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methylation, hypohomocysteine and muscle wasting?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by fozzaw, Nov 17, 2012.

  1. fozzaw

    fozzaw

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    It took me months of building up manganese, molybdenum, choline+inositol and TMG but I can finally tolerate methylfolate with tolerable side effects. Every time I tried taking it before, I got very tense shoulder muscles and too much inflammation from it, and had to stop after a couple days. The first week on methylfolate (400mcg quatrefolic/day) was a little rough with increased inflammation but it seems to have gone away. The best part is that my allergies are hugely improved, starting couple weeks after starting methylfolate, and taking supplemental SAM-e now makes me feel a little weird. I was able to shovel moldy cedar/spruce/pine woodchips, damp compost with heavy trichoderma sporing for hours without taking SAM-e or an antihistamine for the first time since I suddenly acquired my many allergies a few years ago.

    Now I'm having a problem with slowly wasting muscles and some associated fatigue. It's a little too early to say for sure yet, but I think it may be hypohomocysteine because:
    • too much P5P makes it worse, and it also makes me sleep all day (didn't do that before). if i don't take some P5P biweekly or so, my muscles start to ache. I generally avoid P5P as much as possible so that I can tolerate thiol foods.
    • methionine seems to alleviate it temporarily, but it makes me feel heavy in the liver so I've tried only small amounts. it's always made me feel like that but i can tolerate it a lot better than before since adding choline.
    • I notice people often take methionine with TMG but I didn't, presumably for avoiding homocysteine depletion but never stated
    • it gets worse with more methylfolate
    I haven't been able to find much information on this, but if anyone has any experience with this problem, I'm interested in how you dealt with it.
  2. UM MAN

    UM MAN

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    Have you checked the obvious, cortisol, E2, Total and free Testosterone(male?), SHBG, DHT, DHEAs,
    progesterone?
  3. fozzaw

    fozzaw

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    An update: I've found that lysine (1/4 tsp per meal) alleviates almost all the muscle wasting problems. I have also been taking a little threonine at night (1/4 tsp) but it makes me tired the next day. It did help with averting a sinusitis flare-up though. I didn't feel good taking methionine so I haven't taken any this week.

    The reason I decided to try lysine was that I had some minor scratches that drew blood and the skin remains red (slightly inflamed) despite it being many weeks it happened. After five days of lysine, my skin hasn't improved but my muscle wasting has definitely improved.

    I wonder if the methylfolate is increasing my need for some nutrients. I will be thinking about supplementing with other amino acids.
  4. place

    place Be Strong!

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    I had the feeling of muscle waisting or fatigue. I could not put the dishes away without feeling it. L carntine took care of it. D ribose also helps with muscle function.
  5. fozzaw

    fozzaw

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    Thats interesting about carnitine.. lysine is actually a precursor to that. I will give it a try.

    Ribose gives me low blood sugar unfortunately, something that came with starting molybdenum for high copper. This nasty hypoglycemia happens with specific supplements (ribose, TMG, manganese, P5P, iodine, creatine but not others).
    I think it might be related to G6PDH but Yasko doesn't have a lot of information on that in her slides.
  6. triffid113

    triffid113 Day of the Square Peg

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    What do y'all mean by "muscle wasting"? "Muscle wasting" in the scientific literature means low carnitine usually caused by hyperthyroid, but could be caused by insufficient methylation since methyls are required to make carnitine. But the way you reference it here, it sounds like you mean you are getting a lactic acid burn. I have often in the past gotton a lactic acid burn from doing NOTHING (and no one would believe me -- they said I must've exercised too much). I do not get this anymore. Since I started the new additional supplements I was forced to take at age 50. I can only guess it is the DHEA that prevents that because in the past I only got the lactic acid burn duing PMS (low hormone period). I do know what causes it -- it means your Kreb (energy production) cycle is not working. There are some reasons the Kreb cycle may not work that are potentially of interest here:

    you are hypothyroid and thus cannot make enough ubiquinol (active CoQ10) required by the Kreb cycle
    (this can be caused by insufficient zinc, mB12, tyrosine, etc)
    you are not intaking enough B2 and/or B3 (heavily required in the Kreb cycle)
    you do not have sufficient aB12 (required by the Kreb cycle
    I think magnesium is also required by the Kreb cycle and is frequently deficient in the American diet

    When the Kreb cycle cannot work due to nutrient deficiency, your body has to ferment starch/sugar to make energy.
    Fermentation produces only 2 ATPs (instead of the 56 produced by the Kreb cycle) and the byproduct of fermentation is lactic acid.
    dannybex likes this.
  7. triffid113

    triffid113 Day of the Square Peg

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    idk about supplements per se causing low blood sugar and I believe if that happens your blood sugar control must be marginal.

