04/19/2026
This is a very good article if you have been told your B12 level is normal but you still have symptoms.
However, I do not agree with his words that high dose oral B12 is ok for PA patients. We know that it is not.
Most people get a B12 test, see "normal" on the result, and assume they're fine. The problem is that the standard B12 test measures something that isn't quite what most people think it is.
Here's what's actually happening in your blood. B12 rides around attached to one of two different "delivery trucks." About 70-80% of it is bound to a protein called haptocorrin, and this truck is essentially headed to the dump. Your liver grabs it and clears it out of circulation. None of it reaches the cells that actually need B12 to do work. The remaining 20-30% is bound to a different protein called transcobalamin. This is the real delivery truck. It docks with your cells and hands off B12 for actual use.
Your standard B12 test measures both trucks combined. The number that comes back doesn't distinguish between what's being delivered to your cells and what's on its way to the liver for disposal. Two people can have the same total B12 number and one can have plenty of active B12 reaching cells while the other is functionally deficient. The active fraction, called holoTC, can be measured separately. Most doctors don't order it because it costs more and most insurance panels default to the cheaper total-B12 test.
It gets one layer deeper. Even when B12 gets inside your cells, it has to be converted into one of two working forms before it can do anything. One form runs a cleanup reaction in the main body of your cell that's essential for making the chemical your body uses to turn genes on and off, build neurotransmitters, and maintain the insulation around your nerves (called myelin). The other form runs a reaction inside your cells' energy factories (mitochondria) that lets your body process certain fats and amino acids into fuel. Different job, different location, same vitamin.
This matters because of how we test for true B12 deficiency. When the mitochondrial job isn't getting done because B12 is running low, a waste product called methylmalonic acid (MMA) builds up in your blood. MMA only rises for this one reason. Measuring it tells you directly whether your cells actually have enough usable B12, regardless of what the standard test says. A related marker called homocysteine also rises when B12 is low, but homocysteine rises for several other reasons too (low folate, low B6, certain genetic variants, kidney problems, just being older), so it's less specific. A high homocysteine tells you something is wrong. A high MMA tells you B12 specifically is wrong.
So the testing hierarchy looks like this. Total serum B12 is the cheapest test and the most commonly ordered, but it misses about a quarter to a third of people who are actually deficient. HoloTC directly measures the active fraction that reaches your cells. MMA confirms whether deficiency is damaging your biology at the cellular level.
Who should care most about this. Adults over 60, because stomach acid production drops with age and you need stomach acid to release B12 from food. Synthetic B12 from supplements sidesteps this problem because it isn't stuck to food protein. People on metformin long-term, because the drug interferes with B12 absorption and 10-30% of chronic users end up deficient. People on acid-blocking drugs (PPIs) long-term, for the same stomach-acid reason. Vegetarians and vegans without reliable B12 supplementation. Anyone with unexplained fatigue, numbness or tingling in hands or feet, memory or concentration issues, or a type of anemia your doctor might call macrocytic or megaloblastic. Pregnant and breastfeeding women. People who have had weight loss surgery.
A note about all those different B12 supplement forms you see on shelves. Cyanocobalamin, methylcobalamin, adenosylcobalamin, and hydroxocobalamin all get marketed with very different price tags. The "methyl is bioidentical" and "skip the conversion step" claims are supplement marketing, not biology. Every oral B12 form, no matter what it says on the label, gets routed through the same processing step inside your cells before your body decides which working form to make. For the vast majority of people, the form on the label matters less than the dose and whether you take it consistently. The rare exceptions are people with specific genetic variants affecting B12 trafficking, where form-specific treatment can matter clinically, but that's a specialist-diagnosed situation, not a general rule.
On dosing. High-dose oral B12 (1,000 mcg or more daily) works even in people with pernicious anemia, a condition where the normal absorption pathway is broken, because a tiny fraction of each dose (about 1-2%) crosses the gut by plain diffusion regardless of whether the main absorption machinery is working. That said, injections remain the standard of care when deficiency is severe, when nerve symptoms are already present, or when pernicious anemia is actively flaring. High-dose oral is for maintenance, not emergency correction.
The bottom line. If you've been told your B12 is "normal" and you still have symptoms that line up with deficiency, the relevant conversation with your doctor is about holoTC and MMA. These tests exist. Most insurance covers them with appropriate clinical justification. They answer questions that the standard test alone can't.
Sources:
Nexo E, Hoffmann-Lücke E. Am J Clin Nutr. 2011;94(1):359S-365S.
Fedosov SN, et al. Clin Chem Lab Med. 2015;53(8):1215-25.
Hvas AM, Nexo E. Haematologica. 2006;91(11):1506-12.
Allen LH. Adv Nutr. 2012;3(1):54-55.
