scholarly journals Ketogenic Diet for Cancer: Critical Assessment and Research Recommendations

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3562
Author(s):  
Jordin Lane ◽  
Nashira I. Brown ◽  
Shanquela Williams ◽  
Eric P. Plaisance ◽  
Kevin R. Fontaine
Keyword(s):  
Clinical Trials ◽  
Ketogenic Diet ◽  
The United States ◽  
Carbohydrate Content ◽  
Cancer Development ◽  
Antitumor Effects ◽  
Low Protein ◽  
Low Carbohydrate ◽  
Diet And Lifestyle ◽  
Research Recommendations

Despite remarkable improvements in screening, diagnosis, and targeted therapies, cancer remains the second leading cause of death in the United States. It is increasingly clear that diet and lifestyle practices play a substantial role in cancer development and progression. As such, various dietary compositions have been proposed for reducing cancer risk and as potential adjuvant therapies. In this article, we critically assess the preclinical and human trials on the effects of the ketogenic diet (KD, i.e., high-fat, moderate-to-low protein, and very-low carbohydrate content) for cancer-related outcomes. The mechanisms underlying the hypothesized effects of KD, most notably the Warburg Effect, suggest that restricting carbohydrate content may impede cancer development and progression via several pathways (e.g., tumor metabolism, gene expression). Overall, although preclinical studies suggest that KD has antitumor effects, prolongs survival, and prevents cancer development, human clinical trials are equivocal. Because of the lack of high-quality clinical trials, the effects of KD on cancer and as an adjunctive therapy are essentially unknown. We propose a set of research recommendations for clinical studies examining the effects of KD on cancer development and progression.

scholarly journals Hepatic steatosis, inflammation, and ER stress in mice maintained long term on a very low-carbohydrate ketogenic diet

2011 ◽  
Vol 300 (6) ◽  
pp. G956-G967 ◽  
Author(s):  
Joel R. Garbow ◽  
Jason M. Doherty ◽  
Rebecca C. Schugar ◽  
Sarah Travers ◽  
Mary L. Weber ◽  
...  
Keyword(s):  
Ketogenic Diet ◽  
Western Diet ◽  
Whole Body ◽  
Resonance Spectroscopy ◽  
Chow Diet ◽  
High Fat ◽  
Low Protein ◽  
Low Carbohydrate ◽  
Term Administration

Low-carbohydrate diets are used to manage obesity, seizure disorders, and malignancies of the central nervous system. These diets create a distinctive, but incompletely defined, cellular, molecular, and integrated metabolic state. Here, we determine the systemic and hepatic effects of long-term administration of a very low-carbohydrate, low-protein, and high-fat ketogenic diet, serially comparing these effects to a high-simple-carbohydrate, high-fat Western diet and a low-fat, polysaccharide-rich control chow diet in C57BL/6J mice. Longitudinal measurement of body composition, serum metabolites, and intrahepatic fat content, using in vivo magnetic resonance spectroscopy, reveals that mice fed the ketogenic diet over 12 wk remain lean, euglycemic, and hypoinsulinemic but accumulate hepatic lipid in a temporal pattern very distinct from animals fed the Western diet. Ketogenic diet-fed mice ultimately develop systemic glucose intolerance, hepatic endoplasmic reticulum stress, steatosis, cellular injury, and macrophage accumulation, but surprisingly insulin-induced hepatic Akt phosphorylation and whole-body insulin responsiveness are not impaired. Moreover, whereas hepatic Pparg mRNA abundance is augmented by both high-fat diets, each diet confers splice variant specificity. The distinctive nutrient milieu created by long-term administration of this low-carbohydrate, low-protein ketogenic diet in mice evokes unique signatures of nonalcoholic fatty liver disease and whole-body glucose homeostasis.

scholarly journals The ketogenic diet is not effective in preclinical models of IDH1 wild-type and IDH1 mutant glioma

2020 ◽  
Author(s):  
Rodrigo Javier ◽  
Craig Horbinski
Keyword(s):  
Clinical Trials ◽  
Ketogenic Diet ◽  
Sleeping Beauty ◽  
Wild Type ◽  
Preclinical Models ◽  
Isocitrate Dehydrogenase 1 ◽  
Low Carbohydrate ◽  
Cellular Biochemistry

ABSTRACTInfiltrative gliomas are the most common neoplasms arising in the brain, and remain largely incurable despite decades of research. A subset of these gliomas contains mutations in isocitrate dehydrogenase 1 (IDH1mut). This mutation disrupts cellular biochemistry, and IDH1mut gliomas are generally less aggressive than IDH1 wild-type (IDH1wt) gliomas. Some preclinical studies and clinical trials have suggested that a ketogenic diet (KD), characterized by low-carbohydrate and high-fat content, may be beneficial in slowing glioma progression. However, not all studies have shown promising results, and to date, no study has addressed whether IDH1mut gliomas might be more sensitive to KD. The aim of the current study was to compare the effects of KD in preclinical models of IDH1wt versus IDH1mut gliomas. In vitro, simulating KD by treatment with the ketone body β-hydroxybutyrate had no effect on the proliferation of patient-derived IDH1wt or IDH1mut glioma cells. Likewise, KD had no effect on the in vivo growth of these patient-derived gliomas. Furthermore, mice engrafted with Sleeping-Beauty transposase-engineered IDH1wt and IDH1mut glioma showed no difference in survival while on KD. These data suggest that IDH1mut gliomas are not more responsive to KD, and that clinical trials further exploring KD in this subset of glioma patients may not be warranted.

