3 forms with solid human evidence · distinct profile based on MTHFR genetics and clinical case. Avoid cyanocobalamin if smoker or compromised hepatic function.
Active form · methyl group donor
Best for
Ideal use: vegans, >50 years, MTHFR C677T, neuropathy, cognitive decline, general methylation cycle.
Advantages
Sublingual bioavailability ~80% · MTHFR-friendly · direct delivery to methionine cycle without requiring hepatic conversion. RCT evidence in diabetic neuropathy and cognitive decline.
Disadvantages
Only activates the cytoplasmic branch (methionine synthase) · not the mitochondrial one. More expensive (~10-15 €/month).
Active mitochondrial form
Best for
Ideal use: chronic energy fatigue, elevated MMA, endurance athletes, post-COVID recovery.
Advantages
Cofactor of methylmalonyl-CoA mutase → ATP in mitochondria. Useful when MMA is elevated but homocysteine normal (pure mitochondrial fatigue profile).
Disadvantages
Less popular · limited availability in Spain. Generally combined with methylcobalamin in premium stacks.
Stable synthetic form
Best for
Ideal use (limited): young non-smoking adults with normal hepatic function · only if methyl form unavailable.
Advantages
Inexpensive (~3-5 €/month) · temperature stable · base of most classic studies. Conversion to methylcobalamin is efficient in healthy non-smokers.
Disadvantages
Releases cyanide ion when metabolized · contraindicated in active smokers (synergizes with HCN from tobacco), nephropathy and severe MTHFR polymorphisms. Not recommended in pro wellness 2026.
Ideal use: vegans, >50 years, MTHFR C677T, neuropathy, cognitive decline, general methylation cycle.
Ideal use: chronic energy fatigue, elevated MMA, endurance athletes, post-COVID recovery.
Ideal use (limited): young non-smoking adults with normal hepatic function · only if methyl form unavailable.
3 forms with solid human evidence · distinct profile based on MTHFR genetics and clinical case. Avoid cyanocobalamin if smoker or compromised hepatic function.