HoldsUp

Thomas Seyfried

Boston College

Thomas Seyfried, PhD, is a professor of biology at Boston College who specializes in the metabolic origins and treatment of cancer. He is the author of "Cancer as a Metabolic Disease" and co-developed the Glucose Ketone Index. His published research focuses on ketogenic metabolic therapy, mitochondrial metabolic theories of cancer, cellular fermentation mechanisms, and repurposed drug combinations for conditions such as glioblastoma.

26 claims checked on air: 4 context 5 contradicted 3 overstated 11 supported 3 unverified

What they said on air - supported

5 citing their own research

0:10:47supportedmoderateEmily Kaplan and Dr. Seyfried: The oncology field must under

Brain cancer is the leading cause of disease-related death in children.

"Brain can—childhood brain cancer, number one killer of little kids." (said at 0:10:47)

Epidemiological analyses of pediatric oncology data, including the Global Burden of Disease Study and national cancer registries, confirm that childhood brain and central nervous system (CNS) tumors are the leading cause of cancer- and disease-related mortality in children (surpassing leukemia following advances in hematologic cancer therapies).

0:11:59supportedmoderateEmily Kaplan and Dr. Seyfried: The oncology field must under

Parasites utilize glutamine fermentation and mitochondrial substrate-level phosphorylation to survive in host tissues.

"But it turns out that parasites use the same pathway to live in tissues. So I learned that they use the same inside the matrix of the mitochondria. They're fermenting. The parasites are fermenting using glutamine and mitochondrial substrate-level phosphorylation." (said at 0:11:59)

Parasitic protozoans and helminths commonly utilize fermentation pathways and mitochondrial substrate-level phosphorylation (mSLP)—such as via succinyl-CoA synthetase (SCS) coupled with acetate:succinate CoA-transferase (ASCT)—to generate ATP and survive within host tissue environments, particularly under nutrient- or oxygen-restricted conditions.

0:20:05supportedhighEmily Kaplan and Dr. Seyfried: The oncology field must under

The longest living human being ever documented lived to age 122.

"Even the healthiest person in the world, the—the longest-living person, human being, ever recorded was Madame Calment from France, 122. And she's the only human being that ever lived that long." (said at 0:20:05)

Demographic validation studies confirm that Jeanne Calment is the longest-living documented human being, having lived to the validated age of 122 years and 164 days before her death in 1997.

0:21:32supportedlowEmily Kaplan and Dr. Seyfried: The oncology field must under

Pediatric brain tumors are metabolically dependent on both glucose and glutamine for growth.

"And these tumors are also dependent on the sugar glucose and the amino acid glutamine. And I don't see any—any intervention in the pediatric neuro-oncology field of simultaneously targeting glucose and glutamine like we did in our preclinical study published in Cell Reports Medicine" (said at 0:21:32)

Preclinical metabolic profiling, animal xenograft studies, and patient imaging in pediatric brain tumors—including medulloblastoma and diffuse intrinsic pontine glioma (DIPG)—demonstrate a strong metabolic dependence on both glucose (glycolysis/TCA cycle) and glutamine (glutaminolysis) to sustain energy production, macromolecular biosynthesis, epigenetic reprogramming, and tumor progression. Because evidence derives primarily from preclinical cell and animal models alongside translational imaging studies, the certainty is graded as low.

0:29:20supportedhighEmily Kaplan and Dr. Seyfried: The oncology field must under

Ketogenic metabolic therapy has been used clinically in children for decades to manage epilepsy.

"And then, of course, when you realize that ketogenic metabolic therapy has been used in little children for managing epilepsy for decades, and then you have kids with brain cancer right down the hall that should be using the same kind of thing." (said at 0:29:20)

Ketogenic diet therapy (ketogenic metabolic therapy) has been used clinically as an established non-pharmacological treatment for drug-resistant epilepsy in pediatric patients since the 1920s (a century of clinical use). Extensive systematic reviews and randomized controlled trials confirm its established role and efficacy in reducing seizure frequency in children with refractory epilepsy.

0:30:32supportedhighEmily Kaplan and Dr. Seyfried: The oncology field must under

Dr. Russell Wilder introduced the ketogenic diet in 1921 to manage epileptic seizures after observing that water fasting reduced seizures in children.

