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A Fitness Supplement Against Alzheimer’s Disease?

HMB, which is commonly utilized by bodybuilders, could play a role in memory protection and the deceleration of Alzheimer’s disease.

A recent discovery by researchers at RUSH suggests that memory protection, plaque reduction, and the potential prevention of Alzheimer’s disease progression may be facilitated by a muscle-building supplement known as beta-hydroxy beta-methylbutyrate (HMB).

HMB, available over the counter in sports and fitness stores, is neither a prescription medication nor a steroid. It is often employed by bodybuilders for enhancing gains in muscle size and strength induced by exercise, as well as for improving exercise performance. Even with prolonged usage, HMB is considered safe, and no known side effects have been reported.

The words of Kalipada Pahan, Ph.D., the Floyd A. Davis, MD, Professor of Neurology, and a professor of neurological sciences, biochemistry, and pharmacology at RUSH Medical College, express that this might be one of the safest and most straightforward approaches to arresting the progression of the disease and safeguarding the memory of Alzheimer’s disease patients.

Plaque reduction has been observed

Research involving mice with Alzheimer’s disease has demonstrated the successful reduction of plaques and the enhancement of factors conducive to neuronal growth, aimed at safeguarding learning and memory. This insight was provided by neurological researchers at RUSH.

Dr. Pahan stressed the significance of comprehending the disease’s mechanisms in the context of developing effective medications for brain protection and the cessation of Alzheimer’s disease progression.

Prior research has highlighted the significant decline of a protein family referred to as neurotrophic factors in the brains of individuals afflicted with Alzheimer’s disease. These proteins have been linked to the survival and functionality of neurons, the cells responsible for transmitting messages between the body and the brain.


“Our investigation has found that following oral administration, HMB penetrates the brain to augment these advantageous proteins, reestablish neural connections, and ameliorate memory and learning in mice exhibiting Alzheimer’s-like conditions, including plaques and tangles.” – Dr. Pahan explained,

A “promising avenue of treatment” is revealed by the study’s findings. It is suggested that HMB activates a nuclear hormone receptor known as PPARα in the brain, which is responsible for controlling the transportation of fatty acids, a crucial factor in the effectiveness of HMB as a neuroprotective supplement.

Pahan noted that if the results observed in mice with HMB are reproduced in Alzheimer’s disease patients, it could potentially introduce a promising path for treating this debilitating neurodegenerative condition.


  • 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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