By Anthony L. Almada, MSc, FISSN
(Visit the Serious Triathlon podcast to for a discussion with the author on ketones)

You and your 165-pound body have been on the windless flats for 63 minutes, halfway into your 70.3 Springtime jaunt. Before your eyes look up, and before your virtual GPS watch pings its barometric altimeter you know you have some climbing to do in 200 meters—you’ve trained innumerable times on this section before today—race day, year 2027. The flexible, biodegradable biometric sensors implanted in your quads, brain, and love handles offer a heads up display in the accelerometer-sensitive helmet/photochromatic eye visor as you begin your 1,700 meter ascent.  Your wattage over the past hour of power has been 297w (3.97 w/kg).

The heads up dashboard shows that the carbs you incinerated over the past 60 minutes came from muscle carbohydrate (glycogen), blood sugar (fed, in part, by the carb pellet you’ve ingested every 20 minutes during the past 60), stored glucose released from your liver, and recycled lactate. The primary source of the fat thrown into the flames has been intramuscular—the white marbling seen in the raw bison steak you had two nights earlier.

You’re approaching 1:45 of seat time and are contemplating T2, and then the final climb of the run, affectionately dubbed “The Widowmaker”. It’s time to implement Plan BHB and slam some pre-formed ketone pellets—switching to an alternative energy source. What is going to happen?

Ketone Kraze

Dietary fats are hot in 2017, and ketones are almost flammable in certain circles and regions. Unlike gluten, many WANT ketones, and have endured sacrifice and transient discomfort to acquire them—via dietary carb deprivation: the “ketogenic” diet (which typically translates into less than 50 grams of carbs/day—the equivalent of one whole bagel or one medium, cooked sweet potato).

Ketones are downstream metabolic fragments of fats that accumulate from an overflow of fat metabolism—and severely reduced carbohydrate availability and utilization, inside cells, not low blood sugar per se—and are made in the liver. If you are not diabetic, or are not using certain medications1, then the path to bathe your tissues and cells in ketones is to 1) fast for several days, 2) reduce your carb intake to ketogenic amounts (see above), or… prudently supplement with a ketone precursor/”pro-substrate” (unrelated to Elite or Pro)—more below.

There are three molecules that come under the umbrella of “ketones”: acetoacetate, beta-hydroxybutyrate (BHB), and (to a lesser extent), the nail polish remover-like emblem of a ketogenic dieter: acetone (lost through the breath, skin, and urine). Much of the research related to ketones in athletes and exercise performance has centered upon BHB.

Ketone Inspiration

Why go keto? Perhaps the simplest answer is related to FUELING—if an athlete is challenged with tolerating and/or ingesting adequate carbs during training or especially during racing (gut rot, bloating, or platinum status in the porta potty frequent visitors club) then a reduced carb intake—offset by an “alternative” fuel source—could translate into greater focus/less gut distraction and, possibly, enhanced performance. Increased availability of ketones in the body during training or racing would, hypothetically, reduce the reliance upon “onboard” carbohydrate (muscle and liver stored carbs—AKA glycogen) and external carbs (drinks, gels, chews, etc.).

Ketones: HomeMade

The first keto diet/performance study in athletes—five pro cyclists—was published in 1983 and showed that four weeks of a diet providing approximately 20 grams of carbs/day allowed the cyclists to “keto-adapt”, measured in blood from a vein (venous blood)2. The “performance” results from this study revealed two of the five athletes displaying a sharp increase in ride time to exhaustion, two other athletes showing a precipitous drop in ride time, and the fifth having no change. The intensity of the ride to exhaustion was notably below race pace for a 70.3 or IM distance athlete: between 62-64% of VO2max.

After four weeks of keto-adaptation the cyclists showed variable but significantly less muscle glycogen disappearance over the ride to exhaustion, relative to the same ride performed after a 67% carb diet. A salient item not mentioned in this study—but mentioned 21 years later by the lead scientist—related to the sprint capacity of these cyclists: “…[it] remained constrained during the period of carbohydrate restriction” 3. This is an important caveat to consider in the context of race pace/intensity, contrasted to training pace/intensity. More below.

