LONDON — A low-carbohydrate, high-fat (LCHF) diet reduced the progression of nonalcoholic fatty liver disease (NAFLD), and despite no calorie restriction, participants with both NAFLD and type 2 diabetes lost 5.8% of their body weight, according to a randomized controlled study.
“Based on these results, the LCHF diet may be recommended to people with NAFLD and type 2 diabetes,” said Camilla Dalby Hansen, MD, department of gastroenterology and hepatology, Odense University Hospital, Odense, Denmark, who presented the data here at the International Liver Congress (ILC) 2022.
“Basically, if you have fat in your liver, you will benefit from eating fat,” she said.
The LCHF diet was compared with a low-fat, high-carbohydrate diet more typically followed for these conditions. The low-fat diet was also found to reduce the progression of NAFLD, but to a lesser extent than the LCHF diet.
Dalby Hansen called their study one of the most extensive investigations of the LCHF diet in patients with type 2 diabetes and fatty liver disease.
“Combining this [reduction in NAFLD score] with the huge weight loss, the lower HbA1c [blood sugar], the lowering of blood pressure in women, the rise in HDL levels, and reduction in triglycerides — all in all, this diet is very promising,” she said.
Stephen Harrison, MD, visiting professor, University of Oxford, United Kingdom, medical director of Pinnacle Clinical Research, and president of Summit Clinical Research LLC in San Antonio, Texas, commended Dalby Hansen on her methodology, which included before-and-after liver biopsies. “It’s a heinous effort to do paired liver biopsies in a lifestyle modification trial. That’s huge.”
“This study tells me that the way we manage patients doesn’t change — it is still lifestyle modification,” said Harrison, who was not involved with the study. “It’s eat less [rather than] than more. It’s exercise and try to lose weight. In the long term, we give patients benefit, and we show that the disease has improved, and we offer something that means they can maintain a healthy life.”
He added that the relatively small and short trial was informative.
“They improved the NAFLD activity score [NAS],” he said. “I don’t know by how much. There was no change in fibrosis, but we wouldn’t expect this at 6 months.”
“It’s provocative work, and it gives us healthy information about how we can help manage our patients from a lifestyle perspective,” he concluded.
“Do Not Lose Weight. Eat Until You Are Full”
In the study, 110 participants with type 2 diabetes and NAFLD, aged 18-78 years, were allocated to the LCHF diet, and 55 were allocated to the low-fat diet for 6 months.
The researchers performed liver biopsies at baseline and 6 months, which were blinded for scoring.
Participants had ongoing dietitian consultations, with follow-up visits at 3 and 6 months. Compliance was reported continuously through an online food diary platform.
The primary endpoint was change in glycemic control as measured by A1c level over 6 months. The secondary endpoints comprised the proportion of participants with changes in the NAS of at least 2 points over 6 months. Both these measures were compared between the two dietary groups.
The two groups were matched at baseline, with a mean age of 55-57 years, 58% were women, 89% with metabolic syndrome, and a mean BMI 34 kg/m2.
In baseline liver disease, F1 level fibrosis was the most common (58%), followed by hepatic steatosis (S1, 47%; S2, 32%), with a median NAS of 3, and 19% had nonalcoholic steatohepatitis.
The special thing about these diets was that participants were told to “not lose weight, but eat until you are full,” remarked Dalby Hansen.
Those on the LCHF diet consumed an average of 61% energy from fat, 13% from carbohydrates, and 23% from protein, compared with the low-fat diet, which comprised an average of 29% energy from fat, 46% from carbohydrates, and 21% from protein.
“It’s a lot of fat and corresponds to a quarter of a liter of olive oil per day,” said Dalby Hansen. “They really had to change their mindset a lot, because it was difficult for them to start eating all these fats, especially since we’ve all been told for decades that it isn’t good. But we supported them, and they got into it.”
The LCHF diet was primarily comprised of unsaturated fats — for example, avocado, oil, nuts, and seeds — but also included saturated fats, such as cheese, cream, and high-fat dairy products. Participants were free to eat unsaturated and saturated fats, but Dalby Hansen and her team advised participants that “good” unsaturated fats were preferable.
“Also, this diet contained vegetables but no bread, no potatoes, no rice, and no pasta. It was low in carbohydrates, below 20%,” she added.
