From Environmental Toxicants to the Cell Danger Response of Chronic Diseases to the Healing Cycle | Prof Robert Naviaux

◊ Effects of Environmental Toxicants on Immune Function in Autism

Presented by Robert Naviaux, PhD at the Fall 2012 Autism Research Institute Conference

Published: 12/05/2012

◊ Ecosystem AIDS, AAIDS, and Autism

Presented by Robert Naviaux, PhD at the Fall 2012 Autism Research Institute Conference

Published: 12/07/2012

The pace of change in the human ecosystem has accelerated rapidly in the past 30 years. These changes not only affect human health, but the health of plants and animals that share the environment with us. Nine keystone vertebrate, invertebrate and plant species have experienced extinctions or population crashes since the 1980s, and opportunistic human infections are on the rise. These crashes and infections can be traced to changes in metabolism that underlie epigenetics, innate, and adaptive immunity. Epigenetic and immunologic ripple effects have led to new Acquired Immunodeficiency Syndromes (AIDS) in plants and animals, and Acquired Autoimmune Disorders (AAIDS) in humans and domesticated animals. Autism is one of nearly a dozen new, neuroimmune and metabolic spectrum disorders (NIMS) that have emerged as a consequence of these new combinations of environmental factors that have never before been encountered by the human genome. This talk will showcase examples of AIDS, AAIDS, and NIMS that teach us about the unintended, and often-invisible environmental changes caused by human technological progress, and how these changes can be measured and managed systematically.

Dr. Naviaux is Professor of Genetics in the Departments of Medicine, Pediatrics, and Pathology at the University of California, San Diego (UCSD). He is the founder and co-director of the Mitochondrial and Metabolic Disease Center (MM.D.C) at UCSD. He is the cofounder, and former President of the Mitochondrial Medicine Society (MMS). Dr. Naviaux is the discoverer of the genetic basis of the oldest Mendelian form of mitochondrial disease, Alpers Syndrome; his research spans 30 years and embraces the fields of genetics, virology, cancer immunology, mitochondrial medicine, neuroscience, development, metabolism, marine metagenomics, and evolutionary systems dynamics.

◊ Mitochondria and Autism (Spring 2011)

Jan 27, 2013

◊ The metabolism of the cell danger response, healing, and ME/CFS

Sep 28, 2017

Dr. Naviaux is Professor of Medicine, Pediatrics, and Pathology at the University of California, San Diego (UCSD). He is the founder and co-director of the Mitochondrial and Metabolic Disease Center, former President of the Mitochondrial Medicine Society (MMS), and a founding associate editor of the journal Mitochondrion. He is an internationally known expert in human genetics, inborn errors of metabolism, metabolomics, and mitochondrial medicine. Dr. Naviaux discovered the genetic basis of Alpers syndrome, the oldest Mendelian form of mitochondrial disease, and developed the first DNA test to diagnose it. He studied biochemistry at Georg-August University in Göttingen, Germany, and received his MD and PhD in Genetics and Virology from the Indiana University School of Medicine. He is currently the director of the first FDA-approved clinical trial to study the safety and test the effects of suramin on behavior and language in children with autism. Dr. Naviaux is a member of the OMF Scientific Advisory Board.

◊ The Metabolic Features of Myalgic Encephalitis/Chronic Fatigue Syndrome (ME/CFS)

May 25, 2017

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◊ Metabolic features of chronic fatigue syndrome

Dr. Robert Naviaux at the NIH ME Conference in April 2019

Sep 3, 2019

◊ Antipurinergic therapy to address core disabilities of ASD

Dec 2, 2019

◊ April 2020 Functional Forum : From Micro to Macro

Apr 6, 2020

The Evolution of Medicine is thrilled to announce its 76th Functional Forum. From micro to macro, we will be looking across the healing spectrum to better understand the etiology of chronic disease patterns.

Kicking us off is Dr. Mark Hyman, one of the foremost leaders in functional medicine. The last time we featured Dr. Hyman on the Forum, it was 2018 and we took a tour of the Cleveland Clinic Center for Functional Medicine, a project he has spearheaded. In this episode, we will dive deeper into his new book “Food Fix”. His book examines what it will take to fix our food system, which has a direct and significant impact on our health at the macro level. If we don’t fix the food system, we can’t have a sustainable future and we can’t practice effective functional medicine.

