Need sam-e or other methyl donors but don't tolerate them

[Hope78]

Hi!

My lab tests are showing that, due to detoxification issues (leaky gut for sure, probably heavy metals?) all the stuff from the methionine cycle is shunted away to pruduce glutathione. So there's not enough methionine/sam-e for all the other stuff which is in need for methyl groups (like coenzyme q10, carnitine, phospholipds, amico acids with methyl groups, creatine and so on which have all testet low).
My doctor told me to try choline as it's stimulating the parasympathicus. Unfortunately I am prone to asthma and a hyperreactive bronchial system and choline which is metobilized into acetylcholine can lead to bronchial constriction (which it did in my case).

Unfortunately I am very sympathetic-dominant whith lots of catecholimanines in my system (dopamine, norepinephrine), I guess that's due to low COMT activity. I also guess (but still waiting for the results) that I have a slow MAO-A, because I am high in serotonine and 5htp gives me bad side effects as do all the antidepressants. I already have enough of this stuff. I am only lacking epinephrine as sam-e is needed to put a methyl group on it and I am also lacking cortisol. But trying to boost cortisol made me very hyper and I am already dealing with the more severe kind of chronic insomnia.

Methyl-B12 always rose my body temperture and made be lying awake several nights (tried 1mg shots).

So I ordered liquid sam-e from cellfood. It's only 72 mg in it but I was told it's the equivalent dose of 400 mg of normal sam-e in capsule form. So I started very low with 20 mg and was ok. When I took 50 mg several days in a row I noticed an increase in insomnia/anxiety, similar to what I experienced when I took activated B6 (p5p).

I am also working on fixing my gut and liver problems and hope that over time the methionine will not completely used up for glutathione (which is sky high what is not a bad thing, so I am not depleted). But fixing gut/liver-problems won't be a quick fix and I am looking for ways to improve methylation so that I won't be so much depleted in other stuff which is in need of methyl groups.

So are there any possibilities to counteract the effects of sam-e / methyl-b12? I really can't stand more insomnia.

I know there are other methyl donors like TMG, but aren't they also very stimulating? Am I missing something?

Since I got sick I am not able to tolerate normal doses of supplements or medication any more. Even the third of the lowest available dose can give me serious side effects. Really don't know why, but I also can't tolerate other things like noise, heat and stress.

I am able to tolerate carnitine but it does not help as much as I hoped as I am also defient in creatine, Co10 (very stimulating for me) and testosterone which is all need for muscle strength. My muscles are very very weak and going into spasm easily. Magnesium did nothing for me, maybe I have to increase the dose.

Any appreciations are welcome about how to support methylation!

And sorry for mistakes, I am not a native speaker as you may have noticed ;-)

 

[PeterPositive]

I think you have made the same mistake a lot of us make... starting too abruptly with a high dose... then getting scared and not wanting to see B12 ever again.

I have done the same mistake multiple times. A 1mg shot is quite a high dose, definitely higher than taking a 1mg sublingual which doesn't translate to a full 1mg dose in your blood stream.

The suggestion is the usual I give everyone ... and I am not a doctor, but this is just common sense.

Start low.

Really, there's nothing else to it. Just find a dose that is low enough that it doesn't bother you.
For example start at 50mcg, which is already a significant dose, but not as high as 1000mcg.

If possible take it sublingually to bypass the digestion and avoid wasting the B12. You can buy a low dose sublingual and cut it into smaller bits or crush a 1mg tablet and just take a few crumbs.

I started like that and eventually I was able to tolerate higher doses and these days I take ~10 000mcgs a day (it's not a competition, of course! I just found that two 5mgs doses a day are the best dosage for me.

good luck

 

[Hope78]

Hi Peter,

thanx for your reply.
I don't know so much about methylation and biochemistry. But my blood levels of active B12 are in the high normal range, so I am not sure if supplementing B12 will bring any improvement. I have low methionine and in my understanding active B12 is giving a methyl group to methionine to generate "activated methionine" aka sam-e. So without enough methionine there won't be enough sam-e even in the presence of methyl-b12, is that right?

But never the less I think you were right. I started with 500 mcg of methyl-b12 and did not tolerate it, of course 1000 mcg was much worse. I now switched to sublingual methyl B12 but don't know if it is helping (beside that it gives me acne like pimples I never had before).

