Personalized Medicine Cellular Systems Medicine

Personalized Medicine: Identifying & Addressing The Root Cause Of Chronic Disease

A New Paradigm For Health And Disease

This is the first lecture inside our brand-new program: Personalized Medicine: A Cellular & Systems Medicine Approach. This lecture will explore a revolutionary new approach to uncovering the underlying factors that dictate health and disease.

In the remaining curriculum, we’ll systematically examine the specifics of each core biological process and seven core modulators of health (as introduced in this lecture) to gain a more nuanced and holistic view of health and disease.

Our program will teach you how to uncover, identify, and address the root causes of chronic disease, empowering you to deliver personalized, targeted, and holistic care. By the end of the program, you will learn to:

Understand and identify the core biochemical mechanisms driving chronic disease.
Connect your patient’s signs, symptoms, and laboratory results directly to specific biochemical dysfunctions.
Detect subtle clinical clues—signs, symptoms, and laboratory findings—that reveal underlying upstream mechanisms.
Interpret advanced laboratory tests to gain deeper clinical insights into your patient’s health.
Design personalized nutrition and lifestyle interventions to modulate your patient’s underlying cellular dysfunction.
Strategically incorporate supplements and nutraceuticals to support and improve health.
Evaluate the latest research to explore novel approaches for current pharmaceutical options.

We’ll break down the underlying mechanisms so you can understand why one strategy might benefit one person yet be ineffective or even harmful to another.

Each module will directly connect your patient’s signs, symptoms, and laboratory results to specific biochemical dysfunctions. You’ll learn how to strategically modify the core modulators of health and disease to address your patient’s underlying cellular dysfunction.

Join us as we redefine what it means to be healthy.

The Philosophy Of Disease

Medicine is fantastic and lifesaving for acute problems (trauma, infection, etc.) but has many shortcomings for chronic diseases. We have tried to apply the same philosophy we’ve learned from acute to chronic diseases for decades, but it doesn’t work. They follow different rules and principles.

Our training teaches us to label and manage specific patterns. Unfortunately, this management becomes more complex as every chronic disease is classified as progressive. But then again, what other option exists if we never focus on eradicating the disease? With this mindset, there is no other outcome but a progressive illness.

Our current view is focused on the superficial when true healing is done at the cellular level. Unfortunately, the interconnectedness of our bodies won’t allow a single prescription to achieve this.

I want to take a second to introduce Dr. Robert K. Naviaux. He is the founder and co-director of the Mitochondrial and Metabolic Disease Center (MMDC) at UC San Diego and a Professor of Genetics in the departments of Medicine, Pediatrics, and Pathology at the UCSD School of Medicine. He directs the core laboratory for metabolomics. He is also the co-founder and former president of the Mitochondrial Medicine Society (MMS) and the founding associate editor of Mitochondrion.

Dr. Naviaux specializes in mitochondrial medicine and complex chronic disorders, discovered the cause of Alpers syndrome, and was part of the team that reported the first mitochondrial DNA mutation to cause genetic forms of autism.

I will read an excerpt he wrote because I don’t want to paraphrase or butcher any of the language he used.

“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.
Many different triggers, including both genetic and environmental factors, can lead to a chronic illness. The process of disease formation is called “pathogenesis”. 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.
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?
Salugenesis
The steps required for healing are not accomplished simply by “reversing the tape” of pathogenesis. 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. This new word is meant to refer to the evolutionarily conserved, and highly choreographed sequence of molecular steps that comprise the healing cycle.
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. 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.
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. The term salutology has been used to refer to the systematic study of both molecular and lifestyle factors that promote and preserve health of mind and body5.
Salugens
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 applying one of the new terms “Salogy” or “Salugenology” for this new branch of medical science. Only time will tell how the terms, Salogy, Salutology, or Salugenology will help to sharpen the focus of this new branch of medicine and help to distinguish it from the related but distinct medical discipline of Pathology.
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.
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.”