Then we’re going to journey inside the mind of Dr. Bob Naviaux, who is a leading researcher in the field of mitochondrial and metabolic diseases. This content is taken from an amazing lecture he gave at a George Washington University event held last year in Dallas, TX. He shows us how this new understanding of the cell danger response can give us answers to some of the questions asked about chronic inflammatory conditions and autism.

Last but not least, Dr. Andrew Heyman, will talk about how to bring the cell danger response into clinical practice. This brings us to the micro level of understanding health, and how the health of our cells can have just as much significance as our food sources. Dr. Heyman will also share practical tools for empowering your patients to be part of the solution for our food system.

Evolution of Medicine is here for the full transformation of medicine and to provide information that’s important to clinicians, from the macro to the micro level.

◊ References

Naviaux, R. K. (2012). Oxidative Shielding or Oxidative Stress? Journal of Pharmacology and Experimental Therapeutics, 342(3), 608. doi:10.1124/jpet.112.192120


In this review I report evidence that the mainstream field of oxidative damage biology has been running fast in the wrong direction for more than 50 years. Reactive oxygen species (ROS) and chronic oxidative changes in membrane lipids and proteins found in many chronic diseases are not the result of accidental damage. Instead, these changes are the result of a highly evolved, stereotyped, and protein-catalyzed “oxidative shielding” response that all eukaryotes adopt when placed in a chemically or microbially hostile environment. The machinery of oxidative shielding evolved from pathways of innate immunity designed to protect the cell from attack and limit the spread of infection. Both oxidative and reductive stress trigger oxidative shielding. In the cases in which it has been studied explicitly, functional and metabolic defects occur in the cell before the increase in ROS and oxidative changes. ROS are the response to disease, not the cause. Therefore, it is not the oxidative changes that should be targeted for therapy, but rather the metabolic conditions that create them. This fresh perspective is relevant to diseases that range from autism, type 1 diabetes, type 2 diabetes, cancer, heart disease, schizophrenia, Parkinson’s disease, and Alzheimer disease. Research efforts need to be redirected. Oxidative shielding is protective and is a misguided target for therapy. Identification of the causal chemistry and environmental factors that trigger innate immunity and metabolic memory that initiate and sustain oxidative shielding is paramount for human health.

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


The cell danger response (CDR) is the evolutionarily conserved metabolic response that protects cells and hosts from harm. It is triggered by encounters with chemical, physical, or biological threats that exceed the cellular capacity for homeostasis. The resulting metabolic mismatch between available resources and functional capacity produces a cascade of changes in cellular electron flow, oxygen consumption, redox, membrane fluidity, lipid dynamics, bioenergetics, carbon and sulfur resource allocation, protein folding and aggregation, vitamin availability, metal homeostasis, indole, pterin, 1-carbon and polyamine metabolism, and polymer formation. The first wave of danger signals consists of the release of metabolic intermediates like ATP and ADP, Krebs cycle intermediates, oxygen, and reactive oxygen species (ROS), and is sustained by purinergic signaling. After the danger has been eliminated or neutralized, a choreographed sequence of anti-inflammatory and regenerative pathways is activated to reverse the CDR and to heal. When the CDR persists abnormally, whole body metabolism and the gut microbiome are disturbed, the collective performance of multiple organ systems is impaired, behavior is changed, and chronic disease results. Metabolic memory of past stress encounters is stored in the form of altered mitochondrial and cellular macromolecule content, resulting in an increase in functional reserve capacity through a process known as mitocellular hormesis. The systemic form of the CDR, and its magnified form, the purinergic life-threat response (PLTR), are under direct control by ancient pathways in the brain that are ultimately coordinated by centers in the brainstem. Chemosensory integration of whole body metabolism occurs in the brainstem and is a prerequisite for normal brain, motor, vestibular, sensory, social, and speech development. An understanding of the CDR permits us to reframe old concepts of pathogenesis for a broad array of chronic, developmental, autoimmune, and degenerative disorders. These disorders include autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), asthma, atopy, gluten and many other food and chemical sensitivity syndromes, emphysema, Tourette’s syndrome, bipolar disorder, schizophrenia, post-traumatic stress disorder (PTSD), chronic traumatic encephalopathy (CTE), traumatic brain injury (TBI), epilepsy, suicidal ideation, organ transplant biology, diabetes, kidney, liver, and heart disease, cancer, Alzheimer and Parkinson disease, and autoimmune disorders like lupus, rheumatoid arthritis, multiple sclerosis, and primary sclerosing cholangitis.

