Exogenous ketone supplements: Do they work?
Experiments conducted by Kim Gajraj, medical review by Dr. Andreas Eenfeldt, MD – Updated November 6, 2020
What are exogenous ketones?
Ketone supplements: are they a groundbreaking boost to a low-carb diet, or should you be wary of the broad claims that companies make about their benefits? In this article you’ll learn all about exogenous ketone supplements and, what’s more, you’ll read about the experiment we ran on the supplements at our head office in Stockholm. How did ketone supplements perform when we put them to the test? Do they work? Read on to find out our verdict!
As the keto diet increases in popularity, we are seeing more and more keto-related products flooding the market. One of the most popular and best-known of these is the exogenous ketone supplement, which claims to boost the effects of a keto diet and even give you some of the benefits of keto without restricting carbs.
There is big money in play here, with some companies generating huge amounts of income from sale of these supplements. Plus, the claims made about their benefits are so wide-ranging that they are in danger of sounding a bit far-fetched, and misleading marketing is one of our pet peeves.
That’s why we decided to research the supplements and the companies that sell them. We wanted to be objective and keep an open mind, so the solution was to run our own experiment here at Diet Doctor to test some of the claims made about the benefits of the supplements.
I (Kim) researched the topic and planned and ran the experiment under the guidance and supervision of Dr. Andreas Eenfeldt, who touched base with me every step of the way to check the experiment design and execution for scientific rigor (to the greatest degree possible) and who has edited this writeup for quality and trustworthiness reasons. I also consulted with other keto experts and researchers to gather feedback both on the experiment design and the results data. They are referenced in the text when this was the case. If the claims about the benefits of exogenous ketones are accurate and true, then it’s fantastic news for people who are looking to enhance their keto lifestyle and who have the money to spend. But two of our core values are trustworthiness and goodness, and it is important to us to test assumptions made by marketing claims and help make sure that people are getting what they are told they are getting when they spend money on a product.
So, read on for the latest experiment, Diet Doctor style!
What are exogenous ketone supplements?
What are the claimed benefits of exogenous ketones?
Potential problems with the supplements
What are exogenous ketone supplements? What are ketones?
When you restrict carbs (carbohydrates) and consume moderate amounts of protein, the liver begins to convert fat into ketones – small molecules that can be used as fuel when blood sugar is in short supply. Using ketones instead of glucose for fuel is associated with a number of benefits, including appetite control, improved mental performance, more constant energy and increased physical endurance.
What are exogenous ketones?
You may have heard the terms endogenousand exogenous being thrown around in relation to ketone supplements, but what do they actually mean? Well, endogenous ketones are produced naturally inside the body by the liver as a result of restricting carbs and sugar. The word comes from the Greek, endon, which means “within”. But scientists have also discovered a way to administer ketones to people, usually in the form of a drink, meaning that you can take ketones into your body from outside. These are exogenous ketones, which comes from the Greek word exo meaning “outside”.
Ketone salts vs. Ketone esters
First let’s make the distinction between two different kinds of exogenous ketone supplements: ketone salts and ketone esters. Ketone esters consist of a ketone body combined with a ketone precursor. There are a small number of these available on the market to consumers and there appears to be more robust science in support of their benefits. However, we will not be commenting on ketone esters since there are big differences between them and ketone salts, and the ketone salts are the ones that have been heavily commercialized and marketed to the public over recent years. Ketone esters may be more difficult to market due to their having an unpleasant taste. We may look more deeply into the esters in the future. Ketone salts consist of a ketone body combined to a mineral ion, often sodium. There are different types of ketone body, but ketone salts use beta-hydroxybutyrate (BHB). There are a large number of companies selling this form of exogenous ketone, and this is where we are seeing the big marketing strategies and broad claims about benefits. From now on, when we discuss ketone supplements or exogenous ketones in this article, we’ll be referring to ketone salts. What are the claimed benefits of ketone supplements?
Clicking through the websites of different companies selling the ketone supplements, a potential customer will encounter many different claims about the benefits of taking them. They include:
Increased fat burning/ accelerated weight loss
Maximized cognition/ improved focus
Improvement in athletic performance
Help getting back into ketosis after consuming carbs
I carried out a survey among Diet Doctor users as background research to the experiment (a big thank you to the 638 people who responded!). In the survey, 28% of the respondents reported that they do take ketone supplements. The top four benefits that these respondents reported experiencing were increased energy, improved focus/cognition, reduced hunger and weight loss. Potential problems with the supplements If the supplements do have the benefits that companies claim they do, a lot of people could decide it’s worth spending their money on them. However, during my research I encountered a number of potential problems, both with the claims made about the benefits of the supplements and with the companies making them.
