Ketone Ester, Ketosis, and Cognition

Authored by Nate MartinsDr. Brianna Stubbs and Geoffrey Woo • 
April 1, 2019
 • 2 min read

Ketones are brain fuel. In early hominids, ketones evolved to cross the blood-brain barrier and sustain physical and cognitive output when food sources, particularly carbohydrates, were limited; in fact, in certain scenarios, up to 80% of brain energy can come from ketones.1

It should be no surprise that many people claim to feel subjective mental clarity when on the keto diet or when fasting, citing improved cognitive performance as a key reason they enjoy being in a state of ketosis.

So—what exactly do we know about ketones and the brain?

Usually, on a standard American diet, glucose is the main fuel for the brain. Ketones can replace glucose; every ~1mM of BHB (the main ketone body) increase can account for 10% of brain metabolism.2 What’s more, ketones can up-regulate the production of an important protein called brain-derived neurotrophic factor (BDNF), which supports the health of existing neurons and helps grow new ones, as well as increasing the number of connections between cells (synapses). This promotes long-term cognitive health and function.3

Let’s look at the studies that put the hypothetical mechanisms to the test.

Early human models (including pending publication from HVMN, Oxford, and others) suggest ketones improve decision making. One study asked subjects to take a multitasking test both before and after exercise.4 Participants drinking a placebo had more incorrect responses from pre- to post-exercise; those drinking ketone ester performed the same both before and after exercise. This shows the ability of ketones to maintain cognitive function (better than placebo) during stressful situations.

Animal studies also show improved decision-making.5 One study on rats timed how long they took to complete a maze. Before changes to their diets, all rats completed the maze with the same time. After diet alterations, rats fed the ketone ester were 38% faster in completing an eight-arm radial maze compared to rates fed a carbohydrate-heavy or standard American diets. Decision-making ability (as measured by the number of correct maze arm choices) was also studied. Before diet changes, all rats made the same number of correct choices. Ketone ester fed rats made more correct decisions before making a mistake, compared to rats fed other diets, which showed no significant performance difference.

If you’re looking for a boost, remember there are several different kinds of ketone supplements to choose from. Most studies have been done using the ketone ester in HVMN Ketone. Ketone salts nor MCTs have not yet demonstrated any improvement in cognitive experiments on a healthy human population.6

Disclaimer: Employees of HVMN are not medical doctors and are not offering medical advice. Consult with your physician before making diet or lifestyle changes.

Scientific Citations

1.Cahill, G.F., Jr. (1970). Starvation in man. New Engl J Med 282, 668-675.
2.LaManna, J.C., Salem, N., Puchowicz, M., Erokwu, B., Koppaka, S., Flask, C., and Lee, Z. (2009). KETONES SUPPRESS BRAIN GLUCOSE CONSUMPTION. Advances in experimental medicine and biology 645, 301-306.
3.Sleiman SF, Henry J, Al-Haddad R, et al. Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate. Elmquist JK, ed. eLife. 2016;5:e15092. doi:10.7554/eLife.15092.
4.Evans M, Egan B. Intermittent Running and Cognitive Performance after Ketone Ester Ingestion. Med Sci Sports Exerc. 2018;50(11):2330-2338.
5.Murray, A.J., Knight, N.S., Cole, M.A., Cochlin, L.E., Carter, E., Tchabanenko, K., Pichulik, T., Gulston, M.K., Atherton, H.J., Schroeder, M.A., et al. (2016). Novel ketone diet enhances physical and cognitive performance. FASEB J.
6.Waldman HS, Krings B, Basham SA, Smith JW, Fountain BJ, McAllister MJ. Effects of a 15-Day Low Carbohydrate, High-Fat Diet in Resistance-Trained Men. (1533-4287 (Electronic)).
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