Interview: Thomas Seyfried on Glioblastoma, Metabolic Cancer Breakthroughs, with David Gornoski on A Neighbor's Choice

"Dr. Thomas Seyfried, Tucker Goodrich, David Gornoski on Glioblastoma, Metabolic Cancer Breakthroughs" 

"Continuing our exciting overthrow of failed sacred cows with science-driven conversation on health and nutrition, David Gornoski and Tucker Goodrich are joined by Dr. Thomas Seyfried, the leading researcher of the metabolic theory of cancer. Prof. Seyfried of Boston College talks about the experience of Pablo Kelly who treated his brain cancer with ketogenic diet. Is Dr. Seyfried's method compatible with Dr. Lisanti's way of treating cancer? Is cancer a genetic disease? Why is metabolic therapy only considered as a last measure for cancer and epileptic patients after standardized treatments fail? What is the role of Cardiolipin in the cell and how does Cardiolipin damage affect us? How can we stop Cardiolipin damage? 

"Visit Dr. Seyfried's website at https://www.tomseyfried.com 

"For more content by David Gornoski visit https://www.aneighborschoice.com

Here's a link to the podcast, and here's an embedded player:

Here are most of the show notes, which will also be updated (If you listen to it at real speed, I will probably finish before you do!).

And in today's news: "Feasibility and Biological Activity of a Ketogenic/Intermittent-Fasting Diet in Patients With Glioma".

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Show notes:

Long-term glioblastoma survivor, Pablo Kelly, reaches out with a message of hope (https://t.co/tXiSll8xat). Pablo was the subject of our case report published in Frontiers in Nutrition (/doi.org/10.3389/fnut.2021.682243).

— Thomas N. Seyfried (@tnseyfried) July 8, 2021

Pablo Kelly case report (Seyfried et al., 2021)

Media stories (Davies, 2016; Dodd, 2017; “Fighting for Survival -Pablo Battles Brain Tumour with Ketogenic Diet and Healthy Doses ofDetermination and Positivity,” 2016)

Glioblastoma prognosis: “…without any treatment you can expect to live between 8 and 14 months.” (Bailey & Cushing, 1926)

“Current Standards of Care in Glioblastoma Therapy” (Fernandes et al., 2017)

“…showing precisely how Standard of Care contributes to the rapid demise of the patients…” (Seyfried et al., 2019)

IDH1 mutation (Li et al., 2019)

“If you have a tumor, you should never irradiate somebody’s brain! It’s insane! I published a very clear article on this…” TK

Cancer treatment fails (Horgan, 2019)

Cancer depends on glutamine (Seyfried, 2011)

Mutations don’t cause cancer (Sonnenschein & Soto, 2000)

Mitochondrial transfer experiments in cancerous cells (Zampieri et al., 2021)

P53 gene mutations (Baugh et al., 2018) and effects on mitochondria (Moulder et al., 2018)

Warburg effect and metabolic hypothesis for cancer (Seyfried, 2015)

Substrate-Level Phosphorylation (Chinopoulos & Seyfried, 2018)

ATP Synthesis and cancer (Seyfried et al., 2020)

“Michael Lisanti Interview on His Breakthrough Antibiotic Solution for Cancer Metastasis, ATP” (Gornoski, 2021, 2021)

“Nothing in Biology Makes Sense Except in the Light of Evolution” (Dobzhansky, 1973)

Evolutionary concepts of default and quiescent states (Sonnenschein & Soto, 2000)

PD-L1 Inhibitors and patient mortality:

“Findings:  In this systematic review and meta-analysis of 125 clinical trials involving 20 128 patients, the overall incidences of all-grade adverse events were 66.0% and of grade 3 or higher adverse events were 14.0%. The overall mean adverse event incidences were similar across different cancer types but varied between different drugs.” (Wang et al., 2019)

Efficacy and research base of ketogenic diet in cancer (Colin Champ) (Haskins et al., 2020; Klement et al., 2017)

Ketogenic diet as a first-line therapy (in epilepsy) (Kossoff, 2010)

Unknown mechanism for metformin (Vial et al., 2019)

Cardiolipin and cancer (53:49) (Kiebish et al., 2008, 2010; Seyfried, 2015; Ta et al., 2014)

Barth syndrome (Peter & Bellcross, 2019)

“Alzheimer's Disease is Associated with Decreased Risk of Cancer-Specific Mortality” (Romero et al., 2014)

Veech “superfuel” (Cahill & Veech, 2003)

Jim Abrahams and the Charlie Foundation (Abrahams, 2018)

...I ran out of time and energy at 1 hour through the interview. End of show notes.

 And in today's news: "Feasibility and Biological Activity of a Ketogenic/Intermittent-Fasting Diet in Patients With Glioma". (Schreck et al., 2021)

References:

Abrahams, J. (2018, August 29). Charlie’s Story [Informational]. CURE Epilepsy. https://www.cureepilepsy.org/personal_stories/charlies-story/

Bailey, P., & Cushing, H. (1926). A Classification of the Tumors of the Glioma Group on a Histogenetic Basis with a Correlated Study of Prognosis. J.B. Lippincott.

