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William Wallace: Hidden Vitamin B12 Deficiency and Better Testing Methods
William Wallace/X
Apr 21, 2026, 15:46

William Wallace: Hidden Vitamin B12 Deficiency and Better Testing Methods

William Wallace, Co-Founder and Chief Scientific Officer at Supplement Success Solutions, shared a post on X about a recent article by Ralph Carme, published in The American Journal of Clinical Nutrition, adding:

“Your B12 test measures two things and cannot distinguish between them.

Seventy to eighty percent of circulating vitamin B12 is bound to haptocorrin. The liver clears this fraction, and it never reaches the cells.

Twenty to thirty percent is bound to transcobalamin. This is the biologically active fraction that is actually delivered to tissues.

Clinicians refer to it as holo transcobalamin.

Standard serum vitamin B12 tests add both fractions together. A result that appears ‘normal’ can still mask a cellular deficiency, and these

tests miss approximately twenty-five to thirty percent of true deficiency cases.

The better tests are:

  • Holo transcobalamin, which directly measures the active fraction
  • Methylmalonic acid, which rises only when cellular vitamin B12 is truly insufficient and is considered a functional gold standard
  • Homocysteine, which also rises in deficiency but is less specific because it can also increase with low folate, low vitamin B6, mthfr variants, kidney issues, aging. Less specific.

Who should care: adults over sixty years of age, long-term metformin users (ten to thirty percent develop deficiency), proton

pump inhibitor users, vegetarians and vegans, and anyone with unexplained fatigue, neuropathy, cognitive changes, or macrocytic anemia.

If vitamin B12 is reported as normal but symptoms do not match, it is reasonable to request holo transcobalamin and methylmalonic acid

testing.”

Title: Biomarkers of cobalamin (vitamin B-12) status in the epidemiologic setting: a critical overview of context, applications, and performance characteristics of cobalamin, methylmalonic acid, and holotranscobalamin II

Authors: Ralph Carme
William Wallace: Hidden Vitamin B12 Deficiency and Better Testing Methods

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