Highlights
- Both a low-carbohydrate high-polyunsaturated fat (LCPUFA) diet and a Healthy Nordic Diet (HND) significantly reduced liver fat compared to usual care over 12 months.
- The Healthy Nordic Diet led to greater reductions in body weight and HbA1c compared to both the LCPUFA diet and usual care.
- Only the HND group showed significant improvements in systemic inflammation (CRP), triglycerides, and liver enzymes (ALT/AST).
- Both active diets similarly reduced LDL-cholesterol, demonstrating the lipid-lowering potential of replacing saturated fats with plant-based sources or whole grains.
Background and Clinical Context
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a burgeoning global health crisis intimately linked with the twin epidemics of type 2 diabetes (T2D) and obesity. In patients with T2D, the prevalence of MASLD can exceed 70%, significantly increasing the risk of progression to steatohepatitis, cirrhosis, and hepatocellular carcinoma. Beyond hepatic complications, MASLD serves as an independent driver of cardiovascular disease, the leading cause of mortality in this population.
Nutritional intervention remains the cornerstone of MASLD management. Traditionally, weight loss through caloric restriction has been the primary goal. However, the qualitative composition of the diet—specifically the types of fats and carbohydrates consumed—plays a critical role in hepatic lipogenesis. Saturated fatty acids (SFA) are known to promote hepatic fat accumulation, whereas polyunsaturated fatty acids (PUFA) have been shown to reduce liver fat. The “anti-lipogenic” diet concept explores replacing high-glycemic carbohydrates with PUFA to suppress de novo lipogenesis. Conversely, the Healthy Nordic Diet (HND), characterized by high intake of whole grains, berries, root vegetables, and fatty fish, emphasizes fiber and low-glycemic index foods. Until the publication of the NAFLDiet trial, the long-term comparative efficacy of these two distinct dietary patterns on liver fat and systemic metabolic health in a real-world, ad libitum setting remained poorly understood.
The NAFLDiet Study: Design and Methodology
The NAFLDiet trial (NCT04527965) was a three-arm, parallel-group, ad libitum randomized controlled trial conducted at Uppsala Academic Hospital, Sweden. The study enrolled 150 participants (men and women) diagnosed with either prediabetes or T2D. Participants were randomized in a 1:1:1 ratio to one of three groups: an anti-lipogenic LCPUFA diet, a Healthy Nordic Diet (HND), or usual care (UC).
The LCPUFA diet focused on replacing carbohydrates with polyunsaturated fats, primarily from plant-based sources like vegetable oils and nuts, aiming for a low-carbohydrate profile without strict caloric restriction. The HND emphasized traditional Nordic foods, including high-fiber whole grains (rye, oats, barley), rapeseed oil, berries, and fish, also consumed ad libitum. The usual care group received standard dietary advice typically provided in primary care settings for diabetes management. The primary endpoint was the change in liver fat percentage measured by magnetic resonance imaging (MRI) after 12 months. Secondary endpoints included changes in body weight, glycemic control (HbA1c), lipid profiles, liver enzymes, and markers of systemic inflammation.
Primary and Secondary Outcomes
Liver Fat Reduction
The study successfully demonstrated that both dietary interventions were effective in reducing hepatic steatosis. After 12 months, liver fat was significantly reduced in the LCPUFA group by -1.46% (95% CI: -2.42, -0.51) and in the HND group by -1.76% (95% CI: -2.96, -0.57) relative to the usual care group. Notably, there was no statistically significant difference in the magnitude of liver fat reduction between the LCPUFA and HND groups, suggesting that both increasing PUFA intake and increasing fiber-rich whole grains can effectively mitigate hepatic fat accumulation.
Weight and Glycemic Control
While liver fat reduction was similar between the two active diets, the HND demonstrated superior results in other metabolic parameters. Participants in the HND group experienced a significantly greater reduction in body weight and HbA1c compared to both the LCPUFA and UC groups. This is particularly noteworthy as the diets were ad libitum, suggesting that the HND may inherently promote better satiety or metabolic efficiency compared to a high-fat, low-carbohydrate approach in this population.
Lipid Profiles and Systemic Inflammation
Both the LCPUFA and HND interventions resulted in significant reductions in LDL-cholesterol compared to usual care, likely due to the replacement of saturated fats with unsaturated fats or fiber. However, the HND group showed a broader range of benefits, including significant reductions in serum triglycerides and liver enzymes (ALT and AST). Furthermore, the HND was the only intervention to significantly reduce C-reactive protein (CRP), a marker of systemic inflammation, suggesting a more comprehensive anti-inflammatory effect compared to the LCPUFA diet.
Expert Commentary and Mechanistic Insights
The findings of the NAFLDiet trial provide critical insights into the dietary management of MASLD and T2D. The comparable reduction in liver fat between a low-carb, high-PUFA diet and a high-carb, high-fiber Nordic diet challenges the notion that carbohydrate restriction is the only path to reducing hepatic steatosis. Mechanistically, the PUFAs in the LCPUFA diet likely work by activating peroxisome proliferator-activated receptor alpha (PPAR-α) and inhibiting sterol regulatory element-binding protein 1 (SREBP-1), thereby increasing fatty acid oxidation and decreasing de novo lipogenesis.
On the other hand, the success of the HND—despite its higher carbohydrate content—highlights the importance of carbohydrate quality. The high fiber content from whole grains in the HND likely modulates the gut microbiome and increases the production of short-chain fatty acids (SCFAs), which have been shown to improve insulin sensitivity and reduce hepatic inflammation. The superior weight loss and glycemic control observed in the HND group suggest that the combination of fiber, polyphenols from berries, and healthy fats in the Nordic pattern may be more effective for overall metabolic health than focusing solely on the fat-to-carbohydrate ratio.
Clinical feasibility is another major takeaway. Ad libitum diets are generally easier for patients to maintain long-term than calorie-restricted regimens. The fact that HND improved so many markers without intentional energy restriction makes it a highly attractive clinical recommendation for the management of metabolic syndrome.
Conclusion and Clinical Implications
The NAFLDiet trial provides robust evidence that both a plant-based LCPUFA diet and a Healthy Nordic Diet are effective at reducing liver fat and improving LDL-cholesterol in individuals with T2D or prediabetes. However, the Healthy Nordic Diet emerged as the more effective strategy for broader metabolic improvement, offering superior benefits for weight management, glycemic control, triglyceride reduction, and the dampening of systemic inflammation. These results suggest that clinicians should prioritize dietary patterns rich in whole grains, fiber, and unsaturated fats—such as the Healthy Nordic Diet—as a primary therapeutic intervention for MASLD and cardiometabolic disorders.
Funding and Trial Registration
This study was supported by various grants, including the Swedish Research Council and the Swedish Heart-Lung Foundation. The trial is registered at ClinicalTrials.gov under the identifier NCT04527965.
References
1. Fridén M, Rosqvist F, Kullberg J, et al. 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). Nat Commun. 2025;16(1):11130. doi:10.1038/s41467-025-65613-2.
2. Rinella ME, et al. A multi-society Delphi consensus statement on new nomenclature for steatotic liver disease. Hepatology. 2023.
3. Rosqvist F, et al. Overfeeding Polyunsaturated and Saturated Fat Causes Distinct Effects on Liver and Visceral Fat Accumulation in Humans. Diabetes. 2014;63(7):2356-2368.
