended intake of vitamin D, supplement use or dark fish consumption may be prudent.     

Serum vitamin B6, folate,and homocysteine concentrations and oxidative DNA damage in Japanese men and women

ObjectiveHigher vitamin B status has been linked to a lower risk for cancer, but the underlying mechanism remains elusive. The aim of the present study was to examine the association of pyridoxal, folate, and homocysteine (Hcy) with urinary 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage.MethodsThe participants were 500 employees (293 men and 207 women), ages 21 to 66 y, of two municipal offices in Japan. Serum pyridoxal and Hcy concentrations were measured using high-performance liquid chromatography (HPLC) method, and serum folate concentrations were measured using chemiluminescent immunoassay. Urinary 8-OHdG concentrations were measured using HPLC method. Multiple regression was used to estimate means of 8-OHdG for each tertile of pyridoxal, folate, and Hcy with adjustment for potential confounders.ResultsIn multivariate analysis, 8-OHdG concentration was inversely associated with pyridoxal concentration in men (P for trend = 0.045) but not in women. The association in men was confined to non-smokers (P for trend = 0.033) or those who consumed no or < 20 g/d of ethanol (P for trend = 0.048). 8-OHdG concentrations were not appreciably associated with folate and Hcy concentrations.ConclusionThe results suggest that vitamin B₆, but not folate and homocysteine, plays a role against oxidative DNA damage in Japanese men.     

The effects of exercise training and acute exercise duration on plasma folate and vitamin B12

BACKGROUND/OBJECTIVES

Energy production and the rebuilding and repair of muscle tissue by physical activity require folate and vitamin B₁₂ as a cofactor. Thus, this study investigated the effects of regular moderate exercise training and durations of acute aerobic exercise on plasma folate and vitamin B₁₂ concentrations in moderate exercise trained rats.

MATERIALS/METHODS

Fifty rats underwent non-exercise training (NT, n = 25) and regular exercise training (ET, n = 25) for 5 weeks. The ET group performed moderate exercise on a treadmill for 30 min/day, 5 days/week. At the end of week 5, each group was subdivided into 4 groups: non-exercise and 3 exercise groups. The non-exercise group (E0) was sacrificed without exercising and the 3 exercise groups were sacrificed immediately after exercising on a treadmill for 0.5 h (E0.5), 1 h (E1), and 2 h (E2). Blood samples were collected and plasma folate and vitamin B₁₂ were analyzed.

RESULTS

After exercise training, plasma folate level was significantly lower and vitamin B₁₂ concentration was significantly higher in the ET group compared with the NT group (P < 0.05). No significant associations were observed between plasma folate and vitamin B₁₂ concentrations. In both the NT and ET groups, plasma folate and vitamin B₁₂ were not significantly changed by increasing duration of aerobic exercise. Plasma folate concentration of E0.5 was significantly lower in the ET group compared with that in the NT group. Significantly higher vitamin B₁₂ concentrations were observed in the E0 and E0.5 groups of the ET group compared to those of the NT group.

CONCLUSION

Regular moderate exercise training decreased plasma folate and increased plasma vitamin B₁₂ levels. However, no significant changes in plasma folate and vitamin B₁₂ concentrations were observed by increasing duration of acute aerobic exercise.     

Lead Exposure,B Vitamins,and Plasma Homocysteine in Men 55 Years of Age and Older: The VA Normative Aging Study

Background: Lead (Pb) exposure may influence the plasma concentration of homocysteine, a one-carbon metabolite associated with cardiovascular and neurodegenerative diseases. Little is known about the associations between Pb and homocysteine over time, or the potential influence of dietary factors.Objectives: We examined the longitudinal association of recent and cumulative Pb exposure with homocysteine concentrations and the potential modifying effect of dietary nutrients involved in one-carbon metabolism.Methods: In a subcohort of the Veterans Affairs (VA) Normative Aging Study (1,056 men with 2,301 total observations between 1993 and 2011), we used mixed-effects models to estimate differences in repeated measures of total plasma homocysteine across concentrations of Pb in blood and tibia bone, assessing recent and cumulative Pb exposure, respectively. We also assessed effect modification by dietary intake and plasma concentrations of folate, vitamin B₆, and vitamin B₁₂.Results: An interquartile range (IQR) increment in blood Pb (3 μg/dL) was associated with a 6.3% higher homocysteine concentration (95% CI: 4.8, 7.8%). An IQR increment in tibia bone Pb (14 μg/g) was associated with a 3.7% higher homocysteine (95% CI: 1.6, 5.6%), which was attenuated to 1.5% (95% CI: –0.5, 3.6%) after adjusting for blood Pb. For comparison, a 5-year increase in time from baseline was associated with a 5.7% increase in homocysteine (95% CI: 4.3, 7.1%). The association between blood Pb and homocysteine was significantly stronger among participants with estimated dietary intakes of vitamin B₆ and folate below (vs. above) the study population medians, which were similar to the U.S. recommended dietary allowance intakes.Conclusions: Pb exposure was positively associated with plasma homocysteine concentration. This association was stronger among men with below-median dietary intakes of vitamins B₆ and folate. These findings suggest that increasing intake of folate and B₆ might reduce Pb-associated increases in homocysteine, a risk factor for cardiovascular disease and neurodegeneration.Citation: Bakulski KM, Park SK, Weisskopf MG, Tucker KL, Sparrow D, Spiro A III, Vokonas PS, Nie LH, Hu H, Weuve J. 2014. Lead exposure, B vitamins, and plasma homocysteine in men 55 years of age and older: the VA Normative Aging Study. Environ Health Perspect 122:1066–1074; http://dx.doi.org/10.1289/ehp.1306931     

