Going Against the Norm: Treating Cancer as a Metabolic Disease

Submitted by Maureen Kroning, RN EdD

Tags: aging cancer cancer patients cancer risk chemotherapy metabolic metabolic disease oncology preventing cancer therapy treatment treatment options

Going Against the Norm: Treating Cancer as a Metabolic Disease

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Written by Jason Carhart, BSN and Maureen Kroning RN EdD

The current treatment for someone diagnosed with cancer is no longer acceptable. The focus needs to shift away from our standard treatments which so often causes pain as well as physical and emotional suffering. Emerging research about the body’s cellular metabolism provides new hope for cancer prevention and treatment. A number of mechanisms present in the human body are known to inhibit cancer cell growth by providing the body with an alternative fuel source, one that cancer cells cannot metabolize. For instance, induced ketosis offers a physiological means of regulating glucose metabolism in cancer patients while suppressing tumor metabolism and progression while ketone production significantly produces anti-cancer effects by shifting the body’s fuel source from a glucose dependency to one that is ketone based. Even while there remains controversy over the occurrence of many types of cancer, recent research has unveiled promising results towards cancer prevention and treatment. Emerging evidence indicates cancer is primarily a metabolic disease. According to Dana-Farber Cancer Institute (2014) research is being done to look at the connection between body weight, sugar intake, insulin levels and their correlation to cancer. Understanding the cellular metabolism of cancer is necessary in order to find preventative and holistic treatment modalities and for this to occur, a paradoxical shift in our current perception of cancer treatment is necessary.

Introduction

The American Cancer Society estimates that about 1,600 people per day will die from cancer in 2014. What happens from the time a person is diagnosed with a terminal cancer till the time they die if often unbearable to witness. Most of our current cancer treatments are extremely painful and known to have long term negative side effects on the patient’s health, psychosocial well-being, life expectancy. According to American Society of Clinical Oncology (ASCO) (2014) cancer treatments may have long lasting effects that vary depending on the cancer treatment. Furthermore, ASCO reports the adverse effects of cancer treatment include problems to a person’s: heart, lung, endocrine, bone, joint, soft tissue, learning, memory, dental, oral, vision, digestion, emotion, energy, and even secondary cancer development. It’s a wonder that just knowing how harmful current cancer treatments are and how it affects every culture, every socioeconomic group that we have yet to find alternative modalities to treat and prevent this disease. Perhaps, it is time to look at cancer more holistically and to begin to view cancer in a new light as a preventable and treatable metabolic disease.

Background

According to The American Cancer Society (2014) approximately 585,720 people will die from cancer this year. Not everyone diagnosed with cancer will die from the disease however; the treatments alone can have debilitating effects and can adversely affect every system in our bodies. There are many factors to consider when a patient is diagnosed with cancer such as: the type or origin of the cancer itself, the stage of the cancer, the treatment options and the survival rate and most of all how can we prevent these cancers from developing in the first place. It is estimated that for this year alone there will be an estimated 1,665,540 new cases of cancer diagnoses (ACS, 2014). For example, new breast cancer cases are estimated to be 235,030 this year alone and new cases of prostate cancer are estimated at 233,000. Each of these cancers have differences in their origin, treatment options and survival rates.

When looking at the survival rate of someone diagnosed with metastatic cancer, it is necessary to look at the location and aggressiveness of the tumor. For instance, metastatic breast cancer has a 27% survival rate after five years while in comparison, stage IV pancreatic cancer has a 1% survival rate (Gudena, Montero, & Gluck, 2008). Both cancers include harsh treatment modalities which are of extreme concern when research has proven that current treatment modalities damage healthy cells and can even fuel the cancer cells. According to YuSun, Campisi, Higano et al. (2012) chemotherapy used to treat prostate cancer can promote tumor cell survival and disease progression. The use of chemotherapy, a common treatment for the majority of cancers is known to damage healthy cells and can cause so many adverse effects that only cells that can survive the toxic effects of the chemotherapy are the cancer cells.