    However I have had a life time of experience with low blood sugar and I can tell you what worked for me:
    Under 40: eating 20g protein at breakfast (bringing your protein forward in the day, NOT eating more)
    Age 40-50: rhodiola (increases glycogen stores)
    Age 50+: DHEA

    It is your adrenal gland that tells the liver to break down glycogen and low blood sugar is a failure of the adrenal gland. A failure of the adrenal gland causes diabetes. I had a friend who was not diabetic fall on the ice and immediately become a brittle diabetic (her adrenal gland pumped out hormones and ran out and running out resulted in diabetes). She would have been my age but she already died due to diabetes complications (kidney failure). If I do not take my full dose of DHEA, I immediately get an undeserved low blood sugar attack. And it goes on forever. I believe I would have beeen diabetic for 4 years now had I not started DHEA when I did.

    Oh - there is only 1 supplement that causes low blood sugar for me (since I fix my adrenal gland with DHEA) and that is alpha lipoic acid. ALA lowers blood sugar so much that it is used to treat diabetes in germany. Hmmm. now that you mention it...coffee also lowers my blood sugar. I can only take 3 cups a day at my DHEA dose (just before I started taking DHEA I could not tolerate even 1 cup of coffee a day). As a young adult I drank 20 cups of coffee a day (in the days of my high hormone levels). It is a known fact that your DHEA:cortisol ratio governs how much stress you can take. 2 cups of coffee raise cortisol 33%
    dannybex likes this.
  8. fozzaw

    fozzaw

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    The blood sugar problems started with taking molybdenum, but its true that I had less than ideal blood sugar control prior to this. I seem to be very copper toxic as I could not tolerate much molybdenum originally (9mcg/meal was my maximum for a while). I will look into the rhodiola.

    the fact that DHEA helps you sounds like you have pregnenolone steal (where the body preferentially uses pregnenolone to make more cortisol and less sex hormones), as it's the cortisol that raises blood sugar.

    unfortunately carnitine and ALCAR give me some blood sugar problems too. So every mitochondrial supplement I've tried seems to do this (except NADH, which haven't tried that recently). Prior to the molybdenum, these supplements didn't affect my blood sugar so much.
  9. dbkita

    dbkita Senior Member

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    fozzaw:

    I have totally experienced the shoulder and neck pain you are discussing as a result of methylation supplementation.

    Be careful it sounds to me like a classic case of potential over-methylation. Over-methylation will increase inflammation if inflammation is already present. Took me a long time to realize that though I had a partial methylation block that I had jumped in way to deep too fast and stayed there for like two years with ups and downs as I jiggered stuff around. I was on 800 mcg methylfolate, 800 mcg folinic acid, 25 mg P5p sublingual and 5000 mcg mb12 for most of that time. Also I was on TMG 600 mg per day (over 2 doses). Avoided folic acid assiduously in supplements as well as other sources of B6 (no multivitamin for me, had to do it the hard way).

    Took me a long time to realize that increasing P5P and riboflavin-5-phosphate further lead to exacerbation of pain symptoms and increased insomnia and wakefullness though it did improve mental focus, passion, energy, etc.

    Things got a lot worse when I added SAMe and phosphoserine.

    I finally got around to genetic testing and found I have the MTHF A1298c defect meaning my MTHFR receptor does not respond well to feedback allosteric inhibition from SAMe. I also have the COMT heterozygote mutation which means I don't drain methyl donors as well. Turns out I have no genetic problems.

    I then found online at mthfr.net that the simple way to test for over-methylation is to take B3 (as niacin or niacinamide) and see what happened to the pain as it quenches methyl donors at high enough levels. Bam! Pain dropped.

    Also found that if take vitamin C at same time as methyfolate, destabilizes it in gut and reduces effective yield. Less significant an effect but it also reduced pain (note I normally take high dose vitamin C throughout the day for other reasons).

    I dropped the SAMe and Seriphos and got some improvement.

    When I realized this I got out of the deep end of the pool in a hurry.

