Debunking the Myth: Exogenous Ketones Boost Keto Results

Do Exogenous Ketones Work?

As the popularity of the ketogenic diet continues to rise, we’re seeing a tremendous spike in supplements intended to complement a ketogenic lifestyle and boost results. Hands down, the most popular keto-boosting supplement is exogenous ketones, with companies jumping on the bandwagon and new products popping up daily. What’s the deal with exogenous ketones? Are they a magic bullet or just a bunch of hype?

What are Exogenous Ketones?

Simply put, exogenous (which means “outside,” in this case, referring to “outside the body”) ketones are ketones that come from a synthetic source. Contrast that with endogenous (which means “within,” in this case, referring to “within the body”) ketones, which are produced naturally by the body during periods of fasting and severe carbohydrate restriction—most notably the increasingly popular ketogenic diet.

For more on the ketogenic diet, we encourage you to check out our other resources on the topic:

There are three types of endogenous ketone bodies:

  • Beta-hydroxybutyrate (BHB)
  • Acetoacetate (AcAc)
  • Acetone

Most forms of exogenous ketones deliver BHB, which is the most prevalent ketone in the body when produced naturally.

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Ketone Esters vs. Ketone Salts

There are two main types of exogenous ketones: Ketone esters and Ketone salts. Ketone esters are liquid exogenous ketone supplements that have a double bond to oxygen and are bound to a ketone precursor (usually BHB). Ketone salts are powdered exogenous ketone supplements that consist of a ketone molecule (BHB) bound to a mineral salt, such as sodium, calcium, magnesium, or potassium.

By and large, the majority of the scientific research conducted to date has studied ketone esters. This is crucial to note for multiple reasons (some of which will be discussed further below):

  • First, virtually ALL the commercially available exogenous ketone supplements are ketone salts. (At the time of publication, there is only one ketone ester supplement on the market.)
  • Second, compared to ketone esters, ketone salts are not nearly as effective at raising blood levels of ketones. In general, ketone salts elevate BHB levels to about 0.6 – 0.8 mM while a similar dose of ketone esters leads to a 3 times greater increase in BHB levels.1

It’s also important to point out that most ketone salt supplements are a 50/50 mixture of the D- and L-BHB isoforms. It seems as though the body does not use them the same way, and L-BHB seems to be “weaker” than D-BHB.

Ketosis vs Ketogenic State

If there’s one thing exogenous ketones have been shown to do, it’s produce a state of ketosis (which means blood ketones reach a certain level, typically > 0.5mM).1 But this state of ketosis may be quite different than the ketogenic state (i.e., nutritional ketosis) that can be obtained during prolonged fasting or with the ketogenic diet.

For example, with nutritional ketosis, you would typically see high levels of free fatty acids in the blood. However, exogenous ketone supplementation appears to reduce levels of circulating free fatty acids. According to leading exogenous ketone researcher Dr. Brendan Egan, “I think people are conflating the two ideas of whether a ketogenic diet and exogenous ketones are the same thing when they are really quite diverse. We should probably consider exogenous ketones a separate [fuel source].”2

In simple terms, you can be in ketosis without being in a ketogenic state. Whether that’s good and beneficial (especially as advantageous as some may lead you to believe) is a different question altogether. In fact, according to ketone researcher Dr. Brianna Stubbs, “Though nuanced, there’s a big difference between being in a ‘ketogenic’ body and a body ‘in a state of ketosis.’” 3

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How Are Exogenous Ketones Purported to Help?

Generally speaking, exogenous ketones are marketed to help boost the effects of a ketogenic diet and/or provide many of the benefits of keto without restricting carbs. More specifically, here are some of the marketing claims companies promoting exogenous ketones are making:

Increased fat burning. Interestingly, supplementation with exogenous ketones suppresses fat breakdown (lipolysis). In other words, they inhibit fat burning, and the higher the levels of ketones, the stronger the effect.1 Said differently, when you could be burning (endogenous) body fat, you’re burning an exogenous source of fuel. Research does show that supplementation with ketone salts prior to exercise increases fat burning during steady-state aerobic exercise (impaired performance notwithstanding).4

Appetite suppression. In one of Dr. Stubbs’ experiments, published in the journal Obesity, she and her colleagues found that healthy, normal-weight participants experienced a significant reduction in hunger, desire to eat, and the “hunger hormone” ghrelin for 1 ½ hours after consuming an exogenous ketone supplement in the fasted state.5 While the results were quite promising, the sample size was fairly small (15 people). The supplement used was a ketone ester, which raised BHB levels 3 – 4 times what could practically be achieved with a ketone salt supplement.

