Demystifying Fasting and Cancer

All faiths across the globe different faith from Zoroastrians, Buddhism, Christianity, Islam, Judaism, Taoism, Jainism, and Hinduism advocate fasting. Fasting is definitely helpful for health and longevity. Social media is abuzz with Fasting and how it treats cancer. There is a sudden surge of colloquial and rudimentary messages on health. Often, these are relied with credence when it comes especially from revered spiritual leaders. One such message is from Sadhguru, a highly respected spiritual leader. In this video, Sadhguru is talking about the ubiquitously presence of cancer cells in our body. To deter the spread of these cancerous cells, he is recommending fasting.

First and foremost, we need to visit the definition of cancer cells. A key characteristic of cancer cell is uncontrolled growth of cells that have accumulated genetic changes (mutations) due to a carcinogen (a cancer causing agent). Second, cancer cells are not goondas that collect in one place as they advance. In fact, as the cancer stage advances these cells spread across their site of origin. Third, fasting is helpful only in select cases, not every cancer. Also, fasting is helpful beyond cancer, however it depends upon the state of metabolism, activities, age, at the least.

While we need people like Sadhguru to bring the social transformation, we definitely want these messengers to provide a solid rationale that is resting on scientific pedestals, devoid of which we will create confusion and loss of credibility. In this article, I have provided a scientific rationale for understanding the causes of cancer and if fasting can help stop the development or progression of cancer.

Words 2492, reading time 9 – 12 minutes. Background in Medicine helpful.

This 2.34-minute video from Sadhguru is truly insightful.  In the below article, I provided the rationale for reconciling scientific understanding of Cancer and Diet with those Vedic practices that are proposed by Sadhguru. More importantly, scientific literature provides a mixed body of the rationale for dietary practice for cancer prevention and or treatment. To rephrase, dietary restrictions can be a feasible option for select cancers, NOT ALL the types of cancer.

I got this video from Singapore, from a good colleague with whom I worked several years ago. With deep respect and reverence to Sadhguru. I listened to this video wherein Sadhguru talked about cancer as –

1) Always present within the body and get stimulated because of stimulants and intoxication.

2) They get organized into one place and later become overwhelming for the body to counter.

3) That these cancer cells consume 27-28 times the normal calories.

His solution according to Yogic culture is –

1) Spacing meals 8 – 12 hours a day

2) Fasting once or twice a month

It immediately drew my attention to the landmark paper by Hanahan and Weinberg, in which the authors talked about ‘The Hallmark of Cancer”. As an Oncology fellow, I remember having read it at least 2-3 times as it was foundational and disruptive in 2000.

As undergraduates, we were tutored on the existence of Oncogenes (1970) and Tumor Suppressor Genes (1986) and Knudson’s two-hit hypothesis (1971). Then, it might have not had such a reminiscent influence on my mind, until I started my post-graduation in pathology. However, Hanahan and Wienberg’s paper was a step ahead in explaining the different pathways for cancer. It served me when I lead the exploratory search for the epigenetics (methylation of TSG) and downregulation of several caspases (genes) in the apoptotic pathway.

I was definitely perplexed when I read the version of Sadhguru on the existence and or progression of cancer for several reasons –

 

  1. I mentioned the key developments in cancer as a stepwise accumulation of mutations in the genes of the cancer cell. These mutations occur due to several factors called carcinogens – viruses, chemicals, hormones, persistent inflammation, UV radiations, etc. We also know that cancer can occur de novo due to improper repair mechanism or existence of germline mutation (mutation inherited from parents). However, stimulants and intoxicants (especially the former), are definitely not carcinogenic and intoxicants like alcohol are considered co-carcinogens, not directly implicated in the development of cancer causation. I especially exclude the 300 plus carcinogens found in cigarettes as a stimulant and include nicotine as the stimulant, which is not a carcinogen, as proven by ‘comet assay’.