Inherent Flaws In Evidence-Based Medicine

Variables

By definition, it is challenging to prove any of this with a double-blinded, randomized controlled trial (RCT). To do this type of trial, we can only have one variable. However, our bodies don’t work this way; we are much more complex. Let’s walk through a simple example using vitamin B6 (pyridoxine) as the treatment intervention we are looking to use. Pyridoxine is the inactive form of the cofactor and must first be converted into pyridoxine 5′-phosphate (PNP) using magnesium, ATP, and the pyridoxal kinase (PLK) enzyme. The final step is to convert PNP into pyridoxal 5′-phosphate (PLP) using FMN (riboflavin) and the pyridoxine phosphate oxidase (PNPO) enzyme. Only once pyridoxine is converted to PLP can it be used as a cofactor to run biochemical reactions. With this background, let’s walk through two scenarios.

Person A: This person is in a clinical trial to evaluate the efficacy of B6 on their condition. Unbeknownst to the clinical team, they also have a magnesium deficiency. Because of this, pyridoxine supplementation is deemed to be ineffective.

Person B: This person is also participating in a clinical trial to evaluate the efficacy of B6 supplementation. However, they also have an underlying riboflavin deficiency, which was missed. Because of this, pyridoxine supplementation is deemed ineffective.

The consensus is that pyridoxine supplementation did not improve their condition’s outcomes. However, we missed a critically important step by not addressing the associated cofactor deficiency, which prevents the activation of PLP. If the goal is to evaluate pyridoxine supplementation, we must ensure that every participant can activate it. Person A requires magnesium supplementation, and person B requires riboflavin supplementation. Only once nutrients are replete can the trial looking for the efficacy of pyridoxine be conducted.

To complicate matters further, suppose person C in the trial has a genetic polymorphism that impairs the proper function of the PNPO gene. This would also impede the final step in conversion, preventing the activation of PLP. Again, this would lead the researchers to conclude that pyridoxine supplementation was ineffective.

I don’t know about you, but I’ve never encountered a study that ran whole genome sequencing on all participants before evaluating a vitamin’s efficacy. Yet, genetics is one of the five core biological processes that play a role in health and disease. Some might argue that a genetic mutation would have been readily apparent due to obvious symptoms such as seizures at the beginning of life. However, this operates assuming all mutations lead to the classic phenotype. Just like disease lives on a spectrum, so do genetics. Remember, genetics only say what is possible, not what will happen. Many individuals may very well have polymorphisms that only slow down enzymatic production. In other words, they still make enough of the PNPO enzyme to prevent the classic disease type. Still, perhaps not enough is produced, so that is why person C has the condition for which he was initially enrolled in this trial.

Unfortunately, this is the only way we believe something is evidence-based. We have swung so far the other way that our search for evidence potentially harms our patients. The methodology in this type of trial can be overly reductive due to real‐world genetic, biochemical, and environmental differences among patients. By averaging responses into population‐level data and labeling patients under a single disease category, RCTs may fail to capture the nuanced, individual pathways driving the same clinical diagnosis. The data might not reflect or predict each patient’s response, especially when the same disease can arise from multiple etiological pathways.

Performing a randomized double-blinded control trial

First, subjects are randomly assigned to either the intervention or control (placebo or standard-of-care) group. The goal is to minimize selection bias and confounding by evenly distributing known and unknown variables (demographics, comorbidities, etc.) across groups.

To prevent bias in measuring or reporting outcomes, neither participants nor investigators know who receives the active treatment versus placebo/control. Then, a comparable group receives either a placebo or the current standard of care to provide a baseline for comparison.

Outcomes are predefined, systematically measured, and analyzed at set intervals to ensure consistency, reduce subjective interpretation, and allow statistical comparison.

Inherent flaws

Despite being the gold standard, there are inherent flaws, especially regarding the patients’ genetic, biochemical, and environmental differences. These differences can lead to significant variation in how individuals respond to a given treatment, but they may be obscured in the average results.

