Ketogenic diet in the treatment of cancer – Where do we stand?

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

doi:10.1016/j.molmet.2019.06.026

Cited by 289 publications

(290 citation statements)

References 191 publications

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“…We now have some evidence for beneficial effects of a KD on body composition in gynecological cancers [19,21], pancreatic cancer [23] and head and neck cancer patients [21]. We also have some evidence for synergistic effects between KDs and other therapies, in accordance with predictions from animal studies [2]. In stage IV non-small cell lung cancer patients a KD combined with hyperthermia, hyperbaric oxygen, and short-term fasting prior to chemotherapy resulted in a 3 − 8 times longer overall and progression-free survival than expected from other studies applying the same type of chemotherapy [24].…”

Section: Current State Of the Researchsupporting

confidence: 65%

“…This argument is what is usually summarized in mechanistically oriented reviews on this topic, drawing from a wealth of in vitro and in vivo data. There are some central mechanisms how a KD has been shown to affect tumor growth and host metabolism [2]. Given these data, the probability of an antitumor effect hypothesis is much higher than a pro-tumor effect hypothesis.…”

Section: A Mechanistic Argumentmentioning

confidence: 99%

“…KDs have a long history in both human evolution and clinical medicine with treatment applications including cancer, cardiovascular and endocrine diseases, gastrointestinal, neurological and psychological disorders [1]. Concerning cancer, ketone bodies have been shown by some studies to inhibit tumor cell growth in vitro, and indeed there is evidence that feeding a KD can delay tumor growth in many, although not all, animal models of implanted tumors (reviewed in [2]). However, many patients who want to undertake a KD are left alone or discouraged by their physicians.…”

Section: Introductionmentioning

confidence: 99%

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Addressing the controversial role of ketogenic diets in cancer treatment

Klement

2020

Expert Review of Anticancer Therapy

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Section: Current State Of the Researchsupporting

confidence: 65%

Section: A Mechanistic Argumentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Addressing the controversial role of ketogenic diets in cancer treatment

Klement

2020

Expert Review of Anticancer Therapy

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“…A recent review by Weber et al proposed that preclinical and several clinical studies argued for the use of a ketogenic diet (KD) in combination with standard therapies in patients with cancer (255): KD had the potential to enhance the antitumor effects of classic chemo-and radiotherapy and to increase the QoL of patients (255). However, the heterogeneity between studies investigating these effects and low adherence to diet limit the current evidence (256).…”

Section: Nutrition Microbiome and Physical Activity And Its Associamentioning

confidence: 99%

Inflammation-Induced Tryptophan Breakdown is Related With Anemia, Fatigue, and Depression in Cancer

et al. 2020

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Many patients with cancer suffer from anemia, depression, and an impaired quality of life (QoL). These patients often also show decreased plasma tryptophan levels and increased kynurenine concentrations in parallel with elevated concentrations of Th1 type immune activation marker neopterin. In the course of anti-tumor immune response, the pro-inflammatory cytokine interferon gamma (IFN-γ) induces both, the enzyme indoleamine 2,3-dioxygenase (IDO) to degrade tryptophan and the enzyme GTP-cyclohydrolase I to form neopterin. High neopterin concentrations as well as an increased kynurenine to tryptophan ratio (Kyn/Trp) in the blood of cancer patients are predictive for a worse outcome. Inflammation-mediated tryptophan catabolism along the kynurenine pathway is related to fatigue and anemia as well as to depression and a decreased QoL in patients with solid tumors. In fact, enhanced tryptophan breakdown might greatly contribute to the development of anemia, fatigue, and depression in cancer patients. IDO activation and stimulation of the kynurenine pathway exert immune regulatory mechanisms, which may impair anti-tumor immune responses. In addition, tumor cells can degrade tryptophan to weaken immune responses directed against them. High IDO expression in the tumor tissue is associated with a poor prognosis of patients. The efficiency of IDO-inhibitors to inhibit cancer progression is currently tested in combination with established chemotherapies and with immune checkpoint inhibitors. Inflammation-mediated tryptophan catabolism and its possible influence on the development and persistence of anemia, fatigue, and depression in cancer patients are discussed.

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“…Ketogenic metabolic therapy (KMT) is emerging as an effective complementary or alternative therapeutic strategy for managing a broad range of malignant cancers including breast cancer (151)(152)(153)(154)(155)(156)(157)(158)(159)(160). Calorie restriction and low-carbohydrate high-fat ketogenic diets (KD) reduce the glucose needed to propell the Warburg effect while also elevating ketone bodies (34).…”

Section: Ketogenic Metabolic Therapymentioning

confidence: 99%

Consideration of Ketogenic Metabolic Therapy as a Complementary or Alternative Approach for Managing Breast Cancer

et al. 2020

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Breast cancer remains as a significant cause of morbidity and mortality in women. Ultrastructural and biochemical evidence from breast biopsy tissue and cancer cells shows mitochondrial abnormalities that are incompatible with energy production through oxidative phosphorylation (OxPhos). Consequently, breast cancer, like most cancers, will become more reliant on substrate level phosphorylation (fermentation) than on oxidative phosphorylation (OxPhos) for growth consistent with the mitochondrial metabolic theory of cancer. Glucose and glutamine are the prime fermentable fuels that underlie therapy resistance and drive breast cancer growth through substrate level phosphorylation (SLP) in both the cytoplasm (Warburg effect) and the mitochondria (Q-effect), respectively. Emerging evidence indicates that ketogenic metabolic therapy (KMT) can reduce glucose availability to tumor cells while simultaneously elevating ketone bodies, a non-fermentable metabolic fuel. It is suggested that KMT would be most effective when used together with glutamine targeting. Information is reviewed for suggesting how KMT could reduce systemic inflammation and target tumor cells without causing damage to normal cells. Implementation of KMT in the clinic could improve progression free and overall survival for patients with breast cancer.

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Ketogenic diet in the treatment of cancer – Where do we stand?

Cited by 289 publications

References 191 publications

Addressing the controversial role of ketogenic diets in cancer treatment

Addressing the controversial role of ketogenic diets in cancer treatment

Inflammation-Induced Tryptophan Breakdown is Related With Anemia, Fatigue, and Depression in Cancer

Consideration of Ketogenic Metabolic Therapy as a Complementary or Alternative Approach for Managing Breast Cancer

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