Chemotherapy often results in patients needing to spend more time in clinics and hospitals but in the long run it cannot cure their cancer (Span, 2012). According to the American Cancer Society (2014) chemotherapy causes normal cell damage and can adversely affect the cells of: hair follicles, digestive tract, respiratory tract, heart, kidneys, bladder, lungs and nervous system. There are other cancer treatments that are also known to cause harm to the body.

According to National Cancer Institute (NCI) (2014) radiation therapy will be used for approximately half of all patients diagnosed with cancer during their treatment course. The National Cancer Institute reports that even though radiation is effective in irradiating cancerous cells it can also can cell damage and death to normal healthy cells.

Depending on the body site radiated side effects of radiation therapy can include: hair loss, skin changes, mouth problems, trouble swallowing, nausea, vomiting fatigue, diarrhea, hair loss, sexual changes, swelling, as well as urinary and bladder changes (NCI). It is not uncommon for patients suffering with these often debilitating side effects for cancer treatments to have further medications prescribed to help alleviate and lessen the side effects but this can lead to potential for further cancer cell growth. For instance, nausea, a side effect of both chemotherapy and radiation is often treated with steroid medications which can markedly raise a person’s blood sugar level especially in diabetic patients which then creates a real problem since increased sugar levels have been linked to cancer growth (Grisham, 2013). It is time to think away from our current standard for cancer treatments and recognize holistic alternatives. A person’s individual cell metabolism and sugar intake are two areas of innovative research that currently is being done to help eradicate cancer development. “As each individual is a unique metabolic entity, personalization of metabolic therapy as a broad-based cancer treatment strategy will require fine-tuning to match the therapy to an individual’s unique physiology” (Seyfried, Flores, Poff & Agostino, 2014). However, we first need to look at how both the normal cell functions and its relationship to cancer cell production.

Cytology and Cancer

Research has shown that when a damaged nuclei from a cancer cell is transplanted into the cytoplasm of a healthy stem cell, proliferation of normal tissue and cells occur and vice versa when a healthy nucleus is transplanted into the cytoplasm of a cancer cell it results in either cell death or proliferation (Hochedlinger, et al., 2004; Seyfried & Shelton, 2010). Under normal circumstances, 89% of the total energy derived from the cell occurs in the mitochondria as a result of the electron transport chain and oxidative phosphorylation (OxPhos), which produces +36 adenosine triphosphate (ATP) (Vander Helden et al., 2009). Cancer cells have damaged mitochondria (specifically the cristae), which result in cristolysis and thus a malfunction in OxPhos production that requires a compensatory mechanism to derive resources for proliferation (Seyfried & Shelton, 2013). The cancer cell derives its main energy source through the process of glucose fermentation (Seyfried & Shelton 2013). In turn, malignant cells compensate for the lack of OxPhos and the subsequent energy deficit by up regulating insulin receptors, the expression of glycolytic enzymes as well as glucose transporters within the cell known as GLUT1 and GLUT3 (Klement & Kammerer, 2011). Cancer cells continue to ferment in the presence of oxygen, or aerobic glycolysis, a paradoxical energy producing metabolic pathway compared to healthy cells’ anaerobic glycolysis, a phenomenon known as the Warburg effect (Vander Heiden et al., 2009).

Dr. Otto Warburg, a noble prize winning scientist for his work in cancer research, has defined a theory of cancer cell metabolism called, “The Warburg Theory of Cancer” which is based on the malfunctioning mitochondria observed in all cases of tumor cells (Vander Heiden, Cantley, & Thompson, 2009; Seyfried, Flores, Poff, & D'Agostino, 2013). According to this theory cancer arises from damaged cellular respiration and glucose fermentation which gradually compensates for insufficient respiration and respiratory damage eventually becoming irreversible (Seyfried & Shelton, 2010; Vander Heiden et al., 2009). The process of fermentation is considerably less sufficient than the OxPhos pathway, so tumors will burn conceivably thirty times as much blood sugar as normal cells to meet the energy needs of the malignant organism (Taubes, 2008). What research suggests is the mitochondria can suppress the formation of cancer cells (Seyfried & Shelton, 2010). According to Razungles J., Cavailles V., Jalaquier S., & Teyssier C. (2013) “As a cause or a consequence of tumorgensis, the Warburg effect is now considered a promising therapeutic target in fighting against cancer.