scholarly journals Ketogenic Diet in Cancer Prevention and Therapy: Molecular Targets and Therapeutic Opportunities

2021 ◽  
Vol 43 (2) ◽  
pp. 558-589
Author(s):  
Wamidh H. Talib ◽  
Asma Ismail Mahmod ◽  
Ayah Kamal ◽  
Hasan M. Rashid ◽  
Aya M. D. Alashqar ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Ketogenic Diet ◽  
Cell Metabolism ◽  
New Combination ◽  
Antitumor Effects ◽  
Low Carbohydrate ◽  
Therapeutic Mechanisms ◽  
Cancer Cell Metabolism ◽  
Therapy Studies ◽  
Potential Antitumor

Although cancer is still one of the most significant global challenges facing public health, the world still lacks complementary approaches that would significantly enhance the efficacy of standard anticancer therapies. One of the essential strategies during cancer treatment is following a healthy diet program. The ketogenic diet (KD) has recently emerged as a metabolic therapy in cancer treatment, targeting cancer cell metabolism rather than a conventional dietary approach. The ketogenic diet (KD), a high-fat and very-low-carbohydrate with adequate amounts of protein, has shown antitumor effects by reducing energy supplies to cells. This low energy supply inhibits tumor growth, explaining the ketogenic diet’s therapeutic mechanisms in cancer treatment. This review highlights the crucial mechanisms that explain the ketogenic diet’s potential antitumor effects, which probably produces an unfavorable metabolic environment for cancer cells and can be used as a promising adjuvant in cancer therapy. Studies discussed in this review provide a solid background for researchers and physicians to design new combination therapies based on KD and conventional therapies.

scholarly journals Role of Choline Deficiency in the Fatty Liver Phenotype of Mice Fed a Low Protein, Very Low Carbohydrate Ketogenic Diet

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e74806 ◽  
Author(s):  
Rebecca C. Schugar ◽  
Xiaojing Huang ◽  
Ashley R. Moll ◽  
Elizabeth M. Brunt ◽  
Peter A. Crawford
Keyword(s):  
Fatty Liver ◽  
Ketogenic Diet ◽  
Choline Deficiency ◽  
Low Protein ◽  
Low Carbohydrate

scholarly journals Severe ketoacidosis in a non-diabetic lactating woman on a ketogenic diet

2020 ◽  
Vol 20 (2) ◽  
pp. 145-146
Author(s):  
John Alexander ◽  
Dinesh Nagi
Keyword(s):  
Ketogenic Diet ◽  
Breast Feeding ◽  
Carbohydrate Content ◽  
Efficacy And Safety ◽  
High Fat ◽  
Term Efficacy ◽  
Ketogenic Diets ◽  
Low Carbohydrate

Ketogenic diets are high fat, moderate protein, low carbohydrate diets with carbohydrate content usually less than 50 g/day. They are a novel intervention in the management of obesity and there is emerging evidence that they are very effective. Evidence regarding the long-term efficacy and safety of this rather new and popular intervention is still emerging and there is a lack of data on the effect of this diet in specific populations such as breast feeding women. We describe a case of severe ketoacidosis in a non-diabetic breast feeding woman who was successfully treated with conservative measures. This case highlights the need by medical and dietetic professionals for extra caution in initiating special dietary measures in susceptible physiological states.

scholarly journals Cardiac metabolic modulation upon low‐carbohydrate low‐protein ketogenic diet in diabetic rats studied in vivo using hyperpolarized13C pyruvate, butyrate and acetoacetate probes

2019 ◽  
Vol 21 (4) ◽  
pp. 949-960 ◽  
Author(s):  
Desiree Abdurrachim ◽  
Xing Qi Teo ◽  
Chern Chiuh Woo ◽  
Sing Yee Ong ◽  
Nurul Farhana Salleh ◽  
...  
Keyword(s):  
Ketogenic Diet ◽  
Diabetic Rats ◽  
Low Protein ◽  
Metabolic Modulation ◽  
Low Carbohydrate

Developing a Clinical Trials Infrastructure in the United States

2012 ◽  
Vol 2 (5) ◽  
Author(s):  
Paul Eisenberg ◽  
◽  
Petra Kaufmann ◽  
Ellen Sigal ◽  
Janet Woodcock ◽  
...  
Keyword(s):  
United States ◽  
Clinical Trials ◽  
The United States

