🔒Private• Calculated on device

📊Evidence-based• Neurological research

🧠Neurological vitamin• Protects nerve function

Vitamin B12 Explained | The Neurological Vitamin

Essential for nerve function, DNA synthesis, and red blood cell formation. Deficiency can cause irreversible neurological damage — often before blood tests show anemia.

January 2026•10 min read

Evaluate Your B12 →

⚠️

Metformin Users: Important Warning

Metformin, the most widely prescribed diabetes medication, depletes vitamin B12 through multiple mechanisms:

• Interferes with calcium-dependent B12 absorption in ileum

• Up to 30% of long-term users develop deficiency

• Risk increases with dose and duration

• Often unmonitored — many providers don't test B12 routinely

If you take metformin, request annual B12 testing. Consider supplementation (1000 mcg/day) as prevention. Neurological symptoms warrant immediate testing.

Who is this for?

✓Vegetarians and vegans (no reliable plant sources)
✓People taking metformin (depletes B12)
✓Adults over 50 (reduced absorption)
✓Those with digestive issues (celiac, Crohn's, gastric surgery)
✓People taking PPIs or H2 blockers long-term
✓Anyone experiencing fatigue, numbness, or cognitive issues

What is Vitamin B12?

Vitamin B12 (cobalamin) is a water-soluble vitamin essential for DNA synthesis, red blood cell formation, and critically, nerve function. It's the only vitamin that contains a metal ion (cobalt) and requires a complex absorption process involving stomach acid and intrinsic factor.

B12 deficiency is insidious. Unlike other deficiencies, it can cause permanent neurological damage before blood tests show abnormalities. The classic sign — megaloblastic anemia — is often a late finding. Neurological symptoms (numbness, tingling, cognitive decline) frequently appear first.

Your body stores B12 in the liver (3-5 years worth), so deficiency develops slowly. This is both blessing and curse: it means vegetarians don't become deficient overnight, but it also means deficiency can progress silently for years before detection.

The Absorption Problem

B12 absorption is complex and declines with age:

1️⃣

Stomach acid releases B12 from food

PPIs, H2 blockers, and aging reduce stomach acid

2️⃣

B12 binds to intrinsic factor (IF)

IF is made by stomach parietal cells; autoimmune gastritis destroys these

3️⃣

B12-IF complex absorbed in terminal ileum

Crohn's, celiac, or surgical removal of ileum impairs this step

This is why sublingual or injectable B12 can bypass absorption issues when oral supplements fail.

How to Test

Primary test:Serum B12 — widely available but has limitations (see below)

Better test:Methylmalonic Acid (MMA) — more sensitive, especially for early/functional deficiency. Elevated MMA = tissue-level deficiency even if serum B12 is "normal".

Also consider:Homocysteine — rises with B12 deficiency (but also with folate deficiency); active B12 (holotranscobalamin) is most specific but less available.

Fasting:Not required for serum B12; recommended for MMA.

Gray zone:200-400 pg/mL is a diagnostic gray zone. Symptoms + gray zone serum B12 → check MMA.

Retest interval:Every 3-6 months when repleting; annually for maintenance in at-risk groups.

40%

of adults low/deficient

Nearly half of adults have suboptimal B12 (Framingham)

Tucker 2000

30%

metformin users affected

Long-term metformin use causes B12 deficiency

De Jager 2010

500+

pg/mL target

Neurological protection requires higher levels than preventing anemia

Langan & Goodbred 2017

Research Summary

The Framingham Offspring Study found that 39% of adults had B12 levels below 350 pg/mL. Importantly, neurological symptoms can occur at levels that don't meet classic "deficiency" criteria (<200 pg/mL). Research suggests maintaining B12 above 500 pg/mL for neurological protection. Methylmalonic acid (MMA) testing identifies tissue-level deficiency that serum B12 misses.

Symptoms of B12 Deficiency

Early / Subtle

•Fatigue, low energy
•Mild cognitive fog
•Subtle mood changes
•Glossitis (smooth, red tongue)
•Mild numbness/tingling

Advanced / Serious

•Peripheral neuropathy
•Balance problems, ataxia
•Memory loss, dementia
•Depression, psychosis
•Macrocytic anemia

Neurological damage can become permanent if deficiency is prolonged. Don't wait for anemia — neurological symptoms warrant immediate testing and treatment.

Three Interpretation Paradigms

🏥

Standard Medical

Focus: Prevent megaloblastic anemia

<200 pg/mL deficient | 200-300 borderline | >300 normal

Conventional medicine focuses on preventing overt deficiency and megaloblastic anemia. The threshold of 200 pg/mL was established to detect severe deficiency; subclinical deficiency at higher levels is often overlooked.

Action: Treat deficiency with injections; borderline cases often dismissed

🔬

Research Consensus

Focus: Neurological protection

<350 pg/mL low | 350-500 suboptimal | 500-800 optimal | >800 high (investigate)

Research shows neurological symptoms can occur at levels considered "normal" by standard criteria. Optimal B12 for nerve protection is 500-800 pg/mL. MMA testing is recommended for anyone in the gray zone (200-400 pg/mL) with symptoms.

