Liver Enzymes, Triglycerides, and Cholesterol Improved in Individuals with Nonalcoholic Steatohepatitis with Artichoke Leaf Extract
By Carrie Decker, ND
Founder and Medical Director, Blessed Thistle, Eugene, OR
Dr. Decker reports no financial relationships relevant to this field of study.
SUMMARY POINTS
- A recent study found that 2,700 mg of artichoke (Cynara scolymus) leaf extract or placebo was provided to individuals with nonalcoholic steatohepatitis daily for a period of two months.
- Compared to placebo, individuals taking the artichoke leaf extract experienced a significant (P < 0.001) decrease in alanine aminotransferase and asparatate aminotransferase and a significant (P < 0.05) decrease in triglycerides and total cholesterol compared to the placebo group.
- A significant (P < 0.05) decrease in fasting blood sugar and low-density lipoprotein cholesterol also was observed in the group receiving artichoke extract; however, this finding was not significant when compared to the placebo group.
SYNOPSIS: In this randomized, double-blind study, patients with nonalcoholic steatohepatitis who received 2,700 mg of artichoke leaf extract (Cynara scolymus) or placebo daily for two months had a significant improvement in alanine aminotransferase and aspartate aminotransferase, as well as triglycerides and total cholesterol compared to the placebo group.
SOURCE: Rangboo V, Noroozi M, Zavoshy R, et al. The effect of artichoke leaf extract on alanine aminotransferase and aspartate aminotransferase in the patients with nonalcoholic steatohepatitis. Int J Hepatol 2016;4030476. Epub 2016 May 11.
With increasing rate of obesity and the metabolic syndrome, nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD) have become increasingly common, such that they are now the most common cause of liver disease in Western countries.1 As NAFLD progresses to NASH, hepatocyte injury occurs, contributing to an increased risk of cirrhosis, liver failure, and hepatocellular carcinoma. Despite the fairly well-understood factors contributing to NAFLD and NASH, other than weight loss and management of insulin resistance, there is no standard pharmaceutical treatment for these conditions.2 As oxidative stress is known to contribute to the progression of NAFLD to NASH, investigations have been made into the possibility of utilizing antioxidants for improving outcomes in individuals with these conditions.3 Many botanicals, including artichoke leaf extract, have antioxidant action, and have been considered as options for the treatment of NAFLD and NASH.4,5
Sixty consecutive patients diagnosed with NASH were enrolled in this double-blind, randomized, clinical trial. Inclusion criteria were elevated liver enzymes (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]; > 30 mg/dL) and evidence of NASH with abdominal sonography, in addition to one of the following criteria: total cholesterol > 200 mg/dL, high-density lipoprotein (HDL) < 40 mg/dL (men) or < 50 mg/dL (women), serum triglycerides > 150 mg/dL, fasting blood sugar > 100 mg/dL, body mass index > 30 kg/m2, or blood pressure > 130/85 mmHg. Exclusion criteria included daily consumption of alcohol, known issues of hepatitis B or C, autoimmune hepatitis, Wilson’s disease, hemochromatosis, alpha-1-antitrypsin deficiency, biliary obstruction, type 1 diabetes mellitus, or use of hepatotoxic drugs or vitamin C. Groups were shown to be similar initially in baseline characteristics of age, sex, weight, liver enzyme levels, lipid profiles, and fasting blood sugar.
Patients were assigned to receive either artichoke leaf extract (Cynara scolymus) at a dosage of 2,700 mg/day (six tablets) or placebo for a period of two months, and instructed to maintain regular physical activity (20 minutes of walking five days a week) and an appropriate diet, calculated based on weight, height, age, and activity. Measurements were made of weight, cholesterol (total and breakdown including low-density lipoprotein [LDL], HDL, and triglycerides), ALT, AST, blood pressure, and fasting blood sugar.
