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Methyl donors - SAMe, TMG + any others ie DMG

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by topaz, Feb 12, 2012.

  1. dbkita

    dbkita Senior Member

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    I will be trying lithium as you suggest, a mineral test (urine) of mine suggested it is low. I am a little worried about the rat study showing kidney accumulation with lithium orotate, though. But maybe it's safe for humans. Orotic acid has also been linked to cancer in some animal studies.​

    Yes you are right but if I could find it (my electronic papers are a mess sometimes) I have laying around a safety analysis done by the European equivalent of the FDA and they they set a safe limit based on the rat studies of 50 mg per kg body weight (? or something close to that). So for me that would be around 3 g or so. So I figure < 1 gram is well within limits. I would always be cautious though if you have any kidney abnormalities. I think one pill of lithium orotate is like 120 mg containing about 5 mg (?) elemental lithium. It is very BBB penetrable. I have not tried it yet as I am awaiting some test results but I am thinking about it for myself too.


    Regarding magnesium threonate, you really can't compare the low dose to other forms, because absorption is much greater. Take a look at these links:​

    The Mg threonate seems useful. I will have to interpret when I get some time its activity at the NMDA receptor sites.

    But the issue of Mg absorption is fairly complicated.

    Short answer = virtually all Mg amino acid chelates are highly soluble and thus are pretty well absorbed assuming the manufacturer is not defrauding you somehow, meaning ~60-70% or more over the course of the entire digestive track for quality sources.

    Thus my statement above ... since 144 mg of Mg from Mg threonate even if it was 100% (which it is not) would be similar to a 200mg of one of the other chelates, though for some (like citrate) diarrhea limits will vary. So even if we figure you take roughly equivalent to 400 mg per day and 900 mg of calcium and get at ~ 200-200 mg Mg in diet and I assume more in Ca (which is normal) then yeah I think your ratio may still be off. But I can't say for sure. Simple way to assess this is a Mg RBC test. You want that nice and strong.

    Now if you want the long answer ...

    In the interest of lessening the damage to my shoulders and rib cage, let's just say it involves solubility, ionizability, fractional absorption rates per hour, and intake levels. My intake levels are high so maybe a typical citrate gets me 1-2% per hour which will be like say 10-12x total that over the entire stomach. Low intakes will get 5-6% per hour or better. Also these things depend where it is absorbed in the GI tract (di-glycinate is mostly in the small intestines which is why it produces the least diarrhea). And the complexity goes on and on.

    To be honest I am experimenting with lowering my input of Albion Mg - glycinate since a recent 24 hour urine test shows I am excreting magnesium anyways above the top of the range. While not particularly harmful, I am testing to see clinically how the reduced glycinate affects my system. So far it seems my back pain goes up with less Mg glycinate but my body is less stimulated. Fun trade-offs, eh?

    Thanks for your reply. Take a look at Figure 1 in this article, for the link between ACh and glutamate excitotoxicity.​

    Thanks for the paper. I see the connection. Still not clear how this works at lower, normal levels of ACh and perturbations thereof. I will dig deeper if I get a chance.

    Btw the amount of pantethine you take gives me really bad insomnia. I guess results differ person to person.
     
  2. adreno

    adreno 3% neanderthal

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    I have been using both Doctor's Best and LEF. I will try AOR next, as it looks a little more potent for the money.

    I did not tolerate ALA at all, gave me allergies and hives. R-ALA doesn't have the yellow color or sulfur smell, and I seem to tolerate it fine.
     
  3. adreno

    adreno 3% neanderthal

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    To be fair, I have taken 500-650mg magnesium until recently. 200mg glycinate, and 300-450mg citrate. I am experimenting with threonate at the moment. Just one cap, with only 50mg Mg has a pronounced effect.

    I tried increasing my dose of Mg before, and it just made me dullminded and gave me a headache. Threonate seems to be different as it makes me calm but clear. It even seems slightly energizing.

    I have tried lower doses of calcium, but felt depressed, slow, and even anxious. It seems a 2:1 ratio is just about right for me. I don't eat dairy, so I miss a lot of calcium from that. But who knows...maybe 900mg is too much. Maybe it's something to do with me needing a strong pressor response in the veins, and too much vasodilation not being good for me. I'm am not sure at this stage.

