Effect of physiological doses of oral vitamin B 12 on plasma homocysteine: A randomized, placebo-controlled, double-blind trial in India

Diabetes Unit, King Edward Memorial Hospital Research Centre, Pune, Maharashtra, India.
European journal of clinical nutrition (Impact Factor: 2.71). 03/2010; 64(5):495-502. DOI: 10.1038/ejcn.2010.15
Source: PubMed


Vitamin B(12) (B(12)) deficiency is common in Indians and a major contributor to hyperhomocysteinemia, which may influence fetal growth, risk of type II diabetes and cardiovascular disease. The purpose of this paper was to study the effect of physiological doses of B(12) and folic acid on plasma total homocysteine (tHcy) concentration.
A cluster randomized, placebo-controlled, double-blind, 2 x 3 factorial trial, using the family as the randomization unit. B(12) was given as 2 or 10 microg capsules, with or without 200 microg folic acid, forming six groups (B(0)F(0), B(2)F(0), B(10)F(0), B(0)F(200), B(2)F(200) and B(10)F(200)). Plasma tHcy concentration was measured before and after 4 and 12 months of supplementation.
From 119 families in the Pune Maternal Nutrition Study, 300 individuals were randomized. There was no interaction between B(12) and folic acid (P=0.14) in relation to tHcy concentration change and their effects were analyzed separately: B(0) vs. B(2) vs. B(10); and F(0) vs. F(200). At 12 months, tHcy concentration reduced by a mean 5.9 (95% CI: -7.8, -4.1) micromol/l in B(2), and by 7.1 (95% CI: -8.9, -5.4) micromol/l in B(10), compared to nonsignificant rise of 1.2 (95% CI: -0.5, 2.9) micromol/l in B(0). B(2) and B(10) did not differ significantly. In F(200), tHcy concentration decreased by 4.8 (95% CI: -6.3, -3.3) micromol/l compared to 2.8 (95% CI: -4.3, -1.2) micromol/l in F(0).
Daily oral supplementation with physiological doses of B(12) is an effective community intervention to reduce tHcy. Folic acid (200 microg per day) showed no additional benefit, neither had any unfavorable effects.

