Exogenous Ketones – Worth Buying? Scientific Recommendations

Authors
Brandon Roberts (FBResearchgateThe Strength Guys)
Adam Tzur
(Sci-Fit on FB)

Reviewed by
Zad Chow (FB, Less LikelyExamine.com)
Alan Aragon (FBResearchgateResearch Review)
Brianna Stubbs (FB, Researchgate)
Brad Dieter (FBResearchgateScience Driven Nutrition)

Michael Hull (FB, Researchgate, Examine.com)

Length: ~3500 words
Published: 30.05.2018 (updated: 30.05.2018)


 

Plain Language Summary

 

Medical Disclaimer

The information presented in this article is not medical advice. Read more in our full medical disclaimer.

What you will learn

What we did, and why

We’ve analyzed exogenous ketones studies with human participants. Our main goal was to determine if exogenous ketones could improve performance. Marketing can often trick us into buying supplements with little to no effect. Hence, it is useful to know whether a supplement is actually supported by research.

What are exogenous ketones?

Ketones are typically produced by the body during fasting or when on a ketogenic diet. Exogenous ketones are synthetic ketone bodies that now exist as supplements. There are two main types of exogenous ketones: ketone esters (liquid), and ketone salts (powder).

Esters may produce fewer side effects than salts, but neither type seems to taste very good.

Summary of Evidence

Sci-fit Exogenous ketones summary table 1000x747 tinified

Video Summary by PictureFIT

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Exogenous Ketones are not recommended

 

There is currently no evidence that exogenous ketones increase strength or promote hypertrophy in humans. Your money is better spent on other supplements, such as creatine or caffeine.

Marketing Claims and Opportunity Cost

We’ve evaluated some marketing claims by companies such as Pruvit, Ketoforce, and Perfect Keto. For example, they claim ketones improve focus, mood, energy, fat loss, and athletic performance.

In general, these claims are not supported by the current scientific evidence in humans.

We advise consumers to be cautious, and to consider supplements with greater scientific backing. Compared to proven supplements like caffeine and creatine, exogenous ketones can be quite expensive. Check out our price comparison.

Future Potential

Even though the evidence is limited as of 2018, things may change in the future. Future formulations could eliminate side effects and mask the taste. There is also promise for combining ketone esters with carbohydrates.

More short-term and long-term studies are needed. Our evidence matrix and recommendations may change in the future as more research is published.

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The Ketogenic Diet Series

Part 4

Is it Easy to Adhere to the Ketogenic Diet?

Part 5

Side Effects of the Ketogenic Diet

Part 6

Do Ketone Supplements Improve Athletic Performance?

Summary
Overview of Ketogenic Diet Science

 

What Are Exogenous Ketones?

 

Exogenous: “introduced from or produced outside the organism or system” - Merriam-Webster

Ketone Salts and Ketone Esters

Exogenous ketones are a synthetic form of ketone bodies. They come in two forms: ketone esters and ketone salts.

Ketone salts have a sodium (Na+) molecule attached while ketone esters have a double bond (ester) to oxygen (O). They are then bound to another ketone precursor/molecule, avoiding the salt or acid load. Ketone esters can be further divided into B-Hydroxybutyrate esters and Acetoacetate esters. These different esters could give different physiological effects.

See image for comparison. Both forms of exogenous ketones can increase levels of B-Hydroxybutyrate (BHB) in the blood.

There are also important differences in structure between the same type of ketones (isoforms) that are discussed at the end of the article.

Exogenous ketones esters and salts

The first study published in humans using ketones was in 2012 (Clarke et al., 2012). However, ketone esters were first used in a performance study in 2016 (Cox et al., 2016) (the authors currently own a patent for ketone esters in the US).

Since then, multiple studies have used ketone esters and ketone salts. There are currently fewer brands of ketone esters. The main form of ketone salts used in studies is KetoForce which is made by KetoSports (Stubbs et al., 2017, O’Malley et al., 2017, Rodger et al., 2017).

Ketone salts are generally bought in powder form and mixed with liquid, while ketone esters are packaged in liquid form (Scott and Deuster 2017).

