Holistic Cancer Treatment #2

Holistic cancer treatment #2


Aristotle said it first, the whole is greater than the sum of the parts. Christian Smutz brought the holism concept to the modern era with his book Holism and Revolution. This background was highlighted in greater detail in my previous post on Holistic cancer. The general concept is that the whole transcends the individual parts. Holistic medicine is a non-compartmentalized approach to healthcare. With less information, the ancients got it more right than the experts of today with significantly more information.


A holistic approach to cancer is no different. The holistic approach transcends all levels. A holistic approach to cancer is found in causation, testing, treatment, and in maintenance therapy. It is holistic in the whole sense of the word. This post will look at a holistic approach to some of the causes of cancer.


A holistic approach to the causes of cancer include:


  • Lifestyle
  • Epigenetics
  • Hypoxia
  • Inflammation
  • Mitochondria
  • Metabolic dysfunction
  • Voltage
  • Acid/Base balance
  • Redox
  • Tumor Microenvironment (TME)
  • Immune dysfunction
  • Hormones
  • Toxicants and detoxification dysfunction
  • Infection
  • The Gut
  • other associated deficiencies


There are and can be many more contributors, but this post is going to be long enough. To condense the quantity of information in this post, I will break up into a series of posts. I want to highlight each point in detail individually.




Conventional medicine continues to push denial on the connection between lifestyle, particularly diet and cancer. The science is precise on the matter. In contrast to the opinion often espoused by physicians, including conventional Oncologists, we are products of our collective environment, and it is our lifestyle choices that dictate much of our environment. No matter the denial, the evidence points to the contrary. What we put in our mouth effects cancer risk and cancer healing.


Our nutrition choices, or lack there of, can benefit the whole of the body or damage the whole of the body. Lifestyle can include diet, stress, sleep/wake cycles, relationships, exercise/activity level, weight, home, and many others. A recently published article highlighted the connection between diet and cancer [1]. In this study model, dietary choices increase the toxicity of chemotherapy up to 100 fold. The mechanism, by researchers at the University of Virginia, was found to be through the dietary alterations in the gut microbiome. I have often said that diet is love language, or not, with our DNA. This study shows that diet is the means to alter the gut microbiome to increase or possibly decrease chemotherapy toxicity. In essence, the lifestyle choice of what we put in our mouth lays the groundwork for toxicity from chemotherapy. So much for the idea that nutrition plays no role in cancer treatment. In fact, If doctors are telling patients with cancer to eat whatever they want, i.e. hamburgers, steak, sugar… they are in effect increasing the toxicity and morbidity of treatment in patients. Their is an important phrase that should be on the tongue of every physician—“first do no harm”.This study just focused on diet. This point doesn’t take into account all the other individual lifestyle choices, that don’t exist in a bubble, and their collective combination.






Epigenetics is an exciting new science that is making tremendous progress and promise in the treatment of dis-eases like cancer. Epigenetics means “above genetics”. The epigenome is the total number of modifications of the DNA (genome) in response to the environment (i.e., diet, stress…). This is the body’s attempt to regulate the activity and expression of all the genes (epigenetics) within the genome in response to its environment. While DNA is the different pieces of the puzzle that is the body, epigenetics is the directions for how those genes, the “pieces,” are used in response to the environment. This process of adaptation occurs throughout life. These adaptations are inheritable. These adaptations can be passed from generation to generation for generations. This inheritable epigenetic modifications is called Transgenerational Inheritance [2]. Epigenetic alterations can and will occur at any time, including conception, pregnancy, puberty, stress, and beyond. These are normal processes that take place throughout this existence we call life and control how a body changes and adapts to its environment. In addition to these normal processes, it is apparent that environmental factors and life events can affect each individual’s epigenome as well, which means you have a significant amount of control over your health now and your health potential in the future. Epigenetics brings each individual’s healing potential within their grasp.


Scientists are evaluating and testing new therapies that will use the epigenome to fight cancer. Just look at chemotherapy alone. Maximum tolerated chemotherapy is associated with significant, serious side effects.  Instead of using high doses of toxic chemotherapy to attack the cancer cells, patients in trials are receiving lower doses of medication as a result of epigenomic targeting, explicitly directed towards the cancer cells while bypassing healthy cells [3]. These patients are showing positive results and are suffering from fewer side effects from the treatments. Now there is a novel concept, target the cancer and not the patient.




