Colitis Crohn's Gastrointestinal

Curcumin May Support Alcohol Dehydrogenase Activity to Protect Against Liver Damage

alcohol-dehydrogenase

For a growing proportion of Americans, liver damage is a frightening reality. The liver plays an important role in metabolism and detoxification, and patients with liver damage face debilitating symptoms and a significantly higher risk of death from liver failure. The increasing prevalence of liver damage is driven in part by lifestyle issues; the most common cause of liver damage in the United States is excessive alcohol intake, but a high-fat diet can also contribute to the condition, especially when it leads to obesity. However, liver damage is also associated with inflammatory bowel diseases (IBDs) and some of the inflammation-related pathological processes underpinning IBDs, such as ulcerative colitis and Crohn’s disease, are linked to the development of liver disorders. Moreover, recent research indicates that the drugs used to treat IBDs, including immunosuppressants and biologics, can also lead to liver damage.

Regardless of the cause of the liver damage, the health risks are serious, spurring patients to look for ways to support normal functioning and protect against the development of cirrhosis. Unfortunately, depending on the cause of the liver damage, treatments options are limited, which has led to an increase in research interest in the field. Currently, one particular target of research interest is alcohol dehydrogenase, an enzyme found primarily in the liver.

Alcohol dehydrogenase is responsible for catalyzing the oxidation and reduction of various alcohols and aldehydes (which are organic molecules similar to alcohols, but with a slightly different molecular structure). That makes alcohol dehydrogenase a key player in some of the detoxifying processes that protect the liver from damage. More specifically, when high levels of toxins like alcohols, “unhealthy” dietary fats, and certain medications reach the liver, they can contribute to the production of free radicals that increase inflammation and directly damage hepatic tissue. The activities of alcohol dehydrogenase help to fight these effects and minimize the damage.

Emerging research suggests that curcumin, the active compound in turmeric, may effectively support the activity of alcohol dehydrogenase in a way that protects against liver damage. Although clinical trials have yet to be conducted, there are several early studies in mice that offer key insight into the mechanisms through which all-natural curcumin supplements may provide protective benefits for patients.

Exploring the Relationship Between Alcohol Dehydrogenase and Curcumin

The first indication that there might be a relationship between alcohol dehydrogenase and curcumin came in 2011 when a group of Japanese scientists published an article in the Proceedings of the Natural Academy of Sciences of the United States (PNAS) describing their discovery of the curcumin metabolic pathway in an intestinal microorganism. Intriguingly, the unique curcumin-metabolizing enzyme they found (which they called NADPH-dependent curcumin/dihydrocurcumin reductase, or CurA), bore a significant sequence similarity to well-known enzymes in the alcohol dehydrogenase family. This finding provided an initial suggestion that it maybe possible for curcumin to interact directly with the alcohol dehydrogenase enzymes in the human liver.

The strongest evidence for a direct relationship between curcumin and alcohol dehydrogenase, however, came in 2013, when a group of researchers from several universities in South Korea collaborated on an effort to investigate the protection that low doses of curcumin could provide against liver damage caused by a chronic alcohol intake and a high-fat diet. In order to explore this question, they treated mouse models on high-alcohol, high-fat diets with two different doses of curcumin (0.02% and 0.05% body weight) for six weeks. At both levels, they saw significant effects. In addition to reducing the activity of enzymes that are known to contribute to liver damage, the curcumin supplements prevented the alcohol-induced inhibition of alcohol dehydrogenase activity to a statistically significant degree. Notably, curcumin supplementation also led to significant declines in plasma levels of leptin, free fatty acids, and triglyceride levels, all of which contribute to inflammation and liver damage. These results serve as preliminary evidence that by modulating key enzymes like alcohol dehydrogenase, curcumin supplements can effectively prevent liver damage.

The results of the 2013 study were later supported by a paper out of George Washington University, in which the researchers again reported a connection between supplementary curcumin intake and liver damage in mouse models. Like the Korean researchers, the research team from George Washington set out to explore this connection by treating mice on high-fat, high-alcohol diets with curcumin, this time with supplements of 150 mg/kg/day, each day for eight weeks. At the end of the intervention period, they found that the mice in the treatment group were protected from ethanol-induced hepatic steatosis (that is, the accumulation of fatty tissue in the liver) and displayed lower levels of oxidative stress and liver injury markers (as measured in blood samples) than those that did not take the supplements. Thus, like previous researchers, they concluded that curcumin supplements may offer protection from liver damage.

