Medical Bulletin 06/ May/2024

Researchers from Virginia Commonwealth University’s School of Medicine and Richmond VA Medical Center reported that just one meal without meat can lower levels of harmful ammonia in people with advanced liver disease.

High levels of ammonia in the blood are linked to cirrhosis and a type of cognitive decline called hepatic encephalopathy. Ammonia levels are also known to be influenced by factors such as gut bacteria and diet. While earlier studies hinted at the benefits of a vegetarian diet for those with cognitive problems caused by cirrhosis, implementing long-term dietary changes can be challenging for patients to make and sustain. Further research is still needed to investigate the impact of vegan diets on cirrhosis and ammonia.

The study published in the journal Clinical and Translational Gastroenterology found that even a single meatless meal eaten by patients with cirrhosis generates less harmful ammonia.

In the study, researchers examined 30 adults with cirrhosis who typically consumed meat. They divided them into three groups to consume different types of burgers: pork/beef, vegan meat substitute, and vegetarian bean. Each burger provided 20 grams of protein, similar to a typical Western meal. Participants also had low-fat potato chips, a whole-grain bun, and water, without any condiments. Despite similar gut bacteria profiles initially, meal type appeared to influence ammonia levels differently, as observed in blood and urine samples taken before and after meals.

The results revealed that just a few hours after eating, the samples revealed that those who ate a meat burger had higher amino acids associated with ammonia production and hepatic encephalopathy than those who ate the non-meat burgers.

“Skipping meat from just one meal can benefit patients with cirrhosis by reducing ammonia generation. This simple dietary change or substitution can be an accessible method to alleviate symptoms. Physicians should encourage these patients to replace meat with plant- or dairy-based protein sources. Consulting a nutrition expert can provide valuable guidance on suitable foods for liver patients with cirrhosis while ensuring they maintain a balanced diet,” said the study authors.

Reference: Badal, Bryan D. MD, MS1,2; Fagan, Andrew1; Tate, Victoria RD3; Mousel, Travis RN1; Gallagher, Mary Leslie FNP1; Substitution of One Meat-based meal with Vegetarian and Vegan Alternatives Generates Lower Ammonia and Alters Metabolites in Cirrhosis: A Randomized Clinical Trial. Clinical and Translational Gastroenterology, May 02, 2024. | DOI: 10.14309/ctg.0000000000000707

In a study published in journal Cell Metabolism, researchers from the Division of Cardiology at the University of Pittsburgh found that hypertensive pulmonary blood vessel cells have a voracious appetite for two amino acids, glutamine and serine and this metabolism of glutamine and serine is a key driver of pulmonary hypertension disease progression.

Amino acids, the building blocks of proteins, play crucial roles in cellular structures, biological functions, and tissue regulation. In hypertensive pulmonary blood vessels, metabolism of glutamine and serine yields proline and glycine, key components of collagen protein. Elevated levels of proline and glycine due to increased glutamine and serine metabolism drive collagen overproduction in hypertensive vessels, resulting in stiffening and impaired function characteristic of pulmonary hypertension.

Dietary changes can potentially impact pulmonary hypertension by influencing factors such as inflammation, oxidative stress, and vascular function. For instance, a diet rich in antioxidants, omega-3 fatty acids, and phytonutrients from fruits and vegetables may help reduce inflammation and oxidative stress, which are known contributors to pulmonary hypertension. Additionally, reducing sodium intake can help manage fluid retention and lower blood pressure, which are important considerations in pulmonary hypertension management.

In rodent models of the disease, researchers found that drugs inhibiting cellular uptake of glutamine and serine prevented hypertensive pulmonary blood vessels from craving these amino acids. Consequently, the diminished metabolism of glutamine and serine halted the excessive production of collagen building blocks and collagen itself. Additionally, by reducing dietary intake of glutamine- and serine-rich foods, collagen overproduction was mitigated.

“This marks the first instance where a dietary intervention could potentially function as a viable therapy for the condition. For patients with pulmonary hypertension, avoiding foods rich in serine and glutamine, or eating foods with these amino acids depleted, might bolster the effectiveness of current medications. “It opens up a new way that we could treat this disease, because now—instead of just relying on medications and transplantation—there are possibly effective lifestyle interventions,” says Stephen Chan, University of Pittsburgh researcher.

Reference: Nesrine S. Rachedi, Ying Tang, Yi-Yin Tai, Dietary intake and glutamine-serine metabolism control pathologic vascular stiffness, Cell Metabolism, 2024, ISSN 1550-4131; https://doi.org/10.1016/j.cmet.2024.04.010.

In a study published in the journal Nature Metabolism, researchers from Southern Danish University in Denmark found via a mouse model that activating healthy brown fat in the body may help protect against obesity.

Recent research states that more than 1 billion people around the world have obesity, with scientists projecting that number may hit 4 billion by 2050.

Humans and other mammals have two main types of fat in the body — white fat and brown fat. White fat serves as the main site for energy storage in the form of triglycerides, found beneath the skin and around internal organs. In contrast, brown fat specialises in thermogenesis, generating heat through uncoupled respiration. Abundant in newborns and hibernating animals, brown fat helps maintain body temperature during cold exposure and is mainly located in specific regions such as the neck and upper back in adults. Both types of adipose tissue play crucial roles in energy balance and metabolism.

For this study, Wilhelm Kornfeld, co-lead author of the current study, and his team focused on a protein called AC3-AT, which they found was responsible for “switching off” brown fat activation. Using a mouse model to test their theory, they found that mice who had AC3-AT removed from their genome were protected from obesity, as their bodies were better at burning calories and their metabolism sped up due to brown fat activation.

“White fat is an organ that stores calories from foods and whose size expands in obesity and causes medical problems. Brown fat stores only little amounts of fat, but in contrast can convert calories from food into heat which is thereby ‘lost’ for the body. Uniquely, activation of brown fat can lead to turning over calories from food which is beneficial in obesity and cardiometabolic diseases. White fat is much less able to do so. In principle, this shows that inactivation of AC3-AT can lead to weight loss (and) improvement of metabolic health in obesity,” said Kornfeld.

Reference: Khani, S., Topel, H., Kardinal, R. et al. Cold-induced expression of a truncated adenylyl cyclase 3 acts as rheostat to brown fat function. Nat Metab (2024). https://doi.org/10.1038/s42255-024-01033-8