I realized, like thousands of other researchers across the globe, that tumorigenesis is a multi-step process and follows a multistep pathway. Germline mutations (those acquired from parents) like BRCA1, BRCA2 or RB genes occur in hereditary cancers. We can call these as existing in all cells in folks who inherit them from parents. However, the percentage of germline mutations are minuscule, possibly representing less one percent of the population. For these hereditary acquired cancers, one single hit drives a normal cell towards cancer progression. Where, in a normal population, any mutation has to hit two times to drive the cells to cancer progression. This Two hit hypothesis was proposed by Knudson in 1971 and is the underlying mechanism for most genetic aberrations occurring in a normal population. Of note, cancer cells do not exist universally in our bodies unless those are inherited from our parents (a less than 1% probability).

TSG and Cancer

 

  1. Though we know that cancer cells consume most of the host nutrition, it is hard to believe that these (cancer) cells organize (like gangs of Goondas) and rob the body of the nutrition. In fact, it is the other way around. Cancer cachexia, a state common in terminal cancer, is primarily due to diversion of nutrition towards metastasized (spread out) cancer cells, not when they come together.

 

  1. The solution offered by Sadhguru, that we should fast at least once or twice to avoid cancer is so much inadequate if not wrong,  as we all know that those who fast frequently have cancer and those obese who are voracious eaters don’t necessarily have cancer (but other metabolic diseases).

 

I specifically mentioned ‘The Hallmark of Cancer” that was published in 2000. This paper made a major stride in advancing our understanding of cancer (the paper was revised by Hanahan and Weinberg in 2011). It is worth revisiting the 6 facets of the hallmark in the above illustration.

678db3d930094d45ecba7ebdfa6b29b0

 

Warburg Effect

Recently, a debate is intensifying on the existence of the mechanism of cancer causation other than carcinogen-induced genetic abnormalities. Immune modification and metabolic abnormalities have also been implicated. The later is called the Warburg effect. Warburg effect proposes that the cancer cells metabolize via the glycolytic pathway even in the presence of aerobic state instead of the much more efficient oxidative phosphorylation pathway.

Let us understand two aspects –

1) Does fasting help the initiation of cancer and

2) Once established and or advanced, will fasting help cancer to regress and or get into control?

Does fasting help cancer?

Recent Geroscience literature reveals that cancer and aging are characterized by dysregulated metabolism consisting of upregulation of glycolysis and down-modulation of oxidative phosphorylation. Based on the research on Geriatric patients, metabolic interventions have been explored as promising strategies to promote longevity and to prevent or delay age-related disorders including cancer.

Will fasting help regression and or control of Cancer?

Select metabolic intervention approaches include chronic calorie restriction, periodic fasting/ fasting-mimicking diets, and pharmacological interventions mimicking calorie restriction.  These are considered as adjuvant anticancer strategies, not the mainstay of cancer therapeutics. By adjuvant, I mean they are supplemented along with standard cancer therapy (chemotherapy, radiation, and targeted therapy). However, to summarize, calorie restriction is subjective and second, where it is effective, it has an adjuvant effect.

Animal studies (in rodents) have shown that chronic caloric restriction reduces and delays cancer incidence, and inhibits tumor progression and metastasis. Also, there is mounting evidence that cancer incidence and mortality are strongly reduced in chronic calorie-restricted non-human primates. Studies of long-term calorie-restricted human subjects have shown a reduction of metabolic and hormonal factors associated with cancer risk. However, chronic caloric restriction is not a feasible clinical intervention. Evident difficulties, such as the long period required to be effective, and unacceptable weight loss, hamper clinical application in cancer patients.

Autophagy: definition and mechanisms

In the 1990’s Yoshinori Ohsumi first proposed autophagy. He received a Nobel Prize in 2016 for Physiology or Medicine for his seminal work in establishing a morphological and molecular mechanism of autophagy.

