Shopping for vitamin B12 supplements? You’ll notice two forms dominating the market: methylcobalamin and cyanocobalamin. They’re both B12, but they’re not quite the same.
Cyanocobalamin is synthetic and cheaper. Methylcobalamin is natural and often marketed as “superior.” But which actually works better?
The research paints a more nuanced picture than marketing claims suggest.1
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Available on the App StoreThe key differences
Both forms contain a cobalt ion at their core — that’s what makes them “cobalamin.” The difference is what’s attached to it:
Methylcobalamin has a methyl group attached. It’s a natural form found in food sources like meat, fish, eggs, and dairy. It’s also one of the two active forms your body uses directly.
Cyanocobalamin has a cyanide molecule attached. It’s synthetic and not found in nature. Your body must convert it before use. But before you worry about cyanide — the amount is extremely small (about 20 mcg per 1,000 mcg dose) and completely harmless.2
Here’s the thing: your body doesn’t actually use either form as-is. It converts both into two active coenzymes:
- Methylcobalamin — used in the cytoplasm for methylation reactions
- Adenosylcobalamin — used in mitochondria for energy metabolism
So even “natural” methylcobalamin supplements get partially converted to adenosylcobalamin in your body.
Absorption and retention: what the research shows
This is where things get interesting. Different studies favor different forms:13
Cyanocobalamin absorption: Some research suggests cyanocobalamin absorbs slightly better — about 49% of a low dose compared to 44% for methylcobalamin.4
Methylcobalamin retention: Other studies show methylcobalamin is retained better in tissues. One found three times as much cyanocobalamin excreted through urine, suggesting methylcobalamin “sticks around” longer.
Real-world effectiveness: A study in vegans found cyanocobalamin actually maintained higher levels of active B12 (holotranscobalamin) compared to methylcobalamin supplementation.5
The bottom line? Both forms effectively raise B12 levels when taken at adequate doses. The differences in absorption and retention may matter less than whether you’re taking enough.
Advantages of cyanocobalamin
Cost: Significantly cheaper to produce and purchase.
Stability: More stable in storage. Less sensitive to light and heat degradation. Longer shelf life.
Proven track record: Used in supplements for decades with well-documented safety and efficacy.
Food fortification: This is the form added to fortified foods like cereals and plant milks.
Advantages of methylcobalamin
No conversion needed: It’s already in active form for methylation reactions. This may benefit people with certain genetic variations (MTHFR polymorphisms) who have trouble converting B12 forms.
Potentially better for neurological conditions: Some research suggests methylcobalamin may be more effective for nerve-related symptoms, though evidence is limited.6
Natural form: Appeals to those preferring supplements closer to what’s found in food.
Less cyanide: While the cyanide from cyanocobalamin is minimal, methylcobalamin avoids it entirely.
When methylcobalamin might be better
Consider methylcobalamin if you:
- Have B12 deficiency symptoms related to nerve function (numbness, tingling)
- Have known MTHFR gene polymorphisms affecting methylation
- Prefer natural-form supplements
- Have kidney issues (kidneys normally clear the small cyanide load)
Some practitioners recommend combining methylcobalamin with adenosylcobalamin for comprehensive support, since each form has distinct metabolic roles.
Suggested read: Water-soluble vitamins: A comprehensive overview of C and B complex
When cyanocobalamin works fine
Cyanocobalamin is perfectly adequate for most people looking to:
- Prevent or correct B12 deficiency
- Supplement a plant-based diet
- Maintain healthy B12 levels
- Get the most cost-effective option
Multiple studies confirm cyanocobalamin effectively treats deficiency and maintains adequate B12 status.3
Dosage considerations
The recommended dietary allowance for B12 is just 2.4 mcg daily for adults. However, supplements typically contain much higher amounts (500-5,000 mcg) because absorption is limited.
Your body can only absorb about 1.5 mcg through intrinsic factor at a time. Higher doses rely on passive absorption, which captures roughly 1% of the dose.
Taking 1,000 mcg actually delivers about 10-15 mcg when accounting for both pathways. This explains why supplement doses seem disproportionately high compared to the RDA.
Suggested read: Vitamin B12 Dosage: How Much Do You Need Per Day?
Other forms worth knowing
Beyond methylcobalamin and cyanocobalamin, two other forms exist:
Hydroxocobalamin: Another natural form, used primarily in injections. Has excellent retention and is the preferred form for treating cyanide poisoning. Some supplements now include it.
Adenosylcobalamin: The second active coenzyme form. Essential for mitochondrial energy production. Available in some specialized supplements, often combined with methylcobalamin.
For comprehensive B12 support, some experts recommend supplements containing both methylcobalamin and adenosylcobalamin rather than either alone.6
Who’s at risk for B12 deficiency?
Understanding your risk helps determine how seriously to take B12 supplementation:
- Vegans and vegetarians — B12 comes almost exclusively from animal foods
- Adults over 50 — Absorption decreases with age
- People with digestive disorders — Crohn’s disease, celiac disease, or gastritis impair absorption
- Those who’ve had GI surgery — Bariatric surgery affects B12 absorption
- People taking metformin — Long-term use can deplete B12
- Those taking PPIs or H2 blockers — Stomach acid is needed for B12 absorption
If you fall into these categories, consistent supplementation becomes more important than debating which form is marginally better.
The bottom line
Both methylcobalamin and cyanocobalamin effectively prevent and treat B12 deficiency. The differences between them are smaller than marketing suggests.
Choose cyanocobalamin if you want an affordable, stable, well-researched option that works for general supplementation.
Choose methylcobalamin if you have nerve-related symptoms, genetic methylation concerns, prefer natural forms, or want to avoid even trace cyanide.
Consider a combination of methylcobalamin and adenosylcobalamin for the most comprehensive approach, particularly if addressing deficiency symptoms.
Whichever you choose, consistency matters more than the specific form. A daily or weekly B12 supplement, combined with a balanced diet, supports adequate levels for most people.
Paul C, Brady DM. Comparative Bioavailability and Utilization of Particular Forms of B12 Supplements With Potential to Mitigate B12-related Genetic Polymorphisms. Integr Med (Encinitas). 2017;16(1):42-49. PubMed ↩︎ ↩︎
Herbert V. Vitamin B-12: plant sources, requirements, and assay. Am J Clin Nutr. 1988;48(3 Suppl):852-858. PubMed ↩︎
Adams JF, Ross SK, Mervyn L, Boddy K, King P. Absorption of cyanocobalamin, coenzyme B12, methylcobalamin, and hydroxocobalamin at different dose levels. Scand J Gastroenterol. 1971;6(3):249-252. PubMed ↩︎ ↩︎
Okuda K, Yashima K, Kitazaki T, Takara I. Intestinal absorption and concurrent chemical changes of methylcobalamin. J Lab Clin Med. 1973;81(4):557-567. PubMed ↩︎
Greibe E, Mahalle N, Engelsen SB, Lindqvist C, Nexo E. Efficacy of supplementation with methylcobalamin and cyanocobalamin in maintaining the level of serum holotranscobalamin in a group of plant-based diet (vegan) adults. Eur J Clin Nutr. 2022;76(1):176-178. PubMed ↩︎
Stabler SP. Vitamin B12. In: Marriott BP, Birt DF, Stallings VA, Yates AA, eds. Present Knowledge in Nutrition. 11th ed. Academic Press; 2020:257-271. ↩︎ ↩︎
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