Price: The supplements are expensive – very expensive. At the top end, if you follow Prüvit’s guidelines on “getting in the n8tive zone” (which is such a gimmicky marketing slogan it almost makes me cringe), you will require 2 servings of their Keto-OS product per day. This means around 60 servings per month, which will set you back a whopping $390 per month if you buy direct from their website! In the case of Prüvit, this is in part due to the multi-level marketing structure they operate under. Personally, if I am going to be spending that much money per month on a product, it had better be a near-miraculous level of amazing. I would want to be so deeply “in my n8tive zone” that I start spending my time hanging around caves and grunting. In the consumer survey, 31.5% of people who take the supplements said they spend $25-50/month on them, 19.3% spend $51-100 and 16% spend $101-150. But there were smaller percentages of people spending more than this, and 1.7% of people say they spend over $300 per month.
Secret recipes:Some companies do not disclose full information about the contents of their products, stating instead that theirs is a “proprietary blend”. The trouble with this is that although you know the ingredients of the product, you often don’t know the quantities, and you have no idea how much BHB you are getting for your money.
Lack of science:Although at first glance it seems as though ketone supplements are supported by heaps of fantastic science, a closer look shows that a lot of the scientific articles used on the sites refer to the benefits of endogenous ketosis or ketone esters, not ketone salts. I interviewed Dr. Brianna Stubbs, a ketone researcher with a Ph.D. in Metabolic Physiology from the University of Oxford who is now Research Lead at HVMN, specializing in developing ketone esters. She told me that in terms of science on the ketone salts and their effect on physical performance, one of the most-cited benefits of ketone salts, the scientific studies2 that have been done show at best no effect on physical performance and that, currently, there is no peer-reviewed scientific research on the ketone salt products on the market.
Dodgy marketing:These companies’ webpages are dripping with sales spiel and marketing strategy. A couple of examples: If Prüvit’s Keto OS-Max is “not a weight loss supplement” as stated in their disclaimer, why is the official website full of success stories of people who claim to have lost huge amounts of weight from taking the supplements? Ketōnd also feature a number of weight loss success stories on their site. I will get to why there is a problem with weight loss claims later on. Real Ketones promise that by taking their product Kegenix Prime you can “say goodbye to restrictive, hard to follow diets” (in reference to keto) and “let Kegenix do the work for you”. Whenever I see a company claiming you can have fantastic health benefits without doing anything to change your diet or lifestyle, I start to smell a rat. Plus, take a look at this promotional video from Prüvit. It claims that “ketones make the fat melt off your body”, which is simply not true (I’ll get back to this later). It also claims that if you wanted to reach ketosis naturally, you would either need to work out 10x harder and longer or be like one of the “extreme people” who “biohack their bodies” to get into ketosis, which “can take weeks or months”. For me, this is irresponsible. A keto diet can be simple and enjoyable, but this video makes switching to a healthy, real food, keto diet sound extreme and difficult while promoting an easy way out in the form of a drink. And that’s just bad advice. I would also like to point out some information quoted by Angela Poff, Ph.D., in a Community Guidelinesdocument that is distributed to Prüvit reps: Most of the information regarding the effects of ketosis come from studies on the ketogenic diet, wherein ketones are made by the liver and become a major fuel source for the body. The ketogenic diet is currently under investigation for its potential therapeutic effects in a number of healthy and disease states. More recently, studies are beginning to reveal that many of the effects observed with the ketogenic diet are mechanistically attributable to ketones, which is a primary reason that exogenous ketones are being developed and studied. However, because they are such a new technology, there’s not a lot of data on exogenous ketones themselves. In a few pre-clinical studies, exogenous ketones have mimicked the therapeutic effects of the ketogenic diet” From my perspective, this it at odds with the way the benefits of endogenous ketosis are used to describe the benefits of exogenous ketones claimed by Prüvit on their official website and in this video. This is another point that Brianna Stubbs put me onto: often, ketone-salt companies use terms such as “technology developed by Dominic D’Agostino” as a tool to market their products. Dom D’Agostino holds the patent for the technology being used but is not associated with the products and does not necessarily promote them. In many cases, this feels like a marketing strategy that name-drops a famous keto expert in order to make a product sound more legitimate. There is an example of this on Real Ketones’ website.
Other ingredients:Many of the supplements contain large amounts of caffeine – the supplement we tested from Prüvit contains the same amount as a 16 oz cup of coffee! Some supplements also contain malic acid, which is “known for its ability to increase energy and tolerance to exercise”. This leaves the nagging doubt: if the experiment shows an increase in energy and physical performance, for example, how do we know it is the (expensive) BHB causing the effect and not the (inexpensive) other ingredients?
