Zad Chow (FB, Less Likely, Examine.com)
Alan Aragon (FB, Researchgate, Research Review)
Brianna Stubbs (FB, Researchgate)
Brad Dieter (FB, Researchgate, Science Driven Nutrition)
Michael Hull (FB, Researchgate, Examine.com)
Length: ~3500 words
Published: 30.05.2018 (updated: 30.05.2018)
Plain Language Summary
The information presented in this article is not medical advice. Read more in our full medical disclaimer.
What you will learn
- How ketone supplements affect ketosis
- The difference between ketone esters and salts
- How ketone supplements affect athletic performance and recovery
- The benefits and drawbacks of exogenous ketones
- Whether you should spend your money on these supplements
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).
Summary of Evidence
Video Summary by PictureFIT
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.
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
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.
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).
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).
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.
Timeline of Exogenous Ketone Studies
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.
Potential Benefits of Exogenous Ketones
Ketosis, Performance, and Recovery
Researchers propose several reasons why it could be a good idea to supplement ketones:
- 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).
- Ketone bodies serve as fuel for muscles during exercise (Egan and D'Agostino 2016)
- 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).
- This could potentially lead to an increase in athletic performance (Scott and Deuster 2017).
- Exogenous ketones might potentially improve recovery via glycogen resynthesis, and protein synthesis.
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).
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
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.
Green = Symptom Reported
Red = Symptom Not Reported
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.
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
A time trial is a cycling test where your goal is to finish a distance against the clock.
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.
“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
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?
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.
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:
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.
- Caffeine (study collection)
- Creatine (study collection)
- Beta-alanine (study collection)
- Sodium bicarbonate
- Nitrates and Nitric Oxide [i.e. L-citrulline, beetroot juice]
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.
|Product||Calories Per Serving||Price Per Serving|
|Perfect Keto Coffee |
|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.
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).
- Supports a healthy metabolism
- Appetite control
- Increased focus
- Supports athletic performance
- Sustain higher energy levels
- Improved focus
- Better Energy
- Abdominal fat loss
- Better sleep
- Increase strength
- Regulates mood
“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.”
- 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.
- 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.