Interview with Professor Thomas Seyfried: http://bit.ly/34uEW9Z
Dr. Seyfried’s book: https://www.amazon.com/Cancer-Metabolic-Disease-Management-Prevention/dp/0470584920
Dear Eric,
This journal presents data before peer-review. The journal is good, however, because it accepts comments from scientists before the paper is published. The article was removed from the internet after we posted the comments below. It appears that none of the authors were familiar with the details cancer energy metabolism. They will need to reevaluate their data and experimental design.
Regards,
Tom
Comment on Sperry et al., “Metabolism of fatty acids and ketone bodies for glioblastoma growth: Implications for Ketogenic Diet Therapy” (doi: http://dx.doi.org/10.1101/659474).
Sperry et al., have provided another interesting study showing how a ketogenic diet fails to manage glioblastoma growth in the U87-MG xenograft mouse model. The results are consistent with the previous findings of Dang et al (PLoS One. 2015 Jul 20;10(7):e0133633, doi: 10.1371/journal.pone.0133633), and Kalaany and Sabatini (Nature. 2009 Apr 9;458(7239):725-31. doi:10.1038/nature07782.) showing that neither caloric restriction nor ketogenic diet have any therapeutic effects on brain tumor growth when the tumors are grown in the brains of Non-Obese Diabetic/Severely Compromised Immuno Deficiency mice (NOD/SCID). It is important to mention that NOD/SCID mice not only have a compromised innate and/or adaptive immune system but also express characteristics of both Type-1 and Type-2 diabetes (Chaparro et al, PNAS, 2006; DOI:10.1073/pnas.0604317103). These findings are inconsistent with other studies showing that caloric restriction and restricted ketogenic diets can reduce U87-MG growth when the tumors are grown in mice that do not have characteristics of Type 1 or Type 2 diabetes (DOI 10.1007/s11060-013-1154-y; DOI:10.1158/1078-0432.CCR-04-0308; doi:10.1186/1743-7075-4-5). Although Sperry et al were careful in their in vitro experiments to maintain normal glucose physiology, they chose a mouse host for their in vivo studies that has no relevance to either normal human or mouse physiology. It remains unclear whether glucose and ketone levels would be linked to tumor growth in this mouse host. The sensitivity of some tumors to metabolic therapy is dependent on host energy metabolism and microenvironment, which are abnormal in NOD/SCID mice. Hence, their conclusions that ketogenic diet fails to manage glioblastoma growth must be viewed with caution.
Comment on Sperry et al., “Metabolism of fatty acids and ketone bodies for glioblastoma growth: Implications for Ketogenic Diet Therapy” (doi: http://dx.doi.org/10.1101/659474).
In their recent study, Sperry et al conclude that the U87-MG model of glioblastoma can utilize fatty acids and ketone bodies for growth. However, their data presented in Figures 1C & 1D argue against this conclusion. It is clear that neither supplementation with fatty acids (Fig. 1C) nor B-OHB (Fig. 1D) could replace glucose as a fuel for maintaining U87 proliferation under lower glucose conditions. If fatty acids and B-OHB could be utilized for growth, then FA & B-OHB supplementation should be able to replace glucose for U87 growth under low glucose conditions. Their data do not show this.
It is also important to mention that human GBM express abnormalities in mitochondrial number, structure, and function all of which will compromise energy production through OxPhos (DOI: 10.1177/1759091418818261). These abnormalities will force the tumor cell to rely more heavily on fermentation then on OxPhos for growth. Neither fatty acids nor ketone bodies are fermentable fuels and cannot replace either glucose or glutamine, which are fermentable through substrate level phosphorylation in the cytoplasm and mitochondria, respectively (DOI: 10.1177/1759091418818261). The data presented in Figures 1C and 1D support this view in showing that neither fatty acids nor B-OHB could replace glucose for maintaining U87 growth rate. Hence, their data do not support their main conclusion that U87 can utilize fatty acids and ketone bodies for growth.
Thomas N. Seyfried
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Dr. Eric Berg DC Bio:
Dr. Berg, 53 years of age is a chiropractor who specializes in Healthy Ketosis & Intermittent Fasting. He is the author of The New Body Type Guide and other books published by KB Publishing. He has taught students nutrition as an adjunct professor at Howard University. He no longer practices, but focuses on health education through social media.
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