Clinical Guidelines for B12 Deficiency Recognition and Management

Langan RC, Goodbred AJ • Am Fam Physician

Key Finding

Neurological protection requires B12 levels above 500 pg/mL

Original title: “Vitamin B12 Deficiency: Recognition and Management”

Plain English Summary

American Family Physician clinical review on recognizing and managing B12 deficiency, emphasizing neurological protection requires levels above 500 pg/mL.

In-Depth Analysis

Background

Drs. Robert C. Langan and Andrew J. Goodbred published this clinical review in American Family Physician (PMID: 28925645), providing practical guidance for recognizing and managing vitamin B12 deficiency in primary care.

Study Design

Clinical review synthesizing evidence-based recommendations for B12 deficiency diagnosis and treatment.

Key Findings

Diagnostic approach:

Test	Interpretation
Serum B12	<200 pg/mL: deficient; 200-400: borderline
Methylmalonic acid (MMA)	Elevated = tissue deficiency
Homocysteine	Elevated = functional deficiency

Neurological protection threshold: >500 pg/mL

Risk factors identified:

•Age >65 (gastric atrophy, reduced IF)
•Metformin use (15-30% develop low B12)
•PPI use (reduced absorption)
•Vegetarian/vegan diet
•Autoimmune conditions (pernicious anemia)
•Gastrointestinal surgery

Treatment recommendations:

Indication	Route	Dose
Deficiency without neuro sx	Oral	1000-2000 mcg/day
Neurological symptoms	IM	1000 mcg/day × 7, then weekly × 4, then monthly
Maintenance	Oral or IM	Based on levels

Mechanistic Insights

B12 is required for:

•DNA synthesis (blood cell production)
•Myelin maintenance (neurological function)
•Homocysteine metabolism (cardiovascular health)

Deficiency causes dysfunction before anemia appears.

Clinical Implications

Check B12 in all patients on metformin, PPIs, or with neurological symptoms. Target >500 pg/mL for neurological protection. Oral supplementation is effective for most causes except pernicious anemia.

Metabolic Health Perspective

B12 status intersects with metabolic health through metformin use, homocysteine elevation, and energy metabolism. Optimal levels support metabolic function beyond preventing deficiency disease.