I think a lot of what we need to focus on when there is so little human research to guide us is to look at what has the least probability of harm and greatest potential for other benefits.
I couldn’t agree more and very much appreciate your cautions. Several of them (protein restriction/sarcopenia & effect on immune function) have resonated with me, but I’ll address them in a separate post so as to not convolute my message.
I think we DO have mounting evidence that the degree of ketosis necessary to compensate for impaired cerebral hypometabolism (depending on what stage we are intervening) may be MUCH less than that which is required for addressing epilepsy. To suggest that lower levels may have reduced benefit is probably quite accurate when a patient is already experiencing symptoms. That notion may not hold up, however, when applying the strategy earlier in high risk patients. Everything I have learned suggests a continuum may apply here with Dr. Cunnane’s 0.3 - 0.5 mmol/L for high risk patients practicing prevention (E4 carriers; with homozygotes being more severely impacted) ranging to 3.0+ mmol/L (?) for AD patients.
ApropoE4, Richard can better speak to the very high levels of beta-hydroxybutyrate needed to suppress epilepsy; 4.0+ mmol/L(?) They are MUCH higher than the levels we are discussing for preventing or even addressing the initial signs of Alzheimer's. I'm hopeful that the negative side effects for our population will be proportionately less.
For anyone struggling to wrap their heads around this topic, I highly recommend this Medscape article. It’s worth continuing education if you happen to be a neurologist or neurosurgeon
but it’s perfectly suited to our audience as well. (You may need to register to access. It’s free & well worth it.) Brain Glucose Hypometabolism, Ketosis, and Alzheimer Disease: From Controversy to Consensushttp://www.medscape.org/viewarticle/809725_transcript
The research is very clear that our population experiences a reduction in cerebral metabolism in the same brain regions as Alzheimer’s patients decades before the first symptom shows. To simply ignore this because we don’t have enough evidence of the efficacy of utilizing ketone bodies (whether derived via exercise, CR, IF, starchy carb reduction, MUFAs, etc.) could be missing a window of opportunity to prevent the neuronal death that may precede Alzheimer’s pathology.
Dr Isaacson: I try to take a realistic approach with my patients and their families. I tell them we do not have proof, we do not yet have an FDA-approved drug for the prevention of AD. Perhaps one day we will, but until that time, using a combination of these approaches is the best defense we have.
For a better understanding of the mechanism involved and why lower levels of beta-hydroxybutyrate may be enough for us- depending on where we fall on the continuum of affectedness, I highly recommend Dr. Cunnane’s paper:BRAIN FUEL METABOLISM, AGING AND ALZHEIMER’S DISEASEhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3478067/