The Use of Digital Clinical Trial Methods in the Evaluation of Digital Therapeutics: A Scoping Review (Preprint)

2019 ◽  
Author(s):  
Allison Hirsch ◽  
Mahip Grewal ◽  
Anthony James Martorell ◽  
Brian Michael Iacoviello
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Clinical Research ◽  
Scoping Review ◽  
Digital Technologies ◽  
Good Clinical Practice ◽  
The United States ◽  
Clinical Trial Research ◽  
Digital Methods ◽  
Clinical Trial Methods

BACKGROUND Digital Therapeutics (DTx) provide evidence based therapeutic health interventions that have been clinically validated to deliver therapeutic outcomes, such that the software is the treatment. Digital methodologies are increasingly adopted to conduct clinical trials due to advantages they provide including increases in efficiency and decreases in trial costs. Digital therapeutics are digital by design and can leverage the potential of digital and remote clinical trial methods. OBJECTIVE The principal purpose of this scoping review is to review the literature to determine whether digital technologies are being used in DTx clinical research, which type are being used and whether publications are noting any advantages to their use. As DTx development is an emerging field there are likely gaps in the knowledge base regarding DTx and clinical trials, and the purpose of this review is to illuminate those gaps. A secondary purpose is to consider questions which emerged during the review process including whether fully remote digital clinical research is appropriate for all health conditions and whether digital clinical trial methods are inline with the principles of Good Clinical Practice. METHODS 1,326 records were identified by searching research databases and 1,227 reviewed at the full-article level in order to determine if they were appropriate for inclusion. Confirmation of clinical trial status, use of digital clinical research methods and digital therapeutic status as well as inclusion and exclusion criteria were applied in order to determine relevant articles. Digital methods employed in DTx research were extracted from each article and these data were synthesized in order to determine which digital methods are currently used in clinical trial research. RESULTS After applying our criteria for scoping review inclusion, 11 articles were identified. All articles used at least one form of digital clinical research methodology enabling an element of remote research. The most commonly used digital methods are those related to recruitment, enrollment and the assessment of outcomes. A small number of articles reported using other methods such as online compensation (n = 3), or digital reminders for participants (n = 5). The majority of digital therapeutics clinical research using digital methods is conducted in the United States and increasing number of articles using digital methods are published each year. CONCLUSIONS Digital methods are used in clinical trial research evaluating DTx, though not frequently as evidenced by the low proportion of articles included in this review. Fully remote clinical trial research is not yet the standard, more frequently authors are using partially remote methods. Additionally, there is tremendous variability in the level of detail describing digital methods within the literature. As digital technologies continue to advance and the clinical research DTx literature matures, digital methods which facilitate remote research may be used more frequently.

scholarly journals 690 Are participants in obstetrical randomized clinical trials representative of the United States pregnant population?

2021 ◽  
Vol 224 (2) ◽  
pp. S433
Author(s):  
Cynthia Coots ◽  
Stephen Wagner ◽  
Matthew J. Bicocca ◽  
Megha Gupta ◽  
Hector Mendez Figueroa ◽  
...  
Keyword(s):  
United States ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
The United States

scholarly journals A Low-Carbohydrate Ketogenic Diet and Treadmill Training Enhanced Fatty Acid Oxidation Capacity but Did Not Enhance Maximal Exercise Capacity in Mice

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 611
Author(s):  
Sihui Ma ◽  
Jiao Yang ◽  
Takaki Tominaga ◽  
Chunhong Liu ◽  
Katsuhiko Suzuki
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Exercise Capacity ◽  
Ketogenic Diet ◽  
Maximal Exercise ◽  
Treadmill Running ◽  
Acid Oxidation ◽  
Oxidation Capacity ◽  
Low Carbohydrate ◽  
Maximal Exercise Capacity

The low-carbohydrate ketogenic diet (LCKD) is a dietary approach characterized by the intake of high amounts of fat, a balanced amount of protein, and low carbohydrates, which is insufficient for metabolic demands. Previous studies have shown that an LCKD alone may contribute to fatty acid oxidation capacity, along with endurance. In the present study, we combined a 10-week LCKD with an 8-week forced treadmill running program to determine whether training in conjunction with LCKD enhanced fatty acid oxidation capacity, as well as whether the maximal exercise capacity would be affected by an LCKD or training in a mice model. We found that the lipid pool and fatty acid oxidation capacity were both enhanced following the 10-week LCKD. Further, key fatty acid oxidation related genes were upregulated. In contrast, the 8-week training regimen had no effect on fatty acid and ketone body oxidation. Key genes involved in carbohydrate utilization were downregulated in the LCKD groups. However, the improved fatty acid oxidation capacity did not translate into an enhanced maximal exercise capacity. In summary, while favoring the fatty acid oxidation system, an LCKD, alone or combined with training, had no beneficial effects in our intensive exercise-evaluation model. Therefore, an LCKD may be promising to improve endurance in low- to moderate-intensity exercise, and may not be an optimal choice for those partaking in high-intensity exercise.

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