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

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). Consequentl...

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Autores principales: Seyfried, Thomas N., Mukherjee, Purna, Iyikesici, Mehmet S., Slocum, Abdul, Kalamian, Miriam, Spinosa, Jean-Pierre, Chinopoulos, Christos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078107/
https://www.ncbi.nlm.nih.gov/pubmed/32219096
http://dx.doi.org/10.3389/fnut.2020.00021
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author Seyfried, Thomas N.
Mukherjee, Purna
Iyikesici, Mehmet S.
Slocum, Abdul
Kalamian, Miriam
Spinosa, Jean-Pierre
Chinopoulos, Christos
author_facet Seyfried, Thomas N.
Mukherjee, Purna
Iyikesici, Mehmet S.
Slocum, Abdul
Kalamian, Miriam
Spinosa, Jean-Pierre
Chinopoulos, Christos
author_sort Seyfried, Thomas N.
collection PubMed
description 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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spelling pubmed-70781072020-03-26 Consideration of Ketogenic Metabolic Therapy as a Complementary or Alternative Approach for Managing Breast Cancer Seyfried, Thomas N. Mukherjee, Purna Iyikesici, Mehmet S. Slocum, Abdul Kalamian, Miriam Spinosa, Jean-Pierre Chinopoulos, Christos Front Nutr Nutrition 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. Frontiers Media S.A. 2020-03-11 /pmc/articles/PMC7078107/ /pubmed/32219096 http://dx.doi.org/10.3389/fnut.2020.00021 Text en Copyright © 2020 Seyfried, Mukherjee, Iyikesici, Slocum, Kalamian, Spinosa and Chinopoulos. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Nutrition
Seyfried, Thomas N.
Mukherjee, Purna
Iyikesici, Mehmet S.
Slocum, Abdul
Kalamian, Miriam
Spinosa, Jean-Pierre
Chinopoulos, Christos
Consideration of Ketogenic Metabolic Therapy as a Complementary or Alternative Approach for Managing Breast Cancer
title Consideration of Ketogenic Metabolic Therapy as a Complementary or Alternative Approach for Managing Breast Cancer
title_full Consideration of Ketogenic Metabolic Therapy as a Complementary or Alternative Approach for Managing Breast Cancer
title_fullStr Consideration of Ketogenic Metabolic Therapy as a Complementary or Alternative Approach for Managing Breast Cancer
title_full_unstemmed Consideration of Ketogenic Metabolic Therapy as a Complementary or Alternative Approach for Managing Breast Cancer
title_short Consideration of Ketogenic Metabolic Therapy as a Complementary or Alternative Approach for Managing Breast Cancer
title_sort consideration of ketogenic metabolic therapy as a complementary or alternative approach for managing breast cancer
topic Nutrition
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078107/
https://www.ncbi.nlm.nih.gov/pubmed/32219096
http://dx.doi.org/10.3389/fnut.2020.00021
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