Robert Krikorian is a professor in the Department of Psychiatry and Behavioral Neuroscience and the director of the Cognitive Aging Program at the University of Cincinnati Academic Health Center. He is one of the lead researchers exploring ketogenic diet as an intervention for people with cognitive impairment, and on the impact of anthocyanins (antioxidants found in blueberries and other pigmented fruits and vegetables) on cognitive aging. 

What I discuss with Robert in this episode:

  • How an aspiring psychotherapist with no family history of neurodegeneration became one of the leading researchers in dietary methods of fighting cognitive impairment and aging.

  • What Robert believes is the most potent factor in influencing our health and longevity.

  • What happened to a group with mild cognitive impairment (MCI) who observed the low-carb, high-fat ketogenic diet.

  • The implications of these findings for young people seeking to entirely prevent cognitive impairment with the benefit of early awareness.

  • The impact of the humble blueberry (and related pigmented fruits and vegetables) on cognitive aging.

  • And much more!

The cost of treatment for neurodegenerative diseases like Alzheimer's and Parkinson's can be high, and the emotional toll on those affected—from the afflicted to those caring for the afflicted—is even higher. But what if non-pharmaceutical interventions during or before the early stages could stall or halt their progress entirely? In this case, an ounce of prevention would surely be worth, at the very least, a pound of cure. 

University of Cincinnati professor Robert Krikorian, PhD joins us to discuss his research into the positive effects of the low-carb, high-fat ketogenic diet on patients with mild cognitive impairment (MCI) and how anthocyanins (antioxidants found in blueberries and other pigmented fruits and vegetables) may stall the effects of cognitive aging.

Treatment with the Tools at Hand

With scholarly interests ranging from astronomy to philosophy and a career path that initially seemed destined toward psychotherapy, it's perhaps surprising Dr. Robert Krikorian became one of the leading researchers in nutritional methods—namely the ketogenic diet and use of anthocyanin-rich foods like blueberries—to forestall neurodegeneration.

"I have a clinic and we see patients from age seven through old age. I would guess about eight years ago, maybe 10 years ago, we started to see more people who are middle-aged and older with age-related memory changes. The typical patient was sort of dysthymic—had a little bit of depression and increased anxiety—and starting to have some cognitive changes. I noticed some things about them in terms of simple observations about the other health conditions they had, like typically hypertension and sometimes type two diabetes. They seemed to be overweight as a group, and it just occurred to me that this was going to become a major issue in the population as a whole."

While he has no family history of neurodegeneration, Robert recognized the societal implications of this growing segment of the populace and began to examine its causes and ways it might be countered. But there were limitations to how he could proceed.

"I'm not a physician; I'm a PhD, and so I don't have access to medications as treatment tools," says Robert. "I was focused on nutrition, stress control, and exercise...with those tools, I thought that diet or nutrition was the most potent way to approach this, and I really felt strongly that prevention was much prefered relative to cure."

The Ketogenic Diet vs. Mild Cognitive Impairment (MCI) 

The low-carb, high-fat ketogenic diet has been used to treat a number of ailments—from epilepsy to diabetes to obesity—for more than a century. In a nutshell, it creates the conditions for your body to burn fat, rather than sugar, as a fuel. It improves triglyceride and cholesterol levels, lowers blood sugar levels, and it optimizes insulin to name a few of its proven benefits. 

During a six-week intervention (preceded by a three-week pre-pilot phase), patients exhibiting mild cognitive impairment (MCI)—a group at risk for later development of Alzheimer's or other forms of dementia—were instructed to observe a low-carb, high-fat ketogenic diet. And while weight loss typical to such a diet predictably occured, a significant improvement in cognition was also noted.

"Many people over the age of 55-60 in our culture are hyperinsulinemic," says Robert. "They're not yet diabetic, but they're sort of on that path, generally speaking. And they have elevated levels of insulin, but the glucose is not high enough yet to meet standards for treatment as diabetics. But I think damage is still being done in that phase, and that phase can be very long...but in any case, we lowered insulin into the reference range and it was just at the upper limit of the reference range...so I thought part of it was the correction of hyperinsulinemia, but I thought that there was another component which might have been an energetic component—that is, we were improving mitochondrial energy production in the brain."

A smaller extension study under similar conditions included brain imaging; cognition improvements were once again verified, with significant increase in neurochemicals like myo-inositol and trends for increases in N-acetylaspartate, creatine, and phosphocreatine after six weeks on the ketogenic regimen.   

