Metabolic Dysfunction And Chronic Disease

Modern Western medicine has gotten very good at treatments that are reactive. Dealing with broken bones, the flu and other viruses and even asthma and heart attacks is the basis of that practice. But what do we really know about chronic illnesses like heart disease, cancer and diabetes?

According to Centers for Disease Control (CDC) data, more than 50 percent of adults and at least one-third of all teens and children suffer from at least one chronic illness. The National Institute of Health (NIH) says that chronic medical conditions are responsible for more than half of all deaths worldwide.

It’s not an understatement to say that chronic illness is a monumental challenge for modern medicine.


The practice of medicine in most of the industrialized world has become reactive in nature. A bone breaks and doctors set it. A patient gets the flu and a doctor prescribes medicine as a remedy.

That approach, however, has clearly failed as it relates to chronic illnesses. Very often, the “cure” is as bad or worse than the disease. Radiation treatments, chemotherapy and other treatments for chronic disease often put the patient through nearly as much agony as the disease itself.

This is no indictment of modern Western medicine. But what if we could apply all the resources of this massive complex to understanding what causes chronic illness in the first place?


Our progress in diagnosing and treating chronic illness has been challenged, and is lagging behind that of other medical issues. This is partly because the cause of these illnesses is often unknown or even no longer present. The causes of heart disease, cancer and diabetes, for example, are often difficult to assess. Identifying the right treatment, then, is that much harder.

According to recent research, one of the likely culprits in chronic illnesses is metabolic dysfunction. This concept is based on the idea chronic disease may be related to the blocking of the natural healing cycle, specifically blockage caused by disruptions at the metabolic and cellular levels.

Dr. Robert K. Naviaux, MD, PhD, who is professor of medicine, pediatrics and pathology at the University of San Diego School of Medicine believes chronic illness is related to metabolic dysfunction. He published findings related to this claim in a paper in the online journal Mitochondrion.


“The healing process is a dynamic circle that starts with injury and ends with recovery. The molecular features of this process are universal,” said Naviaux, who also directs the Mitochondrial and Metabolic Disease Center at UC San Diego. “Emerging evidence shows that most chronic illnesses are caused by the biological reaction to an injury, not the initial injury or the agent of the injury. The illness occurs because the body is unable to complete the healing process.”

Interestingly, Naviaux says that the chronic illness that comes from the injury doesn’t always manifest itself immediately. He points to secondary impact syndrome, where a second concussion occurs before the first has healed. This can result in more severe symptoms and prolonged recovery time, even if the second impact was less severe than the initial one.

Cancers can be separated from their causes by years. Melanoma, or skin cancer, has been known to occur years or decades after the sun exposure which caused the DNA damage which never healed. Post-traumatic stress disorder (PTSD) can occur months or even years after the original head injury has healed.


“Progressive dysfunction with recurrent injury after incomplete healing occurs in all organ systems, not just the brain,” said Naviaux. “Chronic disease results when cells are caught in a repeating loop of incomplete recovery and re-injury, unable to fully heal. This biology is at the root of virtually every chronic illness known, including susceptibility to recurrent infections, autoimmune diseases like rheumatoid arthritis, diabetic heart and kidney disease, asthma, chronic obstructive pulmonary disease, Alzheimer’s dementia, cancer and autism spectrum disorder.”

Naviaux and his team have spent more than 10 years researching and coming up with a theory. It’s based on the process called cell danger response (CDR.) CDR is a natural, universal cellular reaction to stress or injury. In the paper published in Mitochondrion, Naviaux breaks down the metabolic features of the three stages of CDR that make up the healing cycle,

“The purpose of CDR is to help protect the cell and jump-start the healing process,” said Naviaux, by essentially causing the cell to harden its membranes, cease interaction with neighbors and withdraw within itself until the danger has passed.


“But sometimes CDR gets stuck. At the molecular level, cellular equilibrium is altered, preventing completion of the healing cycle and permanently changing the way the cell responds to the world. When this happens, cells behave as if they are still injured or in imminent danger, even though the original cause of the injury or threat has passed.”

In 2017, Naviaux performed a small, randomized clinical trial involving 10 autistic boys. He treated them with a single dose of a drug which inhibits adenosine triphosphate, or ATP. These small molecules are produced by cellular mitochondria to serve as a warning for impending danger.

When the drug silenced the ATP signals, the boys in the trial who received the drug showed dramatic improvement in communication and social behaviors. Repetitive motions stopped, and the boys spoke and made eye contact. These behaviors returned as the drug exited their systems, however, showing that the effects were transient in nature. Naviaux intends to perform a longer, larger trial to further explore this.


In this paper, Naviaux says there is growing evidence for his belief that chronic disease is driven by metabolic dysfunction. He says the cycle of healing is dependent on the performance of mitochondria and metabokines.

Mitochondria are better known for their function of producing energy for cells. Metabokines are less well-known. They are molecules that signal and regulate cell receptors, preparing them for a variety of actions. These receptors include more than 100 which are associated with healing.

“It’s abnormalities in metabokine signaling that cause the normal stages of the cell danger response to persist abnormally, creating blocks in the healing cycle,” said Navaiux, who noted CDR theory also explains why some people heal more quickly than others and why chronic diseases seemingly treated successfully can relapse. It’s a form of metabolic “addiction” in which the recovering cell becomes conditioned to its impaired state.


Based on what he’s learned, Naviaux thinks it may be time to write a new book of medicine. This one would focus on prevention of chronic diseases. It would also include novel treatments for chronic illnesses that may allow some people to recover completely. The approaches to treating chronic illness which have been tried so far have only led to minor improvements, with most patients dealing with their symptoms for a lifetime.

“The idea would be to direct treatments at the underlying processes that block the healing cycle,” he said. “New treatments might only be given for a short period of time to promote healing, not unlike applying a cast to promote the healing of a broken leg. When the cast is removed, the limb is weak, but over time, muscles recover and bone that was once broken may actually be stronger.”

“Once the triggers of a chronic injury have been identified and removed, and on-going symptoms treated, we need to think about fixing the underlying issue of impaired healing. By shifting the focus away from the initial causes to the metabolic factors and signaling pathways that maintain chronic illness, we can find new ways to not only end chronic illness but prevent it.”

Imagine a medical field that focused on prevention of chronic illnesses and conditions. Proactive instead of reactive. After thousands of years of medical practice and research, we might finally be getting somewhere!

Keep the faith and keep after it!

Related Content –
The Devastating Illness Going Undiagnosed in Children
Is Obesity Killing You Faster?
The Next Global Health Crisis?

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