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Created page with "The Ketogenic Diet may help with the treatment of cancer, including brain tumors<ref name="Seyfried-2011"/><ref name="Seyfried-2009"/><ref name="Seyfried-2005"/>. There ar..."
The [[Ketogenic Diet]] may help with the treatment of cancer, including brain tumors<ref name="Seyfried-2011"/><ref name="Seyfried-2009"/><ref name="Seyfried-2005"/>. There are researchers who believe that the origin of cancer lies with metabolic abnormalities that lead to genetic problems rather than the genetic problems being the root cause<ref name="SeyfriedFlores2013"/>.
=How the Ketogenic Diet may help=
There may be several mechanisms behind the effect of the ketogenic diet on cancer.
* Tumor cells are unable to metabolize ketones<ref name="Maurer-2011"/>.
* Cancers promote the growth of new blood vessels, something the ketogenic diet inhibits, as Ketones are [http://en.wikipedia.org/wiki/Angiogenesis_inhibitor anti-angiogenic]<ref name="Zhou-2007"/>. This is also seen with calorie restriction, which reduces vascularity and increased apoptosis in mouse and human brain tumors<ref name="Mukherjee-2004"/>.
* Cancer cells often don't undergo natural cell death, something the ketogenic diet enhances<ref name="Skinner-2009"/>.
* Ketones may directly reduce the viability of cancer cells<ref name="Skinner-2009"/>.
* The ketogenic diet typically reduces blood glucose levels, and high blood glucose is associated with tumor growth and reduced survival rates in cancer patients<ref name="Chaichana-2010"/><ref name="Derr-2009"/><ref name="McGirt-2008"/> and animal models<ref name="Venkateswaran-2007"/>.
* Carbohydrate restriction lowers insulin and insulin-like growth factor (IGF) which directly stimulate tumor cell proliferation<ref name="Klement-2011"/>.
=Animal Studies=
There are a number of animal studies that have looked at the ketogenic diet and cancer.
* A study of [http://en.wikipedia.org/wiki/Glioma Glioma] tumor cells showed that an unrestricted ketogenic diet in mice that raised ketone levels without lowering glucose levels did not change survival rates<ref name="Maurer-2011"/>.
* The unrestricted diet combined with [[Omega 3]] and [[MCT]] delayed the growth of implanted gastric cancer cells in mice<ref name="Otto-2008"/>.
* The ketogenic diet may need to be combined with calorie restriction to ensure lowered glucose levels for the treatment of brain tumors<ref name="Seyfried-2008"/>. A study that compared an unrestricted standard diet, an unrestricted ketogenic diet and a restricted ketogenic diet in mice with implanted brain tumors, only the restricted ketogenic diet improved survival rates<ref name="Zhou-2007"/>.
* Drugs are being developed for cancer treatment that target metabolic pathways<ref name="Tennant-2010"/>.
* Giving a no-carbohydrate ketogenic diet to rats with grafted prostate cancer tumors resulted in a 33% smaller tumor size than controls fed a western diet<ref name="Freedland-2008"/>. In another study, rats with grafted prostate cancer tumors given 0%, 10% or 20% carbohydrate had similar survival rates<ref name="Masko-2010"/>.
* Rats with grafted prostate cancer tumors given a no-carbohydrate ketogenic diet (83% fat, 0% carbohydrate, 17% protein) had a better survival rate than those given a medium carbohydrate diet (40% fat, 43% carbohydrate, 17% protein), but their survival was similar to those given a low fat diet (12% fat, 71% carbohydrate, 17% protein)<ref name="Mavropoulos-2009"/>.
* Rats with grafted lung cancer tumors showed that a ketogenic diet improved the effectiveness of radiation and chemotherapy<ref name="AllenBhatia2013"/>.
* Rats with metastatic cancer had a 57% longer average survival time on the ketogenic diet than controls, and 78% longer when the ketogenic diet was combined with a hyperbaric oxygen therapy<ref name="TangPoff2013"/>.
=Human Case Studies=
While I have not found any large studies of the ketogenic diet on humans, there are a number of smaller case studies that look promising.
* A case study of two children with inoperable [http://en.wikipedia.org/wiki/Astrocytoma Astrocytoma] brain tumors that regressed under the ketogenic diet that lowered blood glucose levels is promising<ref name="Nebeling-1995"/>. This trial used the [[MCT Diet]] with 60% of calories from [[MCT]], 20% from protein, 10% from carbohydrate, and 10% from other dietary fats, with total calories calculated at 120% of target to ensure weight gain<ref name="Nebeling-2-1995"/>.
