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)
Journal article, 2025
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).
Author
Michael Fridén
Institutionen för folkhälso- och vårdvetenskap
Fredrik Rosqvist
Uppsala University
Institutionen för folkhälso- och vårdvetenskap
Joel Kullberg
Antaros Medical AB
Uppsala University
Lars Berglund
Epistat AB
Institutionen för folkhälso- och vårdvetenskap
Dalarna university
Johan Vessby
Uppsala University
Mats Martinell
Institutionen för folkhälso- och vårdvetenskap
Per Ola Carlsson
Uppsala University
Johannes Hulthe
Antaros Medical AB
Lars Johansson
Antaros Medical AB
Nouman Ahmad
Uppsala University
Hans Erik Johansson
Institutionen för folkhälso- och vårdvetenskap
Fredrik Rorsman
Uppsala University
J. Sundstrom
Uppsala University
L. Lind
Uppsala University
Rikard Landberg
Wallenberg Lab.
Chalmers, Life Sciences, Food and Nutrition Science
M. Orho-Melander
Lund University
Håkan Ahlström
Uppsala University
Ulf Risérus
Institutionen för folkhälso- och vårdvetenskap
Nature Communications
2041-1723 (ISSN) 20411723 (eISSN)
Vol. 16 1 11130Subject Categories (SSIF 2025)
Nutrition and Dietetics
Endocrinology and Diabetes
DOI
10.1038/s41467-025-65613-2