Hi ChetRoi,
A couple of questions for you! Have you already had homocysteine and MMA levels tested and shown to be elevated?
Also did your doctors (or yourself!) have any thoughts on the relevance of your SNPs in TCN2? I haven't had a chance to read too deeply into transcolbalamin deficiency yet, most of what I have read details extremely severe deficits presenting in early years due to homozygous mutation, but I'm encouraged by some newer work that shows late onset symptoms to a milder degree in heterozygotes...could TCN2 be at the root of this or do you feel there is more at play?
The only aspect of B12 I have had tested is the standard total B12 which was normal. I've just been to the doctor to state my case and request MMA and homocysteine tests but was told he can't do it for me, so I have just paid for some private testing. I've also signed up for 23andMe in the hope that I can access some sequencing data for possible relevant genes.
I have taken methylcobalamin for 3 days and there appears to be magic happening... I have so much energy I have been unable to sleep well the past couple of nights (definitely not complaining!)
Only 1.5mg capsules while I wait for higher dose sublingual to arrive. I had tried these same capsules last year when symptoms were at their worst and saw no obvious effect so discontinued, but that was before I started the ketogenic diet.
If I have blood samples taken for MMA and HC next week, would you recommend I stop supplements until these tests are complete? I'm concerned about masking any deficit.
B12 was one of the first things I asked about when I was hospitalised, I wrote it off when I was told that my levels were absolutely fine and that B12 had nothing to do with it. Thankyou so much for bringing this back into my focus!
Best wishes,
Dionne
Hi Dionne—
Glad to hear about the progress you are making.
Let me share a few data points with you concerning methylcobalamin (MeCbl) and its use.
First, the BIG rule of thumb with supplements (as you may know) is
“Start low, go slow.” As you are getting a significant result at 1.5 mg, I would not increase the dosage at this time. In fact, I would consider halving it.
Keep in mind MeCbl is a bioactive form of cobalamin, meaning it will provide methylation to other cellular processes in your body. It is possible that you are NOT cobalamin deficient but that the sudden energy increase is due strictly to the suddenly increased methylation. (Also, be aware that there is medical opinion that the B12 blood test reference range is set too high and that values in the low 400s should be considered as clinically “low”, not falling within the reference range.)
By all means, stop the MeCbl (and any other cobalamin OR folate supplementation) well before the MMA and HCY testing. (I would wait at least a week—very important!). In my case, I did not learn of the MMA and HCY tests until after I had begun MeCbl supplementation so, unfortunately, I had no valid basis to compare.
But it was very obvious in my case with the first MeCbl sublingual I took. Before that, I was close to needing a walker just to get around in my house. Any physical effort using my calf muscles caused that immediate burning pain we have all experienced when overstressing leg muscles (e.g., from too much bicycle pedaling). Within 18 hours of the first MeCbl, my legs felt much stronger and much more stable. Note the difference between this response and strictly an imparted methylation one. Because I had a clear cobalamin deficiency—my muscles and nerves were damaged and for such a long time--I did not intend to stop the supplementation for subsequent verification testing.
IMO, you should proceed with the MMA and HCY testing after a one-week MeCbl abatement. If they show an out of reference range result(s), consult with your Doc for further testing. If they are not out of RR, we may lean toward a possible cellular methylation problem and you should see a biochemical geneticist. But be prepared to get shoulder shrugs because there is so much for clinicians yet to learn about Inborn Errors of Metabolism (IEM). Many do not yet understand that protein expression presents on a gradient; it is not a binary outcome. That fact is why we have “late onset” IEMs as well as those found in newborns.
The genetic testing offered by 23andme is cursory. Yours will probably show methylation deficits but not much more that is useful. Keep in mind that the readout is usually nonspecific and only general guidance for the geneticist, if that. This is true because some folks with methylation deficient alleles (cellular mutations--SNPs) show no symptoms at all; again, medical science has much to learn here.
You may find yourself, over time, with no further diagnosis even though you have apparently demonstrated a hypomethylation situation. In this case, you may opt to continue to take MeCbl on a permanent basis to more “normalize” cellular processes. But a few words of caution here:
There are numerous scholarly papers extolling the benefits of MeCbl supplementation but there are also a few that assert it can cause increased growth of cancerous cells. In my personal situation, I have judged for myself for it to have a low risk of malignancy, and I am a former cancer patient. So, by hypermethylating your cellular processes, you may “activate” ALL processes, some of which may be detrimental to your well-being. YMMV. Keep in mind, though, MeCbl is widely used—at least in the United States.
The cautions are, of course, important to understand. This is why we take no more of a supplement than is necessary to do the job. Sometime “how much” is not obvious but I judge the best I can by body response and try to err on the low side. So, again: Start low, go slow.
With regard to the wakefulness…this is a common side effect of MeCbl supplementation. I take MeCbl at wake-up and only then—just once a day. If sleep remains disturbed for more than a week, consider reducing the amount of MeCbl you are taking. This side-effect passes over time for some people.
With regard to the transcobalamin issues—this is a rare B12 pathway metabolic error. The test for it is called an Unsaturated B12 Binding Capacity (transcobalamin) blood test—very specialized and not inexpensive. It measures the ability of your system to transport B12 to cells for necessary processes (e.g., metabolism). The standard B12 blood test cannot detect this genetic error. Should you decide to ask for this test, you MUST halt all B12 supplementation for at least one week prior to testing. Further, some labs offer this test only one day of the week so check ahead to get the draw date synced up with your B12 abatement.
If you wish to add another test after you have been off the B12 for a week, I’d add in a CBC with differential to examine your platelets. Low platelets can indicate B12 deficiency. If your platelets are low and do not normalize after MeCbl supplementation has been going for two weeks, it may imply more of a problem than B12 deficiency.
I am meeting with a biochemical geneticist next month and will discuss the TCN2 issue with her. I’ll let you know the outcome.
Your statement that “I had tried these same (1.5 mg MeCbl) capsules last year when symptoms were at their worst and saw no obvious effect so discontinued, but that was before I started the ketogenic diet.” is interesting to me. It indicates that to you there may be a relationship between ingested MeCbl and a glucose metabolite. I see such a relationship in my system but it is the inverse of your situation: when I take MeCbl, it reduces the numbness caused by carbohydrate consumption.
If you have more questions, I will try to answer. My own experience, BTW, has taught me clinicians are far from knowing all the answers but many will respond to patient research when offered to them as just an aid, but not a diagnosis. I don’t read any dubiousness of the usefulness of clinicians in your post but this thought reflects my own past errors in working with physicians many of who do not know much about genetics. We walk a narrow path sometimes.
