Jamie-Lee James, RD (SA) 

Introduction 

Cancer is this century’s most prevalent worldwide noncommunicable disease. Claiming thousands of  lives daily, cancer is predicted to overtake heart disease as the leading cause of death in western  societies. Notwithstanding the monumental medical and technological advancements of our era,  cancer’s morbidity rates continue to increase. This leads us to a fundamental question: What is cancer  and why is it so pervasive today? It is only by understanding the biology of the condition and its  evolutionary paradigm that we can begin to develop effective strategies for its treatment and  prevention. 

This article discusses the underlying root causes of cancer and explains why addressing metabolic  dysfunction through ketogenic diet therapy, an overlooked area not embraced within mainstream  medicine, is paramount for the prevention and treatment of cancer. 

Cancer’s evolutionary paradigm: Cancer-diet connection 

It has become a commonly accepted belief that cancer is a predominantly genetic condition or simply  a result of bad luck. Over the last decade, however, many cancer researchers have started to question whether we in fact have more control over patient risk than initially thought. Present treatment  approaches are being re-evaluated, with the focus shifting towards non-toxic cancer therapy and  targeting common underlying metabolic malfunctions. 

Cancer has been traditionally understood to be rooted in our genetics; specifically, a genetic  predisposition to cancer (carrying the oncogene, for example) determines its course (1). However, this belief doesn’t hold up to scrutiny when we consider the fact that the world has witnessed an  exponential increase in cancer prevalence over the past century or so. Regrettably, it is clear from  yearly cancer death rates that most modern treatments, which are based on the genetic theory, are  unable to manage the disease without toxicity (2). 

A more accurate view attributes the rise in cancer prevalence to the increased global rate of sugar  consumption and, by extension, rising rates of type-2 diabetes (T2D). To elaborate, cancer rates began  to increase in industrialised nations in the late nineteenth century while, simultaneously, T2D rates  simultaneously began to rise; both increases were preceded by a rise in global sugar consumption (3). 

To argue that cancer is a modern disease, current and past evidence must be analysed comparatively.  Humans’ original, ancestral diet consisted of real whole-foods, devoid of refined sugar and ultra processed food (UPF), which are the norm today. For example, when analysing the populations of  England and Wales over a hundred-year span, it’s clear that cancer was extremely rare in the early  1800s, accounting for less than 3% of annual deaths (3). By the late 1900s, however, the figure had  climbed above 40% (3). Similar exponential increases can be observed in the vast majority of countries  influenced by western civilisation (3). 

From an evolutionary perspective, it’s evident that a deviation from our natural, species-specific diet  occurred over time due to shifts in the availability of the food sources to which modern humans are  best adapted. Our original, ancestral diet was predominantly animal-based; high in fat and protein, 

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and low in carbohydrates and sugar (3). Driven by the scarcity of large fat mammals that were hunted  into extinction, an alternate food source was needed (3). Enter the late 1800s’ agricultural and  industrial revolution, which fundamentally shaped what most people view as today’s ‘conventional  western diet’ (3). The revolution provided a solution: the cultivation of grains and cereals, which  replaced nutritionally complete, whole-food sources. This new diet consisted of mainly energy-dense  but nutrient-poor options, such as largely white-flour products, sugar, polished rice, vegetable fats and  preserved goods such as jams and canned food (3). More recently, our modern diet consists of UPF, most of which have been designed to be highly addictive and are thus detrimental to human health,  including refined sugar and industrial vegetable seed oils (3). 

As most readers will know, excessive sugar consumption can lead to T2D (3). Since persons with T2D  are insulin resistant, the connection between elevated blood-sugar concentrations and cancer should  be explored. Epidemiological evidence links excess levels of insulin in the blood (hyperinsulinaemia) with increased risk of both cancer incidence and death (3). Considering this fact, it’s logical to conclude  that our current diet hasfuelled the epidemic of chronic human diseases including, of course, T2D and 

obesity, but crucially also cancer (3). These chronic diseases are all driven ultimately by inflammation  and metabolic dysfunction, reflecting particularly high levels of insulin (3). This persistent  hyperinsulinemia would be expected in turn to play a role in cancer causation. 

Indeed, epidemiological evidence links excess sugar consumption with both incidence of and mortality  from colon, rectal, breast, ovarian, prostrate, kidney, nervous system, and testicular cancers (3). The  connection between high sugar consumption to obesity and hyperinsulinemia, reflecting high  inflammation levels, is directly responsible for the rise in rates of a variety of cancers in the developing  world (3). 