Naviaux, R. K., Naviaux, J. C., Li, K., Bright, A. T., Alaynick, W. A., Wang, L., . . . Gordon, E. (2016). Metabolic features of chronic fatigue syndrome. Proc Natl Acad Sci U S A, 113(37), E5472-5480. doi:10.1073/pnas.1607571113


More than 2 million people in the United States have myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We performed targeted, broad-spectrum metabolomics to gain insights into the biology of CFS. We studied a total of 84 subjects using these methods. Forty-five subjects (n = 22 men and 23 women) met diagnostic criteria for ME/CFS by Institute of Medicine, Canadian, and Fukuda criteria. Thirty-nine subjects (n = 18 men and 21 women) were age- and sex-matched normal controls. Males with CFS were 53 (±2.8) y old (mean ± SEM; range, 21–67 y). Females were 52 (±2.5) y old (range, 20–67 y). The Karnofsky performance scores were 62 (±3.2) for males and 54 (±3.3) for females. We targeted 612 metabolites in plasma from 63 biochemical pathways by hydrophilic interaction liquid chromatography, electrospray ionization, and tandem mass spectrometry in a single-injection method. Patients with CFS showed abnormalities in 20 metabolic pathways. Eighty percent of the diagnostic metabolites were decreased, consistent with a hypometabolic syndrome. Pathway abnormalities included sphingolipid, phospholipid, purine, cholesterol, microbiome, pyrroline-5-carboxylate, riboflavin, branch chain amino acid, peroxisomal, and mitochondrial metabolism. Area under the receiver operator characteristic curve analysis showed diagnostic accuracies of 94% [95% confidence interval (CI), 84–100%] in males using eight metabolites and 96% (95% CI, 86–100%) in females using 13 metabolites. Our data show that despite the heterogeneity of factors leading to CFS, the cellular metabolic response in patients was homogeneous, statistically robust, and chemically similar to the evolutionarily conserved persistence response to environmental stress known as dauer.

Naviaux, R. K. (2018). Antipurinergic therapy for autism – An in-depth review. Mitochondrion, 43, 1-15. doi:10.1016/j.mito.2017.12.007


Are the symptoms of autism caused by a treatable metabolic syndrome that traces to the abnormal persistence of a normal, alternative functional state of mitochondria? A small clinical trial published in 2017 suggests this is possible. Based on a new unifying theory of pathogenesis for autism called the cell danger response (CDR) hypothesis, this study of 10 boys, ages 5–14 years, showed that all 5 boys who received antipurinergic therapy (APT) with a single intravenous dose of suraminexperienced improvements in all the core symptoms of autism that lasted for 5–8 weeks. Language, social interaction, restricted interests, and repetitive movements all improved. Two children who were non-verbal spoke their first sentences. None of these improvements were observed in the placebo group. Larger and longer studies are needed to confirm this promising discovery. This review introduces the concept of M2 (anti-inflammatory) and M1 (pro-inflammatory) mitochondria that are polarized along a functional continuum according to cell stress. The pathophysiology of the CDR, the complementary functions of M1 and M2 mitochondria, relevant gene-environment interactions, and the metabolic underpinnings of behavior are discussed as foundation stones for understanding the improvements in ASD behaviors produced by antipurinergic therapy in this small clinical trial.

Naviaux, R. K. (2019). Metabolic features and regulation of the healing cycle — A new model for chronic disease pathogenesis and treatment. Mitochondrion, 46, 278-297. doi:


Without healing, multicellular life on Earth would not exist. Without healing, one injury predisposes to another, leading to disability, chronic disease, accelerated aging, and death. Over 60% of adults and 30% of children and teens in the United States now live with a chronic illness. Advances in mass spectrometry and metabolomics have given scientists a new lens for studying health and disease. This study defines the healing cycle in metabolic terms and reframes the pathophysiology of chronic illness as the result of metabolic signaling abnormalities that block healing and cause the normal stages of the cell danger response (CDR) to persist abnormally. Once an injury occurs, active progress through the stages of healing is driven by sequential changes in cellular bioenergetics and the disposition of oxygen and carbon skeletons used for fuel, signaling, defense, repair, and recovery. >100 chronic illnesses can be organized into three persistent stages of the CDR. One hundred and two targetable chemosensory G-protein coupled and ionotropic receptors are presented that regulate the CDR and healing. Metabokines are signaling molecules derived from metabolism that regulate these receptors. Reframing the pathogenesis of chronic illness in this way, as a systems problem that maintains disease, rather than focusing on remote trigger(s) that caused the initial injury, permits new research to focus on novel signaling therapies to unblock the healing cycle, and restore health when other approaches have failed.

