The Root Cause of Brain Disease: The Metabolic Iceberg

What if the root cause of brain diseases like Alzheimer’s and Parkinson’s is hidden beneath the surface? Like an iceberg, the symptoms we see are only the tip. The real damage happens where we can't see it—deep inside our cells.

Treating the visible symptoms can improve quality of life, but addressing the base and bulk could slow or even prevent disease progression.

Neurodegenerative diseases, like Alzheimer’s (AD), Parkinson’s (PD), Amyotrophic Lateral Sclerosis (ALS), and Huntington’s (HD), are devastating. 

While their symptoms—memory loss, tremors, or muscle weakness—are visible, the root causes remain hidden beneath the surface.

To understand these diseases, we can use the "metabolic iceberg" model, put forward in this study published in Translational Neurodegeneration by researchers Phillips and Picard. 

This framework breaks down the causes into three levels: the tip, the bulk, and the base. 

Each level tells a part of the story, from visible symptoms to the hidden factors driving them.

Tip: The Visible Symptoms of Disease

The tip of the iceberg represents what we can see and measure in patients: the symptoms and biological markers that define these diseases. For example:

• Clinical symptoms: Memory loss in AD, tremors in PD, and muscle weakness in ALS.
• Anatomical changes: Brain areas, like the hippocampus in AD or the substantia nigra in PD, show degeneration. These can be identified using imaging technologies.
• Cellular changes: Clumps of proteins, called aggregates, form inside neurons. These are hallmarks of neurodegenerative diseases.

These visible effects are what doctors diagnose and treat. However, they are the result of deeper, hidden processes happening over years or decades.

Bulk: The Hidden Mitochondrial Damage

Below the surface lies the bulk of the iceberg: impaired mitochondrial biology. 

Mitochondria are the "power plants" of our cells, producing the energy needed to function. 

When they malfunction, cells—especially neurons—suffer. This impairment has many layers:

1. Impaired cellular metabolism: Neurons need a lot of energy. When mitochondria fail, they can't meet the demand, leading to cell stress and death.
2. Cell-specific mitotypes: Mitochondria differ between cell types. In neurons, changes in the number, location, or behavior of mitochondria disrupt cell function.
3. Mitochondrial behaviors: Processes like fusion (joining) and fission (splitting) are crucial for healthy mitochondria. When disrupted, these processes lead to energy failure.
4. Mitochondrial functions: Mitochondria generate ATP (energy), manage calcium, and reduce oxidative stress. Dysfunction in these areas damages cells.
5. Molecular features: Physical damage to mitochondrial DNA, shape, or structure hampers their ability to work.

These mitochondrial problems build over time and remain unnoticed until they cause significant damage. This is the "silent" progression of neurodegeneration.

Base: The Root Causes of Mitochondrial Dysfunction

At the foundation of the iceberg are the factors that trigger mitochondrial damage. These include:

1. Environmental toxins: Chemicals from industrial pollution, pesticides, and heavy metals accumulate in mitochondria, causing oxidative stress.
2. Modern diet: High-sugar, processed foods and constant snacking overload the body with energy. This creates chronic stress on mitochondria.
3. Lifestyle factors: Lack of physical activity, poor sleep, and social isolation weaken the body's natural defenses, putting extra strain on mitochondria.
4. Genetic mutations: In familial cases of AD, PD, ALS, and all cases of HD, specific gene mutations directly damage mitochondria or disrupt their function.

These factors interact and build over time, slowly degrading mitochondrial health and setting the stage for disease.

The Iceberg Pathogenesis: How Diseases Develop

The metabolic iceberg shows how neurodegenerative diseases progress:

1. It begins at the base: Environmental toxins, poor diet, and genetic factors damage mitochondria or force them to adapt in harmful ways.
2. It moves through the bulk: Over years or decades, mitochondrial damage spreads, impairing energy production, increasing oxidative stress, and disrupting cellular processes. Neurons, being highly energy-dependent, are hit the hardest.
3. It surfaces at the tip: Finally, visible symptoms appear. Protein aggregates form, brain regions degenerate, and clinical symptoms emerge.

This progression explains why these diseases are often diagnosed late, when much damage has already occurred.

Rethinking Prevention and Treatment

Understanding the metabolic iceberg shifts our focus from symptoms (the tip) to the root causes (the base). 

Treating the visible symptoms can improve quality of life, but addressing the base and bulk could slow or even prevent disease progression.

• Prevention: Reducing exposure to toxins, adopting a healthier diet, and maintaining an active lifestyle can protect mitochondrial health.
• Early intervention: Identifying mitochondrial dysfunction before symptoms appear could lead to earlier, more effective treatments.
• Research focus: By studying the environmental and genetic factors at the base, we can develop strategies to counteract or prevent mitochondrial damage.

Mushrooms, Metabolism and Mitochondria

Considering this metabolic iceberg framework, medicinal mushrooms offer a powerful tool to support metabolic health, improve mitochondria, and help prevent brain diseases.

Mushrooms like Reishi, Cordyceps, and Lion’s Mane contain natural compounds that protect cells from damage, support energy production, and keep mitochondria working properly.

They also help the body manage stress, reduce inflammation, and remove harmful toxins.

These actions address key causes of brain diseases like Alzheimer’s and Parkinson’s, rather than focusing on treating symptoms.

For brain health, mushrooms offer unique benefits. Lion’s Mane helps repair and grow nerve cells, while Reishi and Cordyceps may reduce harmful protein buildup linked to memory loss and tremors.

These mushrooms also lower inflammation in the brain and improve how the brain uses energy. 

View our full range of mushroom extracts here. 

Conclusion

For a long time, the scientific community has struggled to understand what causes neurodegenerative diseases are complex.

However, the metabolic iceberg model put forward by researchers Phillips and Picard provides a clear framework for understanding their origins. 

By focusing on the root causes at the base and the hidden damage in the bulk, it's possible to work on prevention and more effective treatment options.

While much remains to be learned, this approach offers hope for tackling these devastating diseases at their source.

Source: Neurodegenerative disorders, metabolic icebergs, and mitohormesis - 06/10/2024

Further reading: 

• Metabolic Health Is The Foundation Of Brain Health
• What Mushrooms Are Best For Brain Health?
• How To Prevent Alzheimer’s Disease
• The UK’s First Metabolic Health Centre