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.

Positiv Effects

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

Therapeutic Effects of TMG Administration	Experimental Model	Authors
Prevents hepatic fat accumulation in ALD	Male Wistar rats; C57BL/6 mice; Balb/c mice	[23,27,83,115,121,157,158,160]
Preserves/restores hepatic SAM: SAH ratios by regenerating SAM and lowering SAH and homocysteine levels in ALD	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]
Suppresses the synthesis of DGAT2, a rate-limiting enzyme in triglyceride synthesis, by alleviating ERK1/2 inhibition in ALD	Male C57BL/6 mice	[121]
Upregulates antioxidant defense system and improves oxyradical scavenging activity in ALD	Male Wistar rats	[133]
Prevents/attenuates ER stress in ALD	Male C57BL/6 mice	[83]
Exerts hepatoprotection by preserving mitochondrial function in ALD	Male Wistar rats	[61]
Restores the serum adiponectin levels in ALD	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]
Prevents serum ALT and AST activity elevations in models of ALD and MAFLD	Male Wistar rats	[27,115,121]
Reduces liver oxidant stress, inflammation, and apoptosis in MAFLD	Male C57BL/6 mice	[28]
Remethylates homocysteine, protecting from oxidant stress and restoring phosphatidylcholine generation in MAFLD	C57BL/6 mice	[161]
Stimulates β-oxidation in livers of MCD diet-induced MAFLD	Male Sprague-Dawley rats	[162]
Alleviates steatosis and increases autophagosomes numbers in mouse livers with MAFLD	Male C57BL/6 mice; rats	[120,161]
Enhances the conversion of existing WAT to brown adipose tissue through stimulating mitochondrial biogenesis in MAFLD	Mice	[203]
Alleviates ROS-induced mitochondrial respiratory chain dysfunction in MAFLD	Male Sprague-Dawley rats	[163].
Attenuates different grades of steatosis, inflammation, and fibrosis in MAFLD patients	Human trials	[45,165,166,167]
Prevents adipose tissue dysfunction in ALD	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.