OSU Keto Conference, Day 2 (Part 2)

continued from Day 2, part 1

Day 2, part 2

During this part of the day, the speakers were discussing the effect of ketosis on the brain-- specifically, the effects of ketosis on Alzheimer's and epilepsy.

Stephen Cunnane, PhD: Brain Glucose and Ketone Metabolism (Alzheimer's)

Cunnane talks about how ketones are an essential fuel for infant development. Breast-fed babies spend time in ketosis. There are medium chain triglycerides (MCTs) in mammalian milk.

Glucose is pulled into the brain, while ketones are pushed into the brain.

Alzheimer's sufferers have inhibited glucose uptake into the brain. And glucose uptake deficiency precedes cognitive decline. However, the ketogenic diet shows promise as an Alzheimer's treatment because when brain glucose uptake is impaired, brain ketone uptake is fine.

Cunnane mentioned cerebral metabolic rate. Interestingly, the ketone uptake rate into the brain is not as variable as blood ketone levels. People with Alzheimer's can still uptake ketones!

Cunnane talked about the BENEFIC trial (n=39) where cognitive performance was improved with MCT supplementation (MCTs are easily converted into ketones in the body) ("Conclusion: Ketones from MCT compensate for the brain glucose deficit in AD in direct proportion to the level of plasma ketones achieved.")

The more MCT consumed, the less the brain energy gap there was (glucose was still low, but ketones make up the difference). Also, exercise helps get both glucose and ketones to the brain in Alzheimer's patients. Cunnane noted the difficulty of doing such trials; it took 7 years to get 5 Alzheimer's patients through this protocol.

Summary bullet points (from Cunnane's slides):

• Pre-symptomatic, glucose-specific brain energy deficit.
• Brain energy rescue by ketones is feasible in MCI [Mild Cognitive Impairment] and AD [Alzheimer's Disease].
• Recapitulates role of ketones in infant brain.
• Cognitive benefits and mechanism of action need further evaluation.

Eric Kossoff, MD: Ketogenic Diet and Seizure Management (Epilepsy)

Kossoff is the Director of the Child Neurology Residency Program and a Professor of Neurology at Johns Hopkins. He covered the ketogenic diet's (KD) history in its use as a treatment for epilepsy. We are beyond the tipping point using KD for epilepsy. It is now a mainstream-accepted treatment.

Kossoff noted that in Mark 9:14-29, Jesus recommended prayer and fasting for seizure cure.

In 1921, Dr. Wilder at the Mayo Clinic learned that Low-Carb, High-Fat (LCHF) mimics fasting.

Fasting and ketosis work for epilepsy via different mechanisms.

There was an anticonvulsant drug explosion in 1938, then in the 50s, 70s, and 90s, all of which led to decreased usage of the KD for epilepsy; drugs were now an option, seems easier.

Kossoff mentioned that medical marijuana is now an alternative to the KD (he says it probably won't work).

In the early 1990s, the KD was rarely used. It was a last resport. There was no interest in it at the American Epilepsy Society. Then, in 1993, enter the Charlie Foundation (side note: The Charlie Foundation was started by one of the creators of the best movie of all time [Airplane!] when he went outside the mainstream to use the KD to cure his son's epilepsy. He actually teamed up with Meryl Streep for a related movie titled ...First Do No Harm.)

The number of KD studies has gone up exponentially since the late 1990s.

The Cochrane Collaboration, published in 2012, stated that the KD shows good results for epilepsy.

Today, the KD is usually used after 2 drugs have failed. It is one of the 4 major treatments. Mainstream!

Now, in 2018, the Charlie Foundation has been around for 25 years. 2018 will mark the 6th Ketogenic Diet symposium in South Korea. There is something called KetoCollege and KetoUniversity. The American Epilepsy Society, which showed no interest in the KD in 1993, is holding a symposium on the KD in 2018. Furthermore, the international guidelines are being revised!

Kossoff said we need to know how to make the KD easier and safer.

The traditional KD started with a 24-hour fast. 4:1 ratio of fat to other macronutrients. Kids seen every 3-6 months. After 2 years, they try to wean the kids off the KD.