People carry different gene variants (those affecting drug metabolism, immune tolerance, or disease susceptibility). A highly effective treatment in one genetic subgroup might be ineffective or harmful in another. By design, RCTs aggregate data across all subjects, potentially diluting signals of benefit or harm in specific subgroups.

Varying levels of micronutrients, hormone profiles, or microbiome compositions can modify drug response. The “average” effect (as reported in an RCT’s final statistical analysis) may mask clinically essential differences in these subpopulations.

Individuals categorized under one “disease” label (type 2 diabetes, depression, etc.) can have very different underlying pathophysiological processes (genetic predisposition, inflammatory states, nutritional deficiencies). However, an RCT lumps these diverse patients together, assuming they share a common mechanism and will respond similarly to a single intervention.

The RCT model typically assumes a uniform pathophysiology for a diagnosis, but real-world patients may have multiple overlapping drivers (lifestyle, genetics, environment). This discrepancy means the ultimate average result may not accurately reflect how various individuals, or even large subgroups, will respond.

RCTs use narrow criteria to minimize confounders (excluding comorbidities, extreme age groups, etc.). This homogeneity can improve internal validity but may reduce external validity, meaning real-world patients (who are more heterogeneous) may not mirror RCT participants. Many RCTs, especially in early phases, span weeks or months, whereas chronic conditions can unfold over years. Because of this, the trial may not fully capture long-term side effects, cumulative toxicity, or the natural evolution of disease (potentially including changes in gene expression over time).

The emphasis is on group averages and statistical significance (p-values, confidence intervals), potentially disregarding outliers or subgroup-specific outcomes. A treatment might show a moderate average effect yet work exceptionally well for a small percentage of patients or be ineffective (or harmful) for others. In some RCTs, results are reported in composite measures to boost statistical power, which can obscure how different outcome components (stroke vs. heart attack) impact specific subgroups.

In many cases, giving a placebo is not feasible or ethical if a standard of care already exists. This complicates the structure of RCTs and limits the amount of new information gained from novel interventions.

Large-scale, long-term RCTs are resource-intensive, limiting the number of variations or sub-stratifications that can be tested. Practical constraints often force simplified designs that cannot account for detailed genetic or environmental stratification.

To be clear, I’m not advocating abandoning science. Instead, we need to do more single-patient (n-of-1) trials, mechanistic studies, or studies that track multiple variables concurrently. We also need research frameworks that can handle complex systems. Thanks to technological advancements, we can now gather this evidence, which was impossible just twenty years ago.

Fraud

A systematic review suggested that around 2% of scientists admitted to falsifying or fabricating data at least once. However, around 14% reported observing research misconduct in colleagues. Another study found that misconduct was the reason behind approximately 67% of biomedical paper retractions, highlighting the severe impact of fraud on medical literature.

In 2024, Alzheimer’s research has faced this very problem:

Cassava Sciences faced accusations of data manipulation in trials involving its Alzheimer’s drug, simufilam. Hoau-Yan Wang, a key researcher, was charged with fraud for submitting falsified data. The company later settled with the SEC for $40 million and halted all ongoing clinical trials after failing to demonstrate efficacy.
A highly influential 2006 paper by Sylvain Lesné was retracted due to image manipulation. This paper heavily supported the amyloid hypothesis, a cornerstone theory guiding Alzheimer’s research for decades, causing significant disruption to the field.
Eliezer Masliah, former director at the National Institute on Aging, was found to have engaged in misconduct through extensive image manipulation in 132 published papers from 1997 to 2023, impacting Alzheimer’s and Parkinson’s research integrity. His misconduct negatively influenced many clinical trials over the years, and approximately 238 active patents cite papers by Dr. Masliah, with his name appearing on 28 patents.

Conclusion

I want to be clear that everything I believe is rooted in science. I am not saying we need to discredit all the work that well-designed trials have done. However, we can’t look the other way and pretend that the double-blinded placebo-controlled trial is perfect. There are inherent flaws in the system we use in medicine. If you choose to treat, you must know the nuances behind each study backing the treatment; it’s not enough to know the outcomes. There is too much nuance to mindlessly follow guidelines put forth by humans who are also inherently flawed or may have been influenced by other factors to have their work published.