Autophagy is an evolutionarily conserved lysosomal catabolic process by which cells degrade and recycle intracellular endogenous (damaged organelles, misfolded or mutant proteins, and macromolecules) and exogenous (viruses and bacteria) components to maintain cellular homeostasis. The specificity of the cargo and the delivery route to lysosomes distinguishes the three major types of autophagy –

  • Mircroautophagy involves the direct engulfment of cargo in endosomal/lysosomal membrane invaginations.
  • Chaperone-mediated autophagy (CMA) recycles soluble proteins with an exposed amino acid motif (KFERQ) that is recognized by the heat shock protein hsc70; these proteins are internalized by binding to lysosomal receptors (LAMP-2A) 6.
  • Macroautophagy (herein referred to as autophagy) is the best-characterized process; in this process, cytoplasmic constituents are engulfed within double-membrane vesicles called autophagosomes, which subsequently fuse with lysosomes to form autolysosomes, where the cargo are degraded or recycled. The degradation products include sugars, nucleosides/nucleotides, amino acids and fatty acids that can be redirected to new metabolic routes for cellular maintenance.

Autophagy occurs at basal levels under physiological conditions and can also be upregulated in response to stressful stimuli such as hypoxia, nutritional deprivation, DNA damage, and cytotoxic agents. Autophagy has attracted considerable attention as a potential target of pharmacological agents or dietary interventions that inhibit or activate this process for several human disorders, including infections and inflammatory diseases, neurodegeneration, metabolic and cardiovascular diseases, obesity and cancer.

Autophagy and cancer
The role of autophagy in cancer is complex, and its function may vary according to several biological factors, including tumor type, progression stage, and genetic landscape, along with oncogene activation and tumor suppressor inactivation. Thus, autophagy can be related either to the prevention of tumorigenesis or due to the enabling of cancer cell adaptation, proliferation, survival, and metastasis. The initial indication that autophagy could have an important role in tumor suppression came from several studies exploring the essential autophagy gene BECN1, which encodes the Beclin-1 protein that is frequently deleted in ovarian, breast and testicular cancer.

BECN1 is located adjacent to the well-known tumor suppressor gene BRCA1, which is commonly deleted in hereditary breast cancer. These deletions are generally extensive and affect BRCA1 along with several other genes, including BECN1, suggesting that the deletion of BRCA1, not the deletion of BECN1, is the driver mutation in breast cancer. Furthermore, the activation of oncogenes (e.g., PI3KCA) and inactivation of tumor suppressors (e.g., PTEN and LKB1) are associated with autophagy inhibition and tumorigenesis. Animal models note that the tumor suppressor function of autophagy is associated with cell protection from oxidative stress, DNA damage, inflammation and the accumulation of dysfunctional organelles. Collectively, these phenomena are important factors that could trigger genomic instabilities leading to tumor development.

However, the loss of function of autophagy genes has not yet been identified and demonstrated in humans, raising doubts about the relevance of autophagy to tumor initiation in different types of cancer. In addition, the autophagic machinery is not a common target of somatic mutations, indicating that autophagy may have a fundamental role in the survival and progression of tumor cells.

Once the tumor is established, the main function of autophagy is to provide a means to cope with cellular stressors, including hypoxia, nutritional and growth factor deprivation, and damaging stimuli, thus allowing tumor adaptation, proliferation, survival, and dissemination. Autophagy, by degrading macromolecules and defective organelles, supplies metabolites and upregulates mitochondrial function, supporting tumor cell viability even in constantly stressful environments. Studies have demonstrated that autophagy increases in hypoxic regions of solid tumors, favoring cell survival (a factor that does not favor fasting to help cancer regression and or cure).

The inhibition of autophagy leads to an intense induction of cell death in these regions. Moreover, tumors frequently have mutations or deletions in the tumor suppressor protein p53, which also favors autophagy induction to recycle intracellular components for tumor growth. Although the basal autophagy rate is generally low in normal cells under physiological conditions, some tumors show a high level of basal autophagy, reinforcing the prosurvival role of autophagy in cancer. RAS-transformed cancer cells undergo autophagy upregulation to supply metabolic needs and maintain functional mitochondria, which in turn favors tumor establishment. Autophagy also has a supportive role in metastasis by interfering with epithelial-mesenchymal transition constituents to favor tumor cell dissemination. Finally, studies have demonstrated that autophagy is commonly induced as a survival mechanism against antitumor treatments, such as chemotherapy, radiotherapy and targeted therapy, contributing to treatment resistance.

