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Ketones and Exercise: A New Way to Enhance Athletic Performance?

Ketogenic diets are all the rage at the moment. Advocates of ketogenic diets point to studies showing beneficial effects on fat loss (check out Dan’s blog on this) and disorders including diabetes (which Dan and Stephan recently discussed on humanOS Radio), epilepsy, neurodegenerative diseases such as Alzheimer’s (1), and certain cancers (2). There has also been a recent surge in interest in non-therapeutic uses of ketosis. Athletes have started exploring whether ketosis influences exercise performance, and the media has been quick to latch onto this. But what does the science on ketones and exercise show? 

In this blog we’ll concentrate on this question, focusing specifically on the effects of supplemental ketones on endurance exercise performance. We won’t really consider ketogenic diets. This brings us to the first consideration: the distinction between ketogenic diets and ketosis.

 

Ketonemia: ketogenic diets versus ketosis

Healthy people who haven’t been fasting or severely restricting carbohydrate intake typically have a low concentration of ketones in the blood – about 0.1 to 0.5 mmol/L. However, blood ketone concentrations can exceed 7 mmol/after prolonged fasting (five days, for example), or with sustained carbohydrate restriction (generally no more than 5% of energy intake from carbohydrate, with about 80% of energy from fat), or even with prolonged exercise (3). Such high ketone concentrations are known as hyperketonemia.

Fasting, very-low-carbohydrate diets, and exhaustive exercise accelerate ketogenesis (production of ketone bodies by the liver). However, there is an alternative route to ketonemia: just consume ketones in the diet. This is a far more palatable proposition for most. But why might someone want to consume ketones anyway?

 

What are ketones?

Fasting, severe carbohydrate restriction, and prolonged exercise all deplete stored carbohydrate (glycogen) in your liver and skeletal muscles. This depletion increases mobilization of fatty acids from your fat. These fatty acids are broken down for energy, increasing levels of a molecule (acetyl-CoA) that is then converted by mitochondria in the liver into ketones. Ketones include acetoacetate, acetone, and β-hydroxybutyrate. (The latter is technically not a ketone but is a ketone body. I’ll refer to all as ketones for simplicity though). Now, most acetone is just excreted in sweat or urine, but the other two ketones are transported in your blood to organs that consume lots of energy (like your brain and muscles). The ketones are then used as an alternative energy source by your mitochondria.

When you think about it, the metabolic state induced by supplemental ketones is extraordinary: It is likely that our ancestors could never have had full glycogen stores and raised blood ketones at the same time. (As an aside, you can also now possible boost your muscle phosphocreatine levels above normal by creatine supplementation. This increases how quickly your body can recycle the energy stores it uses to fuel brief, explosive activities like sprinting. The combination of replete glycogen, hyperketonemia induced by supplemental ketones, and elevated phosphocreatine stores really is novel!)

 

Ketone metabolism

Let’s concentrate on exercise. It’s important to understand that your brain can limit exercise performance in many ways to preserve your body’s integrity. When the brain constrains endurance exercise output, people sometimes call this “central fatigue”. By providing the brain with additional energy substrates, ketones should theoretically delay central fatigue.

Now, there is a relatively linear, positive relationship between the concentration of ketones in your blood and ketone uptake by your brain, but if you’re resting then higher blood ketones don’t lead to much higher ketone use by your muscles (4). When you exercise though, your muscles can use far more ketones for energy (5). This is especially true of slow-twitch (Type I) muscle fibres. These fibres efficiently produce lower forces for long periods of time, and endurance athletes tend to have lots them. Interestingly, endurance training also changes the activity of enzymes involved in muscle ketone uptake, increasing the capacity of muscles to use ketones for energy (6). All of this implies that athletes will benefit more from supplemental ketones than couch potatoes.

Other properties of ketones may enhance exercise performance too. Ketones may increase your ability to burn the stores of fat within your muscle fibres. Furthermore, studies of mice have shown that energy is derived more efficiently from ketone bodies than from carbohydrates because of changes in mitochondrial activity (7). When mice produce energy in the presence of oxygen (by aerobic metabolism), the animals produce more energy per unit of oxygen consumed if they’re burning ketones than if they’re relying on carbohydrate.