Action: Target 500+ for neurological protection; check MMA if symptoms with "normal" serum B12

⚡

Metabolic Optimization

Focus: Methylation support

<500 pg/mL suboptimal | 500-800 optimal | 800-1200 acceptable on carnivore | >1200 investigate

In the metabolic health community, B12 is viewed through the lens of methylation and energy production. Higher levels (800-1200 pg/mL) are common and acceptable on carnivore diets. Very high levels (>1500) warrant investigation for liver disease or leukemia.

Action: Methylcobalamin preferred; higher levels expected on meat-heavy diets

Interpretation Table

Units: pg/mL (multiply by 0.738 for pmol/L)

Category	Standard Medical	Research Consensus	Metabolic Optimization
Deficient	< 200	< 350	< 400
Low / Suboptimal	200 - 300	350 - 500	400 - 500
Normal / Optimal	300 - 900	500 - 800	500 - 800
High	> 900	> 800 (check MMA)	800 - 1200 OK; > 1200 investigate

Who's at Risk for B12 Deficiency?

🥗

Dietary

•Vegans (no dietary B12 in plants)
•Vegetarians (limited sources)
•Restrictive diets
•Eating disorders

🔄

Absorption Issues

•Pernicious anemia (autoimmune)
•Gastric surgery / bariatric surgery
•Celiac disease
•Crohn's disease, IBD
•Chronic pancreatitis

💊

Medications

•Metformin (diabetes)
•PPIs (omeprazole, etc.)
•H2 blockers (ranitidine, famotidine)
•Colchicine
•Some antibiotics

👴

Age & Other

•Adults over 50 (reduced absorption)
•Heavy alcohol use
•Nitrous oxide exposure
•Pregnancy/breastfeeding (increased needs)

How to Optimize B12

🥩

Food Sources

Liver
Highest source — 3 oz provides 70+ mcg (2800% DV)
Clams, oysters
Excellent shellfish sources
Beef, lamb
3 oz provides ~2-3 mcg
Fish (salmon, tuna)
Good source, ~2-5 mcg per serving
Eggs, dairy
Moderate sources; less bioavailable

💊

Supplementation

Methylcobalamin
Active form; preferred for neurological support
Adenosylcobalamin
Active form for mitochondrial function
Cyanocobalamin
Synthetic, cheap, requires conversion
Sublingual
Bypasses gut absorption issues
Injections
For severe deficiency or absorption problems

📊

Dosing

Maintenance
250-500 mcg/day sublingual or oral
Repletion
1000-2000 mcg/day for 1-2 months
Severe deficiency
Injections: 1000 mcg weekly × 4, then monthly
Metformin users
1000 mcg/day preventatively
No upper limit
B12 is water-soluble; excess excreted

B12 is non-toxic even at high doses. If you have absorption issues (age, surgery, medications), consider sublingual forms or injections over oral tablets.

Timeline for Improvement

1-2 weeks

Energy improvement often noticed first

4-8 weeks

Blood markers begin normalizing

3-6 months

Neurological symptoms begin improving (if not permanent)

6-12 months

Full neurological recovery (extent depends on duration of deficiency)

Key Takeaways

•Neurological damage can occur BEFORE blood tests show anemia
•Serum B12 200-400 pg/mL is a "gray zone" — check MMA if symptomatic
•Target 500+ pg/mL for neurological protection
•Metformin depletes B12 — up to 30% of users become deficient
•Vegans have NO dietary B12 source — supplementation is mandatory
•Sublingual or injectable B12 bypasses gut absorption problems
•Methylcobalamin is the preferred form for neurological support
•B12 stores last 3-5 years, so deficiency develops slowly but insidiously

References

1. Tucker KL, Rich S, Rosenberg I, et al. Plasma vitamin B-12 concentrations relate to intake source in the Framingham Offspring study. Am J Clin Nutr. 2000;71(2):514-522. PMID: 10648266
2. de Jager J, Kooy A, Lehert P, et al. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency. BMJ. 2010;340:c2181. PMID: 20488910
3. Langan RC, Goodbred AJ Vitamin B12 Deficiency: Recognition and Management. Am Fam Physician. 2017;96(6):384-389. PMID: 28925645
4. Stabler SP Vitamin B12 deficiency. N Engl J Med. 2013;368(2):149-160. PMID: 23301732
5. Lindenbaum J, Healton EB, Savage DG, et al. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N Engl J Med. 1988;318(26):1720-1728. PMID: 3374544
6. Allen LH How common is vitamin B-12 deficiency? Am J Clin Nutr. 2009;89(2):693S-696S. PMID: 19116323
7. Pawlak R, Parrott SJ, Raj S, et al. How prevalent is vitamin B12 deficiency among vegetarians? Nutr Rev. 2013;71(2):110-117. PMID: 23356638
8. Miller JW Proton pump inhibitors, H2-receptor antagonists, metformin, and vitamin B-12 deficiency. Nutr Rev. 2018;76(10):725-738. PMID: 30124891
9. Carmel R Biomarkers of cobalamin (vitamin B-12) status in the epidemiologic setting. Am J Clin Nutr. 2011;94(1):348S-358S. PMID: 21593497
10. Solomon LR Disorders of cobalamin (vitamin B12) metabolism. Blood Rev. 2007;21(3):113-130. PMID: 16814909

This information is for educational purposes only and should not be used to diagnose or treat any medical condition. Always consult with a qualified healthcare provider before making changes to your health regimen.

Ready to Evaluate Your B12 Level?

Use our free evaluator to see what your result means across three different health paradigms.

Evaluate Your B12 →