Active vitamin B12

Active B12, also called holotranscobalamin, measures the portion of circulating vitamin B12 bound to transcobalamin, which is the carrier that delivers it into cells. The rest is bound to haptocorrin and is not available for uptake.

That distinction is the reason this marker is worth measuring instead of total B12. Total B12 counts both fractions, so it can read as adequate while the usable fraction is already falling. Active B12 drops earlier, which makes it the more sensitive early indicator.

B12 is required for red blood cell formation, for the myelin sheath around nerves, and for the methylation cycle that recycles homocysteine.

Below 25 pmol/L indicates that the usable fraction is depleted. Effects commonly reported include fatigue, pins and needles in hands or feet, poor balance, low mood and difficulty concentrating.

The two broad causes are intake and absorption. B12 occurs almost exclusively in animal foods, so vegan and largely vegetarian diets need a supplemented source. Absorption depends on stomach acid and on intrinsic factor, so it falls with age, with atrophic gastritis, with proton pump inhibitor use and with metformin.

Nerve-related effects are the ones worth acting on promptly, so a low result with any neurological symptom is a reason to speak to your practitioner rather than to wait for a retest.

Between 25 and 170 pmol/L your active B12 sits inside the reference range for this panel.

If you eat little or no animal food, a result in range means your current supplemented source is working. It is not a reason to stop, since stores deplete slowly and the result would lag the change by a long way.

Above 170 pmol/L is nearly always supplementation. B12 is water soluble and excess is generally excreted, so high results from food alone are rare.

High-dose oral or injected B12 will push active B12 above the range without that indicating a problem in itself.

A high result in someone who is not supplementing is the case worth investigating, since it can accompany liver or blood conditions. That is a conversation for your practitioner.

Two Western trends push in the same direction. Plant-forward eating has grown without the supplemented B12 source that a diet without animal foods requires, and long-term acid suppression has become common enough to affect absorption at population scale.

Metformin, one of the most widely prescribed drugs in the world, reduces B12 absorption over years of use.

Liver is by a wide margin the densest source. Shellfish, particularly clams, are next.

Fish, meat, eggs and dairy all contribute. There is no reliable unfortified plant source, which is the whole difficulty for plant-based diets.

Nutritional yeast and fortified plant milks are fortified rather than natural sources, and their B12 content depends entirely on the manufacturer.

Methylcobalamin and adenosylcobalamin are the coenzyme forms. Cyanocobalamin is cheaper, stable and effective for most people.

Sublingual tablets bypass the intrinsic factor pathway, which makes them the sensible route where absorption rather than intake is the limiting factor.

If absorption is the problem, oral doses need to be considerably larger than the dietary requirement, because passive diffusion accounts for only a small percentage of a given dose.