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Liver transplant recipients benefited from a low carbohydrate diet (LCD), achieving weight loss and an improved metabolic phenotype profile, according to a randomized trial.

In an interim analysis involving 27 patients, those who followed an LCD had a significantly higher mean weight loss of nearly 8 kg (about 17 lbs) over 6 months, compared to those on a low calorie restricted diet (CRD), who did not experience any significant weight loss (P=0.01), reported Mohammad Siddiqui, DO, of Virginia Commonwealth University in Richmond.

The LCD positively affected patients' metabophenotype, especially for fat depots, he said in a presentation at the American Association for the Study of Liver Diseases (AASLD).

Siddiqui pointed out that the LCD led to a "greater reduction in body fat compartments (liver, visceral, subcutaneous, and muscle)."

As the LCD group lost weight, they experienced a significant improvement in fat tissue depots all over their body, including in both visceral adipose and abdominal subcutaneous adipose tissue, with each showing nearly a 20% reduction in the change from baseline. They also had improvement in muscle fat infiltration (nearly a 10% reduction), and in liver fat content, but this did not reach significance (P=0.06)

Also, there was a "very mild" decrease (about 5%) in skeletal muscle volume in the LCD group, but not in the CRD group (P<0.01).

Reached for comment, Andrew Talal, MD, MPH, of the University at Buffalo in New York, told MedPage Today, "I think that these interim results are encouraging for the potential effectiveness of LCD over caloric restriction, but require caution in drawing any firm conclusions."

"We await the final results of the trial with interest," said Talal, who was not involved in this study.

Although weight gain and even obesity are common after liver transplantation, patients with obesity have an increased risk for cardiovascular disease and mortality. Liver transplant recipients often experience a lot of difficulty in achieving weight loss. Prior studies found these patients present metabolic inflexibility, which causes fatty acids to be released into circulation. In addition, skeletal muscle is less receptive in fatty acid oxidation, resulting in fat re-circulation/re-cycling that deposits fat into different organs, thereby reducing mitochondrial efficiency, and leading to difficulty with weight loss, he explained.

The goal of the trial was "to see if we can achieve weight loss and in doing so, improve metabolic flexibility," Siddiqui said.

The researchers enrolled 27 liver transplant recipients who had obesity and randomized them to receive a CRD (n=13), which involved a total calorie intake of less than 1,200-1,500 calories per day, regardless of macronutrient content, or an LCD (n=14) with a carbohydrate restriction of 20 grams per day for 24 weeks. Adults with a BMI of at least 30 were included. Follow-up occurred every 2 weeks.

Excluded were those with chronic end-organ damage, uncontrolled psychiatric illness, terminal disease, or those receiving weight loss medications, among others.

When asked by an AASLD attendee if those specifically on GLP-1 receptor antagonists were also excluded, Siddiqui responded, "This is the United States, where highly effective medications are not covered by insurance, so that wasn't a problem."

At 7 days, accelerometry results were assessed to ensure patients maintained the same level of physical activity.

A change in weight was the primary outcome assessed by standard weight scales. To better understand patients' body physiology with weight change, several secondary outcomes evaluated metabophenotypes, metabolic flexibility, mitochondrial function, and metabolic risks using tools for whole-body MRI, whole-room calorimetry, respiratory capacity, and lipoproteins/insulin resistance.

Baseline clinical characteristics were similar among groups. Mean age was 55-56 and 60%-61% were men. Overall, 60% were non-Hispanic white and the average BMI was 37-40. Two-thirds had diabetes.

Common comorbidities included hypertension (100% vs 89% in the LCD group), dyslipidemia (60% vs 50%), and non-alcoholic steatohepatitis (NASH; 67% vs 33%). Siddiqui cautioned that "the study is ongoing, and I suspect these differences are going to be even less significant."

At study completion, both diets were well tolerated and did not result in any significant change in renal function.

When looking at metabolic risk, the LCD had no impact on serum lipids (total cholesterol, triglycerides, LDL/HDL), renal function levels (glomerular filtration rate, blood urea nitrogen, or serum creatinine), or insulin resistance (HbA1c and glucose). However, those in the LCD group had a reduced insulin dose, since most were taken off insulin at enrollment, while none in the CRD group were taken off insulin.

The LCD "may potentially improve insulin sensitivity," Siddiqui said.

He said his group plans to further explore the impact of dietary intervention on metabolic flexibility, and to assess the use of baseline metabolic flexibility in predicting a response to diet, among other key areas of research, such as atherogenic lipoproteins.

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