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).

2. 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.

3. 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.

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