Vitamin B12: Everything You Need to Know
Vitamin B12 (cobalamin) is an essential water-soluble micronutrient required for numerous functions in the body. It is crucial in one-carbon metabolism, DNA synthesis, cellular energy production, and the central nervous system.
B12 has several forms, including cyanocobalamin, methylcobalamin, deoxyadenosylcobalamin, and hydroxocobalamin. The cyano form is most often used in supplements.
Deficiency in Vitamin B12 is common worldwide, especially in older people and in populations with low consumption of animal foods.
This article will discuss the role of B12 in the body and how a deficiency can have severe health implications. We will then explain dosage requirements during different stages of life and how best to maintain adequate levels of B12 in the body.
The Benefits of Vitamin B12
Vitamin B12’s role in methylation and one-carbon metabolism makes it essential for proper cell division and differentiation, erythropoiesis (red blood cell production),central nervous system function, hematopoiesis (the production of other blood cells and blood plasma), and maintaining intact gastrointestinal mucosa. Research has demonstrated associations between B12 status and normal growth, neurodevelopment, and anemia.
As a methyl-donor, B12 plays a critical role in DNA synthesis and methylation. It supports the structural stability of important regions of chromosomes, particularly within DNA.
Vitamin B12 works alongside other methyl donors (folate and vitamin B6) as coenzymes in the remethylation of homocysteine to methionine. B12is also involved in converting folic acid to methylfolate, and both B12 and methyl-THF (Methyltetrahydrofolate) are required for the methylation of homocysteine to methionine.
B12 is a cofactor in synthesizing methionine, the precursor of S-Adenosylmethionine (SAMe), which is involved in numerous epigenetic regulatory mechanisms, especially in brain development and mood.
Erythropoiesis (Red Blood Cell Formation)
Erythroblasts require folate and vitamin B12 in order to multiply and divide properly. A lack of B12 causes erythroblast apoptosis, resulting in anemia from ineffective erythropoiesis.
In the mitochondria, vitamin B12 is required for the enzyme methylmalonyl CoA mutase, which converts methylmalonyl CoA (coenzyme A) to succinyl CoA, a vital step in the breakdown of fatty acids and ketogenic amino acids for energy.
B12 is required for synthesizing myelin-producing oligodendrocytes and the myelin sheath, it provides insulation for many nerve axons and ensures proper conduction. In addition, B12 supports the maintenance of an intact gastrointestinal mucosa.
Vitamin B12 is important to DNA synthesis and may affect bone formation. B12 status has been linked to osteoblastic activity (bone production) in clinical studies and cell culture.
Food Sources of Vitamin B12
Vitamin B12 is the only B vitamin not produced by plants but by bacteria that colonize the gut. This means B12is sourced almost exclusively from animal products such as milk, cheese, and eggs, and animal tissues such as liver, kidney, and heart.
The B12 in foods exist in several different forms. Meat and fish contain mostly adenosylcobalamin and hydroxocobalamin. All three forms (methylcobalamin, adenosylcobalamin, and hydroxocobalamin) are in nearly all dairy products, while hydroxocobalamin is the predominant form in milk.
Food sources of B12:
Organ meats: liver, kidney,heart
Meat: beef, pork, poultry
Fish: trout, salmon, tuna
Dairy products: unsweetenedyogurt, milk, cheese
Fortified cereals, bread
Requirements for B12 vary depending on age and health status and recommended dosages reflect this.
The National Institute of Health recommends that adults (aged 14+) take 2.4 micrograms (mcg) of B12 daily.
However, it has been noted that only about one percent of a high dose of supplemental cyanocobalamin is absorbed through the intestinal barrier into the blood.
The average adult would need to take 200 mcgB12/day to absorb 2.4 mcg (1.2% of 200 mcg = 6 mcg).
For Pregnant and Nursing Mothers
Pregnant women are advised to take 2.6 mcg daily, increasing to 2.8 mcg/day while breastfeeding.
Vitamin B12 is crucial for fetal growth and development. It is involved in proper folate metabolism, essential for cell multiplication during pregnancy. In the developing embryo, B12 functions as a coenzyme alongside folate and vitamin B6 in DNA synthesis and numerous methylation reactions.