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Available from: Chittaranjan S Yajnik
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    • "They [41] have reported that the oral vitamin B-12 supplementation reduced plasma tHcy concentration in first two weeks but did not achieve normal plasma tHcy concentrations even after 6 wks. Deshmukh et al [42] studied the effects of physiological doses of oral vitamin B-12 on plasma tHcy and observed that the reduction was 5.5 and 6.8 μ mol/L after 4 and 12 months of 2 μ g supplementation per day respectively, while supplementation of 10 ug per day for 6 and 12 months reduced plasma tHcy concentration by 5.6 and 6.9 μ mol/L respectively. There was no advantage in supplementing with higher dose. "
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    ABSTRACT: Asymptomatic Indian lacto vegetarians, who make up more than half of the Indian population in different geographic regions, have distinctly low vitamin B-12 concentrations than non- vegetarians. Vegetarians consume milk but it seems that the amount is not enough to improve vitamin B-12 status or vitamin B-12 concentration in milk itself may be low. The aim of this study was to determine if daily milk consumption can improve vitamin B-12 status. Fifteen male and 36 female, young healthy post-graduate volunteers participated. Blood from ten participants (4 males and 6 females) was collected (day-1). They continued their regular diet for next fourteen days and on day-15, blood of all 51 participants was collected, plasma vitamin B-12 concentration was measured and were divided into two groups; Normal (vitamin B-12 >148 pmol/L, n = 22) and Vitamin B-12 deficient (<148 pmol/L, n = 29), the remaining plasma was stored. All participants consumed 600 ml. of non-enriched buffalo milk (200 x3) during the day along with their usual diet. Next day blood was collected for plasma holotranscobalamin II measurement. Subjects from deficient group continued to drink 400 ml of milk daily for next 14 days and blood was collected on day-30. Plasma holotranscoabalamin II (day-1, 15, 16, 30), vitamin B-12, folate, total homocysteine, creatinine and hematoloical parameters (day-1, 15, 30), and milk vitamin B-12 concentrations (day-15, 16, 30) were measured. Fifty seven per cent of the participants were vitamin B-12 deficient and 65% were hyperhomocysteinemic. No significant difference in biomarkers was observed when there was no intervention. Plasma holotranscobalamin II concentration increased from 19.6 to 22.27 pmol/L (p < 0.0001) 24 hrs after milk load in the whole group. Plasma vitamin B-12 increased from 92.5 to 122 pmol/L and tHcy concentrations decreased from 31.9 to 24.9 mu mol/L (p < 0.0001 for both) 14 days after regular milk intake in vitamin B-12 deficient subjects. Regular intake of milk improved vitamin B-12 status of vitamin B-12 deficient vegetarians indicating a potential dietary strategy to improve the vitamin status.
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    • "A meta-analysis of 27 observational studies[28] and population-based prospective studies[29] have shown Hcy to be an independent risk factor for CAD, independent of other cardiovascular risk factors. Although supplementation of vitamin B12 has shown to reduce Hcy levels,[3031] a meta-analysis of several trials did not reveal any cardiovascular benefit.[32] "
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    ABSTRACT: There is an increase in awareness about the role of nutritional factors in chronic non-communicable diseases. We therefore conducted this study with an aim to assess the relationship between nutritional factor (vitamin B12 and homocysteine [Hcy]) and its association with insulin resistance and inflammatory markers, and differences in traditional and non-traditional risk factors among diabetics and non-diabetics in known cases of coronary artery disease (CAD). Three hundred consecutive patients with known coronary disease on coronary angiography, who were >25 years old were included in this study. All cases were interviewed using a questionnaire. Blood samples were analyzed for insulin, vitamin B12, Hcy and inflammatory markers (highly sensitive C-reactive protein [hsCRP], interleukin-6 [IL-6], Tumor necrosis factor-alfa [TNF-α]). Insulin resistance was calculated with homeostasis model assessment of insulin resistance (HOMA-IR). Mean age of the patients was 60.95 ± 12.3 years. Body mass index and waist hip ratio were comparable in both groups. Triglyceride, very low-density lipoprotein and HbA1C were significantly higher and high-density lipoprotein (HDL) was significantly lower in patients with diabetes. Patients with diabetes had significantly high levels of IL-6, hsCRP and TNF-α compared with non-diabetic patients. Insulin resistance was twofold higher in diabetic patients. Serum vitamin B12 levels were significantly lower and Hcy was significantly higher in the diabetic group compared with the non-diabetic patients. HbA1C, HOMA-IR and Hcy levels were positively correlated with inflammatory markers in the total study population and in the non-diabetic patients; but, in diabetic patients, HbA1C and Hcy showed this relation. Vitamin B12 deficiency is common in the diabetic population. Hcy levels were higher in diabetics compared with non-diabetics, and were related to glycemic level and insulin resistance in diabetic patients. Patients with diabetes had higher traditional risk factors than patients without diabetes in known patients with CAD. Glycemic status was associated with insulin resistance and inflammatory markers.
    Full-text · Article · Mar 2013
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    • "Our randomised controlled trial showed an improvement in MMA levels and a nonsignificant fall in Hcys following oral B12 supplementation for one month (Table 3). For MMA, our results corroborate observations from three other pertinent trials [17,32] and one equivalent trial comparing oral to parenteral administration [12]. However, our study is the first to follow patients after cessation of treatment. "
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    ABSTRACT: Evidence regarding the effectiveness of oral vitamin B12 in patients with serum vitamin B12 levels between 125-200 pM/l is lacking. We compared the effectiveness of one-month oral vitamin B12 supplementation in patients with a subtle vitamin B12 deficiency to that of a placebo. This multicentre (13 general practices, two nursing homes, and one primary care center in western Switzerland), parallel, randomised, controlled, closed-label, observer-blind trial included 50 patients with serum vitamin B12 levels between 125-200 pM/l who were randomized to receive either oral vitamin B12 (1000 μg daily, N = 26) or placebo (N = 24) for four weeks. The institution's pharmacist used simple randomisation to generate a table and allocate treatments. The primary outcome was the change in serum methylmalonic acid (MMA) levels after one month of treatment. Secondary outcomes were changes in total homocysteine and serum vitamin B12 levels. Blood samples were centralised for analysis and adherence to treatment was verified by an electronic device (MEMS; Aardex Europe, Switzerland). Trial registration: ISRCTN 22063938. Baseline characteristics and adherence to treatment were similar in both groups. After one month, one patient in the placebo group was lost to follow-up. Data were evaluated by intention-to-treat analysis. One month of vitamin B12 treatment (N = 26) lowered serum MMA levels by 0.13 μmol/l (95%CI 0.06-0.19) more than the change observed in the placebo group (N = 23). The number of patients needed to treat to detect a metabolic response in MMA after one month was 2.6 (95% CI 1.7-6.4). A significant change was observed for the B12 serum level, but not for the homocysteine level, hematocrit, or mean corpuscular volume. After three months without active treatment (at four months), significant differences in MMA levels were no longer detected. Oral vitamin B12 treatment normalised the metabolic markers of vitamin B12 deficiency. However, a one-month daily treatment with 1000 μg oral vitamin B12 was not sufficient to normalise the deficiency markers for four months, and treatment had no effect on haematological signs of B12 deficiency.
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