The consumption of a high sugar diet compounded by the current standard of care is not only fueling cancer proliferation but also is sabotaging any hope for remission and complete cure for most cancer patients (Seyfried & Shelton, 2010).

Dietary Implications and Cancer

According to The United States Department of Agriculture (USDA) the average American consumes roughly 150 to 170 pounds of sugar per year; this includes glucose, sucrose, lactose and fructose (Regan, 2009). Less than 100 years ago, the average American consumed roughly 4 pounds in a given year (Regan, 2009). In addition, over the past thirty years, the influx of high sugar diets have subsequently correlated to a rise in health disparities even while total fat consumed in the diet has decreased (Lichtenstein, et al., 1998). Norris (2009) cited Dr. Robert Lustig, a pediatric neurocrinologist, as saying, “Sugar both drives fat storage and makes the brain think it is hungry setting up a “vicious cycle”. According to National Cancer Institute (2014) “Obesity is associated with increased risks of cancers of the esophagus, breast (postmenopausal), endometrium (the lining of the uterus), colon and rectum, kidney, pancreas, thyroid, gallbladder, and possibly other cancer types”. The American Institute for Cancer Research (2014) suggested that of the 12 most common cancers found in the US, a third are preventable by changing our diet which can be done by avoiding sugary drinks and limiting processed food that are high in added sugars. America is not the only country looking into the link between nutrition and cancer growth. In fact, the World Health Organization’s Internal Agency for Research on Cancer is working an international research study called, European Prospective Investigation into Cancer and Nutrition (EPIC) which is considered the largest research study ever to be conducted looking at the link between diet and cancer . The EPIC research study includes 10 countries and 500,000 subjects whose nutritional intake, including overall percentage of glycemic load, is recorded as well as all of all health records. The studies aim is to assess who will develop cancer and who will not and the role of nutrition plays in relationship to cancer risk.

We can no longer ignore the adverse effects of consuming high caloric and high glucose diets for research is confirming that our current diets can put us at an increased risk for cancer. The result of an unhealthy lifestyle has activated a breeding ground for metabolic illness, cancer growth, and subsequently death (Lustig, Schmidt, & Brindis, 2012). Let’s look at just how much both sugar and insulin are linked to cancer.

Sugar, Insulin and Cancer Risk

Glucose consumption from the diet promotes several hallmarks signs of cancer such as excessive proliferation, anti-apoptotic signaling, cell cycle progression, and angiogenesis (Klement & Kammerer, 2011). According to Dr. Sircus, Director International Medical Varitas Association, (2012) “Sugar and cancer are locked in a death grip yet oncologist often fail to do what’s necessary to stop their patients from feeding their cancers with sweets” (p.1). When malignant tissues were cultured in glucose containing mixtures there was a higher consumption of glucose by cancer tissues compared to that of healthy tissues found in both the muscle and liver (Klement & Kammerer, 2011). According to Hatzivassiliou, Zhao & Bauer et al. (2005) cancer is known for its glucose-dependent metabolism and adenosine triphosphate citrate lyase (ACL) is the key link between both glucose metabolism and lipid synthesis and may just be the molecular used for cancer therapy.