The experiment Full disclosure: after carrying out the background research, I was already, as you might imagine, feeling a little less neutral about these products. You may have noticed a hint of that in part 1 of the 2-part video series we made about the project (watch part 2 at the top of this page!). However, and although this was by no means a controlled scientific study under laboratory conditions, we designed the experiment in a very objective way. The aim was to give the supplements the best possible chance of showing the benefits they are claimed to have. We designed a test for each of the chosen benefit claims and enlisted the help of four of our Diet Doctor teammates to try out the supplements and go through the testing. They were Jonatan and Giorgos from the video team, Emőke from the recipe team and Erik from the IT team. We had a mix of people who were naturally in endogenous ketosis during testing, and people who were not. What benefit claims did we test? The claims we tested were based on what the supplements are most commonly used for and what it was realistic and feasible to test here at Diet Doctor.
Blood ketones: It sounds obvious, but we decided it was important to check blood ketones to make sure they do increase after taking the supplement and whether there was any variation between the different brands of supplements. We tested this with ketone strips using a GlucoMen® LX Plus meter.
Mental performance: Tested using an attention test, where the participants had to pay attention to small changes in the length of two lines and indicate when there were subtle changes, and focus test, where participants had to press the relevant key when different circles on the screen changed color. The tests were taken from Quantified Mind.
Physical performance: Performing reps to exhaustion of the following exercises on different testing days: pushups, jump squats, tricep dips, burps and flutter kicks (a big thank you to Dr. Benjamin Bikman, Ph.D. for his input on how to design this part of the experiment!)
We also designed a questionnaire to test some other, more subjective markers. They were benefits that were difficult to check using a test, so we needed to ask the participants how they themselves felt about them. The questionnaire looked at the following things:
Mental claity/ “brain fog”
Why not weight loss?
Why didn’t we test the effects of the supplements on weight loss? Well, first of all, we would probably have had to continue the testing over much longer periods of time to see any change in weight. But there’s a bigger reason, too! Let’s go back to that statement from the Prüvit video, “ketones make the fat melt off your body”. The weight loss claim is just not true. Ketones are fuel molecules that can be used for energy by cells in the body. If you drink ketones, you will burn those ketones. You will not be burning fat. For anyone who wants to get a bit more technical, research by Stubbs and colleaguesshows that BHB shuts off lipolysis (fat breakdown). With endogenous ketosis there are many other factors that stimulate lipolysis meaning that a kind of balance is reached and lipolysis stays constant. But with exogenous ketosis those factors stimulating ketosis are not present, so the overall effect of the ingested BHB is to decrease lipolysis. If the supplements cause enough of a reduction in hunger, this could cause people to eat less and therefore, indirectly, cause weight loss. We will find out just how much of an effect the supplements have on hunger in the experiment. But ketone supplements do not cause weight loss, at least not directly. In fact, a number of people in my consumer survey reported that they stopped using the supplements due to weight gain. This could make sense, as drinking ketones basically means you’re adding empty calories on top of whatever else you’re consuming. What brands were included? We chose 4 major brands of ketone supplement to test. The choice was mostly on which supplements seem to be most popular and most widely available online. It’s worth noting that some companies are a little bit more transparent than others. Here is a quick overview of the brands of supplement included in the experiment and the product we tested: Prüvit: Keto-OS Max, maui punch flavor Amount of BHB per serving: Unknown: proprietary blend Price per serving 3 :$6.50 Multi-level marketing?Yes Other ingredients: Erythritol, L-taurine, fermented L-leucine, malic acid, natural flavor, stevia, xantham gum, citric acid Ketōnd: Advanced ketone blend, grape flavor Amount of BHB per serving: 11.7 g goBHB™ Price per serving: $2.67 Multi-level marketing? No Other ingredients: Citric acid, natural and artificial flavors, beetroot extract, stevia, malic acid, riboflavin (color) Perfect Keto:Base exogenous ketones, chocolate sea salt flavor Amount of BHB per serving: 11.38 g goBHB™ Price per serving: $3.93 Multi-level marketing? No Other ingredients: MCT oil powder, acacia fiber, cocoa powder, natural flavor, stevia leaf extract, monk fruit extract Real Ketones:Kegenix prime, orange blast flavor Amount of BHB per serving:Unknown: proprietary blend* Price per serving: $2.00 Multi-level marketing? Yes Other ingredients: MCT powder, citric acid, natural flavors, silica, guar gum, rebaudioside A and beta carotene (color) *In the case of Kegenix Prime, we are told there are 10 g of Kegenix’s “PRIME ketone blend”, but we are not told how much of those 10 g are BHB and how much are MCT (medium-chain triglyceride) powder. How was it done?
