"What are the first signs of B12 deficiency?"

"Early B12 deficiency often presents with fatigue, weakness, and pallor from megaloblastic anemia. Neurological symptoms come later and can include numbness or tingling in hands and feet, balance problems, memory difficulties, and mood changes. The neurological damage from B12 deficiency can be permanent if not treated promptly. This is why regular monitoring matters for high-risk groups, even before symptoms appear."

"Does methylcobalamin work better than cyanocobalamin?"

"Methylcobalamin and adenosylcobalamin are the active forms of B12 used in the body. Cyanocobalamin is a synthetic form that gets converted to these active forms after absorption. Some supplement brands market methylcobalamin as superior, but clinical evidence for better outcomes or bioavailability vs cyanocobalamin in healthy people is weak. Cyanocobalamin is more stable, better studied, and the standard form in most clinical research. For most people, cyanocobalamin is the practical choice."

"Can you get enough B12 from nutritional yeast?"

"Only if it's been fortified. Nutritional yeast doesn't naturally contain B12. Some brands add it. Check the label specifically for B12 content and the form used (cyanocobalamin or methylcobalamin). Nutritional yeast can be a reasonable source for vegans if consistently consumed in adequate amounts from fortified brands, but it's less reliable than a dedicated supplement."

"Why can't B12 just be absorbed without intrinsic factor?"

"B12 can be passively absorbed in very small amounts (about 1% of the dose) across the gut lining even without intrinsic factor. This is actually the basis for high-dose oral B12 supplementation: if you take 1000mcg, about 10mcg gets absorbed passively, which can eventually correct deficiency. But this passive route is too inefficient to maintain B12 status from food amounts. The active, intrinsic factor-mediated route handles typical dietary doses efficiently. When that system fails (pernicious anemia, gastric surgery), high-dose oral or injectable B12 become necessary."

How Vitamin B12 Works: Absorption, Storage, Deficiency, and Plant-Based Diets

Quick Answer

Vitamin B12 absorption requires intrinsic factor (IF), a protein secreted by the stomach. IF binds B12 and carries it to the ileum (end of the small intestine) where specialized receptors absorb the complex. The liver stores 2-5mg of B12, enough for 3-5 years. This is why deficiency takes years to show up but can cause irreversible nerve damage if untreated. Plant foods contain no reliable B12, making supplementation or fortified foods essential for people on plant-based diets.

The Science

Vitamin B12 is where the gap between “eating a nutrient” and “absorbing a nutrient” becomes medically serious. The absorption system is unusually complicated for a vitamin, and when it breaks down, the consequences can be permanent.

This complexity is why B12 deficiency deserves more attention than it typically gets in nutrition discussions.

The Chemistry of Cobalamin

B12, or cobalamin, is the most structurally complex of all vitamins. It contains a cobalt atom at its center surrounded by a corrin ring, with various chemical groups attached. The specific form matters: methylcobalamin and adenosylcobalamin are the two active forms that function as coenzymes in the body.

B12 participates in two essential reactions. As methylcobalamin, it’s a cofactor for methionine synthase, which converts homocysteine to methionine and is required for DNA synthesis and myelin production. As adenosylcobalamin, it’s a cofactor for methylmalonyl-CoA mutase, involved in fatty acid and amino acid metabolism.

The neurological damage from B12 deficiency comes primarily from impaired myelin synthesis. Myelin is the insulating sheath around nerve fibers. Without adequate B12-dependent methylation reactions, myelin breaks down and nerve conduction fails (Stabler, 2013, New England Journal of Medicine).

The Intrinsic Factor System

Most water-soluble vitamins are absorbed by relatively simple mechanisms. B12 is different.

In the stomach, acid and pepsin release B12 from food proteins. The freed B12 initially binds to a protein called haptocorrin (R protein), which protects it from stomach acid. As the food bolus moves into the small intestine, pancreatic enzymes degrade haptocorrin, releasing B12. Here it binds to intrinsic factor (IF), a glycoprotein secreted by parietal cells in the stomach lining.

