Efficacy of Nutritional Therapy With High Methionine Content in the Treatment of NAFLD

Non-alcoholic Fatty Liver Disease (NAFLD) Clinical Trial

Official title:

Efficacy of Nutritional Therapy With High Methionine Content in the Treatment of Non-alcoholic Fatty Liver: a Randomized Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04450875
• Other study ID #: ISP-CI-003/2014
• Secondary ID: 001/060/0194
• Status: Completed
• Phase: N/A
• Start date: March 24, 2015
• Est. completion date: November 1, 2017

Study information

• Verified date: June 2020
• Source: Universidad Veracruzana
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To assess the effect of a methionine metabolism-based dietary strategy in patients with non-alcoholic fatty liver disease in order to reduce complications while improving the quality of life for patients.

Description:

A randomized controlled clinical trial with parallel design was performed, a ratio of at least one patient in the control group for each subject in the experimental group.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 121
• Est. completion date: November 1, 2017
• Est. primary completion date: February 1, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 99 Years

Eligibility

Inclusion Criteria:

• Diagnosis of Non-alcoholic Fatty Liver Disease by biochemical parameters used by the SteatoTest and Fatty Liver Index (IHG), greater than 60 points on the scale and confirmed by liver ultrasound

Exclusion Criteria:

• Previous diagnosis of cirrhosis, hepatocarcinoma, Wilson's disease, viral hepatitis B and C and neoplasms of any origin

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non-alcoholic Fatty Liver Disease
• Non-alcoholic Fatty Liver Disease (NAFLD)

Intervention

Dietary Supplement:
• Experimental group (with diet)
Two nutritionists performed both diet instruction and 24-hour reminder monitoring monthly. At the end of the three-month follow-up, the 24-hour reminder data such as food consumed, daily rations, and the monthly average of milligrams of consumed methionine contained in the food, were recorded in a database for subsequent analysis.

Locations

Country	Name	City	State
Mexico	Rebeca García Román	Xalapa	Veracruz

Sponsors (3)

Lead Sponsor	Collaborator
Universidad Veracruzana	Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, National Council of Science and Technology, Mexico

Country where clinical trial is conducted

Mexico, 

References & Publications (34)

Abenavoli L, Milic N, Peta V, Alfieri F, De Lorenzo A, Bellentani S. Alimentary regimen in non-alcoholic fatty liver disease: Mediterranean diet. World J Gastroenterol. 2014 Dec 7;20(45):16831-40. doi: 10.3748/wjg.v20.i45.16831. Review. — View Citation

Aller R, Izaola O, Gómez S, Tafur C, González G, Berroa E, Mora N, González JM, de Luis DA. Effect of silymarin plus vitamin E in patients with non-alcoholic fatty liver disease. A randomized clinical pilot study. Eur Rev Med Pharmacol Sci. 2015 Aug;19(16 — View Citation

Anania C, Perla FM, Olivero F, Pacifico L, Chiesa C. Mediterranean diet and nonalcoholic fatty liver disease. World J Gastroenterol. 2018 May 21;24(19):2083-2094. doi: 10.3748/wjg.v24.i19.2083. Review. — View Citation

Bedogni G, Bellentani S, Miglioli L, Masutti F, Passalacqua M, Castiglione A, Tiribelli C. The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol. 2006 Nov 2;6:33. — View Citation

Capanni M, Calella F, Biagini MR, Genise S, Raimondi L, Bedogni G, Svegliati-Baroni G, Sofi F, Milani S, Abbate R, Surrenti C, Casini A. Prolonged n-3 polyunsaturated fatty acid supplementation ameliorates hepatic steatosis in patients with non-alcoholic — View Citation

Chachay VS, Macdonald GA, Martin JH, Whitehead JP, O'Moore-Sullivan TM, Lee P, Franklin M, Klein K, Taylor PJ, Ferguson M, Coombes JS, Thomas GP, Cowin GJ, Kirkpatrick CM, Prins JB, Hickman IJ. Resveratrol does not benefit patients with nonalcoholic fatty — View Citation

Chan R, Wong VW, Chu WC, Wong GL, Li LS, Leung J, Chim AM, Yeung DK, Sea MM, Woo J, Chan FK, Chan HL. Diet-Quality Scores and Prevalence of Nonalcoholic Fatty Liver Disease: A Population Study Using Proton-Magnetic Resonance Spectroscopy. PLoS One. 2015 S — View Citation

Chawla RK, Bonkovsky HL, Galambos JT. Biochemistry and pharmacology of S-adenosyl-L-methionine and rationale for its use in liver disease. Drugs. 1990;40 Suppl 3:98-110. Review. — View Citation

David K, Kowdley KV, Unalp A, Kanwal F, Brunt EM, Schwimmer JB; NASH CRN Research Group. Quality of life in adults with nonalcoholic fatty liver disease: baseline data from the nonalcoholic steatohepatitis clinical research network. Hepatology. 2009 Jun;4 — View Citation

