Big Pharma Banks on Fatty Liver Disease

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1-fatty-liver-diseaseWhere there’s a buck to be made…

Dr Carrie Decker ND explores trends in R&D by pharmaceutical companies and the evolving problem of liver conditions. With increasing rates of obesity and metabolic syndrome, nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) have become increasingly common, such that they are now the most common cause of liver disease in Western countries.[i] This has not gone unnoticed by those in the market of drug development. Where there is a disease to “treat” there is a buck to be made.

As NAFLD and NASH are both considered “silent” liver disease, they are not something that will present with symptoms or be noticed in a physician’s office without screening. As recommended screening exams with increasing age do not necessarily include liver function tests, these tests may not be performed in a routine office visit without patient request. Even if liver function tests are assessed with a metabolic panel, many physicians pass off mild elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as “normal” without further screening, particularly in individuals who are overweight or obese. From the physician’s perspective, the only recommendations they can make that may impact liver enzymes other than alcohol abstinence is weight loss, along with the proper medical management of blood sugar and cholesterol. However, we can rest assured that once a drug is developed everyone, including patients, will be made fully aware of it, and increased screening will also commence.

Nutritional support for fatty liver disease

It is well understood that a prolonged state of oxidative stress and inflammation causes hepatic cellular damage and injury. The same steps of this process are true for both alcoholic liver disease and NAFLD. Despite an understand of this pathology, other than weight loss and management of insulin resistance there is no standard pharmaceutical treatment for these conditions.[ii] As NAFLD progresses to NASH, along with it comes an increased risk of cirrhosis, liver failure, and hepatocellular carcinoma. For this reason, it is important to intervene and manage the earlier state of liver inflammation and oxidative stress.

There is a broad array of options from a nutritional standpoint which have demonstrated action for reducing liver inflammation and oxidative stress. Antioxidants are one natural agent which may improve outcomes in individuals with these NAFLD and NASH.[iii],[iv]  Glutathione is a primary antioxidant in the body, of importance to liver health and function.[v] N-acetylcysteine in particular, as well as other antioxidants including lipoic acid, vitamin C and E support levels of hepatic glutathione.[vi],[vii],[viii] Lipoic acid also supports healthy blood sugar levels which also often is an issue with metabolic syndrome.

Phosphatidyl choline (PC), a primary component of lecithin, has been shown to protect against fibrosis associated with hepatitis.[ix],[x] PC is a normal constituent of bile and facilitates fat emulsification, absorption, and transport.  Studies have shown that recommended minimal dietary intake thresholds of PC may not be sufficient for prevention of symptoms of choline deficiency such as fatty liver.[xi] The risk of choline deficiency is higher in men, postmenopausal women, and vegans or vegetarians.

Many botanicals have hepatoprotective action and may reduce the risk of NAFLD and NASH.[xii] Turmeric (Curcuma longa) and the active constituents the curcuminoids act as antioxidants and are very effective at reducing inflammation throughout the body, including in the liver. [xiii],[xiv] Curcumin also has been shown to significantly improve serum levels of triglycerides and LDL-cholesterol, both of which also are often elevated with metabolic syndrome and may contribute to hepatic inflammation.[xv] Curcumin also has been shown to lower inflammatory markers such as C-reactive protein (CRP).[xvi] Obesity is often associated with a chronic, low grade, inflammatory state, and mild CRP elevation.

Milk thistle (Silybum marianum) is an herb that is best known for its potential hepatoprotective effects. Silymarin, a mixture of the active constituents of milk thistle, acts as an antioxidant and has been shown in animal studies to reduce liver injury caused by acetaminophen, alcohol, iron overload, consumption of the poisonous mushroom Amanita phalloides (Death cap), and radiation among other things with known liver-toxic potential.[xvii] It has been studied in humans for the treatment of alcoholic liver disease, fatty liver disease, acute and chronic viral hepatitis and toxin-induced liver diseases.[xviii],[xix],[xx]

A variety of foods also support the liver and gallbladder function.  This includes dandelion greens, artichokes,[xxi] beets,[xxii] parsley,[xxiii] lemon,[xxiv] and burdock.[xxv] Dandelion (Taraxacum officinale) is used by herbalists to support the liver, gallbladder, and tonify digestive health. The extracts from dandelion have been shown to be protective in settings of alcohol- or diet-induced stress on the liver.[xxvi],[xxvii] Dandelion can be consumed in teas, and even as cooked or raw salad greens, however the safety of the source should be considered.

Perhaps not surprisingly, probiotics have also been studied for their ability to reduce liver inflammation and related issues such as hepatic encephalopathy as well. It is possible that liver enzyme elevation can be due to gastrointestinal issues such as small intestinal bacterial overgrowth (SIBO), coeliac disease, and increased intestinal permeability.[xxviii],[xxix] For this reason, if these conditions are suspected, they also should be addressed as part of a comprehensive treatment plan.

Rather than waiting for the next drug to come down the line to support individuals with an increased liver burden due to diet or other lifestyle choices, integrating some of these potential supportive agents can help them now, reducing potential disease risk.

