Undiagnosed: Numbness After Consuming Carbohydrates

Lamont D said:

Wow!
Wish I could have had that amount of testing decades ago.
Just a quick one.
I had a bacterial infection in my gut years ago, called heliocobacter pylori, and causes your gut brain trigger to create an imbalance in your blood, the successful antibiotic treatment could have also caused some issues, I'm told.
Despite your negative results, you still could have issues with your gut biotic.

Fasting and caloric intake should be quite straightforward balance to find.
Portion size is important in low carb lifestyle. You can alter it to gain weight as well. But again testing and experimentation is useful.
B12, as is other vitamins. For some weird reason, I don't have this sort of deficiency despite my restrictive diet.

I still need an interpreter tho for some of your post!

Best wishes on your forthcoming tests.

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Hey Lamont--

Thanks for the input.

I agree a small intestine bacterial overgrowth could be the problem. I've had a SIBO breath test and it was negative BUT they tested only for hydrogen gas, not methane as well. I will have this test repeated in the future as the symptoms are a pretty good match for my clinical phenotype and the test is sometimes hit or miss, as I understand.

With regard to B12 insufficiency or deficiency, the quick and easy (and inexpensive) test is to take a B12 supplement for a week to see if any improvements occur. Most folks agree that Methylcobalamin (not Cyanocobalamin) is the best form to take since the body does not have to break down the cyano into methyl and adeno; so the Methylcobalamin is ready to do its job. I would take a 5 mg lozenge (under the tongue) but for the first time, cut it in half. Second day, a full 5 mg; the same 5 mg for days 3 through 7. But check with your doctor first.

If there are no B12 pathway blockages (which are rare) and you DO have a B12 deficiency, you will have good results within a week--B12 is that fast. There is no prescribed upper dosage limit for Methylcobalamin BUT, as is the case with any medication/supplement, do not take more than needed. If you feel uncomfortable after taking it, of course, discontinue!

DionneT said:

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

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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.

DionneT said:

Hi ChetRoi,

Thanks for your insight. I will hold off on any more MeCbl until these tests are done. Do you think it may also be worth incorporating more carbohydrate into my diet in the days before testing?

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I would continue with the keto diet as you have applied it.

DionneT said:

I know that muscle burn well! When symptoms peaked early last year it was hard to walk properly because of it, it improved during the weeks of rest that followed but only to a point. Holding my arms up only briefly would result in burning. For me it was 2-3 days into ketogenic eating that this massively improved. It appears again after eating carbs, along with the numbness, some shooting bone pain and tinnitus.

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I also have (infrequent) tibial shooting pain and suddenly worsening tinnitus. How long have you had sinusitis, how often have you taken antibiotics for it, and which antibiotic? (Ongoing infection is also a symptom of B12 deficiency.)

DionneT said:

Maybe had I tried AdCbl instead of/as well as MeCbl last year I might have seen an improvment in nerve/muscle symptoms if it is the adeno- form that is required for healthy myelin. Do the two inter-convert efficiently? Or maybe the conversion is my issue... I will trial the different forms in isolation when I resume supplements.

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Typically, a person titrates MeCbl to the "best" level, then adds in smaller amounts of MethylFolate (bioactive B-9, which works intimately with MeCbl). Subsequently, add in a small amount of Adenosylcobalamin (AdoCbl). AdoCbl improved my apparent connective tissue inelasticity. Once you have a formula of these supplements that work well for you, stop taking one at a time to confirm the beneficial effect of the supplement. (i.e., the benefit should stop when no longer taking the supplement.)

Cyanocobalamin, the B-12 form everyone buys in the store, must be converted by the body to both MeCbl and AdoCbl before it can be used. MeCbl has effect in the cellular cytosol, AdoCbl is used by the cellular mitochondria. This why we often take both bioactive types of B-12 in lieu of Cyanocobalamin. Also, some folks cannot break down the cyano into its bioactive cofactors of MeCbl and AdoCbl.

I started MeFolate about 4 months after starting MeCbl. The dramatic change was in my lipid panel results. Lipids improved across the board between about 25% to 50%. IMO, you should run a lipid panel before restarting supplementation and a couple of months or so afterward to observe any change.

Every six months, I get the following blood tests:
Lipid panel
CBC with differential
Reticulocyte panel (if reticulocytes have ever shown out of the RR)
CMP (Comprehensive Metabolic Panel - glucose level, electrolyte and fluid balance, kidney function, and liver function.)

A question--Have you ever been exposed to organophosphates or other similar type poison (pesticide)?

***

DionneT said:

I've been prone to sinusitis for as long as I can remember, and had a fairly constant low level of discomfort from them since my teens. Usually every time I had a common cold my sinuses would flare up and would take weeks to settle back to baseline. I'm also very sensitive to weather changes to low pressure, I can tell a storm is coming when my brain feels swollen I unfortunately don't have these records but have had antibiotics for sinus infection maybe 5 times in past 10 years, usually amoxicillin. Last year's flare of symptoms began with numbness that started 4 days into a course of doxycycline. I had a run of infections the preceding months; chest infection, stomach virus, then cold/sinus infection. My grandmother had fairly constant sinusitis and it's an increasing issue for my sister who also has cystic acne. My cousin who has chronic pain has recurrent UTI. So there is certainly some recurrent infection in the family. Both sister and cousin have digestive issues too. I had a spell of gastritis/possible stomach ulcer in 2012 but no cultures or tests done to determine H. pylori or other cause. It was treated with omeprazole.