Oxygen is essential to life on earth. Hypoxia is the lack of oxygen. Without oxygen, life in its current form would not exist. Hypoxia is present at the genesis of cancer—called carcinogenesis. As critical as oxygen is to life, the absence of oxygen is equally essential to the development of cancer. The whole body cannot be hypoxic, which equals no life. Instead, hypoxia is critical in the Tumor Microenvironment (TME). Hypoxia in the TME alters energy production via the Warburg effect. Hypoxia increases lactate production to increase the acidic environment that is so characteristic of the cancer TME. Hypoxia alters the immune system in the TME to protect and preserve the growing tumor from the immune system. All at the expense of the body. Beyond the driving force that is hypoxia in the genesis of cancer, hypoxia is the push to spread cancer. Hypoxia drives the production of blood vessel growth (angiogenesis) that is so critical to the physical cell escape in metastasis. Hypoxia is also essential in how cancer can escape the immune system, both locally and systemically, in metastasis.





Inflammation is the bed that cancer lies in. Inflammation is not de-facto the enemy of the body. That is an over-simplified view. Inflammation is in fact a critical, necessary component of the healing process. Just look at a paper cut. Immediately, the site is painful, red, swollen, and hot. These are the cardinal signs and symptoms of inflammation that prevent secondary infection and initiate the healing process. However, in the described setting of the paper cut, the inflammation subsides once the threat of secondary infection is gone and the healing process is in full motion. In cancer, inflammation does not turn off, but in fact, turns on the body. In many ways, cancer uses the immune system and inflammation signaling to co-opt the immune system against the body.


Cancer requires chronic inflammation, yet cancer stimulates the production of inflammation. Inflammation is a by-product of immune system signaling. Immune system signaling and inflammation can inhibit cancer initiation, growth, and spread. Likewise, Immune signaling and inflammation can promote cancer initiation, growth, and spread. In many ways, NF-kappaB sits at this crossroad of inflammation and cancer [4]. NF-kappaB is a key genetic transcription factor that stimulates inflammation in cancer to promote tumorigenesis [5]. Disordered immune function and Inflammation are present in the Tumor Microenviroment (TME) [6]. The inflammatory TME promotes NF-kappaB activation. It is the activation of NF-kappaB that further stimulates the production of inflammatory signals, called cytokines, that further increase pro-carcinogenic inflammation and even immune suppression. The result is dysfunction of the immune system, evasion of the immune system, and even suppression of the immune system, which leads to growth [7], survival [8], invasion and metastasis of cancer [9].



Inflammation is the bed that cancer lies in. Inflammation is not de-facto the enemy of the body and is an over-simplified view of inflammation. Inflammation is, in fact, a critical, necessary component of the healing process. Just look at a paper cut. Immediately, the site is painful, red, swollen, and hot. These are the cardinal signs and symptoms of inflammation that prevent secondary infection and initiate the healing process. However, in the described setting of the paper cut, the inflammation subsides once the threat of secondary infection is gone, and the healing process is in full motion. In cancer, inflammation does not turn off, but in fact, turns on the body. In many ways, cancer uses the immune system and inflammation signaling to co-opt the immune system against the body.


Cancer requires chronic inflammation, yet cancer stimulates the production of inflammation. Inflammation is a by-product of immune system signaling. Immune system signaling and inflammation can inhibit cancer initiation, growth, and spread. Likewise, Immune signaling and inflammation can promote cancer initiation, growth, and spread. In many ways, NF-kappaB sits at this crossroads of inflammation and cancer . NF-kappaB is a critical genetic transcription factor that stimulates inflammation in cancer to promote tumorigenesis . Disordered immune function and inflammation are present in the Tumor Microenvironment (TME) . Inflammatory TME promotes NF-kappaB activation. It is the activation of NF-kappaB that further stimulates the production of inflammatory signals, called cytokines that also increase pro-carcinogenic inflammation and even immune suppression. The result is the dysfunction of the immune system, evasion of the immune system, and even suppression of the immune system, which leads to growth , survival , invasion, and metastasis of cancer .





What is the meaning of life? Not from a spiritual perspective. Not from a psychological perspective, but ather, from a biochemistry perspective? Life is about energy—energy to heal, energy to repair, energy to fight infection. The capacity to produce energy is at the core of whether life exists or not. A body that can make energy efficiently can do all the things that are required to survive and thrive. A body that can not make energy does not thrive and does not survive. In fact, a cell that cannot make energy is targeted for destruction and recycling through the normal biochemical processes of apoptosis and autophagy.


Mitochondria are at the core of this biochemical life perspective. Mitochondria are the energy powerhouses of the cell. Mitochondria exist within ever cell, because every cell requires energy production to perform the day to day tasks required to survive. The energy production pathways of glycolysis, kreb’s cycle, and electron transport exist within mitochondria.