This is Your Brain on Blueberries

Robert was particularly inspired by a 1999 study done by James A. Joseph of Tufts University in which middle-aged rats given strawberry, spinach, and blueberry supplements were able to perform mental tasks as well as rats belonging to a younger group. Its conclusion: These findings suggest that, in addition to their known beneficial effects on cancer and heart disease, phytochemicals present in antioxidant-rich foods may be beneficial in reversing the course of neuronal and behavioral aging.

"Blueberries, in particular, contain five of the six major anthocyanins [antioxidants found in blueberries and many other purple-hued fruits and vegetables]...they seem to have a lot of benefits for us with respect to the antioxidant and anti-inflammatory benefits, but also they do some of the things we talked about with ketone metabolism."

Robert mentions that, additionally, they seem to improve glucose disposal independent of the level of insulin that the body produces.

Another curious observation is that the metabolic processes triggered by the introduction of anthocyanins seem to linger long after the anthocyanins themselves have been digested.

"The question becomes: is it the metabolic process? Is it what the organism is doing with the anthocyanins that's switching on the signals and producing the benefit, or is it the acute consumption of the parent—the food form compounds? The data we have from these two studies...suggest that it's the acute consumption. It's the parent compounds that the cognitive benefits seem to be associated with."

Listen to this full episode to learn more about the details behind how Robert believes (and research suggests) ketosis facilitates cognitive improvement, how young people might use this information to prevent cognitive impairment early on, Robert's take on the use of MCT oil and exogenous ketones, Robert's aspirations to compare the benefits of blueberry supplementation against ketogenic diet for cognitive improvement, what Robert's own diet looks like, and lots more. 

Resources from this episode:

Robert Krikorian at University of Cincinnati's Department of Psychiatry and Behavioral Neuroscience

Cognitive Aging Program , University of Cincinnati 

Dietary Ketosis Enhances Memory in Mild Cognitive Impairment by Robert Krikorian et al., Neurobiology of Aging

What Is Mild Cognitive Impairment? National Institute on Aging

What is the Ketogenic Diet? A Comprehensive Beginner's Guide, ruled.me

Enhanced Cerebral Bioenergetics with Dietary Ketosis in Mild Cognitive Impairment by Robert Krikorian et al., Nutrition and Aging

Scientists Reveal Why People with the ApoE4 Gene Are More Susceptible to Alzheimer's Disease, Salk Institute

What is Myo-inositol? Examine.com

What is N-acetylaspartate? N-acetylaspartate.com

What is Creatine? Examine.com

What is Autophagy? by Ananya Mandal, News-Medical.Net

A Ketogenic Diet Reduces Amyloid Beta 40 and 42 in a Mouse Model of Alzheimer's Disease by Ingrid Van der Auwera et al., Nutrition & Metabolism

Exercise Promotes the Expression of Brain Derived Neurotrophic Factor (BDNF) through the Action of the Ketone Body Beta-Hydroxybutyrate by Sama F Sleiman et al., eLife

Can Ketones Help Rescue Brain Fuel Supply in Later Life? Implications for Cognitive Health during Aging and the Treatment of Alzheimer's Disease by Stephen Cunnane, Frontiers in Molecular Neuroscience

Reversals of Age-Related Declines in Neuronal Signal Transduction, Cognitive, and Motor Behavioral Deficits with Blueberry, Spinach, or Strawberry Dietary Supplementation by James A. Joseph et al., The Journal of Neuroscience

What Are Anthocyanins and Why Are Purple Foods So Healthy? by Sarah Lienard, BBC

Neuroprotective Effect of Anthocyanins on Acetylcholinesterase Activity and Attenuation of Scopolamine-Induced Amnesia in Rats by JM Gutierres et al., International Journal of Developmental Neuroscience

Blueberry Extract Enhances Survival of Intraocular Hippocampal Transplants by L. Willis et al., Cell Transplant

Impact of Diet on Adult Hippocampal Neurogenesis by Doris Stangl and Sandrine Thuret, Genes & Nutrition

Blueberry Supplementation Improves Memory in Older Adults by Robert Krikorian et al., Journal of Agricultural and Food Chemistry

Cognitive Improving Effects by Highbush Blueberry (Vaccinium Crymbosum L.) Vinegar on Scopolamine-Induced Amnesia Mice Model by SM Hong et al., Journal of Agricultural and Food Chemistry

ORAC Values: Antioxidant Values of Foods & Beverages, Superfoodly

Nutritional Dangers of Acid Reflux Medications by Kimmi Le, lifeextension.com

Genius Foods: Become Smarter, Happier, and More Productive While Protecting Your Brain for Life by Max Lugavere and Paul Grewal M.D.

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