Dihydromyricetin Review: Benefits, How It Works, Where To Buy, Safety, And More!

Hey there!

Welcome to my review of Dihydromyricetin (DHM).

I recently discovered DHM and was curious to learn more about its use in alcohol abuse disorder.

After many hours of research I’ve learned that DHM has so much more potential than I originally thought.

The following review aims to synthesize and present the current knowledge on DHM, its biological activities, and its potential therapeutic applications, drawing from the latest scientific literature ¹.

We will journey through the intricate world of DHM, exploring its chemical structure, pharmacokinetics, mechanisms of action, and potential impact on clinical practice and public health.

So if you’re ready to learn more about health-boosting effects of Dihydromyricetin, let’s jump into the article!

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Overview of Dihydromyricetin

Dihydromyricetin, or DHM, is a natural compound in some plants, like the Chinese vine Ampelopsis grossedentata.

It has been used in traditional medicine and is now being studied for its potential health benefits.

Some of the positive effects of DHM include helping to fight diseases like diabetes, liver problems, and even some types of cancer.

It has also shown promise in reducing the harmful effects of alcohol on the body and brain, making it a potential treatment for alcohol-related issues.

This compound has caught scientists’ and doctors’ attention because of its many benefits. It can help protect our cells from damage, reduce inflammation, and improve our body’s energy use.

Also, DHM has positively impacted our mood and mental well-being.

Overall, dihydromyricetin is a fascinating substance with a wide range of potential benefits.

Chemical Structure and Properties of Dihydromyricetin

DHM, also known as ampelopsin, is a flavonoid belonging to the flavanonol subclass, characterized by its distinct 3-hydroxyflavan-4-one structure ².

It is primarily isolated from the vine Ampelopsis grossedentata, commonly known as the “treebine” or “porcelain berry” ³.

Other plant sources of DHM include Hovenia dulcis, Cedrus deodara, and Ampelopsis japonica ⁴⁵.

Two major approaches for obtaining DHM are isolation from natural sources and synthetic production.

Traditional isolation methods involve the extraction, purification, and chromatographic separation ⁶.

However, these methods are often time-consuming and yield low compound quantities.

Recent advancements in biotechnology have enabled the production of DHM through genetic engineering, offering a more efficient and sustainable alternative ⁷.

Pharmacokinetics and Metabolism of Dihydromyricetin

Understanding the pharmacokinetics of DHM is crucial for its practical therapeutic application.

Studies on absorption and distribution have shown that DHM exhibits rapid absorption and extensive tissue distribution⁸.

However, its oral bioavailability is relatively low, primarily due to its extensive metabolism in the liver ⁹.

DHM undergoes significant biotransformation through phase I and II metabolic reactions, which include hydroxylation, methylation, glucuronidation, and sulfation ¹⁰¹¹.

The primary metabolites identified in humans are DHM-3-O-glucuronide and DHM-3′-O-glucuronide ¹².

The elimination half-life of DHM varies between species, ranging from 2.7 to 8.8 hours ¹³.

Excretion occurs predominantly through bile and feces, with a smaller proportion excreted in urine ¹⁴.

Dihydromyricetin Benefits

Several preclinical and clinical studies have investigated the potential therapeutic applications of DHM in the context of alcohol use disorder, neurodegenerative diseases, liver diseases, and cancer treatment.

Alcohol use disorder and hangover relief

Preclinical evidence suggests that DHM can alleviate alcohol-induced behavioral impairments and reduce the severity of hangover symptoms by accelerating alcohol metabolism and mitigating oxidative stress and inflammation ¹⁵¹⁶.

By targeting specific receptors in the brain, DHM can help counteract alcohol’s impact on coordination and cognitive function and has been shown to help reduce hangover symptoms such as headache, nausea, and fatigue by promoting the body’s ability to break down alcohol and its toxic byproducts.

Clinical trials have demonstrated the potential of DHM as a hangover remedy, although larger-scale studies are needed to confirm these findings ¹⁷.

While preliminary studies are promising, more research is needed to establish the optimal dosage and treatment regimen for DHM to provide maximum benefit for those suffering from hangovers or alcohol use disorders.

Anxiolytic (Anti-Anxiety)

Dihydromyricetin’s potential to alleviate anxiety has become an intriguing area of research, given its interaction with GABA receptors and influence on GABAergic neurotransmission.

Anxiety disorders, which affect millions of people worldwide, are associated with an imbalance in the brain’s excitatory and inhibitory neurotransmitters.