Baugh, E. H., Ke, H., Levine, A. J., Bonneau, R. A., & Chan, C. S. (2018). Why are there hotspot mutations in the TP53 gene in human cancers? Cell Death & Differentiation, 25(1), 154–160. https://doi.org/10.1038/cdd.2017.180

Cahill, G. F., & Veech, R. L. (2003). Ketoacids? Good medicine? Transactions of the American Clinical and Climatological Association, 114, 149–161; discussion 162-163. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194504/

Chinopoulos, C., & Seyfried, T. N. (2018). Mitochondrial Substrate-Level Phosphorylation as Energy Source for Glioblastoma: Review and Hypothesis. ASN Neuro, 10, 1759091418818261. https://doi.org/10.1177/1759091418818261

Davies, M. (2016, July 15). Terminal cancer patient claims giving up CARBS kept him alive. Mail Online. https://www.dailymail.co.uk/health/article-3691808/Quitting-carbs-saved-life-Cancer-victim-given-months-live-refuses-chemo-claims-diet-meat-dairy-s-alive-two-years-later.html

Dobzhansky, T. (1973). Nothing in Biology Makes Sense except in the Light of Evolution. The American Biology Teacher, 35(3), 125–129. https://doi.org/10.2307/4444260

Dodd, R. (2017, August 11). This man had his brain tumour cut out while he was still awake. PlymouthLive. http://www.plymouthherald.co.uk/news/local-news/man-brain-tumour-cut-out-316430

Fernandes, C., Costa, A., Osório, L., Lago, R. C., Linhares, P., Carvalho, B., & Caeiro, C. (2017). Current Standards of Care in Glioblastoma Therapy. In S. De Vleeschouwer (Ed.), Glioblastoma. Codon Publications. http://www.ncbi.nlm.nih.gov/books/NBK469987/

Fighting for survival—Pablo battles brain tumour with ketogenic diet and healthy doses of determination and positivity. (2016, July 5). Dartmouth Chronicle. http://www.dartmouth-today.co.uk/article.cfm?id=104128&headline=Fighting%20for%20survival%20-%20Pablo%20battles%20brain%20tumour%20with%20ketogenic%20diet%20and%20healthy%20doses%20of%20determination%20and%20positivity&sectionIs=news&searchyear=2016

Gornoski, D. (2021, June 9). Michael Lisanti Interview on His Breakthrough Antibiotic Solution for Cancer Metastasis, ATP. https://www.youtube.com/watch?v=ljw7QfWkqco&t=3s

Gornoski, D. (2021, June 9). Michael Lisanti Interview on His Breakthrough Antibiotic Solution for Cancer Metastasis, ATP (No. 2021-06–10) [Mp3]. https://aneighborschoice.com/michael-lisanti-interview-on-his-breakthrough-antibiotic-solution-for-cancer-metastasis-atp/

Haskins, C. P., Champ, C. E., Miller, R., & Vyfhuis, M. A. L. (2020). Nutrition in Cancer: Evidence and Equality. Advances in Radiation Oncology, 5(5), 817–823. https://doi.org/10.1016/j.adro.2020.05.008

Horgan, J. (2019, August 1). Cancer Medicine Is Failing Us [Blog]. Scientific American Blog Network. https://blogs.scientificamerican.com/cross-check/cancer-medicine-is-failing-us/

Kiebish, M. A., Bell, R., Yang, K., Phan, T., Zhao, Z., Ames, W., Seyfried, T. N., Gross, R. W., Chuang, J. H., & Han, X. (2010). Dynamic simulation of cardiolipin remodeling: Greasing the wheels for an interpretative approach to lipidomics [S]. Journal of Lipid Research, 51(8), 2153–2170. https://doi.org/10.1194/jlr.M004796

Kiebish, M. A., Han, X., Cheng, H., Chuang, J. H., & Seyfried, T. N. (2008). Cardiolipin and electron transport chain abnormalities in mouse brain tumor mitochondria: Lipidomic evidence supporting the Warburg theory of cancer *. Journal of Lipid Research, 49(12), 2545–2556. https://doi.org/10.1194/jlr.M800319-JLR200

Klement, R. J., Feinman, R. D., Gross, E. C., Champ, C. E., D’Agostino, D. P., Fine, E. J., Kämmerer, U., Poff, A., Rho, J. M., Seyfried, T. N., & Scheck, A. C. (2017). Need for new review of article on ketogenic dietary regimes for cancer patients. Medical Oncology, 34(6), 108. https://doi.org/10.1007/s12032-017-0968-4

Kossoff, E. H. (2010). The ketogenic diet: An appropriate first-line therapy? Expert Review of Neurotherapeutics, 10(6), 843–845. https://doi.org/10.1586/ern.10.35

