Who Is Thomas Seyfried?
Thomas N. Seyfried is a professor of biology, genetics, and biochemistry at Boston College. He received his PhD from the University of Illinois Urbana-Champaign in 1976. His research focuses on mechanisms of chronic diseases such as cancer, epilepsy, neurodegenerative lipid storage diseases, and caloric restriction diets. He wrote the 2012 book: Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer.
What Is the Approach? Ketogenic Diet (KD)
Thomas Seyfried’s research argues that a person may be able to “starve” tumor cells by controlling their food source: glucose and glutamine. He does this by helping patients reach a state of “ketosis” through caloric restriction and a ketogenic diet (low sugar, high fat). This causes blood sugar to drop and the body uses ketones as a source of fuel rather than glucose. The idea is that this makes less glucose available for the cancer to grow on. His theory also states that normal cells in the body can use ketones as a food source, but cancer cannot.
What Does Research Say?
Controlling a person’s blood sugar levels appears to help slow growth and prevent cancers that are affected by high blood sugar levels. Not all cancers are as necessarily affected by blood sugar, but many are. Research has found that breast cancer is one of the cancers where blood sugar may increase the risk of developing the cancer.[1] As such, the 2020 study below found benefit to those with breast cancer using a low-sugar diet (the ketogenic diet).
Positive Research Studies
A 2020 study on breast cancer taking chemotherapy compared 30 patients on KD and 30 on SD. Those on the KD had a 100% survival rate at 25 months while those on SD had a 60% survival rate.[2] This was a statistically significant finding.
Mixed Research
The following studies are considered “mixed” evidence because the results showed no benefit or because the study did not assess something concrete, such as overall survival.
A 2017 study was completed on pancreatic and lung cancer (it only had nine patients however so it is difficult to draw conclusions).[3] The patients with the highest adherence to the KD as measured by level of ketones had an average survival of 14.9 months, while the patients with lower adherence and lower ketone levels had an average survival of 18.28 months (non-statistical significance).[4] This difference was mostly due to the patients with pancreatic cancer however. Those with lung cancer in the study had around the same length of survival. In the end this study is very small, so it is difficult to know whether it was random chance given the results did not reach statistical significance.
A 2014 study of 10 patients with brain cancer concluded that a ketogenic diet is feasible and safe but probably has no significant clinical activity when used as a stand alone treatment.[5] They found that it appeared to improve the efficacy of bevacizumab therapy.
A 2022 study on patients with head and neck cancers compared KD to standard diet (SD) and found similar overall survival and rates of cancer progression, with no statistical differences in either measure.[6]
A 2021 study in patients with rectal cancer found that a KD led to significant muscle and weight loss at the onset of the diet. Afterwards a continued small decline in weight was noticed (0.4 kg body weight per week). Quality of life remained stable in the SD group but increased in the KD group from a score of 66.7 to 75.0 (p = 0.20).[7]
A 2020 study on patients with breast cancer patients found that those in the KD group lost body weight and fat free and skeletal muscle mass quickly after diet onset, which for the most part was related to water losses.[8] However, the KD did not cause further substantial changes in fat free or skeletal muscle mass, but was associated with a gradual decrease of 0.4 kg body weight and fat mass per week (p < 0.0001).
A 2021 study in patients with breast cancer found that those consuming a ketogenic diet had significant improvements in sleep, quality of life and cancer-related side effects. There were no signs of adverse effects to the liver or kidney function. In contrast, biomarkers of metabolic health improved in the ketogenic diet group (GGT, creatinine, triglycerides, IGF-1, free T3).[9]
A 2020 study in patients with breast cancer found higher quality of life at 6 weeks compared to patients not on a ketogenic diet, but no improvement at 12 weeks.[10]
A 2018 study on those with endometrial cancer found improvement in energy and physical function in those using the KD.[11]
A 2018 study on ovarian and endometrial cancer found greater weight loss and lower insulin in the KD group.[12]
Cautions
Ketogenic diets are very restrictive and can cause nutritional deficiencies, metabolic acidosis, and other complications. It is important to be monitored by a health professional before considering the ketogenic diet.