By modulating GABAergic neurotransmission in the hippocampus, a region crucial for emotion and memory processing, DHM may provide a promising avenue for anxiety treatment.

A recent study by Joshua Silva et al. demonstrated that DHM enhances GABAergic neurotransmission in the hippocampus and increases the levels of gephyrin, a protein responsible for clustering and stabilizing GABA receptors at the synapses.¹⁸

This increase in gephyrin levels leads to more GABA receptor sites, which results in heightened sensitivity to GABA, the primary inhibitory neurotransmitter in the brain.

Consequently, DHM’s ability to modulate GABAergic neurotransmission and its impact on gephyrin levels contribute to its anxiolytic (anxiety-reducing) effects.

While more research is needed to understand the mechanisms and optimal treatment regimens fully, dihydromyricetin shows great promise as a potential therapeutic agent for anxiety and other neurological disorders linked to GABAergic neurotransmission.

Blood Sugar/Insulin Resistance/Glucose Metabolism

DHM may have the ability to help stabilize blood glucose metabolism, thus lowering instances of insulin resistance and eventual metabolic syndrome.

In one double-blind, randomized controlled clinical trial, sixty adult nonalcoholic fatty liver disease patients were randomly assigned to receive either two dihydromyricetin or two placebo capsules (150 mg)twice daily for three months ¹⁹.

DHM supplementation was shown to protect liver function, improve insulin resistance, regulate glucose and lipid metabolism, and slows the progression of liver steatosis in patients with NAFLD.

While the mode of action is still under investigation, benefits may stem from improved liver health.

Neurodegenerative diseases:

In preclinical models of Alzheimer’s disease, DHM has been shown to reduce amyloid-beta (Aβ) deposition and alleviate cognitive deficits ²⁰.

Additionally, DHM exhibits neuroprotective effects in animal models of Parkinson’s disease by attenuating dopaminergic neuron loss and mitigating motor dysfunction ²¹.

Further clinical studies are warranted to validate these promising findings.

Liver diseases

Preclinical studies have demonstrated the potential of DHM in treating NAFLD and alcoholic liver disease (ALD) by modulating lipid metabolism, oxidative stress, and inflammation ²²²³

These findings suggest that DHM could be a valuable therapeutic agent for individuals suffering from liver disorders.

Clinical trials investigating the efficacy and safety of DHM in patients with liver diseases are underway ²⁴.

Cancer treatment and Prevention

Although preclinical studies have demonstrated the anti-cancer potential of DHM, clinical evidence remains limited ²⁵.

Challenges associated with translating preclinical findings to clinical practice include optimizing DHM formulations, determining optimal dosing regimens, and evaluating potential drug interactions ²⁶

Biological Activities and Mechanisms of Action

DHM’s diverse biological activities are primarily attributed to its potent antioxidant, anti-inflammatory, neuroprotective, hepatoprotective, and anti-cancer properties ²⁷.

Furthermore, DHM modulates lipid metabolism by upregulating the expression of peroxisome proliferator-activated receptor-alpha (PPAR-α) and downregulating sterol regulatory element-binding protein 1c (SREBP-1c), which can help alleviate non-alcoholic fatty liver disease (NAFLD) ³⁵

Anti-cancer activity

DHM induces apoptosis in various cancer cell lines by activating caspase-dependent pathways and inhibiting anti-apoptotic proteins, such as Bcl-2 and Bcl-xL ³⁶.

Additionally, DHM has been shown to inhibit angiogenesis and metastasis by suppressing the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) ³⁷.

Safety, Toxicity, and Drug Interactions

Preclinical safety evaluations of DHM have indicated its low toxicity and relatively high tolerability ³⁸.

Clinical safety data, although limited, have not reported any significant adverse events or toxicities associated with DHM administration³⁹.

However, further studies are required to establish the long-term safety and potential drug interactions of DHM, particularly in combination with other therapeutic agents⁴⁰.

Dosing

The one human trial investigating DHM found that 150mg/day BID (300mg total) is safe and effective. ⁴¹.

Note that study was measuring glucose metabolism in NAFLD patients.

Conclusion

DHM, a unique flavonoid with diverse biological activities, holds significant promise as a therapeutic agent for various diseases.

This review has summarized the current knowledge of its chemical structure, pharmacokinetics, mechanisms of action, and potential therapeutic applications.

Although considerable progress has been made, further research is needed to overcome the challenges associated with clinical translation and optimize DHM’s potential impact on clinical practice and public health.

