The concentrations of blood d-βHB after KE drinks were highly repeatable whether consumed whilst fasted or fed (Figures 4F,G). The d-βHB Cmax values ranged from 1.3 to 3.5 mM when fed and 2.3 to 4.7 mM when fasted. There was no significant effect of visit order on d-βHB kinetics, with the maximal difference in d-βHB Cmax reached by one individual being 1.2 mM when fed and 1.9 mM when fasted. Approximately 61% of the variation in the data was attributable to feeding (fed vs. fasted), <1% to visit order, 16% to inter-participant variability, and the residual 24% variability due to non-specific random effects.
Caveat emptor: the following post doesn’t come close to answering most of these questions. I only document my experience with BHB salts (and a non-commercial version at that), but say little to nothing about my experience with BHB esters or AcAc esters. But it will provide you will some context and understanding about what exogenous ketones are, and what they might do for athletic performance. We’ll likely podcast about the questions and topics above and cover other aspects of exogenous ketones in more detail.

The liver is always producing ketones to some small degree and they are always present in the bloodstream. Under normal dietary conditions, ketone concentrations are simply too low to be of any significant benefit. A ketogenic diet and exogenous ketone supplements will increase the amount of ketone in your body. The idea that ketones are “toxic” is ridiculous. Ketones are a normal physiological substance that play many important roles in the human body.
Miriam, Thank you for the questions. I am going to do my best here to provide you with answers: Q: The manufacture of BHB salts involves ionic bonding of an anion (beta-hydroxybutyrate) with a cation (Na+, K+, Ca+, Mg+). At least one of the exogenous ketone products you listed does in fact contain potassium ions. People taking potassium-sparing drugs need to know this and that raises concerns about leaving it off your chart. A: The table lists the BHB and the mineral content from the BHB salts (no added minerals). Therefore, since potassium BHB is not in any of the… Read more »
Exogenous ketones are created in a lab to accelerate both physical and mental performance. These ketone drinks were actually used in pro cycling races back in 2015, trading at prices that would make using your kidney as a bartering tool seem like a cut price deal. Fortunately, they’ve now come down in cost and are used often in between meals as a way of blackmailing your body into getting into ketosis way faster.
Because they’re so expensive, you want to make sure you pick a good one. Griffin and Langer say to ignore the companies that make these supplements sound too good to be true. Just like with any supplement, Griffin says it’s important to look at what’s in it. Beware of products with lots of fillers and instead go for one with a short, straightforward list of ingredients (Griffin likes the options from KetoSports).
When your body transitions from using energy from carbohydrates to ketones, there can be a lot of nasty and unwanted side effects. These include low energy, bloating, irritability, headaches and fatigue. This is because your body is “in between” burning carbs and burning ketones and hasn’t become efficient at burning ketones and producing them from your fat stores yet.
Let me introduce myself. My name is Mark Sisson. I’m 63 years young. I live and work in Malibu, California. In a past life I was a professional marathoner and triathlete. Now my life goal is to help 100 million people get healthy. I started this blog in 2006 to empower people to take full responsibility for their own health and enjoyment of life by investigating, discussing, and critically rethinking everything we’ve assumed to be true about health and wellness...
To enter ketosis, up to 80%of your daily calories should come from fat. To put this into a frame of reference, if you eat 2,000 calories a day, 1,600 of those calories should come from fat sources. This comes out to roughly 144-170 grams of fat. Both quantity and quality are equally important, so consume fats from high-quality sources, like omega-3 and omega-6 fatty acids.
Every 7 days, animals were briefly fasted (4 h, water available) prior to intragastric gavage to standardize levels of blood metabolites prior to glucose and βHB measurements at baseline. Baseline (time 0) was immediately prior to gavage. Whole blood samples (10 μL) were taken from the saphenous vein for analysis of glucose and βHB levels with the commercially available glucose and ketone monitoring system Precision Xtra™ (Abbott Laboratories, Abbott Park, IL). Blood glucose and βHB were measured at 0, 0.5, 1, 4, 8, and 12 h after test substance administration, or until βHB returned to baseline levels. Food was returned to animals after blood analysis at time 0 and gavage. At baseline and week 4, whole blood samples (10 μL) were taken from the saphenous vein immediately prior to gavage (time 0) for analysis of total cholesterol, high-density lipoprotein (HDL), and triglycerides with the commercially available CardioChek™ blood lipid analyzer (Polymer Technology Systems, Inc., Indianapolis, IN). Low-density lipoprotein (LDL) cholesterol was calculated from the three measured lipid levels using the Friedewald equation: (LDL Cholesterol = Total Cholesterol - HDL - (Triglycerides/5)) [51, 52]. Animals were weighed once per week to track changes in body weight associated with hyperketonemia.
When taken as a drink, the ester bonds are broken down to release butanediol (BDO) and D-BHB into the blood. BDO is easily metabolized by the liver to form D-BHB. Then, both molecules of D-BHB reach the blood, as the liver is unable to use ketones. Consumption of this ketone ester elevates blood ketone levels in humans safely, with few side effects.10 HVMN Ketone is WADA compliant and safe to use in all levels of sports. It is designated as a foodstuff and is FDA GRAS. Each lot is 3rd party certified and batch tested for banned substances. 
Neuroprotection: As humans age, the brain becomes more susceptible to neurodegeneration and subsequent conditions such as Alzheimer’s and Parkinson’s disease. Exogenous ketone supplementation appears to ameliorate the typical decline in cognitive function that comes with aging. The likely mechanism for this neuroprotective property is that ketone bodies reduce the inflammation and hyperexcitability that is normally exhibited as glucose metabolism declines in the brain.18, 19
Would this be helpful for someone with Hypothyroidism and HPA Axis dysfunction? I started a Keto/IF lifestyle after watching your videos early July and though I feel so much better inflammation wise, I am not seeming to be super fat adaptive as of yet. Would KetoEdge stress out my body with these things going on? I’d love to try it but want to make sure first.
I began by simply playing all of the games over and over again (each game many dozens of times over the period of a week) to remove any “learning effect.” I then selected two games from each category (for a total of 10 games) and for a period of five days prior to “ketone-day” played each game five times each day. My “before ketones” baseline scores put me in the top 4% of all Lumosity users, so I was already in a good place. But could I improve even more, just one hour after consuming the ketones?
Onnit is an incredible company that’s making a massive impacts in the lives of athletes in nearly every sport. From Olympic Gold Medalists, to NFL middle linebackers, Onnit has taken athletic performance to a new level. Providing supplements, food, and training equipment, Onnit was an early adopter of the elite performance booster that is exogenous ketones!
Effects of ketone supplementation on blood βHB. a, b Blood βHB levels at times 0, 0.5, 1, 4, 8, and 12 h post intragastric gavage for ketone supplements tested. a BMS + MCT and MCT supplementation rapidly elevated and sustained significant βHB elevation compared to controls for the duration of the 4-week dose escalation study. BMS did not significantly elevate βHB at any time point tested compared to controls. b BD and KE supplements, maintained at 5 g/kg, significantly elevated βHB levels for the duration of the 4-week study. Two-Way ANOVA with Tukey’s post hoc test, results considered significant if p < 0.05. Error bars represent mean (SD)
Elliot received his BS in Biochemistry from the University of Minnesota and has been a freelance writer specializing in nutritional and health sciences for the past 5 years. He is thoroughly passionate about exercise, nutrition, and dietary supplementation, especially how they play a role in human health, longevity, and performance. In his free time you can most likely find him lifting weights at the gym or out hiking through the mountains of Colorado. He will also host the upcoming BioKeto podcast. You can connect with him on Facebook (https://www.facebook.com/elliot.reimers) and Instagram (@eazy_ell)
As repeated KE consumption would be required to maintain nutritional ketosis, we investigated the kinetics of drinks in series and of continuous intra-gastric infusion. During starvation, the accumulation of ketones (>4 mM) reportedly inhibited ketone clearance from the blood, however the underlying mechanism is unknown (Hall et al., 1984; Wastney et al., 1984; Balasse and Fery, 1989). In Study 3, βHB uptake and elimination were identical for the second and third KE drinks, suggesting that βHB may have reached a pseudo-steady state should further identical boluses have been given at similar intervals. Furthermore, when the KE was given at a constant rate via a NG tube, blood ketone concentrations remained ~3 mM. Therefore, repeated KE drinks effectively maintain ketosis at the intervals and doses studied here.
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 studies 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.