References

[i] Review Team, LaBrecque DR, et al. World Gastroenterology Organisation global guidelines: Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. J Clin Gastroenterol. 2014;48:467-73. View Abstract

[ii] Ahmed A, et al. Nonalcoholic Fatty Liver Disease Review: Diagnosis, Treatment, and Outcomes. Clin Gastroenterol Hepatol. 2015;13:2062-70. View Abstract

[iii] Chen G, et al. Micronutrient Antioxidants and Nonalcoholic Fatty Liver Disease. Int J Mol Sci. 2016 Aug;17. View Abstract

[iv] Mehta K, et al. Nonalcoholic fatty liver disease: pathogenesis and the role of antioxidants. Nutr Rev. 2002 Sep;60(9):289-93. View Abstract

[v] Yuan L, Kaplowitz N. Glutathione in liver diseases and hepatotoxicity. Mol Aspects Med. 2009 Feb-Apr;30(1-2):29-41. View Abstract

[vi] Ali MH, et al. Protective effect of ursodeoxycholic acid, resveratrol, and N-acetylcysteine on nonalcoholic fatty liver disease in rats. Pharm Biol. 2015 Jul 1:1-11. View Abstract

[vii] Bustamante J, et al. Alpha-lipoic acid in liver metabolism and disease. Free Radic Biol Med. 1998 Apr;24(6):1023-39. View Abstract

[viii] Singh U, et al. Vitamin E, oxidative stress, and inflammation. Annu Rev Nutr. 2005;25:151-74. View Abstract

[ix] Ma X, et al.  Polyenylphosphatidylcholine attenuates non-alcoholic hepatic fibrosis and accelerates its regression. J Hepatol. 1996 May;24(5):604-13. View Abstract

[x] Lieber CS, et al. Phosphatidylcholine protects against fibrosis and cirrhosis in the baboon. Gastroenterology. 1994 Jan;106(1):152-9. View Abstract

[xi] Fischer LM, et al. Sex and menopausal status influence human dietary requirements for the nutrient choline. Am J Clin Nutr. 2007 May;85(5):1275-85. View Full Paper

[xii] Jadeja R, et al. Herbal medicines for the treatment of nonalcoholic steatohepatitis: current scenario and future prospects. Evid Based Complement Alternat Med. 2014:648308. View Full Paper

[xiii] Reyes-Gordillo K, et al. Curcumin protects against acute liver damage in the rat by inhibiting NF-kappaB, proinflammatory cytokines production and oxidative stress. Biochim Biophys Acta. 2007 Jun;1770(6):989-96. View Abstract

[xiv] Miyakoshi M, et al. Hepatoprotective effect of sesquiterpenes in turmeric. Biofactors. 2004;21(1-4):167-70. View Abstract

[xv] Shin SK, et al. Long-term curcumin administration protects against atherosclerosis via hepatic regulation of lipoprotein cholesterol metabolism. Mol Nutr Food Res. 2011 Dec;55(12):1829-40. View Abstract

[xvi] Sahebkar A. Are curcuminoids effective C-reactive protein-lowering agents in clinical practice? Evidence from a meta-analysis. Phytother Res. 2014 May;28(5):633-42. View Abstract

[xvii] Abenavoli L, et al. Milk thistle in liver diseases: past, present, future. Phytother Res. 2010 Oct;24(10):1423-32. View Abstract

[xviii] Xiao J, et al. Recent advances in the herbal treatment of non-alcoholic Fatty liver disease. J Tradit Complement Med. 2013 Apr;3(2):88-94.  View Full Paper

[xix] Malaguarnera M, et al. Silybin-vitamin E-phospholipids complex reduces liver fibrosis in patients with chronic hepatitis C treated with pegylated interferon α and ribavirin. Am J Transl Res. 2015 Nov 15;7(11):2510-8. View Full Paper

[xx] Flora K, et al. Milk thistle (Silybum marianum) for the therapy of liver disease. Am J Gastroenterol. 1998 Feb;93(2):139-43. View Abstract

[xxi] Rangboo V, et al. The Effect of Artichoke Leaf Extract on Alanine Aminotransferase and Aspartate Aminotransferase in the Patients with Nonalcoholic Steatohepatitis. Int J Hepatol. 2016;2016:4030476. View Full Paper

[xxii] Agarwal M, et al. Hepatoprotective activity of Beta vulgaris against CCl4-induced hepatic injury in rats. Fitoterapia. 2006 Feb;77(2):91-3. View Abstract

[xxiii] Bolkent S, et al. Effects of parsley (Petroselinum crispum) on the liver of diabetic rats: a morphological and biochemical study. Phytother Res. 2004 Dec;18(12):996-9. View Abstract

[xxiv] Bhavsar SK, et al. Investigation into Hepatoprotective Activity of Citrus limon. Pharmaceutical Biology. 2007 Jan 1;45(4):303-11. View Abstract

[xxv] Predes FS, et al. Antioxidative and in vitro antiproliferative activity of Arctium lappa root extracts. BMC Complement Altern Med. 2011 Mar 23;11:25. View Full Paper

[xxvi] You Y, et al. In vitro and in vivo hepatoprotective effects of the aqueous extract from Taraxacum officinale (dandelion) root against alcohol-induced oxidative stress. Food Chem Toxicol. 2010 Jun;48(6):1632-7. View Abstract

[xxvii] Davaatseren M, et al. Taraxacum official (dandelion) leaf extract alleviates high-fat diet-induced nonalcoholic fatty liver. Food Chem Toxicol. 2013 Aug;58:30-6. View Abstract

[xxviii] Ilan Y. Leaky gut and the liver: a role for bacterial translocation in nonalcoholic steatohepatitis. World J Gastroenterol. 2012 Jun 7;18(21):2609-18. View Abstract

[xxix] Li DY, et al.  Nonalcoholic fatty liver disease: for better or worse, blame the gut microbiota? JPEN J Parenter Enteral Nutr. 2013 Nov;37(6):787-93. View Abstract

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