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

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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.