The main distraction which we have these days in our lives are the gadgets. Therefore, in order to fall asleep early, you need to make sure that you turn off your phones, tablets, computer, TV etc… at least 30 minutes before bedtime. This helps avoid insomnia as well as keep you away from the bright blue light which can interfere with your biorhythm.

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.
When you are in a state of ketosis, the body turns fatty acids into ketones - these appear as beta-hydroxybutyrate in the blood. Measuring blood ketones is regarded as the gold standard and most accurate way to track ketone levels. Testing this way can be expensive, its can cost up to $3 a strip, so if you're testing multiple times a day it can get pricey.
I have, though, recently been diagnosed with ovarian cancer. After reading through your blog, I noticed there was a little about Ketogenetic diet and cancer. I purchased the MCT oil powder in hopes that will help me get into ketosis for the purpose of “starving” the cancer cells. Other then focus, I didn’t see any particular format for something like this. Here are my questions: How much of the powder should I take? And do you think the diet plus the MCT oil is a good idea for 1) aiding chemotherapy and 2) helping shrink the number of cancer cells?

Exogenous ketones cause the body to rely less on fat as fuel (see Fig 3). Fat takes longer to metabolise for energy than muscle glycogen. This is why fatty acids are not the preferred fuel under heavy exercise. This could be useful for keto-adapted athletes performing high-intensity cardiovascular or strength training.12 This is particularly useful for the Keto-adapted athlete who wants to undergo high-intensity cardiovascular or strength training.


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.