Certain cancers already cause severe weight loss, such as pancreatic and lung cancer. Caution is warranted in these cancers because ketogenic diets and caloric restriction may worsen weight loss. This is important because with too much weight loss the body starts to use the muscles as an energy source. This leads to a loss of muscle mass and studies have found that cancer patients with higher muscle mass tend to have greater overall survival.[13] The immune system also kills cancer cells and too much weight loss may compromise the immunity.
Contrary to Thomas Seyfreid’s research, some studies have also found that certain types of cancer may be able to survive on ketones.[14]
Conclusion
Dr. Baker (ND) can help determine whether the ketogenic diet is suitable for your stage and type of cancer. While on the diet, he will also often recommend a panel of blood testing to monitor for common complications and nutritional deficiencies that may occur. These should be addressed as early as possible to reduce the risk of side effects. The ketogenic diet can worsen some of the common side effects of certain types of cancer, such as weight and muscle loss. This diet is not suitable for certain contexts and it is important to speak with a health provider to help assess its safety for your situation.
References
[1] Diabetes and breast cancer risk: a meta-analysis; P Boyle, M Boniol, A Koechlin, C Robertson, F Valentini, K Coppens, L-L Fairley, M Boniol, T Zheng, Y Zhang, M Pasterk, M Smans, M P Curado, P Mullie, S Gandini, M Bota, G B Bolli, J Rosenstock & P Autier; British Journal of Cancer volume 107, pages1608–1617 (2012)
[2] Cohen CW, Fontaine KR, Arend RC, Gower BA. A Ketogenic Diet Is Acceptable in Women with Ovarian and Endometrial Cancer and Has No Adverse Effects on Blood Lipids: A Randomized, Controlled Trial. Nutr Cancer. 2020;72(4):584-594. doi: 10.1080/01635581.2019.1645864. Epub 2019 Jul 27. PMID: 31352797.
[3] Zahra A, Fath MA, Opat E, Mapuskar KA, Bhatia SK, Ma DC, Rodman SN III, Snyders TP, Chenard CA, Eichenberger-Gilmore JM, Bodeker KL, Ahmann L, Smith BJ, Vollstedt SA, Brown HA, Hejleh TA, Clamon GH, Berg DJ, Szweda LI, Spitz DR, Buatti JM, Allen BG. Consuming a Ketogenic Diet while Receiving Radiation and Chemotherapy for Locally Advanced Lung Cancer and Pancreatic Cancer: The University of Iowa Experience of Two Phase 1 Clinical Trials. Radiat Res. 2017 Jun;187(6):743-754. doi: 10.1667/RR14668.1. Epub 2017 Apr 24. PMID: 28437190; PMCID: PMC5510645.
[4] Zahra A, Fath MA, Opat E, Mapuskar KA, Bhatia SK, Ma DC, Rodman SN III, Snyders TP, Chenard CA, Eichenberger-Gilmore JM, Bodeker KL, Ahmann L, Smith BJ, Vollstedt SA, Brown HA, Hejleh TA, Clamon GH, Berg DJ, Szweda LI, Spitz DR, Buatti JM, Allen BG. Consuming a Ketogenic Diet while Receiving Radiation and Chemotherapy for Locally Advanced Lung Cancer and Pancreatic Cancer: The University of Iowa Experience of Two Phase 1 Clinical Trials. Radiat Res. 2017 Jun;187(6):743-754. doi: 10.1667/RR14668.1. Epub 2017 Apr 24. PMID: 28437190; PMCID: PMC5510645.
[5] ERGO: A pilot study of ketogenic diet in recurrent glioblastoma; JOHANNES RIEGER1,7*, OLIVER BÄHR1*, GABRIELE D. MAURER1*, ELKE HATTINGEN2; KEA FRANZ3; , DANIEL BRUCKER1; STEFAN WALENTA4, ULRIKE KÄMMERER5; JOHANNES F. COY6, MICHAEL WELLER7,8 and JOACHIM P. STEINBACH1,7 Link
[6] Klement RJ, Sweeney RA. Impact of a ketogenic diet intervention during radiotherapy on body composition: V. Final results of the KETOCOMP study for head and neck cancer patients. Strahlenther Onkol. 2022 Nov;198(11):981-993. doi: 10.1007/s00066-022-01941-2. Epub 2022 May 2. PMID: 35499696; PMCID: PMC9059453.