Naviaux, R. K. (2019). Incomplete Healing as a Cause of Aging: The Role of Mitochondria and the Cell Danger Response. Biology (Basel), 8(2). doi:10.3390/biology8020027


The rate of biological aging varies cyclically and episodically in response to changing environmental conditions and the developmentally-controlled biological systems that sense and respond to those changes. Mitochondria and metabolism are fundamental regulators, and the cell is the fundamental unit of aging. However, aging occurs at all anatomical levels. At levels above the cell, aging in different tissues is qualitatively, quantitatively, and chronologically distinct. For example, the heart can age faster and differently than the kidney and vice versa. Two multicellular features of aging that are universal are: (1) a decrease in physiologic reserve capacity, and (2) a decline in the functional communication between cells and organ systems, leading to death. Decreases in reserve capacity and communication impose kinetic limits on the rate of healing after new injuries, resulting in dyssynchronous and incomplete healing. Exercise mitigates against these losses, but recovery times continue to increase with age. Reinjury before complete healing results in the stacking of incomplete cycles of healing. Developmentally delayed and arrested cells accumulate in the three stages of the cell danger response (CDR1, 2, and 3) that make up the healing cycle. Cells stuck in the CDR create physical and metabolic separation — buffer zones of reduced communication — between previously adjoining, synergistic, and metabolically interdependent cells. Mis-repairs and senescent cells accumulate, and repeated iterations of incomplete cycles of healing lead to progressively dysfunctional cellular mosaics in aging tissues. Metabolic cross-talk between mitochondria and the nucleus, and between neighboring and distant cells via signaling molecules called metabokines regulates the completeness of healing. Purinergic signaling and sphingolipids play key roles in this process. When viewed against the backdrop of the molecular features of the healing cycle, the incomplete healing model provides a new framework for understanding the hallmarks of aging and generates a number of testable hypotheses for new treatments.

Naviaux, R. K. (2020). Perspective: Cell danger response Biology — The new science that connects environmental health with mitochondria and the rising tide of chronic illness. Mitochondrion, 51, 40-45. doi:


This paper is written for non-specialists in mitochondrial biology to provide access to an important area of science that has broad implications for all people. The cell danger response (CDR) is a universal response to environmental threat or injury. Once triggered, healing cannot be completed until the choreographed stages of the CDR are returned to an updated state of readiness. Although the CDR is a cellular response, it has the power to change human thought and behavior, child development, physical fitness and resilience, fertility, and the susceptibility of entire populations to disease. Mitochondria regulate the CDR by monitoring and responding to the physical, chemical, and microbial conditions within and around the cell. In this way, mitochondria connect cellular health to environmental health. Over 7,000 chemicals are now made or imported to the US for industrial, agricultural, and personal care use in amounts ranging from 25,000 to over 1 million pounds each year, and plastic waste now exceeds 83 billion pounds/year. This chemical load creates a rising tide of manmade pollutants in the oceans, air, water, and food chain. Fewer than 5% of these chemicals have been tested for developmental toxicity. In the 1980s, 5–10% of children lived with a chronic illness. As of 2018, 40% of children, 50% of teens, 60% of adults under age 65, and 90% of adults over 65 live with a chronic illness. Several studies now report the presence of dozens to hundreds of manmade chemicals and pollutants in placenta, umbilical cord blood, and newborn blood spots. New methods in metabolomics and exposomics allow scientists to measure thousands of chemicals in blood, air, water, soil, and the food chain. Systematic measurements of environmental chemicals can now be correlated with annual and regional patterns of childhood illness. These data can be used to prepare a prioritized list of molecules for congressional action, ranked according to their impact on human health.

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◊ Healing Cycle Research

Research in our lab has led to a new understanding of the ancient biology that underlies the circle of injury and recovery. New medicines and treatments are being developed that can remove the blocks to healing and help people get back on the road to recovery from disorders that were once thought to be permanent and irreversible.

Figure 1. Silos of Knowledge. Study of a single disease can show how it is different from all other diseases. However, it is knowledge of how complex disorders are the same that will lead to new cures of disorders that were previously thought to be permanent and irreversible. Abbreviations: CDR — cell danger response, ME/CFS — myalgic encephalomyelitis/chronic fatigue syndrome, GWI — Gulf War Illness, PTSD — post-traumatic stress disorder, TBI — traumatic brain injury, PANDAS — pediatric acute neurologic disorder associated with streptococcal infection.


