Beyond Starvation – What role does diet and metabolism have in cancer prevention and treatment?

Beyond Starvation – What role does diet and metabolism have in cancer prevention and treatment?

Authors

James Hall-Kenney. PREKURE Certified Health Coach and Metabolic Nutrition Coach. Wellington, New Zealand. Corresponding author.  

Grant Schofield. PREKURE, Chief Science Officer, Human Potential Centre, Auckland University of Technology, Auckland, New Zealand 

Introduction

The question of the role of diet, metabolic health and metabolism in cancer is both an old and a new one. Since the 1920s when Otto Warburg observed that cancer cells metabolise energy in an unusual manner and at extreme levels, scientists have pondered whether this anomalous energy metabolism, and any other metabolic factors, offer any potential targets for cancer prevention and treatment.   

At the same time, a burgeoning rate of “diseases of civilisation” that demonstrate metabolic dysfunction such as Type 2 Diabetes, Metabolic Syndrome, and Hyperinsulinemia was seemingly being matched by a growing rate of cancer diagnoses.  It has been demonstrated that people with poor metabolic health have a marked risk of developing some types of cancers. Equally, metabolic diseases are a common comorbidity of cancer. 

The work of modern scientists such as Professors Thomas Seyfried, Dominic d’Agostino, Adrienne Scheck and Angela Poff; as well as clinical practitioners such as Doctors Matthew Phillips and Jethro Hu has rejuvenated the concept that cancer metabolism and metabolic health can play a multi-factor role in the prevention of cancer and act as an adjuvant treatment for cancer. Indeed, metabolic dysfunction is now one of the acknowledged “Hallmarks of Cancer” – a framework that describes the common attributes of cancer and drugs that target cancer metabolism are currently in development and trials.

The Lancet Oncology recently published an article titled “Starving cancer and other dangerous dietary misconceptions” in their “Perspectives: Quackery” category.  The core premise of the article is that people are self-prescribing and administrating diets, including a ketogenic diet, instead of following the standard of care (chemotherapy, radiation etc) based on recommendations on social media and from “wellness influencers”.  The focus of their argument was around the role of glucose and whether it is possible to use a diet to “starve” a cancer cell of energy. The article does not address the other metabolic factors that a well-formulated diet may play in a cancer context.   

We wrote a response to their article utilising their “Correspondence” mechanism, which is included below.  We have also included their feedback when rejecting the response. 

“Anyone that’s actually familiar with the literature on diet and cancer I don’t think can any longer claim that it makes no impact.”  Dr. Angela Poff, PHD, Department of Molecular Pharmacology and Physiology in the University of South Florida. 

The Lancet Oncology Paper 

The original The Lancet Oncology article can be found here: Starving cancer and other dangerous dietary misconceptions – The Lancet Oncology 

Unfortunately, it is not Open Access so to read it you would need a subscription or academic access. 

Our Response

A recent article published in The Lancet Oncology authored by Grimes and O’Riordan asserted that the promotion of the concept of “starving cancer” is misleading cancer patients to self-prescribe a ketogenic diet with potentially dangerous results.1 The subsequent arguments made imply that diet, glucose, metabolism, and metabolic health have minimal-to-no role to play in cancer prevention and/or treatment. 

The evidence supporting or discrediting the role that “starving” glucose and other nutrients plays in cancer pathology and therapy remains preclinical. However, the relationship between poor metabolic health, especially when presenting as Metabolic Syndrome (MetS), Hyperinsulinemia and/or Type 2 Diabetes Mellitus, as risk factors for, and common comorbidities of, cancer is well established. 2-3 The role of insulin as a contributor to pro-tumorous growth factors has also been well established.4 

Dietary strategies that address metabolic health, of which low carbohydrate and ketogenic diets are possibly the most studied, have shown favourable outcomes in improving metabolic health and reversing metabolic conditions.6-8 

Additionally, there is growing evidence that nutrient deficiencies, commonly associated with the standard Western diet of nutrient-deficient ultra-processed foods, contribute to cancer pathogenesis.9 

The referenced 2022 meta-analysis indeed highlights the inconsistency of the design, implementation, and measurement in clinical trials of ketogenic therapies and emphasises the need for more standardised trial methodologies. 

Preclinical data shows that the pleiotropic effect of ketogenic therapy can play a positive role as an adjuvant to the standard of care in anti-cancer functions such as inflammation, angiogenesis, cell cycle, apoptosis, MTOR signalling, reactive oxidative species, hypoxia, epigenetic regulation10, DNA repair, metastasis, edema, growth factors, cachexia, and immunity.10-18 

The “starving cancer” perspective is rarely a focal point of most researchers and clinicians supporting the role of diet in the prevention and treatment of cancer. Oncology nutritionists and dieticians selectively utilise ketogenic strategies, amongst others, as adjuvants to chemotherapy, radiation, and surgical therapies. They construct well-formulated, oncology-specific ketogenic diets that are nutrient-dense, address specific nutrient deficiencies and improve metabolic health. Calories and protein levels are adjusted to address concerns about undesirable weight loss (cachexia and/or sarcopenia). 

The idea that diet is associated with the pathogenesis of cancer and has potential useful adjunctive roles in cancer therapy shouldn’t be dismissed on arguments that entirely miss many of the major important effects of diet on metabolic health and cancer metabolism. 

We declare no competing interests.  

Additional references have been added to this version of the response as The Lancet Oncology submission guidelines limit the number of references to five. 

The Lancet Oncology Response

This is the response from The Lancet: 

“Thank you for your recent submission to The Lancet Oncology. We have now had time to consider your manuscript and unfortunately, on this occasion, we have decided not to publish it because we believe the message would be better suited elsewhere. 

Although this decision has not been a positive one, I thank you for your interest in the journal and hope it does not deter you from considering us again in the future.” 

Further Resources

Further resources regarding cancer, metabolic health, and cancer metabolism: 

• Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer: Seyfried, Thomas (Book) 

• Tripping over the Truth: How the Mitochondrial Metabolic Theory of Cancer Is Overturning One of Medicine’s Most Entrenched Paradigms: Christofferson, Travis, D’Agostino, Dominic (Book) 

• Hallmarks of Cancer: New Dimensions | Cancer Discovery | American Association for Cancer Research (aacrjournals.org) (Article) 

• Diet Doctor podcast #44 — Angela Poff, PhD – Diet Doctor (Podcast) 

• Dr. Adrienne Scheck – Tumor Metabolism and the Ketogenic Diet – YouTube (Video) 

• Metabolic therapy in glioblastoma: Ancestral strategies | Dr Matthew Phillips | FOM23 – YouTube (Video)