It is beyond the scope to offer solutions to improve clinical trials. However, it is essential to discuss potential pitfalls, which are rarely discussed yet dramatically impact every clinical decision. Awareness of the problem is the first step.

Chronic Disease

According to the CDC, 60% of adults in the United States have at least one chronic disease, 40% have at least two or more chronic diseases, and 70% of all deaths are secondary to a chronic disease.

According to the National Council on Aging, nearly 95% of adults 60 and older have at least one chronic condition, while almost 80% have two or more. The CDC states that 60% of school-aged children in the United States have at least one chronic disease (including mental health disorders).

It’s estimated that 80% of chronic diseases and premature deaths could potentially be prevented.

Interestingly, there isn’t a clear consensus on the definition of a disease. Intuitively, we all know what it is; however, depending on the source, you’ll find a different definition. This is partly why there is often debate regarding what should be classified as a disease, one of the more recent examples being obesity.

The World Health Organization doesn’t even bother to define disease. Instead, it defines health as complete physical, mental, and social well-being, not merely the absence of disease or infirmity.

In other words, the lack of disease doesn’t automatically equate to health, as many believe.

A chronic disease is any disease lasting more than 6 – 12 months. It usually develops gradually and often persists for a lifetime. Conventional medicine teaches the clinician to manage, slow the progression, and reduce complications; cure is rarely an option.

Stop Treating The Disease

Traditionally, a disease must have an officially recognized medical diagnosis with an associated ICD-11 code. This medical diagnosis is an arbitrary label we’ve chosen to help us communicate patterns seen in patients (signs and symptoms). A clinician will then use this label to guide management (slow the progression and reduce complications).

This thinking assumes that every pattern has the same causative factors. However, this isn’t true and often creates a revolving door of questions that leaves the patient without answers. Take depression as an example:

Question: Why is this patient presenting with fatigue, migraines, depressed mood, diminished interest in activities, and insomnia?
Answer: Because he has major depressive disorder.

Question: How do you know he has major depressive disorder?
Answer: Because he fits the criteria and is presenting with fatigue, migraines, depressed mood, diminished interest in activities, and insomnia.

This provides us with a pattern and a label (ICD-11 code), which we use to indicate that first-line therapy is a selective serotonin reuptake inhibitor (SSRI). This algorithm only works if everyone with depression needs more serotonin to linger at the synaptic cleft. The SSRI doesn’t address:

Lack of purpose or meaning
Chronic daily stressors (finances, relationships, etc.)
Trauma
Isolation
Insulin resistance
Hormone (cortisol, sex, thyroid, etc.) imbalances
Toxin (heavy metals, environmental, etc.) exposure
Nutritional deficiencies (magnesium, folate, tryptophan, etc.)
Inflammatory cytokines (IL-6, TNF-α, etc. )
Mitochondrial disease
Gut-Brain axis dysfunction
Dysregulated sleep
Genetic polymorphisms
Other neurotransmitter dysregulation (dopamine, glutamate, GABA, etc.)

As you can see, one medical diagnosis can result from many things happening upstream. The label (medical diagnosis) is only helpful in identifying a person’s pattern of superficial dysfunction; it tells us nothing about why this dysfunction is occurring.

If we can’t identify the reason for dysfunction based on the chosen label, why are we using this label to choose therapy? It’s no wonder we can’t cure any chronic disease and why we’ve shifted to a time where the majority now live with a chronic disease.

This is why I view disease as a shorthand for the signs and symptoms; it is nothing more than a way to communicate the clinical picture, but it can’t ever be used in isolation to help someone become genuinely healthy.

Clinicians also struggle with the fact that these upstream problems can manifest in various downstream manifestations depending on many individual factors. For example, a disruption in one biochemical pathway might present as major depressive disorder in one person and as hyperglycemia in another.

