Review: Ketogenic diet in the treatment of cancer – Where do we stand? 評論:生酮飲食治療癌症-我們的立場是什麼?

Daniela D.Weber, Sepideh Aminzadeh-Gohari, Julia Tulipan, Luca Catalano, René G.Feichtinger, Barbara Kofler

Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, Müllner Hauptstraße 48, 5020, Salzburg, Austria

Received 1 May 2019, Revised 17 June 2019, Accepted 28 June 2019, Available online 27 July 2019.

Highlights

Ketogenic diets (KDs) can enhance the efficacy of classical antitumor therapies.•

Effect of KDs on proliferation is tumor type dependent.•

Application of KDs to cancer patients is generally well tolerated.•

Low-carbohydrate and KDs increase quality of life of cancer patients.•

More standardized studies are needed before KDs can be advised for cancer patients.

Abstract
Background

Cancer is one of the greatest public health challenges worldwide, and we still lack complementary approaches to significantly enhance the efficacy of standard anticancer therapies. The ketogenic diet, a high-fat, low-carbohydrate diet with adequate amounts of protein, appears to sensitize most cancers to standard treatment by exploiting the reprogramed metabolism of cancer cells, making the diet a promising candidate as an adjuvant cancer therapy.
Scope of review

To critically evaluate available preclinical and clinical evidence regarding the ketogenic diet in the context of cancer therapy. Furthermore, we highlight important mechanisms that could explain the potential antitumor effects of the ketogenic diet.
Major conclusions

The ketogenic diet probably creates an unfavorable metabolic environment for cancer cells and thus can be regarded as a promising adjuvant as a patient-specific multifactorial therapy. The majority of preclinical and several clinical studies argue for the use of the ketogenic diet in combination with standard therapies based on its potential to enhance the antitumor effects of classic chemo- and radiotherapy, its overall good safety and tolerability and increase in quality of life. However, to further elucidate the mechanisms of the ketogenic diet as a therapy and evaluate its application in clinical practice, more molecular studies as well as uniformly controlled clinical trials are needed.

1. Introduction

Worldwide, cancer is a major public health problem [1]. Although the war against cancer is being fought with the latest technologies on many fronts, there is still considerable room for improvement. In 2009, cancer-associated expenses in the EU amounted to 126 billion € [2].

In cancer cells, most energy comes from glucose even if oxygen is present. This shift from oxidative phosphorylation (OXPHOS) to glycolysis is called the Warburg effect [3]. Increased glycolysis and diminished tricarboxylic acid (TCA) cycle activity and OXPHOS are seen very early in tumorigenesis and constitute one of the hallmarks of cancer [4].

The ketogenic diet (KD) is a promising opportunity to target these metabolic alterations in tumor cells. Recent research shows that the KD potentially has a tumor growth-limiting effect, protects healthy cells from damage by chemotherapy or radiation, accelerates chemotherapeutic toxicity toward cancer cells [5], [6], and lowers inflammation [7]. Moreover, compared to anticancer drugs and standard treatments, the KD is inexpensive, fairly easy to implement (numerous good recipes are available in books and via the internet), and well tolerated [8], [9].

In the present review, we summarize the fundamentals of the KD, its proposed antitumor mechanisms, and currently available evidence from preclinical and clinical studies concerning efficacy. Finally, we discuss the future role of the KD as adjuvant therapy.

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