Replacing meat with plant-based proteins for just one meal reduced ammonia levels in patients with cirrhosis, a proof-of-concept study showed.

High levels of serum ammonia after protein loads may predict poor outcomes, including hepatic encephalopathy (HE), in patients with cirrhosis, whereas vegetable protein diets are associated with decreased serum ammonia, according to Jasmohan Bajaj, MD, a gastroenterologist at Virginia Commonwealth University School of Medicine and the Richmond VA Medical Center, Richmond, Virginia, and colleagues.

However, changing from meat-based to non–meat-based meals is difficult to do over a long period.

“Previous studies have changed people’s diets completely, expecting them to be on a meatless or vegetarian diet with a similar amount of protein when they’ve been eating meat their entire life,” Bajaj told Medscape Medical News. “That’s not really sustainable in the long run.”

“Our hope is that occasional meal substitutions would be beneficial,” he said. “This study is a first step toward seeing if that works.”

The study was published online on May 2 in Clinical and Translational Gastroenterology.

Meal Type Affects Ammonia Levels Differently

The researchers randomized 30 men with cirrhosis and on a traditional Western meat-based diet into three groups, where they received a pork/beef burger, a vegetarian bean burger, or a burger made of vegan meat substitute. The burgers provided 20 g of protein each, and all meals contained low-fat potato chips, a whole-grain bun, water, and no condiments.

The participants’ median age was 66 years in the meat and vegetarian arms and 71 years in the vegan arm. About half had diabetes, and half had prior HE and were evenly distributed across the treatment arms. Cirrhosis etiologies included hepatitis C virus infection, alcohol, and metabolic-associated steatohepatitis.

Stool microbiome characteristics, changes in ammonia, and metabolomics were compared between and within groups.

In the 3 days prior to the intervention, participants had similar intakes of red meat, poultry, fish, eggs, bread, cheese, rice, fruits, vegetables, yogurt, coffee, tea, and carbonated caffeinated and decaffeinated beverages.

Blood for metabolomics and ammonia was drawn at baseline and hourly for 3 hours post-meal while patients were under observation. All participants completed the entire meal, as shown subsequently by markers of food consumption, and none developed HE symptoms during the observation period.

The composition of the stool microbiome was similar at baseline across groups and remained unchanged. However, serum ammonia increased from baseline in the meat group but not in the vegetarian or vegan groups. The serum microbiome was not analyzed because of the low yield.

Serum metabolomics showed beneficial changes over time associated with branched-chain amino acid metabolism and urea cycle, phospholipid, and acylcarnitine levels in the vegetarian and vegan meal groups compared with the meat-based group.

In contrast, alterations in lipid profiles (higher sphingomyelins and lower lysophospholipids) were seen in the meat group.

The study was limited by its relatively small sample size, focus on the impact of only one meal, and lack of clinical outcomes, sarcopenia assessment, cognitive testing, or urine collection.

“Intermittent meat substitution with vegan or vegetarian alternatives could be helpful in reducing ammonia generation in cirrhosis,” the authors concluded.

The next step “is to substitute one meal two or three times a week, so we can move forward with this analysis and eventually be able to show that the liver is in better shape,” Bajaj said.

Meanwhile, clinicians should encourage patients with liver disease who eat meat regularly to try to substitute it with protein from plant or dairy sources, at least occasionally, he said. When doing so, “clinicians should ask their patients’ preferences before assuming that they will do everything that you ask them to do because nutrition in cirrhosis is really critical — not only what they eat but also when they eat. Working with a dietitian, like we did in our study, is critical, or at least having access to one if you don’t have one in your practice.”

Positive Results From a Simple Change

Commenting on the study for Medscape Medical News, Nancy S. Reau, MD, section chief, hepatology and associate director of organ transplantation at Rush Medical College in Chicago, said, “My biggest concern is making sure patients are ingesting enough quality protein and calories because anorexia is a common complication in cirrhosis, and sarcopenia is associated with poor outcomes.”

“You don’t want to suggest a change that will result in eating less or skipping a meal,” she said. So, “it is encouraging to see that suggesting a small change, just one meal a day, that may not impact calorie intake could have positive results.”

Reau added that “it is great to see evidence that this small change also could be a way of decreasing the risk of HE while not compromising on patient nutrition.”

Larger studies with outcome data showing that this approach could prevent readmission in patients hospitalized for HE would be helpful, she said.

The study was partly supported by the ACG Clinical Research Award, VA Merit Review 2I01CX001076, I01CX002472, and NIAAA RO1AA29398. Bajaj and Reau reported no conflicts of interest.

Marilynn Larkin, MA, is an award-winning medical writer and editor whose work has appeared in numerous publications, including Medscape Medical News and its sister publication MDedge, The Lancet (where she was a contributing editor), and Reuters Health.