Could New Drug Lower Cholesterol in lean people on a Keto diet?

Summary

This video explores the potential for a new drug, resmon, to treat high cholesterol levels in lean people on ketogenic diets who experience the 'lean mass hyper-responder' phenomenon. The presenter discusses the drug's effects on fatty liver disease and cholesterol levels, and hypothesizes that it could either significantly lower or raise LDL cholesterol in this specific population. By testing this drug in a different metabolic context, the results could provide valuable insights into fat metabolism, the lipid energy model, and offer new treatment options for high LDL cholesterol beyond traditional approaches.

Takeaways

• 📚 A new drug called Resmon, a liver-directed thyroid hormone receptor beta selective agonist, shows promise in treating fatty liver disease (NASH) and reducing LDL cholesterol, according to a phase 3 trial published in the New England Journal of Medicine.
• 📌 Lean mass hyperresponders (LMHRs), individuals on ketogenic diets with high LDL cholesterol, high HDL, and low triglycerides, might benefit from exploring the effects of Resmon, despite not being the original target demographic for this drug.
• 🧭 The lipid energy model and the role of thyroid hormone in energy metabolism provide a theoretical basis for investigating Resmon's potential impact on LMHRs.
• 🔥 Free T3, a thyroid hormone, has been identified as independently predictive of elevated LDL cholesterol in lean individuals on low-carb diets, suggesting a link between thyroid function and lipid metabolism.
• ⚡️ There's an interesting possibility that Resmon could either significantly lower or, alternatively, increase LDL cholesterol in LMHRs, based on its mechanism of action on liver metabolism.
• 📡 The drug's effect on cardiac risk markers and LDL cholesterol reduction in fatty liver patients raises provocative questions about its potential use and effectiveness in LMHRs.
• 🛠 Mechanistic insights into fat metabolism and the lipid energy model could be gained from a hypothetical trial of Resmon in LMHRs, offering a new perspective on managing high LDL cholesterol levels.
• 🏦 LMHRs typically do not have fatty liver or high visceral fat levels, highlighting the need for tailored research into the drug's effectiveness in this unique population.
• 💻 The concept of changing metabolic context affecting drug outcomes underscores the importance of targeted interventions in nutrition and metabolism research.
• 🚩 The potential for Resmon to provide alternative LDL lowering strategies for LMHRs beyond traditional methods like statins or dietary adjustments is a key area of interest.

Q & A

What is the new drug mentioned in the script for treating fatty liver disease?

The new drug mentioned for treating fatty liver disease is called Resmetirom (referred to as 'resmon' in the script), which is a liver-directed thyroid hormone receptor beta selective agonist.

Can Resmetirom be used to treat high cholesterol levels in lean people on ketogenic diets?

The script raises the question of whether Resmetirom, initially used for treating fatty liver disease, could also lower high cholesterol levels in lean people on ketogenic diets, known as the lean mass hyper-responder phenotype. However, it suggests that further research is needed to confirm this potential use.

What is the lean mass hyper-responder phenotype?

The lean mass hyper-responder phenotype refers to lean individuals on low carbohydrate diets who experience high LDL cholesterol levels, alongside high HDL and low triglycerides, potentially influenced by energy metabolism and thyroid hormone levels.

How does free T3 predict LDL cholesterol levels?

Free T3, a thyroid hormone, has been shown to independently predict elevated LDL cholesterol levels in lean individuals on low carbohydrate diets, suggesting a link between thyroid hormone levels and cholesterol metabolism.

What are the potential effects of Resmetirom on lean mass hyper-responders?

The script hypothesizes that Resmetirom could either significantly lower LDL cholesterol in lean mass hyper-responders or, alternatively, increase it due to enhanced liver fat metabolism, indicating the need for specific trials to determine the actual outcome.

What are the results of Resmetirom in its phase 3 trial?

In its phase 3 trial, Resmetirom resolved fatty liver in a significant percentage of patients, reduced LDL cholesterol by 13.6% or more depending on the dose, and positively affected other cardiac risk markers.

Why might lean mass hyper-responders not be the intended use population for Resmetirom?

Lean mass hyper-responders typically do not have fatty liver disease; they tend to have very low levels of liver fat and visceral fat, differing from the phenotypic profile for which Resmetirom is initially intended.

What could a trial of Resmetirom in lean mass hyper-responders reveal about fat metabolism?

A trial of Resmetirom in lean mass hyper-responders could provide mechanistic insights into fat metabolism and the lipid energy model, potentially offering new options for LDL cholesterol management beyond traditional methods.

What is the significance of thyroid hormone receptor beta in the context of the script?

Thyroid hormone receptor beta, expressed in the liver, plays a crucial role in energy metabolism and intersects with pathways involved in ketosis, suggesting its involvement in the effects observed with Resmetirom treatment.

What are the broader implications of the script's discussion on nutrition, metabolism, and medicine?

The script emphasizes the importance of exploring new therapeutic uses for existing drugs in different metabolic contexts, potentially leading to innovative treatments and a deeper understanding of nutrition, metabolism, and medicine.