    Shifted to 1/2 tablet mb12 (2500 mcg) and shifted the other half given up to hydroxy b12 and adb12. Got rid of folinic acid (takes days to get out of the CNS) and lowered methylfolate to 400 mcg. Lowered P5p back to < 25 mg.

    But the BIG impact was removing TMG altogether and getting rid of ribofalvin-5-phosphate and going to normal riboflavin since the body only absorbs 30-40 mg max of B-2 in one dose if riboflavin but way more when in active form.

    Anyways the last two really changed my sleep and helped reduce pain a lot. Turns out over-stimulation of BHMT can also cause imbalances in norepinephrine relative to dopamine (bad for inflammation). And check out the last reaction to make 5mthf and see what is the co-factor. It is R5p not p5p as often mislabeled.

    Also if you have a CBS Mutation, increasing methylation and P5p will just feed the trans-sulfuration pathway and you end up with high sulfites, sulfates, ammonia, AKG, etc. So that can complicate things also.

    Note that overmethylation will kill histamine production at the expense of turning histidine into a form of glutamate which is excitatory and can cause pain at the NMDA receptors. So your (and my allergies got better) but ... there is a price.

    I am not a doctor (well not medicine at least) so please take this with a grain of salt. Methylation is very important but not everyone has the crippling level of mutations that Freddd and others have in MTR and MTHFR. But overmethylation is a real thing and for a long time I bought into the BS about detox reactions which after nearly two years is completely worthless in my own experience. Yes potassium can be a factor but I get massive amounts of potassium (and excrete a lot in a 24 hour urine test) so that was not a mitigating issue for me whatsoever.

    You can simply test this with B3. I prefer niacinamide since I hate the silly niacin flushes, and see your reaction.

    Keep an open mind. I am sure (like me) you need some methylation support but be careful of over-methylating.
    The telling sign for you is your reaction to P5p (unless a CBS mutation is at work as well). Your reaction to SAMe is also a tell-tale sign. If anything my reaction to SAMe is what started pushing me to look for answers and not standing pat.

    I am still fine tuning my optimal state (which is hard to do since I have a rough auto-immune disease and am on HRT) but I can tell I am MUCH closer to being in the right ballpark now as I can sleep better, feel better emotionally, reduced pain, and still have decent energy. I will likely experiment with upping my R5p a little bit or maybe slightly altering my methyfolate or mb12 levels. But I won't go back to TMG, SAMe, etc. or mass

    Btw taking methionine directly is not a particularly good long term strategy since it can slow down the methylation cycle and long term BHMT supplementation is the short cut that can increase norepinephrine sadly. Of course what no one focuses on is betaine HCL supplies TMG and carnitine will always turn into methionine and lysine in your gut (I am pretty sure about this) so just watch that you don't take carnitine and methionine on top of one another at least.
    Carnitine is also sadly a strong down-regulator of T3 binding at the nuclear receptor sites. So just be careful.

    Lastly, I too have some issues with molybdenum making me tired and possibly affecting blood sugar. Manganese has a stronger effect on me. But taking even 75 mcg of Mo will tire me some. 200+ in a day kicks my you know what. But ... I really have a hard time seeing how 9 mcg has that impact. That is like taking < 1 oz of cashews. So be careful again it is not something else involved.

    Good luck and God bless!
    Jarod and xjhuez like this.
  10. adreno

    adreno 3% neanderthal

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    Zinc deficiency? Also it is important that you take methylcobalamin with methylfolate, or you will end up with methyl trapping.
  11. Little Bluestem

    Little Bluestem Senescent on the Illinois prairie, USA

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    Is this the T3 that is produced from the T4 that is produced by the thyroid?
  12. dbkita

    dbkita Senior Member

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    Yes. That does not mean carnitine isn't good for you. It is essential. But people with hypothyroid are often advised to not go too far with carnitine supplementation without being careful.

    Oddly enough as pointed out earlier in this same thread, carnitine = methionine + lysine. Carnitine whether as L-carnitine and carnitine fumarate will disassociate in the gut into methionine + lysine and will be recombined inside the cellular membranes by the body as needed.

    Acetly-l-carnitine is blood brain barrier penetrable and is more stable until the acetyl group is removed.

    So in reality unless you overdo things the body will be in control and recombine the methionine + lysine as needed if you take the first two forms. The latter form is a bit trickier to manage and has been shown to affect T3 binding in the brain and CNS.

