Calories May Outweigh Nutrients in Diets for Fatty Liver

Laird Harrison

June 25, 2021

Intermittent calorie restriction offers only modest advantages over a low-carbohydrate, high-fat diet (LCHF) for treating nonalcoholic fatty liver disease (NAFLD), researchers say.

The intermittent diet offers more benefit for liver stiffness and low-density lipoprotein (LDL) cholesterol, and might be easier to maintain, said Magnus Holmer, MD, head of the Hepatology Unit at the Karolinska Institute in Stockholm, Sweden.

But the intermittent diet also has drawbacks and the differences between the two were slight, he told Medscape Medical News.

"They were more or less identically effective in reducing liver steatosis in NAFLD and also reducing body weight," he said. "And from this, we can say that the composition of macronutrients such as fat or sugar seems to be less important than how many calories you eat."

Holmer and colleagues presented their findings at the International Liver Congress (ILC) 2021 and published them in JHEP Reports.

While previous studies have shown that dieting can effectively treat NAFLD, researchers have debated whether popular low-carbohydrate, high-fat diets might cause more harm than good.

At the same time, intermittent-calorie restriction diets have also been gaining in popularity, particularly the 5:2 diet in which participants eat normally for 5 days a week and restrict their calories the other 2 days.

How Do the Two Diets Compare?

To see if one was more effective than the other, the researchers recruited 74 people with NAFLD. They diagnosed the patients either by radiologic assessment or a combination of controlled attenuation parameter (CAP) >280 dB/m and obesity, or a CAP >280 dB/m, elevated alanine aminotransferase, and overweight. Sixteen of the patients were being treated with statins.

The researchers randomly assigned 25 people to an LCHF diet, 25 to a 5:2 diet, and 24 to standard care. The groups were similar in diet, age, body mass index (BMI), liver stiffness, and most other criteria at baseline, although there were more women in the standard care group.

At the start of the study, the participants in the standard care group consulted with a hepatologist who advised them to avoid sweets and saturated fats, eat three meals a day, and avoid large portions.

The researchers asked women in the 5:2 diet to eat up to 500 kcal/day each of 2 days per week and up to 2000 kcal/day each of the other 5 days. They asked men in the group to eat up to 600 kcal/day each of 2 days per week and up to 2400 kcal/day the other 5 days.

They provided all the 5:2 participants with recipes that followed the Nordic Nutrition Recommendations, an adaptation of the Mediterranean diet that emphasizes foods traditional in Nordic countries, particularly grains such as whole-grain rye, oats, and barley; fruits such as apples, pears, berries, and plums; root vegetables, cabbages, onions, peas, beans, fish, boiled potatoes, and dairy products; and the use of rapeseed (canola) oil. The calories provided in the recipes were composed of 45%-60% carbohydrates, 25% fat, and 10%-20% protein.

The researchers asked women in the LCHF diet to eat an average of 1600 kcal/day and men to eat an average of 1900 kcal/day. All the participants used recipes based on meat, fish, eggs, low-carbohydrate vegetables, and dairy fat. Participants avoided sugar, bread, pasta, rice, pies, potatoes, and fruit. The calories in the recipes were composed of 5%-10% carbohydrates, 50%-80% fat, and 15%-40% protein.

All the participants reported what they ate over the previous 3 days, both at the start of the study and after 12 weeks. Participants in the 5:2 and LCHF groups also received follow-up calls to report their past 24 hours of eating at 2, 4, 8, and 12 weeks, and also at week 6, when they visited a dietitian.

In addition, the researchers measured the participants' linoleic acid and α-linolenic acid intake to verify that the participants' diets were different among the groups.

After 12 weeks, all three groups lost a significant amount of liver fat, but the LCHF and 5:2 groups lost more than the standard care group. Liver stiffness decreased significantly in the 5:2 and standard care groups, but not in the LCHF group.

Table. Change in Body Composition

Diet Mean Change in Liver Steatosis, % Mean Change in Liver Stiffness, kPa Mean Change in Body Weight, kg
Standard Care -3.6 -1.5 -2.5
LCHF -7.2 -0.3 -7.3
5:2 -6.1 -1.8 -7.4


The differences in steatosis change between the standard care and LCHF groups was statistically significant (P = .001), as it was between the standard care and 5:2 groups (P = .029). The differences between the LCHF and 5:2 groups were not statistically significant for weight or steatosis, but they were statistically significant for liver stiffness.

In addition, the 5:2 group significantly reduced total and LDL cholesterol, while the standard care group did not. In the LCHF group, levels of LDL, HDL, and total cholesterol all increased.

The long-term implications of the cholesterol findings are unclear, Holmer said. He hopes to follow up on these patients after 18-24 months. But the initial cholesterol findings are perhaps enough to constitute a red flag for anyone with a history of cardiovascular disease, Holmer said.

Diet Adherence

Only one person dropped out of the 5:2 group, compared with 5 in the LCHF group and 4 in the standard care group. More people in the LCHF group reported adverse events, such as gastrointestinal upset.

"With LCHF, it's a drastic change for most people," Holmer said. "Many patients are a bit shocked when they realize how much fat they are supposed to eat for breakfast, for lunch, and for dinner. They might eat bacon and eggs for breakfast every day." The diet could be challenging for people who want to reduce their consumption of meat for environmental reasons, he added.

The 5:2 group offers the advantage that people can choose what they want to eat as long as they adhere to the calorie restrictions, he pointed out. Still, he cautioned that the diet would not work well for people with insulin-dependent diabetes because of the difficulty of adjusting insulin levels on fasting days. He also recommended against this diet for people with cirrhosis because they need to eat frequent meals.

LCHF and 5:2 Diets Can Work

But for most people the good news is that a variety of diets will work to treat NAFLD, Holmer said.

"I begin with saying to my patients that this can be completely cured, as long as you're able to lose weight," he said. "Then the next question is, how are they going to go ahead with that task? And if they're already interested in some sort of specific diet, then I can, based on these findings, encourage that."

Stephen Harrison, MD, a visiting professor of hepatology at Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom, said that longer term results will be important. For example, it will be interesting to see if the diets had effects on ballooning or inflammation, he told Medscape Medical News.

Another limitation of the study is that it is relatively small in size, he said. He pointed out that people with NAFLD should increase their physical activity as well as eating less.

Still, Harrison greeted the findings enthusiastically, saying, "This is an important study."

It's useful to compare two popular diets head-to-head, and it's also encouraging to get confirmation that either one can work, he added.

The study was supported by grants from the Stockholm County Council, the Dietary Science Foundation (Kostfonden), the Skandia Research Foundation, and the Åke Wiberg Foundation. Holmer has disclosed no relevant financial relationships. Harrison is a consultant to Madrigal Pharmaceuticals.

International Liver Congress (ILC) 2021: Abstract OA-1627. Presented June 25, 2021.

JHEP Reports. Published February 17, 2021. Full text

Laird Harrison writes about science, health and culture. His work has appeared in national magazines, in newspapers, on public radio and on websites. He is at work on a novel about alternate realities in physics. Harrison teaches writing at the Writers Grotto. Visit him at or follow him on Twitter@LairdH


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