This shows an older lady.
HMB is not a prescription drug or a steroid, but an over-the-counter supplement that is available in sports and fitness stores. Credit: Neuroscience News

Is A Fitness Supplement A Potential Ally Against Alzheimer’s?

Summary: Researchers have found that the muscle-building supplement HMB (beta-hydroxy beta-methylbutyrate), commonly used by bodybuilders, could help protect memory and slow the progression of Alzheimer’s disease.

Mouse studies showed HMB reduced Alzheimer’s plaques and enhanced factors for neuronal growth, safeguarding learning and memory. HMB enters the brain after oral consumption, increasing beneficial proteins and restoring neuronal connections.

If these findings replicate in humans, HMB could offer a promising new treatment for Alzheimer’s.

Key Facts:

  1. HMB, an over-the-counter supplement used by bodybuilders, may protect memory and slow Alzheimer’s progression.
  2. In mice with Alzheimer’s disease, HMB has been shown to reduce plaques, enhance factors for neuronal growth, and protect learning and memory.
  3. HMB stimulates a nuclear hormone receptor in the brain that is crucial to its neuroprotective role.

Source: Rush University

RUSH researchers recently discovered that a muscle-building supplement called beta-hydroxy beta-methylbutyrate, also called HMB, may help protect memory, reduce plaques and ultimately help prevent the progression of Alzheimer’s disease.

Results from the study were published in Cell Reports.

HMB is not a prescription drug or a steroid, but an over-the-counter supplement that is available in sports and fitness stores. Bodybuilders regularly use HMB to increase exercise-induced gains in muscle size and strength while improving exercise performance. HMB is considered safe even after long-term use, with no known side effects.

“This may be one of the safest and the easiest approaches to halt disease progression and protect memory in Alzheimer’s disease patients,” said Kalipada Pahan, Ph.D., the Floyd A. Davis, MD, Professor of Neurology and professor of neurological sciences, biochemistry and pharmacology at RUSH Medical College.

Reduces plaques

Studies in mice with Alzheimer’s disease have shown that HMB successfully reduces plaques and increases factors for neuronal growth to protect learning and memory, according to neurological researchers at RUSH.

“Understanding how the disease works is important to developing effective drugs to protect the brain and stop the progression of Alzheimer’s disease,” Pahan said.

Previous studies indicate that a family of proteins known as neurotrophic factors are drastically decreased in the brains of people with Alzheimer’s disease and have been found to help in survival and function of neurons, which are cells that receive and send messages from the body to the brain and vice versa.

“Our study found that after oral consumption, HMB enters into the brain to increase these beneficial proteins, restore neuronal connections and improve memory and learning in mice with Alzheimer’s-like pathology, such as plaques and tangles,” Pahan said.

‘Promising avenue of treatment’

The study findings indicate that HMB stimulates a nuclear hormone receptor called PPARα within the brain that regulates the transport of fatty acids, which is key to the success of HMB as a neuroprotective supplement.

“If mouse results with HMB are replicated in Alzheimer’s disease patients, it would open up a promising avenue of treatment of this devastating neurodegenerative disease,” Pahan said.

About this Alzheimer’s disease research news

Author: Kalipada Pahan
Source: Rush University
Contact: Kalipada Pahan – Rush University
Image: The image is credited to Neuroscience News

Original Research: Open access.
Muscle-building supplement β-hydroxy β-methylbutyrate binds to PPARα to improve hippocampal functions in mice” by Kalipada Pahan et al. Cell Reports


Muscle-building supplement β-hydroxy β-methylbutyrate binds to PPARα to improve hippocampal functions in mice


  • Muscle-building supplement HMB binds to PPARα
  • HMB increases morphological plasticity of hippocampal neurons via PPARα
  • Oral HMB improves hippocampal functions in 5XFAD mice using PPARα
  • Oral HMB lowers plaques in 5XFAD mice through PPARα


This study underlines the importance of β-hydroxy β-methylbutyrate (HMB), a muscle-building supplement in human, in increasing mouse hippocampal plasticity.

Detailed proteomic analyses reveal that HMB serves as a ligand of peroxisome proliferator-activated receptor α (PPARα), a nuclear hormone receptor involved in fat metabolism, via interaction with the Y314 residue.

Accordingly, HMB is ineffective in increasing plasticity of PPARα−/− hippocampal neurons. While lentiviral establishment of full-length PPARα restores the plasticity-promoting effect of HMB in PPARα−/− hippocampal neurons, lentiviral transduction of Y314D-PPARα remains unable to do that, highlighting the importance of HMB’s interaction with the Y314 residue.

Additionally, oral HMB improves spatial learning and memory and reduces plaque load in 5X familial Alzheimer’s disease (5XFAD) mice, but not in 5XFADΔPPARα mice (5XFAD lacking PPARα), indicating the involvement of PPARα in HMB-mediated neuroprotection in 5XFAD mice.

These results delineate neuroprotective functions of HMB and suggest that this widely used supplement may be repurposed for AD.

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