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Here is why some people supplement thier diets with b -12
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Methylcobalamin and 5-deoxyadenosylcobalamin are the forms of vitamin B12 that are active in human metabolism [5].
Vitamin B12 is required for proper red blood cell formation, neurological function, and DNA synthesis [1-5]. Vitamin B12 functions as a cofactor for methionine synthase and L-methylmalonyl-CoA mutase. Methionine synthase catalyzes the conversion of homocysteine to methionine [5,6]. Methionine is required for the formation of S-adenosylmethionine, a universal methyl donor for almost 100 different substrates, including DNA, RNA, hormones, proteins, and lipids. L-methylmalonyl-CoA mutase converts L-methylmalonyl-CoA to succinyl-CoA in the degradation of propionate [3,5,6], an essential biochemical reaction in fat and protein metabolism. Succinyl-CoA is also required for hemoglobin synthesis.
Vitamin B12, bound to protein in food, is released by the activity of hydrochloric acid and gastric protease in the stomach [5]. When synthetic vitamin B12 is added to fortified foods and dietary supplements, it is already in free form and, thus, does not require this separation step. Free vitamin B12 then combines with intrinsic factor, a glycoprotein secreted by the stomach's parietal cells, and the resulting complex undergoes absorption within the distal ileum by receptor-mediated endocytosis [5,7]. Approximately 56% of a 1 mcg oral dose of vitamin B12 is absorbed, but absorption decreases drastically when the capacity of intrinsic factor is exceeded (at 1-2 mcg of vitamin B12) [8].
Vitamin B12 status is typically assessed via serum or plasma vitamin B12 levels. Values below approximately 170–250 pg/mL (120–180 picomol/L) for adults [5] indicate a vitamin B12 deficiency. However, evidence suggests that serum vitamin B12 concentrations might not accurately reflect intracellular concentrations [6]. An elevated serum homocysteine level (values >13 micromol/L) [12] might also suggest a vitamin B12 deficiency. However, this indicator has poor specificity because it is influenced by other factors, such as low vitamin B6 or folate levels [5]. Elevated methylmalonic acid levels (values >0.4 micromol/L) might be a more reliable indicator of vitamin B12 status because they indicate a metabolic change that is highly specific to vitamin B12 deficiency [5-7,12].
Evidence from the Framingham Offspring Study suggests that the prevalence of vitamin B12 deficiency in young adults might be greater than previously assumed [15]. This study found that the percentage of participants in three age groups (26–49 years, 50–64 years, and 65 years and older) with deficient blood levels of vitamin B12 was similar. The study also found that individuals who took a supplement containing vitamin B12 or consumed fortified cereal more than four times per week were much less likely to have a vitamin B12 deficiency.
Folic acid and vitamin B12
Large amounts of folic acid can mask the damaging effects of vitamin B12 deficiency by correcting the megaloblastic anemia caused by vitamin B12 deficiency [3,5] without correcting the neurological damage that also occurs [1,31]. Moreover, preliminary evidence suggests that high serum folate levels might not only mask vitamin B12 deficiency, but could also exacerbate the anemia and worsen the cognitive symptoms associated with vitamin B12 deficiency [6,11]. Permanent nerve damage can occur if vitamin B12 deficiency is not treated. For these reasons, folic acid intake from fortified food and supplements should not exceed 1,000 mcg daily in healthy adults [5].
Vitamin B12 and Health
Cardiovascular disease
Cardiovascular disease is the most common cause of death in industrialized countries, such as the United States, and is on the rise in developing countries. Risk factors for cardiovascular disease include elevated low-density lipoprotein (LDL) levels, high blood pressure, low high-density lipoprotein (HDL) levels, obesity, and diabetes [45].