Li, S., Sun, C., Gu, Y., Gao, X., Zhao, Y., Yuan, Y., Zhang, F., Hu, P., Liang, W., Cao, K., Zhang, J., Wang, Z., & Ye, J. (2019). Mutation of IDH1 aggravates the fatty acid‑induced oxidative stress in HCT116 cells by affecting the mitochondrial respiratory chain. Molecular Medicine Reports, 19(4), 2509–2518. https://doi.org/10.3892/mmr.2019.9903

Moulder, D. E., Hatoum, D., Tay, E., Lin, Y., & McGowan, E. M. (2018). The Roles of p53 in Mitochondrial Dynamics and Cancer Metabolism: The Pendulum between Survival and Death in Breast Cancer? Cancers, 10(6), 189. https://doi.org/10.3390/cancers10060189

Peter, M., & Bellcross, C. A. (2019). Barth Syndrome [Informational]. NORD (National Organization for Rare Disorders). https://rarediseases.org/rare-diseases/barth-syndrome/

Romero, J. P., Benito-León, J., Louis, E. D., & Bermejo-Pareja, F. (2014). Alzheimer’s Disease is Associated with Decreased Risk of Cancer-Specific Mortality: A Prospective Study (NEDICES). Journal of Alzheimer’s Disease, 40(2), 465–473. https://doi.org/10.3233/JAD-132048

Schreck, K. C., Hsu, F.-C., Berrington, A., Henry-Barron, B., Vizthum, D., Blair, L., Kossoff, E. H., Easter, L., Whitlow, C. T., Barker, P. B., Cervenka, M. C., Blakeley, J. O., & Strowd, R. E. (2021). Feasibility and Biological Activity of a Ketogenic/Intermittent-Fasting Diet in Patients With Glioma. Neurology. https://doi.org/10.1212/WNL.0000000000012386

Seyfried, T. N. (2011). Abstract 985: Mitochondrial glutamine fermentation enhances ATP synthesis in murine glioblastoma cells. Cancer Research, 71(8 Supplement), 985. https://doi.org/10.1158/1538-7445.AM2011-985

Seyfried, T. N. (2015). Cancer as a mitochondrial metabolic disease. Frontiers in Cell and Developmental Biology, 3. https://doi.org/10.3389/fcell.2015.00043

Seyfried, T. N., Arismendi-Morillo, G., Mukherjee, P., & Chinopoulos, C. (2020). On the Origin of ATP Synthesis in Cancer. IScience, 23(11), 101761. https://doi.org/10.1016/j.isci.2020.101761

Seyfried, T. N., Shelton, L., Arismendi-Morillo, G., Kalamian, M., Elsakka, A., Maroon, J., & Mukherjee, P. (2019). Provocative Question: Should Ketogenic Metabolic Therapy Become the Standard of Care for Glioblastoma? Neurochemical Research, 44(10), 2392–2404. https://doi.org/10.1007/s11064-019-02795-4

Seyfried, T. N., Shivane, A. G., Kalamian, M., Maroon, J. C., Mukherjee, P., & Zuccoli, G. (2021). Ketogenic Metabolic Therapy, Without Chemo or Radiation, for the Long-Term Management of IDH1-Mutant Glioblastoma: An 80-Month Follow-Up Case Report. Frontiers in Nutrition, 8. https://doi.org/10.3389/fnut.2021.682243

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Ta, N. L., Jia, X., Kiebish, M., & Seyfried, T. N. (2014). Autosomal Dominant Inheritance of Brain Cardiolipin Fatty Acid Abnormality in VM/DK Mice: Association with Hypoxic-Induced Cognitive Insensitivity. Lipids, 49(1), 113–117. https://doi.org/10.1007/s11745-013-3857-4

Vial, G., Detaille, D., & Guigas, B. (2019). Role of Mitochondria in the Mechanism(s) of Action of Metformin. Frontiers in Endocrinology, 10. https://doi.org/10.3389/fendo.2019.00294

Wang, Y., Zhou, S., Yang, F., Qi, X., Wang, X., Guan, X., Shen, C., Duma, N., Vera Aguilera, J., Chintakuntlawar, A., Price, K. A., Molina, J. R., Pagliaro, L. C., Halfdanarson, T. R., Grothey, A., Markovic, S. N., Nowakowski, G. S., Ansell, S. M., & Wang, M. L. (2019). Treatment-Related Adverse Events of PD-1 and PD-L1 Inhibitors in Clinical Trials: A Systematic Review and Meta-analysis. JAMA Oncology, 5(7), 1008–1019. https://doi.org/10.1001/jamaoncol.2019.0393

Zampieri, L. X., Silva-Almeida, C., Rondeau, J. D., & Sonveaux, P. (2021). Mitochondrial Transfer in Cancer: A Comprehensive Review. International Journal of Molecular Sciences, 22(6), 3245. https://doi.org/10.3390/ijms22063245