An Evolutionary and Mechanistic Perspective on Dietary Carbohydrate Restriction in Cancer Prevention

Fine, Eugene J.; Champ, Colin E.; Feinman, Richard D.; Márquez, Samuel; Klement, Rainer J.

doi:10.15310/2334-3591.1036

Cited by 5 publications

(3 citation statements)

References 130 publications

(136 reference statements)

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“…The available data also confirm the hypothesis that KDs are generally safe for cancer patients. In fact, nutritional ketosis is a physiological condition that probably was highly prevalent during human evolution [115,116], providing little a priori reason to believe that nutritional ketosis per se is unsafe or even dangerous. Again, a fundamentalist sceptic would reject the prior assumption of the safety of a diet appearing extreme compared to dietary guidelines and could point to putative side effects that have been mostly observed in the pediatric population treated with very strict and partially outdated forms of KDs [117].…”

Section: Discussionmentioning

confidence: 99%

Beneficial effects of ketogenic diets for cancer patients: a realist review with focus on evidence and confirmation

Klement

2017

Med Oncol

122

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Ketogenic diets (KDs) have gained popularity among patients and researchers alike due to their putative anti-tumor mechanisms. However, the question remains which conclusions can be drawn from the available human data thus far concerning the safety and efficacy of KDs for cancer patients. A realist review utilizing a matrix analytical approach was conducted according to the RAMESES publication standards. All available human studies were systematically analyzed and supplemented with results from animal studies. Evidence and confirmation were treated as separate concepts. In total, 29 animal and 24 human studies were included in the analysis. The majority of animal studies (72%) yielded evidence for an anti-tumor effect of KDs. Evidential support for such effects in humans was weak and limited to individual cases, but a probabilistic argument shows that the available data strengthen the belief in the anti-tumor effect hypothesis at least for some individuals. Evidence for pro-tumor effects was lacking completely. Feasibility of KDs for cancer patients has been shown in various contexts. The probability of achieving an anti-tumor effect seems greater than that of causing serious side effects when offering KDs to cancer patients. Future controlled trials would provide stronger evidence for or against the anti-tumor effect hypothesis.

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Section: Discussionmentioning

confidence: 99%

Beneficial effects of ketogenic diets for cancer patients: a realist review with focus on evidence and confirmation

Klement

2017

Med Oncol

122

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“…Restricting carbohydrates consumption is an additional dietary approach associated to weight loss and improved health markers [43]. From an evolutionary perspective, a low-carbohydrate intake (<40% of energy) would have been the norm and result in cancer protection by avoiding hyperglycemia and hyperinsulinemia [44]. In overweight individuals, a low-carbohydrate, high-protein weight loss diet had no effect on the proportion of different bacterial phyla but triggered significant decreases in Collinsella aerofaciens and E. rectale relatives [45].…”

Section: Low-carbohydrate Diet Microbiota and Cancermentioning

confidence: 99%

Impact of Different Types of Diet on Gut Microbiota Profiles and Cancer Prevention and Treatment

2019

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: Diet is frequently considered as a food regimen focused on weight loss, while it is actually the sum of food consumed by the organism. Western diets, modern lifestyle, sedentary behaviors, smoking habits, and drug consumption have led to a significant reduction of gut microbial diversity, which is linked to many non-communicable diseases (NCDs). The latter kill 40 million people each year, equivalent to more than 70% of all deaths globally. Among NCDs, tumors play a major role, being responsible for 29% of deaths from NCDs. A link between diet, microbiota, and cancer prevention and treatment has recently been unveiled, underlining the importance of a new food culture based on limiting dietary surplus and on preferring healthier foods. Here, we review the effects of some of the most popular “cancer-specific” diets on microbiota composition and their potential impact on cancer prevention and treatment.

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“…Obesity, chronic low-grade inflammation, and high blood glucose, insulin and insulin-like growth factor 1 (IGF-1) levels have been associated with a higher risk not only of developing but also of dying from various cancers [2,3]. We [4] and others [5,6,7] have argued that the deviation from our ancestral dietary patterns [8], most notably the strong increase of carbohydrate consumption, plays a significant role in this metabolic transition and tumorigenesis. Consistent with this are reports from the first half of the 20th century of a complete lack of or much fewer cancer cases among native societies compared to civilized white people [5,9,10,11,12,13], despite many natives reaching an old age [9,13].…”

Section: Introductionmentioning

confidence: 99%

Fasting, Fats, and Physics: Combining Ketogenic and Radiation Therapy against Cancer

Klement¹

2017

Complement Med Res

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Radiotherapy (RT) is a mainstay in the treatment of solid tumors and works by physicochemical reactions inducing oxidative stress in cells. Because in practice the efficacy of RT is limited by its toxicity to normal tissues, any strategy that selectively increases the radiosensitivity of tumor cells or boosts the radioresistance of normal cells is a valuable adjunct to RT. In this review, I summarize preclinical and clinical data supporting the hypothesis that ketogenic therapy through fasting and/or ketogenic diets can be utilized as such an adjunct in order to improve the outcome after RT, in terms of both higher tumor control and lower normal-tissue complication probability. The first effect relates to the metabolic shift from glycolysis towards mitochondrial metabolism, which selectively increases reactive oxygen species (ROS) production and impairs adenoside triphosphate (ATP) production in tumor cells. The second effect is based on the differential stress resistance phenomenon describing the reprogramming of normal cells, but not tumor cells, from proliferation towards maintenance and stress resistance when glucose and growth factor levels are decreased and ketone body levels are elevated. Underlying both effects are metabolic differences between normal and tumor cells. Ketogenic therapy is a non-toxic and cost-effective complementary treatment option that exploits these differences and deserves further clinical investigation.

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An Evolutionary and Mechanistic Perspective on Dietary Carbohydrate Restriction in Cancer Prevention

Cited by 5 publications

References 130 publications

Beneficial effects of ketogenic diets for cancer patients: a realist review with focus on evidence and confirmation

Beneficial effects of ketogenic diets for cancer patients: a realist review with focus on evidence and confirmation

Impact of Different Types of Diet on Gut Microbiota Profiles and Cancer Prevention and Treatment

Fasting, Fats, and Physics: Combining Ketogenic and Radiation Therapy against Cancer

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