“Ketone bodies, acetoacetate (AcAc) and D-β-hydroxybutyrate (βHB), are respiratory fuels that can be oxidised by most body tissues [21] and are formed in large quantities (up to 150 g/day) by the liver in response to low blood glucose and insulin [23,24].” - Cox and Clarke 2014

“Ketone esters are not commercially available to date, but ketone salts represent a cheaper, more readily-available exogenous ketone supplement. These salts comprise of the free acid form of βHB buffered with sodium, potassium, and/or calcium salts but are less effective at elevating plasma βHB concentrations compared to the ketone monoester (Stubbs et al., 2017). ” - Evans et al., 2018

“... two prominent ketone esters in the published literature are the R,S-1,3-butanediol acetoacetate diester (Kesl et al., 2016) and the (R)-3-hydroxybutyl (R)-3-hydroxybutyrate ketone monoester (Clarke et al., 2012; Cox et al., 2016). Acute ingestion of either ester can result in short-term (~0.5 to 6 h) nutritional ketosis indicated by [βHB] >1 mM (Clarke et al., 2012; Kesl et al., 2016). For the ketone monoester, ingestion at a dose 573 mg/kg body mass (BM)resulted in [βHB] of ~3 mM after 10 minutes and rising to ~6 mM 30 min after ingestion (Cox et al., 2016).” - Evans et al., 2017

Will Exogenous Ketones get you into ketosis?

Exogenous ketones can rapidly increase the level of ketones in the blood (Clarke et al., 2012). The increase occurs within 30–45 minutes after drinking the supplement. Blood ketone levels can remain elevated for ~2–3 hours after ingestion. Some studies use multiple doses of exogenous ketones to keep blood levels elevated (Leckey et al., 2017, Stubbs et al., 2017).

Ketones are frequently measured by looking at B-Hydroxybutyrate (BHB) levels in blood. In the graph below you can see examples of human studies that use exogenous ketones. Ketone esters are better at increasing BHB levels and act in a dose-response manner (Shivva et al., 2016; Stubbs et al., 2017).

Ketone esters also elevate BHB levels higher, for those who have not eaten a meal beforehand (Stubbs et al., 2017). Lower ketone levels in a fed state could be due to reduced ketone uptake or reduced gastric emptying (Pinckaers et al., 2017).

Exogenous ketones BHB levels

Higher ketone levels aren’t necessarily better. Some scientists think there might be a “goldilocks zone” where performance can be improved (Egan 2017). The idea is that high ketone levels could cause a negative feedback loop where uptake by skeletal muscle is reduced (Pinckaers et al., 2017). High levels could also potentially inhibit glycolysis (anaerobic energy system).

Some scientists speculate that BHB levels above 2 mmol/l is needed to get performance benefits (Stubbs et al., 2018). We need more research to see if there are optimal ketone levels for performance.

“... while skeletal muscle is able to extract ~50 % of circulating ketone bodies when concentrations are low (0.1–0.5 mmol/L), this uptake capacity is reduced to only ~5 % when concentrations reach ~6–7 mmol/L. However, exercise may increase ketone body uptake, as recent pilot data [58] and preliminary reports [67] suggest that exercise increases the absolute rate of ketone body uptake and oxidation by skeletal muscle [58, 67].” -  Pinckaers et al., 2017

“Reaching blood ketone concentrations >2 mM is likely a key mediator of any potential ergogenic effect” - Stubbs et al., 2018

Timeline of Exogenous Ketone Studies

The use of exogenous ketones dates back to the 1980s (Fery et al., 1988, Fery et al., 1986, Fery et al., 1983). If they have been studied for so long, then why are they becoming popular now?

A string of studies from 2016 to 2018 have brought keto supplementation to the forefront of endurance exercise. Starting with Cox et al., in 2016  a new study was published almost every other month. The last study used in our analysis was published in early 2018.

Timeline of exogenous ketone studies

 

Potential Benefits of Exogenous Ketones

 

Ketosis, Performance, and Recovery

Researchers propose several reasons why it could be a good idea to supplement ketones:

  1. Exogenous Ketones quickly increase ketone levels in the blood. This leads to ketosis, which is also the effect of the ketogenic diet. Except, you don’t have to diet to use exogenous ketones (Pinckaers et al 2017).
  2. Ketone bodies serve as fuel for muscles during exercise (Egan and D'Agostino 2016)
  3. We might be able to reduce fatigue by sparing carbohydrate stores or reducing the accumulation of lactate in the body (Egan and D'Agostino 2016).
  4. This could potentially lead to an increase in athletic performance (Scott and Deuster 2017).
  5. Exogenous ketones might potentially improve recovery via glycogen resynthesis, and protein synthesis.