    I have tried higher doses of D, but didn't feel any better. I don't where to get a 1,25 test. For the 25 test, 2000IU is right for me.

    DHEA, I think 25mg would be right for my age (40), but I also get some from the preg. I find it hard to control the conversion. It gives me acne if I don't take the high doses of zinc, so I suspect I need the zinc to block aromatase. Zinc was very low on my mineral test. I also take broccoli extract to help the metabolism of estrogens. And pantethine depletes prolactin, which can also be a problem (my nipples felt somewhat sensitive and tingly before adding that). Since I have added these supplements, I have been able to gain some muscle, and libido seems normal. But I would like to do more testing. I had very high (total) T before I added any supps, but they didn't test free T or E2, so that was useless (that's endocrinologists for you, sigh). Still I would like to go higher on DHEA as it has been very helpful for POTS, mood, anxiety, strength, immunity etc. Some acne is not a big problem for me, but I believe it is a symptom of an underlying hormonal imbalance, so it can't be good in the long run. Many seem to believe that acne is caused by DHT, but I think that is wrong. I believe the problems is T and E2 balance. I do not block DHT. It is very androgenic, more so than T, and we really need the DHT as males, for building muscle mass etc. It is also extremely important for libido. Check out the horror stories of DHT blockers on the net, there are entire forums dedicated to guys who never got over them. Sounds like nasty drugs.

    Regarding zinc, I don't eat nuts (allergies) and have meat 1-2 times daily. Without the zinc, I get acne, dry skin, fatigue, weakness and can't seem to put on any muscle. So I guess I need it, but I just go by symptoms.

    Did you look into pharmGABA? Not sure how solid the science is, but it feels distinctly different from regular GABA, more like theanine, but without the nasty rebound. It is claimed to pass the BBB much more easily.
    http://www.bioclinicnaturals.com/ca...tural-support-for-stress-anxiety-and-insomnia

    100mg Ubiqiunol is low? I thought that was plenty. I have tried higher dose for a few weeks, didn't really make a difference. I could bump it to 200mg just on faith that it will help in the long run...sometimes we notice no immediate effects, but after a few months we realize we are simply doing better overall. It's sometimes hard to pin down causality.

    I do not notice much from benfotiamine, slight increase in energy and wellbeing perhaps. I take it mostly in the hope that it does something good for my nerves. Sulbutiamine was a terrible experience, though.
     
  4. dbkita

    dbkita Senior Member

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    I have not doubt the Mg-threonate is helping you. I am just saying it may not be the magnesium component of it. All the chelates will be close enough in absorption so that the Mg cannot be the difference makes. Maybe it is the threonate?

    If high amounts of magnesium are making you dull and you like having a healthy amount of calcium then it seems to support your earlier thesis that this not a simple NMDA issue.

    I get about maybe 500 mg Ca in my calcium pyruvate tablets throughout the day + maybe 300-400 mg in my diet. I get maybe 300-400 mg Mg in my diet + conservatively 1000-1400 mg Mg in supplements. I excrete a lot of Mg in my urine as seen on a 24 hour test, but if I lower my Mg significantly my spine locks on me (good times).

    What is your 25 test results on 2000IU if I might ask? Still you need at least an occasional 1,25 active form result to know where you really are. Do you have a parathyroid value? That can also be indicative. I get my 1,25 at Labcorp alongside my 25 results from my neuroendocrinologist.

    For reference sake I take 100-150 mg DHEA per day but no pregnenolone. But then again I can take small doses of T cypionate twice a week and get no estradiol effects and really high T (total and free). So we are each different. My brother for example had to discontinue T cypionate in 4 weeks due to lower limb edema, acne, and anger issues (a bad sign of estradiol ). My T half life is crazy long apparently. C'est la vie.

    Anyways the DHEA is very helpful for me and is a stalwart in preventing osteoporotic degradation from the corticosteroids I am on.

