Trimethylglycine (TMG)

Trimethylglycine, commonly known as TMG or betaine, is an amino acid derivative that naturally occurs in various plant and animal sources. With its three methyl groups attached to a glycine molecule, TMG has garnered attention in both the dietary supplement market and the scientific community due to its role as a methyl donor in vital biochemical processes.

Although trimethylglycine supplementation decreases the amount of adipose tissue in pigs, research on human subjects has shown no effect on body weight, body composition, or resting energy expenditure when used in conjunction with a low calorie diet.

Protective Effects

Protective effects of TMG in experimental animal models, cell culture systems, and clinical studies. Removed ADL and MAFLD

Therapeutic Effects of TMG Administration	Experimental Model	Authors
	Male Wistar rats; C57BL/6 mice; Balb/c mice	[23,27,83,115,121,157,158,160]
	Male Wistar rats; hepatocytes; male C57BL/6 mice	[23,60,61,81,82,83,84,86,88,91,92,117,119,121,234,235]
Restores activities of various liver methyltransferases (PEMT, ICMT, PIMT, PRMT) to increase phosphatidylcholine levels, preventing apoptosis and accumulation of damaged proteins, and restoring proteasome activity	Male Wistar rats; hepatocytes	[23,90,91,92]
	Male C57BL/6 mice	[121]
	Male Wistar rats	[133]
	Male C57BL/6 mice	[83]
	Male Wistar rats	[61]
	Mice	[123]
Prevents elevations of CD14, TNFα, COX2, GADD45β, LITAF, JAK3, TLR2, TLR4, IL1β, and PDCD4 and NOS2 mRNA levels in alcoholic liver injury	Male Wistar rats	[115,133]
	Male Wistar rats	[27,115,121]
	Male C57BL/6 mice	[28]
	C57BL/6 mice	[161]
	Male Sprague-Dawley rats	[162]
	Male C57BL/6 mice; rats	[120,161]
	Mice	[203]
	Male Sprague-Dawley rats	[163].
	Human trials	[45,165,166,167]
	Male C57BL/6 mice	[194]
Reduces the inflammatory adipokines, IL6, TNFα, and leptin in human adipocytes	Human visceral adipocytes	[204]
Inhibits lipid peroxidation, hepatic inflammation, and expression of transforming growth factor-β1 in liver fibrosis	Male chicks	[148]
Suppresses alcoholic liver fibrosis	Rats	[116]
Prevents the formation of Mallory–Denk bodies through epigenetic means by attenuating the decrease of MAT1A, SAHH, BHMT, and AMD1 expression	C3H male mice	[138]
Reverses the inhibitory effects of acetaldehyde on IFN signaling and decreases de-methylation of STAT1 by JMJD6	HCV-infected Huh7.5 CYP2E1 (+) cells and human hepatocytes	[141,143]
Enhances expression of PPARα and elevates fatty acid catabolism	Male C57BL/6 and ApoE−/− mice	[158].
Inhibits lipogenic activity in liver by activation of AMPK	ApoE−/− mice; Male C57BL/6 mice	[159,160]
Regulates colonic fluid balance	Rats	[21,200]
Improves intestinal barrier function and maintains the gut microbiota	Porcine epithelial cells; Caco-2 cells; rat small intestinal cell line IEC-18	[22,197,198]
Activates GI digestive enzymes and ameliorates intestinal morphology and microbiota dysbiosis	Male Sprague Dawley rats	[200]
Attenuates alcoholic-induced pancreatic steatosis	Male Wistar rats	[125]
Associated with resilience to anhedonia and prevention of stress-related psychiatric disorders	Male C57BL/6 mice	[218]
Treats asthma-induced oxidative stress, thus improving airway function of lung tissue	BALB/C mice	[207]
Protects against cadmium nephrotoxicity	Male Wistar rats	[206]
Protects against isoprenaline-induced myocardial dysfunction	Male Wistar rats	[205]
Anti-nociceptive and sedative role via interactions with opioidergic and GABA receptors	Male albino mice	[220]
Normalizes fetal growth and reduces adiposity of progeny from obese mice	C57BL/6J mice	[229]
Anti-cancer effect in alcohol-associated breast cancer cell growth and development	Breast adenocarcinoma cell line (MCF-7)	[213]
Reduces rectal temperature in broiler chickens	Chickens	[226,227]
Improves post-natal lamb survival	Lambs	[230]

Taking TMG

Side effects

Trimethylglycine supplementation may cause diarrhea, bloating, cramps, dyspepsia, nausea or vomiting. Although rare, it can also causes excessive increases in serum methionine concentrations in the brain, which may lead to cerebral edema, a life-threatening condition.

Trimethylglycine supplementation lowers homocysteine but also raises LDL-cholesterol in obese individuals and renal patients.