Using ketones also spares glycogen stores, which should theoretically enhance endurance performance by keeping carbohydrates available for the kinds of sprints that occur late in most competitions. This said, it is also plausible that ketones 1) reduce how well carbohydrates are mobilized from stores, and 2) impair muscle use of lactate for energy. Lactate has an undeserved bad rap. When the concentration of lactate increases in your muscles during intense exercise, you experience a burning sensation. But this burning isn’t because of the lactate. Instead, it results from increased levels of hydrogen ions (which are positively charged), which reduce the pH in your muscles, making the tissues more acidic. Lactate is actually a really important energy source!

Together, these mechanisms mostly support the rationale that ketones might enhance endurance exercise performance. But are all supplemental ketones alike?

 

Ketone supplements

Early studies on supplemental ketones used ketone salts, and the salts you can buy generally provide 8 to 12 g of β-hydroxybutyrate (and about 1 g of sodium) per serving and mildly raise blood ketone concentrations.

Ketone esters have recently become available too. Ketone esters seem to more effectively raise blood ketone levels, which have been found to reach about 6 mmol/L just 45 minutes after consumption of about 270 mg of an ester per lb bodyweight (600 mg/kg) (8). This concentration would take several days of fasting to reach!

Blood ketone concentrations are dose-dependent and are higher when the ketones are consumed in isolation versus with other macronutrients (carbohydrates, etcetera). Just keep in mind that some people experience digestive discomfort after ingesting ketones.

Okay, let’s now review actual exercise performance studies.

 

Ketones and endurance exercise performance

Few studies have yet been done on the effects of ketones on performance in endurance exercise tests. An unpublished study of trained rowers reported that consumption of 230 calories from ketones improved 30-minute rowing distance by 1% compared to fasting.

Nothing to get excited about.

A study of competitive cyclists found that ketone salts had no effect on how far cyclists went in a four-minute test after 90-minutes of cycling at a steady pace.

You’re still not excited, I know.

In another study of fasted, untrained men, consumption of about 0.14 g/lb (0.3 g/kg) of a β-hydroxybutyrate ketone salt 30-minutes before exercise actually worsened performance by 7% in a cycling sprint after the participants had been cycling at a steady pace (9).

Okay, they’re useless for endurance athletes…

… Not so fast. In perhaps the best study on effects of supplemental ketones on exercise, participants consumed about 260 mg of a ketone ester supplement per lb bodyweight (573 mg/kg) in conjunction with what is generally considered an optimal rate of carbohydrate intake (1.2 g carbohydrate/minute). This was compared to a drink containing the same number of calories from carbohydrate alone, and participants consumed the drinks shortly before exercise. When participants consumed the carbohydrate-plus-ketone drink, they performed 2% better in a 30-minute cycling test that followed an hour of cycling at a steady pace (5). I really want to emphasize that this is a single study of just eight people though!

 

Ketones and recovery from exercise

Beyond acute effects on exercise, what about effects of ketosis on recovery? Ketones have a couple of characteristics that may enhance recuperation from exercise – and this topic is germane to all athletes (including team sport athletes and strength and power athletes).

As noted, ketones may hasten muscle glycogen recovery (10). There is also evidence that β-hydroxybutyrate increases the synthesis of new muscle tissue and reduces muscle protein breakdown when infused into people’s blood (11). Far more research is needed before we reach conclusions, but these beneficial effects should hasten post-exercise recovery.

There are other reasons to think ketones may bolster your adaptations to exercise. β-hydroxybutyrate may regulate adaptive processes in muscle by acting as a signalling metabolite, for example, inhibiting what are known as histone deacetylases and thereby increasing expression of genes like PPARGC1A. All else being equal, such gene expression changes might produce favourable effects (like building new mitochondria) but this is mere speculation right now.

 

Tentative recommendations

There is far more evidence that carbohydrates boost exercise performance than there is evidence that ketones do (12). You should consider this if consuming ketones hinders your ability to take in carbohydrates (even if only because ketones taste so bad). This said, this isn’t an either/or scenario, and it’s possible that combining ketones with other nutrients is the best strategy for some people.