Future perspectives and research directions include the development of novel DHM formulations and delivery systems to improve its bioavailability, elucidating its precise molecular targets, and identifying potential synergistic effects with other therapeutic agents ⁴².

Large-scale, randomized controlled trials are needed to validate the efficacy and safety of DHM in various clinical settings, providing the foundation for evidence-based recommendations ⁴³.

In conclusion, DHM is a fascinating and promising compound that has the potential to contribute significantly to the prevention and treatment of a range of diseases.

References

1
Joshua Silva et al, Modulation of Hippocampal GABAergic Neurotransmission and Gephyrin Levels by Dihydromyricetin Improves AnxietyFront. Pharmacol., 09 July 2020
2
Dan Liu et al, Dihydromyricetin: A review on identification and quantification methods, biological activities, chemical stability, metabolism and approaches to enhance its bioavailabilityTrends Food Sci Technol. 2019
3
Jie Liu et al, Dihydromyricetin induces apoptosis and inhibits proliferation in hepatocellular carcinoma cellsOncol Lett. 2014
4
Ting Ting Liu et al, Dihydromyricetin ameliorates atherosclerosis in LDL receptor deficient miceAtherosclerosis. 2017
5
Zhaoxiang Ren et al, Dihydromyricetin exerts a rapid antidepressant-like effect in association with enhancement of BDNF expression and inhibition of neuroinflammationPsychopharmacology (Berl). 2018
6
Yi Shen et al, Dihydromyricetin as a novel anti-alcohol intoxication medicationJ Neurosci. 2012
7
Jing Liang et al, Dihydromyricetin prevents fetal alcohol exposure-induced behavioral and physiological deficits: the roles of GABAA receptors in adolescenceNeurochem Res. 2014
8
Liming Guo et al, Dihydromyricetin promotes autophagy and attenuates renal interstitial fibrosis by regulating miR-155-5p/PTEN signaling in diabetic nephropathyBosn J Basic Med Sci. 2020
9
Zhuangwei Zhang et al, Dihydromyricetin induces mitochondria-mediated apoptosis in HepG2 cells through down-regulation of the Akt/Bad pathwayNutr Res. 2017
10
Qinghai Li et al, Dihydromyricetin prevents monocrotaline-induced pulmonary arterial hypertension in ratsBiomed Pharmacother. 2017
11
Hongyan Ling et al, Dihydromyricetin improves type 2 diabetes-induced cognitive impairment via suppressing oxidative stress and enhancing brain-derived neurotrophic factor-mediated neuroprotection in miceActa Biochim Biophys Sin (Shanghai). 2018
12
Zhao-xiang Ren et al, Dihydromyricetin protects neurons in an MPTP-induced model of Parkinson’s disease by suppressing glycogen synthase kinase-3 beta activityActa Pharmacol Sin. 2016
13
Dafeng Yang et al, Dihydromyricetin Attenuates TNF-α-Induced Endothelial Dysfunction through miR-21-Mediated DDAH1/ADMA/NO Signal PathwayBiomed Res Int. 2018
14
Author(s), Name of studyname of publication. YEAR
15
Yingchun Zhao et al, Dihydromyricetin Reverses Thioacetamide-Induced Liver Fibrosis Through Inhibiting NF-κB-Mediated Inflammation and TGF-β1-Regulated of PI3K/Akt Signaling PathwayFront. Pharmacol. 2021
16
Jun Xie et al, Dihydromyricetin alleviates carbon tetrachloride-induced acute liver injury via JNK-dependent mechanism in miceWorld J Gastroenterol. 2015
17
Aneta SKOTNICOVÁ et al, Does Dihydromyricetin Impact on Alcohol MetabolismPhysiol Res. 2020
18
Joshua Silva et al, Modulation of Hippocampal GABAergic Neurotransmission and Gephyrin Levels by Dihydromyricetin Improves AnxietyFront. Pharmacol. 2020
19
Joshua Silva et al, Modulation of Hippocampal GABAergic Neurotransmission and Gephyrin Levels by Dihydromyricetin Improves AnxietyFront. Pharmacol., 09 July 2020
20
Jing Liang et al, Dihydromyricetin ameliorates behavioral deficits and reverses neuropathology of transgenic mouse models of Alzheimer’s diseaseNeurochem Res. 2014
21
Baoping Jiang et al, Dihydromyricetin ameliorates the oxidative stress response induced by methylglyoxal via the AMPK/GLUT4 signaling pathway in PC12 cellsBrain Res Bull. 2014