The question is which came first, the chicken or the egg? Does mitochondrial dysfunction initiate cancer or does the process of cancer initiate mitochondrial dysfunction? As in most cases, the answer is likely yes. Yes, mitochondrial dysfunciton initiates cancer and yes, cancer initiates mitochondrial dysfunction. Both have proven to be true [10]. The process of the biochemistry of cancer can not be viewed through the linear, one-dimensional sequence that we view biochemistry though. The scientific literature really leaves little evidence for any other conclusion but that cancer is the result of poor adaptation to metabolic stress in attempt for survival. In fact, cancer is the body’s attempt to adapt,

though this be a poor attempt, to an inhospitable environment for the purpose of survival. At the core of survival is energy production maintenance. In the short-term, this adaptation in energy production pays dividends for survival, but in the

long-term this adaptation leads to survival of very dysfunctional cells in what is known as

cancer. The mitochondrial defects often found in cancer are more often the result of massive metabolic dysfunction in an attempt for cell survival.



Metabolic dysfunction


“Complexity is the prodigy of the world. Simplicity is the sensation of the universe. Behind complexity, there is always simplicity to be revealed. Inside simplicity, there is always complexity to be discovered.”

Gang Yu


Cancer is a complex metabolic disease. As simple as this statement is to write, it does nothing to reveal the complexity that actually is cancer metabolism. Numerous research and medical journal publications have been published on this very topic. Even the top researcher on the topic, Dr. Thomas Seyfried entitled his 2010 paper and his 2012 book Cancer as a Metabolic Disease [11]. As prominent as these recent publications are, it all began with Dr. Otto

Warburg and his description of the aerobic glycolysis metabolism of cancer in the article On the Origins of Cancer [12] back in 1956—justly named “the Warburg effect”.


Dr. Warburg described the complexity of the metabolic changes in cancer in the simple—aerobic glycolysis. Let’s take a stroll back down the biochemistry memory lane. All cells must make energy to live. The cell’s complete pathway for energy production includes 3 separate, yet connected pathways: glycolysis, the Kreb’s cycle, and the electron transport chain. Energy production begins with glucose, amino acids, and/or fats.


The glycolysis pathway uses glucose as its sole source for energy production. In contrast, the Kreb’s cycle and the electron transport chain, can use amino acids and/or fats, in addition to glucose, as additional sources for energy production.


Aerobic glycolysis is the cancer cells use of glucose in the inefficient energy pathway of glycolysis under aerobic conditions. This use of glycolysis by cancer cells in the mismatched aerobic environment on face value is a paradox. Glycolysis should dominate in the presence of a low oxygen environment (anaerobic), instead of the oxygen rich environment (aerobic). The oxygen rich environment favors the more efficient energy pathway of oxidative phosphorylation (kreb’s cycle and the electron transport chain).


The paradoxical state of cancer cell metabolism, aerobic glycolysis, has been the debated dogma of cancer cell metabolism since its first description by Dr. Otto Warburg. This is the simple truth that lies behind the statement that cancer loves sugar. As in so many things, the story does not end there. Cancer Stem Cells (CSC) can use the building blocks of protein, amino acids, to drive energy production via the efficient oxidative phosphorylation metabolism pathway of energy production [13]. This amino acid driven oxidative phosphorylation has been shown to be the predominant cell metabolism in leukemia, brain, breast, and pancreatic cancer CSCs. Some cancer, i.e. triple negative breast cancer, types just prefer oxidative phosphorylation rather than Otto Warburg’s described anaerobic glycolysis [14]. I’ll take it one step further; cancer can even alter fat metabolism to support survival and spread [15].





The body is energy. Don’t doubt me. Just look at some of the tests that are so often used in medicine. The EKG measures the energy pattern output from the heart to look for damage to the heart in those individuals with suspected or known heart attack. The EEG measures the energy output from the brain to look for damage to the brain in those individuals with seizures. Even the basal body temperature can be used to assess the heat output to determine thyroid function. Heat is energy, thus it is measure the energy output by the thyroid through heat.


The cell is essentially a battery with stored energy potential. The energy potential is used for the cells to process its day to day activities that required to heal and survive. A cell without energy potential is a cell that will not heal and will die. This battery power potential of the cell  is stored in the polarization of the cell membrane. Remember the mitochondria is the energy powerhouse of the cell. The mitochondrial membrane polarization maintains and supports the cell membrane polarization. The loss of either will result in lost of healing potential.


It has been postulated that inflamed, damage cells have an approximate voltage of -20 mV. This is a state of low potential for healing. This compares to an optimal voltage of -50 to -70 mV. This is a high stored energy potential for healing. What about cancer? Cancer is just the opposite. The typical voltage of cancer is + 20 mV and higher. This is a state of no stored energy. The battery has no juice. Thus the reason for the altered energy production in cancer. No energy equals no healing.


