Why the form of vitamin B12 you take may be more important than your intake

Why the form of vitamin B12 you take may be more important than your intake

A new scientific study weighs natural and synthetic forms of vitamin B12, showing where methylcobalamin can outperform traditional supplements and why deficiency remains a clinical blind spot.

Vitamin B12 refers to one of the three forms of cobalamin: cyanocobalamin, methylcobalamin and adenosylcobalamin. It is a vital vitamin for humans and is mainly obtained from animal foods.

Vitamin B12 deficiency can lead to megaloblastic anemia, neuropathy, and pregnancy complications. While nutritional supplementation increases values ​​in healthy people in a similar way to food intake, in the case of an obvious deficiency disease, nutritional supplementation is required in addition to food intake. A recent review in the magazineCureuscompares the natural forms of B12 in food with synthetic B12 (cyanocobalamin) in terms of absorption and clinical-physiological effects.

Physiology of dietary B12 intake

Vitamin B12 is a polar molecule that occurs in protein-bound form in foods. B12 is released from dietary protein through proteolytic digestion. It is then protectively bound to haptocorrin, a glycoprotein that protects it from denaturation by stomach acid.

Haptocorrin is broken down by pancreatic proteases in the duodenum. Free B12 forms a complex with intrinsic factor (IF), a glycoprotein produced by the parietal cells of the stomach. After absorption in the distal ileum via receptors, it leaves the enterocytes and enters the portal blood, where it binds to the transport protein transcobalamin II and is transported to the bone marrow and other tissues.

Core metabolic functions of cobalamin

In humans, B12 plays a central role as a cofactor for the synthesis of methionine from homocysteine ​​and at the same time for the regeneration of the methyl donor tetrahydrofolate. The latter is essential for DNA synthesis, including red blood cell formation, and for several other cellular pathways, including energy metabolism.

B12 is also a cofactor for methylmalonyl coenzyme A mutase (MMCoA), which is critical for protein and lipid metabolism, including myelination.

Clinical and neurological consequences of deficiency

B12 deficiency interrupts DNA synthesis, resulting in ineffective red blood cell formation. The cell nucleus cannot mature normally, resulting in large, immature red blood cells (macrocytes), with a decrease in the number of red blood cells and overall hemoglobin concentration, resulting in macrocytic anemia.

Other clinical features include neuropathy and cognitive impairment. Early symptoms may include mouth or tongue pain, yellowing of the skin, weight loss, numbness or tingling in the extremities, and vision problems. Pregnancy complicated by B12 deficiency can lead to spina bifida and other neural tube defects.

Some cases of depression respond to B12 supplementation with delayed onset of symptoms and increased antidepressant efficacy. While observational and mechanistic studies suggest that impaired one-carbon metabolism, elevated homocysteine, and mitochondrial dysfunction may contribute to neurodegenerative pathways, current evidence does not support a direct causal relationship between B12 deficiency and Alzheimer's disease.

Impaired MMCoA function in B12 deficiency can lead to demyelination of the lateral and posterior spine, leading to subacute combined degeneration. Its role in immune regulation is currently being investigated, including possible antiviral effects. B12 increases lymphocyte number and activity and counteracts systemic inflammation, but the clinical relevance remains uncertain. New research has examined possible roles for B12 in coronavirus disease 2019 (COVID-19), but results are mixed and benefits are not yet proven.

B12 lowers homocysteine ​​levels. Since homocysteine ​​predisposes lipid peroxidation by reactive oxygen species, thereby causing endothelium damage, adequate B12 status may reduce the risk of thromboembolic complications, although the evidence remains associative. B12 also contributes to muscle and gut health; Deficiency can reduce vagal tone, disrupt the muscle-gut-brain axis, and contribute to neurobehavioral disorders. Severe deficiency can lead to peripheral neuropathy, loss of bowel control, paralysis, erectile dysfunction, depression and paranoia. Pernicious anemia is sometimes followed by stomach cancer.

Dietary intake, risk factors and requirements

Older people, vegans and vegetarians are at increased risk of B12 deficiency. It can also occur due to gastritis, pernicious anemia, Crohn's disease, celiac disease, intestinal surgery, alcoholism and Sjögren's syndrome. Excessive use of medications such as metformin, proton pump inhibitors, histamine H2 blockers, and oral contraceptives can lower B12 levels.

Most people have normal B12 levels. Around 3% of people between the ages of 20 and 39 suffer from a deficiency, and among those over 60 the figure is as high as 6%. Given the wide range of manifestations and blood levels, testing to confirm deficiency, defined as <150 pg/mL, is essential. In most cases, food intake is not the problem; Rather, malabsorption or impaired utilization is responsible.

The best food sources of B12 include beef liver, fortified yeast, salmon, Greek yogurt, eggs and shellfish. Beef liver can contain about 71 μg per serving, versus 0.5 μg per serving of egg. The recommended intake for adults is 2.4 μg/day, increasing to 2.6 μg during pregnancy and to 2.8 μg during breastfeeding.

Comparison of natural and synthetic forms of cobalamin

Cobalamin from foods or supplements is activated by its conversion into methylcobalamin and adenosylcobalamin. Both are chemically identical to natural vitamin B12.

In contrast, cyanocobalamin, the synthetic form commonly used in dietary supplements, must first be converted to cobalamin by removing the cyanide group before activation. Mutations in B12 metabolic pathways may impair this conversion in a subset of individuals.

The storage of cyanocobalamin in the liver is lower than that of natural vitamin B12. Some studies also suggest greater urinary losses of cyanocobalamin compared to methylcobalamin. The liver may not adequately convert cyanocobalamin to its biologically active form, potentially affecting neuronal health.

The methyl group in methylcobalamin can increase serotonin production and protect the brain from excitatory toxins. Current evidence suggests, but does not conclusively prove, that the overall results favor methylcobalamin supplementation over cyanocobalamin. It may also be preferable in megaloblastic anemia due to its higher bioavailability and possible conversion to S-adenosylmethionine, which promotes metabolic health. Nevertheless, both cyanocobalamin and methylcobalamin effectively increase serum B12 levels, and comparative outcome data remain limited.

Clinical implications and future directions

The review suggests screening for B12 deficiency in older adults, vegetarians and vegans, and people with certain gastrointestinal diseases. Early detection and treatment can help prevent long-term neurological and hematological complications.

Both methylcobalamin and cyanocobalamin can be used as dietary supplements and both increase B12 levels in the blood. However, methylcobalamin appears to be consistently more potent and bioavailable and may be preferable for individuals with impaired absorption or methylation pathways. Future research should clarify long-term outcomes and preventive benefits in high-risk groups.

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