    I was lowish on zinc myself for a while, until I went on molybdenum. Now the I seem to have hit some saturation limit and had to down scale zinc intake somewhat (~25 mg per day). Before that I still got the weird metallic taste phenomena when taking zinc, but after the Mo and some time that all disappeared. I await new results. We will see.

    Panthethine is great in principle. I am just saying 300-400 mg gives me impressive insomnia. I take 50 mg of pantothenic acid right now. That is the best I can do. I know I need more, but .. c'est la vie again.

    Yeah I would not touch the DHT blockers. Fortunately I don't seem to make much DHT. Hormones are so individual to each person it is nuts.

    Going by symptoms is the best way to proceed in my experience. Just gets tricky when we take so many things.
    That is why I keep record of everything I take every day and jot down every night how I felt, so if I make changes
    I can interpret the results as experiments. Sometimes a valuable historical baseline documented is worth its weight in gold.


    PharmaGABA is the brand, one of my doctors had me do the 500 / 500 / 1000 mg test I discussed in another thread. I could try it again I suppose. I still think it is not BBB penetrable for most people. I saw nothing in the link in terms of chemistry that would suggest otherwise. They are stressing purity and source. That doesn't change the kinetics or efflux pumps at the BBB. They avow claims of its effects but that I suppose just shows which of their clients have leaky BBB issues (which may be quiet a few of us since we are the "unhealthy" part of the population).

    Sorry I thought you meant ubiquinone. Ubiquinol 100 mg is fine. You may benefit from more a bit but the 100 mg ubiquinol means you are not depleted almost certainly.

    That is too bad. I know the theory about benfotiamine but I wondered how it compared to plain old thiamin HCL.

    Always a pleasure :)
     
  5. dbkita

    dbkita Senior Member

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    Thanks for the info. Reason I ask is I think the regular ALA is doing some funky stuff. High doses make me tired and hit me in my gut / lower esophagus. Dropping the doses seem to calm me down some. Odd.

    Time to try some R-ALA methinks.

    Btw do you take the R-ALA all in one dose or split it up as some on these forums have proposed?
     
  6. adreno

    adreno 3% neanderthal

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    I take it all in the morning on an empty stomach. R-ALA has pro-oxidant effects, so I believe you do not want multiple doses of it.
     
  7. adreno

    adreno 3% neanderthal

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    Ok, but you are aware that those are supraphysiological doses. 50mg will bring a 60 year old man back to youthful (20-year old) levels. Then again, you are also taking supraphysiological doses of glucocorticoids.

    DHEA dose not convert to aldosterone, so I guess I might be more interested in preg. I tried some progesterone cream yesterday (about 20mg) and that seemed to help. It is just one step removed from aldo.

    Likewise :)
     
  8. dbkita

    dbkita Senior Member

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    I thought the studies that showed pro-oxidant effects for r-ala were in rats at really big doses (like equivalent to 3000 mg or something). Do you have any sources for this at lower doses in humans?

    For example things are kind of murky when it comes to vitamin C supplementation at higher doses. Speaking of which what are your thoughts on high dose vitamin C (like 4-8 grams per day) beyond the stomach implications.

    I have been thinking about magnesium ascorbate which is partly why I am asking. I take 6-8 grams per day now of powdered C but I am thinking my stomach cannot handle it so the magnesium ascobate may be a better buffered form.

    Yes I know. For some reason if I go a long time at < 100 mg my DHEA crashes. At 125 it is at the top of the range (sometimes). At 150 it is 20% above range and my endocrinologist is fine with that if it makes me feel better which it does. I

    I am double replacement for the glucorticoids. Honestly my neuroendocrinologist is happy we have not (yet) had to go to the expensive, nasty stuff (yes nasty) to further mitigate things. We draw the line at double replacement unless I have a serious flares and then only for a short time.

    I would not supplement progesterone for a man unless you know what your current levels are. Your 50 mg pregnenolone is already converting on that pathway. It would be grand if you could manage your dysautonomia with pregnenolone and progesterone to get your aldosterone up enough to help ... I have just never heard of it ever working that way due to all the metabolic paths, metabolites, and temporal properties. Sorry.
     
