The Use of Ketogenic Triglycerides to Improve Cognitive Function

Stephen Cunnane, PhD, Research Center on Aging, Universite de Sherbrooke, discussed the ketogenic drink used in his recent study and the action of ketogenic diets.

A recent study found that a ketogenic medium chain triglyceride (kMCT) drink improved executive function, episodic memory, and language by increasing blood ketone levels and brain energy status in patients with evidence of mild cognitive impairment (MCI). These findings reinforce the potential of brain energy rescue as a strategy to reduce cognitive decline in MCI and Alzheimer Disease (AD).1,2

The brain energy rescue process is achieved by offering the brain more ketones to metabolize when brain glucose metabolism decreases, which is a common effect of these disorders. Study author Stephen Cunnane, PhD, Research Center on Aging, Universite de Sherbrooke, and colleagues found that when compared to placebo, the kMCT group scored higher on free and cued recall (P = .047), verbal fluency (P = .024), Boston Naming Test (P = .033), and the Trail-Making Test (P = .017) after a 6-month randomized, controlled trial.

This study followed up the Brain Energy, Functional Imaging, and Cognition (BENEFIC) study (NCT02551419) that showed a kMCT drink improved brain energy status and aimed to assess the effect of kMCT on cognitive outcomes. NeurologyLive spoke with Cunnane to learn more about the ketogenic drink used in the study and the potential of ketogenic diets to mediate Alzheimer Disease.

NeurologyLive: How does the kMCT drink work to initiate brain energy rescue?

Stephen Cunnane, PhD: It should be able to replicate what happens during fasting, and what happens in infant brain development. In fact, the supply of ketones during infant brain development comes from medium chain triglycerides in mother's milk. The mother will produce medium chain triglycerides in the mammary gland, and they will be supplied to the baby and converted to ketones. This is nature's solution to meeting the energy challenge of early development. So, we took the same approach with MCT in Alzheimer's disease. We were able to show with PET imaging that the ketones are taken up by the brain normally and increasing proportion in relation to the level in the plasma or in the diet. There absolutely was the same relationship, as you would see in the young, healthy adult, across brain regions, across gray matter and white matter. And we've been detailing these results over the past 5 years.

Do you believe ketogenic diets could be complimentary to brain energy rescue and do they have potential to be prescribed to patients suffering from MCI?

The answer is yes, and no. Ketogenic diets have been around for 100 years. They’re initially and still predominantly used for epilepsy, and that strikes more in children—it's easier in some ways to control the diets of children than it is in adults and in older people. So, it becomes a logistical problem, how do you actually reduce the carbohydrate intake to well below 10% of our calorie intake? It’s very difficult for most people to adapt to reducing bread, pasta, rice, potatoes, and refined sugar, of course, so dessert, too. 

Scientifically, I think it is an effective approach. It's a question of the practical elements and the logistics of it that that make it very challenging. But there are clinics that specialize in this now and some even have remote sites you can find online, so you don't have to physically go to the clinic. You can buy a sort of subscription and get medical support at home to manage this type of approach yourself—and with your family because they have to get involved, too. If you're living with someone else, cooking 2 sets of meals every time is going to be a nightmare, and it's simply not going to work. So, this is an adjustment for the person who has Alzheimer's disease, or MCI, but it's an adjustment for their family, too. And the physician often needs to learn more about the merits of this approach because ketogenic diets are very high fat, and high fat has been always been associated with gaining weight and cardiovascular risk. In fact, ketogenic diets are now used for weight loss. They're used for type 2 diabetes control, because they reduce the carbohydrate and the strain on insulin. People have shown for up to 12 weeks now in older people that the cardiovascular risk simply does not materialize in any measurable fashion. So, I think there's a learning curve that we as scientists, clinicians, patients, and families that are affected, need to adapt to. And if the ketogenic diet is not something that can be managed, for various reasons, a ketogenic supplement becomes a practical alternative.

Transcript edited for clarity.

REFERENCES
1. Fortier M, Castellano CA, Croteau E, et. al. A ketogenic drink improves brain energy and some measures of cognition in mild cognitive impairment. Alzheimer’s Dement. 201915(5):625-634. doi: 10.1016/j.jalz.2018.12.017 
2. Fortier M, Castellano CA, St-Pierre V, et. al. A ketogenic drink improves cognition in mild cognitive impairment: Results of a 6-month RCT. Alzheimer’s Dement. Published online Oct 26, 2020. doi: 10.1002/alz.12206