“KBs are utilized by skeletal muscle during exercise (Balasse and Fery, 1989), and their uptake and oxidation during exercise are enhanced by exercise training (Winder et al., 1975). These, in addition to a glucose-sparing action in skeletal muscle (Robinson and Williamson, 1980) and potential to lower the exercise-induced rise in plasma lactate (Balasse and Fery, 1989), suggest potential performance benefits of KBs if provided as an exogenous fuel source..” - Egan and D'Agostino 2016

“... orally ingested ketone body supplements may represent a more practical alternative to increase circulating ketone body concentrations in athletes [11, 15] since they do not require adherence to a high fat, low carbohydrate ketogenic diet to induce ketosis.” - Pinckaers et al 2017

“A potential role for ketosis as a performance enhancer was first introduced in 1983 with the idea that chronic ketosis without caloric restriction could preserve submaximal exercise capability by sparing glycogen or conserving the limited carbohydrate stores. Few human studies on the effects of a ketogenic diet on performance have yielded positive results, and most studies have yielded equivocal or null results, and a few negative results.” - Scott and Deuster 2017

“The dietary [ketone ester] could maintain ketosis using drinks taken regularly around a normal meal pattern” - Stubbs et al., 2017

Ketones for Fat Loss?

You might have come across claims that ketone supplements burn fat and improve weight loss. We know that ketones may reduce appetite over 4 hours compared to dextrose (Stubbs et al., 2018). Curbing hunger could help with long-term fat loss.

However, there are some other issues:

1 - Ketones inhibit fat breakdown and the creation of new ketones

The body breaks down fat to create ketones. Yet, it needs to prevent excessively high ketone levels (ketoacidosis). Hence, ketones limit the breakdown of fat (lipolysis) and thus their own production (ketogenesis) (Taggart et al., 2005; Balasse and Neef, 1975; Mikkelsen et al., 2015; Pinckaers et al 2017; Evans et al., 2017; Leckey et al., 2017; Stubbs et al., 2017; Harvey et al., 2018).

The higher the ketone levels, the stronger the effect. This means that exogenous ketones actually prevent body fat from being used (Taggart et al., 2005; Mikkelsen et al., 2015; Leckey et al., 2017).

[in humans] “... during starvation ketone bodies exert “a fine regulatory adjustment” of their own synthesis by inhibiting adipocyte lipolysis. Such a mechanism would potentially conserve fat stores during extended starvation and attenuate excessive formation of ketoacids from unrestrained lipolysis and ketogenesis.” - Taggart et al., 2005

“An increase in HOB from the basal 160-450 μmol/L elicited 14 ± 2% reduction (P = .03) in glucose appearance and 37 ± 4% decrease (P = .03) in lipolytic rate while insulin and glucagon were unchanged.“ - Mikkelsen et al., 2015

“Ketone bodies exert negative feedback on their own production by reducing hepatic FFA supply through βHB-mediated agonism of the PUMA-G receptor in adipose tissue, which suppresses lipolysis (Taggart et al., 2005). Exogenous ketones from either intravenous infusions (Balasse and Ooms, 1968; Mikkelsen et al., 2015) or ketone drinks, as studied here, inhibit adipose tissue lipolysis by the same mechanism, making the co-existence of low FFA and high βHB unique to exogenous ketosis.” - Stubbs et al., 2017

“While it is clear that exogenous ketones increase serum BOHB, they are not ketogenic, and may, in fact, inhibit endogenous ketone production (Balasse & Neef, 1975). In other words, they promote ketonaemia but do not encourage the creation of ketone bodies in the liver. So, it is more accurate to say that exogenous ketones mimic the effects, many of which are positive, of [nutritional ketosis], rather than inducing it.” - Harvey et al., 2018

“... ketone bodies have also been shown to reduce circulatory FFA availability via inhibiting the lipolytic effect of catecholamines [28], and/or via stimulation of hyperinsulinemia, which subsequently reduces lipolysis” - Pinckaers et al 2017

“Beyond 5 days without food, plasma ketone body concentrations plateau and rarely exceed ~10 mmol/L [22]. This upper limit of ketonemia has been suggested to be the result of an inherent feedback mechanism by which ketone bodies inhibit their own production via exerting an insulinotropic [25, 26, 27] and anti-lipolytic effect [28] ” - Pinckaers et al 2017