* A study looked at the use of the Ketogenic Diet in 16 patients with advanced cancer and no other treatment options concluded that the diet was a suitable possibility and might improve some aspects of their quality of life<ref name="SchmidtPfetzer2011"/>. Not all the patients maintained the diet, with only 5 completing the 12 week study. Because of the low number of subjects and their heterogeneity, it was not possible to evaluate the impact of the diet on the tumors. However, the outcome for the 16 patients is intriguing:
** 4 patients dropped out early.
** 2 patients died early.
** 5 patients discontinued the diet and their disease progressed.
** 5 patients followed the diet and their disease was stable.
* A 65 year old woman with Glioblastoma multiforme (the most malignant primary brain tumor in adults and children) was treated with partial tumor resection and a combination of standard therapy and a restricted ketogenic diet. The diet was a calorie restricted (600 kcal/day) [[Ketogenic Ratio Diet]] (4:1) for two months, resulting in a 20% reduction in body weight. After the two months there were no discernable signs of the tumor with FDG-PET or MRI imaging<ref name="ZuccoliMarcello2010"/>. When a normal diet was resumed for 10 weeks there were signs of the tumor resurging on MRI scans. (See timeline of treatment below.)
* A (non-ketogenic) high fat diet may help maintain body weight and improve quality of life<ref name="Breitkreutz-2005"/>.
[[File:KetogenicCancerTimeline.jpg|none|thumb|500px|Timeline of the treatment of a 65 year old woman with Glioblastoma multiforme ..]]
=Non-Ketogenic Fat Intake and Cancer=
There are a number of studies that have looked at the general relationship between fat intake and cancer.
* Fat intake in a non-ketogenic diet impacts tumor growth<ref name="Welsch-1992"/>.
* [[Omega 3]] supplementation may improve the effectiveness of conventional chemotherapy and radiation therapy treatments of cancer<ref name="Hardman-2004"/><ref name="Hardman-2002"/><ref name="Xue-2009"/><ref name="Dupertuis-2007"/>, as well as directly impacting the tumor<ref name="Gutt-2007"/><ref name="Hardman-2007"/><ref name="Kato-2002"/><ref name="Rose-1995"/><ref name="Rose-1996"/> and metastasis<ref name="Rose-1995"/><ref name="Rose-1996"/>.
* Omega-6 oils may increase tumor growth<ref name="Rose-1995"/><ref name="Rose-1991"/><ref name="Welsch-1992"/>.
* Saturated fat tends to stimulate tumor growth, Omega-6 stimulates more than saturated fat, and Omega-3 inhibits growth<ref name="Welsch-1992"/>.
** [[Fiber]] may reduce the impact of fats on cancer risk<ref name="Hursting-1990"/>.
* Omega-3 supplementation may reduce the risk of some cancers<ref name="Karmali-1989"/><ref name="Terry-2003"/><ref name="de Deckere-1999"/>.
* In a study of 35,298 Singapore Chinese women aged 45-74 years, those with the lowest intake of fish Omega-3 had a 26% higher risk of breast cancer<ref name="Gago-Dominguez-2003"/>. For those with the lowest intake of Omega-3, the intake of Omega-6 was inversely related to their breast cancer risk. However, another study of 23,693 postmenopausal women showed that fish consumption increased the risk of estrogen receptor-positive breast cancer by 50% in those with the highest intake compared with the lowest<ref name="Stripp-2003"/>. It has been suggested that this may be due to contamination with organochlorines or other endocrine disrupters in the fish<ref name="Terry-2004"/>. Other studies have found no relationship between fish intake and cancer<ref name="Holmes-2003"/><ref name="Missmer2002"/>.
* The results of trials with mono-unsaturated oils such as olive oils on tumor growth have been inconsistent<ref name="Welsch-1992"/>.
* Restricting calories intake also impacts tumor growth, with 12% restriction reducing tumor growth in rodents<ref name="Welsch-1992"/>.
* Even modest amounts of Omega-6 or saturated fat may negate the benefit of Omega-3<ref name="Welsch-1992"/>.