B12 levels decline throughout pregnancy due to hemodilution, hormonal changes, reductions in B12 binding proteins, and delivery of B12 to the fetus via the placenta. Deficiency occurs in around10–28% of uncomplicated pregnancies.
B12 deficiency can affect both mother and the fetus by increasing the risk of preeclampsia, preterm labor, intrauterine growth retardation, and many other complications. Children of deficient mothers are at risk for low birth weight and neural tube defects. Supplementation is highly recommended.
Vitamin B12 deficiency is common in seniors, estimated to affect 10%-15% of people over 60. This is often due to a restricted diet or dementia. Poor absorption of B12 is also a major factor, owing to a high prevalence of atrophic gastritis in this age group. Atrophic gastritis results in a low acid-pepsin secretion by the gastric mucosa, resulting in a reduced release of free vitamin B12 from food proteins.
The prevalence of pernicious anemia is also higher in older people.
Severe and persistent deficiency can cause hematological changes and irreversible neurological damage in older adults.
Although the official RDI (Recommended Dietary Intake) for vitamin B12 in older adults is the same (2.6mg), it is highly advisable for this age group to supplement with B12.
Can You Overdose on B12?
No. B12 has a low toxicity rating, and overdosing is not possible. As a water-soluble vitamin, anything the body cannot absorb is flushed out.
Various studies have shown that much higher doses are required to maintain adequate B12 status, including 4-7mcg B12/daily and even 500mcg/day.
Vitamin B12 Deficiencies
Patients with B12 levels below 200 pg/mL are considered deficient, and levels between 200 and300 pg/mL are considered borderline.
B12 deficiency is a serious disorder. An untreated deficiency can lead to severe and permanent neurological symptoms, and other effects on cognition and mood.
Symptoms may manifest as:
Fatal and non-fatal coronary disease,myocardial infarction, stroke, and other circulatory health problems due toenlarged red blood cells
One of the most common causes is food-bound cobalamin malabsorption, in which there is an impaired release of vitamin B12from ingested food. Achlorhydria (a condition in which the stomach does not produce enough stomach acid), gastritis, and medications such as proton pump inhibitors or antacids can reduce hydrochloric acid, reducing the breakdown of vitamin B12 from food.
Surgical history such as gastrectomy, resection of the terminal ileum, gastric bypass, or gastrointestinal disorders such as Crohn's or celiac disease may also result in malabsorption of B12.
Medications such as acid-suppressing agents can also lead to vitamin B12 deficiency, as well as the use of metformin.
In other cases, poor nutrition or a strict vegan diet may be the cause.
If neither gastrointestinal nor dietary, the cause is likely autoimmune. Pernicious anemia may indicate gastric carcinoma and other autoimmune conditions, such as thyroid disease, type 1 diabetes mellitus, and vitiligo.
Genetic mutations in metabolic enzymes such as methylenetetrahydrofolate reductase MTHFR have been associated with vitamin B12 deficiency. MTHFR catalyzes the conversion of 5,10-methylenetetrahydrofolate to5-methyltetrahydrofolate, which is then required for the conversion of homocysteine to methionine by methionine synthase, a vitamin B12-dependent enzyme.
An MTRR polymorphism may also increase the risk of B12 deficiency as methionine synthase reductase (MTRR) is required for activation of methionine synthase (an enzyme dependent on folate and B12).
Diagnosing a Deficiency
No “gold standard” test exists for diagnosing vitamin B12 deficiency. Diagnosis requires consideration of both the patient's clinical state and the investigations' results.
B12 deficiency is usually diagnosed if serum cobalamin levels are tested as <148 pmol/l. Most tests measure total serum cobalamin as levels bound to both transcobalamin II and haptocorrin. Newer tests may measure holotranscobalamin II: B12 attached to transcobalamin. This is the biologically active amount of B12 that can be delivered into all cells that synthesize DNA.
