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.
Nutritional ketosis enhances drug delivery across the blood-brain barrier, allowing for lower therapeutic dosages.
"Once you bring the body into a state of nutritional ketosis, you can use very low doses of these drugs. They pass right through the blood-brain barrier. So that's why Purna Mukherjee said it's a facilitator. It's the way to get these drugs—a vehicle for getting drugs through the blood-brain barrier, which we've established through mass spec analysis, and you don't have to use as much dosage." (said at 0:22:03)
No published clinical or preclinical studies verify the claim that nutritional ketosis broadly enhances drug delivery across the blood-brain barrier to allow lower therapeutic dosages. Preclinical studies on ketogenic diets have primarily investigated neurovascular integrity, monocarboxylate transporters, and clearance mechanisms (such as P-glycoprotein and LRP1-mediated efflux of amyloid-beta), but not enhanced brain penetration of general pharmaceuticals.
The compound IP6 was too toxic when tested in clinical settings and animal models for pancreatic cancer, but became non-toxic and therapeutically synergistic when combined with metabolic therapy.
"And one of the drugs, IP6, was used in the clinic for pancreatic cancer and it was a bust. It was too toxic. We gave it to the mice and it was too toxic. But when we gave it to them in metabolic therapy, it was not toxic and it was super powerful." (said at 0:48:05)
No published clinical trials or animal studies were identified demonstrating that inositol hexaphosphate (IP6 / phytic acid) was too toxic in pancreatic cancer models, nor that combining it with metabolic therapy eliminated toxicity. IP6 is a naturally occurring polyphosphorylated carbohydrate found in high-fiber foods and dietary supplements, and existing preclinical research in pancreatic cancer cell lines has examined it as a non-toxic dietary agent rather than a toxic compound requiring metabolic rescue.
Feeding mice an ad libitum ketogenic diet containing non-sugar sweeteners causes insulin resistance, high blood glucose, and accelerated tumor progression in brain and colon cancer models.
"This new one that just came out on colon cancer in the mice where they ate tubs of lard and the tumors grew faster. We showed it in brain cancer, too. When you give the animals all the lard they want, all the sweet fat, blood sugar stays... Well, they put in KetoCal was a they put a sweetener in there. It was a a sugar substitute not raising blood sugar but making the food taste a little more palatable. The mice chowed down like there was no tomorrow. And we gave it to them ad libitum without any calorie restriction. Oh my god, the tumors were blowing out going through their ears and the blood sugar was high. They created insulin insensitivity eating a ketogenic diet unlimited amounts with a sweetener in it" (said at 1:15:45)
A systematic search across PubMed and Europe PMC did not identify any published studies demonstrating that feeding mice an ad libitum ketogenic diet formulated with non-sugar sweeteners causes insulin resistance, elevated blood glucose, and accelerated tumor progression across brain and colon cancer models. While studies (such as PMID 17313687) have compared calorie-restricted versus unrestricted commercial ketogenic formulas (e.g., KetoCal) in mouse brain tumor models, they focused on caloric restriction and metabolic fuel availability rather than attributing adverse metabolic and oncologic outcomes specifically to non-sugar sweeteners.