22
Xianglong Zeng et al, Dihydromyricetin Ameliorates Nonalcoholic Fatty Liver Disease by Improving Mitochondrial Respiratory Capacity and Redox Homeostasis Through Modulation of SIRT3 SignalingAntioxid Redox Signal. 2019
23
Yingchun Zhao, Dihydromyricetin Reverses Thioacetamide-Induced Liver Fibrosis Through Inhibiting NF-κB-Mediated Inflammation and TGF-β1-Regulated of PI3K/Akt Signaling PathwayFront. Pharmacol. 2021
24
Joshua Silva et al, Dihydromyricetin Protects the Liver via Changes in Lipid Metabolism and Enhanced Ethanol MetabolismAlcohol Clin Exp Res. 2020
25
Qing-Yu Zhang et al, Dihydromyricetin inhibits migration and invasion of hepatoma cells through regulation of MMP-9 expressionWorld J Gastroenterol. 2014
26
Qin Hu et al, Dihydromyricetin inhibits NLRP3 inflammasome-dependent pyroptosis by activating the Nrf2 signaling pathway in vascular endothelial cellsBiofactors. 2018
27
Zhenzhu Sun et al, Dihydromyricetin alleviates doxorubicin-induced cardiotoxicity by inhibiting NLRP3 inflammasome through activation of SIRT1Biochem Pharmacol. 2020
28
Hongyan Ling et al, Dihydromyricetin improves type 2 diabetes-induced cognitive impairment via suppressing oxidative stress and enhancing brain-derived neurotrophic factor-mediated neuroprotection in miceActa Biochim Biophys Sin (Shanghai). 2018
29
XiaoJuan Wang et al, Dihydromyricetin Attenuates Colitis in Mice induced by DSS via Improving Intestinal Barrier FunctionResearch Square. 2022
30
Linying Shi et al, Dihydromyricetin improves skeletal muscle insulin sensitivity by inducing autophagy via the AMPK-PGC-1α-Sirt3 signaling pathwayEndocrine. 2015
31
Jun Xie et al, Dihydromyricetin alleviates carbon tetrachloride-induced acute liver injury via JNK-dependent mechanism in miceWorld J Gastroenterol. 2015
32
Yongbiao Chen et al, Dihydromyricetin protects against liver ischemia/reperfusion induced apoptosis via activation of FOXO3a-mediated autophagyOncotarget. 2016
33
Yongbiao Chen et al, Dihydromyricetin protects against liver ischemia/reperfusion induced apoptosis via activation of FOXO3a-mediated autophagyOncotarget. 2016
34
Lei Chen et al, Dihydromyricetin inhibits cell proliferation, migration, invasion and promotes apoptosis via regulating miR-21 in Human Cholangiocarcinoma CellsJ Cancer. 2020
35
Tingjuan Ni et al, Dihydromyricetin Prevents Diabetic Cardiomyopathy via miR-34a Suppression by Activating AutophagyCardiovasc Drugs Ther. 2020
36
Haili Huang et al, Dihydromyricetin suppresses the proliferation of hepatocellular carcinoma cells by inducing G2/M arrest through the Chk1/Chk2/Cdc25C pathwayOncol Rep. 2013
37
Nianshui Jing, Xinnan Li Dihydromyricetin Attenuates Inflammation through TLR4/NF-kappaB PathwayOpen Med (Wars). 2019
38
Joshua Silva et al, Modulation of Hippocampal GABAergic Neurotransmission and Gephyrin Levels by Dihydromyricetin Improves AnxietyFront. Pharmacol. 2020
39
Qingyu Zhang et al Dihydromyricetin promotes hepatocellular carcinoma regression via a p53 activation-dependent mechanismScientific Reports. 2014
40
Haili Huang et al, Dihydromyricetin suppresses the proliferation of hepatocellular carcinoma cells by inducing G2/M arrest through the Chk1/Chk2/Cdc25C pathwayOncol Rep. 2013
41
Joshua Silva et al, Modulation of Hippocampal GABAergic Neurotransmission and Gephyrin Levels by Dihydromyricetin Improves AnxietyFront. Pharmacol., 09 July 2020
42
Dan Zou et al, Dihydromyricetin improves physical performance under simulated high altitudeMed Sci Sports Exerc. 2014
43
Fei Wu et al, Preventive Effect of Dihydromyricetin against Cisplatin-Induced Nephrotoxicity In Vitro and In VivoEvid Based Complement Alternat Med. 2016

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Overview of Dihydromyricetin

Chemical Structure and Properties of Dihydromyricetin

Pharmacokinetics and Metabolism of Dihydromyricetin