However, measuring only serum B12concentration may be unreliable as many people with clinical signs of B12deficiency may still test as within the “normal” population reference limit (above140 pmol/L). This may be because serum B12 test may not always accurately reflect actual vitamin B12stores. In such situations, it is recommended to also test the patient’s methylmalonic acid and homocysteine levels.
Folate levels should also be measured be tested, as falsely low cobalamin levels may occur in folate deficiency.
The most common symptoms of vitamin B12 deficiency are neurologic; these include prickling/burning in hands and feet (paresthesia), dizziness, problems with coordination, balance, speech, and cognition, fatigue, depression, muscle cramps, and macrocytic anemia.
It is crucial to determine the cause of a B12deficiency and treat it as soon as possible.
Deficiency is usually treated with vitamin B12 injections to bypass barriers to absorption. For patients without neurological symptoms, injections are given as1000 mcg intramuscularly (i.m.) three times a week for two weeks.
Patients with neurological symptoms may receive 1000 mcg via injections on alternate days until there is no further deficiency.
It should be noted that B12 injections are often given as cyanocobalamin (a synthetic form of B12). However, natural forms of B12 (methylcobalamin or hydroxocolbalamin) are more bioavailable than cyanocobalamin, and patients may prefer these options.
High doses of oral vitamin B12 might also be effective. There is evidence that oral B12 treatment has similar effects to B12 injections and costs less. It has also been found that supplementing with a combination of all 3 naturally occurring forms of B12(methyl-, hydroxo-, and adenosylcobalamin may be the most effective way to achieve clinical results.
Supplementing for B12
Although B12 is naturally present in food, food sources are unlikely to restore a deficiency. Food-bound cobalamin malabsorption is the most common reason for the deficiency. The bioavailability of vitamin B12 from food varies by the type of food source and the capacity of intrinsic factor.
It has been reported that vitamin B12 is about 50% more bioavailable in dietary supplements than in food sources.
B12 supplementation is especially recommended in those with greater needs, including during pregnancy and breastfeeding, and people over 60.
Should People with MTHFR Gene Mutations Supplement with B12?
Vitamin B12 deficiencies appear to be more prevalent in those with MTHFR mutations. A homozygous C677T mutation is strongly associated with B12 deficiency and can lead to endothelial dysfunction. This can be corrected with vitamin B12 and folate treatment.
MTHFR mutations result in insufficient levels of folate in the body. The metabolism of folate and B12 are intimately linked and required for synthesizing of S-adenosylmethionine (SAMe), the major methyl group donor in methylation reactions. Both folate and B12 are involved in the methylation pathway and its related enzymatic processes in homocysteine conversion and the synthesis of DNA and neurotransmitters.
For these reasons, people with MTHFR gene mutations are advised to supplement with B12 to support good health.
Deficiency in either folate or vitamin B12 can lead to elevated homocysteine and subsequent cardiovascular health issues.
Vitamin B12 is one of the most critical nutrients for human health. It is an essential cofactor in numerous enzymatic reactions, most notably one-carbon metabolism. It is required to generate S-adenosylmethionine (SAM), the body's major methyl donor.
The proper functioning of these processes is crucial to almost every bodily function, particularly for growth, development, neurological and cardiovascular health.
A deficiency in B12 can have severe and lasting complications. This is especially serious for pregnant women and older people. Individuals with MTHFR gene mutations depend on readily-available B12to work alongside folate in the methylation cycle.
Maintaining adequate B12 levels may not always be achieved through diet alone, and supplementation is advised.
Methylcobalamin, hydroxocobalamin, and adenosylcobalamin are the three forms of B12 clinically proven to improve vitamin B12 status. Unlike synthetic cyanocobalamin, these forms are immediately available for use in the body.
Methyl-Life’s® Active B12 Complete contains all three of these forms for optimal absorption and efficiency. It provides a high dose (5,000 mcg) to help restore deficiency and maintain healthy B12status. A lower dose option is Methyl-Life’s® Hydroxocobalamin, which provides 2.5 mg of the highly bioavailable precursor of methylcobalamin and adenosylcobalamin. Both products are formulated without extraneous fillers or additives and are suitable for all adults.
Updated On: September 20, 2022
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