Accelerated weight loss. At this stage in the game, this is a speculative claim, as there are no human studies showing supplementation with exogenous ketones enhances weight loss. One could certainly argue a reduction in hunger and desire to eat could help promote weight loss, but again, there are no short- or long-term studies to corroborate that speculation. Also, it’s important to point out that exogenous ketones provide about 4.8 calories per gram, and some exogenous ketone supplements contain additional calories (e.g., from medium-chain triglycerides). And remember, extra calories promote weight gain.

Improved focus. Banish brain fog, optimize cognitive function, biohack mental performance… there is no shortage of brain-related benefits associated with exogenous ketones. And it makes sense given that endogenous ketones are a preferred source of brain fuel, and high levels of blood ketones are reported to be associated with superior mental clarity. However, at this time, there are no studies in healthy humans to back up these claims. In one very recent study, researchers found supplementation with ketone salts did not improve measures of cognitive performance in elite cyclists. 6 That being said, animal studies have shown improved cognitive performance with exogenous ketones. And there is one case study involving a patient with Alzheimer’s showing that daily supplementation with ketone esters may improve mood and cognitive performance. 7,8

Increased energy. Fundamentally, this is true. However, it may not be for the reason you think or have been led to believe. Simply put, exogenous ketones are a source of fuel for the body. In other words, just like carbs or fats, the body can use ketones to produce energy. Along those lines, ketones are viewed as the most energy-efficient source of fuel, yielding more usable energy than glucose (sugar) or fat.

Better mood. This is yet another benefit that remains to be seen in humans, at least in the scientific research. For what it’s worth, animal research has shown exogenous ketones may have a positive effect on anxiety.

Improvement in athletic performance. This is arguably the most well-researched area of exogenous ketones (although there is still a LOT we don’t know). For the most part, the scientific research has focused on ketone esters, which have been shown to improve endurance and recovery from exercise (increased muscle glycogen re-synthesis and increased protein synthesis). 9, 11 Even with some promising performance results, many questions (and skeptics) still remain. 12 Among the current published studies investigating the effects of ketone salts in athletes, none have demonstrated an improvement in performance. In one study, performance actually decreased by 7%. Among the participants, 60 – 78% reported GI distress (e.g., nausea, diarrhea, vomiting, lightheadedness) when the exogenous ketones were taken alongside exercise. 4,13,14

Help getting back into ketosis after consuming carbs. There are currently no human studies on this topic, and any potential benefit is anecdotal. As mentioned, exogenous ketones are effective at getting you into a state of ketosis. However, that does not mean they get you into a ketogenic state. And while there’s evidence that supplementation with a ketone ester may lower the blood glucose response to an oral glucose tolerance test, exogenous ketones are not to be misconstrued as a carb blocker, guilt eraser, or Band-Aid. In other words, they’re not a replacement for an overall healthy diet. 15

Preventing keto flu and/or accelerating keto adaptation. Presently, there are no human studies on this topic. While exogenous ketones can certainly accelerate ketosis, there’s no current evidence that supplementing with ketone bodies accelerates getting into a ketogenic state. Having said that, the initial phase of a ketogenic diet is often accompanied by an increase in the excretion of electrolytes. To that end, consumption of ketone salts (in which case the salts are electrolytes) might compensate for those losses. In other words, exogenous ketones (ketone salts) may help…but maybe not for the reasons you might think.

Decreased inflammation. This is a bold, if not risky, claim for any supplement company to make. It appears to stem from animal research and research showing nutritional ketosis (a ketogenic state) can reduce markers of inflammation. There’s a general consensus that ketone bodies act as signaling molecules that positively influence inflammatory and longevity pathways. 16 It is difficult to say, however, whether the state of ketosis (as induced by exogenous ketones) would have the same effects as a ketogenic state (induced by fasting and/or a ketogenic diet).

Better sleep. This appears to be purely anecdotal at this point.

What Are the Problems with Exogenous Ketones?