Nutritional ketosis achieved by either AcAc infusion (Fery & Balasse, 1988) or KE ingestion (Cox et al., 2016) inhibits the lipolytic effect of exercise, i.e. the amount of lipid-derived substrates available for working muscle is reduced. - Evans et al., 2017

“... above a threshold concentration, the capacity for skeletal muscle to oxidise KBs becomes saturated, and/or that hyperketonemia itself is a self-inhibitory factor” -  Evans et al., 2017

“... inhibition of ketogenesis was probably partially related to the direct antilipolytic effect of infused ketones. Indeed, there was a concomitant fall in FFA and in glycerol levels averaging respectively 13.5% and 17.3%” - Balasse and Neef, 1975

“... there is some concern that the presence of high circulating concentrations of ketone bodies could inhibit the flux of other muscle substrates, either by impairing (rather than “sparing”) muscle CHO oxidation and/or inhibiting adipose tissue lipolysis ...” - Leckey et al., 2017

2 - No studies in humans

There are currently no short-term or long-term studies that evaluate how exogenous ketones fat loss or weight loss. We only have mechanistic evidence, as discussed in the 1st point.

3 - Ketones are calories

Since ketones are used as a fuel source, it stands to reason that they contain energy.  Ketone esters should have around ~4.8 to ~4.9 kcal per gram 1Thanks to Alan Aragon for his investigation into this.  

A single dose of Pruvit Keto OS contains 41-110 kcal, depending on which product you use. If you take multiple servings per day, that could add up.

4 - Appetite reduction due to ketones or nausea?

Side effects are common with the ketone formulations we currently have. They often lead to nausea and gut discomfort. You can read more about the side effects here.

It is quite possible that exogenous ketones could reduce appetite by themselves. For example, they can reduce ghrelin, which subsequently reduces appetite. It is also possible that the reduction in appetite is due to the commonly reported side effects.

Conclusion for fat loss

Based on the evidence we have, there’s little reason to think that exogenous ketones help burn fat or speed up weight loss.

Preventing Keto Flu with Ketones?

There are currently no human studies on this topic. Any potential benefit is therefore anecdotal.

 

Potential Drawbacks of Exogenous Ketones

 

Side Effects

People experience negative side effects in some ketone studies. Adverse effects such as nausea, diarrhea, abdominal pain, dry retching, and reflux are reported (Evans 2017, Waldman et al., 2018,  Harvey et al., 2018, Leckey et al., 2017, Vandoorne et al., 2017). This might happen because exogenous ketones taste bad, or because of the high osmolarity of salts.

Others report no side effects (Holdsworth et al., 2017, Cox et al., 2016, Stubbs et al., 2017, O’Malley et al., 2017, Rodger et al., 2017). Of note, all of these studies use exercise except for Stubbs et al., 2017.

Note that newer ketone supplements could be formulated to eliminate side effects. Time will tell.

Side Effects of Exogenous ketones

Green = Symptom Reported
Red = Symptom Not Reported

“Side effects of KE ingestion have been reported in humans (Clarke et al., 2012). Specifically, in a repeated dose design over five days, adverse effects such as flatulence, nausea, diarrhoea, and dizziness were reported in five out of twenty-four participants at doses ranging from 420 to 1071 mg/kg BM. Such issues were prevalent in almost all participants when the dose was increased to 2142 mg/kg BM per day, indicating a possible upper limit of tolerability in adults (Clarke et al., 2012).” - Evans 2017

“The present investigators utilized an absolute dosing protocol and 30 min time frame based on the supplement directions. As seen in previous literature …, our pilot data suggested significant gastrointestinal distress (i.e., abdominal pain, diarrhea, nausea) when the time duration after ingestion exceeded 60 min followed by no further elevations in ßHB.” - Harvey et al., 2018

“All participants reported gastrointestinal discomfort associated with the intake of the ketone diester. Symptoms ranged from major (dry retching and nausea; n = 2), to moderate nausea (n = 5) or moderate reflux (n = 1), and minor discomfort (mild nausea; n =2).” - Leckey et al., 2017

“The ketone drink, which had no side effects, contained 0.573 mL/kgj of the ketone ester, (R)-3- hydroxybutyl (R)-3-hydroxybutyrate (12,13).” - Holdsworth et al., 2017

“Taking the supplement was not without side effects. One subject dropped out due to gastrointestinal symptoms and two others reported similar but milder problems” - Fischer et al., 2018

Taste

Both companies and consumers report that exogenous ketones may taste bad. When taken alone, they may be bitter (i.e. Leckey et al., 2017; Stubbs et al., 2017; Holdsworth et al., 2017), “pungent” (Evans et al., 2018), or “horrendous” (Perfect Keto).