For the ketone esters, on the other hand, repeated doses of 20-30 grams in any one day may be possible. Thus these products may be able to maintain a modest level of ketonemia without dietary carbohydrate restriction. Thus some of the cardiac and brain fueling benefits may follow, not to mention the epigenetic effects limiting oxidative stress and inflammation. But given the recent observation that administered ketone esters markedly reduce circulating free fatty acids (Myette-Cote 2018) — possibly due to an insulin-tropic effect or direct suppression of lipolysis (Taggart 2005) — their sustained use in people with underlying insulin resistance may compromise their long-term benefits by promoting weight gain unless combined with carbohydrate restriction.
Unless otherwise stated, statistical analysis was conducted using Prism 6™ software. Values, expressed as means ± SEM, were considered significantly different at p < 0.05. Initial tests were undertaken to ensure that normality and sphericity assumptions were not violated. Subsequently, either one or two way repeated measures ANOVA, or Freidman's test with post-hoc Tukey or Dunnet's correction were performed, to compare changing concentrations of substrates, electrolytes, pH, insulin, breath and urinary βHB: both over time and between study interventions. In Study 2, data from each of the two study visits in each condition (fed and fasted) completed by an individual were included in the analysis.

Ketones may be a better source of fuel than glucose, and a far better beverage than Fruitopia, but it's a question of whether or not you can spare the extra fuel. Because just like adding sugar to a diet, it's like pressing pause on the fat burning process since the body preferentially burns it for fuel. Adding ketones to the diet does the same thing.


Ketone Salts: While the body uses and makes BHB ketones salts naturally, in supplement form ketone salts are synthetically (lab) made compounds that combine sodium (and/or potassium, calcium, or magnesium) with BHB. The salt is used to raise the pH and make things less acidic. Currently, all ketone supplements on the market are made from ketone salts. While they raise ketone levels, most people will only experience mild nutritional ketosis (~0.6-1.0 mmol/L).
Exercising is undoubtedly important when it comes to losing weight. An added bonus of being in a state of ketosis is the ability to improve your exercise performance, but you should also remember that entering ketosis for the first time can be a bit of a challenge for a lot of people. The body is still adjusting to such a dramatic diet change, so exercising may prove to be difficult at first. The key here is to keep going.
I heard a rep from Perfect Keto on a podcast and your Exogenous Ketones. I ordered and received it the other day. I see from this article that I should not do a full scoop at once, but break it up in a day. Good to know. I had about a half scoop before I worked out this morning and could tell I had more energy. Loved that. Just curious….any ideas how long it will take me to get back into ketosis and fat burning?? (I know it depends on what I eat, but a general idea that I promise not to hold you too! (I’m actually missing having ‘keto breath!)
The protocols carried out in these studies were approved by the the South West Frenchay NHS REC (15/SW/0244) (Study 1) and London Queen's Square REC (14/LO/0288) (Study 2 and 3). The studies were carried out in accordance with the recommendations of the Declaration of Helsinki, apart from pre-registration in a database. All subjects gave written informed consent in accordance with the Declaration of Helsinki.

Another source of the D-BOHB isomer is an evolutionarily ancient energy source for micro-organisms. Poly-BOHB is a long chain of D-BOHB molecules strung end-to-end. It functions in many single-cell organisms as a concentrated energy source similar to glycogen in mammals, but whereas glycogen breakdown releases individual glucose molecules, poly-BOHB hydrolysis releases single D-BOHB molecules.
Next, BHB salts are the only supplement that elevates BHB levels while muscle glycogen remains at capacity (low muscle glycogen can drastically impede long-duration athletic performance). In short, athletes who consume carb-based diets, and those on low-carb diets, stand to benefit from exogenous ketone supplements taken prior to training/exercise.
For all studies, the area under the curve (AUC) of blood [βHB] was calculated using the trapezium rule. In Study 3, for each of the three drinks, the initial rate of d-βHB appearance was estimated using d-βHB concentrations at baseline and 30 min post-drink, and d-βHB elimination was estimated using the AUC between the post-drink peak (60 min) and trough (180 min) d-βHB concentrations, with a baseline correction to the value at 180 min.
On day 29, rats were sacrificed via deep isoflurane anesthesia, exsanguination by cardiac puncture, and decapitation 4–8 h after intragastric gavage, which correlated to the time range where the most significantly elevated blood βHB levels were observed. Brain, lungs, liver, kidneys, spleen and heart were harvested, weighed (AWS-1000 1 kg portable digital scale (AWS, Charleston, SC)), and flash-frozen in liquid nitrogen or preserved in 4 % paraformaldehyde for future analysis.
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.
Comments are welcomed and encouraged. The purpose of comments on our site is to expand knowledge, engage in thoughtful discussion, and learn more from readers. Criticism and skepticism can be far more useful than praise and unflinching belief. There’s an art and science to critical thinking and how to conduct yourself. There’s a multitude of fallacious appeals we could spell out, but a good rule of thumb is not to attack the person, attack the ideas. Don’t look for the flaws in the person, look for the flaws in the hypothesis. Let’s keep the brawling to movies depicting minor league hockey teams and political “news” shows. Thank you for adding to the discussion.

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