The B12-IF complex travels to the ileum (the final section of the small intestine), where it binds to cubilin receptors on ileal enterocytes and gets absorbed. Without intrinsic factor, this receptor-mediated uptake doesn’t happen.

Inside the cell, B12 is released from IF, converted to its active coenzyme forms, and enters circulation.

This multi-step process has several vulnerable points. Reduced stomach acid (from aging, proton pump inhibitor use, or H. pylori infection) impairs B12 liberation from food protein in the first step. Autoimmune destruction of gastric parietal cells (pernicious anemia) eliminates intrinsic factor. Ileal damage or removal eliminates the absorption site. Each creates a different type of B12 deficiency with different correction strategies.

Why Deficiency Takes Years

The liver stores 2-5mg of B12. Daily requirements are roughly 2.4mcg. At that burn rate, liver stores can last 3-5 years before depleting.

This long runway has two consequences. It means people transitioning to plant-based diets don’t notice deficiency symptoms quickly, which leads to serious underestimation of the risk. It also means that once deficiency is established, stores take years to deplete fully, creating a window where neurological damage accumulates before obvious symptoms appear.

A systematic review by Pawlak et al. (2013, Nutrition Reviews) found B12 deficiency rates of 40-86% in vegans and vegetarians across studies, depending on whether they supplemented and for how long. The longer the dietary restriction without supplementation, the higher the deficiency rates.

Plant Foods and B12

This point is unambiguous: no plant food reliably provides bioavailable B12. Some algae, fermented foods, and certain mushrooms contain B12 analogs (cobamides), but these are mostly inactive forms that can actually compete with true B12 for absorption, potentially worsening deficiency (Watanabe et al., 2014, Nutrients).

This is not a matter of controversy in nutrition science. The claim that spirulina, nori, tempeh, or nutritional yeast (unless specifically fortified) provide reliable B12 is not supported by the evidence.

B12 is produced exclusively by microorganisms, primarily bacteria. Animals (including humans) accumulate it by consuming bacteria or eating animals that consumed bacteria. Plants grown in sterile soil have no B12 at all.

Supplementation for Plant-Based Eaters

The practical recommendations are clear. Vegans who don’t eat fortified foods should supplement. The two main options are regular lower doses (250mcg cyanocobalamin daily, which uses the active intrinsic factor pathway) or weekly high doses (2,000-2,500mcg weekly, which relies partly on passive absorption).

Carmel (2008, Blood) reviewed B12 correction protocols and found that high-dose oral B12 is as effective as intramuscular injections for most people, including those with pernicious anemia, because even 1% passive absorption of a large dose delivers enough to restore status over time.

Older Adults: A Separate Concern

Age-related changes in stomach acid production affect B12 absorption from food even in meat eaters. Hypochlorhydria (low stomach acid) impairs the first step of B12 release from food protein. Estimates suggest 10-30% of people over 50 have impaired B12 absorption from food (Andrès et al., 2004, Canadian Medical Association Journal).

Crystalline B12 in supplements and fortified foods doesn’t require acid liberation, so it bypasses this problem. This is why the US Dietary Guidelines recommend that adults over 50 get most of their B12 from fortified foods or supplements, regardless of dietary pattern.

This article is for educational purposes only. It’s not medical advice. Talk to your doctor or a registered dietitian before making significant changes to your diet.

What This Means for You

Vegans and vegetarians who don't eat dairy or eggs should take a B12 supplement. Cyanocobalamin (the most common and studied form) is well-absorbed and stable. A dose of 250mcg daily or 2,500mcg weekly provides adequate absorption accounting for the fact that passive absorption (without intrinsic factor) is less efficient. People over 50 also have reduced stomach acid production, which affects B12 liberation from food protein, so supplementation or fortified foods are recommended for older adults even if they eat meat.