Preoperative HMB supplement improves liver regeneration quality after major surgery

In the experiment conducted at the Faculty of Applied Sciences (FCA) at UNICAMP in Limeira, the animals received a daily dose of HMB equivalent to the dose used in humans (approximately three grams for a 70-kilogram adult) for ten days. At the time of surgery, the supplementation was discontinued and approximately 70% of the animals' livers were removed – a classic model for studying liver regeneration. The researchers observed that the liver tissue of the animals that regularly received the supplement was metabolically better prepared during recovery.

The benefit of supplementation became more evident when the scientists tested the organ under a new stress scenario. Seven days after surgery, the mice were exposed to a second injury induced by a high dose of acetaminophen, a widely used model for simulating liver toxicity. At this stage, the animals that had previously received HMB supplementation showed a better response. They exhibited fewer signs of damage, maintained mitochondrial function, and showed more appropriate signs of cellular regeneration.

Igor Luchini Baptista, biologist, associate professor at the FCA and advisor to the studyWe didn't see faster regeneration, but higher-quality regeneration. That liver seems better prepared to handle a new challenge."

What is HMB?

HMB is a metabolite derived from leucine, an essential amino acid that is obtained through diet. Only about 5% of ingested leucine is converted into HMB in the body, primarily in the liver. For this reason, HMB supplementation has been used to increase its levels, particularly in contexts related to preserving muscle mass, such as aging, prolonged immobilization, or recovering from illness. Nevertheless, its effects are considered modest, and there are few robust clinical studies in humans.

"It's a supplement that's already widely used outside the gym, but the described effects, especially on muscle, are still subtle. We still lack good clinical studies to support its broader use," says Baptista.

The fact that HMB is produced in the liver motivated the research. "We started with a simple question: If it's produced in the liver, why has almost no one investigated its direct effect on that organ?" says the researcher. Based on this research gap, the group decided to explore the role of the compound in liver regeneration, a process involving a complex cascade of cellular and metabolic events.

In the first phase of the study, the results were modest. Although some molecular markers indicated a more favorable profile in the supplemented animals, there was no significant difference in regeneration time. As expected, all the mice recovered their liver mass in about seven days. "The liver has an impressive regenerative capacity. It'll recover anyway. Our question was about the quality of that process. The most curious thing is that the entire effect we observed was due to the treatment administered before surgery," Baptista explains.

This question led to the design of the second stage of the experiment, in which the scientists tested the "quality" of the recovery. By subjecting the regenerated liver to a new injury, they were able to more clearly observe differences between the groups. The animals that did not receive HMB showed more tissue damage, cellular distress, and structural changes, as well as poorer metabolic performance. In contrast, the animals that received the supplement showed a better-preserved, more functional organ.

According to Baptista, this effect is primarily related to the preservation of mitochondria, the cellular structures responsible for energy production. In stressful situations, such as major surgery or poisoning, maintaining mitochondrial function is essential for cellular survival and proper tissue regeneration. "Our initial focus was precisely to look at mitochondrial parameters, and that appeared consistently. The tissue that received HMB seems to be more metabolically prepared, which makes a difference when it's challenged again," says the researcher.

Another notable finding was that all the beneficial effects occurred even after supplementation was discontinued. "That was the most curious part. The animal received HMB before surgery, and all the benefits appeared afterward, even though it was no longer receiving the supplement," says Baptista. About 18 days passed in total between the end of supplementation and the second injury. According to the researcher, this timeframe reinforces the idea of a lasting effect on tissue conditioning.

Despite the promising results, Baptista emphasizes that the study was conducted in an animal model and that it is not yet possible to extrapolate the findings directly to humans. He says the main contribution lies in paving the way for further research. "In theory, it's an interesting concept because we're talking about a supplement that's already in use, accessible, and relatively safe. But turning that into a clinical recommendation requires a series of human studies. That's the next step, and it'll likely be carried out by other research groups," he states.

The research also fits into a broader field seeking to understand how nutrients and metabolites influence the body's response to stressful situations, such as surgeries, trauma, or illness. In this context, strategies of "metabolic preparation" prior to medical procedures are garnering increasing interest. "The idea is simple: Can we better prepare the body before a major challenge? This study suggests that we can, at least at the experimental level. But we still have much to learn about how that can be applied in practice," the researcher concludes.

Source:

São Paulo Research Foundation (FAPESP)

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