We carried out the testing across five different days, leaving at least two days between the different testing days so that my teammates had time to recover from the physical performance test each time. The reason we needed five days was that we included a placebo (an artificially flavored drink with no caffeine content) alongside the four brands we tested. Our teammates didn’t know that one of the supplements was a placebo. We also gave everyone a different supplement each time, to rule out any improvement in the tests being a result of people simply getting better at those tests over time. The participants ran through all the tests and then drank the supplement, waited an hour, and ran through all the tests again. This would allow us to compare the results of the tests before and after taking the supplement, and also compare this against the results of the placebo. The reason for testing after one hour was based on Prüvit’s “59-minute test”, which recommends testing ketones 45-60 minutes after taking the supplement (by the way, saying “59 minutes” instead of 60 minutes or 1 hour just sounds like another marketing gimmick to me). Kegenix Prime also promises “ketosis in 60 minutes” on its packaging. We carried out the testing at more or less the same time each day. As I mentioned before, this was by no means a scientific experiment carried out under lab conditions, and this means we can only draw tentative conclusions from any of the data. Nonetheless, carrying out the testing in the way described above should give most people a good idea of how well the ketone supplements show the noticeable benefits they are marketed to have and provide a clear enough basis for a decision on whether or not to buy them. The results
You‘ll see from looking at the tables, the performance of the ketone supplements was not particularly impressive. The first table shows the average results of all the brands of ketone supplements grouped together and compared to the placebo in this graph. The second table shows how the different brands performed against each other, and against the placebo, too.
Table 1 compares exogenous ketones collectively with the placebo. It shows the total average change in markers tested before and after the supplements as a group, versus the placebo. Table 2 compares different brands of exogenous ketones with the placebo It shows the total average change in markers tested before and after the different ketone supplements, versus the placebo. When the results for the supplement and the placebo were within 0.2 (either % or mmol/L) of each other, we classed the supplement as neither “better” nor “worse” than the placebo. We gave a “winning brand” sticker to the brand that scored highest against the placebo for each marker, but not for physical performance, since none of the supplements performed better than the placebo for that marker. Blood ketones This was a big surprise. We were at the very least expecting that drinking a ketone supplement would cause blood ketones to rise, but an average increase of 0.33 mmol/L is very small. The supplement associated with the highest average increase in blood ketones was Prüvit’s Keto-OS Max, but it was only an increase of 0.6 mmol/L. Brianna Stubbs, the ketone researcher I consulted with, agrees that an increase of below 2.0-3.0 mmol/L is unlikely to be of much use. I had the chance to interview Dr. Ryan Lowery, Ph.D. about this in person. He performs some (not peer-reviewed) research on different brands of ketone salts and is listed as one of the “specialists” on Prüvit’s website. He suggested that we had perhaps ran the tests too long after the supplements were taken, stating that blood ketones tend to peak at 30 minutes. This is, however, not what Prüvit themselves state in their article on the 59-minute test, or the promise to reach ketosis in 60 minutes on the Kegenix Prime packaging. Plus, do you really want to spend up to $390/month on a product that gives you the benefits of ketosis for half an hour? I also chatted to some Prüvit reps, who told me that it might be necessary to keep taking the supplements for a couple of months to start to see more elevated ketones. Well, the proof is in the pudding (or in this case, in the fluorescent-coloured, artificial-tasting pink drink). But I would hesitate before spending money on a two-month supply just to find out if that’s true. Real Ketones’ Kegenix Prime was associated with a decrease blood ketones. Not a good start, and we’ll get back to this point later. Other markers For many of the other markers, the ketone supplements performed pretty poorly, especially for physical performance! The ketone supplements were associated with a 5.4% decrease in physical performance while the artificially-sweetened, non-caffeinated beverage I used as a placebo was associated with a 20.3% increase: a big difference in favour of the placebo. Before you go rushing out to buy some, remember that this experiment was not performed under fully-controlled, laboratory conditions, and we were working with too small a group to prove that the placebo caused an increase in physical performance. But what we can say is that we couldn’t find any correlation between ketone supplements and an increase in physical performance in this experiment. According to Brianna Stubbs, some of the work currently being done on new kinds of ketone salts is starting to show more promise in relation to physical performance, so there may be better news on this down the line. There were small improvements in mental performance and moderate improvements in mood. There was a 1.25% greater increase in mental performance with the supplements than the placebo and a 17.6% greater increase than the placebo in mood. There was not much difference at all in perceived mental clarity between the supplements and