I started taking TMG 1 cap and NAC 1 cap day before yesterday night.
I have been feeling more off episodes for the last two days.
Does TMG increase the production of dopamine resulting in an increased need for ldopa? Also any suggestions on the time to take the combo?
I am generally under-medicated by choice.
Edit 21-10-24:
I had taken Ropark 0.25 x 2/day for 3 days --> 0.5 for two days (experienced dizziness) --> 0.25 for 4 days before stopping while starting TMG and NAC.
TMG is a methyl donor, if you feel worse you may be overmethylated. Methylation plays a role in dopamine production and should decrease off time.
What do you suggest? Stop TMG and take only NAC for the time being?
Are you taking any other methyl donors (methylfolate, msm, methylcobalamin (B12), choline, etc.). I'm not a doctor, How long have you been taking TMG. Might should give another few days.
Patients with an intolerance to methyl donors can experience worsening symptoms as well as the appearance of neurological symptoms, regardless of their need for methylation support. Neurological symptoms may include, anxiety, depression, irritability, and brain fog, among other symptoms. linkedin.com/pulse/intolera...
Yes. I take it methylated B-Complex and Magnesium L-Threonate in the morning.
If over methylation is suspected, should I try Glycine and NAC instead of TMG and NAC?
I had started TMG and NAC with the objective that TM will reduce my slightly elevated Homocysteine while G+NAC will boost Glutathione.
TMG = Trimethylglycine. en.wikipedia.org/wiki/Trime...
As Gcf51 said, TMG contributes to methylation. In the process, it elevates SAMe, which is usually a good thing, but may not be in PD.
sciencedirect.com/science/a....
"The major symptoms of Parkinson's disease (PD) are due to degeneration of the nigrostriatal pathway and depletion of dopamine (DA). Tyrosine hydroxylase (TH), norepinephrine (NE), serotonin (5-HT), and melanin pigments are also decreased and acetylcholinergic activity increased. Biochemically, increased methylation can cause the depletion of DA, NE, 5-HT, and melanin pigments and also an increase of acetylcholine; thus, increased methylation can present a biochemical picture that resembles the biochemical changes that occur in PD. During the therapy of PD with l-dopa, it is well known that l-dopa reacts avidly with (SAM), the biologic methyl donor, to produce 3-O-methyl-dopa. Correspondingly, l-dopa has been shown to deplete the concentration of SAM, and SAM has been found to induce PD-like motor impairments in rodents; therefore, an excess of SAM-dependent methylation may be associated with Parkinsonism."
Thank you 🙏
Just learned something else that I thought was interesting. COMT inhibitors, taken to delay "off" periods, work by interfering with the production of 3-O-methyldopa from L-dopa. So they do the opposite of what SAMe apparently does.
I don't know if one 1000 mg TMG pill will raise SAMe enough to increase the production of 3-O-methyldopa or not. If it does, 3-OMD will compete with levodopa for transporters, reducing the amount of dopamine available to the CNS. Healthline says 3.5 ounces of beets contains 114 to 297 mg. of TMG. You could try eating a pound of beets to see if you get the same effect. 😝
Seriously though, I would try the two supplements separately, to see if it's one or the other or an interaction between the two that's giving you trouble. It would surprise me if NAC is the problem since many here take it, and 600 mg is a small dose. It's thought to increase dopamine release, but maybe you're an outlier!
From what I understand, TMG is present in food and if its a small dose it could be similar to eating beetroot etc. Whereas NAC acts more like a drug, since it is a modified amino acid. I'd suspect more the NAC, but I have no real idea. I'm definitely not a doctor.
How many mg in each of these caps? The dose makes the medicine/poison, as they say.
It seems that the clear path through all this underbrush is to reduce the amount of methyl donors you are taking. That would suggest simply using alternatives that aren't methylated... Perhaps anything that has methyl in its chemical name might be a clue as to what to reduce and avoid. Plus adding a bit more of your L-dopa...which opens a question: exactly why is it that you are, as you said at the very beginning, intentionally under-medicated?
I take NAC first thing in the morning and TMG at night. You may want to reduce the dosage and gradually build up.
Have you done genetic testing? Do you know if you have the MTHFR gene polymorphisms. Having the variant means your body may not break down folate as well as it should and can lead to increased homocysteine levels. This past month we found out that my mom who has PD since 2002 has the double C677T MTHFR gene SNP and other many methylation and detox issues. I wonder how many patients with PD have these methylation gene SNPs.
You can run your 23andme, myheritage, etc. raw DNA data in a couple of different websites for free (without making an account) to see if you have methylation and detox genes SNPs.. nutrahacker.com/, geneticgenie.org/
If you decide to come off methylated B vitamins, be sure not to use artificial B9 folic acid and B12 cyanocobalamin, but B9 folinic acid (5-formyl tetrahydrofolic acid) and B12 hydroxocobalamin.
So far, TMG and SAM-e have had a positive effect on my mom's Parkinson's movement. We were able to lower her CL, and her body doesn't seem as rigid. We have also eliminated all artificial folic acid and B12 found in enriched grains from her diet.
I found this study about L-DOPA and methylation --pmc.ncbi.nlm.nih.gov/articl... --that talks about how L-DOPA can raise homocysteine levels.
My MTHFR test:
MTHFR C677T Not Detected
MTHFR A1298C Detected – Heterozygous
I understand that Heterozygous A1298C is not deemed to be of any consequence, so my Homocysteine elevation is probably due to Levodopa medication.
NAC symptomatic or disease modifying? 
Any NAC users out there ?
Parkin, glutamate, NAC, mitophagy