Look at vitamin C and membrane potential of immune cells for the perfect example. Cancer and infections are low vitamin C states in the body. In actuality, cancer and infections deplete the body of vitamin C. Research in sepsis has shown this. Vitamin C maintains the mitochondrial membrane polarization, which maintains the cell membrane polarization. Low vitamin C leads to immune cell death, immune suppression, and immune paralysis—the perfect set up for cancer.



Acid/Base balance


Most have heard that there is a link between an acid environment and cancer. The concept is true, but the generalization is inaccurate. The entire body cannot be acidic. This would mean non-sustainability. We also know this as death. It is the Tumor Microenvironment that is acidic. Why? How is this possible? The cause, interestingly enough, is the altered metabolism so often described and found in cancer—aerobic glycolysis. This what Dr. Otto Warburg described all the way back in 1957. Not all cancer survives and thrives on the Warburg effect alone. In addition to the reliance on glucose in anaerobic glycolysis, cancer can use many different amino acids and fats. Got that. High protein and high fat does not eliminate cancer’s ability to survive. There is even the reverse Warburg effect. So little time.


The acid environment is localized to the Tumor Microenvironment because it is the result of the altered of hypoxia and cellular metabolism of cancer. The result is epigenetic modification to increase HIF-1alpha which increases lactate dehydrogenase activity through the up-regulation of pyruvate dehydrogenase kinase. Oversimplified, but the basics are true. After all, cancer is the epigenetic response to an inhospitable toxic environment. What?! The simple is that anaerobic glycolysis increases lactic acid production. Cancer cells then pump the lactic acid outside the cell which creates an acidic environment in the TME. This acidic TME actually creates a buffer zone that protects the growing tumor and its local environment from the immune system.


Alkalinity is important in the fight against cancer. However, the alkalinity of the TME is the target, not the entire body. One cannot alkalinize the entire body. Like acidity, this too would be unsustainable. The body works to buffer the extremes to maintain homeostasis. It is in the TME that this debate applies and rages.





Redox is short for reduction and oxidation. The foundation of redox is electrons. Going back aways…I know. Reduction is the process of gaining electrons. Oxidation is the process of losing electrons. In a very similar way, even connected, think of this redox balance as a buffering homeostasis mechanism used by the body.


The older, general thought was that increased Reactive Oxygen Species (ROS) were the result. This would then lead to oxidative stress or what I like to call cellular rust. The ideas is that oxidation requires a counter, a buffer if you will, to prevent unrepareable damage to cell structures, i.e. DNA, proteins, cell membranes… The imagery of cellular rust creates a good teaching picture. The knowledge of Reactive Nitrogen Species (RNS) and Reactive Sulphuric Species (RSS) expands the impact of redox. However, the thinking was only that redox was a negative process via the oxidation requiring reduction via detoxification.


Now, new discovery is changing the thinking around redox. More and more, the discussion is around redox potential as a necessary cellular process. Redox potential is a part of the internal cellular secondary messenger system. In essence, redox modifies internal signaling to create these secondary messengers via the addition or removal of electrons. Got that? Redox potential is key to cell communication, to cell healing potential, to cell survival potential, to cancer potential. No longer is this simply believed to be an oxidative, destructive process.


This is what I love about science and medicine: new questions beget new answers, new thoughts, this challenges entrenched paradigms, and breaks down walls of rigid thinking. Unfortunately, this creates new walls and paradigms which should lead to new questions. Science and medicine is for the curious mind. Unfortunately, curious minds need not apply in the current scientific, medical environment.



Tumor Microenvironment (TME)


The perfect example of new thinking through new discovery is the TME. Sounds kind of like the TMZ zone between North and South Korea, but similarity of sounds is as close as they come. The TME is an environment where tumor meets body. No longer can a cancerous tumor be said to be a solid ball of cells entirely walled off from the body. The TME is actually a transition zone between cancer and non-cancer. As much as the TME is key to cancer growth, the same TME is key to cancer suppression. “The outlook on cancer has changed dramatically and the tumor is no longer viewed as a bulk of malignant cancer cells, but rather as a complex tumor microenvironment (TME) that other subpopulations of cells corrupted by cancer cells get recruited into to form a self-sufficient biological structure. The stromal component of the tumor microenvironment is composed of multiple different cell types, such as cancer-associated fibroblasts, neutrophils, macrophages, regulatory T cells, myeloid-derived suppressor cells, natural killer cells, platelets and mast cells”.