Luckily, the taste can be somewhat masked by using artificial sweeteners and other agents. Companies are now creating new supplements that avoid the poor taste. Drinking a small amount of diet cola after a ketone drink could mask the taste (Leckey et al., 2017).

“Exogenous ketones are not delicious. They are not meant to be delicious. In fact, when taken alone, they are horrendous. We engineered our products to deliver the many benefits of exogenous ketones without losing your lunch. However, many people will still find the product slightly bitter, or to have a strange aftertaste.” - Perfect Keto

We recommend reading through these amazon comments discussing exogenous ketone taste.

“It was not possible to completely replicate the taste of the [ketone] drink, but a comparably novel and bitter-tasting [placebo] was prepared from a mixture of flavor essences (rum, almond, and bitters Angostura). Pilot testing revealed that the intake of a small volume of diet cola immediately after the [ketone drink] and [placebo] was able to quickly mask the taste and texture of the previous drink.” - Leckey et al., 2017

“The dextrose drink was taste-matched using a bitterness additive“ - Stubbs et al., 2017

“The natural bitter taste was partially masked with citrus flavoring ... and proprietary sweetener ... The control drink contained the same citrus and sweetener components as the ketone drink. The bitter taste was matched with the addition of a weight-dosed commercial bitter agent ...” - Holdsworth et al., 2017

“The open-label design was chosen because of the difficulty in masking the pungent taste of the βHB salts” - Evans et al., 2018

[discussing placebo] “Our experience is that it is extremely difficult to mask or even mimic the distinct taste of KEs, which could be an issue for those familiar with the taste by experience or reputation.” - Egan and D'Agostino, 2016

Reduced Athletic Performance

In some studies, exogenous ketones reduced athletic performance. We discuss this in greater detail in the performance section below.

 

Performance and Recovery with Exogenous Ketones

 

Athletic performance

Time trials

A time trial is a cycling test where your goal is to finish a distance against the clock.

We have three time trials: O’Malley et al., 2017, Leckey et al., 2017, Cox et al., 2016

Two studies used ketone esters. Cox et al. (2016) found a 2% performance improvement for the ketone plus carbohydrate group (60+30 minute trial). Yet, in Leckey et al. (2017), the ketone group had a 2% performance reduction and a 3.7% reduction in mean power (31.2 km trial).

The last study used ketone salts and the ketone group spent 46s (~6.5%) more time finishing the time trial. Their average power output was also ~7% lower (O’Malley et al., 2017). The trial lasted about 11–12 minutes.

Exogenous Ketones Performance time trial

“While a 2% improvement in performance may appear modest, in elite sport, the difference between winning and losing is often less than that (Malcata and Hopkins, 2014). However, in laboratory tests of performance such as those employed by Clarke and colleagues, the coefficient of variation is typically 1% to 3%. “- Egan and D'Agostino 2016

“... we observed that average power output during the time-trial was reduced in the ketone versus placebo condition. A high degree of CHO oxidation to support ATP demand is necessary to maintain the workload during the time trial as supported by blood lactate values of 10 mmol/L at the end of the time-trial (Fig. 1E). Attenuation of CHO metabolism during high-intensity exercise by ketone salts is likely to reduce power output during heavy workloads as seen here” - O’Malley et al., 2017

“Contrasting results from existing studies using different ketone compounds, performance tests, dosages, and analytic techniques highlight that further research is required to determine the role of exogenous ketones in athletic performance” - Stubbs et al., 2018

Shorter races and sprints

Participants in Rodger et al. (2017) did a 4 minute cycling sprint after 90 minutes of cycling (ketone salt).
No group differences were found for mean power (W) or Vo2 (L-min).

Waldman et al., 2018 used a cycle ergometer. After a brief cycling + cognitive test, participants did four Wingate sprints lasting 15 seconds. They rested for 4 minutes between each sprint. There were no differences between groups for mean or peak power (W). However, the ketone salt group felt slightly more fatigued.

