Vitamin B12 is comprised of a class of related, water-soluble compounds, namely methyl-, hydroxyl- and cyanocobalamin (among others). B12 is involved in DNA synthesis and regulation in every cell of the body. It also plays a role in energy production and synthesis of fatty acids.
Only bacteria are capable of synthesizing B12, and as such, it is found almost entirely in animal food products due to animal-bacteria symbiosis. Rich food sources of vitamin B12 include meat, fish, poultry, eggs and dairy.
Conditions Supported by Vitamin B12
- Blood sugar
- Bone health
- Brain health
- Heart health
- Women’s health
What Does the Research Say?
A study published in 2013 indicates that the pharmaceutical metformin is associated with vitamin B12 deficiency and neuropathy in subjects with type 2 diabetes.1 Metformin is believed to be the most widely prescribed anti-diabetic drug in the world. In the U.S., more than 48 million prescriptions were filled in 2010 for its generic formulations.
The researchers evaluated type 2 diabetic subjects, including 84 individuals who had taken metformin and 52 subjects who had not taken the drug. The investigators collected data including age, sex, vegetarian status and hemoglobin A1c (HbA1c) levels, which assess long-term blood sugar control. Additionally, the researchers measured vitamin B12 levels and assessed the severity of peripheral neuropathy.
The researchers determined that the mean serum B12 levels were significantly lower and the mean neuropathy score was significantly higher in the metformin group compared with the subjects who had not taken the drug. The investigators also showed that the risk of possible vitamin B12 deficiency was more than four-times higher in the metformin group compared to the non-metformin exposed group. Furthermore, the researchers showed that increasing cumulative metformin dose correlated to decreasing vitamin B12 levels.
The researchers concluded, “Metformin use is associated with vitamin B12 deficiency and clinical neuropathy in type 2 diabetes patients.”
Research has determined that B vitamins are an important yet overlooked factor in maintaining bone health and preventing osteoporosis. Most people know that minerals such as calcium and magnesium are the cornerstones of bone health, but research has determined that other nutrients play equally critical roles, and deficiencies can increase risk of weakened bones.
In a review and meta-analysis, researchers from the National Institutes of Health looked at the B vitamins folate, B12 and B6 and their function in bone turnover and fracture risk.2
They found that all three have benefits individually, and together they influence total plasma homocysteine concentrations (tHcy). (Newly emerging evidence links high homocysteine to increased risk of osteoporosis. In fact, these scientists found that elevated tHcy “has a small but significant association with bone fracture risk and bone quality.”)
In addition, meta-analyses and other studies suggest a small but significant role of vitamin B12 status on risk of fracture.
The researchers concluded by saying that the role of tHcy and B12 in reducing fracture risk needs to be further examined.
Similarly, a study published in January 2012 found that homocysteine levels in women with osteoporosis were “significantly” higher than in women with osteopenia and normal bone mineral density. Further, homocysteine levels were inversely related to lumbar spine and hip bone mineral density, and to vitamin B12 status.3
A separate September 2009 study looked at levels of folic acid, B12 and homocysteine in postmenopausal women. It found that osteoporosis was associated with a high homocysteine level and with a low B12 level.4
In April 2013, a study reported that low folate and B12 levels are associated with cognitive impairment in seniors.5
Researchers evaluated serum levels of folate and vitamin B12 in 593 seniors over the age of 65 years. The investigators assessed cognitive impairment using the Mini-Mental State Examination. Additionally, the researchers analyzed data from previous research, including 12 studies on folic acid and cognition and nine studies on vitamin B12 and cognition.
The investigators found that cognitive impairment was associated with lower education level in both males and females; decreased social activity, depressive symptoms and low folate levels in males; and older age in females. The researchers determined from the meta-analysis that low folate levels were associated with a 66 percent increase in the risk of cognitive impairment. Low vitamin B12 was associated with an 11 percent increase in the likelihood of cognitive impairment.