Elevated homocysteine levels have also been identified as an independent risk factor for cardiovascular disease [46-48]. Homocysteine is a sulfur-containing amino acid derived from methionine that is normally present in blood. Elevated homocysteine levels are thought to promote thrombogenesis, impair endothelial vasomotor function, promote lipid peroxidation, and induce vascular smooth muscle proliferation [46,47,49]. Evidence from retrospective, cross-sectional, and prospective studies links elevated homocysteine levels with coronary heart disease and stroke [46,49-58].
Vitamin B12, folate, and vitamin B6 are involved in homocysteine metabolism. In the presence of insufficient vitamin B12, homocysteine levels can rise due to inadequate function of methionine synthase [6]. Results from several randomized controlled trials indicate that combinations of vitamin B12 and folic acid supplements with or without vitamin B6 decrease homocysteine levels in people with vascular disease or diabetes and in young adult women [59-67]. In another study, older men and women who took a multivitamin/multimineral supplement for 8 weeks experienced a significant decrease in homocysteine levels [68].
Evidence supports a role for folic acid and vitamin B12 supplements in lowering homocysteine levels, but results from several large prospective studies have not shown that these supplements decrease the risk of cardiovascular disease [48,62-67]. In the Women’s Antioxidant and Folic Acid Cardiovascular Study, women at high risk of cardiovascular disease who took daily supplements containing 1 mg vitamin B12, 2.5 mg folic acid, and 50 mg vitamin B6 for 7.3 years did not have a reduced risk of major cardiovascular events, despite lowered homocysteine levels [65]. The Heart Outcomes Prevention Evaluation (HOPE) 2 trial, which included 5,522 patients older than 54 years with vascular disease or diabetes, found that daily treatment with 2.5 mg folic acid, 50 mg vitamin B6, and 1 mg vitamin B12 for an average of 5 years reduced homocysteine levels and the risk of stroke but did not reduce the risk of major cardiovascular events [63]. In the Western Norway B Vitamin Intervention Trial, which included 3,096 patients undergoing coronary angiography, daily supplements of 0.4 mg vitamin B12 and 0.8 mg folic acid with or without 40 mg vitamin B6 for 1 year reduced homocysteine levels by 30% but did not affect total mortality or the risk of major cardiovascular events during 38 months of follow-up [66]. The Norwegian Vitamin (NORVIT) trial [62] and the Vitamin Intervention for Stroke Prevention trial had similar results [67].
The American Heart Association has concluded that the available evidence is inadequate to support a role for B vitamins in reducing cardiovascular risk [48].
Dementia and cognitive function
Researchers have long been interested in the potential connection between vitamin B12 deficiency and dementia [47,69]. A deficiency in vitamin B12 causes an accumulation of homocysteine in the blood [6] and might decrease levels of substances needed to metabolize neurotransmitters [70]. Observational studies show positive associations between elevated homocysteine levels and the incidence of both Alzheimer's disease and dementia [6,47,71]. Low vitamin B12 status has also been positively associated with cognitive decline [72].
Despite evidence that vitamin B12 lowers homocysteine levels and correlations between low vitamin B12 levels and cognitive decline, research has not shown that vitamin B12 has an independent effect on cognition [73-77]. In one randomized, double-blind, placebo-controlled trial, 195 subjects aged 70 years or older with no or moderate cognitive impairment received 1,000 mcg vitamin B12, 1,000 mcg vitamin B12 plus 400 mcg folic acid, or placebo for 24 weeks [73]. Treatment with vitamin B12 plus folic acid reduced homocysteine concentrations by 36%, but neither vitamin B12 treatment nor vitamin B12 plus folic acid treatment improved cognitive function.
