Firstly, in a randomized four-arm cross-over study, blood βHB concentrations were compared following ingestion of equal amounts of βHB as a KE or a KS at two doses by healthy volunteers at rest (Study 1; n = 15). Secondly, in a randomized five-arm cross-over study, inter- and intra-participant repeatability of ketosis was examined following ingestion of identical KE drinks, twice whilst fed and twice whilst fasted. As a control, participants also consumed one isocaloric (1.9 kCal.kg−1) dextrose drink (Study 2; n = 16). Finally, blood d-βHB was measured after equal amounts of KE were given as three drinks (n = 12) or a constant nasogastric (NG) infusion (n = 4) (Study 3; total n = 14) over 9 h.

The classical KD consists of a 4:1 ratio of fat to protein and carbohydrate, with 80–90 % of total calories derived from fat [27]. The macronutrient ratio of the KD induces a metabolic shift towards fatty acid oxidation and hepatic ketogenesis, elevating the ketone bodies acetoacetate (AcAc) and β-hydroxybutyrate (βHB) in the blood. Acetone, generated by decarboxylation of AcAc, has been shown to have anticonvulsant properties [28–32]. Ketone bodies are naturally elevated to serve as alternative metabolic substrates for extra-hepatic tissues during the prolonged reduction of glucose availability, suppression of insulin, and depletion of liver glycogen, such as occurs during starvation, fasting, vigorous exercise, calorie restriction, or the KD. Although the KD has clear therapeutic potential, several factors limit the efficacy and utility of this metabolic therapy for widespread clinical use. Patient compliance to the KD can be low due to the severe dietary restriction - the diet being generally perceived as unpalatable - and intolerance to high-fat ingestion. Maintaining ketosis can be difficult as consumption of even a small quantity of carbohydrates or excess protein can rapidly inhibit ketogenesis [33, 34]. Furthermore, enhanced ketone body production and tissue utilization by the tissues can take several weeks (keto-adaptation), and patients may experience mild hypoglycemic symptoms during this transitional period [35].
I am a little confused. I can see how EK’s can help up the state of ketosis, but as far is weight loss is concerned, aren’t the ketones you produce naturally created by the breaking down of your own fat? If I supplement with exogenous ketones, will that slow the natural creation of ketones? Especially if I am eating a higher amount of carbs. Would exogenous ketones speed fat loss, or slow it?

While exogenous ketones (EK) are a newer supplement, having entered the market for consumers in just the past few years, scientists have been synthesizing ketone bodies in a lab since the 1960’s. They were useful for scientists studying their use for specific disease conditions, most notably childhood seizure disorders, though they were prohibitively expensive for consumers (1, 2).
In a subset of participants (n = 7) the effect of 3.2 mmol.kg−1 of βHB as KE and KS on blood pH and electrolytes after ketone drinks was investigated. Blood d-βHB kinetics were similar to those in the initial experiment (Figure ​(Figure3A).3A). After 60 min, blood pH declined from 7.41 to 7.31 following a KE drink (p < 0.001, Figure ​Figure3B).3B). Bicarbonate fell significantly from 23.6 ± 0.7 to 17.0 ± 0.8 mM following KE drinks (p < 0.001), but remained within the normal range (Figure 3C). Both ketone drinks significantly decreased blood potassium concentrations by 0.7 mM (both drinks p < 0.05, Figure 3D) and increased sodium and chloride concentrations (Sodium: both drinks p < 0.05, Chloride: KE = p < 0.05, KS = p < 0.005, Figures 3E,F).
The table below shows the same measurements and calculations as the above table, but under the test conditions. You’ll note that BHB is higher at the start and falls more rapidly, as does glucose (for reasons I’ll explain below). HR data are almost identical to the control test, but VO2 and VCO2 are both lower. RQ, however, is slightly higher, implying that the reduction in oxygen consumption was greater than the reduction in carbon dioxide production.

Thank you, Mark! I am an ME/CFS patient, and I have improved quite a bit on a ketogenic diet, which I have been following for the past 3 months. I am slowly losing weight (much needed) and I wondered, does using exogenous ketones inhibit fat loss? I’m trying to balance the benefits of continuing weight loss with benefits in dealing with ME/CFS symptoms. Thank you for any info you can offer!
The same question posed in a different way can be, what’s better, getting protein from powder or from a grass-fed steak or wild salmon? Omega-3 from supplements or from a variety of healthy wild fish? Just like with health supplements where you consume an isolated nutrient instead of the whole food where it comes from, if it’s possible to get what you need from whole food or nutrition, then that’s probably the best choice.
Working memory involves temporarily storing and manipulating information. The game involves seeing three cards – a top card with a symbol that then moves along a track and is flipped over, exposing a new card above. The goal is to remember the symbol of the cards two cards back and indicate whether it matches the visible card or not. If you have ever played dual n-back games, this is very similar.
Dusty you assume only everyone wants fat burning. I think this is silly. The brain and heart will prefer ketones over carbohydrates when both are present in the blood stream. Look at the research and mechanism. I don’t want fat loss, I want better brain function. I also regularly eat carbs myself. This is one of the reasons I myself use exogenous ketones. No this isn’t a magic fat loss powder, but don’t sit here and quote T-nation trying to rebuttal this article acting like that is a credible source.

