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Choose methylcobalamin if: You have confirmed MTHFR mutations Elevated homocysteine levels Neurological or mood symptoms You tolerate methylated supplements well Choose hydroxocobalamin if: Sensitive to methyl-B12 (anxiety, insomnia) Histamine intolerance or MCAS Need gentle, balanced B12 support Want detoxification benefits Choose adenosylcobalamin if: Chronic fatigue is your primary concern Mitochondrial dysfunction Want to combine with methyl-B12 for comprehensive support Consider combination formulas: Many practitioners recommend combining forms: Methyl-B12 + Adeno-B12 (methylation + energy) Hydroxy-B12 + Adeno-B12 (gentle + energy) All three forms for comprehensive support The bottom line: For MTHFR mutations, methylcobalamin is typically most effective for supporting methylation and lowering homocysteine