OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Dihydromyricetin – Generic

DRUG CLASS

Herbal and Dietary Supplements

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NUMBER	MOLECULAR FORMULA	STRUCTURE
Dihydromyricetin	27200-12-0	C15-H12-O8

A polyphenolic hydroxy dihydroflavonol.

ANNOTATED BIBLIOGRAPHY

References updated: 16 August 2023

Abbreviations: DHM, dihydromyricetin; HDS, herbal and dietary supplements.

• Zimmerman HJ. Unconventional drugs. Miscellaneous drugs and diagnostic chemicals. In, Zimmerman, HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott,1999: pp. 731-4.

  (Expert review of hepatotoxicity published in 1999; several herbal medications are discussed, but not dihydromyricetin [DHM]).
• Jacobsson I, Jönsson AK, Gerdén B, Hägg S. Spontaneously reported adverse reactions in association with complementary and alternative medicine substances in Sweden. Pharmacoepidemiol Drug Saf 2009; 18: 1039-47. [PubMed: 19650152]

  (Among 778 spontaneous reports of adverse reactions to herbal and alterative medicines to a national Swedish Registry, no cases were attributed to DHM).
• Shen Y, Lindemeyer AK, Gonzalez C, Shao XM, Spigelman I, Olsen RW, Liang J. Dihydromyricetin as a novel anti-alcohol intoxication medication. J Neurosci. 2012;32:390-401. [PMC free article: PMC3292407] [PubMed: 22219299]

  (Rats given intraperitoneal injections of DHM had decreased voluntary intake of alcohol, less evidence of alcohol central nervous system effects, and fewer signs of subsequent alcohol withdrawal, the effects were attributed to DHM’s effects on GABA signaling).
• Teschke R, Wolff A, Frenzel C, Schulze J, Eickhoff A. Herbal hepatotoxicity: a tabular compilation of reported cases. Liver Int 2012; 32: 1543-56. [PubMed: 22928722]

  (A systematic compilation of all publications on the hepatotoxicity of specific herbal products identified 185 publications on 60 different herbs, herbal drugs and supplements but does not list or mention DHM).
• Bunchorntavakul C, Reddy KR. Review article: herbal and dietary supplement hepatotoxicity. Aliment Pharmacol Ther 2013; 37: 3-17. [PubMed: 23121117]

  (Systematic review of literature on HDS associated liver injury does not mention DHM).
• Navarro VJ, Seeff LB. Liver injury induced by herbal complementary and alternative medicine. Clin Liver Dis 2013; 17: 715-35. [PubMed: 24099027]

  (Review of the epidemiology, regulatory status, diagnosis, pathogenesis and causes of liver injury from herbal products with specific discussion of conjugated linoleic acid, ephedra, germander, green tea, usnic acid, flavocoxid, aloe vera, chaparral, greater celandine, black cohosh, comfrey, kava, skullcap, valerian, noni juice, pennyroyal and traditional herbal remedies; no mention of DHM).
• Navarro VJ, Barnhart H, Bonkovsky HL, Davern T, Fontana RJ, Grant L, Reddy KR, et al. Liver injury from herbals and dietary supplements in the U.S. Drug-Induced Liver Injury Network. Hepatology 2014; 60: 1399-408. [PMC free article: PMC4293199] [PubMed: 25043597]

  (Among 839 cases of liver injury from drugs collected in the US between 2004 and 2013, 130 were due to HDS products, including 45 from body building agents [probably anabolic steroids] and 85 from diverse HDS products, but no case was attributed specifically to DHM).
• Chen S, Zhao X, Wan J, Ran L, Qin Y, Wang X, Gao Y, et al. Dihydromyricetin improves glucose and lipid metabolism and exerts anti-inflammatory effects in nonalcoholic fatty liver disease: A randomized controlled trial. Pharmacol Res. 2015;99:74-81. [PubMed: 26032587]

  (Among 60 Chinese adults with nonalcoholic fatty liver disease treated with DHM [150 mg] or placebo twice daily for 3 months, weight did not change and hepatic steatosis as assessed by ultrasound improved similarly in the two groups, while serum ALT, AST and GGT levels decreased more in the DHM- than placebo treated subjects as did fasting glucose, LDL cholesterol, tumor necrosis factor alpha, CK-18 and FGF21 levels, and there were no adverse events in either group).
• Brown AC. Liver toxicity related to herbs and dietary supplements: Online table of case reports. Part 2 of 5 series. Food Chem Toxicol 2017; 107: 472-501. [PubMed: 27402097]

  (Description of an online compendium of cases of liver toxicity attributed to HDS products, does not list or discuss DHM).
• Medina-Caliz I, Garcia-Cortes M, Gonzalez-Jimenez A, Cabello MR, Robles-Diaz M, Sanabria-Cabrera J, Sanjuan-Jimenez R, et al.; Spanish DILI Registry. Herbal and dietary supplement-induced liver injuries in the Spanish DILI Registry. Clin Gastroenterol Hepatol. 2018;16:1495-1502. [PubMed: 29307848]

  (Among 856 cases of hepatotoxicity enrolled in the Spanish DILI Registry between 1994 and 2016, 32 were attributed to herbal products, the most frequent cause being green tea [n=8] and Herbalife products [n=6], no mention of DHM).
• Ran L, Wang X, Lang H, Xu J, Wang J, Liu H, Mi M, Qin Y. Ampelopsis grossedentata supplementation effectively ameliorates the glycemic control in patients with type 2 diabetes mellitus. Eur J Clin Nutr. 2019;73:776-782. [PubMed: 30089792]