Graded exercise tests

Evans et al. (2018) used a ketone salt. They put participants on a cycle ergometer and gradually increased intensity. They found no improvement in muscular efficiency or perceived exertion:

“No differences in %VO2peak, VO2, VCO2, or VE were observed between conditions” - Evans et al. (2018)

Recovery from exercise

Recovery from exercise could also improve performance. For example, exogenous ketones could promote glycogen resynthesis. Glycogen is carbohydrates that are stored in the liver and muscle. Glycogen synthesis is when the body increases these stores by creating more glycogen from glucose.

Let’s use an example:

You’re an elite cyclist racing multiple days in a row. You’re eating all the carbohydrates you can handle, but your glycogen stores are depleting quickly. What if you could take a ketone supplement to increase glycogen synthesis? Or prevent the use of these stores until later?

Three studies have measured glycogen levels in athletes using ketone esters (Cox et al., 2016, Holdsworth et al., 2017, Vandoorne et al., 2017).

In Cox et al., 2016, participants exercised for 2 hours. Afterwards, those who supplemented a ketone ester plus carbohydrates had higher glycogen levels. They also used more muscle fat as a fuel. The participants who only took carbs had lower glycogen stores and used less muscle fat as fuel.

“after 2 hr of exercise at 70% VO2 Max, intramuscular lipids fell by 24% during KE+CHO, but only 1% on CHO (p < 0.01)“ - Cox et al., 2016

This could indicate that ketones spare glycogen, but it could also mean that they impair glycogen use (Leckey et al., 2017).

“... there is some concern that the presence of high circulating concentrations of ketone bodies could inhibit the flux of other muscle substrates, either by impairing (rather than “sparing”) muscle CHO oxidation and/or inhibiting adipose tissue lipolysis ...” - Leckey et al., 2017

Another study finds no difference between a ketone ester and placebo for post-exercise glycogen resynthesis (Vandoorne et al., 2017).

The third study, Holdsworth et al., 2017, suggests that a ketone ester + carb drink significantly increases post-exercise glycogen resynthesis (+40%) compared to glucose.

Glycogen synthesis with exogenous ketones

The evidence on exogenous ketones helping glycogen synthesis is weakly in favor of the use of ketone esters plus carbohydrates. However, drastically different protocols were used in the studies. Therefore, we should be very careful with our conclusions.

Below you can see the protocols:

Study protocols glycogen synthesis exogenous ketones

“As expected after 2 hr of exercise, glycogen concentrations fell on both arms with reductions in dark PAS staining and proportionate increases in moderate and light staining intensities. The degree of change was most marked on CHO, where significantly more glycogen deposits appeared moderate or light, or were no longer visible versus KE+CHO (p < 0.05).” - Cox et al., 2016

 

Should You Buy Exogenous Ketones?

 

Price and Opportunity Cost

“An opportunity cost represents an alternative given up when a decision is made” - Investopedia

Every dollar you spend on a supplement could be spent on something else. Therefore, we have opted to look at the opportunity cost of buying exogenous ketones compared to other supplements.

It is well established that the following supplements boost athletic performance (Naderi et al., 2016; Burke, 2017; IOC consensus statement of 2018; Peeling et al., 2018):

Therefore, these supplements are the safe baseline which new supplements can be compared to. It is our opinion that expensive supplements should be moderately or strongly supported in the literature to justify a purchase.

Below is a price comparison of different products:

Note: Prices and calories are taken from Amazon, MyFitnessPal, or from the webpage of the producer. Note that the products listed here are not affiliate links. We list them here for price comparison purposes only. Sci-Fit does not recommend any particular brand.

ProductCalories Per ServingPrice Per Serving
Perfect Keto Coffee
(BHB salt)
15 kcal$3.93
Keto OS 3 Chocolate Swirl (OTG)56 kcal$5.5
KetoSports KetoForce Dietary Supplement (Liquid)55 kcal$3.16
[Caffeine Powder] BulkSupplements Pure Green Coffee Bean Powder-$0.03
Genius Caffeine Pills-$0.14
Optimum Nutrition Micronized Creatine Monohydrate Powder-$0.13
Creatine Monohydrate Powder Micronized by BulkSupplements-$0.09
Nutricost Beta Alanine Powder (300g)-$0.13
NOW Foods Beta Alanine Powder (500g)-$0.09
1200mg Nitric Oxide Supplement [L-arginine and L-Citrulline]-$0.63
SHEER N.O. Nitric Oxide Supplement  [L-arginine and L-Citrulline]-$0.92

As you can see in the comparison above, you can buy creatine, beta alanine, and caffeine powder for $0.03-$0.09 per serving. The price is somewhat higher for NO-boosters. Exogenous ketones are priced above $3 per serving. Creatine, beta-alanine, and caffeine are therefore 1-3% of the cost. These supplements are more likely to give better short-term and long-term performance and body composition benefits.