"But that goes back to Wilder, 1921, when he first used ketogenic metabolic therapy to manage epileptic seizures because he found that children or people, when they just drank water for a few days, the seizures would subside. But you can't do that for very long. So he developed then this high-fat diet that would create an internal metabolic environment similar to water-only fasting." (said at 0:30:32)

Historical medical literature confirms that Dr. Russell Wilder introduced the ketogenic diet at the Mayo Clinic in 1921. He proposed the diet as a way to mimic the biochemical effects of fasting (ketonemia/ketogenesis), which had previously been observed to reduce epileptic seizures.

0:31:28supportedhighEmily Kaplan and Dr. Seyfried: The oncology field must under

A clinical trial led by Helen Cross demonstrated that ketogenic metabolic therapy significantly reduces epileptic seizures in children.

"So Helen Cross from England and a group from Johns Hopkins, Beth Zupec-Kania, and all these folks that I know set up a clinical trial. And clearly, without any ambiguity, the ketogenic metabolic therapy was powerful in reducing epileptic seizures for children." (said at 0:31:28)

A landmark randomized controlled trial led by J. Helen Cross and colleagues (Neal et al., 2008, The Lancet Neurology) evaluated 145 children aged 2-16 years with treatment-resistant epilepsy. The trial demonstrated that after 3 months, seizure frequency was significantly lower in children assigned to a ketogenic diet compared to controls (mean percentage of baseline seizures: 62.0% vs. 136.9%, p < 0.0001), with 38% of children on the diet achieving a >50% seizure reduction compared with 6% of controls.

0:37:00supportedmoderateEmily Kaplan and Dr. Seyfried: The oncology field must under

Cancer cachexia involves the mobilization of skeletal muscle proteins for gluconeogenesis and direct tumor utilization of glutamine.

"And cachexia, which is the action of the tumor on the muscles, they will mobilize proteins out of the muscles and create sugar from gluconeogenesis and using glutamine directly." (said at 0:37:00)

Cancer cachexia is established to involve systemic host hypercatabolism, characterized by skeletal muscle proteolysis that releases free amino acids into circulation to fuel hepatic gluconeogenesis and meet the metabolic demands of the growing tumor (such as glutaminolysis and energy production).

0:38:25supportedhighEmily Kaplan and Dr. Seyfried: The oncology field must under

All mitochondria in the human body are derived exclusively from the maternal egg.

"And when I look at mitochondria, all of the mitochondria in our body were derived from the egg, the mother's egg." (said at 0:38:25)

Human mitochondrial DNA (mtDNA) is inherited exclusively through the maternal lineage. Although sperm introduce mitochondria into the oocyte during fertilization, paternal mitochondria are devoid of intact mtDNA and lack the transcription factor TFAM required for mtDNA maintenance, and paternal mitochondrial structures are targeted for elimination via mitophagy and ubiquitin-proteasome pathways. While isolated reports proposed biparental transmission, large-scale genomic analyses showed these were artifacts caused by nuclear insertions of mitochondrial DNA (mega-NUMTs) rather than paternal mitochondrial transmission.

1:12:20supportedlowEmily Kaplan and Dr. Seyfried: The oncology field must under

Burning ketone bodies significantly reduces the cellular production of reactive oxygen species.

"Also uh when you burn ketones, you reduce reactive oxygen species. That's one of the that's why they call it a superfuel. you don't produce reactive ROS, reactive oxygen species when you're burning ketones." (said at 1:12:20)

Preclinical and in vitro studies demonstrate that the metabolism of ketone bodies (notably beta-hydroxybutyrate) attenuates cellular and mitochondrial reactive oxygen species (ROS) production while enhancing antioxidant defenses (such as glutathione). However, this evidence is primarily established in cellular models and animal tissues rather than direct in vivo human outcome measurements, warranting a low certainty rating.

1:20:42supportedmoderateEmily Kaplan and Dr. Seyfried: The oncology field must under

Individuals with inborn carnitine deficiency may need carnitine supplementation to achieve a low Glucose Ketone Index.

"And don't forget carnitine deficiency which is an inborn error of metabolism. Most people never even recognize it. May have to have carnitine supplementations to get down into the low GKI." (said at 1:20:42)

Carnitine is an essential cofactor for the transport of long-chain fatty acids across the inner mitochondrial membrane via carnitine palmitoyltransferases for beta-oxidation and subsequent hepatic ketogenesis. Primary (inborn) carnitine deficiency impairs fatty acid oxidation, classically resulting in hypoketotic hypoglycemia during fasting or metabolic stress. Because achieving a low Glucose Ketone Index (GKI) requires substantial ketone body production relative to blood glucose, individuals with inborn defects in carnitine transport or metabolism require L-carnitine supplementation to restore mitochondrial fatty acid transport and enable ketogenesis.

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