I started clinical practice in 1992. Over my 30-year career, I have found it important to keep up with the current literature. One case in point is a patient I saw in my clinic in 1996. This was a 50-year-old type one diabetic who had a creatinine of 2.5 and 5000 mg of protein in his urine at the time. His clinical prognosis was that he had a significant chance of being on dialysis within two years; he was initially treated with an ACE inhibitor, and his protein went down to 500 mg. His diabetes and hypertension were aggressively controlled. I found a paper sometime during the course of the treatment that suggested dual ACE inhibitor and Angiotensin II receptor blocker. After 9 years of treatment, His creatinine dropped to 1.5 and persisted for six months. Regression of kidney disease is unheard of in diabetic nephropathy
My goal has always been to reverse disease as much as possible. In the early 2000s, I started working on peripheral neuropathy. I remember getting mason jars with liquid proteins, trying to help with neuropathy. A breakthrough came in approximately 2016. I had a patient who was a guard in the prison system with severe neuropathy below his knees, to the point that he was thinking about retiring. He wanted to go to the world’s expert, and I sent him only to come back with the prescription for gabapentin. At that time, I placed him on a homeopathic regimen for mitochondrial support by Desiret Biologic’s: Bio Cytotox Phase, Bio Co-Enzyme Phase, and Bio Glyoxal Phase. At the end of six months, his neuropathy had completely resolved; he actually advanced his career from being a guard and the person system to working at the state capital.
It was then that I realized the potential of treating mitochondrial dysfunction. The literature is now replete with articles suggesting that mitochondrial dysfunction is at the root of all chronic illnesses, and one of the tenets of anti-aging medicine is that we live as long as our mitochondrial number and function are intact.
Mitochondria produce adenosine triphosphate, or ATP, which supplies energy, and most people think of mitochondria as the powerhouse of the cell. However, mitochondria play numerous functions. They are being metabolic of coordinating catabolism and biosynthesis, are a source and regulator of reactive Oxygen species, central regulators of apoptosis (programmed cell death), Calcium homeostasis, fusion (maintains function, dilutes damage), and fission (facilitates mitophagy (clearing on damaged organelles). They maintain quality control and mitophagy (getting rid of damaged mitochondria). They play a key role in innate immunity and inflammation. They are essential for biosynthesis of factors and iron – sulfur clusters. They also help with regulation of cellular homeostasis and disease. Mitochondria are not just energy producers—they are regulatory organelles that integrate metabolism, redox balance, signaling, immunity, and cell fate.
The next topic is thyroid function. Thyroid hormone receptors are present in nearly all tissues of the body. Their abundance, distribution, and functional importance vary among cell types. Triiodothyronine (T3), the active form of thyroid hormone, influences a remarkably broad range of biologic processes, including mitochondrial function, energy production, expression, metabolic regulation, growth, and nervous system function. Optimal thyroid function is needed to achieve these benefits. It should also be noted that around 85% of thyroid disease is autoimmune thyroiditis. I have always said you need to treat the body that surrounds the thyroid, not just the thyroid numbers, to be successful in treating thyroid disease.
Inflammation is the next broad category. The chapter on autoimmunity is one of the two longest chapters in the book dealing with inflammation; it must be done in order again to be successful in treating patients. Nuclear Factor Kappa Beta (NF-κB) is the ultimate transcription factor stimulating inflammation and is formed in the cell in response to abnormal stimuli and goes to the nucleus to turn on genes to stimulate the inflammation pathways. Nuclear Regulatory Factor 2 (NRF2) is the transcription factor that is anti-inflammatory.
Gut barrier function and intestinal permeability are one of the next 12 steps. Intestinal permeability was highlighted by Doctor Alessio Fasano in his 2009 classical paper: Surprises from Celiac Disease: Study of a Potentially Food-Triggered Disease has uncovered a process that may contribute to many autoimmune disorders. Dr Alessio’s team is the group that found zonulin, which is now to be the gatekeeper of intestinal permeability. Intestinal permeability is now linked to most autoimmune diseases. Therefore, a thorough understanding of intestinal permeability is needed to address these issues.
Oxidative stress is an imbalance between the production of reactive oxygen and nitrogen species (ROS/RNS) and the capacity of antioxidant defense systems, leading to excess oxidants that can damage molecules and disrupt signaling. Oxidative stress can be implicated in numerous diseases, including cardiovascular disease, neurovascular disease, cancers, etc. Therefore, appropriate management and control of oxidative stress is indicated in disease.
Autoimmune disease is the next major section. The incidence of autoimmune disease has significantly increased in the last 30 years due to the environment and intestinal permeability. An understanding of autoimmune disease is needed in order to treat it effectively. Traditionally, loss of self-tolerance, molecular mimicry, and genetic susceptibility were thought to be the primary ideologies of autoimmune disease. However, this book brings in concepts such as mitochondrial control, redox buffering, autophagy, related debris clearance, and other topics. This expands the approach that one can take to autoimmune disease.
Autonomic dysfunction or imbalance in the sympathetic and parasympathetic nervous system has not traditionally been associated with many disorders; however, my research has shown that almost all chronic diseases can be associated with autonomic dysfunction, and therefore consideration of treatment, I think, should be undertaken. Common illnesses that this is associated with include diabetes with neuropathy, Parkinson’s disease, postural orthostatic tachycardia syndrome, and numerous others.
Metabolic regulation and disorders of this are widespread and growing in the population, as noted by the increasing incidence of diabetes mellitus. As noted in the book, there are wide-ranging abnormalities with diabetes, including intestinal permeability, oxidative stress, nutrient deficiencies, and one article even stated that type two diabetes mellitus is a disorder of mitochondria.
Nutritional status is again a widespread problem. Nutrients are needed as cofactors for multiple different enzyme systems. Our diet which is high in ultraprocessed foods predisposes us especially to nutrient deficiencies. These are discussed within the book as well.
Autophagy is a relatively new process as far as its understanding. The Nobel Prize in Medicine was awarded in 2016. This process is fundamental for degrading and recycling cellular components. It has been broken down according to the individual organelles, including mitochondria, mitophagy, and other cellular apparatus. This is reported to be beneficial for inflammatory disorders because it eliminates damaged organelles and helps maintain homeostasis.
The renin-angiotensin system is a process tightly controlled to blood pressure. However, it has now been noted to be a powerful pro-inflammatory mediator, specifically within rheumatoid arthritis, lupus, and multiple sclerosis. Expression of the angiotensin receptor has been noted in immune systems and implicated in several models of autoimmune diseases. There is also interaction with estrogen, thyroid, cortisol, and others.
The 12th step is endocrine balance. Much like thyroid, endocrine receptors are widespread throughout the body. As noted in the book, they play a role in mitochondrial function, energy regulation, new activation, and information, barrier function, detoxification, and biotransformation, cellular repair and regeneration, and others.
Finally, during my research for the book, I found a publication entitled Systems Medicine: the Future of Medical Genomics, Healthcare and Wellness from 2016, again, relatively new in the medical scene. Once I found this, I was able to do systems approach using AI with references from the literature on how to empirically approach many different illnesses. These are crossed between the 12 steps. I believe this summarizes the most important concepts of the book.
