What Causes All Chronic Diseases

What if I told you there was one single cause for almost every chronic disease you could think of and even for aging? Buckle up because this blog will introduce the Cell Danger Response (CDR) theory, which explains just about everything including:

• how people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID get stuck in a low energy state;
• how people with environmental sensitivities (MCS) and mast cell activation syndrome (MCAS) become highly sensitive to low levels of toxins;
• why people get chronic pain and fibromyalgia;
• what causes neurodevelopmental conditions like autism and neurodegenerative diseases like Alzheimer’s disease;
• what causes emotional and behavioral disorders like anxiety, depression, and post-traumatic stress disorder (PTSD);
• how the body balances inflammatory and anti-inflammatory signals;
• why biological and psychological safety signals are important to healing; and
• what the biological basis of health span and longevity is.

Perhaps, most importantly, the CDR theory suggests that careful self-management is an important tool to heal from chronic disease.

Why We Need a New Paradigm for Health Care

• Our current disease-based health-care model hasn’t been successful in decreasing the incidence, prevalence, or severity of chronic disease. Rates and complexity of chronic disease increase every year and now account for 80% of health-care spending in developed countries.
• Most treatments for chronic disease—such as insulin for diabetes or statins for high cholesterol—must be taken for a lifetime because they don’t address the root cause of the symptoms. They are costly and have significant side effects.
• We don’t have any cures for any chronic disease. We are in desperate need of effective treatments.

Chronic Disease Is Not Linear—It’s Complicated

One reason for the lack of success is that our acute care medical model is linear and simplistic. It assumes that single external causes lead to single health conditions and that if we can address the single cause, the health condition will get better. This is wrong on several fronts.

Chronic diseases are not linear; they are pluricausal, meaning that the same disease can have different causes in different people.

The triggers of chronic disease are pleiotropic meaning the same trigger can cause different diseases in different people. Which disease an individual develops is due to individual variables.

How Can Different Chronic Diseases Have a Single Cause?

In his 2023 paper Mitochondrial and Metabolic Features of Salugenesis and the Healing Cycle, Professor Robert Naviaux argued that all chronic diseases (biological, psychological, environmental, and more) are the result of incomplete healing at the cellular level. We tend to focus on the apparent triggers such as stress, infection, childbirth, trauma, sleep deprivation, and so on. These are the triggers but not the cause of chronic disease.

The cause is how the body responds to these triggers. First, it mounts a 3-phase CDR to address the threat and save the life of the cell and the host (us). In normal circumstances, cells pass through these three phases and return to full health. But in some cases, cells get stuck and don’t recover. If enough cells get stuck, chronic disease is the result. The type of disease depends upon which organs are affected (e.g., the brain, the muscles, the liver) and at which phase in the healing cycle the process is blocked.

Phase 1: Inflammation – The immune system ramps up to kill invaders and get rid of inflammatory debris. Blocks at this phase lead to chronic inflammatory disorders such as Gulf War Illness, chronic inflammatory response syndrome (CIRS), mast cell activation syndrome (MCAS), and chronic infection.

Phase 2: Proliferation – The goal of Phase 2 is to grow new cells to replace those that were damaged in the inflammatory response. Blocks at this phase lead to chronic proliferative disorders, such as heart disease, diabetes, autoimmune disorders, and cancer.

Phase 3: Differentiation – Now that cells have been replaced, they must be trained to fill their specialized tissue-specific roles. And, ideally, recovery sets the stage for the ability of cells and organisms to become more resilient when faced with small doses of stressors like fasting, heat, or exercise. Blocks at this phase lead to neurodevelopmental disorders such as autism, neurodegenerative disorders such as Parkinson’s disease, and psychiatric disorders such as depression and post-traumatic stress disorder (PTSD).

An additional orphan category called hypometabolic (low energy) survival state includes diseases such as myalgic encephalomyelitis/chronic fatigue syndrome ME/CFS, long COVID, and post-treatment chronic Lyme disease.

The ultimate cause of all chronic disease
is the failure of the healing cycle to progress to full health

From Naviaux, R. K. Mitochondrion, 70, 131-163.

You can see the possible outcomes of the CDR in the diagrams above.