    Ironically, for Fozzaw the reason lysine probably helped her muscle problems is increased energy from being able to make carnitine. On the other hand without methylation cycle working, carnitine production is low. Sadly lysine is often sold in the lysine mono-hydrochloride form which while cheap and highly absorbable for some people poses a real problem in terms of reflux, gastritis, etc.

    Too much supplemental methionine for a long period will slow the methylation cycle via feedback inhibition in most people. I suspect the reason why methionine damps some of Fozzaw's pain symptoms is it slows down methylation somewhat. That is certainly what happened to me for a long time. I was just to stubborn to see it over the last two years
    when I briefly at times supplemented with methionine directly.
    Little Bluestem likes this.
  13. dannybex

    dannybex Senior Member

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    Hi Fozzaw,

    Do you mean you were able to stop losing muscle, or did you actually notice gains in muscle while taking lysine?

    Thanks in advance,

    Dan
  14. dannybex

    dannybex Senior Member

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    I'm curious how much DHEA you're taking Triffid113, how often do you take it (what time of the day) and also did you slowly increase your dose?

    And last question...did you base your need for dhea on salivary adrenal hormone testing?

    Thanks!
  15. triffid113

    triffid113 Day of the Square Peg

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    Dannybex, um, nothing scientific - I was in search of something to control my blood pressure and I knew it was a hormonal cure because my bp was only elevated during PMS (but then it was stage 3). Normal bioidentical hormone replacement did not work (and nothing else provided a stable long lasting solution) so I turned to DHEA. I had read tons of studies and the study dose was 50mg so I wanted to be with the pack and take the studied dose. The day I went to the health food store I was having a panic attack / blood sugar shakes and, being over 50, I was also panicking that it would go on eforever (normally I would get 1 day panic attacks during my cycle, but menopause is PMS forever). My father came by to see if I wanted to go get lunch and I said sure, after you drive me to the health food store. I felt too dizzy from panic to go myself. I popped the pills like a shaking drug addict, felt like I went through a fun house mirror, and in 15 minutes I was sorted - no panic and no high b.p.

    I did break out - it lasted only as long as the initial episode took to heal. I did - er - become extremely - er - horny, which I discovered is due to the rise in testosterone (in other words, it goes away once stabilized). However I also found the half life is 10 hours and I mistakenly believed that meant it would be out of my system in 20 hours. I did note that in the mornings I was sluggish and likely to piss the day away so I started taking a smaller dose of 25mg later in the day. Supposedly it keeps you awake so I didn't take it past 7pm. It seemed to help even thing out for me. I have never determined if I could do with less, except to be quite sure that 50mg is not enough. Each and every time I have cut back to 50 mg I get panic/shakes if not immediately then within 3 days.
    dannybex likes this.
  16. triffid113

    triffid113 Day of the Square Peg

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    Yes, I suspect my body is making cortisol out of pregnenolone. When I run out of DHEA I never run out of everything at once...so I have tried 100mg pregnenolone to hold the line until more DHEA comes in the mail, but it doesn't work for me. I still wind up with the shakes. Freddd takes 100mg pregnenolone and 25mg DHEA and I tried that ratio but it does nothing for me. I have to get something over 50mg DHEA to function. Maybe something to do with me being CBS +/+ and also CBS +/- (two CBS defects) and that supposedly affects G6PD. Wish I knew more about that - I hate to be so addicted to something that I suffer bad consequences if I run out for a few days...
  17. triffid113

    triffid113 Day of the Square Peg

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    Dannybex I take 50mg with water first thing in the am before breakfast. I just do it that way because it never bothers my stomach and I have so many pills to take that I like to take the DHEA, pregnenolone (25mg), C, E, and CoQ10 right away, whereas I take the others, some of which may irritate, with food later. I take 25mg whenever I can later in the day...supposedly at dinner, but even at lunch, just so it is at least 4 hours after the first dose (I do that to try to stabilize the amount in my blood...someday I may look ito finding a time release form).

    But as to testing...I did take a saliva adrenal test and it showed I was low but not too low (by what standards I have no idea and it was not during allergy season). Here is what I wrote on another thread about how you can tell some things about your adrenals w/o testing (well some people like me can tell anyway):

    My adrenals do go out during allergy season and I need no test to prove this - my blood pressure which is genetically high goes low and I actually will pass out if I don't eat salt. So...you can look at your blood pressure, if you have blood pressure issues, to do an easy self diagnosis.