The ketogenic diet has reduced my sinusitis to almost none. Has diet/b12 also improved this for you?

The only pesticide exposure I have had was in 2014 to a nicotinamide whilst pregnant. A plant growth facility at work had been sprayed without our knowledge, I had dizziness and nausea briefly but no lasting effects.
My symptoms of numbness, muscle burn etc. had already appeared briefly before this point, in 2011 after the carbemazepine.

Have you had MRI of spine? My worst neuropathy symptoms affect c6 and s2 dermatomes. A herniated disc was found at c5/c6 but no mention of degeneration of the cord itself, and only head and neck were screened. Damage to dorsal root ganglia may explain our pattern of neuropathy? As I understand it they have high permeability so may be sensitive to toxic metabolites from carb dysmetabolism? I have some permanent numbness of heel and thumb/forefinger but sensation slowly returns everywhere else, maybe a gradual clearing of these metabolites, or possibly regeneration? I assume that the more often this assault happens, the more chance there is of permanent damage. So I should probably keep my carb challenges to a minimum...

Out of interest, is medicine your scientific background?

Best wishes,
Dionne

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Hi Dionne, finally getting back.

"The ketogenic diet has reduced my sinusitis to almost none. Has diet/b12 also improved this for you?"

I've had sinusitis since my days as a teenager; I'm approaching 71. The essentially life-long infections stopped with MeCbl repletion a little more than four years ago. I typically got three or four sinus infections annually that required three weeks of doxy to resolve.

"Have you had MRI of spine? "

Yes, about three years ago, investigating Subacute Combined Degeneration of the Spinal Cord. Relatively easy to diagnose--it has a characteristic butterfly appearance in the imaging. I did not have it suggesting my B12 problem either had not progressed to that point or, the problem was not a B12 deficiency at all.

I do not understand very well the neurological aspects of this disease. Can't comment on "Damage to dorsal root ganglia may explain our pattern of neuropathy" but I'll put it on my list to investigate; I, too, am most interested in syndrome commonality between us.

"I have some permanent numbness of heel and thumb/forefinger but sensation slowly returns everywhere else, maybe a gradual clearing of these metabolites, or possibly regeneration? I assume that the more often this assault happens, the more chance there is of permanent damage. So I should probably keep my carb challenges to a minimum..."

IMO, the damage will become permanent if enough assaults occur. Fingers/toes/feet are first because the disease attacks long nerves (axons, in my case) first.

"Out of interest, is medicine your scientific background?"

No, I'm not a student of medicine. Simply a case of a research interest borne of necessity. Truth be told, my background is counterintelligence and white hat hacking--medically retired ten years ago.

Finally, I want to give you a heads-up. Partly based on information from you about your signs and symptoms, I am investigating more deeply the possibility of a rare form of a diabetes-like condition, one in which MeCbl and alpha lipoic acid are antagonists to the toxic metabolitic byproducts produced when the carb dysmetabolism occurs, that I think may be behind this pathology.

Brunneria said:

Hi @ChetRoi

I must admit to having a bit of a problem distinguishing between your words and the quoted texts in your posts.

Any chance that you could give references for the source of the info when it isn't your own words?
Members often like to follow links back to the original websites and medical information, plus the forum has to be careful about plagiarism, so always best to give references, where possible.

Having said that, I am extremely impressed with the frequency and variety of the tests you have undergone.
Are you from the UK?

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Hi @Brunneria --

Thanks for the interest in my posts. I confess confusion though over your reference to "quoted texts". I would have to go back and review my posts but in general, I do not offer quotes. One that does come to mind was from a cell biopsy; it was clearly identified as such. If you have encountered something I have posted that to you is of questionable accuracy or appears to be the work of others, put it out here so I can address it. I do strive to use medical terms whenever possible--I have found clinicians actually *listen* instead of pushing out a dismissive suggestion of one's mental state when you can speak with understanding in their more precise language.

You've asked about my methods and perhaps motives; I understand policing of BBs so I'll open the kimono a bit for you. I do a good bit of research and often apply and discuss my findings when apropos. And I have been accused of being anal--a fair criticism as my diagnostic odyssey continues on and on and on, some of it on behalf of my bed-ridden youngest daughter in pain management for over ten years now and just diagnosed with Hypermobile Ehlers-Danlos Syndrome. I have been keeping daily excel spreadsheets for more than four years. And tracking of more than a year's worth of daily consumables, broken out by macronutrient until last year when my keto diet was well established and I learned no physician I had been seeing had an interest in them.

I have learned that in the absence of both professional medical leadership and basic scientific curiosity, trend spotting is one of the best tools the patient can use. It's also important to track the testing that I've done--in particular, supplementation testing because there are so many options, and dosage plus interactions are very important to review.

