What B12 does
- Methylation (with folate)
- DNA synthesis
- Red blood cell formation
- Neurological function (myelin synthesis)
- Energy metabolism
- Homocysteine clearance
Deficiency symptoms
- Numbness, tingling (peripheral neuropathy)
- Brain fog, memory issues
- Fatigue
- Mood changes
- Macrocytic anemia
- Glossitis (sore tongue)
- Balance problems
Optimal ranges
- Reference range: 200-900 pg/mL (highly variable by lab)
- Suboptimal: 200-400
- Optimal: >500
- "Normal" lower limit (200) misses many functional deficiencies
Methylcobalamin vs cyanocobalamin
- Methylcobalamin, active methylated form; bypasses methylation enzyme variants; preferred for many
- Cyanocobalamin, cheap stable form; requires conversion; less preferred
- Hydroxycobalamin, injectable form; intermediate
- Adenosylcobalamin, mitochondrial form; sometimes paired with methyl
Absorption issues
B12 absorption requires:
- Stomach acid for protein release
- Intrinsic factor (parietal cells)
- Healthy ileum (where it's absorbed)
Common impaired-absorption causes:
- Aging (reduced stomach acid)
- PPIs (reduced acid)
- Metformin (impairs absorption)
- Pernicious anemia (intrinsic factor deficiency)
- Crohn's, celiac disease
- Vegan/vegetarian diet (limited dietary sources)
Monitoring
- B12 level
- Methylmalonic acid (functional marker; rises with B12 deficiency)
- Homocysteine (B12 affects)
- CBC (look for macrocytic anemia)
The clinical pearl: B12 in the 200-400 range is often functionally deficient even if "normal." Add methylmalonic acid for confirmation. Methylcobalamin is preferred for supplementation in patients with MTHFR variants or methylation issues.
Bottom line
B12 affects methylation, neurological function, and energy. Reference ranges miss functional deficiency. Methylcobalamin is preferred form. Test routinely; supplement liberally in deficient or borderline patients.
>500
pg/mL optimal B12
Methyl
form preferred for supplementation
MMA
functional marker confirms deficiency
Pillar Guide · Longevity & Cellular Health
Read the full guide: Longevity Protocols: The Evidence Map →