    Other adrenal issues though involve DHEA. Everyone's DHEA, put out by the adrenal gland, peaks at age 30. So here is another thing to observe -- the amount of stress you can tolerate is dependent on how much DHEA you've got. There is a cortisol to DHEA ratio and in young people it's either 10 to 1 or 1 to 10 (sorry I don't actually know which way it goes!). However you can observe this...when you were 20 you could prolly drink a lot of coffee w/o getting he shakes...I personally used to drink 20 cups a day as I used caffeiene to keep functioning while anemic. 2 cups of coffee raise cortisol 33% so coffee is like liquid stress. After 50, I could barely and not always tolerate even 1 cup of coffee / day. After I supplemented DHEA I could reliably tolerate 3 cups and usually as many as I wanted - so maybe 7. Your ability to handle stress is a function of your DHEA level, and your adrenal is not considered fatigued because your DHEA level is low, it is simply considered old.

    I don't know if any of that helps you. Everyone is low in DHEA by age 50 compared to age 30. But people who need it to regulate their genes may notice a bigger impact from taking it whereas those w/o genetic issues may not ever feel a need to bother IMHO.
  18. dannybex

    dannybex Senior Member

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    Same here...from 2011 (already!)...my dhea was a 2 (ug/ml) with 3-10 being the normal range. Then there were kind of vague, generalized recommendations for supplementation included with the report. Unfortunately I didn't have the $$ to get back to the doctor ($180) for a consult on the results...so just kind of forgot about it (besides googling some horror stories about side effects including hair loss (which I don't need...my bald spot has grown enough in the last 5 years as it is! I know, shallow, but can't help it).

    It does. I haven't been able to tolerate coffee in at least 10 years, and haven't had any in at least 7 or 8. The last time I tried a cup, if I had it after say 1pm or even noon, I'd be up until 3am. I wake up feeling like I've been hit by a truck, but also tense up (stress out) within an hour or less after I get up.

    My salivary adrenal profile showed low cortisol at 8am, then it shoots up at noon (which is unusual, but makes sense stress-wise), then was in the 'normal' range at 4pm and then midnight. Normal, but perhaps a little on the low-normal side. I was diagnosed with adrenal 'burnout', not to be confused with adrenal fatigue, because I was still putting out too much cortisol during part of the day.

    So...I'm guessing I should give it a try...maybe start with a low dose and try it for a few days. ???
  19. dannybex

    dannybex Senior Member

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    Thanks for this too Triffid113 -- I meant to reply to this earlier as well. After staring at my NutrEval test off and on for 3 years, I've finally realized how broken my krebs cycle is. Back in the day, everything was methylation, methylation, methyl...well, you know, and in hindsight, I don't think enough attention was paid to the non-b12/folate issues that have nothing or very little to do with the krebs cycle.

    And I, like you did, get lactic acid burn in my feet, within I'd say 15 minutes after I get up in the morning. I found some great advice on one of Catseye's threads (from about a year ago) and along with your suggestions will try to raise the $ to get the supps I need to help at least begin to correct this before I use the rest of my muscle for "fuel".

    I'm hoping (and I think this is true) that "fixing" the krebs cycle will also help improve digestion, among many other things.

    THANKS!
  20. triffid113

    triffid113 Day of the Square Peg

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    Dannybex I toot that OATS test and it said I was low in CoQ10 which was an eye-opener since I was taking 100mg ubiquinone. I do not know how much ubiquinol is needed for the Kreb cycle but it made me wonder if I could convert ubiquinone to ubiquinol. I read somewhere that you need thyroid hormone to turn ubiquinone to ubiquinol. No proof, so can't be sure. Well when we'uns were younger our thyroids made more hormone. I have a theory that it gets hardr to absorb zinc and copper as our hormones wane because metallothionein needed to absorb them is governed by hormones. It may be just me that has trouble with this because of my allergies you understand. I have a radar for this and I see it in other people too. Anyway unless you TSH < 2.0 your thyroid needs help (possibly more of the input nutrients which include zinc and copper). But actually it may be better to have your TSH closer to 1 as far as energy. Well we all know thyroid affects energy but one mechanism is via CoQ10 needed for the Kreb cycle. I can't say if taking ubiquinol helps that much. The thing about thyroid problems is they affect your brain too (the number one consumer of Kreb cycle energy) and it's thus hard to perform an experiment on yourself.

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