A Very Low-Carbohydrate Program in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease and Phospholipase Domain-Containing Protein 3 Risk Genotype: Pre-Post Intervention Study

Abstract

Background: Insulin resistance and the G allele of rs738409 interact to create a greater risk of metabolic dysfunction-associated steatotic liver disease.

Objective: This study aims to confirm that one promising way to reduce insulin resistance is by following a very low-carbohydrate (VLC) dietary pattern.

Methods: Adults with rs738409-GG or -CG with liver steatosis and elevated liver function tests, were taught an ad libitum VLC diet, positive affect and mindful eating skills, goal setting, and self-monitoring and given feedback and coaching for 4 months. We measured liver steatosis, anthropometric, serum metabolic diet adherence, and quality of life measures.

Results: In this small pilot trial, of the 11 participants enrolled, 9 (82%) participants completed outcomes. All 11 participants viewed at least 1 session of the intervention, and 8 (73%) participants viewed at least half of the sessions. Among the 9 participants who provided 4-month self-report information, intervention satisfaction was high (mean 6.22, 95% CI 5.58-6.85), with 5 (56%) participants rating the intervention the top score, and 4 (44%) participants reporting they did not plan to stop following the VLC diet. Across participants with a 4-month hepatic liver fat percent measurement, the percent change in liver fat was -33.17% (95% CI -86.48 to 20.14), and in only the participants who were adherent to the eating pattern, the percent change in liver fat was -53.12% (95% CI -71.25 to -34.99). Amongst participants with a 4-month hepatic liver fat percent measurement, 6 out of 8 (75%) participants were considered responders, with a relative decline in liver fat ≥30%, and of the 9 participants with a 4-month body weight, 9 (100%) participants lost ≥5% of their body weight. There were no serious adverse events.

Conclusions: Results suggest the feasibility, acceptability, and preliminary efficacy of the VLC intervention in adults with higher genetic risk for metabolic dysfunction-associated steatotic liver disease, although there is a need for further studies given the small sample size and the high risk of substantial biases in this small pilot study.

Keywords: liver function test; T2DM; adult; dietary pattern; genome; genotype; insulin; insulin resistance; ketogenic diet; low carbohydrate; metabolic dysfunction; metabolic dysfunction–associated steatotic liver disease; non-alcoholic fatty liver disease; single-arm pilot trial; type 2 diabetes.