Dong F, Zhang Y, Huang Y, Wang Y, Zhang G, Hu X, Wang J, Chen J, Bao Z. Long-term lifestyle interventions in middle-aged and elderly men with nonalcoholic fatty liver disease: a randomized controlled trial. Sci Rep. 2016 Nov 10;6:36783. doi: 10.1038/srep3 — View Citation

Eslamparast T, Eghtesad S, Poustchi H, Hekmatdoost A. Recent advances in dietary supplementation, in treating non-alcoholic fatty liver disease. World J Hepatol. 2015 Feb 27;7(2):204-12. doi: 10.4254/wjh.v7.i2.204. Review. — View Citation

European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty live — View Citation

European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016 Jun;64(6):1388-402. doi: 10.1016/j.jhep.2015.11.004. Epub 2016 Apr 7. PubMed 27062661

Fedewa MV, Nickerson BS, Esco MR. Associations of body adiposity index, waist circumference, and body mass index in young adults. Clin Nutr. 2019 Apr;38(2):715-720. doi: 10.1016/j.clnu.2018.03.014. Epub 2018 Apr 4. — View Citation

Fraser A, Abel R, Lawlor DA, Fraser D, Elhayany A. A modified Mediterranean diet is associated with the greatest reduction in alanine aminotransferase levels in obese type 2 diabetes patients: results of a quasi-randomised controlled trial. Diabetologia. — View Citation

Gepner Y, Shelef I, Schwarzfuchs D, Zelicha H, Tene L, Yaskolka Meir A, Tsaban G, Cohen N, Bril N, Rein M, Serfaty D, Kenigsbuch S, Komy O, Wolak A, Chassidim Y, Golan R, Avni-Hassid H, Bilitzky A, Sarusi B, Goshen E, Shemesh E, Henkin Y, Stumvoll M, Blüh — View Citation

Harrison SA, Torgerson S, Hayashi P, Ward J, Schenker S. Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis. Am J Gastroenterol. 2003 Nov;98(11):2485-90. — View Citation

Klein EA, Thompson IM Jr, Tangen CM, Crowley JJ, Lucia MS, Goodman PJ, Minasian LM, Ford LG, Parnes HL, Gaziano JM, Karp DD, Lieber MM, Walther PJ, Klotz L, Parsons JK, Chin JL, Darke AK, Lippman SM, Goodman GE, Meyskens FL Jr, Baker LH. Vitamin E and the — View Citation

Kobyliak N, Abenavoli L, Falalyeyeva T, Mykhalchyshyn G, Boccuto L, Kononenko L, Kyriienko D, Komisarenko I, Dynnyk O. Beneficial effects of probiotic combination with omega-3 fatty acids in NAFLD: a randomized clinical study. Minerva Med. 2018 Dec;109(6) — View Citation

Kobyliak N, Abenavoli L, Mykhalchyshyn G, Kononenko L, Boccuto L, Kyriienko D, Dynnyk O. A Multi-strain Probiotic Reduces the Fatty Liver Index, Cytokines and Aminotransferase levels in NAFLD Patients: Evidence from a Randomized Clinical Trial. J Gastroin — View Citation

Lieber CS. Role of S-adenosyl-L-methionine in the treatment of liver diseases. J Hepatol. 1999 Jun;30(6):1155-9. — View Citation

Miller ER 3rd, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005 Jan 4;142(1):37-46. Epub 2004 Nov 10. — View Citation

Mora SI, García-Román J, Gómez-Ñañez I, García-Román R. Chronic liver diseases and the potential use of S-adenosyl-L-methionine as a hepatoprotector. Eur J Gastroenterol Hepatol. 2018 Aug;30(8):893-900. doi: 10.1097/MEG.0000000000001141. Review. — View Citation

Pervez MA, Khan DA, Ijaz A, Khan S. Effects of Delta-tocotrienol Supplementation on Liver Enzymes, Inflammation, Oxidative stress and Hepatic Steatosis in Patients with Nonalcoholic Fatty Liver Disease. Turk J Gastroenterol. 2018 Mar;29(2):170-176. doi: 1 — View Citation

Rao HY. [Assessment methods and research status of quality of life in patients with nonalcoholic fatty liver disease]. Zhonghua Gan Zang Bing Za Zhi. 2020 Mar 20;28(3):278-283. doi: 10.3760/cma.j.cn50113-20190719-00255. Chinese. — View Citation

Ryan MC, Itsiopoulos C, Thodis T, Ward G, Trost N, Hofferberth S, O'Dea K, Desmond PV, Johnson NA, Wilson AM. The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease. J Hepatol. 2013 — View Citation

Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM, Neuschwander-Tetri BA, Lavine JE, Tonascia J, Unalp A, Van Natta M, Clark J, Brunt EM, Kleiner DE, Hoofnagle JH, Robuck PR; NASH CRN. Pioglitazone, vitamin E, or placebo for nonalcoholic — View Citation