An introduction to the concepts on this web page, with a focus on chronic fatigue syndrome, can be viewed in the video link of a lecture given at NIH by Dr. Naviaux below time stamped: 55:00 to 1:28:15:

Video Link:

Writing A Second Book of Medicine

For 5,000 years of written history, medicine has been focused on the treatment of acute injuries from trauma, infections, and poisoning1. This is the topic of the First Book of Medicine (“Book I”). The First Book of Medicine is taught to every physician and biomedical scientist in the 21st Century. However, if an injury or illness is not healed in 6 months, it is considered a chronic illness, and the rules of acute care medicine no longer suffice. To treat chronic illness effectively, we need a new book of medicine. The treatment and prevention of chronic illness is the focus of the Second Book of Medicine (“Book II”).

The rules that doctors learn to care for acute illness in Book I depend critically on the mechanisms and the pathway of the healing cycle to be intact. If death or serious deformity can be prevented in the first days or weeks after an acute illness, then the process of healing will lead the patient back to health and chronic illness can be prevented. The process of healing was so reliable in past centuries that modern physicians and scientists have not studied it well enough to know how to alter the outcome of a healing cycle once it has been disrupted. Today, the rising tide of environmental chemicals and manmade changes in the human environment have conspired to impose blocks on the process of healing. When blocks to healing occur, chronic illness results. Now 40% of children and 60% of adults must live with a chronic illness (see:

Many different triggers, including both genetic and environmental factors, can lead to a chronic illness. The process of disease formation is called “pathogenesis” (Figure 2). Virtually all the resources of biomedical research organizations around the world have tried to tackle the problem of chronic illness by cataloging the triggers and molecular mechanisms that derail the health cycle, and produce chronic diseases like diabetes, heart disease, cancer, and dementia. Once a trigger is found, a strategy is engineered to turn the trigger off or to reduce its effects. This engineering approach to disease effectively attempts to “reverse the tape of pathogenesis” in order to treat the illness (Figure 2).

Research in the Naviaux Lab has led us to the conclusion that a simple removal of a trigger, or treatment of a target that appears to be the “cause” of a symptom in a chronic disease, almost never leads to a cure. Instead, the symptom is palliated, but at the cost of having to take a medicine for life in order to keep that symptom in check. For example, insulin does not cure diabetes, and statins do not cure high cholesterol. These “pathogenesis-based” treatments almost never allow a person to shed their chronic disease and return to a drug-free state of health. Why?


The steps required for healing are not accomplished simply by “reversing the tape” of pathogenesis (Figure 2). Surprisingly, there is no name that describes the molecular stages and dynamics of healing. This void in our language has slowed scientific progress in understanding the mechanisms of healing.

Scientists cannot hold sharp focus on a problem unless they give it a name. The word “salugenesis” comes from the Latin root, Salus, the Roman goddess of health, safety, and prosperity (Figure 2). This new word is meant to refer to the evolutionarily conserved, and highly choreographed sequence of molecular steps that comprise the healing cycle (Figure 3).

There is a related word, “salutogenesis” that was coined by the Israeli-American medical sociologist, Aaron Antonovsky (1923-1994)2-4 to describe the lifestyle choices and coping skills that were associated with the production and preservation of health despite sociologic, economic, or environmental hardships. Salugenesis is not the same as salutogenesis. Salugenesis refers to molecular, metabolic, and cellular features of the healing cycle (Figures 2 and 3). Both salutogenesis and salugenesis refer to the integrative process of self-organization, regeneration, and restoration required for health. These processes redirect cellular energy to oppose and reverse the arrow of entropy. Pathogenesis, on the other hand, is a disintegrative process that disrupts the biological systems that characterize health, and lead to disorganization and an increase in entropy.

Figure 2. Salugenesis is Not the Reverse of Pathogenesis. Thousands of mechanisms have been identified that destroy health and lead to chronic illness. This is the study of “pathogenesis” — the mechanisms that lead from health to chronic illness, from left to right above. Finding a trigger and removing it or treating it to reverse the tape of pathogenesis uses engineering principles to treat disease. These principles are form the basis of the First Book of Medicine. However, only one major pathway has evolved in all plants and animals that allows injuries of any kind to be contained and healed. Salugenesis is the pathway that leads from right to left, from illness back to health. Finding the factors that block normal healing and removing them, and using salugens to promote and restore normal healing uses biological principles to treat disease. These principles will form the basis of the Second Book of Medicine. M1, M0, and M2 refer to different kinds of mitochondria that are needed for each stage of healing.