The TME is not a singular process. Wherever circulating tumor cells (CTC) land and prosper, so is created a TME. Just as there are millions of cancer cells in a primary tumor, and just as there are millions of circulating tumor cells released from the primary tumor, so are there likely millions of TME. It is simply an interaction zone between a collection of tumor cells and the body. It is the front lines. It is the battleground of acid/base, redox potential, ROS, immune system activity, altered cellular metabolism…



Immune dysfunction


There are 2 answers to cancer: the prevention of cancer and the immune system. The first and best answer is always to never get cancer. However, if cancer occurs, the best answer to cancer is not found in a drug, in a surgery, or in radiation… The answer is the immune system—the already present, though dysfunctional immune system. The immune system is the inherent, created defense system designed to protect the body from all invaders, foreign and/or domestic. Foreign invaders would be virus’, bacteria, parasites… Cancer falls in the domestic category. Dysfunction and suppression of the immune system is key to cancer survival, growth, spread, and metastasis. Equally important, the support and targeting of the immune system is a significant answer to the many questions that is cancer.


Though cancer is an adaptation to its environment for the purpose of survival, cancer manipulates the local environment to further its survival. For cancer to survive and thrive:


  • cancer must change the tumor microenvironment (TME)
  • undergo epithelial to mesenchymal change
  • invade locally
  • avoid apoptosis (programmed cell death)
  • change genetic expression (epigenetics)
  • get mobile
  • recruit lymphatics (lymphagenesis)
  • recruit vascular supply (angiogenesis)
  • intravasate
  • disseminate
  • extravasate
  • escape the primary tumor
  • escape the immune system
  • metastasize


As important as these steps are, immune suppression and immune escape are critical to tumor survival locally and its spread systemically.





I have written so much about hormones over the years. I recently have reviewed some of these older posts and ugh. Thank goodness, skills can be cultivated and improved over time.


So much can be said about hormones: hormones are signals, hormones are a language, hormones are a means of communication, hormones are metabolites, hormones can be toxins… The old, overused cliche still works best—hormones are best when working together in symphony. Men are not just testosterone, no more than women are just estrogen. It is amazing how long that marketing bit has stucked. There was a marketing slogan for awhile, “know your number”…as if we health was simply a number of a hormone. So factually and intellectually dishonest.  Hormones symphony requires:


  • proper hormone evaluation
  • knowledge of hormone levels
  • hormone balance
  • knowledge of hormone metabolites
  • hormone receptors
  • knowledge of outside influences
  • physiologic hormone therapy if required


Hormone metabolites are the often overlooked and are the most under appreciated perspective of hormones. Yet, they can be the most impactful from a cancer perspective. Hormones are much more than just “know your number”, high or low. In many cases in patients with cancer, what the body is doing with the hormones through metabolism is the problem. Actual estrogen levels can be low in ER+ breast cancer, but the metabolism of estrogens produces metabolites that are even more estrogenic than the parent compound itself.


The general call is that all progesterone is safe in women with breast cancer. From a hormone metabolite perspective, irrespective of the PR status, that could not be further from the truth. If a woman has dominant 5-alpha reductase enzyme activity, then the resulting progesterone metabolites can actually increase breast cancer risk through the production of 5alpha-pregnane metabolites. But, if the 4-pregnenes are the dominant progesterone metabolite pathway, then progesterone does appear to reduce breast cancer risk.


Toxicants and detoxification dysfunction


Toxins and Toxicants are words often used interchangeably. However, they are not the same. Toxins are something the body produces. Toxicants are something the body is exposed to. Toxins are endogenous and toxicants are exogenous. According to Merriam-Webster, Toxins are “a poisonous substance that is a specific product of the metabolic activities of a living organism and is usually very unstable, notably toxic…”. Hormone metabolites can be the perfect example of an endogenous toxin. The estrone metabolite, 2-OH estrone, damages DNA, has a high affinity for estrogen receptors, and increases cancer risk. Endotoxins, such as LPS, produced from bacteria in the gut are also another example of an endogenous toxin that can increase recurrence and metastatic risk through the upregulation of TLR-4. This has even been shown to be one of the mechanisms by which chemotherapy causes metastasis. You did read that right. Chemotherapy, just like radiation and surgery, can cause metastasis of the very cancer it is intended to treat.


In contrast, toxicants are an exogenous toxic substance. There are many examples to choose from here. Politics, both left and right, need not corrupt this. Mycotoxins (fungal toxins), heavy metals, pesticides… are all examples of toxicants. The interesting thing about toxicants is that they don’t just damage DNA and compromise detoxification to contribute to cancer, many of them can hormonal. The heavy metal cadmium (Cd), is referred to as a metalloestrogen due to its high estrogenic activity. Mycotoxins are also very estrogenic. So, in ER+ breast cancer patients, I have seen estrogen levels low, yet estrogenic mycotoxins or cadmium are significantly elevated. That is a holistic approach to toxins, toxicants, and detoxification.