Focus On Problems Upstream

Instead of playing signs and symptoms whack-a-mole, the focus should be addressing the dysfunction as upstream as possible. This strategy will also alleviate other seemingly unrelated problems a patient may be experiencing. This is how we can leverage one plan to address multiple diseases. Let’s walk through an example using magnesium.

Person A has hyperglycemia.
Pancreatic beta cells require magnesium to help regulate various enzymes and ion channels (including ATP-sensitive potassium) essential for insulin synthesis and release. When magnesium is lacking, the beta cells cannot effectively secrete insulin in response to elevated blood glucose.

Magnesium is a cofactor for many enzymes involved in phosphorylation and signaling steps within the insulin pathway. Low magnesium disrupts these enzymatic reactions, leading to post-receptor defects. Insulin-mediated glucose transporter (GLUT4) activity in muscle and adipose tissue is impaired when magnesium levels are low, further decreasing glucose uptake from the bloodstream.

This person now has impaired insulin signaling and insufficient insulin secretion. Their skeletal muscle and adipose tissue fail to efficiently remove glucose from the bloodstream, leading to hyperglycemia over time. The elevated glucose results in osmotic diuresis, further depleting magnesium and creating a vicious cycle.

Person B has major depressive disorder.
Magnesium blocks excessive calcium influx through NMDA receptors in neurons. When magnesium is low, NMDA receptors can become overactive, leading to heightened glutamate signaling (excitotoxicity). Excessive glutamate activity is associated with neuronal damage and stress responses linked to depressive symptoms.

Magnesium deficiency can exacerbate the hypothalamic-pituitary-adrenal (HPA) axis response to stress, increasing cortisol release. Chronic elevations in cortisol can promote mood disturbances and neuronal atrophy in areas associated with depression.

Magnesium is also involved in enzymes critical for neurotransmitter synthesis and function. Low magnesium can reduce the production or availability of monoamine neurotransmitters (like serotonin and dopamine) and impair GABAergic (inhibitory) transmission. These disruptions may directly contribute to depressive symptoms.

Lastly, magnesium deficiency can stimulate the release of inflammatory mediators (TNF-α, IL-6, etc.), resulting in chronic neuroinflammation.

This example shows how one upstream problem (magnesium deficiency) results in two labels that usually get two different management options. Suppose person C walks in with an elevated fasting blood glucose and symptoms of major depressive disorder. Is it possible to leverage one plan (magnesium supplementation) to address seemingly unrelated labels? Absolutely, as long as magnesium was the upstream problem identified after a thorough investigation.

Important reminder: A deficiency in magnesium doesn’t always result in hyperglycemia or major depressive disorder, and not everyone with hyperglycemia or major depressive disorder has a magnesium deficiency. This nuance is partly why the algorithmic approach to medicine is failing us.

Optimizing Health

Regardless of the manifestation (signs and symptoms), the cell will always be the common denominator. In its simplest form, disease (with few exceptions) represents cellular dysfunction. Irrespective of the patient’s complaint, our primary goal is to optimize cellular health.

Being free of disease is not enough for an individual to be healthy. While it is a requirement, we must remember that dysfunction is present long before a disease occurs and often long after it has been removed. Because of this, a comprehensive approach must address the underlying processes at the cellular level.

That is why we focus on five core biological processes that must be functional for health to exist: metabolism, immune function, genetics, internal environment, and cell-to-cell communication. Remember that these five core biological processes are not isolated or siloed; they overlap, intersect, and dynamically interact as integrated components within one interconnected biological system.

