Your B12 status deserves a closer look
B12 has always been something I’ve had to keep an eye on.
For much of my life, my B12 sat at the low end of normal. Because it was technically within range, it was never flagged.
It wasn’t until I looked at my genetics that it started to make sense. I have variants in several genes involved in B12 transport and metabolism — including TCN2, MTRR and FUT2. Suddenly, my lifelong low B12 didn’t seem so random.
Why B12 matters
B12 is essential for red blood cell formation, DNA synthesis, energy production and nerve health — including maintaining myelin, the protective layer around your nerves. It also plays a key role in methylation. [1, 2]
A deficiency can show up as fatigue, brain fog, mood changes, pins and needles, a sore or smooth tongue, balance issues and cognitive changes. On a blood test, it can also show up as enlarged red blood cells (macrocytic anaemia). And if it goes on long enough, some nerve damage may not be fully reversible. [1]
The problem with a single blood test
The standard test, serum B12, measures all the B12 in your blood — but not all of it is in a form your body can actually use. In Australia, a deficiency is generally only considered likely below around 133 pmol/L, which is crazy. Between 133 and 258 pmol/L, the result is officially “indeterminate” — meaning the test can’t say either way. Some labs have even treated anything at or below 400 pmol/L as inconclusive and run extra testing. In my view, that’s not a grey zone, it’s a red flag. [1, 7, 8]
These days, I rely on two more useful markers instead:
Active B12 (holotranscobalamin) — the portion available to your cells. [3]
MMA (methylmalonic acid) — a by-product your cells need B12 to clear. If they’re not getting enough, MMA builds up — even while serum B12 still looks normal. It can be tested in blood or urine. [1, 3]
Even with my serum B12 sitting comfortably above 400, my MMA came back right at the top of the range last year — a sign my body may have been working hard to use it. It’s since started to come down, which is exactly what I wanted to see.
Neither active B12 nor MMA is always part of a standard blood test, and they can come with an out-of-pocket cost. Active B12 is included in the blood panel in our Foundation Program, and MMA is part of the DUTCH test in our Perimenopause Program.
Where my genes come in
TCN2 makes the protein that transports B12 around the body. I’m homozygous for a variant linked with less efficient B12 delivery. [4]
MTRR keeps methionine synthase — a key B12-dependent enzyme — working. I’m homozygous here too. [2]
FUT2 — I carry one copy of a variant linked with higher serum B12, but mostly the inactive form. So a serum test can make B12 status look better than it is. [5]
I’m also compound heterozygous for MTHFR (C677T and A1298C).
None of these explain everything on their own. But together with a lifelong pattern of low B12, they gave me a better question to ask than “Is my B12 in range?”
It’s not just what you eat
B12 comes mainly from animal foods, so food first is always my starting point. But absorbing it depends on a healthy gut — low stomach acid (which becomes more common as we age), gut conditions like Crohn’s or coeliac disease, and long-term use of medications like metformin or acid blockers can all affect your B12 status, no matter how much you eat. If your B12 is low, gut health needs to be looked at first. [1, 7]
B12 and folate need to work together
I learned this one the hard way. Before I knew better, I was taking methylfolate to support my MTHFR variants when I had very little B12 on board — and I started experiencing anxiety.
B12 and folate are closely connected. Without enough B12, a key step in the methylation pathway slows down and folate can become trapped — what’s known as the methylfolate trap. [6]
High doses of folate can also mask a B12 deficiency — correcting those enlarged red blood cells while nerve damage quietly continues. [1, 6]
These days, I make sure my B12 is on board first, get most of my folate from food, and look at the whole pathway rather than just adding more methylfolate.
So don’t stop at “normal”
Ask what your active B12 and MMA look like, whether you’re absorbing B12 properly, and what else might be going on.
Because the most useful information isn’t always a result that gets flagged.
References
National Institute for Health and Care Excellence. (2024). Vitamin B12 deficiency in over 16s: Diagnosis and management (NICE Guideline NG239). https://www.nice.org.uk/guidance/ng239
Lyon, P., Strippoli, V., Fang, B., & Cimmino, L. (2020). B vitamins and one-carbon metabolism: Implications in human health and disease. Nutrients, 12(9), 2867. https://doi.org/10.3390/nu12092867
Green, R., Allen, L. H., Bjørke-Monsen, A.-L., Brito, A., Guéant, J.-L., Miller, J. W., Molloy, A. M., Nexo, E., Stabler, S., Toh, B.-H., Ueland, P. M., & Yajnik, C. (2017). Vitamin B12 deficiency. Nature Reviews Disease Primers, 3, 17040. https://doi.org/10.1038/nrdp.2017.40
Oussalah, A., Levy, J., Filhine-Trésarrieu, P., Namour, F., & Guéant, J.-L. (2017). Association of TCN2 rs1801198 c.776G>C polymorphism with markers of one-carbon metabolism and related diseases: A systematic review and meta-analysis of genetic association studies. The American Journal of Clinical Nutrition, 106(4), 1142–1156. https://doi.org/10.3945/ajcn.117.156349
Velkova, A., Diaz, J. E. L., Pangilinan, F., Molloy, A. M., Mills, J. L., Shane, B., Sanchez, E., Cunningham, C., McNulty, H., Cropp, C. D., Bailey-Wilson, J. E., Wilson, A. F., & Brody, L. C. (2017). The FUT2 secretor variant p.Trp154Ter influences serum vitamin B12 concentration via holo-haptocorrin, but not holo-transcobalamin, and is associated with haptocorrin glycosylation. Human Molecular Genetics, 26(24), 4975–4988. https://doi.org/10.1093/hmg/ddx369
Scott, J. M., & Weir, D. G. (1981). The methyl folate trap: A physiological response in man to prevent methyl group deficiency in kwashiorkor (methionine deficiency) and an explanation for folic-acid-induced exacerbation of subacute combined degeneration in pernicious anaemia. The Lancet, 2(8242), 337–340. https://doi.org/10.1016/S0140-6736(81)90650-4
Bedz, D., & Forsyth, C. (2026). Vitamin B12 deficiency: Testing and treatment. Australian Prescriber, 49(2), 55–60. https://doi.org/10.18773/austprescr.2026.012
Smith, A. D., & Refsum, H. (2012). Do we need to reconsider the desirable blood level of vitamin B12? Journal of Internal Medicine, 271(2), 179–182. https://doi.org/10.1111/j.1365-2796.2011.02485.x