The individuals receiving artichoke leaf extract daily were found to have a significant decrease in ALT (P < 0.001), AST (P < 0.001), total cholesterol (P = 0.008), and triglycerides (P = 0.016) compared to the placebo group. A significant decrease in fasting blood sugar (P = 0.029) and LDL (P = 0.039) also was observed within the group receiving the artichoke extract, but was not observed in the placebo group. Both groups were observed to have a significant decrease in weight and systolic blood pressure at the end of the two-month intervention compared to levels at the beginning. The researchers report did not indicate if there any adverse effects were seen with the intervention, or if there was any deviation from adherence to the prescribed intervention. Assessment of results included all 60 individuals enrolled in the study.
COMMENTARY
As a botanical, artichoke is known for its cholagogue and choleretic effects, that is, the stimulation of bile flow and bile production, respectively. These effects have been observed in animal studies.6 A relationship between increased bile excretion in feces and improvement of lipid profiles also has been observed.7 As bile acids are synthesized from cholesterol, a relationship between these two would be expected. Medications such as bile acid sequestrants are effective for reducing cholesterol because they disrupt bile acid reabsorption as well as increase bile secretion.8 Although artichoke extract does not alter bile reabsorption, increased fecal excretion of bile also would inevitably have a similar effect. Artichoke extracts also have been shown to potentially reduce cholesterol by inhibiting HMG-CoA reductase in an animal model.9 Increased bile flow also inevitably affects the gut microbiota, which was not assessed in any of these studies but also may play a role.
One mechanism by which artichoke extract affects liver enzymes may be due to the antioxidant effect of several compounds such as chlorogenic acid found in it.10 Animal and cellular studies have assessed the antioxidant effect of artichoke extracts and how this affects hepatocytes, finding a beneficial effect when subject to oxidative stress.11,12 This is the first study assessing the effect of artichoke leaf extract on liver enzymes in humans with NASH; however, animal studies in which NASH was induced with high-fat diet feeding found improvement in ALT with artichoke extract treatment.13 Chlorogenic acid also may be the agent responsible for the improvements in glucose and triglycerides that were seen as it has been shown in an animal model to inhibit hepatic glucose 6-phosphatase.14 Hypoglycemic effects have also been seen with use of artichoke in other human and animal studies.15,16 Multiple studies have assessed the effect of artichoke leaf extract on cholesterol, and show reduction of total cholesterol levels with mild and infrequent adverse events.17
Interestingly, both groups experienced significant changes in multiple parameters from the beginning to the end of the study. The parameters that were decreased within both groups were weight, AST, ALT, and systolic blood pressure. The authors did not speculate on the reason for these improvements, leaving one to wonder if the time of year or general recommendation for maintaining an appropriate diet or regular exercise of 20 minutes of walking five days a week were factors leading to these overall improvements.
Other factors that may affect liver enzymes and progression of liver disease were not fully considered with the study criteria. Although daily alcohol consumption led to exclusion from the study, other drinking patterns or total weekly intake of alcohol was not considered. In addition to this, although the use of hepatotoxic drugs was an exclusion criterion, it was not stated if the use of acetaminophen, which may have an effect on liver enzymes, particularly in combination with alcohol, was to be avoided during the study. Although the use of vitamin C was an exclusion criterion, many other things, such as turmeric and probiotics, have been shown to improve liver function tests18,19 but were not screened for use in this population. A final limitation and drawback of this study was that no assessment of safety or adverse events was included.
Given the findings of this study and other research utilizing artichoke extracts, it would be reasonable to recommend inclusion of an artichoke leaf extract product as a supplement for individuals who have documented evidence of NASH, or those who meet the criteria of metabolic syndrome. The multiple parameters (blood sugar, liver enzyme elevation, and cholesterol) that artichoke leaf extract was observed to affect positively are often issues for these patients. Although tolerability was not assessed in this study, tolerability has been well-documented in other studies.
REFERENCES
- Review Team, LaBrecque DR, Abbas Z, et al. World Gastroenterology Organisation global guidelines: Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. J Clin Gastroenterol 2014;48:467-473.
- Ahmed A, Wong RJ, Harrison SA. Nonalcoholic fatty liver disease review: Diagnosis, treatment, and outcomes. Clin Gastroenterol Hepatol 2015;13:2062-2070.