Further, when the body experiences metabolic stress ATP can be inhibited or accelerated which leads to AMP-activated Protein Kinase (AMPK) which acts as an “energy sensor” that plays a vital role in both cancer treatment and prevention (Fogarty & Hardie, 2010). When AMPK becomes activated it has the ability to work as “novel therapies for both metabolic disorders and for cancer which together constitute two of the most prevalent groups of diseases worldwide” (Fogarty & Hardie, 2010 p. 581). The good news is that with increased proliferation, the dependence of the cancer towards aerobic glycolysis makes the malignancy susceptible to glucose deprivation and starvation (Poff, Ari, Seyfried, & D'Agostino, 2013). Research has shown the dependence of cancer proliferation and sugar has been nullified when malignant cells are deprived of a steady supply of glucose (Magee, Potezny, Rofe, & Conyers, 1979; Poff et al., 2013; Seyfried et al., 2013).Just like glucose, insulin also plays a role in cancer development as well as cancer treatment and prevention.

According to Frasca, Pandini, Sciacca, Pezzino et al., insulin plays a significant role in cancer biology with the proof lying in several epidemiological studies which have shown increased insulin levels or hyeprinsulinaemia puts a person at increased risk for breast, prostate, colon and kidney cancer (2008). According to Johnson & Gale (2010) type 2 diabetics who are insulin dependent are more likely to develop cancer compared to those in the general populations and insulin are strongly associated with these cancers. When blood glucose levels are high, insulin will stimulate insulin-like growth factor (IGF) receptors and along its binding protein, IGFBP-3 which controls both growth and survival of cells and thought to be a vital component for increasing cancer risk and the development of tumor cells (Renechan, Zwahlen, Minder, O’Dweyer et al, 2004). Knowing that insulin plays a role in cancer development allows researchers to also look at the role of insulin for cancer treatment and prevention.

Renato Baserga, a medical researcher, from Thomas Jefferson University, stated, “Shutting down the IGF receptor in mice will lead to a strong inhibition, if not total suppression of tumor growth” (Taubes, 2008, p. 215). Increased levels of IGF are strongly linked to diabetic cancers, insulin resistance and obesity (Johnson & Gale, 2010). Research indicates, hyperinsulinaemia, is associated with insulin resistance and obesity and needs to be treated by “changes in life style and/or pharmacological approaches’ and insulin administration carefully monitored for increased cancer risk (Frasca, Pandini, Sciacca, Pezzino et al, 2008 p. 23). To win the war against cancer, it is necessary to recognize the correlation of both sugar and insulin on cancer risk and look for alternative therapeutic treatment modalities to treat and prevent cancer.

Therapeutic Treatment for Cancer Patients

Due to cancer’s affinity towards both sugar and insulin it is necessary to approach cancer therapy by finding an alternative fuel source that healthy cells can metabolize for energy and cancerous cells cannot. According to Seyfried, Flores, Poff & D’Agostino (2013) The key to managing cancer from growing and metastasizing is through transforming the entire body from fermentable metabolites such as glucose and glutamine to respiratory metabolites found in ketone bodies. The alternate fuel source of ketone bodies, are the byproduct of the liver’s ability to make energy molecules out of fatty acids through an evolutionary adaptation to calorie restriction. The liver, when depleted of glycogen reserves, under conditions of carbohydrate (CHO) restriction, will utilize glycerol. Glycerol is then mobilized by lipase in a process called lipolysis. Lipolysis is controlled by insulin, which inhibits its activity. Therefore, if insulin levels are high due to the constant state of CHO ingested in the diet, fat oxidation for fuel is blocked (Taubes, 2008). When a patient is provided with approximately two weeks of a therapeutic diet consisting of vitamins, minerals, electrolyte supplements and consuming less than 50 grams of CHO per day blood glucose levels decrease and ketone levels elevate which provides an alternative fuel source for healthy cells (Volek, et al., 2009).

For over 80 years, therapeutic ketogenic diets have been used in medical treatment primarily in the treatment of patients with refractory epilepsy (Gasior, Rogawski & Hartman, 2008). Research has also shown the ketogenic diet to be effective in the treatment of both Alzheimers and Parkinson’s disease as well as for treating traumatic brain injury and stroke (Gasior, Rogawski & Hartman, 2008). A study, funded by The Journal of the American College of Nutrition, placed two pediatric patients diagnosed with advanced malignant brain tumor on ketogenic diets supplemented with 60% medium chain triglyceride oil for eight weeks and found that both patients had a significant decrease in blood glucose, inversely effect of ketone levels and Postron Emission Tomography (PET) scans showed a 21.8% decrease in glucose uptake at the tumor site. The patients continued the ketogenic diet for an additional 12 months and remained free of disease progression while improving both their mood and motor skill development (Nebeling et al., 1995). Decrease blood glucose levels have been shown to be directly linked to cancer survival.