Metabolism

Macronutrients
- Glucose
- Fatty acids
- Amino acids
Micronutrients
- Vitamins
- Minerals
Balanced redox environment
- Antioxidants
- Oxidative stress
Mitochondria
Oxygen

Immune function

Microbiome
Inflammation
Immune tolerance
White blood cells
Antibodies
Pathogens
Toxins

Genetics

Germline mutations
Genomic stability
Epigenetics
Autophagy
Apoptosis

Internal environment

Fluid, electrolyte, and ion balance
Proper pH
Temperature
Waste removal and detoxification

Cell-to-cell communication

Functional phospholipid bilayer
Proper signal transduction
Working receptors
Intact gap junctions
Regulated hormones, growth factors, and neurotransmitters

It’s important to remember that the core biological processes explain why the person remains in an unhealthy state rather than necessarily describing the inciting trigger—though they sometimes overlap. Conversely, if these processes are running smoothly, then we have health. The five interconnected core biological processes can be optimized via seven core modulators as they directly modulate and shape the internal biological state. Just as the core biological processes overlap, intersect, and dynamically interact, so do the core modulators; each modulator will address every core biological process:

Nutrition
Movement and resistance
Light exposure, circadian rhythm, and sleep
Rest and recovery
Toxic load
Psychosocial health
Community and living environment

Although each modulator affects every core biological process, not all modulators impact all core biological processes equally in all situations. Context and individual variation (genetics, environment, health status, etc.) dictate the strength and immediacy of each modulator’s influence on each core biological process.

Another critical detail is that these modulators can improve health or perpetuate disease. Depending on various factors, these inputs can be used positively or negatively.

Everyone should optimize the seven core modulators above before considering more intensive therapeutic interventions (pharmacological or surgical therapies) whenever possible. There are exceptions, especially if there is an increased urgency to save a life. However, if this urgency doesn’t exist and if possible, these modulators should be used first.

Unfortunately, we don’t live in an ideal world, and many people have most likely been on multiple pharmacological therapies for some time. This complicates matters because when a medication is prescribed, it will invariably affect other systems (even if we don’t know how to quantify those interactions). Our entire body is interconnected. Nothing we put into our bodies is entirely neutral; it will always have a positive or negative effect. Sometimes, the body can handle these effects, so signs and symptoms don’t occur. However, that doesn’t mean that subclinical cellular metabolic changes aren’t happening. This statement isn’t isolated to prescriptions; it also holds for every core biological process and modulators of health. If we manipulate one thing in the system, it will invariably impact the entire system (this could be good or bad).

It would also be ignorant to say that everyone can achieve health by optimizing these seven core modulators alone. While core modulators are typically sufficient to maintain or restore health, specific conditions involving foundational biological damage or dysfunction (genetic disorders, irreversible organ failure, etc.) may require more intensive therapeutic interventions. For example, insulin therapy for type 1 diabetes or intravenous immunoglobulin (IVIG) for primary immunodeficiency cannot be effectively replaced solely by modulators. Advanced interventions are critical for survival and optimal health outcomes in such cases. Additionally, pharmacological treatments can sometimes be utilized temporarily to help rebalance disrupted core biological processes, after which ongoing health can often be effectively maintained by leveraging core modulators.

However, even in these situations, addressing all modulators will maximize the patient’s potential for health; there will be a synergistic effect. By focusing on the fundamentals, we can shift the focus to a more health-centric model rather than a disease-centric model.

Because these five core biological processes are so profoundly interwoven into basic physiology, almost any chronic disease will eventually involve all of them to some degree. While one core biological process might be more clearly “front and center” in a given chronic disease, others tend to be drawn in—either as a contributing factor or a downstream consequence—over time. It’s hard to find any chronic condition that doesn’t touch all five to some extent, precisely because they’re the foundational processes that keep cells and organs running.

I also want to clarify that although the modulators appear simple theoretically, they are not easy to execute. I won’t teach a one-size-fits-all approach to these topics, either. There isn’t one way to eat, sleep, etc., that will benefit everyone. The methodology varies considerably based on underlying disruptions in the five core biological processes. A nuanced scientific approach is fundamental to applying these principles in the real world.

We will examine the specifics of each core modulator and core biological process in future lessons. We will explore their interconnectedness and how each modulator can directly affect and shape the internal biological state.

