BCAA Levels & Liver Health: New Research Explained

clinical-trial PMID: 36801448

Quick Summary: Scientists found that a drug that targets how your body uses energy might lower levels of branched-chain amino acids (BCAAs) in people with liver problems and diabetes. This could be a step toward new treatments!

What The Research Found

This study looked at how a drug called MSDC-0602K affects BCAA levels. BCAAs are important building blocks for your body, but high levels can be linked to health problems. The research showed that the drug helped lower BCAA levels in people with a liver condition called NASH and type 2 diabetes. It seems the drug works by changing how the body breaks down BCAAs.

Study Details

Who was studied: The main study involved 195 adults with NASH and type 2 diabetes. Some got the drug, and some got a placebo (a "dummy" pill). Researchers also studied cells in the lab and mice.

How long: The main study lasted for 52 weeks (about a year).

What they took: People in the study took 250mg of MSDC-0602K daily.

What This Means For You

This research is exciting because it suggests a new way to help people with liver problems and diabetes. It shows that targeting how your body uses energy might also help manage BCAA levels. However, the drug used in the study is not a BCAA supplement. It's a medicine still being tested.

If you have liver problems or diabetes: This research is a promising step. Talk to your doctor about the latest treatments and research.

If you take BCAA supplements: This study doesn't directly relate to BCAA supplements. It focuses on a drug that affects how your body uses BCAAs.

Study Limitations

The study was relatively short (one year).

The drug's effects on BCAA levels weren't always the same in different groups (humans vs. animals).

More research is needed to fully understand how this drug works and if it's safe for long-term use.

Key Findings

The study demonstrated that inhibiting the mitochondrial pyruvate carrier (MPC) with MSDC-0602K reduced plasma BCAA concentrations in humans with nonalcoholic steatohepatitis (NASH) and type 2 diabetes. This effect was linked to decreased phosphorylation (activation) of the BCAA catabolic enzyme BCKDH via the phosphatase PPM1K, coupled with activation of AMPK and mTOR signaling pathways. However, in Zucker diabetic fatty (ZDF) rats, MSDC-0602K improved glucose homeostasis without lowering plasma BCAA levels, suggesting dissociation between these effects.

Study Design

The study combined a 52-week Phase IIB randomized, placebo-controlled clinical trial (EMMINENCE, NCT02784444) with mechanistic in vitro and in vivo experiments. Clinical trial participants included 195 adults with NASH and type 2 diabetes (placebo: n=94; MSDC-0602K: n=101). In vitro, human hepatoma cell lines and mouse primary hepatocytes were treated with MPC inhibitors (MPCi). In vivo, hepatocyte-specific Mpc2-knockout mice and ZDF rats were analyzed for BCAA metabolism.

Dosage & Administration

In the clinical trial, MSDC-0602K was administered orally at 250 mg daily. In vitro studies used varying concentrations of MPCi (specific doses not detailed in the summary), while animal experiments involved MSDC-0602K treatment without specified dosing regimens.

Results & Efficacy

Human Trial: MSDC-0602K significantly decreased plasma BCAA levels from baseline (no exact p-values or confidence intervals provided in the summary), whereas placebo had no effect.
In Vitro: MPCi reduced BCKDH phosphorylation (activation of BCAA catabolism) in human hepatoma cells, dependent on PPM1K phosphatase.
In Vivo:
Obese LS-Mpc2-/- mice showed reduced BCKDH phosphorylation and mTOR activation compared to wild-type controls.
ZDF rats treated with MSDC-0602K exhibited improved glucose homeostasis but no reduction in plasma BCAAs.

Limitations

The clinical trial lacked detailed statistical reporting (e.g., p-values, confidence intervals).
Discrepancies between human and rodent results (e.g., ZDF rats showed no BCAA reduction) suggest species-specific differences in BCAA metabolism.
In vitro models may not fully recapitulate systemic metabolic interactions.
The study did not assess tissue-specific BCAA flux or dietary intake, which could confound results.
Short duration (52 weeks) and moderate sample size limit long-term conclusions.

Clinical Relevance

This study suggests that MPC inhibition could lower plasma BCAAs in humans with NASH and diabetes, potentially improving metabolic health by enhancing BCAA catabolism. However, the dissociation between BCAA reduction and glucose improvements in ZDF rats indicates that these effects may not always align. For supplement users, the findings highlight the importance of mitochondrial metabolism in BCAA regulation but do not directly support the use of BCAA supplements. Instead, they point to MPCi as a therapeutic strategy for metabolic diseases, though further research is needed to translate these results into supplement or drug development.

Note: MSDC-0602K is a pharmaceutical agent, not a dietary supplement. The study does not address BCAA supplementation but rather the metabolic consequences of targeting mitochondrial pyruvate transport.