Cancer’s modern paradigm: Somatic mutation theory vs. metabolic theory 

According to Dr Thomas N. Seyfried, cancer is a systemic disease involving multiple time- and space dependant changes in the health status of cells and tissues that ultimately lead to neoplastic  (malignant) tumours (4). From a genetic standpoint, cancer is based on the ‘somatic mutation theory,’  which proposes that cancer cells are regulated by genes and DNA mutations cause cancer (4). Simply  put, if a mutation in the genetic code occurs, it amplifies the uncontrollable growth of tumour cells  (i.e., cancer). Most cancers have been treated on this basis using toxic anti-cancer therapy, regrettably  to the detriment of the patient’s health (5). 

Recent research challenging the somatic mutation theory, and offering an alternative non-toxic  approach to cancer treatment, has enhanced our understanding of cancer’s metabolic complexities.  These novel perspectives are rooted in metabolic science. Based on Otto Warburg’s central theory – coined the ‘Warburg effect’ – cancer is a mitochondrial metabolic disease whereby mitochondrial  damage causes fermentation to gradually replace respiration for cellular energy (5). It is a deregulated  form of energetics whereby cancer cells “switch” to a very inefficient method of cellular energy  generation, the glycolysis pathway, for their metabolic demands. Anaerobic fermentation is a glucose 

based metabolic process in which prime fermentable fuels, glucose and glutamine, are used as the  drivers for cancer growth (5). Glucose is converted to lactic acid, a byproduct of glycolysis, which  promotes inflammation and further favours the growth of tumour cells. Cancer cells are known to  carry extra insulin receptors on their cell surface due to their defective respiration, which demonstrates  a direct causal link between hyperinsulinaemia and cancer (5).

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Neoplastic cells within tumours cell are unlike normal cells. They share a unique underlying metabolic malfunction which is primarily characterised by rapid neoplastic growth, cell immortality, metastatic  ability and glucose metabolism via glycolysis, all of which promote the growth of cancer cells (5). All  cancers have the same metabolic demands to proliferate, and neoplastic cells share common  metabolic features. Therefore, it makes more sense to treat such commonalities rather than target  gene mutations. 

Therapeutic diet strategies which disrupt the metabolic pathways for cancer growth Ketogenic diet metabolic therapy: a promising anticancer intervention 

A ketogenic diet (KD) is an evidenced-based, effective, non-invasive and practical approach for the  treatment and prevention of cancer (4). Such a diet serves as a buffer (4) and an anti-inflammatory  approach to directly starve cancer cell growth (4). A ‘modifiable ketogenic diet’ (KD-M) incorporates principles of therapeutic carbohydrate restriction (TCR), but allows for a high degree of flexibility and  customisation in the development of macronutrient prescriptions. The primary goal of any well 

formulated ketogenic plan for cancer ultimately involves achieving a high level of nutritional ketosis. Practising a more rigid form of the diet is key to remain in ketosis. 

KDs target inflammation at the root by lowering circulatory blood levels of glucose and insulin. They  are low-carbohydrate high-fat (i.e., healthy fats) diets used to induce ketosis by effectively reducing  blood glucose concentrations while elevating ketone body concentrations. Ketones and fatty acids  become the main source of fuel for metabolism, allowing healthy cells’ mitochondria to use these non 

fermentable fuels, while starving cancer cells of their preferred fuel (glucose). 

Fasting is another well-known and long-existing therapeutic strategy to induce ketosis. It effectively allows patients to reach therapeutic targets quicker than typically achievable with a KD alone. If fasting  is deemed a contraindication, then a ‘restricted KD’ (KD-R) is recommended (6). A KD-R limits  carbohydrate intake to 20g net per day and restricts protein intake to between 1.0 and 1.4g / kg of  lean body mass per day (6). 

Cancer thrives in a high-glucose environment so the ketogenic diet aims to shut down the glucose arm  of the metabolic pathway supporting cancer growth by limiting fermentable fuels and inducing the  elevation of ketones (from ketosis). The restriction of fermentable fuels places tumour cells under  energy stress because such cells struggle to adapt and use ketones for energy when the supply of  glucose be restricted, thereby making the microenvironment unfavourable for the growth of tumour  cells (6). 

Press-pulse ketogenic metabolic therapy: a non-toxic cancer treatment 

Press-pulse therapy is a non-toxic therapeutic strategy which essentially aims to eradicate tumour cells  by placing stress on them and their microenvironment. This can be accomplished by therapeutic  fasting, a restrictive KD or a combination of both to achieve and maintain a therapeutic state of ketosis.  This creates chronic metabolic “stress” on the cancer cells. It is this energy stress which acts as the  ‘press’ disturbance; the ‘pulse’ disturbance is caused by the pharmacological agents or chemotherapy, which aim to reduce the availability of tumour-dependant fuels (glucose and glutamine). This  therapeutic strategy targets the fermentation metabolism, which is common in neoplastic tumour  cells, thereby gradually reducing tumour burden (7).

