• Researchers investigated the effects of the bodybuilding supplement HMB on Alzheimer’s disease markers in mice.
• HMB improved cognitive ability and reduced the buildup of amyloid plaques in mouse models of Alzheimer’s.
• Further studies are needed to see how these findings may apply to humans.

Alzheimer’s disease is the most common neurodegenerative condition worldwide and the most common kind of dementia. As the global population ages, cases of Alzheimer’s are expected to increase. By 2050, around 13 million people are expected to live with Alzheimer’s in the U.S., up from 6 million at present.

Research is ongoing to develop treatments and prevention strategies for Alzheimer’s. There is currently no cure for the condition.

One study found that a bodybuilding protein supplement called β-hydroxy-β-methylbutyric acid (HMB) may protect against age-related cognitive decline in rats. HMB is available as an over-the-counter supplement and is generally considered safe to use.

Understanding more about how HMB affects cognitive decline could aid the development of Alzheimer’s treatment and prevention strategies.

Recently, researchers examined the effects of HMB on mouse models of Alzheimer’s.

The study was published in Cell Reports.

HMB improves brain plasticity

The researchers began by studying the effects of adding HMB to cultured mouse hippocampal neurons. The hippocampus is an area of the brain linked to memory formation and retrieval. It is among the first areas of the brain that are damaged in Alzheimer’s.

Ultimately, the researchers found that HMB significantly increased the density of dendritic spines—small protrusions from neurons that help them communicate with each other. Larger and more dense dendritic spines indicate better functioning neuronal circuits.

They further found that HMB increased levels of various neurotrophic factors that are known to aid neuronal function. These included BDNF—known to stimulate the growth and differentiation of neurons and synapses, and CREB— which regulates gene expression and is important for dopaminergic neurons.

The researchers noted that these changes mean that HMB improves hippocampal plasticity, at least in cultured hippocampal neurons from mice.

Enhanced learning and memory with HMB

The researchers next sought to see how their findings translate to live mice. To do so, they orally administered HMB to mouse models of Alzheimer’s for a month.

Similarly to the cell cultures, HMB increased hippocampal plasticity in the live mice, as evidenced by increased numbers of neurotrophic factors and dendritic spines.

The researchers also investigated how HMB affected memory and learning via a maze test.

In doing so, they found that HMB improved performance among Alzheimer’s mouse models, indicating that the supplement enhances learning and memory.

The researchers next investigated how HMB affects the buildup of amyloid-beta plaques in the hippocampus. They found that oral administration of HMB significantly decreased amyloid-beta levels in the hippocampus and cortex- the brain’s outer surface, which plays a key role in learning, reasoning, and problem-solving.

From further tests, the researchers found that HMB exerts its cognitive effects by interacting with peroxisome proliferator-activated receptor alpha (PPARα), a signal receiver in the brain that helps metabolize fatty acids. Mouse models of Alzheimer’s lacking PPARα did not experience the same cognitive benefits as those with the receptor.

Limitations 

Medical News Today spoke with Dr. Howard Pratt, psychiatrist and board-certified medical director at Community Health of South Florida, Inc. (CHI), who was not involved in the study, about its limitations.

“One limitation is that the mice’s memory was assessed based on their ability to navigate through mazes. Now, HMB is also known to increase muscle strength, so we cannot rule this out as a factor in the mice’s improved performance,” he noted.

He added that as the study involved mice, further research is needed to see whether the findings apply to humans.

Dr. Thomas Gut, associate chair of medicine at Staten Island University Hospital, who was not involved in the study, noted, however, that due to variance in how Alzheimer’s presents in humans, there is “no guarantee that HMB could benefit all Alzheimer’s patients, even if similar findings can be produced in clinical trials.”

Could HMB be used as an oral supplement for Alzheimer’s?

Dr. Gut said HMB had potential as a treatment for Alzheimer’s.

“Based on studies in mice, it’s been found that HMB can help reduce some of the findings that are commonly associated with Alzheimer’s disease and memory loss. HMB has been found to reduce the presence of certain plaque deposits as well as improve potential connections within critical areas of the brain,” he told MNT.

Dr. Swerdlow, meanwhile, noted that one of the key findings from this study is the idea that energy metabolism may control the buildup of proteins, as opposed to the other way around.

“Accordingly, treatments targeting brain energy metabolism may impact the brain in Alzheimer’s more than treatments that directly target the plaques,” he said.

“If an oral supplement of [HMB] is proven to be either preventative or a treatment for dementia, it would help improve outcomes for dementia patients as well as the quality of life for their families.”
— Dr. Howard Pratt

MNT also spoke with Dr. Russell Swerdlow, neurologist and co-director of the University of Kansas Alzheimer’s Disease Research Center, who was also not involved in the study.

“Extrapolating findings from mouse models to humans is always tricky, but there are sometimes important lessons. Perhaps the lesson here is that energy-related metabolism not only plays an important role in brain function but also profoundly affects Alzheimer’s-associated features like amyloid plaques,” he said.

How to reduce dementia risk 

“While we don’t know the cause of dementia, there are things you can do to reduce your risk of it,” said Dr. Pratt.

“[Ways to reduce dementia risk] include stopping smoking, if you do, getting your blood pressure under control, checking yourself for diabetes and getting treatment if you have it, and having a healthy, balanced diet. And when it comes to dementia, the earlier that you treat it, the better.”
— Dr. Howard Pratt

“While we can’t yet stop its progression, medications are available that can mask its effects. So, if you have symptoms or are alerted by close ones that you may show signs of it, don’t delay in seeking a diagnosis and getting treatment,” he concluded.

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