Similarly, a randomized controlled trial published on December 14, 2011 supports these findings.6 In this study, the subjects included 900 older adults between 60 and 74 years of age with elevated psychological stress. The subjects received 400 mcg of folic acid plus 100 mcg of vitamin B12 daily or a placebo for two years. The subjects completed 10 modules by mail and the study authors followed up with the subjects using telephone tracking calls. Researchers evaluated cognitive function at 12 and 24 months using questionnaires over the telephone, which evaluated orientation, attention, semantic memory and processing speed.
Compared to placebo, the subjects who received folic acid and vitamin B12 had enhanced performance on the Cognitive Status-Modified questionnaire administered by telephone interview. More specifically, the subjects in the B-vitamin group demonstrated enhanced immediate and delayed recall.
The researchers stated that long-term supplementation of daily oral 400 mcg folic acid plus 100 mcg vitamin B12 promotes enhanced cognitive functioning, particularly in immediate and delayed memory performance.
Finally, a study published in 2012 tested serum levels of folate and holotranscobalamin (the biologically active fraction of vitamin B12) in 274 people (aged 65-79) with normal cognition.7 After seven years, the scientists reevaluated these people for various levels of cognitive performance. They found that higher levels of these two B vitamins were associated with enhanced performance in key cognitive tests.
The Journal of the American Medical Association reported in December 2013 that proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2-blockers) that decrease stomach acid are associated with vitamin B12 deficiency.8 These pharmaceuticals are widely used medications. In 2008, Americans spent more than $14 billion on PPIs, making them one of the best-selling drug classes in the country.
The subjects included 25,956 individuals with vitamin B12 deficiency and 184,199 subjects without vitamin B12 deficiency. The investigators evaluated the subjects for prescriptions for PPIs or H2-blockers using electronic pharmacy, laboratory and diagnostic databases.
The researchers found that among the subjects with vitamin B12 deficiency, 12.0 percent had received two or more years’ supply of PPIs, 4.2 percent had received two or more years’ supply of H2-blockers and 83.3 percent had not received prescriptions for either.
Among the subjects without vitamin B12 deficiency, the investigators showed that 7.2 percent had received two or more years’ supply of PPIs, 3.2 percent had received two or more years’ supply of H2-blockers and 89.6 percent had not received prescriptions for either PPIs or H2-blockers.
The investigators determined that two or more years’ supply of PPIs was associated with a 65 percent increased risk of vitamin B12 deficiency and a two or more years’ supply of H2-blockers was associated with a 25 percent increased risk of vitamin B12 deficiency.
Furthermore, the researchers showed that doses of more than 1.5 pills per day of a PPI was associated with a 95 percent increased risk of vitamin B12 deficiency, as compared to 0.75 pills per day, which was associated with a 63 percent increased risk.
The researchers concluded, “Previous and current gastric acid inhibitor use was significantly associated with the presence of vitamin B12 deficiency. These findings should be considered when balancing the risks and benefits of using these medications.”
In April 2013, researchers reported that vitamin B12 deficiency and elevated homocysteine levels influence cardiovascular risk factors in subjects with coronary heart disease.9 Coronary heart disease is the most common form of heart disease, and is responsible for an estimated 385,000 deaths annually. Folate and vitamin B12 are essential for the metabolism of homocysteine, and elevated homocysteine is associated with cardiovascular disease.
The researchers evaluated 300 subjects between 25-92 years of age with coronary artery disease diagnosed with angiography. The investigators assessed anthropometry and cardiovascular risk factors and measured levels of vitamin B12, folate, homocysteine, lipids, blood sugar and inflammatory markers, including C-reactive protein (CRP) and interleukin-6.
The researchers found that 86.7 percent of the subjects were deficient in vitamin B12 and
2.7 percent were deficient in folate. Additionally, 95.3 percent of the subjects had elevated homocysteine. The investigators determined that the subjects with dyslipidemia, diabetes and/or hypertension had significantly lower vitamin B12 and significantly higher homocysteine levels.