As you can see, there’s currently very little evidence to back up the bold marketing claims. We can’t necessarily extrapolate the results of animal research to humans, although those types of studies do give us important clues. What’s more, the benefits of nutritional ketosis (a ketogenic state) can’t necessarily be translated into benefits you expect from exogenous ketones.

In addition to the lack of supporting scientific evidence, there are some other key downsides to point out as it pertains to exogenous ketones:

They are expensive. There are many options when it comes to exogenous ketones, and seemingly more pop up every day. One of the biggest downsides is that they are expensive—very expensive—which may be quite surprising given the paucity of scientific support. The most popular brands of ketone salts run anywhere from $4 – $5 a pop, and many companies recommend using 2 or more servings daily. At the time of publication, there’s only one commercially available ketone ester supplement, and it is currently priced at $33 per serving.

They are not provided in the best form. As mentioned a few times, the research suggests that the ketone ester form of exogenous ketones outshines the ketone salt form, which has very little supporting evidence. Pretty much all of the commercially available exogenous ketone supplements are provided in the seemingly inferior ketone salt form.

They are not provided in appropriate amounts. The minimum effective dose—to raise blood ketones to a meaningful level—with ketone salts appears to be about 12 grams or so. While many exogenous ketone products are in this neighborhood, there are certainly some not delivering on their promises.

They are often “fairy dusted.” Along those lines, many companies are taking full advantage of the popularity of exogenous ketones by including ketone salts (in ineffective levels) in products just so they can market them as such. This is a practice known as “fairy dusting,” and these products often contain other “experiential” ingredients—namely, caffeine—so the user “feels” like the supplement is “working.”

They may cause GI distress. What’s worse than an expensive product that doesn’t work? An expensive product that doesn’t meet your expectations and makes you feel bad. As mentioned, studies investigating ketone salts suggest that negative side effects, such as nausea, diarrhea, abdominal pain, and reflux, are relatively common, and they are probably the result of the accompanying salt load and/or taste.

They taste bad. The taste of exogenous ketone supplements has improved markedly over the last few years. However, there is still quite a bit left to be desired, as few would describe the taste any better than tolerable. Most supplement companies selling exogenous ketones don’t hide this either. In fact, one popular company says in a blog post on its website, “Make no mistake, if we drink exogenous ketones for a great taste and pleasant mouthfeel, we will be disappointed. If we drink ‘ketones’ that taste ‘great,’ it is because there’s little to no actual ketone bodies in the product [and/or] there’s an enormous filler/garbage to ketone ratio.” 17

Who May Benefit from Exogenous Ketones?

Now, just because there’s a lot we don’t know about exogenous ketones, that doesn’t mean they may not be beneficial for some people in certain situations. By no means do I think the jury is out and that exogenous ketones are worthless. Quite the contrary, I think there are many questions that still need to be asked and investigated, and thankfully, there are brilliant, inquiring minds looking into them.

As I mentioned in this article on intermittent fasting, some researchers believe certain key benefits of fasting may be triggered by the presence of ketones. And many scientists believe the same thing about the ketogenic diet (i.e., ketone bodies may themselves underlie its efficacy). As I mentioned above, research shows that ketone bodies may be important signaling molecules.

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At this stage in the game, I’m not feeling all that confident about ketone salts. However, I am excited to see more research unfold pertaining to ketone esters. And as it does, I’m looking forward to seeing the price drop, as it is currently very cost-prohibitive. Currently, exogenous ketone supplements may hold promise for: 18

  • Recovery from brain injury
  • Cancer
  • People with cognitive impairment
  • Endurance exercise performance
  • Recovery from exercise/athletic activity
  • Appetite management

Debunking the Exogenous Ketones Myth: Recap

The biggest take-home, however, is that achieving a state of ketosis by supplementing with exogenous ketones does not equal a ketogenic state (that’s accomplished via fasting and/or a ketogenic diet). Exogenous ketones suppress endogenous production of ketones, and just because exogenous ketones increase blood ketone levels does not make you a better fat burner. Exogenous ketones are certainly not the magic bullet we’re often led to believe, and they’re not a substitute for eating a healthy diet or living a healthy lifestyle.

Of course, I’m not averse to experimenting with things, including exogenous ketones. I just think it’s important to take a pragmatic view of the evidence, which is hard to do with so much hype. Have you tried exogenous ketones? What were your experiences? I’d love to hear from you!

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References