"The supplements discussed here are separated into three categories based on the level of evidence supporting their use for enhancing sports performance: (1) established (caffeine, creatine, nitrate, beta-alanine, bicarbonate) ...” https://www.ncbi.nlm.nih.gov/pubmed/29465269

"... a number of supplements have received plentiful and insightful attention from sports scientists to produce robust evidence of the scenarios in which they can enhance sports performance. These include caffeine [4, 5], creatine monohydrate [6, 7], bicarbonate [8, 9], beta-alanine [10, 11], and beetroot juice/nitrate [12, 13]." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5371635/

"Many sport supplements are available, however, it is only a few that are supported by enough evidence to have a performance effect including β-alanine, beetroot juice (nitrate), caffeine, creatine, sodium bicarbonate, carbohydrate and protein" - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5545206/

What about the Marketing Claims?

We have checked some marketing claims by prominent keto companies. Per the evidence presented in this article, we find that most of these claims are not currently supported in the literature. And if the claims do have some support, it is very limited (see our evidence matrix for more details).

Perfect Keto Coffee claims:

  • Supports a healthy metabolism
  • Appetite control
  • Increased focus
  • Supports athletic performance
  • Sustain higher energy levels

Keto OS 2.1 claims:

  • Improved focus
  • Better Energy
  • Abdominal fat loss
  • Better sleep
  • Increase strength
  • Regulates mood

Ketoforce claims:

“It is suggested that this product be consumed during the initial stages of a ketogenic diet (three times a day for first 2-3 days) to accelerate ketosis and ease metabolic transition. It can be consumed once a day once ketosis has been achieved for help with ketosis maintenance. The product may also be consumed prior to high intensity aerobic exercise to enhance performance, especially for those on a low carb/ketogenic diet.”

 

Other Considerations

 

  • BHB ketone esters have two isoforms: L-BHB and D-BHB. Isoforms are slightly different structures of the same molecule. Which variant we use might matter.
  • There are many animal studies on ketones and ketosis, but we have excluded those because some findings may not apply to humans due to physiological and biomechanical differences.
  • Acute studies using ketone supplements may not translate to long-term gains in performance. For example, a proven performance enhancement supplement –  creatine monohydrate – increases performance after you have consumed it for a while. In addition, the benefits slowly wear off once you’ve stopped supplementation.

“There are metabolic differences between the ketone molecules delivered by exogenous ketones. This can impact their physiological and neurological effects. Optical isoforms of BHB are not equivalent: D-BHB is released by the liver, whereas L-BHB is an intracellular metabolite ... elevating L-BHB may not improve athletic performance ... These data highlight the importance of distinguishing between D-BHB, L-BHB, and AcAc, and accounting for this in study design and interpretation” - Stubbs et al., 2018

““The difference in peak blood D-βHB concentrations between matched amounts of βHB as ester or salts arose because the salt contained L-βHB, as the blood concentrations of D- plus L-βHB isoforms were similar for both compounds. It is unclear if kinetic parameters of KE and KS drinks would be similar if matched D-βHB were taken in the drinks. Unlike D-βHB, blood L-βHB remained elevated for at least 8h following the drink, suggesting an overall lower rate of metabolism of L-βHB as urinary elimination of L-βHB was in proportion to plasma concentration.” - Stubbs et al., 2017

Study Limitations

  • Some studies use fasted participants and others use fed participants. This could make a difference in performance. Practically, most endurance athletes would eat a few hours before a race. If there is a specific zone where blood ketone levels are optimal, then fasting vs fed comparisons are critical.
  • There are multiple ways to measure ketones in the blood. The use of different methods is difficult to compare directly.
  • The optimal dosage of ketone salts or esters have not yet been established for performance. Much more research is needed. Formulas will also likely improve over time. For example, carbohydrates could be combined with ketone esters.
  • GI distress or poor taste might cause the performance decrements, not the ketones themselves. This could be improved with further development of exogenous ketones.

“Contrasting results from existing studies using different ketone compounds, performance tests, dosages, and analytic techniques highlight that further research is required to determine the role of exogenous ketones in athletic performance” - Stubbs et al., 2018