datadragon
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This may be helpful in earlier stages of ME/CFS where inflammation is overactive. At minimum it explains there are additional effects of Betaine to consider and why some cannot tolerate Betaine or at higher dose (including most likely in later stage of ME/CFS) when inflammation levels are not currently high.
Betaine, also known as trimethylglycine (TMG), is a chemical compound that can be found in both natural and synthetic forms. Two common variations are betaine anhydrous (TMG) and betaine hydrochloride (HCl) that some use for stomach acid. Mechanistically betaine inhibits nuclear factor-κB (NF-kB) activity and NLRP3 inflammasome activation, regulates energy metabolism, and mitigates endoplasmic reticulum stress and apoptosis. In addition, betaine can also reduce endogenous damage-associated molecular pattern (DAMP) generation to inhibit the NF-κB pathway. Betaine improved the intestinal mucosal barrier by upregulating expression of zonula occludens-1 (ZO1) and occluding-tight junction proteins as well as maintained the normal gut microbiota composition in an acute liver failure model by inhibiting the TLR4/MyD88 signaling pathway. Interestingly, in another study, betaine could restore abnormal adipokine levels in NAFLD, and it upregulated adiponectin and downregulated leptin and resistin in adipose cells to attenuate the dysregulated lipid metabolism. It should be noted that factors involved in feeding (such as glucose, ghrelin, and leptin) inhibit the activity of orexin neurons involved in the regulation of sleep and wakefulness among many other things. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4345701/ and https://pubmed.ncbi.nlm.nih.gov/21907138/
https://www.frontiersin.org/articles/10.3389/fimmu.2018.01070/full
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224793/
Betaine, also known as trimethylglycine (TMG), is a chemical compound that can be found in both natural and synthetic forms. Two common variations are betaine anhydrous (TMG) and betaine hydrochloride (HCl) that some use for stomach acid. Mechanistically betaine inhibits nuclear factor-κB (NF-kB) activity and NLRP3 inflammasome activation, regulates energy metabolism, and mitigates endoplasmic reticulum stress and apoptosis. In addition, betaine can also reduce endogenous damage-associated molecular pattern (DAMP) generation to inhibit the NF-κB pathway. Betaine improved the intestinal mucosal barrier by upregulating expression of zonula occludens-1 (ZO1) and occluding-tight junction proteins as well as maintained the normal gut microbiota composition in an acute liver failure model by inhibiting the TLR4/MyD88 signaling pathway. Interestingly, in another study, betaine could restore abnormal adipokine levels in NAFLD, and it upregulated adiponectin and downregulated leptin and resistin in adipose cells to attenuate the dysregulated lipid metabolism. It should be noted that factors involved in feeding (such as glucose, ghrelin, and leptin) inhibit the activity of orexin neurons involved in the regulation of sleep and wakefulness among many other things. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4345701/ and https://pubmed.ncbi.nlm.nih.gov/21907138/
https://www.frontiersin.org/articles/10.3389/fimmu.2018.01070/full
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224793/
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