Although salugenesis and salutogenesis differ by referring to molecular vs life-style scale events, respectively, their conceptual origin is the same; the path to health proceeds by different mechanisms than the path to disease (Figure 2). Therefore, the term salutology can be used to refer to the systematic study of both molecular and lifestyle factors that promote and preserve health of mind and body5.


Just as the search for “pathogens” that trigger disease has led to important medical advances, our lab believes that the search for “salugens” will lead to a revolution in medical treatments. Salugens are interventions that promote the completion of the healing cycle, restore health, decrease mortality, and create heightened states of health and resilience. Salugens create an integrated, multisystem resistance to future chronic illness. Salugens need not be restricted to drugs. Exercise is a salugen6. Adaptogens are salugens7. Certain electrophysiologic interventions designed to promote healing associated with slow wave sleep are salugens8. Given the importance of the search for and study of salugens, a strong case can be made for adopting the term “Salugenology” for this new branch of medical science. Only time will tell how the terms, Salutology and Salugenology will help to sharpen the focus of this new branch of medicine.

The Healing Cycle

The molecular, metabolic, cellular, autonomic, and neuroendocrine steps that are activated by injury occur as an ontogenetically programmed sequence that underlies both the process of healing1,9 and aging10. The healing cycle is illustrated in Figure 3.

Figure 3. The Healing Cycle. Once the cell danger response (CDR) is activated by any stress of injury, a stereotyped and programmed sequence of events is initiated that enables healing from almost any injury. Like the cell cycle, the steps of the healing cycle cannot be skipped or reversed. The mitochondrial and metabolic features of CDR1, CDR2, and CDR3 have been described in a recent review1.

Three Different Kinds of Mitochondria

The three stages of the healing cycle are made possible by metabolic patterns that are produced by 3 different kinds of mitochondria. M1 mitochondria are proinflammatory. M0 mitochondria support Warburg metabolism, aerobic glycolysis, and cell growth. M2 mitochondria are anti-inflammatory and tumor suppressing. The role and characteristics of these different developmental forms of mitochondria has recently been reviewed1,10, and new treatments have been developed that help promote these mitochondrial transitions11.

Environmental Impacts on Human Health

Environmental pollution has been found by a Lancet commission to be responsible for 940,000 deaths of children each year around the world12,13. This pollution is the result of both a growing human population, and to the castoff of chemical waste from current farming and industrial practices used to support that population. New incentives are needed to stimulate green farming and industrial practices that can reduce this waste. Recent environmental monitoring efforts have shown that 42% of freshwater lakes and rivers in Europe now contain sufficient levels of toxins to cause chronic illness in plants and animals in and around those waterways14. Similar environmental monitoring efforts have not been done in the US, and many areas in India, China, and Africa have suffered similar trends in pollution that are causing chronic illness in children and adults. New technologies of metabolomics and exposomics15,16 will need to be applied to create the databases needed for governments around the world to reverse these trends. Every citizen of the world deserves the right to be born into an environment that does not cause chronic disease (