The second study conducted in venous blood confirmed, long term (average of 20 months; approximately 10% carbs and 70% fat intakes—self-reported) keto-adapted athletes (elite ultra runners and IM distance triathletes)—the so-called F.A.S.T.E.R. study—measured the use of fuel substrates over a three hour, moderate intensity treadmill run (64% of VO2max), yet not to exhaustion4. The pre-run meal/drink taken 90 minutes before was fat-rich in the keto athletes (13 grams of protein [whey] + 4 grams of carbs + 31 grams of fat, primarily from heavy cream and olive and walnut oils), and (uncharacteristically) fat-rich (same fat sources) for the carb-adapted athletes (12 grams of protein [whey] + 43 grams of carbs [fruits + high fructose syrup: agave] + 14 grams of fat). Surprisingly, the keto-adapted athletes had an equal amount of glycogen disappear from their quads after this moderate pace run as the carb-adapted athletes (no apparent carb “sparing”), despite breath measures in the keto-adapted athletes showing paradoxically lower carb “disappearance”, and a markedly greater utilization of fat during the exercise. No performance tests were conducted.

The most recent study was conducted in elite/world class race walkers who were assigned to a three week, low carb/high fat diet (less than 50 grams carbs/day and 75-80% fat), a high carb diet (60-65% carb and 15-20% fat), or a periodized high carb diet (same macro ratios as high carb; high muscle glycogen pre-training with carbs during interspersed with low glycogen/fasted, with delayed post-exercise refueling)5. NOTE: Two of the primary researchers in this study spoke at the 2016 Ironman Sports Medicine Conference in Kona, HI. After three weeks of increased intensity training the low carb group displayed keto-adaptation (confirmed by finger stick blood ketone measurements and greatly increased fat utilization during exercise) but showed significantly reduced race performance, compared to the carb groups, which showed significant performance improvements. Distinctively, this is the first study with keto-adaptation in athletes where ALL of the meals were provided (rather than self-selected), creating a more rigorous control of calorie and macronutrient intake.

Takeaway: Some athletes implementing a very low carb, high fat diet (< 50 grams of carbs/day) may respond exceptionally well, some may respond very poorly, and some may not respond at all. Muscle carbohydrate is always used as a fuel, even among keto-adapted athletes exercising at moderate intensity. Higher intensity performance (think race pace) would likely suffer in a keto-adapted state, and require carbohydrate supplementation.

Ketones: Outside In

The early stage rigors of a low carb/high fat or ketogenic diet, for some athletes (during training periods), are akin to mild starvation, with nearby humans and small dogs being subjected to irritable outbursts and spontaneous kicking, respectively. Exercising muscle is flexible and promiscuous, selecting varying ratios of carbohydrate and fat throughout the entire spectrum of exercise intensity6,7. What if one could have their cake and ketones, too? Enter ketone supplements, providing a precursor to ketones.

The products currently offered in the market are centered upon “salts” of BHB—typically sodium, calcium, or potassium associated with BHB. To get gram quantities of BHB typically means gram quantities of the companion salts, which can challenge the guts of some persons (read diarrhea). An alternative form of BHB is as an ester—a ketone pro-nutrient—where the BHB is connected to a companion molecule that is not a salt, or may even be attached to a precursor of another ketone, with a ketone being released through the process of digestion.

A number of commercially available products are also mixed with Medium Chain Triglycerides (MCTs), providing a longer lasting metabolic precursor to ketones. However, MCTs can cause gut distress when ingested during exercise and appear to improve performance in trained athletes only when combined with a carbohydrate supplement8,9.

Takeaway: BHB salts are all we can get right now. Attempts to increase the dose require prudence and patience, as they may upset the stomach. The addition of MCTs can prolong the elevation in blood ketones but can also magnify tummy tremors.

