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

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.

Graphical abstract

Fig. 1

Flowchart of screening and inclusion of participants.

Fig. 2

Change in liver steatosis. (A) Boxplot showing MR fat percent at baseline and at end of treatment, per group: SoC: −3.6% (95% CI = −5.8 to −1.5); 5:2: −6.1% (95% CI = −8.1 to −4.2); LCHF: −7.2% (95% CI = −9.3 to −5.1). ∗^,∗∗p values for change within each group from baseline to end of treatment. p values at brackets, significance for between-group comparison with linear mixed model. (B) Relative change in MR fat from baseline to end of treatment, per group. ∗^,∗∗p values for change within group with linear mixed model. 5:2, the 5:2 diet; LCHF, the low-carb high-fat diet; MR, magnetic resonance spectroscopy; SoC, standard of care.