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The ultimate goal of press-pulse therapy is not to introduce toxicity but to transform the body  metabolically and manage cancer more effectively than current, toxic therapies. Knowing how to use KD effectively as well as how to use drugs or treatments that work synergistically with therapeutic  ketosis will lead to improved long-term management and eventual eradication of cancer. 

Fasting  

This physiological state enhances the efficacy of chemo and radiation, while simultaneously reducing  their side-effects (8). One of the primary benefits of fasting is the activation of autophagy, which only  occurs in the absence of food intake as the production of glucose and insulin is paused (9). Autophagy  is the automatic process through which the body cleanses itself of all its old, broken-down cells,  including cancer cells. Fasting encourages the body to enter a state of deeper ketosis; blood glucose concentrations are reduced, as are majorspikes when eating. Moreover, insulin secretion is minimised  due to little or no stimulation by caloric or carbohydrate intake. In effect, due to a reduction in the  availability of fermentable fuels and growth factors such as insulin, cancer cells become stressed and  starved, and begin to die off (8). 

Evidently, fasting can be utilised as an adjunct therapy to chemo to improve efficacy, reduce side effects  and improve outcomes and quality of life (8). Further metabolic pressure is placed on cancer cells by  fasting during and up to one day before and after each chemo treatment (8). A liquid fast consisting of  unsweetened beverages and/or a water-only fast has proven effective, and is best combined with a KD  during the non-fasting period (8). Liquid fasts should be overseen by a knowledgeable healthcare  professional. 

Conclusion  

In summary, it is clear that cancer is a modern disease which, prior to 1960, was considered rare. There  remains a direct causal link between cancer and metabolic abnormalities such as obesity, T2D and  insulin resistance. Among the treatment modalities, press-pulse therapy and KD have proved effective  therapies due to cancer’s selective metabolism of fermentable fuels (specifically, glucose and  glutamine), in conjunction with ketones’ non-fermentability. Furthermore, fasting causes additional  selective stress to cancers cells by reducing the availability of fermentable fuels and growth factors  such as insulin, thereby reducing inflammation. With cancer genetic research stagnating and  conventional treatments causing more harm than good, such alternative metabolic treatment  modalities offer a holistic and non-toxic approach to the treatment and prevention of cancer.

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Bibliography 

1. Fung J. The Evolving Paradigms of Cancer: What is Cancer. [Online].; 2022. Available from:  https://www.youtube.com/watch?v=2_hJzPQN3S0. 

2. Seyfried TN, Shelton LM. Nutrition & Metabolism. [Online].; 2010. Available from:  https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/1743-7075-7-7. 

3. Noakes TD. ‘Cancer as a modern disease’ in Ketogenic: The Science of Therapeutic Carbohydrate  Restriction in Human Health. 1st ed. Nutrition Network , editor. London: Elsevier Inc; 2023. Pages 976-1001. 

4. Seyfried TN, Mukherjee P, D’Agostino DP. ‘Cancer management using press-pulse ketogenic  metabolic therapy’ in Ketogenic: The Science of Therapeutic Carbohydrate Restriction in Human  Health. 1st ed. Nutrition Network , editor. London: Elsevier Inc; 2023. Pages1032-1054. 

5. Seyfried TN. Cancer as a Mitochondrial Metabolic Disease. [Online].; 2019. Available from:  https://www.youtube.com/watch?v=KusaU2taxow. 

6. Kalamian M. ‘Implementation of modifiable ketogenic diets in cancer’ in Ketogenic: The Science of  Therapeutic Carbohydrate Restriction in Human Health. 1st ed. Nutrition Network , editor.  London: Elsevier Inc; 2023. Pages 1054-1082. 

7. Seyfried TN. Press-Pulse – A Novel Strategy for the Metabolic Management of Cancer. [Online].;  2017. Available from: https://www.youtube.com/watch?v=9WFxjO3OHy0. 

8. Tettenborn M. ‘Fasting and chemotherapy’ in Ketogenic: The Science of Therapeutic Carbohydrate  Restriction in Human Health. 1st ed. Nutrition Network , editor. London: Elsevier Inc; 2023. Pages  1082-1090. 

9. Nolte M, Tettenborn M. Using Therapeutic Fasting and Keto to Starve Cancer. [Online].; 2022.  Available from: https://www.youtube.com/watch?v=RIXbPJmtQJs.