Clinical Trials Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 7, 2019; 25(9): 1116-1131
Published online Mar 7, 2019. doi: 10.3748/wjg.v25.i9.1116
Comprehensive lifestyle intervention vs soy protein-based meal regimen in non-alcoholic steatohepatitis
Peter Deibert, Adhara Lazaro, Denise Schaffner, Aloys Berg, Daniel Koenig, Wolfgang Kreisel, Manfred W Baumstark, Daniel Steinmann, Martin Buechert, Thomas Lange
Peter Deibert, Adhara Lazaro, Denise Schaffner, Manfred W Baumstark, Faculty of Medicine, Department of Medicine, Institute of Exercise and Occupational Medicine, Medical Center, University of Freiburg, Freiburg D-79106, Germany
Aloys Berg, Daniel Koenig, Department of Nutrition, Institute for Sports and Sports Science, University of Freiburg, Freiburg D-79106, Germany
Wolfgang Kreisel, Faculty of Medicine, Department of Medicine, Division of Gastroenterology, Hepatology, Endocrinology and Infectious Diseases, Medical Center, University of Freiburg, Freiburg D-79106, Germany
Daniel Steinmann, University Hospital of Freiburg, Occupational Medicine, Freiburg 79110, Germany
Martin Buechert, Thomas Lange, Faculty of Medicine, Department of Radiology - Medical Physics, Medical Center, University of Freiburg, Freiburg D-79106, Germany
Author contributions: Deibert P, Berg A and König D designed the study; Schaffner D took care of the patients and collected data; Kreisel W and Steinmann D organized recruiting patients; Buechert M and Lange T performed the MRI body composition analyses and spectroscopies; Baumstark M and Deibert P analyzed data; all authors reviewed and discussed the data; Deibert P and Lazaro A wrote the paper.
Supported by (in part) Almased® Wellness Company, Bienenbuettel, Germany. The planning, organisation, monitoring and analysis of the study were performed independently by the investigators. Aloys Berg received a study grant from Almased® Wellness Company. Thomas Lange received a study grant from Helmholtz Alliance ICEMED.
Institutional review board statement: The study was reviewed and approved by the Ethics Review Board of the University of Freiburg Medical Center.
Clinical trial registration statement: The study is registered in the German Clinical Trials Register (DRKS), which is an approved Primary Register in the WHO network.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: all authors declared no conflict of interest.
Data sharing statement: No additional data are available.
CONSORT 2010 statement: The manuscript was prepared and revised according to the CONSORT 2010 Statement.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Peter Deibert, MD, Professor, Faculty of Medicine, Department of Medicine, Institute of Exercise and Occupational Medicine, Medical Center, University of Freiburg, Hugstetter Str. 55, Freiburg D-79106, Germany.
Telephone: +49-761-27074540 Fax: +49-761-27074700
Received: October 30, 2018
Peer-review started: November 1, 2018
First decision: December 5, 2018
Revised: February 15, 2019
Accepted: February 15, 2019
Article in press: February 15, 2019
Published online: March 7, 2019
Research background

Non-alcoholic steatohepatitis (NASH) is one of the leading causes of chronic liver disease in western countries. The ideal approach to reduce hepatic inflammation and liver fat content is not found yet. Dietary restrictions and physical activity have been shown to be effective, however there is no gold standard established so far.

Research motivation

Many different dietary approaches may be effective in weight reduction. We have shown that by meal replacement therapy with a high-quality soy protein supplementation as well as by comprehensive lifestyle change a weight reduction without loss of muscle mass is achievable. Both interventions can reduce fat mass and liver fat mass. However, blood lipids are changed in different ways with these two interventions. Now we wanted to study whether liver fat quality is differently affected with either intervention.

Research objectives

The main questions of this study were: is there a correlation between loss of liver fat and reduction in body fat, and is one intervention superior to the other in this respect? Is it possible to analyze liver fat quality, and is there a difference in changes in liver fat quality between the two therapeutic interventions?

Research methods

For body composition analysis a Bod pod device was used. Liver fat content was measured by magnetic resonance imaging. For analysis of liver fat quality a magnetic resonance spectroscopy protocol was adapted to quantify the mean chain length and grade of saturation of liver fat. For meal replacement therapy we used a commercially available product based on a soy-yogurt-honey preparation. The lifestyle intervention program consisted of guided exercise sessions orientated on individual exercise capacity and dietary counselling.

Research results

Both groups significantly reduced body mass index, fat mass and liver fat content. The lifestyle intervention group showed a tendency for greater weight loss. In both groups ALT and AST declined significantly. Triglycerides significantly decreased only in meal replacement group. With respect to liver fat quality the grade of saturation and mean chain length of hepatic fatty acids were quantifiable in a subset of participants. Total unsaturated lipids and mean chain length were significantly reduced only by meal replacement.

Research conclusions

With both interventions body fat and liver fat content were significantly reduced. Though the participants tended to lose more weight by lifestyle intervention the reduction of liver fat was comparable in both groups. Thus, for the reduction in liver fat a meal replacement strategy could be more effective in relation to body weight loss than a lifestyle intervention. This study confirms the finding of preserving muscle mass during a weight reduction period once high quality protein supplementation or physical activity is added in a guided and supervised manner. The pronounced reduction of serum triglycerides is attributed to specific soy properties. Given the study protocol further analysis of liver fat in humans by magnetic resonance spectroscopy was possible. Both interventions had different effects on liver fat quality.

In conclusion, with both approaches a significant weight loss and loss of intrahepatic fat content is achievable. Reduction in fat content is accompanied by a decline in hepatic inflammation, reflected in reduction of aminotransferases. In patients with NASH both therapeutic interventions can be advocated in order to reduce liver fat content and hepatic inflammation.

Research perspectives

Both interventions had distinct effects on liver fat quality. The reduction of serum triglycerides is a known effect of soy protein supplementation thus, we hypothesize that the different changes in liver fat quality were also related to soy protein intake. However, the physiologic consequence of a shortened chain length or of a different grade of saturation in hepatic lipids is not clear yet. This has to be addressed in future investigations. Furthermore, our research results demonstrated the practicability of magnetic resonance spectroscopy to analyze liver fat quality. The validity has to be confirmed by further studies.