Substitution of One Meat-Based Meal With Vegetarian and Vegan Alternatives Generates Lower Ammonia and Alters Metabolites in Cirrhosis: A Randomized Clinical Trial

Abstract

Introduction: Diet can affect ammoniagenesis in cirrhosis and hepatic encephalopathy (HE), but the impact of dietary preferences on metabolomics in cirrhosis is unclear. As most Western populations follow meat-based diets, we aimed to determine the impact of substituting a single meat-based meal with an equal protein-containing vegan/vegetarian alternative on ammonia and metabolomics in outpatients with cirrhosis on a meat-based diet.

Methods: Outpatients with cirrhosis with and without prior HE on a stable Western meat-based diet were randomized 1:1:1 into 3 groups. Patients were given a burger with 20 g protein of meat, vegan, or vegetarian. Blood for metabolomics via liquid chromatography-mass spectrometry and ammonia was drawn at baseline and hourly for 3 hours after meal while patients under observation. Stool microbiome characteristics, changes in ammonia, and metabolomics were compared between/within groups.

Results: Stool microbiome composition was similar at baseline. Serum ammonia increased from baseline in the meat group but not the vegetarian or vegan group. Metabolites of branched chain and acylcarnitines decreased in the meat group compared with the non-meat groups. Alterations in lipid profile (higher sphingomyelins and lower lysophospholipids) were noted in the meat group when compared with the vegan and vegetarian groups.

Discussion: Substitution of a single meat-based meal with a non-meat alternatives results in lower ammoniagenesis and altered serum metabolomics centered on branched-chain amino acids, acylcarnitines, lysophospholipids, and sphingomyelins in patients with cirrhosis regardless of HE or stool microbiome. Intermittent meat substitution with vegan or vegetarian alternatives could be helpful in reducing ammonia generation in cirrhosis.

Graphical abstract

Figure 1.

Study flow and CONSORT diagram. (a) Flowchart of the study design: subjects were randomized in a 1:1:1 fashion to meat, vegan, and vegetarian meals, and blood was drawn hourly for 3 hours after meal for serum ammonia and metabolomics. Stool was collected at baseline for microbiome analysis. (b) CONSORT diagram: There were no dropouts after consent, and all subjects were included in the analysis. CONSORT, Consolidated Standards of Reporting Trials.

Figure 2.

Serum ammonia changes from baseline in meat, vegan, and vegetarian groups. (a) There was a statistically significant increase in serum ammonia from baseline at each hourly time point in the meat group but not in the vegan or vegetarian group using repeated-measures ammonia analysis. (b–d) Changes in serum ammonia based on prior hepatic encephalopathy or no prior hepatic encephalopathy. There was a similar trend in ammonia with prior HE vs no prior HE with no statistically significant differences in either the meat, vegan, or vegetarian meals. Red: HE, Black: No-HE. HE, hepatic encephalopathy.

Figure 3.

Baseline stool microbiome. (a–c) Alpha diversity values of stool microbiome at baseline. (d) Beta diversity of stool microbiome at baseline. No significant differences were seen.

Figure 4.

Summary of notable differences in the metabolomic profile comparing meat vs vegetarian/vegan meals. Metabolites higher in the meat group are colored red while those that were lower in the meat group compared with the vegetarian/vegan group are colored green. GPC, glycerophosphocholine; GPE, glycerophosphatidylethanolamine; TCA cycle, the citric acid cycle.