  (Among 80 patients with type 2 diabetes on various antidiabetic medications treated with DHM [760 mg] or placebo once daily for 1 month, fasting glucose levels decreased in DHM treated subjects compared to placebo but there were no changes in lipid or insulin levels, and there were “no adverse reactions” in either group).
• Skotnicová A, Boubínová G, Boštíková Z, Dušková Š, Šulc M, Kutinová-Canová N, Mráz J, et al. Does dihydromyricetin impact on alcohol metabolism. Physiol Res. 2020;69(Suppl 4):S573-S581. [PMC free article: PMC8603706] [PubMed: 33656905]

  (Studies in vivo and in vitro in rats found no evidence that DHM affects alcohol metabolism or has hepatoprotective effects against alcohol induced liver injury).
• Silva J, Yu X, Moradian R, Folk C, Spatz MH, Kim P, Bhatti AA, et al. Dihydromyricetin protects the liver via changes in lipid metabolism and enhanced ethanol metabolism. Alcohol Clin Exp Res. 2020;44:1046-1060. [PMC free article: PMC7211127] [PubMed: 32267550]

  (In a mouse model of alcohol induced liver injury, oral administration of DHM was associated with less liver steatosis and triglyceride levels which was attributed to changes in lipid metabolism and enhancement of ethanol metabolism as well as suppression of immune responses).
• Chen J, Wang X, Xia T, Bi Y, Liu B, Fu J, Zhu R. Molecular mechanisms and therapeutic implications of dihydromyricetin in liver disease. Biomed Pharmacother. 2021;142:111927. [PubMed: 34339914]

  (Review of the potential mechanisms of action of DHM in treating liver disease as shown in multiple animal models and in vitro systems of cell injury).
• Verster JC, van Rossum CJI, Scholey A. Unknown safety and efficacy of alcohol hangover treatments puts consumers at risk. Addict Behav. 2021;122:107029. [PubMed: 34225031]

  (Analysis of over-the-counter or internet available dietary supplements advertised to treat or prevent hangovers [n=82], found that most contained vitamins and minerals, and 49% contained milk thistle, 48% DHM, 45% N-acetyl cysteine [NAC], 27% alpha lipoic acid, and at least two dozen other herbs, but without providing information of concentration and without any clinical studies of efficacy or safety in support of the use of any of the components).
• Ballotin VR, Bigarella LG, Brandão ABM, Balbinot RA, Balbinot SS, Soldera J. Herb-induced liver injury: Systematic review and meta-analysis. World J Clin Cases. 2021;9:5490-5513. [PMC free article: PMC8281430] [PubMed: 34307603]

  (Systematic review of the literature on HDS induced liver injury identified 446 references describing 936 cases due to 79 different herbal products, the most common being He Shou Wu [91], green tea [90] Herbalife products [64], kava kava [62] and greater celandine [48]; DHM is not listed or discussed).
• Bessone F, García-Cortés M, Medina-Caliz I, Hernandez N, Parana R, Mendizabal M, Schinoni MI, et al. Herbal and dietary supplements-induced liver injury in Latin America: experience from the LATINDILI Network. Clin Gastroenterol Hepatol. 2022;20:e548-e563. [PubMed: 33434654]

  (Among 367 cases of hepatotoxicity enrolled in the Latin American Drug-Induced Liver Injury Network between 2011 and 2019, 29 [8%] were attributed to herbal products, the most frequent being green tea [n=7], Herbalife products [n=5] and garcinia [n=3]; DHM is not mentioned).
• Wang Y, Wang J, Xiang H, Ding P, Wu T, Ji G. Recent update on application of dihydromyricetin in metabolic related diseases. Biomed Pharmacother. 2022;148:112771. [PubMed: 35247719]

  (Review of the in vitro and in vivo studies of dihydromyricetin demonstrating antiinflammatory, antitumor, antioxidant and antibacterial activity with applications in nonalcoholic fatty liver, alcoholic liver disease, chemical injury to the liver, acute liver failure and liver cancer, “with almost no toxicity”).
• Gong H, Xu H, Li M, Zhang D. Molecular mechanism and therapeutic significance of dihydromyricetin in nonalcoholic fatty liver disease. Eur J Pharmacol. 2022;935:175325. [PubMed: 36265611]

  (Review of the possible mechanism of action of DHM in treating nonalcoholic fatty liver from many in vitro and in vivo studies suggests that it has antiinflammatory and antioxidant activities and may act via sirtuin-dependent pathways).
• Al Omran AJ, Watanabe S, Hong EC, Skinner SG, Zhang M, Zhang J, Shao XM, et al. Dihydromyricetin ameliorates social isolation-induced anxiety by modulating mitochondrial function, antioxidant enzymes, and BDNF. Neurobiol Stress. 2022;21:100499. [PMC free article: PMC9755067] [PubMed: 36532369]

  (In mice housed alone suffering from “social isolation-induced anxiety”, administration of DHM decreased evidence of the mouse anxiety as well as changing mitochondrial function, levels of antioxidant enzymes and brain derived neurotrophic factor).
• Miao X, Luo P, Liu J, Wang J, Chen Y. Dihydromyricetin ameliorated nonalcoholic steatohepatitis in mice by regulating the composition of serous lipids, bile acids and ileal microflora. Lipids Health Dis. 2023;22:112. [PMC free article: PMC10394885] [PubMed: 37533083]

  (In mice given a methionine and choline deficient diet, treatment with DHM was associated with similar degrees of weight loss, but less hepatic fat and triglycerides and lower serum ALT [but not AST] levels, which was attributed to less increase in toxic bile acids and lipids and more benign ileal microflora).