Since your questions implied an interest in my bonafides, I will tell you my research and subsequent trials are the reason I am not in a wheelchair today--or worse. In the United States where I live (Florida), clinicians have their practices and druthers; they simply are not interested in dealing with zebras. That is a fact. And one does not waltz into a Mayo Clinic for tertiary center care--their triage effort can exclude you ("your case is too complex for us").

Now, going forward I certainly can and am willing to cite the scholarly papers I draw information from, although I will mention some of them will not be reachable for less than US $35.00 because they are recently published and vended through portals.

In general, a lot can be learned by anyone interested in doing the research work through www.scholar.google.com. And that especially includes physicians whose clinical practice office routine often does not include time to read journals in their own discipline. It's too bad because folks like myself and others who were drawn to post in these forums might then have a more realistic chance for a diagnosis instead of having to spend so much time carrying the water in an area in which we lack formal training.

Sorry I could not be more sun-shiny but today this is about my best.

DionneT said:

Hi ChetRoi, thanks for getting back to me. Subacute combined degeneration of spinal cord has dominated my reading for the past couple of days and was my next thing to ask you about, but you have already ruled that out so I will move on!

The rare diabetes-like condition sounds intriguing, is this something that has been identified before or something entirely new? Would that be the possible means by which the MeCbl had little to no effect on me pre-keto, because it would be sequestered by the toxic metabolite?

One more symptom that I don't think I have mentioned yet but may be relevant involves joints - I had ongoing pain/clicking of TMJ for years (right side, same as most symptoms) and this largely resolved with a ketogenic diet. After carb challenge this comes back, along with pain and 'looseness' of right knee joint and clicking of spine.

Has your daughter had any relief from b12 supplements or carb restriction?

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My daughter responded well to MeCbl over a year ago but it exacerbated her pain. Her pain levels at the time were 7-8 when under very strong pain management. She has permanent damage to her stomach lining, a lot of vomiting; some carbs are the only thing she can sometimes keep down.

Here's a link to a summary of a new finding (about one year old): http://www.cell.com/cell-metabolism/fulltext/S1550-4131(18)30114-1
"Elevated Levels of the Reactive Metabolite Methylglyoxal Recapitulate Progression of Type 2 Diabetes"

I'm just starting to look at it; haven't purchased the article yet (Cell Metabolism) from the portal. The research was done with flies, not human subjects but that's not unusual. Point is it's leading edge and can offer educated ideas.


"Would that be the possible means by which the MeCbl had little to no effect on me pre-keto, because it would be sequestered by the toxic metabolite?"

This is a puzzle. Try to think of things that may have been different the first time you took MeCbl.

Lamont D said:

Wow!
Wish I could have had that amount of testing decades ago.
Just a quick one.
I had a bacterial infection in my gut years ago, called heliocobacter pylori, and causes your gut brain trigger to create an imbalance in your blood, the successful antibiotic treatment could have also caused some issues, I'm told.
Despite your negative results, you still could have issues with your gut biotic.

Fasting and caloric intake should be quite straightforward balance to find.
Portion size is important in low carb lifestyle. You can alter it to gain weight as well. But again testing and experimentation is useful.
B12, as is other vitamins. For some weird reason, I don't have this sort of deficiency despite my restrictive diet.

I still need an interpreter tho for some of your post!

Best wishes on your forthcoming tests.

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Lamont--

I expect you haven't had this type of testing but have you had anyone measure your methylation status, or have you gotten any indication your system is hypomethylated? While I am not suggesting this, one way to test is to take a methylated supplement (e.g., methylcobalamin) to determine if symptoms such as fatigue are reduced or eliminated. Another way to get some indication, though not precise by any measure, is to determine if you have genetic mutations (and which ones) in the MTHFR gene. Lots of research being done to understand this gene and its more commonplace mutations.

Comments from you and some others in the UK indicate to me that medical testing is not as commonplace in the UK as in the US but I wanted to ask because it is possible my symptoms are less from a B12 deficiency than from systemic hypomethylation, so I am probing in this area.

I will be asking a biochemical geneticist next week about this possibility but I was curious if you had any such experience.

Hi @DionneT and @J_Eicher,

I have just begun a personal trial of a supplement widely used for glucose regulation. It’s early for me to draw a conclusion but the result in eliminating the acute carb-induced distal numbness over the past two weeks has been dramatic.

Berberine is known to many endocrinologists. I am taking 500 mg just before each meal, i.e., t.i.d. and have found not only carb-heavy meals but even added well-sugared desserts do not cause the distal numbness to occur, for the first time in 4 1/2 years.

Many clinical trials have apparently substantiated the efficacy of this supplement in glucose regulation; here is one from NIH:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2410097/

It is chemically similar to metformin and reportedly just as effective.

Jana, the B12 I found to be effective in reducing the sensorimotor polyneuropathy was methylcobalamin and not the OTC cyanocobalamin B12, which you may already know. My neuropathy is largely axonal, which may be different from yours.

If either of you decide to run a trial, please let me know how it goes.

—Bob