[7] Klement RJ, Koebrunner PS, Meyer D, Kanzler S, Sweeney RA. Impact of a ketogenic diet intervention during radiotherapy on body composition: IV. Final results of the KETOCOMP study for rectal cancer patients. Clin Nutr. 2021 Jul;40(7):4674-4684. doi: 10.1016/j.clnu.2021.05.015. Epub 2021 May 31. PMID: 34233255.
[8] Klement RJ, Champ CE, Kämmerer U, Koebrunner PS, Krage K, Schäfer G, Weigel M, Sweeney RA. Impact of a ketogenic diet intervention during radiotherapy on body composition: III-final results of the KETOCOMP study for breast cancer patients. Breast Cancer Res. 2020 Aug 20;22(1):94. doi: 10.1186/s13058-020-01331-5. PMID: 32819413; PMCID: PMC7441712.
[9] Klement RJ, Weigel MM, Sweeney RA. A ketogenic diet consumed during radiotherapy improves several aspects of quality of life and metabolic health in women with breast cancer. Clin Nutr. 2021 Jun;40(6):4267-4274. doi: 10.1016/j.clnu.2021.01.023. Epub 2021 Jan 27. PMID: 33551218.
[10] Khodabakhshi A, Seyfried TN, Kalamian M, Beheshti M, Davoodi SH. Does a ketogenic diet have beneficial effects on quality of life, physical activity or biomarkers in patients with breast cancer: a randomized controlled clinical trial. Nutr J. 2020 Aug 22;19(1):87. doi: 10.1186/s12937-020-00596-y. PMID: 32828130; PMCID: PMC7443288.
[11] Cohen CW, Fontaine KR, Arend RC, Soleymani T, Gower BA. Favorable Effects of a Ketogenic Diet on Physical Function, Perceived Energy, and Food Cravings in Women with Ovarian or Endometrial Cancer: A Randomized, Controlled Trial. Nutrients. 2018 Aug 30;10(9):1187. doi: 10.3390/nu10091187. PMID: 30200193; PMCID: PMC6163837.
[12] Cohen CW, Fontaine KR, Arend RC, Alvarez RD, Leath CA III, Huh WK, Bevis KS, Kim KH, Straughn JM Jr, Gower BA. A Ketogenic Diet Reduces Central Obesity and Serum Insulin in Women with Ovarian or Endometrial Cancer. J Nutr. 2018 Aug 1;148(8):1253-1260. doi: 10.1093/jn/nxy119. PMID: 30137481; PMCID: PMC8496516.
[13] Pierobon ES, Moletta L, Zampieri S, Sartori R, Brazzale AR, Zanchettin G, Serafini S, Capovilla G, Valmasoni M, Merigliano S, Sperti C. The Prognostic Value of Low Muscle Mass in Pancreatic Cancer Patients: A Systematic Review and Meta-Analysis. J Clin Med. 2021 Jul 7;10(14):3033. doi: 10.3390/jcm10143033. PMID: 34300199; PMCID: PMC8306134.
[14] Bonuccelli G, Tsirigos A, Whitaker-Menezes D, Pavlides S, Pestell RG, Chiavarina B, Frank PG, Flomenberg N, Howell A, Martinez-Outschoorn UE, Sotgia F, Lisanti MP. Ketones and lactate "fuel" tumor growth and metastasis: Evidence that epithelial cancer cells use oxidative mitochondrial metabolism. Cell Cycle. 2010 Sep 1;9(17):3506-14. doi: 10.4161/cc.9.17.12731. Epub 2010 Sep 21. PMID: 20818174; PMCID: PMC3047616.
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