  9. adreno

    adreno 3% neanderthal

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    I must admit that I have not researched this deeply. I trust what the experts at Geronova are saying:

    http://www.geronova.com/content/r-lipoic-acid-information-studies

    I don't have a deep enough understanding to really have an opinion on this. I have found 4-8g to be a good range from trial and error. Less than 3-4g and higher than 8 and I start feeling worse.

    Are you using ascorbic acid? No wonder you have reflux in that case. I use natrium ascorbate and I like it :)

    I know, it was just an experiment. Would you be worried to increase the preg beyond my moderate dose of 50mg? Weirdly, I seemed to get some increased anxiety from the progesterone, maybe this ties to what you say about androgens being calming. Progesterone will block DHT. Also, DHEA seems to be anxiolytic, and strangely it also seems to help my POTS, though I have no idea why.

    I might attempt to reset my HPAA somehow. I have been discussing this on other forums. The idea is to suppress the HPA even further for a while, allowing the negative feedback to diminish, sort of the opposite of taking adrenal extracts or steroids. It works in mathematical models, but the question is will it work in real life? It will certainly be unpleasant. One drug that might do this is Prazosin, an alpha blocker. It reduces HPA output. It is used for PTSD. Now you think I'm crazy ;)
     
  10. dbkita

    dbkita Senior Member

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    Heh I have to go bed after this post.

    Meh I am not convinced personally about the pro-oxidant stuff with ALA. I have seen the studies in rats for improved insulin signaling and higher glucose in muscle tissue.

    I did not know though that the r-ala metabolite r-dhla regulated cox-2. Very interesting. Hmm. So I probably have been shooting myself in the foot with the racemic mix. Well always learning is what I say :)

    Yeah I take ascorbic acid but I learned to mix it in blended drinks (i.e. blend nuts, vegetables, some meat), etc. I take 6-8 g that way in say 3 doses. I have a lot of issues with my SPS eating solid food so I get like 2/3 of my calories from blended food with liquids. C'est la vie. I am more thinking of a way to take some of my magnesium and potassium supplement load off of glycinate and gluconate. I have issues with citrate. Hmm I have to think this through a bit more.

    I think 8 g tends to amp me a bit more (ascorbic acid is a cofactor in converting dopamine to NE along with copper).
    I might go back to six for a while.

    Ok regarding hormones...

    http://en.wikipedia.org/wiki/File:Progesterone_biosynthesis.png

    Pregenolone is the master hormone. What is often ignored is 17-OH progesterone can lead into the androgen path, which can feed right into estrogen. I don't think the figure I linked does justice. There is something missing I think, but I can't put my finger on it, seems a bit simplistic in that diagram.

    So your pregnenolone can be going anywhere. You may wish all your progesterone goes where you want it to ... but if wishes were horses. In this regard I defer to my neuroendocrinologist. Progesterone is almost never used by him in a male. He can always bring it up with the other steroids.

    Ironically my progesterone is above normal now (used to be dirt low before HRT) and I don't take pregnenolone either. Two things, my doctor reduced inflammation in me, so the cortisol drain is less (but this was even true when I took physiological levels of medrol) and I take a lot of DHEA. So via feedback inhibition the pregnenolone I now make on a less inflamed body goes to progesterone, which I think in my case also ends up at testosterone and which luckily sits there for a long time making little estrogen and DHT (my doctor can't believe how little of those I make relative to my other inputs).

    One missing piece to the puzzle is cholesterol. As my doctor alerted me to, people who have hormonal imbalances often have high cholesterol since the body is under stress to make pregnenolone. But the cholesterol doesn't transform fast enough due to say immune system problems and the numbers climb. On HRT my cholesterol went from high to 160 or so with a very high (~70+) HDL. Voila!

    So you can see how you can actually take something off the beaten path to say aldosterone but affect its synthesis by feedback inhibition of one of the cross pathways, right? That is my theory at least for what it is worth.

    Eep not sure what to think about suppressing HPA signaling. You might never get it to restore correctly. The H & P are parts I don't think I ever want to mess with directly. Besides I think signaling issues get called into question too often when there can be a functional reason ... like the immune system. My two cents at least.

    Later.
     
