Vitamin B12 and Testosterone in Adult Males
Vitamin B12 supplementation should be considered in men with low testosterone, as emerging evidence demonstrates a direct association between B12 status and testosterone levels, though B12 is not a primary treatment for hypogonadism itself. 1
Evidence for B12-Testosterone Relationship
The most recent high-quality study examining this relationship found that among 303 men with infertility, serum vitamin B12 demonstrated a significant independent correlation with total testosterone levels (ρ = 0.19, P = 0.001). 1 Men in the highest tertile of B12 had 56% reduced odds of testosterone deficiency compared to those in the lowest tertile (adjusted OR = 0.44; 95% CI: 0.22,0.87, P = 0.02). 1
This relationship appears clinically meaningful: For every unit increase in serum B12, there was a corresponding increase in total testosterone (adjusted β = 0.0005, P = 0.03). 1 The study specifically demonstrated that low serum B12 is associated with impaired androgenic hormonal profiles that impact spermatogenesis. 1
Mechanistic Considerations
Animal studies provide biological plausibility for this relationship. In rats fed a B12-deficient diet for 100 days, testicular B12 content decreased distinctly, accompanied by significant reductions in testes weight and morphological changes including atrophy of seminiferous tubules and aplasia of sperms and spermatids. 2 These testicular findings were directly ascribable to B12 deficiency. 2
Clinical Application Algorithm
When evaluating men with low testosterone:
Screen for B12 deficiency in men presenting with symptoms of hypogonadism (decreased libido, erectile dysfunction) by measuring morning total testosterone using an accurate assay. 3
Measure serum B12 in men with confirmed low testosterone, particularly those with risk factors for B12 deficiency (age >60, metformin use >4 months, PPI use >12 months, vegetarian/vegan diet). 4
Consider functional B12 testing if serum B12 is borderline (180-350 pg/mL) by measuring methylmalonic acid (MMA), as standard serum B12 testing misses functional deficiency in up to 50% of cases. 4, 5, 6
Treat B12 deficiency when identified: Use oral supplementation with 1000-2000 μg daily of methylcobalamin, hydroxocobalamin, or adenosylcobalamin (preferred over cyanocobalamin for superior bioavailability). 4, 7
Important Caveats
B12 is not a replacement for testosterone therapy. The American Diabetes Association guidelines clearly state that testosterone replacement in men with symptomatic hypogonadism has established benefits including improved sexual function, well-being, muscle mass and strength, and bone density. 3 B12 supplementation should be viewed as an adjunctive intervention that may optimize the hormonal milieu, not as primary treatment for hypogonadism.
In one study of men with chronic testicular pain, 76% had relative deficiencies in testosterone or B12, and when these deficiencies were corrected, over 80% reported symptom improvement. 8 However, this was a pain syndrome population, not men with primary hypogonadism.
The prevalence of combined deficiencies is notable: Mean testosterone levels are lower in men with diabetes compared to age-matched controls, though obesity is a major confounder. 3 Given that B12 deficiency is also common in diabetes (particularly with metformin use), screening for both is clinically prudent. 4
Practical Recommendations
For men with confirmed testosterone deficiency and B12 deficiency: Correct the B12 deficiency first or concurrently with testosterone replacement, as optimizing B12 status may enhance the androgenic profile. 1 Use bioidentical B12 forms (methylcobalamin, hydroxocobalamin, or adenosylcobalamin) at 1000-2000 μg daily orally, which is as effective as intramuscular administration for most patients. 4, 7
Monitor response by rechecking testosterone levels after 3-6 months of B12 repletion, along with B12 levels to confirm normalization. 4 If testosterone remains low despite B12 correction, proceed with standard testosterone replacement therapy per Endocrine Society guidelines. 3