Harnessing the Potential Links Between Alcohol Dehydrogenase and Curcumin in the Clinical Setting

Like the research community, more patients and practitioners than ever are intrigued by the hepatoprotective benefits that curcumin may provide, partially through its mediation of the alcohol dehydrogenase enzymes in the liver. For patients who are seeking to avoid the health risks of liver damage—whether it is associated with alcohol intake, dietary fats, medications, or inflammatory bowel conditions—a curcumin supplement may offer therapeutic benefits. In the future, clinical research will likely shed more light on the effects in humans, but for now, the animals studies suggest that it may be worth exploring curcumin supplements as an option and monitoring their impacts on the individual patient’s liver.

As patients and practitioners work together to develop a curcumin supplementation strategy to effectively prevent liver damage, it is important to choose a curcumin supplement with high bioavailability. Even though the researchers from Korea reported that the mice in the study were treated with “low-dose” curcumin supplements, curcumin is well-known for its low bioavailability, meaning that it is poorly absorbed in the GI tract. This means its impact on the body can be limited by formulation, even when it is taken at higher doses. In order to maximize the likelihood that a curcumin supplement will be absorbed, metabolized, and provide the desired protective benefits, patients and practitioners should therefore look for curcumin supplements that were specifically designed for optimal bioavailability.

Foundational Medicine Review covers cutting-edge research related to innovative treatment strategies for gastrointestinal issues, neurological disorders, and other health conditions. Join our mailing list today for more insight and analysis.

Works Cited

Casas-Grajales S, Muriel P. 2015. Antioxidants in liver health. World Journal of Gastrointestinal Pharmacology and Therapeutics. 6(3):59-72. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4526841/

Edinberg HJ, Bosron WF. 2010. Biotransformation. Comprehensive Toxicology. https://www.sciencedirect.com/topics/medicine-and-dentistry/alcohol-dehydrogenase

Hassaninasab A, Hashimoto Y, Tomita-Yokotani K, Kobayashi M. 2011. Discovery of the curcumin metabolic pathway involving a unique enzyme in an intestinal microorganism. PNAS. 108(16):6615-20. http://www.pnas.org/content/108/16/6615

Koller T, Galambosova M, Filakovska S, Kubincova M, Hlavaty T et al. 2017. Drug-induced liver injury in inflammatory bowel disease: 1-year prospective observational study. World Journal of Gastroenterology. 23(22):4102-11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473129/

Lee H, McGregor RA, Choi MS, Seo K, Jung UJ et al. 2013. Low doses of curcumin protect alcohol-induced liver damage by modulation of the alcohol metabolic pathway CYP2E1 and AMPK. Life Sciences. 93(18-19):693-9. https://www.ncbi.nlm.nih.gov/pubmed/24063989

Prsad S, Tyagi AK, Aggarwal BB. 2014. Recent developments in delivery, bioavailability, absorption and metabolism of curcumin: The golden pigment of golden spice. Cancer Research and Treatment. 46(1):2-18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918523/

Tran-Minh M, Sousa P, Maillet M, Allez M, Gornet J. 2017. Hepatic complications induced by immunosuppressants and biologics in inflammatory bowel disease. World Journal of Hepatology. 9(13):613-26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5424291/

Uko V, Thangada S, Radhakrishnan K. 2012. Liver disorders in inflammatory bowel disease. Gastroenterology Research and Practice. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3296398/

Varatharajalu R, Garige M, Lackey LC, Gordillo K, Shah R, Lakshman MR. 2016. Protective role of dietary curcumin in the prevention of the oxidative stress induced by chronic alcohol with respect to hepatic injury and antiatherogenic markers. Oxidative Medicine and Cellular Longevity. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4736425/

Welty FK. 2013. How do elevated triglycerides and low HDL cholesterol affect inflammation and atherothrombosis? Current Cardiology Reports. 15(9):400. https://www.ncbi.nlm.nih.gov/pubmed/23881582

Yoon Y, CHen CM. 2016. Liver cirrhosis mortality in the United States: National, state, and regional trends, 2000-2013. US Department of Health and Human Services. https://pubs.niaaa.nih.gov/publications/surveillance105/Cirr13.pdf

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