the placebo. Energy levels decreased in the testing with the ketone supplements. Really, though, these small changes do not seem particularly significant to us. We would have needed to see much bigger increases across numerous markers to persuade me that the supplements are worth spending money on. Satiety decreased in both cases, slightly less with the supplements than with the placebo: participants reported feeling less hungry after taking the supplements than after taking the placebo. However, we are doubtful whether this would be enough of a difference to impact food intake and therefore induce weight loss indirectly, compared to not taking a supplement at all. Especially since, as noted before, BHB switches off lipolysis. Taste In terms of taste, the placebo was the winner, with a taste score of 7/10 versus a combined 4.6/10 for the supplements. One of the reasons that exogenous ketone supplements need to be sweetened is that the ketones themselves taste pretty bad (this is one of the reasons why it is difficult to market ketone esters). The following graphic shows how Diet Doctor team members rated the different supplements on taste: Taste scores for the placebo and different supplement brands The results for Kegenix Prime: Exogenous ketones exposed? The results for Kegenix Prime deserve a special mention. First, it is interesting that the Kegenix Prime supplement scored so high on taste (nearly as high as the placebo). The Kegenix Prime supplement showed, in our experiment, to be ineffective at raising blood ketones. In fact, on average blood ketones dropped by 0.03 mmol/L with this supplement. Could the better taste of the Kegenix Prime and the lack of effect on blood ketones mean that Kegenix Prime doesn’t really contain much BHB at all? Remember that Kegenix Prime has a “proprietary blend” that doesn’t tell you how much BHB is in the supplement. It certainly makes you wonder… Second, take a look back at table 2. Kegenix Prime scored as the “winning brand” for 4 out of the 7 markers tested: mental performance, satiety, mental clarity and energy. Compared to the other supplements, it also scored highest for physical performance, although none of the supplements were listed as a “winner” since the placebo outperformed them all for that marker. BUT, the Kegenix Prime did not even raise blood ketones! The participants’ ketones went down by an average of 0.03 mmol/L in our testing. This really raises the question we brought up in the section on the potential problems with the supplements: the other ingredients added to the supplements. The fact that the supplement that did not raise blood ketones is also the one that outperformed the other supplements for so many of the markers, really does suggest that any effects that the supplements dohave may well be down to the other ingredients that the supplements contain. The verdict
I don’t think we even need a drumroll here… Based on my background research into ketone-supplement companies, the survey of Diet Doctor users and the experiment itself, we cannot recommend taking these supplements. I can personally think of many more beneficial ways to invest money in my health, such as buying grass-fed meat and organic vegetables, or even buying a bicycle and riding it outside in the sunshine. Importantly, at Diet Doctor we do not think you need to spend any extra money at all in order to revolutionize your health. You can achieve radiant health just by enjoying authentic food that is naturally low in carbohydrates, getting plenty of sleep and some exercise (going for a walk is free) and reducing stress. A lot of you who answered the survey made exactly these points in your explanations of reasons for not taking the supplements. I whole-heartedly agree. Of course, there may be some people who choose to take these supplements because they genuinely do feel they benefit from them. This is of course your choice and this article in no way aims to shame or criticize anybody. However, I do think that, for most people, eating a low-carb diet based on real foods is a lot more likely to be associated with the benefits that the supplements claim to provide than the supplements themselves. As Dr. Ryan Lowery pointed out to me, ketone supplements could play an important role in the future for elite sports performance, for example, or for people with brain injuries who cannot metabolize glucose properly. I am encouraged that scientists are working to develop these possibilities and, as long as plenty of peer-reviewed scientific research is done into the products being developed, I could feel more positive about the ketone salts in the future. For now, that scientific support is lacking. Dr. Brianna Stubbs made another important point when I interviewed her about the science on ketone supplements. She told me: It is important to define what it means to be “in ketosis”. If being “in ketosis” means having ketones in your blood, then of course ketone supplements get you into ketosis. But that is different from being in an endogenous ketogenic, fat-burning state as a result of following a ketogenic diet. Getting this distinction right will go a long way towards stopping ketone salts companies from using misleading marketing about the issue. We need to reach a consensus about what being “in ketosis” means and then force companies to use that definition. I think the key point here is misleading marketing, and this goes for all commercial food and health products, not just ketone supplements. Being a conscious consumer means being aware and critical of the marketing schemes that companies use. It is important to keep a clear head and not be taken in. To stay objective and be aware that when a company appears to be providing you with “information”, it may well just be using clever marketing to make you buy a product.