Women at high risk of cardiovascular disease who participated in the Women’s Antioxidant and Folic Acid Cardiovascular Study were randomly assigned to receive daily supplements containing 1 mg vitamin B12, 2.5 mg folic acid and 50 mg vitamin B6, or placebo [76]. After a mean of 1.2 years, B-vitamin supplementation did not affect mean cognitive change from baseline compared with placebo. However, in a subset of women with low baseline dietary intake of B vitamins, supplementation significantly slowed the rate of cognitive decline. In a trial conducted by the Alzheimer's Disease Cooperative Study consortium that included individuals with mild-to-moderate Alzheimer's disease, daily supplements of 1 mg vitamin B12, 5 mg folic acid, and 25 mg vitamin B6 for 18 months did not slow cognitive decline compared with placebo [77]. Another study found similar results in 142 individuals at risk of dementia who received supplements of 2 mg folic acid and 1 mg vitamin B12 for 12 weeks [75].
The authors of two Cochrane reviews and a systematic review of randomized trials of the effects of B vitamins on cognitive function concluded that insufficient evidence is available to show whether vitamin B12 alone or in combination with vitamin B6 or folic acid has an effect on cognitive function or dementia [78-80]. Additional large clinical trials of vitamin B12 supplementation are needed to assess whether vitamin B12 has a direct effect on cognitive function and dementia [6].
Health Risks from Excessive Vitamin B12
The IOM did not establish a UL for vitamin B12 because of its low potential for toxicity. In Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline, the IOM states that "no adverse effects have been associated with excess vitamin B12 intake from food and supplements in healthy individuals" [5].
Findings from intervention trials support these conclusions. In the NORVIT and HOPE 2 trials, vitamin B12 supplementation (in combination with folic acid and vitamin B6) did not cause any serious adverse events when administered at doses of 0.4 mg for 40 months (NORVIT trial) and 1.0 mg for 5 years (HOPE 2 trial) [62,63].
Interactions with Medications
Vitamin B12 has the potential to interact with certain medications. In addition, several types of medications might adversely affect vitamin B12 levels. A few examples are provided below. Individuals taking these and other medications on a regular basis should discuss their vitamin B12 status with their healthcare providers.
Chloramphenicol
Chloramphenicol (Chloromycetin®) is a bacteriostatic antibiotic. Limited evidence from case reports indicates that chloramphenicol can interfere with the red blood cell response to supplemental vitamin B12 in some patients [82].
Proton pump inhibitors
Proton pump inhibitors, such as omeprazole (Prilosec®) and lansoprazole (Prevacid®), are used to treat gastroeso****eal reflux disease and peptic ulcer disease. These drugs can interfere with vitamin B12 absorption from food by slowing the release of gastric acid into the stomach [83-85]. However, the evidence is conflicting on whether proton pump inhibitor use affects vitamin B12 status [86-89]. As a precaution, health care providers should monitor vitamin B12 status in patients taking proton pump inhibitors for prolonged periods [82].
H2 receptor antagonists
Histamine H2 receptor antagonists, used to treat peptic ulcer disease, include cimetidine (Tagamet®), famotidine (Pepcid®), and ranitidine (Zantac®). These medications can interfere with the absorption of vitamin B12 from food by slowing the release of hydrochloric acid into the stomach. Although H2 receptor antagonists have the potential to cause vitamin B12 deficiency [90], no evidence indicates that they promote vitamin B12 deficiency, even after long-term use [89]. Clinically significant effects may be more likely in patients with inadequate vitamin B12 stores, especially those using H2 receptor antagonists continuously for more than 2 years [90].
Metformin
Metformin, a hypoglycemic agent used to treat diabetes, might reduce the absorption of vitamin B12 [91-93], possibly through alterations in intestinal mobility, increased bacterial overgrowth, or alterations in the calcium-dependent uptake by ileal cells of the vitamin B12-intrinsic factor complex [92,93]. Small studies and case reports suggest that 10%–30% of patients who take metformin have reduced vitamin B12 absorption [92,93]. In a randomized, placebo controlled trial in patients with type 2 diabetes, metformin treatment for 4.3 years significantly decreased vitamin B12 levels by 19% and raised the risk of vitamin B12 deficiency by 7.2% compared with placebo [94]. Some studies suggest that supplemental calcium might help improve the vitamin B12 malabsorption caused by metformin [92,93], but not all researchers agree [95].
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