Vitamin Status among Breastfed Infants in Bhaktapur,Nepal

Vitamin deficiencies are known to be common among infants residing in low- and middle-income countries but relatively few studies have assessed several biochemical parameters simultaneously. The objective of the study was to describe the status of vitamins (A, D, E, B₆, B₁₂ and folate) in breastfed infants. We measured the plasma concentrations of trans retinol, 25 hydroxy vitamin D, α-tocopherol, pyridoxal 5′-phosphate, cobalamin, folate, methylmalonic acid, homocysteine, hemoglobin and C-reactive protein from 467 randomly selected infants. One in five (22%) was deficient in at least one vitamin. Mean (SD) plasma folate concentration was 73 (35) nmol/L, and no infant in the sample was folate deficient. Vitamin B₆ deficiency and vitamin B₁₂ deficiency was found in 22% and 17% of the infants, respectively. Elevated plasma methylmalonic acid or total homocysteine concentration was found in 82% and 62% of infants, respectively. Fifteen percent of infants were vitamin A deficient and 65% were marginally deficient in vitamin A. Fewer than 5% of infants had low plasma vitamin D concentration or vitamin E concentration (α-tocopherol <9.3 µmol/L). Our results illustrate the importance of continued supplementation campaigns and support the expansion of food fortification and dietary diversification programs that target children and women in Nepal.     

Effects of dietary supplementation of high-dose folic acid on biomarkers of methylating reaction in vitamin B12-deficient rats

Folate is generally considered as a safe water-soluble vitamin for supplementation. However, we do not have enough information to confirm the potential effects and safety of folate supplementation and the interaction with vitamin B₁₂ deficiency. It has been hypothesized that a greater methyl group supply could lead to compensation for vitamin B₁₂ deficiency. On this basis, the present study was conducted to examine the effects of high-dose folic acid (FA) supplementation on biomarkers involved in the methionine cycle in vitamin B₁₂-deficient rats. Sprague-Dawley rats were fed diets containing either 0 or 100 µg (daily dietary requirement) vitamin B₁₂/kg diet with either 2 mg (daily dietary requirement) or 100 mg FA/kg diet for six weeks. Vitamin B₁₂-deficiency resulted in increased plasma homocysteine (p<0.01), which was normalized by dietary supplementation of high-dose FA (p<0.01). However, FA supplementation and vitamin B₁₂ deficiency did not alter hepatic and brain S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) concentrations and hepatic DNA methylation. These results indicated that supplementation of high-dose FA improved homocysteinemia in vitamin B₁₂-deficiency but did not change SAM and SAH, the main biomarkers of methylating reaction.     

Comparing costs of intramuscular and oral vitamin B12 administration in primary care: A cost-minimization analysis

Objective: To establish whether savings could be made by changing patients from intramuscular to high doses of oral vitamin B₁₂ in primary care without compromising their wellbeing. Methods: Cost-minimization analysis from a UK perspective, using secondary data obtained from the literature available and expert opinion. Results: The cost of the resources used to treat patients with vitamin B₁₂ deficiency with intramuscular vitamin B₁₂ was calculated as between £55.99 (€83.1) and £99.99 (€148.5) per year. The cost of treating patients with high doses of oral vitamin B₁₂ during the first year was between £125.55 (€186.5) and £248.55 (€369.1). However, once patients receiving intramuscular treatment had been converted to oral treatment, or in new patients treated orally from the outset, the cost was £35.55 per year (€52.8). One variable, home visits, had a high impact on the calculations.

Conclusion: Switching patients with vitamin B₁₂ deficiency from intramuscular to high-dose oral therapy and treating patients newly diagnosed with vitamin B₁₂ deficiency with oral vitamin B₁₂ from the outset could save resources in the medium and long term, and in newly diagnosed patients. Savings would come particularly in the form of nursing time.     

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

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

Higher Plasma Homocysteine Is Associated with Increased Risk of Developing Colorectal Polyps

Colorectal adenomas are considered to be precursors of colorectal cancer. B-vitamins (i.e., folate, vitamin B₆ and B₁₂) are involved in homocysteine metabolism and play an important role as coenzymes in 1-carbon metabolism, which is thought to have a critical role in the progression of colorectal polyps. The purpose of this study was to examine the effects of B-vitamins and homocysteine on the risk of developing colorectal polyps. Forty-eight participants with colorectal polyps [29 adenomatous polyps (AP), 19 hyperplastic polyps (HP)], and 96 age- and sex-matched healthy controls were recruited. Fasting blood was drawn from each participant to measure hematological parameters, plasma pyridoxal 5′-phosphate (PLP), serum folate and vitamin B₁₂, and plasma homocysteine. Participants with AP and HP had significantly higher plasma homocysteine levels than did healthy controls. There was no significant difference in serum folate and vitamin B₁₂ and plasma PLP among the 3 groups. B-vitamins had no significant effect on the risk of colorectal polyps. However, participants with higher plasma homocysteine [odds ratio (OR) = 1.87, 95% confidence interval (CI) = 1.13, 3.08) level exhibited significantly increased risk of colorectal polyps after adjusting for potential confounders. Plasma homocysteine was a strong predictor of the risk of colorectal polyps in participants with adequate B-vitamins status.