Infections include viruses, bacteria, parasites, and fungi. Infections involving bacteria, viruses, and parasites have been linked to cancer for years. The most common link is between the virus and cancer. It is estimated that 15% of cancers are caused by viruses. Common viruses implicated in cancer include the Epstein-Barr virus (EBV) in lymphomas, stomach and nasopharyngeal cancer, Human Papilloma virus (HPV) in certain head and neck, cervical, penile, vaginal, and rectal cancers, hepatitis B and C (HBV, HCV) in liver cancer, HIV in cervical cancer, Karposi sarcoma, and non-Hodgkin’s lymphoma, Human T-lymphotrophic virus-1 (HTLV-1) in leukemia and lymphoma…


Parasites are not as common in the U.S. as in other parts of the world. As a result, the connection between parasites and cancer is often over-looked.  Despite the oversight, the link between parasites and cancer is strong. The most common link is with the fluke parasites. The liver flukes, Opisthorchis viverrini and Clonorchis sinensis, can cause cholangiocarcinoma. The  blood flukes are not to be left overshadowed. These flukes include Schistosoma japonicum, Schistosoma mansoni, and Schistosoma haematobium. Schistosoma haematobium can cause bladder cancer, but also has been implicated in other adenocarcinomas and squamous cell carcinomas. Schistosoma japonicum can cause colorectal and squamous cell cancer. Schistosoma mansoni can cause liver and colorectal cancer. Plasmodium falciparum, one of the causes of malaria, is linked to the development of Burkett’s lymphoma. Even tapeworms are implicated in human cancer [16].


Don’t forget about the link between bacteria and cancer. Helicobacter pylori is the bacteria that can cause stomach ulcers. Now, the presence of Helicobacter pylori is linked to the development of stomach cancer and lymphoma. That doesn’t even include the connection between the bacteria in the gut microbiome and cancer.



The Gut


Could this be where it all begins? Could the gut environment, including the gut microbiome be key in the development of cancer and key in the future of cancer treatment? Could diet influence healing versus dis-ease potential through its effects on the gut? Research is early here, but the sunrise view is looking like yes.


A recent study on the idea found that diet does influence the toxicity potential of chemotherapy by up to 100 fold [17]. The mechanism is through the alteration of the gut microbiome. Now, this was just a human gut microbiome model in earthworms, but the implications are enormous. If diet increases chemotherapy toxicity through the gut microbiome, then it makes sense that the opposite can be true. Of course, this connection is known [18]. Simple stated, diet is the first treatment that dictates treatment toxicity and likely treatment response. Of course, the same would apply to health versus dis-ease potential.


We really are at a Galileo threshold moment. The evidence is leading away from the old paradigm. Whether because of willful or un-willful ignorance, there will be those that ignorant resistance. The historical perspective has been to look at the solid tumor as the problem. Maybe that is a distraction…that is a diversion. The diet, the gut microbiome, the immune system, the TME, and their interrelated connections is the actual frontier in the fight against cancer and for healing.


Another study highlights the link between the gut, inflammation, and cancer. In this study, the gut microbiome in the presence a leaky gut results in an increase in LPS endotoxins (gram negative bacterial toxin) that increases TLR4 expression in colorectal cancer to increase growth signaling through a very important and heavily utilized cancer growth pathway, the Akt/PI3k/mTOR pathway, to increase liver metastasis [19]. Bam! This comes as no surprise as the same TLR4 receptor is the mechanism by which surgery causes recurrence and metastasis via increase in NF-kappaB signaling [20],  LPS borne out of the altered gut microbiome and leaky gut has been shown to cause insulin resistance and diabetes. This has direct connection between Diet—>LPS—>TLR4—>cancer is found in prostate cancer also [21].


Other associated deficiencies


Cancer is a dis-ease of many different deficiencies. These deficiencies include vitamins and minerals. Cancer is a vitamin C deficient state [22]. Cancer is a Vitamin D deficient state [23] [24]. Cancer is a Vitamin A deficient state [25] [26]. Finally, cancer also is a state of zinc [27] [28] and selenium [29] [30] deficiency.  All these deficiencies contribute to compromise of the immune system which favors the cancer immune escape (link) that is so critical to cancer survival and spread.





Holistic approach to causation



—fuel type and car analogy

—exercise/physical activity




—evolving understanding of genetic involvement

—result of and then change in function; not really cause as previously thought

—“Cancer initiation and progression are accompanied by profound changes in                                                      DNA methylation that were the first epigenetic alterations identified in                                                      cancer”

—Tumor Suppressor Genes (p53, p21)

—“hypermethylation increases tumorigenesis by silencing tumor                                                                                     suppressor genes”


—“hypomethylation increases genomic instability and activates proto-                                                               oncogenes”