How does dietary restriction modulate autophagy and cancer therapy?

Autophagy and cancer therapeutics have a mixed relationship. Because autophagy can inhibit tumor development or favor tumor growth, progression, invasion and treatment resistance, researchers proposed that autophagy modulation could be a new therapeutic strategy in the treatment of some malignancies. In preclinical studies, dietary restriction (DR) has been shown to extend the lifespan and reduce the development of age-related diseases such as diabetes, cancer, and neurodegenerative and cardiovascular diseases. DR promotes metabolic and cellular changes in organisms from prokaryotes to humans that allow adaptation to periods of limited nutrient availability. The main changes include decreased blood glucose levels and growth factor signaling and the activation of stress resistance pathways affecting cell growth, energy metabolism, and protection against oxidative stress, inflammation, and cell death. Nutrient starvation also activates autophagy in most cultured cells and organs, such as the liver and muscle, as an adaptive mechanism to stressful conditions.

Studies demonstrate that dietary interventions can reduce tumor incidence and potentiate the effectiveness of chemo- and radiotherapy in different tumor models, highlighting dietary manipulation as a possible adjunct to standard cancer therapies. Among the many diet regimens that have been assessed, caloric restriction (CR) and fasting are the methods under intense investigation in oncology. CR is defined as a chronic reduction in the daily caloric intake by 20-40% without the incurrence of malnutrition and with the maintenance of meal frequency. In contrast, fasting is characterized by the complete deprivation of food but not water, with intervening periods of normal food intake. Based on the duration, fasting can be classified as –

(i) intermittent fasting (IF—e.g., alternate day fasting (≥16 hours) or 48 hours of fasting/week) or
(ii) periodic fasting (PF—e.g., a minimum of 3 days of fasting every 2 or more weeks).

Conclusion

Every stride in translational medicine helps in advancing our understanding of cancer and subsequently, the management of this malady. However, when a person of Sadhguru’s respected stature talks about fiction based on Yogic culture, we tend to degrade our Yogic culture and deprive the credibility of our repute.

However, as stated earlier, there is a mixed bag of information on dietary restriction and cancer prevention or treatment. 

There is a perfect need for interpreting a way of life (Sanatan Dharma and its various plural forms of ideologies for a living). I accept and understand that ancient Vedic science stood on significantly advanced scientific thinking, however, our times are different and we should rely on the current body of knowledge and refine our thinking of ancient yogic culture.

Note: I believe in providing direct feedback. I made an attempt to reach Sadhguru’s office at Coimbatore. No one answered. Possibly, I will make a few more attempts.

Citations:

http://cubocube.com/dashboard.php?a=1582&b=1585&c=1

Effect of short term fasting on cancer treatment https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530042/

Autophagy and intermittent fasting: the connection for cancer therapy? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6257056/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608686/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648937/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5442682/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5107564/

Nicotine: Carcinogenicity and Effects on Response to Cancer Treatment – A Review (2015)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4553893/

https://www.britannica.com/topic/fasting

 

Consciousness, Death, and Persistent Vegetative State

Background

Consciousness, Death, Coma and Persistent Vegetative State

John Paul II Institute has organized a symposium on Death and Organ Donation. Dr. Coimbra, a neurologist, has shared a video opposing the idea of organ harvesting and donation. Below, is the link on that discourse along concerning the John Paul II symposium (the link is included at the end of the blog). I differ with Dr. Coimbra and have provided a justification for my perspective. 

Dr. Coimbra raised an interesting question – not alone in medicine but one that touches spirituality and philosophy and extends to encompasses life and living. These questions have been an enigma ever since mankind has been dabbling cognitively exploring to understand it.

However, let us discern select issues at first. At the center of the debate is the definition of death and a downstream question, after objectively defining death, is harvesting and or donating the organs. The discussion rests on a select premise and some experiments. Also, it exists in a milieu of ethics and moral values. Let me take this opportunity to untangle the issues in a reverse chronology as that helps discern and render the problem space in a simpler light.

