Panel Q&A — Is cancer a metabolic disease? — Yes, and also genetic and epi-genetic. Concerns in chronic HDAC inhibition in ketosis with medical imaging and air travel? Colin Champ — pre-clinical data suggests less toxicity from radiation in ketosis. Antioxidant response could be protective. Could PET scan be missing tumors on ketogenic diets? Tracking other health markers and toxicities. OSU KETO-Care project is collecting more data than just the PET scan. Symptom burden of having cancer and on chemotherapy. Cancer patients face discrimination — job loss, frequent treatment, etc. Limitation to the field — funding (no pharma dollars) and then data. Need to treat 1000s of patients in trials. Ketosis is NOT a miracle cure and it should never be positioned that way. It is a tool. There is the reverse Warburg effect. There are mutations that get around glucose. There is the perception that it is “just food” — needs to be taken seriously in terms of implementation. NIH perception that diets should not be studied. The glucose-ketone ratio (GKI) promoted from mouse model work is not realistic for patients and there is no data supporting what level is best. One way to promote this work is to volunteer for NIH study sections — it is an opportunity to have a voice. RFA opportunity. Lack of support for Institutional IRBs are also an issue. Funding from foundations is key to date. The Hopkins et al. 2018 Nature article (Mukherjee, Cantley) is bringing attention to the field. University of Pennsylvania — Penn Center for Nutrition Science and Medicine will be announced this fall — predominantly mouse studies.

Panel — Lustberg, Poff, Champ, Scheck, Hyde, Fine

Clinical Applications for Neurology

Dr. Ken Lee, OSU, Moderator

“Hi, I’m Ken and it’s been 7 years and 3 months since my last carbohydrate.”

Dr. Ken Lee, OSU

Dr. Stephen Cunnane, Universite de Sherbrooke

Brain Glucose and Ketone Metabolism. Fuel requirement for the brain — glucose and ketones — parallel to a hybrid car that runs on gasoline and electricity. Ketones are an ESSENTIAL fuel for development of the infant brain — both for fuel and lipids for cells. Human milk contains medium chain fatty acids (MCT). Using ketosis — recapitulate what the infant brain does. Ketones as the preferred fuel for the brain & glucose sparring. In Alzheimer’s disease, glucose-specific brain energy deficit precedes cognitive decline. Deficit shows up on PET scan before any measurable cognitive decline. Imaging — dual tracer PET and MRI, n=300. CMR is cerebral metabolic rate. Ketone may be able to bypass the glucose deficient in the Alzheimer’s brain — MCT supplementation, or ketogenic diet, or exogenous ketones. (MCT 30 g/d) BENEFIC trial n=39, MCT patients improved relative to controls. MCT 30 g/d was arbitrary chosen — may need a higher dose. Provides proof-of-concept of metabolic rescue. Target is 1 mM BHB in order to have therapeutic effect. Ketogenic diet — more energy into the brain 113% vs. usual diet.