{{KetoSeeAlso}}
=References=
<references>
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<ref name="Masko-2010">EM. Masko, JA. Thomas, JA. Antonelli, JC. Lloyd, TE. Phillips, SH. Poulton, MW. Dewhirst, SV. Pizzo, SJ. Freedland, Low-carbohydrate diets and prostate cancer: how low is "low enough"?, Cancer Prev Res (Phila), volume 3, issue 9, pages 1124-31, Sep 2010, doi [http://dx.doi.org/10.1158/1940-6207.CAPR-10-0071 10.1158/1940-6207.CAPR-10-0071], PMID [http://www.ncbi.nlm.nih.gov/pubmed/20716631 20716631]</ref>
<ref name="Venkateswaran-2007">V. Venkateswaran, AQ. Haddad, NE. Fleshner, R. Fan, LM. Sugar, R. Nam, LH. Klotz, M. Pollak, Association of diet-induced hyperinsulinemia with accelerated growth of prostate cancer (LNCaP) xenografts., J Natl Cancer Inst, volume 99, issue 23, pages 1793-800, Dec 2007, doi [http://dx.doi.org/10.1093/jnci/djm231 10.1093/jnci/djm231], PMID [http://www.ncbi.nlm.nih.gov/pubmed/18042933 18042933]</ref>
<ref name="AllenBhatia2013">B. G. Allen, S. K. Bhatia, J. M. Buatti, K. E. Brandt, K. E. Lindholm, A. M. Button, L. I. Szweda, B. J. Smith, D. R. Spitz, M. A. Fath, Ketogenic Diets Enhance Oxidative Stress and Radio-Chemo-Therapy Responses in Lung Cancer Xenografts, Clinical Cancer Research, volume 19, issue 14, 2013, pages 3905–3913, ISSN [http://www.worldcat.org/issn/1078-0432 1078-0432], doi [http://dx.doi.org/10.1158/1078-0432.CCR-12-0287 10.1158/1078-0432.CCR-12-0287]</ref>
<ref name="TangPoff2013">Chih-Hsin Tang, Angela M. Poff, Csilla Ari, Thomas N. Seyfried, Dominic P. D'Agostino, The Ketogenic Diet and Hyperbaric Oxygen Therapy Prolong Survival in Mice with Systemic Metastatic Cancer, PLoS ONE, volume 8, issue 6, 2013, pages e65522, ISSN [http://www.worldcat.org/issn/1932-6203 1932-6203], doi [http://dx.doi.org/10.1371/journal.pone.0065522 10.1371/journal.pone.0065522]</ref>
</references>
=How the Ketogenic Diet may help=
There may be several mechanisms behind the effect of the ketogenic diet on cancer.
* Tumor cells are unable to metabolize ketones<ref name="Maurer-2011"/>.
* Cancers promote the growth of new blood vessels, something the ketogenic diet inhibits, as Ketones are [http://en.wikipedia.org/wiki/Angiogenesis_inhibitor anti-angiogenic]<ref name="Zhou-2007"/>. This is also seen with calorie restriction, which reduces vascularity and increased apoptosis in mouse and human brain tumors<ref name="Mukherjee-2004"/>.
* Cancer cells often don't undergo natural cell death, something the ketogenic diet enhances<ref name="Skinner-2009"/>.
* Ketones may directly reduce the viability of cancer cells<ref name="Skinner-2009"/>.
* The ketogenic diet typically reduces blood glucose levels, and high blood glucose is associated with tumor growth and reduced survival rates in cancer patients<ref name="Chaichana-2010"/><ref name="Derr-2009"/><ref name="McGirt-2008"/> and animal models<ref name="Venkateswaran-2007"/>.
* Carbohydrate restriction lowers insulin and insulin-like growth factor (IGF) which directly stimulate tumor cell proliferation<ref name="Klement-2011"/>.
=Animal Studies=
There are a number of animal studies that have looked at the ketogenic diet and cancer.
* A study of [http://en.wikipedia.org/wiki/Glioma Glioma] tumor cells showed that an unrestricted ketogenic diet in mice that raised ketone levels without lowering glucose levels did not change survival rates<ref name="Maurer-2011"/>.
* The unrestricted diet combined with [[Omega 3]] and [[MCT]] delayed the growth of implanted gastric cancer cells in mice<ref name="Otto-2008"/>.
* The ketogenic diet may need to be combined with calorie restriction to ensure lowered glucose levels for the treatment of brain tumors<ref name="Seyfried-2008"/>. A study that compared an unrestricted standard diet, an unrestricted ketogenic diet and a restricted ketogenic diet in mice with implanted brain tumors, only the restricted ketogenic diet improved survival rates<ref name="Zhou-2007"/>.
* Drugs are being developed for cancer treatment that target metabolic pathways<ref name="Tennant-2010"/>.
* Giving a no-carbohydrate ketogenic diet to rats with grafted prostate cancer tumors resulted in a 33% smaller tumor size than controls fed a western diet<ref name="Freedland-2008"/>. In another study, rats with grafted prostate cancer tumors given 0%, 10% or 20% carbohydrate had similar survival rates<ref name="Masko-2010"/>.
* Rats with grafted prostate cancer tumors given a no-carbohydrate ketogenic diet (83% fat, 0% carbohydrate, 17% protein) had a better survival rate than those given a medium carbohydrate diet (40% fat, 43% carbohydrate, 17% protein), but their survival was similar to those given a low fat diet (12% fat, 71% carbohydrate, 17% protein)<ref name="Mavropoulos-2009"/>.
* Rats with grafted lung cancer tumors showed that a ketogenic diet improved the effectiveness of radiation and chemotherapy<ref name="AllenBhatia2013"/>.