Emerging research has shown that dietary restriction of CHO along with a high fat diet, which lowers blood glucose and elevates blood ketone levels, puts the cancer in a vulnerable position by cutting off its fuel supply (Seyfried & Shelton, 2010). Cancer cells cannot metabolize ketone bodies due to their inherent mitochondrial dysfunction (Klement & Kammerer, 2011; Poff et al., 2013; Seyfried et al., 2013; Shaw & Cantley, 2012). During this time, healthy cells regulate insulin receptors due to the subsequent deprivation of glucose in the diet putting additional pressure on cancer cells (Seyfried & Shelton, 2010). When Metformin, an oral antidiabetic medication that suppresses glucose production, was used in patients with cancer, it improved their outcome by both prolonging life and decreased cancer diagnoseses (Franciosi et al., 2013). Further, “nutritional ketosis” is a benign metabolic state that gives the human metabolism the ability to be flexible under periods of starvation, such as famine. A ketogenic diet is therapeutic because the levels of ketones in the body never go above 3 millimolar (mM) due to the presence of insulin (Volek, et al., 2009).

Memorial Sloan-Kettering Cancer Center in New York’s President and Chief Executive Officer, Dr. Craig Thompson, discussed the connection between dietary intake of sugar and cancer growth and has even made this the focus of his cancer research. He stated, “I have eliminated sugar from my diet, and eat as little as I possibly can...sugar scares me”. If medical doctor, cancer specialist and the president of a world renowned cancer center states “sugar scares me” and his focus of his own research supports such statements and explains that sugar is the nutrient that initiates cells to divide and once this occurs “you are off to the races of initiating the formation of human cancer” (Grisham, 2013). As healthcare professionals it is essential that we advocate for the health of everyone and to educate people about the dangers of sugar and the prevention of cancer. In today’ fast paced world and fast food choices it is often hard to avoid sugar. According to Dr Robert Lustig, from the University Of California, San Francisco, the obesity epidemic is “a societal issue that puts the food-selling agenda of federal agencies and profit-seeking behavior of major corporations against public health needs” (Norris, 2009). The result of an unhealthy lifestyle has activated a breeding ground for metabolic illness, cancer growth, and subsequently death (Lustig, Schmidt, & Brindis, 2012). According to Rahib, Smith, Aizenberg et al. (2014) a concerted effort is needed by researchers and healthcare communities in order to make advancements in the prevention and treatment of cancer and to make significant changes in our present fight against cancer.

Conclusion

Research has shown that there are innovative nontoxic interventions, such as lowering blood glucose levels, limiting sugar intake and eating a ketogenic diet to both treat and prevent cancer. However, studies tell us that many patient are unaware of not only their prognosis but the alternative in treatment options. A questionnaire study was performed on 273 patients with a cancer diagnosis and found that more than half of the respondents were ill informed about prognosis, alternative treatments and the effects of cancer treatment on the body (Sainio & Eriksson, 2003). It is imperative that nurses understand the importance of current evidence based practices while pushing towards innovation and alternative therapies for both the treatment and prevention of cancer. Nurses are patient advocates and need to be at the forefront in the fight against cancer. As essential healthcare workers, it time to learn about current research on cancer prevention and treatment and in turn teach our patients, families and communities about the lifestyle changes needed to prevent cancer. It is our role as nurses to take note when a well renowned hospital president and CEO tells us that sugar scares him and he eats as little as possible. As nurses this should signal as a wakeup call so that we can begin to advocate for ourselves and the patients, families, communities and society that we care for.

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