- Chen G, Ni Y, Nagata N, et al. Micronutrient antioxidants and nonalcoholic fatty liver disease. Int J Mol Sci 2016; Aug 17 [Epub ahead of print].
- Jadeja R, Devkar RV, Nammi S. Herbal medicines for the treatment of nonalcoholic steatohepatitis: Current scenario and future prospects. Evid Based Complement Alternat Med 2014:648308.
- Speroni E, Cervellati R, Govoni P, et al. Efficacy of different Cynara scolymus preparations on liver complaints. J Ethnopharmacol 2003;86:203-211.
- Saénz Rodriguez T, Garcia Gimenez D, de la Puerta Vazquez R. Choleretic activity and biliary elimination of lipids and bile acids induced by an artichoke leaf extract in rats. Phytomedicine 2002;9:687-693.
- Qiang Z, Lee SO, Ye Z, et al. Artichoke extract lowered plasma cholesterol and increased fecal bile acids in Golden Syrian hamsters. Phytother Res 2012;26:1048-1052.
- Einarsson K, Ericsson S, Ewerth S, et al. Bile acid sequestrants: Mechanisms of action on bile acid and cholesterol metabolism. Eur J Clin Pharmacol 1991;40(Suppl 1):S53-S58.
- Gebhardt R. Inhibition of cholesterol biosynthesis in primary cultured rat hepatocytes by artichoke (Cynara scolymus L.) extracts. J Pharmacol Exp Ther 1998;286:1122-1128.
- Wang M, Simon JE, Aviles IF, et al. Analysis of antioxidative phenolic compounds in artichoke (Cynara scolymus L.). J Agric Food Chem 2003;51:601-608.
- Mehmetçik G, Ozdemirler G, Kocak-Toker N, et al. Effect of pretreatment with artichoke extract on carbon tetrachloride-induced liver injury and oxidative stress. Exp Toxicol Pathol 2008;60:475-480.
- Miccadei S, Di Venere D, Cardinali A, et al. Antioxidative and apoptotic properties of polyphenolic extracts from edible part of artichoke (Cynara scolymus L.) on cultured rat hepatocytes and on human hepatoma cells. Nutr Cancer 2008;60:276-283.
- Mohamed SH, Ahmed HH, Farrag ARH, et al. Cynara scolymus for relieving on nonalcoholic steatohepatitis induced in rats. Int J Pharm Sci 2013;5:57-66.
- Arion WJ, Canfield WK, Ramos FC, et al. Chlorogenic acid and hydroxynitrobenzaldehyde: New inhibitors of hepatic glucose 6-phosphatase. Arch Biochem Biophys 1997;339:315-322.
- Nazni P, Vijayakumar TP, Alagianambi P, Amirthaveni M. Hypoglycemic and hypolipidemic effect of Cynara scolymus among selected type 2 diabetic individuals. Pakist J Nutr 2006;5:147-151.
- Soofiniya Y, Heidarian E. Hypolipidemic and hypoglycemic effects of aerial part of Cynara scolymus in streptozotocin-induced diabetic rats. J Med Plants Res 2011;5:2717-2723.
- Wider B, Pittler MH, Thompson-Coon J, Ernst E. Artichoke leaf extract for treating hypercholesterolaemia. Cochrane Database Syst Rev 2013;(3):CD003335.
- Loguercio C, Federico A, Tuccillo C, et al. Beneficial effects of a probiotic VSL#3 on parameters of liver dysfunction in chronic liver diseases. J Clin Gastroenterol 2005;39:540-543.
- Bulboaca A, D Bolboaca S, Suci S. Protective effect of curcumin in fructose-induced metabolic syndrome and in streptozotocin-induced diabetes in rats. Iran J Basic Med Sci 2016;19:585-593.
In this randomized, double-blind study, patients with nonalcoholic steatohepatitis who received 2,700 mg of artichoke leaf extract (Cynara scolymus) or placebo daily for two months had a significant improvement in alanine aminotransferase and aspartate aminotransferase, as well as triglycerides and total cholesterol compared to the placebo group.
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