Improved Glycemic Control, Reduced Liver Fat
“We found that the LCHF diet improved diabetes control, it reduced the fat in the liver, and, even though they’re eating as many calories as they were used to until they were full, they lost 5.8% of body weight,” said Dalby Hansen in reporting the results. Participants in the low-fat group lost only 1.8% of body weight.
However, mean calorie intake dropped in both groups, by -2.2% in the LCHF group and -8.7% in the low-fat group.
“The LCHF diet improved the primary outcome of A1c by 9.5 mmol/mol, which is similar to some anti-diabetic medications, such as DPP-4 inhibitors and SGLT2 inhibitors,” she said.
The low-fat group reduced A1c by 3.4 mmol/mol, resulting in a between-group difference of 6.1 mmol/mol.
“Upon follow-up of 3 months, after stopping the diets, on average the participants in both groups returned their HbA1c levels to nearly baseline values,” she said. Results were adjusted for weight loss and baseline values.
Both diets also improved the NAS. The proportion of participants who improved their NAS score by 2 or more points was 22% in the LCHF group vs 17% in the low-fat group (P = 0.58). Additionally, in the LCHF group, 70% of participants improved their score by 1 or more points, compared to 49% in the low-fat group, and fewer in the LCHF group experienced a worsening of their score (1% vs 23%, respectively).
One participant on LCHF had high triglycerides of 12 mmol/L after 3 months. Overall, the low-density lipoprotein increased marginally by 0.2 mmol per liter in the high-fat group, said Dalby Hansen.
Dalby Hansen noted some limitations. The findings might not be applicable in more severe NAFLD, dietary assessment relied on self-reporting, no food was provided, and participants had to cook themselves. It was also an open-label study because of the nature of the intervention.
Some Hope for More Sustainable Dieting
Many diets are difficult to adhere to, remarked Dalby Hansen. “We thought this [diet] might be easier to comply with in the longer term, and we hope that these results might provide patients with more options.”
She added that most people who started the diet adapted and complied with it. “However, it might not be for everyone, but I think we can say that if people try, and it fits into their lives, then they go for it.”
However, “it is not about going out and eating whatever fat and how much of it you want. It’s important that you cut the carbohydrates too,” she said. “With this approach, we really saw amazing results.”
Dalby Hansen added that having various diets available, including the LCHF one, meant that as clinicians they could empower patients to take control of their metabolic health.
“We can ask them directly, ‘What would fit into their life?’ ” she said. “We know that one size does not fit at all, and I believe that if we could engage patients more, then they can take control of their own situation.”
Asked whether these findings were enough to change guidelines, Zobair Younossi, MD, professor and chairman, department of medicine, Inova Fairfax Medical Campus, Falls Church, Virginia, remarked that it was the sugar at work here.
“Dietary fat — it’s not the same as fat in the liver, and this diet has more to do with the sugar levels,” he said.
“I’m always reluctant to take results from a short-term study without long-term follow-up,” Younossi said. “I want to know will patients live longer, and long-term data are needed for this. Until I have that strong evidence that outcomes are going to change, or at least some sign that the outcome is going to change, it is too early to change any guidelines.”
Dalby Hansen reports no relevant financial relationships.
Harrison discloses the following financial relationships with a commercial interest:
Scientific advisor or consultant for Akero, Altimmune, AstraZeneca, Axcella, Echosens, Galectin, Gilead, GSK, Hepion, HistoIndex, Intercept, Madrigal, Medpace, Metacrine, NGM Bio, Northsea, Novartis, Novo Nordisk, PathAI, Poxel, Sagimet, SonicIncytes, Terns, and Viking.
Stock options: Akero, Cirius, Galectin, Genfit, Hepion, HistoIndex, PathAI, Metacrine, NGM Bio, Northsea.
Grant/research support: Akero, Altimmune, Axcella, BMS, Cirius, CiViBiopharma, Conatus, Cymabay, Enyo, Galectin, Genentech, Genfit, Gilead, Hepagene, Hepion, Hightide, Intercept, Ionis, Madrigal, Metacrine, NGM Bio, Novartis, Novo Nordisk, Northsea, Pfizer,Sagimet, Viking, 89 Bio.
Younossi reports the following financial relationships: research funds and/or consultant to Abbott, Allergan, Bristol Myers Squibb, Echosens, Genfit, Gilead Sciences, Intercept, Madrigal, Merck, and Novo Nordisk.
International Liver Congress (ILC) 2022: Abstract GS012. Presented June 24, 2022.
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