• In normal healing, there is a spike of eATP, and then the cells pass through the phases of healing and return to full health.
• In chronic disease, the cells are unable to resolve the problem, and eATP remains elevated, which leads to chronic inflammation and immune activation.
• In other cases, the cells are in the process of healing but encounter further injury which blocks recovery.
• In the future, we hope to apply therapies such as purinergic blockers, which aid in healing.

Mitochondria in different phases of the healing cycle.

From Naviaux, R. K. Mitochondrion, 70, 131–163.

Mitochondria Are in Charge of . . . Everything

What determines whether a cell enters the CDR and whether it heals or not?

We normally think of mitochondria as the unintelligent powerplants of the cell, the tiny organelles working away to produce ATP, cellular energy. Recent research has suggested that mitochondria are much more than tiny powerplants. They are the sentinels and central processing units in animal cells. They are the early warning system that determines the nature and location of problems and when to sound the alarm.

• When threatened, mitochondria leak ATP into the rest of the cell and beyond. This extracellular ATP (eATP) sends danger signals to surrounding cells and starts a domino-like response.
• If enough mitochondria in a given cell begin leaking ATP and shut down energy production, the cell goes offline into a hibernation-like state, and the tissue or organ doesn’t function as well.
• Believe it or not, cells have long-term metabolic memory. Even when danger has passed, this memory can last for weeks to years and can block the healing cycle. Metabolic memory leads to decreased ATP synthesis and persistent innate immune activation, typical in ME/CFS and long COVID.

Cellular and Psychological Safety Are Critical for Healing

Safety at the cellular level is determined by whether the cell has enough food, is able to excrete waste, and has the ability to create energy to function. At the level of the body and mind, we need to feel safe. If we are caught in fight, flight, or freeze, we’re wasting valuable energy putting out real or imaginary fires and don’t have the needed resources to reboot the mitochondria and encourage healing. Our cells will feel safer if we provide what they need to function: food, rest, and metabolic challenges—all possible through self-management.

Potentially harmful stress responses are the body’s default. We must inhibit these ancient stress responses by creating safety signals with our higher brain centers like the prefrontal cortex. A person whose cells are recovering should use practices which signal safety to the body, such as meditation, positive emotions, and social connection. That person must also practice excellent self-care and self-management to ensure that the cells get what they need. This care includes restorative sleep, paced activity, healthy diet, minimal toxic exposures, and connection to nature and trusted people. Sound familiar? Self-management is powerful and works at a biological level to enhance healing.

How to Induce, Consolidate, and Maintain Healing

Because extracellular ATP is driving most of the problem processes, it’s possible that blocking ATP signaling may reverse the changes and allow cells to heal. Once cells are healed and the mitochondria have returned to full function, the initial trigger is no longer relevant—it’s in the past.

Professor Naviaux has tested the antipurinergic drug suramin in a small group of children with autism and reported lasting positive results with few side effects. He is enthusiastic about a new class of drugs called PAN X1 channel inhibitors as the potential intervention to decrease the release of ATP and induce healing.

Unlike many current treatments for chronic diseases, antipurinergic drugs are needed only in the short term to induce healing. Once the mitochondria are reprogrammed to full health, ongoing treatment is not needed.

Conclusion

Naviaux’s model is holistic. It assumes the constant biological interaction between the mind, body, our microbiome, and the environment. He emphasizes that cells respond similarly to psychological, social, and biological stresses. Cells can’t tell the difference. The mind–body split is purely a figment of our imaginations. Therefore, a combination of biological and psychosocial self-care is the most effective approach to healing.

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References

Naviaux, R. K. (2014). Metabolic features of the cell danger response. Mitochondrion, 16, 7–17.

Naviaux, R. K. (2019). Incomplete Healing as a Cause of Aging: The Role of Mitochondria and the Cell Danger Response. Biology, 8(2), 11.

Naviaux, R. K., Curtis, B., Li, K., Naviaux, J. C., Bright, A. T., Reiner, G. E., et al. (2017). Low-dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial. Annals of Clinical & Translational Neurology, 4(7), 491–505.

Naviaux, R. K., Naviaux, J. C., Li, K., Bright, A. T., Alaynick, W. A., Wang, L., et al. (2016). Metabolic features of chronic fatigue syndrome. Proceedings of the National Academy of Sciences of the United States of America, 113(37), E5472–5480.

Naviaux, R. K. (2023). Mitochondrial and metabolic features of salugenesis and the healing cycle. Mitochondrion, 70, 131–163.