* Rats with metastatic cancer had a 57% longer average survival time on the ketogenic diet than controls, and 78% longer when the ketogenic diet was combined with a hyperbaric oxygen therapy<ref name="TangPoff2013"/>.
=Human Case Studies=
While I have not found any large studies of the ketogenic diet on humans, there are a number of smaller case studies that look promising.
* A case study of two children with inoperable [http://en.wikipedia.org/wiki/Astrocytoma Astrocytoma] brain tumors that regressed under the ketogenic diet that lowered blood glucose levels is promising<ref name="Nebeling-1995"/>. This trial used the [[MCT Diet]] with 60% of calories from [[MCT]], 20% from protein, 10% from carbohydrate, and 10% from other dietary fats, with total calories calculated at 120% of target to ensure weight gain<ref name="Nebeling-2-1995"/>.
* A study looked at the use of the Ketogenic Diet in 16 patients with advanced cancer and no other treatment options concluded that the diet was a suitable possibility and might improve some aspects of their quality of life<ref name="SchmidtPfetzer2011"/>. Not all the patients maintained the diet, with only 5 completing the 12 week study. Because of the low number of subjects and their heterogeneity, it was not possible to evaluate the impact of the diet on the tumors. However, the outcome for the 16 patients is intriguing:
** 4 patients dropped out early.
** 2 patients died early.
** 5 patients discontinued the diet and their disease progressed.
** 5 patients followed the diet and their disease was stable.
* A 65 year old woman with Glioblastoma multiforme (the most malignant primary brain tumor in adults and children) was treated with partial tumor resection and a combination of standard therapy and a restricted ketogenic diet. The diet was a calorie restricted (600 kcal/day) [[Ketogenic Ratio Diet]] (4:1) for two months, resulting in a 20% reduction in body weight. After the two months there were no discernable signs of the tumor with FDG-PET or MRI imaging<ref name="ZuccoliMarcello2010"/>. When a normal diet was resumed for 10 weeks there were signs of the tumor resurging on MRI scans. (See timeline of treatment below.)
* A (non-ketogenic) high fat diet may help maintain body weight and improve quality of life<ref name="Breitkreutz-2005"/>.
[[File:KetogenicCancerTimeline.jpg|none|thumb|500px|Timeline of the treatment of a 65 year old woman with Glioblastoma multiforme ..]]
=Non-Ketogenic Fat Intake and Cancer=
There are a number of studies that have looked at the general relationship between fat intake and cancer.
* Fat intake in a non-ketogenic diet impacts tumor growth<ref name="Welsch-1992"/>.
* [[Omega 3]] supplementation may improve the effectiveness of conventional chemotherapy and radiation therapy treatments of cancer<ref name="Hardman-2004"/><ref name="Hardman-2002"/><ref name="Xue-2009"/><ref name="Dupertuis-2007"/>, as well as directly impacting the tumor<ref name="Gutt-2007"/><ref name="Hardman-2007"/><ref name="Kato-2002"/><ref name="Rose-1995"/><ref name="Rose-1996"/> and metastasis<ref name="Rose-1995"/><ref name="Rose-1996"/>.
* Omega-6 oils may increase tumor growth<ref name="Rose-1995"/><ref name="Rose-1991"/><ref name="Welsch-1992"/>.
* Saturated fat tends to stimulate tumor growth, Omega-6 stimulates more than saturated fat, and Omega-3 inhibits growth<ref name="Welsch-1992"/>.
** [[Fiber]] may reduce the impact of fats on cancer risk<ref name="Hursting-1990"/>.
* Omega-3 supplementation may reduce the risk of some cancers<ref name="Karmali-1989"/><ref name="Terry-2003"/><ref name="de Deckere-1999"/>.
* In a study of 35,298 Singapore Chinese women aged 45-74 years, those with the lowest intake of fish Omega-3 had a 26% higher risk of breast cancer<ref name="Gago-Dominguez-2003"/>. For those with the lowest intake of Omega-3, the intake of Omega-6 was inversely related to their breast cancer risk. However, another study of 23,693 postmenopausal women showed that fish consumption increased the risk of estrogen receptor-positive breast cancer by 50% in those with the highest intake compared with the lowest<ref name="Stripp-2003"/>. It has been suggested that this may be due to contamination with organochlorines or other endocrine disrupters in the fish<ref name="Terry-2004"/>. Other studies have found no relationship between fish intake and cancer<ref name="Holmes-2003"/><ref name="Missmer2002"/>.
* The results of trials with mono-unsaturated oils such as olive oils on tumor growth have been inconsistent<ref name="Welsch-1992"/>.
* Restricting calories intake also impacts tumor growth, with 12% restriction reducing tumor growth in rodents<ref name="Welsch-1992"/>.
* Even modest amounts of Omega-6 or saturated fat may negate the benefit of Omega-3<ref name="Welsch-1992"/>.
{{KetoSeeAlso}}
=References=
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