A New Paradigm For Health

Let’s recap five critical concepts that address this new line of thinking:

Health is a distinct biological state, not merely the reversal or absence of disease. The pathways involved in disease development often differ from those needed to restore health.
Cellular dysfunction begins with asymptomatic (subclinical) metabolic changes to the cell, which is always the first step towards disease.
Specialization (from an organ-based system approach) can potentially hurt the patient. Instead, we must become experts in addressing the five core biological processes of health.
Everyone should optimize the seven core modulators of health whenever possible; they can improve health or perpetuate disease.
Every core biological process and modulator overlap, intersect, and dynamically interact as integrated components within one interconnected biological system. No external input is entirely neutral; it will always positively or negatively affect the organism with associated cellular metabolic changes.

Concept 1

Health is a distinct biological state, not merely the reversal or absence of disease. The pathways involved in disease development often differ from those needed to restore health. Medicine has historically focused on acute illnesses, relying on the body’s innate healing mechanisms, but this approach is insufficient for chronic conditions. Current strategies that focus solely on reversing disease triggers provide symptom relief but rarely cure chronic illness, leaving patients dependent on lifelong medications.

The concept of salugenesis addresses this gap by describing the molecular, metabolic, and cellular processes necessary for proper healing, emphasizing the body’s integrative capacity for regeneration and restoration. Unlike pathogenesis, which leads to increased disorder (entropy), salugenesis actively promotes a return to health through organized biological processes. Pathogenesis and salugenesis are two distinct paths. Understanding and promoting mitochondrial transitions (M1, M0, M2 mitochondria) is central to harnessing salugenic treatments and advancing medicine toward sustainable health restoration.

Concept 2

Cellular dysfunction begins as asymptomatic (subclinical) metabolic changes to the cell. These changes eventually become functional and morphological, and eventually, we get the recognized disease state. Disease is the clinical manifestation with a recognized pattern of signs and symptoms.

Clinicians often like to give things time to unravel. The phrase “wait and see” is not in short supply. However, that is not a sound strategy. Fixing a leaking faucet is easier and cheaper than fixing a broken pipe. If you hold off on addressing the simple problem, the pipe could burst, potentially leading to irreversible damage.

Like the pipe, addressing a disease is more complicated, time-intensive, and expensive than addressing subclinical metabolic changes in the cell. Of course, we must acknowledge that specific problems may be irreversible and largely dependent on the time it takes to address the cellular dysfunction. The longer we wait to address the imbalance, the bigger it will grow and the more it will transverse to other body parts.

Addressing subclinical metabolic changes is difficult because they are subclinical, meaning the patient is asymptomatic.

How often have we been told to treat the patient, not the labs? I used to believe this until I realized that labs can show signs of dysfunction long before signs and symptoms become apparent. I think we can all agree that prevention is far better than treatment. So, why are we always told to wait before we take action? This is contradictory.

For many, this dysfunction takes decades to cause permanent damage, giving us ample time to address things long before they ever become anything permanent. The caveat is that the younger a person is when the dysfunction starts, the quicker the recognized diseased state occurs. For example, if cellular metabolic changes begin in utero, a chronic disease can start within the first year of life. It’s essential to recognize that although the recognized disease state (pattern of signs and symptoms) begins in the first year of life, the dysfunction has been occurring quietly in the background from the beginning of this child’s life; it didn’t suddenly happen.

Concept 3

Specialization (from an organ-based system approach) can potentially hurt the patient. Instead, we must focus on the five core biological processes of health: metabolism, immune function, genetics, internal environment, and cell-to-cell communication. Remember that these processes are not siloed; many topics within each core biological process overlap, intersect, and dynamically interact.

Let’s take a look at the four most common buckets of chronic disease in the United States:

Atherosclerotic disease: No identifiable etiology, but we know it’s multifactorial.
Cancer: No identifiable etiology, but we know it’s multifactorial.
Metabolic disease: No identifiable etiology, but we know it’s multifactorial.
Neurodegenerative disease: No identifiable etiology, but we know it’s multifactorial.