1) Oxygen

  1. A) where it all begins
  2. B) Essence of life
  3. C) Where cancer begins

2) hypoxia

  1. A) the beginning of cancer
  2. i) where it all begins
  3. ii) adaptation to survive
  4. B) Body
  5. i) short-term survival advantage
  6. ii) long-term survival disadvantage

iii) how hypoxia develops

  1. iv) hypoxia impact on cancer

1) initiation

2) progression


—the bed in which cancer lies


—metabolic dysfunction

—Warburg effect

—Sacrifice efficiency in energy production for speed of energy production

—Glycolytic dominant


—more thought to be the root cause

—altered/damaged energy production promotes adaptation


—result of altered mitochondrial function

—altered polarization of mitochondrial membrane

—altered polarization of cell membrane

—+/- apoptosis

—cancer vs immune cells


—clarity on acidity and cancer


—manifestation of metabolic alteration

—leads to immune dysfunction in TME


—define reduction vs oxidation

—contribution to cancer

—As an example, vitamin C at the core


—new paradigm thinking in cancer

—key interaction point between tumor and its environment with body and its                                                    separate environment

—Immune dysfunction

—altered TME

—M2 polarization




—all hormones

—hormone receptors

—hormone metabolites

—don’t forget neurotransmitters (very similar to hormones)

—toxicants and detoxification compromise

—toxins versus toxicants

—heavy metals

—environmental toxins



—15% of all cancers





—liver flukes



—altered immune system

—systemic inflammation


—Associated deficiences

—vitamin C

—vitamin A

—vitamin D




—leaving out other points that are known contributors

—leaving out other points that are unknown contributors


Holistic approach to testing

Holistic approach to treatment






Holistic approach to maintenance

[1] Ke W, Saba JA, Yao C et al. Dietary serine-microbiota interaction enhances chemotherapeutic toxicity without altering drug conversion. Nat Commun 11, 2587 (2020). https://doi.org/10.1038/s41467-020-16220-w

[2] Bošković A, Rando OJ. Transgenerational Epigenetic Inheritance. Annual Review of Genetics. Nov 2018;52:21-41. https://doi.org/10.1146/annurev-genet-120417-031404

[3] Chan TS, Hsu CC, Pai VC, et al. Metronomic chemotherapy prevents therapy-induced stromal activation and induction of tumor-initiating cells. J Exp Med. 2016;213(13):2967-2988. doi:10.1084/jem.20151665

[4] Karin M. NF-kappaB as a critical link between inflammation and cancer. Cold Spring Harb Perspect Biol. 2009;1(5):a000141. doi:10.1101/cshperspect.a000141

[5] Hagemann T, Lawrence T, McNeish I, Charles KA, Kulbe H, Thompson RG, Robinson SC, Balkwill FR. “Re-educating” tumor-associated macrophages by targeting NF-kappaB. J Exp Med. 2008;205:1261–1268. doi: 10.1084/jem.20080108.

[6] Mantovani A. Molecular pathways linking inflammation and cancer. Curr Mol Med. 2010;10:369–373. doi: 10.2174/156652410791316968.

[7] Joyce D, Albanese C, Steer J, Fu M, Bouzahzah B, Pestell RG 2001. NF-κB and cell-cycle regulation: The cyclin connection. Cytokine Growth Factor Rev 12:73–90

[8] Liu ZG, Hsu H, Goeddel DV, Karin M 1996. Dissection of TNF receptor 1 effector functions: JNK activation is not linked to apoptosis while NF-κB activation prevents cell death. Cell 87:565–576

[9] Huang S, Pettaway CA, Uehara H, Bucana CD, Fidler IJ 2001. Blockade of NF-κB activity in human prostate cancer cells is associated with suppression of angiogenesis, invasion, and metastasis. Oncogene 20:4188–4197

[10] Senyilmaz D, Teleman AA. Chicken or the egg: Warburg effect and mitochondrial dysfunction. F1000Prime Rep. 2015;7:41. Published 2015 Apr 2. doi:10.12703/P7-41

[11] Seyfried, T.N., Shelton, L.M. Cancer as a metabolic disease. Nutr Metab (Lond) 7, 7 (2010). https://doi.org/10.1186/1743-7075-7-7

[12] Warburg O. On the Origins of Cancer Cells. Science. Feb 1956;123(3191):309-314.

