Journal Article

Effects of an anti-lipogenic low-carbohydrate high polyunsaturated fat diet or a healthy Nordic diet versus usual care on liver fat and cardiometabolic disorders in type 2 diabetes or prediabetes: a randomized controlled trial (NAFLDiet)

Rorsman, Fredrik, Ahmad, Nouman, Martinell, Mats, Orho-Melander, Marju, Kullberg, Joel, Sundström, Johan, Risérus, Ulf, Hulthe, Johannes, Ahlström, Håkan, Rosqvist, Fredrik, Berglund, Lars, Landberg, Rikard, Fridén, Michael, Lind, Lars, Johansson, Lars, Johansson, Hans-Erik, Carlsson, Per-Ola, Vessby, Johan

2025

Overview

Polyunsaturated fatty acids (PUFA) have been shown to reduce liver fat compared to saturated fat, but effects of a novel “anti-lipogenic” diet replacing carbohydrates with PUFA (LCPUFA) or a low-fat healthy Nordic diet (HND) rich in whole-grains are unknown. The objective of this study was to investigate the effects of these diets, as compared with usual care (UC), on liver fat (primary outcome) and related glycemic and lipid disorders after 12 months of intervention, in individuals with prediabetes or type 2 diabetes (T2D). A three-arm parallel ad libitum randomized trial was completed in December 2022 (NCT04527965). Outcome assessors and care providers were blinded to participants’ diets. Men and women (n=150) with prediabetes or T2D (55%) were randomized in a 1:1:1 allocation ratio, stratified by sex and T2D status, and were assessed at the Uppsala Academic hospital. General linear models were employed to estimate intention-to-treat effects. Liver fat was reduced after the LCPUFA diet (n=54) and the HND (n=51) when compared to UC (n=43); -1.46% (95% CI: -2.42, -0.51)) and -1.76 % (95% CI: -2.96, -0.57), respectively. No difference in liver fat between LCPUFA and HND was observed. Body weight and HbA1c decreased more in the HND versus the other diets, whereas no differences were observed between LCPUFA and UC. LDL-cholesterol was reduced to a similar extent during the HND and LCPUFA diet, compared to UC, whereas only HND reduced triglycerides, inflammation and liver enzymes. In total, n=4 serious adverse events occurred, distributed among groups. An ad libitum mainly plant-based LCPUFA diet and HND similarly reduced liver fat and LDL-cholesterol, compared with UC. Even without intentional energy restriction, the HND further improved body weight, glycemic control, liver biochemistry, triglycerides, and inflammation, suggesting a HND as a clinically feasible diet for the management of T2D and metabolic dysfunction-associated steatotic liver disease (MASLD). Previous short-term clinical trials suggested plant-derived polyunsaturated fatty acids (PUFA) reduced liver fat. Here the authors report in a controlled randomised clinical trial that low-fat Nordic diet and a low-carbohydrate diet rich in polyunsaturated fat lowered liver fat content in individuals with prediabetes or diabetes.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 45 / 692/163/2743/137/773 / 692/4019/2776 / 692/4020/1503/1607/2750 / 82/16 / Adult / Aged / Blood pressure / Body mass index / Body weight / Carbohydrates / Cholesterol / Clinical Medicine / Clinical trials / Diabetes / Diabetes mellitus (non-insulin dependent) / Diabetes Mellitus, Type 2 - diet therapy / Diabetes Mellitus, Type 2 - metabolism / Diet / Diet, Carbohydrate-Restricted - methods / Diet, Healthy - methods / Disorders / Endocrinology and Diabetes / Endokrinologi och diabetes / Energy intake / Fatty acids / Fatty Acids, Unsaturated - administration & dosage / Fatty liver / Female / Flowers & plants / Glucose / Health Sciences / High carbohydrate diet / High fat diet / Homeostasis / Humanities and Social Sciences / Humans / Hälsovetenskap / Inflammation / Klinisk medicin / Lipids / Lipogenesis / Liver / Liver - metabolism / Liver - pathology / Liver diseases / Low carbohydrate diet / Low density lipoprotein / Low fat / Low fat diet / Male / Medical and Health Sciences / Medicin och hälsovetenskap / Metabolic disorders / Middle Aged / multidisciplinary / Non-alcoholic Fatty Liver Disease - diet therapy / Nutrient deficiency / Nutrition and Dietetics / Näringslära och dietkunskap / Polyunsaturated fatty acids / Prediabetic State - diet therapy / Prediabetic State - metabolism / Proteins / Science / Science (multidisciplinary) / Sex ratio / Triglycerides / Womens health