Now. . . they don't need the 24-hour fast to initiate. Kids often don't need admission to the hospital for treatment. Kids can be gradualized in to the KD.

Kossoff detailed 4 ketogenic diets and said they are all equally valid (slight differences in macronutrient ratios-- Ketogenic Diet vs. Medium Chain Triglyceride Diet vs. Modified Atkins Diet vs. Low Glycemic Index Treatment).

Can the KD be replaced with a pill? People are trying. Certainly not definitive. Maybe as a supplement.

History of: "Can KD help infants?"

1963: No. Not helpful.

2002: Yes. Safe and effective.

2015: Yes. Kids under 2 do even better than older kids.

Johns Hopkins started an Adult Epilepsy Diet Center in August 2010 (previously there had been issues where it was tough to get treatment after turning 18 and no longer being eligible for pediatric care). There are now over 300 adults in the clinic. About 20% were already on the KD. 80% were not doing keto; they get put on the Modified Atkins diet (10-20 g carbohydrate per day, approximately 25% protein, 70% fat).

Outstanding questions to look into: How to improve compliance? What are the implications when patients see elevated lipids? Is the diet safe in pregnancy? (He says he thinks it probably is. In the Q&A below, he touches on this further)

Q&A Session, Cunnane and Kossoff

Is there any research on ketosis for Multiple Sclerosis since it may be an inflammatory brain disease like Alzheimer's? Kossoff said there is not much, although he noted there is some work looking at intermittent fasting for MS.

Dr. Scheck asked about people going off the KD. . . why wouldn't the epilepsy symptoms come back after going off the diet? Kossoff said the mechanism is debated. Said there is some evidence that the KD can alter underlying brain. Cunnane said that with AD patients, going off the KD leads to immediately diminished cognition.

Could the effects of ketones partially be an autophagy effect? Cunnane said they are trying to get funding to study just this.

Someone asked about the APOE4 gene allele-- that tends to lead to problems with saturated fat. . . my notes are slightly confused here. What I jotted down was that the APOE4 gene dampened cognitive benefit and metabolic benefit. But his study saw no difference between APOE4 and non-APOE4. So maybe the dampened benefits are what is typically thought, but his results did not support those.

Is there trouble getting trials for kids? Kossoff said institutional review boards (IRBs) are definitely keto-friendly for epilepsy now. But there are pregnancy exclusions for trials (hence, why he listed "Is it safe for pregnancy?" as an outstanding question in his speech). Just can't do pregnancy trials. Cunnane said the problem is that IRBs are scared of ketoacidosis (toxically high ketone levels) in those cases.

A sports medicine physician from Georgia asked about brain blood flow. Cunnane said you can get the acute effect with exogenous ketones. Cunnane then asked whether it is a desirable effect to get increased blood flow. He answered his own question by saying he's not sure that is a requirement.

A health coach from Detroit asked what the mechanism from exercise is for getting increased glucose and increased ketones to the brain in AD patients. Cunnane said he was not sure. Increased ketones because of increased capacity. Increased glucose: open question.

Someone asked abot children with autism (as approximately 30% of autistic children experience seizures). Is there any research of the KD for autism? Kossoff said the autism community is desperate for answers and treatments. He said a 2003 Greece study showed a very modest benefit. A 2017 Hawaii gluten free modified Atkins beneft also showed a very modest benefit. The mechanism is a hot topic. He said there is some work being done in animal models.

A functional registered dietician asked what may change after long-term KD adherence. Kossoff said only 5% of patients use the KD for > 2 years. He said there are very few long-termers. He said the results of long-termers have been "not great but not bad". He referenced that bone density and bone fractures have been issues. Growth has been an issue. He has seen good lipids and good GI results.

A family doctor from Canada asked about Alzheimer's studies with Metformin, as it can sometimes be helpful with insulin resistance. Cunnane said there are two schools of thought with Metformin. One says it is beneficial because it decreases insulin resistance. The other says it increases the risk.

A neuroscientist asked about nasal insulin as an AD treatment. And about nasal ketones. Cunnane said getting ketones to the brain is the goal. Unknown for both, but I thought Cunnane seemed skeptical.