The researchers showed that as vitamin B12 levels decreased, triglyceride and very low-density lipoprotein (VLDL) cholesterol increased, while high-density lipoprotein (HDL) decreased. The investigators also found that as homocysteine levels increased, triglyceride and VLDL cholesterol also increased and HDL cholesterol decreased. Furthermore, increasing vitamin B12 was associated with decreased inflammatory markers directly related to insulin resistance, and increased homocysteine was associated with increased inflammatory markers.
The researchers concluded, “Serum vitamin B12 deficiency and hyperhomocysteinemia are related with cardiovascular risk factors in Indian patients with coronary artery disease.”
A 2014 study from China had similar findings. Researchers found that low-dose supplementation with B vitamins improves heart health by reducing the Framingham risk score (FRS).10 FRS utilizes age, sex, total cholesterol, HDL cholesterol, smoking status, systolic blood pressure and the use of blood pressure medication to calculate cardiovascular risk over 10 years.
The researchers followed 390 people aged 60-74. They were randomly selected to receive 50 mg daily of vitamin C (control group) or 400 mcg of folic acid, 2 mg of B6 and 10 mcg of B12 every day (treatment group) for 12 months. The researchers also calculated FRS for all participants.
Results showed that, in the treatment group, folic acid and B12 concentrations increased by 253 percent and 80 percent, respectively, after only six months and stayed that way for the duration of the study period. Compared to the control group, B supplementation had no dramatic effect on FRS after six months, but researchers observed a significant improvement after 12 months. (However, the benefits disappeared six months after supplementation ended.)
Furthermore, the reduced cardiovascular risk was greater in people who started out with a folate deficiency versus those who had ample amounts of this nutrient to begin with. The researchers also noted that B vitamin supplementation raised levels of protective HDL cholesterol by 9.2 percent after 12 months.
They concluded, “Daily supplementation with a low dose of B vitamins for 12 months reduced FRS, particularly in healthy elderly subjects with a folate deficiency. These reduced effects declined after supplementation cessation, indicating a need for persistent supplementation to maintain the associated benefits.”
A study published in the American Journal of Clinical Nutrition in May 2013 reported that low levels of vitamin B12 and folate and elevated homocysteine were associated with age-related macular degeneration.11
Researchers measured serum folate, vitamin B12 and homocysteine in subjects 55 years of age or older in 1997-1999. The investigators evaluated 1,790 subjects for age-related macular degeneration using retinal photographs in 2002-2004 and 2007-2009. The subjects completed food-frequency questionnaires to assess vitamin B12 and folate intake. The researchers also collected data including age, sex, current smoking, white cell count and fish consumption to adjust the data for potential confounding factors.
The investigators found that for each 1-standard deviation increase in serum homocysteine, there was a 33 percent increased risk of developing early or any age-related macular degeneration. The subjects with vitamin B12 deficiency (less than 185 pmol/L) showed a 58 percent increased risk of early age-related macular degeneration and a 156 percent increase risk of developing late age-related macular degeneration.
The investigators also determined that the subjects with folate deficiency (less than 11 nmol/L) had a 75 percent increased risk of early age-related macular degeneration and an 89 percent increased risk of late age-related macular degeneration. Furthermore, the researchers found that subjects who reported supplementary vitamin B12 intake had 47 percent reduced risk of developing age-related macular degeneration.
The researchers concluded, “Elevated serum total homocysteine and folate and vitamin B12 deficiencies predicted increased risk of incident age-related macular degeneration, which suggests a potential role for vitamin B12 and folate in reducing age-related macular degeneration risk.”
A study published in April 2002 highlighted the role of B12 in cervical dysplasia. Investigators found that B12 levels were inversely associated with human papilloma virus (HPV) persistence after adjusting for other risk factors.
Further, women with the highest levels of B12 had a reduced incidence of persistent infection. This is important, as cervical human papilloma virus infection is a primary risk factor for cervical cancer.12
How to Use Vitamin B12
The commonly recommended dosage for vitamin B12 is 25-100 mcg for adults, and can be taken in capsule form, sublingually or via injection.
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