Treatment of NAFLD with intermittent calorie restriction or low-carb high-fat diet - a randomised controlled trial

Magnus Holmer; Catarina Lindqvist; Sven Petersson; John Moshtaghi-Svensson; Veronika Tillander; Torkel B Brismar; Hannes Hagström; Per Stål

doi:10.1016/j.jhepr.2021.100256

Treatment of NAFLD with intermittent calorie restriction or low-carb high-fat diet - a randomised controlled trial

JHEP Rep. 2021 Feb 17;3(3):100256. doi: 10.1016/j.jhepr.2021.100256. eCollection 2021 Jun.

Authors

Magnus Holmer^{1

2}, Catarina Lindqvist^{3

4}, Sven Petersson^{5

6}, John Moshtaghi-Svensson⁷, Veronika Tillander⁸, Torkel B Brismar^{6

9}, Hannes Hagström^{1

2

10}, Per Stål^{1

2}

Affiliations

¹ Division of Hepatology, Department of Upper GI, Karolinska University Hospital, Stockholm, Sweden.
² Unit of Gastroenterology and Hepatology, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
³ Medical Unit Clinical Nutrition, Karolinska University Hospital, Stockholm, Sweden.
⁴ Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
⁵ Department of Clinical Science, Intervention and Technology at Karolinska Institutet, Division of Medical Imaging and Technology, Stockholm, Sweden.
⁶ Department of Medical Radiation Physics and Nuclear Medicine, Karolinska University Hospital, Stockholm, Sweden.
⁷ Godjy AB, Stockholm, Sweden.
⁸ Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
⁹ Department of Radiology, Karolinska University Hospital in Huddinge, Stockholm, Sweden.
¹⁰ Clinical Epidemiology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.

Abstract

Background & aims: The first-line treatment for non-alcoholic fatty liver disease (NAFLD) is weight reduction. Several diets have been proposed, with various effects specifically on liver steatosis. This trial compared the effects of intermittent calorie restriction (the 5:2 diet) and a low-carb high-fat diet (LCHF) on reduction of hepatic steatosis.

Methods: We conducted an open-label randomised controlled trial that included 74 patients with NAFLD randomised in a 1:1:1 ratio to 12 weeks' treatment with either a LCHF or 5:2 diet, or general lifestyle advice from a hepatologist (standard of care; SoC). The primary outcome was reduction of hepatic steatosis as measured by magnetic resonance spectroscopy. Secondary outcomes included transient elastography, insulin resistance, blood lipids, and anthropometrics.

Results: The LCHF and 5:2 diets were both superior to SoC treatment in reducing steatosis (absolute reduction: LCHF: -7.2% [95% CI = -9.3 to -5.1], 5:2: -6.1% [95% CI = -8.1 to -4.2], SoC: -3.6% [95% CI = -5.8 to -1.5]) and body weight (LCHF: -7.3 kg [95% CI = -9.6 to -5.0]; 5:2: -7.4 kg [95% CI = -8.7 to -6.0]; SoC: -2.5 kg [95% CI =-3.5 to -1.5]. There was no difference between 5:2 and LCHF (p = 0.41 for steatosis and 0.78 for weight). Liver stiffness improved in the 5:2 and SoC but not in the LCHF group. The 5:2 diet was associated with reduced LDL levels and was tolerated to a higher degree than LCHF.

Conclusions: The LCHF and 5:2 diets were more effective in reducing steatosis and body weight in patients with NAFLD than SoC, suggesting dietary advice can be tailored to meet individual preferences.

Lay summary: For a person with obesity who suffers from fatty liver, weight loss through diet can be an effective treatment to improve the condition of the liver. Many popular diets that are recommended for weight reduction, such as high-fat diets and diets based on intermittent fasting, have not had their effects on the liver directly evaluated. This study shows that both a low-carb high-fat and the 5:2 diet are effective in treating fatty liver caused by obesity.

Clinical trials registration: This study is registered at Clinicaltrials.gov (NCT03118310).

Keywords: 5:2 diet; ALA, α-linolenic acid; ALT, alanine aminotransferase; CAP, controlled attenuation parameter; CT, computed tomography; Diet treatment; E%, energy percent; EoT, end of treatment; HOMA-IR, homeostatic model assessment for insulin resistance; ICR, intermittent calorie restriction; IR, insulin resistance; ITT, intention-to-treat analysis; Intermittent calorie restriction; LCHF, low-carb high-fat diet; Low-carb-high fat (LCHF); MRS, magnetic resonance spectroscopy; MUFA, monounsaturated fatty acids; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; NNR, Nordic Nutrition Recommendations 2012; OGTT, oral glucose tolerance test; Obesity; PP, per protocol analysis; PUFAs, polyunsaturated fatty acids; SFAs, saturated fatty acids; SoC, standard of care; T2DM, type 2 diabetes mellitus; WHR, waist-to-hip ratio; low-CHO, low-carbohydrate diet.

Associated data

ClinicalTrials.gov/NCT03118310