Sayiner M, Stepanova M, Pham H, Noor B, Walters M, Younossi ZM. Assessment of health utilities and quality of life in patients with non-alcoholic fatty liver disease. BMJ Open Gastroenterol. 2016 Aug 16;3(1):e000106. doi: 10.1136/bmjgast-2016-000106. eCol — View Citation

Spadaro L, Magliocco O, Spampinato D, Piro S, Oliveri C, Alagona C, Papa G, Rabuazzo AM, Purrello F. Effects of n-3 polyunsaturated fatty acids in subjects with nonalcoholic fatty liver disease. Dig Liver Dis. 2008 Mar;40(3):194-9. Epub 2007 Dec 4. — View Citation

Worm N. Beyond Body Weight-Loss: Dietary Strategies Targeting Intrahepatic Fat in NAFLD. Nutrients. 2020 May 6;12(5). pii: E1316. doi: 10.3390/nu12051316. Review. — View Citation

Younossi ZM, Stepanova M, Henry L, Racila A, Lam B, Pham HT, Hunt S. A disease-specific quality of life instrument for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis: CLDQ-NAFLD. Liver Int. 2017 Aug;37(8):1209-1218. doi: 10.1111/liv.1 — View Citation

Zang S, Chen J, Song Y, Bai L, Chen J, Chi X, He F, Sheng H, Wang J, Xie S, Xie W, Yang Y, Zhang J, Zheng M, Zou Z, Wang B, Shi J; Chinese NAFLD Clinical Research Network (CNAFLD CRN). Haptoglobin Genotype and Vitamin E Versus Placebo for the Treatment of Nondiabetic Patients with Nonalcoholic Steatohepatitis in China: A Multicenter, Randomized, Placebo-Controlled Trial Design. Adv Ther. 2018 Feb;35(2):218-231. doi: 10.1007/s12325-018-0670-8. Epub 2018 Feb 6. — View Citation

Zhu FS, Liu S, Chen XM, Huang ZG, Zhang DW. Effects of n-3 polyunsaturated fatty acids from seal oils on nonalcoholic fatty liver disease associated with hyperlipidemia. World J Gastroenterol. 2008 Nov 7;14(41):6395-400. — View Citation

Zúniga MA, Carrillo-Jiménez GT, Fos PJ, Gandek B, Medina-Moreno MR. [Evaluation of health status using Survey SF-36: preliminary results in Mexico]. Salud Publica Mex. 1999 Mar-Apr;41(2):110-8. Spanish. — View Citation

* Note: There are 34 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	ALT (Level of liver damage enzymes)	Alanine aminotransferase (ALT) High levels (>50) indicate damage to liver cells. It will be expressed as mean and standard deviation and will be compared in both groups.	Three months
Other	AST (Level of liver damage enzymes)	A high result on an AST test might indicate a problem with the liver or muscles. It will be expressed as mean and standard deviation and will be compared in both groups.; The normal range for AST is typically up to 40 IU/L	Three months
Other	GGT(Level of liver damage enzymes)	High levels of GGT in the blood could indicate that the enzyme is leaking out of the liver cells and into the blood, suggesting damage to the liver or bile ducts. A typical range for GGT levels in adults is between 0 and 30 international units per liter (IU/L). It will be expressed as mean and standard deviation and will be compared in both groups.	Three months
Other	Glucose	Elevated fasting glucose = 100 mg/dl. It will be expressed as mean and standard deviation and will be compared in both groups.	Three months
Other	Triglycerides	Elevated triglycerides =150 mg/dL (1.7 mmol/L). It will be expressed as mean and standard deviation and will be compared in both groups.	Three months
Other	Cholesterol	Reduced HDL colesterol <40 mg/dL (1.03 mmol/L) in men <50 mg/dL (1.3 mmol/L) in women. It will be expressed as mean and standard deviation and will be compared in both groups.	Three months
Other	Weight	Measurement in kilograms	Three months
Other	Height Height	Measurement in meters	Three months
Other	Body mass index (BMI)	Weight and height will be combined to report BMI in kg/m^2. It will be expressed as mean and standard deviation and will be compared in both groups.	Three months
Other	Waist	Measurement in centimeters	Three months
Other	Hip	Measurement in centimeters	Three months
Other	Waist-hip ratio	Wast and hip will be combined to report WHR in cm. It will be expressed as mean and standard deviation and will be compared in both groups.	Three months
Other	Systolic BP	Report SBP in mmHg, will be assessed during the study period	Three months
Other	Diastolic BP	Report DBP in mmHg, will be assessed during the study period	Three months
Primary	NAFLD reversal	Change in FLI to a level less than 60 points at the end of the dietary intervention. FLI was the result of the algorithm based on waist circumference, body mass index, serum GGT level and triglycerides. Bedogni, et al developed this fatty liver prediction model. The total possible score ranges from 1 to 100 points, where a score greater than or equal to 60 is considered to be NAFLD probable, and a level below 30 points is considered normal	Three months
Secondary	The Short Form (36) Health Survey (SF-36).	The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. .This questionnaire has been adapted to the Mexican population	Three months