  1. Naviaux RK. Metabolic features and regulation of the healing cycle – A new model for chronic disease pathogenesis and treatment. Mitochondrion 2019; 46: 278-297.
  2. Antonovsky A. Health, stress, and coping. Jossey-Bass Inc., Publishers. 1979.
  3. Antonovsky A. Unraveling the mystery of health: How people manage stress and stay well. Jossey-Bass Inc., Publishers. 1987.
  4. Antonovsky A. The structure and properties of the sense of coherence scale. Soc Sci Med 1993; 36(6): 725-733.
  5. Charlton BG. A new science of health: salutology and the evolutionary perspective. QJM 1996; 89(3): 233-236.
  6. Hupin D, Roche F, Gremeaux V, Chatard JC, Oriol M, Gaspoz JM et al. Even a low-dose of moderate-to-vigorous physical activity reduces mortality by 22% in adults aged >/=60 years: a systematic review and meta-analysis. Br J Sports Med 2015; 49(19): 1262-1267.
  7. Panossian A, Wikman G. Evidence-based efficacy of adaptogens in fatigue, and molecular mechanisms related to their stress-protective activity. Current clinical pharmacology 2009; 4(3): 198-219.
  8. Huang MX, Swan AR, Quinto AA, Matthews S, Harrington DL, Nichols S et al. A pilot treatment study for mild traumatic brain injury: Neuroimaging changes detected by MEG after low-intensity pulse-based transcranial electrical stimulation. Brain Inj 2017; 31(13-14): 1951-1963.
  9. Naviaux RK, Le TP, Bedelbaeva K, Leferovich J, Gourevitch D, Sachadyn P et al. Retained features of embryonic metabolism in the adult MRL mouse. Molecular genetics and metabolism 2009; 96(3): 133-144.
  10. Naviaux RK. Incomplete Healing as a Cause of Aging: The Role of Mitochondria and the Cell Danger Response. Biology (Basel) 2019; 8(2).
  11. Naviaux RK. Antipurinergic therapy for autism – An in-depth review. Mitochondrion 2018; 43: 1-15.
  12. Landrigan PJ, Fuller R, Acosta NJR, Adeyi O, Arnold R, Basu NN et al. The Lancet Commission on pollution and health. Lancet 2018; 391(10119): 462-512.
  13. Landrigan PJ, Fuller R, Fisher S, Suk WA, Sly P, Chiles TC et al. Pollution and children’s health. Science of The Total Environment 2019; 650: 2389-2394.
  14. Malaj E, von der Ohe PC, Grote M, Kuhne R, Mondy CP, Usseglio-Polatera P et al. Organic chemicals jeopardize the health of freshwater ecosystems on the continental scale. Proceedings of the National Academy of Sciences of the United States of America 2014; 111(26): 9549-9554.
  15. Smith MT, de la Rosa R, Daniels SI. Using exposomics to assess cumulative risks and promote health. Environ Mol Mutagen 2015; 56(9): 715-723.
  16. Rattray NJW, Deziel NC, Wallach JD, Khan SA, Vasiliou V, Ioannidis JPA et al. Beyond genomics: understanding exposotypes through metabolomics. Hum Genomics 2018; 12(1): 4.

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◊ The 28th Amendment Project – Giving all Americans the right to be born into a healthy environment that does not cause chronic disease.

The 28th Amendment Project — Giving all Americans the right to be born into a healthy environment that does not cause chronic disease.

What is more important for the long-term health of a nation than the health of its citizens? A nation grows weak as its people fall to disease. In 1985, 5-10% of children born in the US lived with a chronic disease. Today, just thirty years later, 40% of children live with chronic disease. Many diseases have increased 2-10 times from 1985 to 2015 (Figure 1). Children with chronic disease grow up to be adults with disabilities and disease. This increase in chronic disease is not due to a change in our genes, or a failure in our healthcare system. The increase in disease is the result of measureable chemical changes in our food chain, air, water, and soil. The Environmental Protection Agency (EPA) was given the task of protecting human health by protecting the environment, but economic cuts have handicapped it since its last major contribution to public health, the banning of leaded gasoline in 19961.

Figure 1. 40% of Children Born Today Suffer with Chronic Disease. The prevalence of over 20 diseases has increased 2-to-10-times since 1980s.

The Naviaux Lab is seeking help to start a movement to create, refine, and ratify a 28th Amendment to the Constitution of the United States. This amendment will enunciate a new right for all American citizens. This is “right to be born into a healthy environment”, an environment that will not cause chronic childhood and adult disease. This right is an inalienable right of citizens of the 21st century. The text of this amendment will serve as a template for similar amendment in all nations of the world.

We didn’t need to think about preserving a healthy environment much in past centuries because the number of humans on the planet was not enough to permanently intoxicate and degrade the natural resources of the biosphere. This situation reached a tipping point in 19882-5. In 1988, there were 5.1 billion people on Earth. In that year, the human population consumed resources and released waste products at a rate the Earth could renew and recycle sustainably. After that, we began to live on biological principle. In 2016, the human population is 7.4 billion. Ever since 1988, we have been consuming natural resources faster than they can be replaced, and releasing waste that is accumulating in both obvious in less obvious places. The Great Pacific Garbage patch is a slow moving swirl of plastics and non-biodegradable detritus that is now twice the size of Texas and continuously releasing pesticides and organic pollutants on a global scale6.

Nanoscale chemical waste is the natural cast-off of an unregulated industrial economy. Many of these chemicals can be shown to produce neurodevelopmental disease during fetal development and in the newborn period. Whole ecosystems have begun to sicken7-9. The Naviaux Lab is developing new mass spectrometry methods that will enable the rapid and regular testing of our environment and food chain to give scientists and policy makers the data needed to crack down on companies and practices that endanger the health of our children, the health of our nation, and the health of the natural world.