If you want to try ketones, I’d go for the (R)-3-hydroxybutyl (R)-3-hydroxybutyrate ketone monoester used in the study that reported enhanced performance. This product hits the market this month and appears to be much the same as the studied ketone monoester. At this point we just don’t know what the optimal dose is, so I’d use the quantity used in the study – about 260 mg/lb bodyweight (573 mg/kg) perhaps 30 minutes before exercise. The same dose was used immediately post-exercise only in the study that reported enhanced muscle glycogen resynthesis.

 

Summary

There is still so much to learn about this topic. Which ketones are best and in what circumstances? When is the best time to take ketones? And how do effects of ketones interact with other nutrients?

Don’t write ketones off – I’m sure we’ll identify more instances in which ketone supplements are useful, and better ketone supplements will soon be available. Nevertheless, few supplements have so much hype with so few studies showing beneficial effects in humans. Personally, I’d be far quicker to buy supplements proven to substantially boost endurance time and time again, like caffeine and carbohydrate sources. These are much cheaper than ketones too.

Ketones are recognized to be safe, but the results of preliminary studies frankly aren’t particularly impressive. Nevertheless, elite endurance athletes seeking a competitive edge generally want to consider anything that could give them an edge and should therefore consider trying supplemental ketones. 

 

Key takeaways

Both ketogenic diets and supplemental ketones can markedly increase blood ketone levels.

Some metabolic roles of ketones are hypothesized to enhance endurance exercise performance, recovery from exercise, and exercise training adaptations.

There is very little evidence regarding effects of ketones on exercise performance.

Ketone esters seem to raise blood ketone concentrations more effectively than ketone salts and may improve exercise performance conditions in certain circumstances.

 

References

  1.      Augustin K, Khabbush A, Williams S, Eaton S, Orford M, Cross JH, et al. Mechanisms of action for the medium-chain triglyceride ketogenic diet in neurological and metabolic disorders. Lancet Neurol. 2018;17(1):84-93.
  2.      Chung HY, Park YK. Rationale, Feasibility and Acceptability of Ketogenic Diet for Cancer Treatment. J Cancer Prev. 2017;22(3):127-34.
  3.      Pinckaers PJ, Churchward-Venne TA, Bailey D, van Loon LJ. Ketone Bodies and Exercise Performance: The Next Magic Bullet or Merely Hype? Sports Med. 2017;47(3):383-91.
  4.      Mikkelsen KH, Seifert T, Secher NH, Grondal T, van Hall G. Systemic, cerebral and skeletal muscle ketone body and energy metabolism during acute hyper-D-beta-hydroxybutyratemia in post-absorptive healthy males. J Clin Endocrinol Metab. 2015;100(2):636-43.
  5.      Cox PJ, Kirk T, Ashmore T, Willerton K, Evans R, Smith A, et al. Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes. Cell Metab. 2016;24(2):256-68.
  6.      Beattie MA, Winder WW. Mechanism of training-induced attenuation of postexercise ketosis. Am J Physiol. 1984;247(5 Pt 2):R780-5.
  7.      Sato K, Kashiwaya Y, Keon CA, Tsuchiya N, King MT, Radda GK, et al. Insulin, ketone bodies, and mitochondrial energy transduction. FASEB J. 1995;9(8):651-8.
  8.      Balasse EO, Fery F, Neef MA. Changes induced by exercise in rates of turnover and oxidation of ketone bodies in fasting man. J Appl Physiol Respir Environ Exerc Physiol. 1978;44(1):5-11.
  9.      O’Malley T, Myette-Cote E, Durrer C, Little JP. Nutritional ketone salts increase fat oxidation but impair high-intensity exercise performance in healthy adult males. Appl Physiol Nutr Metab. 2017;42(10):1031-5.
  10.    Holdsworth DA, Cox PJ, Kirk T, Stradling H, Impey SG, Clarke K. A Ketone Ester Drink Increases Postexercise Muscle Glycogen Synthesis in Humans. Med Sci Sports Exerc. 2017;49(9):1789-95.
  11.    Nair KS, Welle SL, Halliday D, Campbell RG. Effect of beta-hydroxybutyrate on whole-body leucine kinetics and fractional mixed skeletal muscle protein synthesis in humans. J Clin Invest. 1988;82(1):198-205.
  12.    Jeukendrup A. A step towards personalized sports nutrition: carbohydrate intake during exercise. Sports Med. 2014;44 Suppl 1:S25-33.