In my understanding it is the following that happened to me and why I am short in substances which depend on sam-e:

"Oxidative stress: When the generation of free radicals (superoxide, hydroxyl, and hydrogen peroxide) outpaces our ability to neutralize them with endogenous (e.g. superoxide dismutase) or exogenous (supplemental antioxidants), we suffers from a buildup of free radicals. To address this immediate threat to health, Homocysteine metabolism down the CBS pathway (irrespective of genomic status) will increase. Homocysteine (and with it the potential to create new SAMe) will be irreversibly diverted away from remethylation (via MTR and BHMT back into methionine for conversion to SAMe) and towards the production of glutathione, taurine, and cysteine.
This all makes sense. Oxidative stress damages our physiology and kills cells. When faced with oxidative death, it makes sense to divert Methyl Cycle resources towards antioxidant generation. After oxidative stress has been neutralized, CBS flow will decrease, Homocysteine will start flowing back towards SAMe, and useful methylation reactions will resume. Our problem is that most ill Americans suffer from unremitting oxidative stress (we can measure your individual level of oxidative stress with the NutrEval study). Homocysteine will thus be shunted down the CBS pathway, such that useful methylation of DNA, estrogen molecules, and catecholamines will be compromised. If you cannot methylate catecholamines, then oxidative stress will develop within your blood vessels. If you cannot methylate your DNA, than you cannot silence inflammatory genes. You thus make more inflammatory molecules, more free radicals build up, more Homocysteine is diverted away from SAMe regeneration, and you are now chronically ill."
http://www.heartfixer.com/AMRI-Nutrigenomics.htm

I think there're different sources of oxidative/nitrosative stress in my case, like:

- unresolved emotional trauma/distress (working on it )
- food intolerances/leaky gut/gut dysbiosis (I am working on it!)
- heavy metal/environmental toxins
- and, that's a biggie: thyroid hormones (synthroid)

The problem with the thyroid hormones is a bit complicated. I have several cold nodules in my thyroid. There's a small chance that cold nodules will turn into cancer or grow. My thyroid specialist wants to prevent that happening and says I have to be on thyroid hormones live long with a TSH between 0.4 and 1.0. A tsh in the lower range is supposed to prevent further growth of the nodules.

Before I started synthroid my TSH was between 1.3 and 2.5, I would say perfectly normal and far far away from being hypo.

A short time after introducing thyroid supplementation I felt a decline in energy. As I am also low in cortisol I guess the thyroid hormones are demanding greater production of cortisol, but my already exhausted adrenals were not able to.
Beside that it is known that thyroid hormones increase oxidative stress and there's also strong evidence that thyroid hormones can decrease improtant enzymes like SOD.

My oxidative stress levels were sky high and I am feeling really bad since taking these hormones.

But my doctor does not want to know something about cfs or oxidative stress nor does he know about adrenal fatigue (does not exist in his opinion). I visited some other thyroid specialists. But since the consence of treating cold nodules (struma nodosa) is the comination of thyroid hormones and iodine (or surgery!!) all they say is "it is not possible that you feel so bad from only 50 mcg of thyroid hormones, must be something else like depression (HAHA)". One doctor even asked me "do you want to get cancer? No? Then take your hormones".

So I am very anxious about reducing my thyroid hormones on my own without medical advice/support :-(

I am sure these nasty thyroid hormones have a great negative impact on my health as I really never was hypothyroid.

I always had low energy levels, even as a child and I guess these additional hormones put an extra burden on my metabolism/adrenals.

Sorry for the long explanation, probably a bit off topic!

I am looking for a doctor who is specialiaced in thyroid disorders and knows something about cfs/related conditions. But I really don't know when this will be, most thyroid specialists are very conservative and in the typical "academic medicine".

Whilst I am working on eleminating all these oxidative stress sources I'd like to support my methylations as I am really suffering (not able to walk half a mile and feeling constantly "poisoned" and weak)

 

[PeterPositive]

Hi Peter,

thanx for your reply.
I don't know so much about methylation and biochemistry. But my blood levels of active B12 are in the high normal range, so I am not sure if supplementing B12 will bring any improvement. I have low methionine and in my understanding active B12 is giving a methyl group to methionine to generate "activated methionine" aka sam-e. So without enough methionine there won't be enough sam-e even in the presence of methyl-b12, is that right?

Are you low in methionine (the amino acid) or SAMe?
If the former you will likely need to fix your diet, probably introducing more complete proteins or, if your digestion is not breaking them down correctly, add a methionine supplement.

If you're low on SAMe, then B12 will probably help. Serum level of B12 are not very telling by itself. Did you also your homocysteine? A pattern with elevated homocysteine and low methionine would be indicative of a B12 deficiency. Also MMA (methyl malonic acid) would be useful.

cheers

 

[Hope78]

Hi Peter,

I only know I am low in methionine despite enough proteins in my diet. Did not test for sam-e but will probably do next week.
My homocysteine is in the normal range as is MMA, both were tested some time ago. I was not tested for normal B12 levels, it's called holotranscobalamin, don't know the exact difference, values below 35 pmol/l show deficiency, mine was 85. MCV & MCHC were also normal meanwhile (they were not normal when I once was defient in B12/folic acid and iron but I hopefully supplemented with success!).

As homocysteine & MMA were both normal, but methionine was low and I am lacking substances which need methyl groups it was my guess that I am low in sam-e.

I tried to take some small amounts of methionine (250 mg) but it gave me sharp bladder pain!? I know it's used to acidify the urine (in cases of cystitis) and I have a very sensitive bladder, so I stopped but will probably try again. Supplementing methionine is also a double edged sword as it's said to promote cancer in some cases.

