Can Ketones Fuel Cognitive And Physical Performance?

Brett Melanson - PhD Candidate in Behavioural Neuroscience. 

A study by Brownlow et al. (2017) designed a study to investigate the effects of a ketogenic diet, ketone supplement, or standard diet on stress-induced changes in behavior and physiology. Key finding:

It is a form of memory we use when distinguishing familiar and novel objects, events, and/or people in our environment (Mahoney, 2015). Moreover, both keto-fed and keto-supplemented rats performed more efficiently in a spatial task following stress, suggesting a proficient hippocampal-based memory ability in these animals (Brownlow et al., 2017). 

Importantly, stress is known to reduce levels of the trophic factor, BDNF, in the hippocampus—this effect was reduced when animals were fed a ketogenic diet or supplemented with ketones, suggesting that,

Another study by Hyatt et al. (2016) compared the effects of ketogenic and typical western diets on exercise training in rodents. They found that:

This was measured in terms of mitochondrial coupling, a measure of efficiency for mitochondria (Hyatt et al., 2016), which we should all know as the powerhouse of the cell responsible for producing ATP. 

Importantly, a clear distinction regarding the use of high-fat diets must be made: the findings for improved mitochondrial efficiency and enhanced cognitive performance were primarily discovered using diets involved medium-chain triglycerides (MCTs; Hyatt et al., 2016, Brownlow et al., 2017). Other studies have found impairments in exercise performance and mitochondrial respiration, but these studies focus on high-fat diets involving long-chain triglycerides, such as butter and lard (Iossa et al., 2002, Jorgensen et al., 2015). 

The effects of exogenous ketone supplementation

In an interesting study conducted by Murray et al. (2016), rats were provided with a chow diet comprised of 30% ketone esters (i.e., ketone body bound to an alcohol molecule) to investigate the effects of this supplemental keto-diet on cognitive performance and exercise. They found that:

Although the behavioural effects of this keto-ester supplementation were a result of a relatively shorter window of supplementation (5 days of keto esters), their long-term study on the metabolic effects of keto esters for 66 days indicated that:

Moreover, the authors found that muscles had lower levels of lactate activity, which is a metabolite commonly found in muscles that have high rates of glycolysis and thus utilisation of glucose. They hypothesised that rats fed a keto ester supplement performed better on exercise tasks possibly as a result of primarily utilising ketone bodies as a primary energy source and preserving glycogen stores for additional energy reserves upon keto ester depletion.

Other studies have compared and contrasted the combinatorial and isolated effects of ketone-esters, ketone-salts, and medium chain triglycerides (MCT). It was found that keto esters or a ketone-salt/MCT combination suppressed neural activity indicative of epileptic seizures in rats (Kovacs et al., 2017), while another study found that keto esters enhance motor performance acutely when combined with medium-chain triglycerides (MCT), and are generally beneficial when consumed chronically in several strains of rodents (Ari et al., 2020). 

Interestingly, the authors found that combining keto esters with ketone-salts or MCTs enhanced motor performance in a specific strain of rat, while keto ester supplementation alone was sufficient to boost performance in other strains, suggesting potential genetic differences in how these compounds and/or their combinations may benefit performance. This assertion is further supported by  strain-specific effects of keto esters or ketone-salt/MCT combinations on reducing anxiety-like behavior (Ari et al., 2016). 

Together, these findings suggest that exogenous ketone supplementation, precisely in the form of a keto ester, can enhance performance and possibly reduce an anxiety-like state, which may be a useful tool to combat performance anxiety.

Companies have already utilised the idea of keto ester supplementation and consumer reviews by cyclists have been generally positive, claiming a boost to their typical performance compared to training without keto ester supplementation.  

Examples of such performance-enhancing products can be found in the form of sports drinks offered by Ketone Aid.

Ketogenic Diet and Athletic Performance

Interestingly, there is also evidence that ketogenic diets are primarily good for enhancing body mass and body composition, while the effect of keto-based diets on endurance exercise remains controversial (Kang et al., 2020), despite the subjective approval from long distance cyclists and triathletes. This disparity is likely due to objective differences in how these effects were measured - more about this shortly. Importantly,

How long does it take to become fat adapted on the keto diet?

The controversial evidence on exercise performance in humans may be a result of the keto-adaptation process, in which the body transitions to keto-based energy. Specifically, studies indicate that short-term keto-diets ranging from 1-7 days impaired athletic performance (Burke et al., 2017, Starling et al., 1997, Pitsiladis & Maughan, 1999), but long-term keto diets of roughly 12 weeks in duration actually improved exercise performance (McSwiney et al., 2018, Mohorko et al., 2019). 

This assertion is further supported by a study that examined the keto-adaptation process over time as it relates to athletic performance in the same individuals. They found that in the first week of a ketogenic diet, exercise performance declined; however, after 6 weeks, performance increased. Another set of studies found beneficial outcomes following a medium-term, 3-week ketogenic diet (Lambert et al., 1994, Zajac et al., 2014). 

Importantly, the findings by McSwiney et al. and Mohorko et al. provided consistently positive results following a 12-week ketogenic diet in both well-trained athletes and in individuals facing obesity. This indicates an important concept when considering the ketogenic diet, in that it may actually take time to achieve its performance-enhancing benefits and is likely due to the adaptation process the body undergoes when transitioning from glucose-based to ketone-based energy resources. 

But, the added benefit of reducing insulin spikes and lowering carbohydrate intake by switching to keto-based diets may be appealing to individuals experiencing pre-diabetic conditions or those dealing with gluten sensitivity. In this context, the 2-3 months it would take to generate a state of ketosis would definitely seem to pay off in the long-term.

Ketogenesis in Health and Disease

Within the medical field, ketogenic diets have been widely used in treatment for epilepsy and are now implicated as plausible treatments for dementia-related diseases such as Alzheimer’s (Pinto et al., 2018). Moreover, ketogenic diets are now being revisited as possible diet-based interventions to treat a variety of other metabolic and systems-related disorders and disease (Watanabe et al., 2020), though it is highly recommended that these diets be prescribed on a case-by-case basis as ketogenesis may not be suitable for everyone. 

Finally, it is well-known that ketogenic diets are beneficial to those facing obesity. However, an important caveat is that if one wishes to use the ketogenic diet as a tool to reduce fat content, only to return to their previous non-keto-oriented lifestyle, it is recommended that the transition from keto- to carb-based diets be gradual and occur in a slowly-tapering manner, to avoid any unwanted side effects of increased carbohydrate intake (Paoli, 2013, 2014). 

Ideally, the best approach is to take advantage of natural sugars (i.e., apples, raspberries, etc.) when incrementally adding carbs back into the diet, and to introduce hard-to-digest carbohydrates, such as those with high fibre and protein content that won’t cause a large spike in blood sugar.