Editing Trimethylglycine (TMG)

[[Information on nutritional supplements people with ALS have been taking]]

*[https://en.wikipedia.org/wiki/Trimethylglycine Wikipedia page]
*[https://examine.com/supplements/trimethylglycine/ Examine.com]

== Effects on ALS ==

[https://examine.com/supplements/trimethylglycine/ Examine.com]: ''The main mechanisms of betaine are either its usage as a methyl donor, where it either directly donates a methyl group to reduce homocysteine into L-methionine (seen as cardioprotective) or it increases bodily levels of S-Adenosyl Methionine (SAMe) or active folate molecules, and those two can then go on to donate methyl groups to other parts of the body. Due to this, supplementation of betaine is able to '''indirectly support whole-body methylation, and directly support a reduction in homocysteine''' (which is reliably observed following moderate to high dose supplementation. The other major mechanism is that betaine is as an osmolyte, or a molecule that is shuttled in and out of a cell to affect its hydration status. '''Similar to Creatine, increased intracellular concentrations of betaine promote cell hydration and resilience to stressors'''.''

''In conclusion, several types of evidence show that '''accumulation of homocysteine may increase the risk and progression of motoneuronal degeneration'''. If this is confirmed, '''early interventions to decrease homocysteine levels may be useful to modify ALS progression and possibly onset'''.'' {{#pmid:19551535|Zoccolella2010}}

''[...] at the mammalian '''neuromuscular junction homocysteine largely increases the inhibitory effect of oxidative stress on transmitter release, via NMDA receptors activation'''. This combined effect of homocysteine and local oxidative stress can specifically contribute to the damage of presynaptic terminals in neurodegenerative motoneuron diseases, including ALS.'' {{#pmid:26500495|Bukharaeva2015}}

''Here we show that '''homocysteine acts as an agonist at the glutamate binding site of the N-methyl-D-aspartate receptor, but also as a partial antagonist of the glycine coagonist site'''.'' {{#pmid:9159176|Lipton1997}}

''These results suggest that '''betaine contributes to both the decrease in the plasma homocysteine concentration and the suppression of plasma homocysteine elevation''' through the activation of liver BHMT.'' {{#pmid:16967763|Yagisawa2006}}

'''''Significant lowering of homocysteine concentration after the drinking period was found in subjects with concurrent folate and betaine supplementation'''. Vitamin B12 and vitamin B₆ supplementation did not lead to a statistically significant change in homocysteine. According to a multiple linear regression model, the homocysteine change in the wine-only group was mainly determined by the interaction between the higher baseline homocysteine concentration and the change in dimethylglycine levels. Folate and betaine can attenuate possible adverse effects of moderate alcohol consumption. Dimethylglycine should be interpreted together with data on alcohol consumption and homocysteine concentration.''{{#pmid:26771632|Rajdl2016}}v

''The study recruited patients with stage 1 essential hypertension and hyper-homocysteinemia (HCys ≥15 μmol/L), without a history of cardiovascular and cerebrovascular disease. They were sequentially randomized to receive a combined nutraceutical containing 400 μg folate-6-5-methyltetrahydrofolate, 3 mg vitamin B6, 5 μg vitamin B12, 2.4 mg vitamin B2, 12.5 mg zinc and 250 mg betaine (Normocis400®) once daily for two months, or supplementation with highly dosed folic acid (5 mg/day) (control group). Differences in serum HCys values were compared by ANOVA for repeated measures. A significant HCys reduction in comparison to baseline was found in both groups at the end of the study treatment, from 21.5±8.7 to 10.0±1.7 μmol/L for Normocis400® subjects (p less than 0.0001), and from 22.6±6.2 to 14.3±2.8 μmol/L for controls (p less than 0.0001). HCys reduction was significantly higher among patients treated with Normocis400® (p less than 0.035). The ideal HCys level (i.e. less than 10 μmol/L) was reached in 55.8% of cases in theNormocis400® group, and it was significantly higher than in controls. No side effects were observed in either treatment group. Randomized clinical trials are ongoing to test the effect of folate, B6, and B12 supplementation in primary prevention of cardiovascular and cerebrovascular events. In the meantime, especially when the ideal HCys level is far from being reached, Normocis400® appears to be safe, well tolerated and effective in reducing HCys levels.'' {{#pmid:27655522|Mazza2016}}

''Prior to supplementation, piglets had lower concentrations of plasma folate, betaine, and choline compared to baseline with no change in homocysteine. Post-supplementation, phenylalanine oxidation levels were 20-46 % lower with any methyl donor supplementation (P = 0.006) with no difference among different supplementation groups. Furthermore, both methyl donors led to similarly lower concentrations of homocysteine following supplementation (P < 0.05).'' {{#pmid:26419586|McBreairty2016}}

''Interestingly, treatment with betaine significantly inhibited Hcy-induced MMP-9 activity in the frontal cortex but not in the hippocampus after acute Hcy injection. These results suggest that the changes in MMP-9 activity after betaine treatment might have been partially responsible for the amelioration of the memory deficits and that MMP-9 might be a candidate therapeutic target for HHcy.'' {{#pmid:26057356|Kunisawa2015}}

''The present results show beneficial antioxidant and methyl donor properties of betaine versus oxidative stress and hyperhomocysteinemia induced by levodopa and benserazide in an animal model.'' {{#pmid:25665954|Alirezaei2015}}

==Homocysteine metabolism ==

http://1.bp.blogspot.com/-a3BtMR98ehw/Ug5PNwm8NtI/AAAAAAAAAEY/1DKVB_4Epto/s640/Homocysteine_metabolism.png

== Discussion threads on the ALSTDI forum ==

* [http://www.als.net/forum/yaf_postst53867_homocysteine-and-als.aspx Homocysteine and ALS]

== Where to get it ==

* [http://eu.iherb.com/tmg-anhydrous-betaine iHerb]

== References ==

[[Category:Supplement data pages]]