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!