    Lotus97 likes this.
  11. adreno

    adreno 3% neanderthal

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    Ok, so it looks like it actually makes more sense to work on getting my DHEA up to snuff.

    Sorry, I don't get that argument. Everything affects the H and P, neurotransmitters, hormones, drugs, supps etc. Alpha blockers are used for prostate problems and kidney stones. They antagonize the alpha-1 adrenoceptor. They are no more affecting H and P than a beta blocker, an antidepressant or many other things. So I really don't see the danger.

    I do take your point on the gorilla bashing the crap out of the HPA though. So an underlying immune problem might depress the HPA right back. But in my case, the problems started virtually overnight, from the adrenal extracts (and the supps I mentioned), so it seems to me that it's likely that my HPA setpoint was shifted. The extracts likely contained aldosterone (I don't know if that is absorbable in the gut) and this might have set off the feedback inhibition. Or is it possible I reactivated a virus? From one day to the next I couldn't stand up any more, and it seemed like my NE was way out of control. Epinephrine from the extracts do not absorb in the gut. Cheney has suggested that adrenal extracts contain some unwanted signaling factors, and recommends brain and heart extracts instead. I am not eager to take his advice, lol.

    Also, take a peek at this, if you have time:
    Model-Based Therapeutic Correction of Hypothalamic-Pituitary-Adrenal Axis Dysfunction
     
  12. dbkita

    dbkita Senior Member

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    Hopefully I adequately voiced my reluctance to hit the HP part of the HPA axis directly in the other thread "CBS Revisited".

    From what you listed about the incident in question, I can't see anything else than the extracts unless blind coincidence, the latter being non-productive to contemplate.

    Not sure if aldosterone is bioavailable orally, but even if it was it doesn't match most of your symptoms. You would have gotten edema, some headaches, and maybe some vascular effects like your veins look bigger. I can't see beyond that since you took the extracts like 2 days, sorry. Besides feedback inhibition by itself doesn't work like that. You can't high dose something for two days and have long term shutdown of the HPA axis for that hormone. No one would ever go near a Medrol pack.

    Besides you are telling me you have many hormones that were are are low to low normal now. The very fact you benefit from pregnenolone tells you this, right? This in my opinion means at least some broad level of adrenal suppression and based on my own limited experience I would always point the gun at the immune system first.

    In principle cortisol is the first to go but is one of the hardest to clearly measure since first it climbs and then it drops. Almost no one usually looks at cortisol readings until the going gets bad and I believe everyone's 'normal' baseline is pretty individual. A more telling sign is how you handle stress clinically. If it amps you a lot and you call NE, yes you may be wired that way, but ask yourself is it worse now than before. The first reason was genetic, but if it changes time then it is lower or at least variable cortisol. Do you get afternoon dips? Need to reach for coffee then?

    But while cortisol is the first to go erratic the other one will eventually fall one by one. If you have gotten to pregnenolone then to borrow a quote from Aliens (and also used in Starcraft): "your are in pipe 5 by 5".

    This may not be your main problem but given you seem to be experiencing effects from trying to tone down NE, it is likely imo a problem. Sadly regardless what some posters may think on these forums, not everything can be fixed by methylation.

    Note I have sworn off most hormonal related extracts from my own bad experiences (nothing as severe as your reaction though).

    Good luck, let me know how the NE experiments play out. Don't knock it too low you need some :)
     
  13. UM MAN

    UM MAN

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    I have been makeing my own LIPOSOMAL Vitamin C, for over a year. I find it very efficacious. Having Vitamin C delivered through the lymphatic system avoids having to dose every three hours, and worring about how it will interact with other supplements.
     
  14. adreno

    adreno 3% neanderthal

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    dbkita

    I was on the extract for about 8 weeks. Sorry for any confusion. It was the cholinergic supps (Memory Support) I took for 2 days. I would never claim downregulation of the HPA could happen in 2 days.

    Anyway, I believe you are right about the immune system being the key player. It would make sense from an evolutionary perspective. I guess the HPA is really just a lever that the immune system can adjust to adapt individuals to behavior which will maximize their chance of survival. Unfortunately, like you say, we can't lie around in our beds the whole day.