Interestingly, we’ve become hyperspecialized but have yet to uncover why most people aren’t healthy. We know the epidemiology (sort of), pathophysiology (with limitations), risk factors, histological changes, and potential mechanisms. However, we can’t pinpoint a true etiology for each disease inside these buckets. This is partly because chronic disease isn’t caused by one thing; it results from many things going wrong across multiple organ systems.

There isn’t one clear-cut genetic or environmental factor to blame. Humans are far too complex, and everything doesn’t fit neatly into the boxes we created over a century ago. Our world is too diverse, and humans have unlimited variability, resulting in infinite etiological combinations.

Medicine is becoming increasingly fragmented, and clinicians must remember to zoom out and look at the whole picture. This is a classic example of losing the forest for the trees, albeit in a more sophisticated fashion.

Clinicians must shift their focus from specializing in organ systems to becoming experts in addressing the five core biological processes that transverse all organ systems.

Clinicians need to know about the entire organism they are treating. The disease is unaware of these arbitrary lines in the sand we’ve set for what we should know in our given specialty. If the goal is health for the organism, then the entire organism must be addressed. After all, every single chronic disease eventually crosses into every domain. In every example, without fail, you will have multiple systems that involve all five core biological processes. How this manifests will differ depending on where the dysfunction first occurs.

In future lessons, we will explore the specifics of each core biological process and how they drive health and disease.

Concept 4

Everyone should optimize the seven core modulators of health whenever possible. Just as the biological processes overlap and intersect, so do the modulators; each modulator will address more than one core biological process:

Nutrition
Movement and resistance
Light exposure, circadian rhythm, and sleep
Rest and recovery
Toxic load
Psychosocial health
Community and living environment

Everyone should optimize the seven core modulators above before considering more intensive therapeutic interventions (pharmacological or surgical therapies) whenever possible. There are exceptions, especially if there is an increased urgency to save a life. However, if this urgency doesn’t exist, and if possible, these modulators should be used first.

While core modulators are typically sufficient to maintain or restore health, specific conditions involving foundational biological damage or dysfunction (genetic disorders, irreversible organ failure, etc.) may require more intensive therapeutic interventions. Additionally, pharmacological treatments can sometimes be utilized temporarily to help rebalance disrupted core biological processes, after which ongoing health can often be effectively maintained by leveraging core modulators.

In future lessons, we will examine each modulator’s specifics and discuss how they directly affect and shape the internal biological state. We will also discuss how they impact the underlying mechanisms for each core biological process.

Concept 5

Every core biological process and modulator overlap, intersect, and dynamically interact as integrated components within one interconnected biological system. No external input is entirely neutral; it will always positively or negatively affect the organism with associated cellular metabolic changes. Even something as simple as supplementing with one vitamin to address a deficiency will have second- and third-order consequences (they may be good or bad). This must be considered when navigating health, as this process is continuously dynamic with ever-moving goal posts. Health is not a set-it-and-forget-it situation.

Introducing:

Personalized Medicine: A Cellular & Systems Medicine Approach

Identifying & Addressing The Root Cause of Chronic Disease

Our program, Personalized Medicine: A Cellular & Systems Medicine Approach, will teach you how to uncover, identify, and address the root causes of chronic disease, empowering you to deliver personalized, targeted, and holistic care.

By the end of the program, you will learn to:

Understand and identify the core biochemical mechanisms driving chronic disease.
Connect your patient’s signs, symptoms, and laboratory results directly to specific biochemical dysfunctions.
Detect subtle clinical clues—signs, symptoms, and laboratory findings—that reveal underlying upstream mechanisms.
Interpret advanced laboratory tests to gain deeper clinical insights into your patient’s health.
Design personalized nutrition and lifestyle interventions to modulate your patient’s underlying cellular dysfunction.
Strategically incorporate supplements and nutraceuticals to support and improve health.
Evaluate the latest research to explore novel approaches for current pharmaceutical options.

We’ll break down the underlying mechanisms so you can understand why one strategy might benefit one person yet be ineffective or even harmful to another.

Join me as we redefine what it means to be healthy.