I have very elevated levels of reduced glutathione (oxidized is normal) and very high levels of citrulline (should be below 100, is at about 1200), nitrotyrosine - another marker for nitrostress - is in the normal range.

Any suggestions why my citrulline is sky high? Did not supplement with arginine or glutamine (which can lead to elevated levels, too).

Btw, your cat has nice glasses

 

[aaron_c]

Hi @Hope78

I am NOT an expert on thyroid stuff. But I have a limited, eclectic understanding. So a few things that I hope you and a good doctor might find useful:

1. I see that you mention iodine as a possible treatment for cold thyroid nodule(s). You might consider trying that instead of the thyroid hormone, which seems to disagree with you so much. Here is one testimonial where someone's goiter started shrinking and becoming more squishy after they started taking high doses of potassium iodide.

As a side note, potassium iodide (KI) and iodine (I) work differently in the body. At least, I and others can take a whole lot of potassium iodide, but too much iodine causes problems for me. I am trying to titrate up...we'll see. For reference, Lugol's solution is a combination of KI and I, but there are pills with just KI.

Of course, if you are genetically prone to Hashimoto's (a family history of the disease would be one good clue) then this becomes riskier and more controversial. I believe that the very pro-iodine people still think it is a good idea, but even they suggest a slow increase in dosage. And I have yet to find what they mean by "slow." Here is a link to a well-sourced article by a pro-iodine doctor on iodine and Hashimoto's...one who, unlike Dr.'s Abraham and Brownstein, does not rely on Noah's Ark to make his argument.

Most everyone else, of course, would suggest you stay away from high doses of iodine if you have some Hashimoto's genes.

2. Here is a good article on the benefits of carnitine for hyperthyroidism--essentially carnitine gets used up at an increased rate when you are hyperthyroid, and this is particularly bad because carnitine works to blunt the effects of T3--at least in hyperthyroid patients. This was studied in people who, like yourself, had benign thyroid nodules and were given thyroid hormone. The hyperthyroid side-effects disappeared while they took carnitine at 2 or 4 grams per day.

Oh, I see you have tried carnitine with limited benefits. Well, maybe the article will still be of interest.

3. It seems like your hypersensitivity to methyl groups might be related to your hyperthyroidism. But if it is a separate issue, I want to second what @PeterPositive said: low and slow might help.

4. On another note entirely, I am not sure how much you can rely on blood levels of B12 to tell you whether you have enough. As Rich Van Konynenburg pointed out some years ago, CblC, an enzyme involved in cobalamin use and possibly transport within the cell requires glutathione to function well. Without enough glutathione, it reduces the availability of both methylcobalamin and adenosylcobalamin to their respective enzymes--and if this were the case I think your serum B12 would be unchanged. So all of the oxidative stress you have might be serving to increase your need for B12 without affecting your serum B12.

As far as I can tell, most people experiment to find the dose and mix of B12's that works for them.

Best of luck, I hope you find some answers.

Aaron C

 

[Hope78]

Hi,

@aaron, thanx a lot for this helpful input!

I'd really like the link about hyperthyroidism and l-carnitine. Carnitine seems to be the only supplement right now I am tolerating in normal doses. Maybe 500 mg to 1 g wasn't enough as the study pointed out to use 4 g at minimum. I am always cautious with high doses as I tend to have strange reactions on most of the supplements. But it's definitely worth a try.

Also very interesting what you wrote about iodine. Fortunately I am not prone to Hashimoto.

Last time my glutathione levels were measured, reduced g. was very elevated but oxidized g. was in the normal range. But I will redo this test this week as my feelings of being "poisoned" worsened over the last year.
I will also test for sam-e this week as being low in it was only my personal conclusio

 

[aaron_c]

the study pointed out to use 4 g at minimum

I think they used both 2 g and 4 g daily doses at different times and reported success with both.

Last time my glutathione levels were measured, reduced g. was very elevated but oxidized g. was in the normal range.

That sure is weird. I don't have enough experience looking at test results to know if that happens sometimes, but...are you sure that's not backwards?

I am always cautious with high doses as I tend to have strange reactions on most of the supplements.

As I mentioned before, Iodine might be another problematic supplement to take at high doses because as you may have read iodine can displace bromine and fluoride, causing a detox. I don't think that potassium iodide causes this, for whatever reason, so you might have easier going trying that to shrink your nodule(s). The pro-iodine people suggest that goiters are mostly caused by stuff like bromine and fluoride, so I think they would suggest trying elemental iodine at some point.

I have to take chlorella and cilantro extract with my moderately high dose of iodine/potassium iodide (750 mcg iodine/day) in order to avoid getting a headache.

 

[kyzcreig]

How do you feel if you take p5p? It's needed to metabolize protein, so if you have a high protein diet you'll need much more than the average bear.