    I will focus my future endeavors on the immune system. Thanks for your help.
     
  15. dbkita

    dbkita Senior Member

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    Ah I see. Oops my bad. Well 8 weeks is a long time. I don't have enough experience to say though that they may have forced some permanent HPA signal disruption. On the other hand the coincidental timing of your cholinergic supplements + your symptoms that seemed like poisoning ... well let's just say the jury is still open on that one imho.
    You expressed basically having an intense set of almost psychotic emotions. I would tender that you can't get that from anything but extreme HPA disruption and even then I think that would only be a part of the issue. Like I said the brief psychosis is the inexplicable but core symptom if you are try to do a reverse diagnosis.

    That is very eloquently put. Better than I can do lol. Yes I think the immune system is almost been grafted on top of many other systems in a way that it can exert command override authority when it sees fit. This is why when the immune system is ascendant T4 is shunted to RT3. Or why the adrenals are told to reduce production (since from the immune system's standpoint cortisol prevent it from doing its job, not to mention that other hormones like testosterone are anti-inflammatory also). But the immune does not understand that chronic conditions sometimes don't go away and it keeps hammering these systems. Until that in itself becomes as big or more of a problem.

    The first place to always look imo is the gut based on Occam's principle. If not then other places are of course non-gut infections and even autoimmune disorders. That is my two cents at least. For 90% of the people on these forums who have an immune system component, i.e. not nervous system dysfunction only, the problem is probably in the gut. One of the likeliest of that is of course a leaky gut since that really pisses off the immune system.

    Of course once things have progressed long enough that is when you can get into a bear trap where the norepinphrine has risen and the immune system keeps going and the two egg each other on since many of your other controls are shot. That SSRI has probably helped you more than you may realize.

    Anyways I am still trying to work out my gut. There has to be a reason I eat 3600-4000 calories a day and cannot gain weight. I have been between 153 and 164 lbs over the last four years and I am 6' 2". Not right. Lab test show I have a bacterial overgrowth and I am rampant with sulfate reducing bacteria. But I have had issues with molds and candida in the past so we are going after that first.

    Good luck!
     
  16. dbkita

    dbkita Senior Member

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    What brand to you use and what doses?
     
  17. UM MAN

    UM MAN

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  18. Crux

    Crux Senior Member

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    Hi dbkita;
    I'm reading that you're having problems gaining weight. I agree that gut problems can certainly cause this, but I'll also plug B12 for help with weight gain. I've been taking HC too, and it did bring me back from skin and bones, but sometimes I would lose my appetite and drop down again.

    It looks like you have a good appetite, so I could be off base, but I thought to bring this up anyway. How much B12, which forms, are you taking now?
     
  19. dbkita

    dbkita Senior Member

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    I take 2500 mcg of mb2 (jarrows), 1/8 adb12 of source naturals dibenzocide, and no hb12.

    I have also been on up to 5000 mcg of jarrows with no benefit for weight, and I only started the dibenzocide in the last two months.

    Like I said though the low weight problems have persisted for many years. My dramatic weight loss was before any meds in 2008-early 2009 when I lost 80 lbs and dropped to 130. The hope was that the corticosteroids would have me gain weight no such luck.

    That is why I am starting to suspect something sinister in the gut. If I don't eat 200 g protein, 120+ or so fat and 3500 calories a day, I feel like I am wasting away.

    There was one round of gut testing in 2011 that showed an intestinal overgrowth, undetectable lactobacillus, and lot of sulfate reducing bacteria. But I have been on really powerful probiotics for a long time now (50 Billion CFU Klaire Labs one) and am on gluten free, corn free, soy free, dairy free diet. Very paleolithic. I am currently going on another Candida protocol (some diet alterations and diflucan / nystatin). That has helped me a bit before to feel better, but not to gain weight. It is a puzzle.

    The ironic thing is people usually gain weight on HC and other glucocorticoids. Sigh.
     
  20. dbkita

    dbkita Senior Member

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    Hey Adreno just curious how much mb12 and / or adb 12 do you take?

    I am debating if the adb12 (like ~1 mg sublingual per say) is too much every day.
     

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