Caveat: Like certain biomolecules, the ketone BHB can exist in a few three dimensional shapes/conformations, not unlike a right shoe being a “shoe” but not fitting the left foot. L-amino acids, like L-leucine, are examples, with D-leucine being metabolically undesirable/toxic if ingested in high amounts. The available BHB supplements are 50:50 mixes of a “native” form and a non-native form (a “racemic” mixture), yet no studies in humans have compared the utilization and effects of a racemic BHB to a native only BHB.

Synthetic Ketones: Super Fuel?

To date, only one study has assessed the effects of oral ketone supplements,10, which was published in 2016 from a research collaborative with abundant experience in ketone metabolism outside of exercise. An underlying assumption is that BHB can serve as a super fuel substrate, yielding more energy per breath of oxygen than carbohydrate (based on rat heart studies in non-physiological conditions)11. However, this has yet to be demonstrated in the skeletal muscle of humans.

This initial study used an ester of the native, 3D form of BHB, attached to a precursor to the other dominant ketone, acetoacetate—effectively a double ketone: precursor + pro-nutrient. The dose of BHB ester was 573 mg/kg body weight, or 260 mg/lb, and was mixed with dextrose (providing 60% of the calories), compared to an equal calorie carb mixture (1:1:2 mixtures of dextrose, fructose, and maltodextrin). Half of the drink was consumed before exercise, the remainder ingested during exercise. NOTE: gut distress was not noted among any of the elite cyclists ingesting the BHB ester drink. During 45-minute rides at 40% or 75% of maximal workload (Wmax; slightly higher % than %VO2max), BHB made significant contributions (16-18%) to energy utilization. Additionally, after performing a 60-minute ride at 75% of Wmax, cyclists that received the BHB + dextrose mixture displayed a 2% improvement over the carb cocktail treatment. Muscle glycogen disappearance was also reduced by the BHB ester—a glycogen sparing effect.

This initial study offers some very intriguing promise, suggesting alternative fuel provision with native BHB (delivered as an ester) may improve endurance performance. The blood concentrations seen in these cyclists would be very challenging, if not impossible, to attain from a ketogenic diet. Additionally, according to one of the researchers in this study (a world champion rower), higher doses, not unlike caffeine, could impair exercise performance. This inverted U-shaped curve—low doses being ineffectual, a peak dose range being ideal, and higher doses being ergolytic—reducing performance, warrants additional, “limbo” dose-response studies: how low one can go with BHB dosing to acquire the maximum performance benefit? What also merits exploration, as has been observed in ketogenic diets, is the impact upon high intensity exercise (greater than 75% of VO2max; again, race pace for much of a race for elite/pro triathletes) performance: BHB supplements would not be expected to improve exercise performance.

Caveat: Ketone supplements have a distinctive taste profile that makes “blinding” of subjects (at this stage), impossible.

One Door Closes…70.3 More Open

Skeletal muscle’s voracious appetite and promiscuity—amplified during exercise—allows for various fuels to be selected, on demand. At lower exercise intensities muscle can be a glutton and devour all thrown at it—in metabolically healthy, trained athletes. As the intensity increases the obligate reliance upon carbohydrate increases—the irrefutable race pace phenomenon. Indeed, many keto-adapted athletes ingest notably greater amounts of carbs the night before and/or morning of races, and during races, to accommodate the higher carbohydrate demands of race intensity. Ketone supplements may emerge as a new alternative fuel source that removes the challenges of keto/low carb dieting while supporting muscle fuel needs during moderate intensity exercise. The next, applied frontier will be the effect of ketone supplementation in real world race pace conditions. Unfortunately the BHB ester used in this study remains “Unobtainium”—not available for sale due to the still prohibitive cost for manufacture. Studies done with commercially available BHB salts are eagerly anticipated. Lastly, given the personal metabolism profile unique to each athlete, there will likely be those that are responders, and non-responders, to BHB supplements. Where will you land? Test, don’t guess.

References

1. Rosenstock J and Ferrannini E. Euglycemic diabetic ketoacidosis: a predictable, detectable, and preventable safety concern with SGLT2 inhibitors. Diabetes Care 2015;38:1638–42.

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