Ethical Milieu and the Messiah Syndrome

Generally, I am averse to the idea of a conspiracy being unleashed on mankind unless it is by a select group of corporate interests or a select few individuals. I hate to consider an idea wherein, someone questions the ethical and moral commitment of a hoard of well-meaning high caliber individuals and their intellect and commitment, especially when these are not connected and/or affiliated, except for the cause and dedication to their quest for scientific (systemic) understanding. To rephrase, it is hard for me to question the integrity of these folks if these people have no common thread, except a persistent quest to unravel science. Especially, when this cohort is not bound by country, religion, business, generations, ethnicity, ideology, etc. Generally, I don’t subscribe to the ‘Messiah’ ideology. So, I would debunk this Messiah Syndrome at the outset. Calling it ‘Conspiracy’ is unjust and uncalled for. Let us not subscribe to questioning the ethical and moral commitment of all these independent contributors.

Scientific Design and Validation

Experiments have validity if the design and or collection of data is methodical, unbiased and satisfies statistical and or inferential framework. Dr. Coimbra has not substantiated his observations with adequate scientific findings and their correlations except inferences based on his precepts and biased beliefs. This defeats the purpose of any scientific study and helps his contentions to falls from the high scientific pedestals.

Conscious Connectedness

Death and Persistent Vegetative State are inextricably related to consciousness. For any discussion on the death to proceed, we need to understand, the very abstract concept of consciousness and its finite and sublime association with organ(ic) rhythmicity and the circadian cycle. The finite but abstract state of consciousness has always endured cognitive and spiritual interests for generations of the elite and of intellectuals. Suffice it to say that with humility, I am attempting to articulate ideas in this subtle and undefined area. Definitely, I want to stay away from sounding like an authority, which I am not except in my capacity as a sincere contemplative scientific seeker.

Consciousness is a culmination of awareness, cognitive interpretation, and our own limited potential to respond to the inputs from the senses and the surrounding we exist. A vegetative state is the loss of this connection between soma and conscious awareness. At times, it is transient and sometimes, it is permanent and irreversible. Loss of connection does not necessarily mean loss of somatic function. We have had several anecdotes wherein, people have risen after long durations of disconnect if their bodies are kept functional. We know that the duration of brain death is longer in frigid conditions or in infants. Similarly, we also know that sages have practiced an extended ‘state of mind and body’ dissociation during their trance phases. We have seen them reverting to normal bodily functions after reversing the soma – conscious association. Their experiences have been very different. We also have heard patients going through the near-death phenomenon, experiencing those bright flashes of light. These are just a few select examples. However, based on all these, it is evident that this is as intriguing an area as ever. However, one thing is clear that once that association between soma and conscious is irreversibly broken, we can closely approximate it with death (exception is Locked-In Syndrome, wherein, the patient is awake and conscious but disconnected with the body.

Consent and Compliance

Under these circumstances, it is best to go by the consent or implied consent of the individual (best interest standards/Substituted judgment). If those are not available, family discretion comes into play. However, religion, culture, and laws of countries define and influence this space of ethics and compliance. Evidently, we see several versions that act out, depending upon the circumstances.

Inference

Labeling this complex cornucopia of facts and diverse facets into a generalized assumption of the immorality of harvesting organ post-death is grossly inadequate if not possibly wrong.

References

Persistent Vegetative State
https://www.sciencedirect.com/topics/neuroscience/persistent-vegetative-state

The Challenges of Defining and Diagnosing Brain Death
https://www.hopkinsmedicine.org/news/articles/the-challenges-of-defining-and-diagnosing-brain-death

The Legal Definition of Death and the Right to Life
https://link.springer.com/chapter/10.1057/978-1-137-58328-4_8

Neuroethics of death in the United States – PeerJ

https://peerj.com/preprints/2890.pdf

Spiritual  –

Kundalini Yoga
https://en.wikipedia.org/wiki/Kundalini_yoga

Advaita Vedanta
https://en.wikipedia.org/wiki/Advaita_Vedanta