Exogenous Ketones For Brain Health and Cognition

This post originally appeared as my weekly newsletter, which you can subscribe to HERE.

The metabolic and cardiovascular harms of obesity are well known, which is alarming given that obesity rates in the US are somewhere around 40%, with similar statistics around the world. 

Obesity also poses a danger to brain health — increasing the risk for cognitive impairment and decline. Why this occurs could be due to several reasons but in part, is proposed to involve reduced blood flow to the brain and lower levels of a molecule known as brain-derived neurotrophic factor (BDNF) — which has been called “Miracle Gro for the brain” because of its effects on the growth and strength of neurons.

Along with reduced blood flow, hyperglycemia (elevated blood glucose) following meals can also impair cognitive function and negatively impact brain health. Obese and diabetic individuals may also suffer from insulin resistance, which reduces glucose availability to the brain and impairs brain metabolism.

While these effects are pronounced in obesity, all of us are concerned with maintaining, or better yet improving, our brain health and cognitive abilities. Supplements for brain performance are pretty scarce (as is the research to support them), however, exogenous ketones are gaining popularity as a supplement with potential neurological benefits.

Our body produces ketones when we are in a “fat-burning” state — which can be leveraged through fasting or a very low-carbohydrate diet. When one is in ketosis, their liver is using fatty acids to produce ketones (beta-hydroxybutyrate or 𝛃-OHB being one) which can then be used by muscles, the heart, and the brain for energy. In particular, the brain seems to readily utilize ketones for energy and does so quite efficiently. This “alternative” energy source might be superfuel for the brain and body.

Ketone metabolism in the brain and body. Source: https://doi.org/10.3390/ijms21228767

Very few studies have looked at how prolonged ketone supplementation may impact brain health and performance. Some acute infusion studies (where 𝛃-OHB is infused at a high dose into the body) suggest beneficial effects, but the impact of elevating ketones via supplementation over weeks to months are not well established.

A new study published in The Journal of Physiology investigated the impact of a 14-day ketone supplementation period on markers of brain blood flow and cognitive performance in a group of otherwise healthy adults with obesity.

Brief study methods

This was a randomized, placebo-controlled, crossover, counter-balanced study — meaning that all participants completed both the experimental and placebo conditions, did so in a random order, and neither the investigators nor the participants were aware of which condition they were in until the end of the study.

Two different experimental conditions were completed, each lasting 14 days:

Ketone supplement condition: participants consumed a ketone supplement three times per day (once before breakfast, lunch and dinner) for 14 days.

Placebo condition: participants consumed a placebo supplement three times per day for 14-days as in the ketone supplement condition.

Diets were controlled — all of the food consumed by participants during the study was provided by the researchers (major strength) and contained approximately 50% carbohydrate, 30% fat, and 20% protein.

Cerebral blood flow (CBF) was measured using ultrasound in the common carotid (CCA), vertebral (VA), and internal carotid (ICA) arteries. Cognitive performance was measured using three tests: the digital symbol substitution task (DSST), the Stroop test, and the task-switching test (TST). These have all been shown to reliably measure aspects of cognition including working memory, processing speed, selective attention, and inhibitory control. BDNF was measured in serum and plasma.

All measures were taken pre- and post-intervention.

Results

  • Cognitive performance: performance on the DSST significantly improved after the ketone supplementation condition, but no differences were observed during the Stroop test or TST.
  • Blood flow: flow in the common carotid (CCA) and vertebral (VA) arteries was elevated after the ketone supplementation condition
  • Vascular conductance (CVC) and shear rate increased in the vertebral artery (VA) following ketone supplementation
  • Blood flow increases in the common carotid (CCA) and vertebral (VA) arteries was correlated with improvement on the DSST
  • No changes were observed in BDNF in either the ketone or placebo condition

As far as I know, this is the first study to look at the cognitive effects of supplementing with exogenous ketones, at least in a population that is more or less healthy. By this I mean that, although they were categorized as obese, none of the participants had any indications of cognitive impairment nor did they have any other comorbidities or for that matter, even elevated blood glucose.

For this reason, I’d consider generalizing these findings to “healthy adults” in terms of how ketones might impact brain function. This is quite promising. The keto diet and fasting are both purported to help with mental clarity, performance, focus, etc. Exogenous ketones are more appealing, in my opinion, because they can be used as a nootropic (cognition-enhancing supplement) without requiring much lifestyle modification. It is one thing to improve cognitive function in someone with low levels at baseline, and another (exciting) thing to enhance cognition in normally-functioning individuals.

The results of this study suggest that the improvements in cognitive performance were caused in part by elevated blood flow to the brain. The same group conducting this study has published that exogenous ketone supplementation also improves peripheral endothelial function (brachial artery flow-mediated dilation) in the same group of participants. Add cardiovascular benefits to the cognitive benefits of exogenous ketones and you start to build a pretty compelling case for regular (i.e. daily) supplementation with ketones.

Right now, this may not be feasible due to the somewhat cost-prohibitive nature of exogenous ketones (around $8 for a serving right now for the cheapest commercially-available product). However, companies are developing more cost-effective alternatives. For what it’s worth, the supplement used in this study was the BHB monoester sold by H.V.M.N. (a company to which I have no financial ties).

If you are interested in experiencing the effects of these novel supplements, I would suggest trying one of the few ketone esters available right now. Disclosure: I have no investments in any of these companies, but do freelance work for Juvenescence as a content writer.

Juvenescence: Metabolic Switch ketone ester

H.V.M.N.: ΔG Ketone monoester

KetoneAid: Ketone monoester


As always, thanks for reading.

Studies cited

Walsh JJ, Caldwell HG, Neudorf H, Ainslie PN, Little JP. Short‐term ketone monoester supplementation improves cerebral blood flow and cognition in obesity: A randomized cross‐over trial. J Physiol. Published online October 4, 2021:JP281988.

Walsh JJ, Neudorf H, Little JP. 14-day ketone supplementation lowers glucose and improves vascular function in obesity: a randomized crossover trial. The Journal of Clinical Endocrinology & Metabolism. 2021;106(4):e1738-e1754.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s