Empowering the EPA — Keeping Americans Safe from Pollution

  1. Establish a permanent Office of Pollution Monitoring (OPM) and an associated observatory network consisting of 50 sentinel cities, with outlying factories, farms, forests, lakes, rivers, and marine coastal sites throughout the United States.
  2. Create a list of the specific samples to be collected at each of the 50 sentinel sites. These will include GIS-tagged samples of: air, water (from municipal tap and waste, rivers, lakes, well/aquifer/groundwater, and ocean samples), sediments (from specific parks, lakes, reservoir, and marine coastal samples), and regional sentinel foods such as organic and non-organic cow’s milk, honey, corn, soybeans, rice, wheat, oats, fruit (grapes, apples, pears, cherries), strawberries, blueberries, spinach, kale, celery, tomatoes, peanuts, walnuts, almonds, beef, pork, poultry, and fish.
  3. Collect GIS-tagged samples annually for sites with municipal populations > 1 million, and every 2 years for sites < 1 million, and measure the chemicals, including antibiotics, antifungal drugs, and common pharmaceuticals.
  4. Create a publicly-accessible electronic database with the results of these surveys as a congressionally-mandated public service.
  5. Work with the US Department of Agriculture (USDA), National Institutes of Health (NIH) and the American Medical Association (AMA) to correlate the trends of environmental chemical concentrations and the activities that produce them, with the trends of chronic illness in children in the sentinel areas.
  6. Generate a biannual report that prioritizes for US Congressional action, the chemicals that are found to be associated with the greatest health risks.


  1. 12 Steps Towards Health
  2. Healthy Child Guide


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Reproduced from: 12 Steps Towards Health

◊ 12-Steps to Help Build a Safer World and Healthier Life for our Children

Robert K. Naviaux, MD, PhD
University of California, San Diego
School of Medicine

What Can We Do?

12 Simple steps to help our children and grandchildren thrive.
  1. Clean the “bad actors” out or your home
    –Teflon pots (PTFE) and pans, most plastics (BPA, Pthalates), upholstery and blankets with synthetic fabrics with flame retardants (BDEs) and stain repellants
  2. Back to basic materials (Pre-1900 Materials — “Back to the Future”)
    –Wooden chairs, tables, and toys, glass, ceramic, clay pottery, cast iron pots and pans, stainless steel boiling pots, stainless steel eating utensils (or chop sticks), stone, brick, cotton, wool, leather, rubber, wax paper, linen table cloths, flowers and plants for decorations
  3. Reduce your Personal Care Product consumption
    Many lotions, perfumes, colognes, cosmetics, and hair products contain Phthalates and Parabens. Phthalates cause genital birth defects and are endocrine disrupters. Parabens during pregnancy can alter fetal brain and immune system development.
  4. Breast Feeding is best if you can for the first year of life — avoid cow’s milk until after the first year
    –This decreases the risk of asthma, food allergies, Type I Diabetes, and other autoimmune disorders
    –When you do add cow’s milk, think about A2/A2 (Jersey, some Guernsey) milk instead of A1/A1 (Holstein) or A1/A2 (most Guernsey) milk
  5. Buy Local, Organic, and Seasonal Fruits and Vegetables — find a farmers market and make some new friends
  6. Avoid candies and foods with food dyes and colorings — these can cause hyperactivity (Dyes are a big problem. Its not all about sugar.)
  7. Avoid most processed foods in boxes and bags
    –They last a long time because they have preservatives that kill bacteria and affect your metabolism
    –BHA is an endocrine disruptor, BHT is a mitochondrial uncoupler, and both BHA and BHT bioaccumulate in aquatic animals
  8. Avoid Bottled Water in the US — plasticizers leach into the water
    –Use a good carbon filter. Bottled water may be preferred in developing countries with unsafe water supplies.
  9. Buy hormone- and antibiotic-free meat — beef, pork, lamb, chicken, turkey
  10. When you eat fish, avoid farmed fish, and avoid too many servings per month of long-lived fish like tuna or swordfish.
    –The longer a fish lives, the more pesticides and mercury it concentrates. Sardines anyone?
  11. Avoid travel by internal combustion engines whenever you can
    –Walk, bike, ride a horse, lease a hybrid or electric car (although there are trade-offs because of battery manufacturing)
  12. Build in walks and play in the parks, green spaces, hills, by rivers, lakes and bays, through a forest, tide pools and beaches, or through a botanical garden each week. Point out all the other living creatures around us. Plant a vegetable garden.
    –Help your kids get reconnected to the wild. Explore the outdoors. Put a stop to “Nature Deficit Disorder”.

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