Table 1.
Protective effects of betaine in experimental animal models, cell culture systems, and clinical studies.
| Therapeutic Effects of Betaine 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] |