Have i messed up the MMA/Homocysteine test by only ceasing B Complex and B12 sublingual for 3 days prior?

[Gillybean1]

My booking for the blood test came earlier than expected, so i was only able to ceased supps for 3 days prior. I am looking to see if i have a 'functional B12 deficiency' to explain many of the typical unresolved and getting worse symptoms i have had for 10 years+.

Result MMA serum 23.0 ug (range <32)

Homocysteine 5.22 (range 3.70- 10.40 umol)

All other bloods were good, Kidney, WBC,RBC, Liver all ok except ALP slightly up at 129 (range 35-104 ) but this was in line with gut inflammation/flare on the day of test, all other Liver results in range and been passed as ok.

I gather on this forum that although the MMA/Homocysteine may look 'good' on paper ,that it may not be a conclusive test.

Any thoughts ,greatly appreciated, thank you , G

[fbirder]

A functional deficiency is when you have plenty of B12 in the blood but it's not going to the right places in the tissues.

To prove a functional deficiency you need to a) have high levels of B12 in your blood and, b) show that it's not getting into the cells

The MMA/hCys tests can prove b). But if you do not have a) then you have low levels of B12 in your blood - a normal B12 deficiency.

So you need to keep up with your normal routine of supplementation to prove a functional deficiency.

[Gillybean1 in reply to fbirder]

Hello fbirder, Thank you for your reply.

Sorry i have confused myself now. I meant to add that my B12 Active was 256.0 pmol (25.1-165)

Homocysteine 5.22 (3.70-10.40)

MMA serum 23.0 (<32)

So does the B12 being high, and still supplementing up until 3 days before the blood test , and the MMA being higher end of the range indicate a 'functional B12 deficiency' or not please?

Hoping you can advise, kind regards, G

[fbirder in reply to Gillybean1]

Not.

You have high levels of B12 in the blood, but you do not have raised MMA or hCys. So there is no evidence for a functional deficiency.

[jimmel196 in reply to fbirder]

I am definitely not a scientist and am now confused. I thought that high serum b12 levels would potentially cause a false normal homocysteine level and mma level. As always, thank you for your information.

[fbirder in reply to jimmel196]

MMA and hCys are chemicals that are used up in reactions mediated by B12. If there isn't enough B12 in the body, or it's not getting to the right places in the cells, then levels of MMA and/or hCys will increase.

In the overwhelming majority of people high (or normal) levels of B12 will keep levels of MMA and hCys down. You will get true normal levels. There's no such thing as false normal levels.

There are other problems that can cause them to be raised, however, such as liver/kidney problems. So raised levels alone aren't a definite indication of a B12 deficiency.

High levels of B12 in the blood, with raised MMA and/or hCys can indicate a functional deficiency. But that is rare. It's more likely that the MMA or hCys is raised by one of the other factors. Once those have been ruled out then a diagnosis of a functional deficiency can be made.

A lot of people assume that they have a functional deficiency because they need to inject very often, even though their blood B12 is astronomically high. But most of the time they will have normal MMA and hCys. Nobody known why they need to inject more often.

I still believe that there's a third function of B12 that doesn't have a handy marker like MMA or hCys (at least not one we know about). I'd love to do a metabolomic study to look for such a thing. Where you have a group of people with a B12 deficiency (untreated) and a control group of people with no B12 problems.

You collect blood and urine from them all and look at all the components of the bodily fluids, trying to find a difference - something that is in the test group and not the control, or vice-versa. But it wouldn't be easy - there are thousands of different chemicals, all of which will vary a lot between individuals.

But if somebody has a spare £20 million, it should be doable.

[jimmel196 in reply to fbirder]

Thank you for that great explanation. I now have a much better understanding of the association of b12 to mma and homocysteine.

[Gillybean1 in reply to jimmel196]

me too, confused that is, G

[Gillybean1 in reply to Gillybean1]

Hello fbirder,

Thank you for your reply, and taking the time to reply.

Hmm, i think im rather disappointed now,as i have no explanation for burning scalloped tongue, numb fingers, tinnitus, curling under toes, weakness, digestive issues with protein,facial nerve numbness and spasms, and many more, a Mother and Grandmother with PA.

Can you help me understand the pathways please? Why and how does sublingual B12 and Injecting B12 get to do the job, when ordinary supplements or food can not. I understand the HCL,Pepsin, I Factor with PA, but how does under tongue and intramuscular get to the right place?

Kind regards, G.

[fbirder in reply to Gillybean1]

Under the tongue doesn't work if you have PA, otherwise nobody would ever need injections.

Normal people can produce the protein Intrinsic Factor (IF) in their stomach. When that meets up with a B12 molecule in the duodenum (the first part of the small intestine) the two bind together. The IF-B12 combination moves down the small intestine until it reaches the ileum (the last bit before it all goes into the large intestine). In the wall of the ileum are special cells whose job is to recognise IF-B12, grab hold of it and suck it into itself. Inside these special cells the IF is split from the B12, which is then squirted into the bloodstream.

If you have PA then you can't make IF, so any B12 in the gut passes straight through and goes down the toilet.

So the only way you can get B12 into the blood is to bypass the gut. Injecting B12 into muscle or fat tissue allows the B12 to pass through the tissue in the intracellular fluid (the fluid between the cells). When it encounters a blood vessel it passes into that and gets taken away. As far as the body can tell, its exactly the same as if it had been absorbed from the gut - because it is exactly the same.

The blood then carries the B12 around the body. The B12 is bound to one of two proteins - haptocorrin (HC) and transcobalamin (TC). TC-B12 is the only sort that can enter the cells, it's called 'Active' B12. Nobody knows what HC-B12 is for.

When a cell needs B12 receptors on the outside of the cell grab hold of TC-B12 and drag it into the cell. The TC is removed as is the top bit of the molecule - the hydroxo, cyano, adenosyl, or methyl, forming cob(II)alamin. From then on all forms of B12 are identical.

The cob(II)alamin then gets carried to the places in the cell where it is needed.

B12 from gut to cell

[Gillybean1 in reply to fbirder]

Hello fbirder,

Got it, thank you for that.

And finally,the NLM paper PMID 10337865 May 1999 doi, 10.1016/s0026-0495(99)90062-8 J Dierkes, re Supplementation with Vit B12 decreases Homocysteine , Folate and MMA , only refers to ESRD end stage renal disease?

Kind regards G