All about B12 Testing

B12 is usually measured at total B12 (NHS) and is not necessarily a good guide to usable B12 levels. In blood it is bound either to haptocorrin (inactive) or transcobalamin (active). If we have a measure for active, then that gives us a better picture of B12 available for utilisation, although still might not be the whole story of course, because it still doesn’t tell us about clinical need or actual utilisation, as is the case with any blood test. What do the enzymes do with it when they use it as a cofactor? This is where SNPs (giving us a picture of potential reduced or upregulated enzymatic function) or biomarkers that are a reflection of B12 activity (homocysteine/MMA etc), can help.

In terms of levels, we'll use OptimalDX (in UK, FunctionalDX), as a reference point, although there is some variation in opinions on ranges as usual. There is no 'one truth' as levels are agreed upon by various scientific bodies by consensus. OptimaDx range for total is 450-800 pg/mL (advise investigation if below 542 pg/mL (400 pmol/L) or above 881 pg/mL (650 pmol/L). As Active is roughly 10 - 30% of total, someone in “normal,” range might actually be B12 deficient. OptimalDx benchmarks active B12 at 54-188 pmol/L, suggesting investigation if below 70 (see below).

So, low total B12 is likely to be an issue, whatever. If we see that (and of course in context of SNPs), we’ll want to do something. BUT..

‘Normal' total B12 may still not be sufficient. UK NHS considers above 250 pg/mL to be normal (BUT OptimalDx value is at least 542 pg/mL) And of course we would want to consider if it’s sufficient for the person’s needs, available, and being utilised. So if between approximately 25 and 500, we’d want to look at active B12 if we can, and/or MMA/homocysteine (functional biomarkers that indicate if being used), symptoms (fatigue, neurological), and SNPs (potential down regulation of genes using B12). In other words - NHS ’normal’ - look at the number and investigate further.

Even if we are at or above our optimal levels, there might be too little active available or, if there is, being utilised, so we could we should always consider SNPs, checking active levels if we don’t know, and/or MMA/homocysteine as biomarkers. Again, blood tests only tell us levels of availability NOT need/usage.

High blood levels of B12 are poorly understood. For one thing, some ranges can go as high as 1300pmol. For another, we don’t know high is unsafe (no evidence it is). Here’s a useful article that looks at some reasons for high B12. There are the pathologies that are arguably rare and unlikely, but should be ruled out, like liver dysfunction etc, or that in fact the high B12 might be reflective of a functional  deficiency: that it might not be  active B12 that is high (also citing antibody-transcobalamin complexes as a source of high B12 - autoimmunity), that there could be compounding factors that reduce B12 utilisation like oxidative stress, and we would add, folate cycle issues resulting in a ‘B12 block’ so that there is inadequate 5MTHF to use up B12 in the methionine cycle.
So, for high B12, probably don’t supplement high doses of B12. Rule out major pathologies - cancer/liver/kidney issues. Look at markers/clinical presentation SNPS to see if folate issues, oxidative stress, and work on what is needed to  support B12. It's unlikely some B12 supplementation would harm and it might help utilisation (by increasing active to some degree), but only if addressing wider issues.
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