[13] Jones CL, Stevens BM, D’Alessandro A, et al. Inhibition of Amino Acid Metabolism Selectively Targets Human Leukemia Stem Cells [published correction appears in Cancer Cell. 2019 Feb 11;35(2):333-335]. Cancer Cell. 2018;34(5):724‐740.e4. doi:10.1016/j.ccell.2018.10.005

[14] Lee KM, Giltnane JM, Balko JM, et al. MYC and MCL1 Cooperatively Promote Chemotherapy-Resistant Breast Cancer Stem Cells via Regulation of Mitochondrial Oxidative Phosphorylation. Cell Metab. 2017;26(4):633‐647.e7. doi:10.1016/j.cmet.2017.09.009

[15] Munir, R., Lisec, J., Swinnen, J.V. et al. Lipid metabolism in cancer cells under metabolic stress. Br J Cancer 120, 1090–1098 (2019). https://doi.org/10.1038/s41416-019-0451-4

[16] Muehlenbachs A, Bhatnagar J, Agudelo CA, et al. Malignant Transformation of Hymenolepis nana in a Human Host. N Engl J Med. 2015;373(19):1845‐1852. doi:10.1056/NEJMoa1505892

[17] Ke, W., Saba, J.A., Yao, C. et al. Dietary serine-microbiota interaction enhances chemotherapeutic toxicity without altering drug conversion. Nat Commun 11, 2587 (2020). https://doi.org/10.1038/s41467-020-16220-w

[18] Alexander, J., Wilson, I., Teare, J. et al. Gut microbiota modulation of chemotherapy efficacy and toxicity. Nat Rev Gastroenterol Hepatol 14, 356–365 (2017). https://doi.org/10.1038/nrgastro.2017.20

[19] Hsu RYC, Chan CHF, Spicer JD, Rousseau MC, Giannias B, Rousseau S, Ferri LE. LPS-Induced TLR4 Signaling in Human Colorectal Cancer Cells Increases β1 Integrin-Mediated Cell Adhesion and Liver Metastasis. Cancer Res. March 2011;71(5):1989-1998; DOI: 10.1158/0008-5472.CAN-10-2833

[20] O’Leary DP, Bhatt L, Woolley JF, et al. TLR-4 signalling accelerates colon cancer cell adhesion via NF-κB mediated transcriptional up-regulation of Nox-1. PLoS One. 2012;7(10):e44176. doi:10.1371/journal.pone.0044176

[21] Parsons JK, Zahrieh D, Mohler JL, et al. Effect of a Behavioral Intervention to Increase Vegetable Consumption on Cancer Progression Among Men With Early-Stage Prostate Cancer: The MEAL Randomized Clinical Trial. JAMA. 2020;323(2):140‐148. doi:10.1001/jama.2019.20207

[22] Maryland CR, Bennett MI, Allan K. Vitamin C deficiency in cancer patients. Palliative Medicine. Jan 2005;19(1):17-20. https://doi.org/10.1191%2F0269216305pm970oa

[23] Young MRI, Xiong Y. Influence of vitamin D on cancer risk and treatment: Why the variability?. Trends Cancer Res. 2018;13:43‐53.

[24] Dev R, Del Fabbro E, Schwartz GG, et al. Preliminary report: vitamin D deficiency in advanced cancer patients with symptoms of fatigue or anorexia. Oncologist. 2011;16(11):1637‐1641. doi:10.1634/theoncologist.2011-0151

[25] Doldo E, Costanza G, Agostinelli S, et al. Vitamin A, cancer treatment and prevention: the new role of cellular retinol binding proteins. Biomed Res Int. 2015;2015:624627. doi:10.1155/2015/624627

[26] Niles R. M. Signaling pathways in retinoid chemoprevention and treatment of cancer. Mutation Research. 2004;555(1-2):81–96. doi: 10.1016/j.mrfmmm.2004.05.020.

[27] Prasad AS, Beck FW, Snell DC, Kucuk O. Zinc in cancer prevention. Nutr Cancer. 2009;61(6):879‐887. doi:10.1080/01635580903285122

[28] Dhawan DK, Chadha VD. Zinc: a promising agent in dietary chemoprevention of cancer. Indian J Med Res. 2010;132(6):676‐682.

[29] Hughes DJ et al. Prediagnostic selenium status and hepatobiliary cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort. The American Journal of Clinical Nutrition, Volume 104, Issue 2, August 2016, Pages 406–414, https://doi.org/10.3945/ajcn.116.131672

[30] Hughes DJ, Fedirko V, Jenab M, et al. Selenium status is associated with colorectal cancer risk in the European prospective investigation of cancer and nutrition cohort. Int J Cancer. 2015;136(5):1149‐1161. doi:10.1002/ijc.29071

About Dr. Nathan Goodyear
About Dr. Nathan Goodyear

Dr. Nathan Goodyear, a medical doctor with years of experience in the field of integrative cancer care, has announced the launch of an online training program. This program, available on his new website, will provide individuals with access to video trainings led by Dr. Goodyear himself, covering a range of topics related to integrative cancer care. These trainings will include information on the latest research and techniques in the field, as well as guidance on how to incorporate these approaches into a patient’s overall cancer treatment plan. With this online program, Dr. Goodyear hopes to make his expertise and knowledge more widely accessible, and help more people understand the benefits of integrative cancer care.


Leave a Comment

Your email address will not be published. Required fields are marked *

Skip to content