But some people chose to use supplements to benefit from ketosis (Therapeutic Ketosis), and finally there is the MCT Ketogenic Diet – which in a form of nutritional ketosis (ULC, limited protein, high fat) with a twist – about 30-60% of the fat intake in the diet comes from MCT (Medium Chain Triglyceride) fats. Sources of MCT fats include Pure MCT Oil, Coconut oil and coconut products. The MCT Ketogenic Diet is often used with epilepsy suffers, as the high levels MCT oil create a higher level of ketones in the blood – which helps prevent seizures.


Animal research findings report that BHB supplementation also enhances oxygen utilization, especially in the central nervous system (CNS).[11] While molecular oxygen is a crucial molecule for health and longevity, too much of it can be potentially toxic and speed the effects of aging in tissues throughout the body.Therefore, using a BHB supplement can effectively mitigate the toxic buildup of molecular oxygen, particularly in the CNS/brain.
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.

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For anyone who wants to get a bit more technical, research by Stubbs and colleagues shows 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.
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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”
The current USDA recommendations reflect “unachievable goals” that do not match what research suggests our normal physiological ranges might be[10]. There is not enough evidence to show that sodium restriction is associated with less mortality or cardiovascular morbidity in healthy individuals or individuals with high blood pressure, and there is evidence that sodium restriction might actually be harmful to individuals with heart failure[11]. For serious athletes, and individuals who are active daily, the current recommendations might not only be unwise but unsafe. If you are eating a carbohydrate-restricted diet, this applies to you even more. Don’t stress about the high amounts of sodium in a lot of these ketone supplements, being that they allow for a fast delivery of ketones to the body, which has unique benefits that will be discussed in a separate article.  Instead, change out the frozen dinner and experiment with an effective dose of exogenous ketones.
The ‘carb-sparing’ effect from BHB suppresses the break down of muscle glycogen. This leads to lower lactate levels. When increasing exercise intensity, fat oxidation (burning) reaches a limit. At that point the muscle burns carbohydrates as fuel. But when consuming Ketone esters, the body does not make this switch. This suggests Ketones are being used instead. 11
Hi Rob thanks so much, many people experience inconclusive results from the pee strips, as the ketone concentration in our pee is a measure of ketones not being used by the body. Basically the overflow or unused ketones. As our body becomes more adapted to using ketones, there will be less in our urine. It’s tough to keep the variable constant of how hydrated you are across many pee tests. Don’t be discouraged by pee test results. We have had many times where our blood tests show 1-3mmol/dl BHB but our pee test showed no results. Definitely keep testing (consider using a precision Xtra) and changing the dose to suit your needs. Hope this is helpful!
This fasting process will not only activate autophagy in your cells, it will also increase your ketones much more quickly than if you were just eating a standard ketogenic diet. If you start implementing intermittent fasting and activities (like walking, cycling, or lifting weights) together, you can raise ketone levels and increase autophagy more than you would with intermittent fasting alone. This suggests that intermittent fasting would be a great addition to your life, but it is important to be familiar with the negative symptoms that can arise before you start.

Skipping breakfast on a keto diet is a popular way to boost ketone levels. Despite the age-old myth that breakfast is the most important meal of the day, research shows that breakfast skipping is not only safe but beneficial. Skipping breakfast causes intermittent ketosis and also suppresses appetite [6]. Make sure your next meal of the day isn't too late in the evening as studies show that eating meals late at night causes weight gain and impairs fat metabolism [7].
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.

Geek note: Technically speaking, beta hydroxybutyrate is NOT a legitimate ketone body. Ketone bodies, or ketones are technically molecules with carbonyl carbons which are bonded to two additional carbon atoms. One carbon has four available bonds. When that carbon is double bonded to oxygen and also has two single bonds to carbon, we have a ketone body. If you have a carbon atom that is double bonded to an oxygen (carbonyl group), which is also bound to an -OH group instead of two different carbon atoms, that would be a carboxylic acid, but that really doesn’t matter in this case. For all intents and purposes of the ketogenic diet, betahydroxybutyrate should be considered one of the three ketone bodies and a “ketone” nonetheless. Your body uses BHB pimarily for energy in the state of ketosis, so it’s a ketone, okay?
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.
Response inhibition is the ability to suppress inappropriate responses that interfere with goal-directed actions. Two cards are shown, one above the other, each containing the name of a color in a certain color. The goal is to rapidly indicate if the meaning of the color on top (i.e. “yellow”) matches the color of the color on the bottom (i.e., card says “red” but is colored yellow).
Exogenous ketones provide the body with another fuel to employ. Think about it like an electric car that runs on both gas and electricity: by consuming ketones along with carbohydrates, the body will preferentially burn the ketones first, saving the carbohydrates for later. Exogenous ketones allow us to enter a metabolic state that wouldn't occur naturally: the state of having full carbohydrate stores, as well as elevated ketones in the blood. This could be advantageous to athletes looking to boost their physical performance. 
First and foremost, one of the most important factors is to be discipline when following the ketogenic diet. This means heavily restricting your carbohydrate intake, while switching to high-fat foods and moderate proteins. The general rule of thumb when it comes to splitting your macros out should look something like this: 5% (carbs)/ 80% (fats)/ 15% (proteins). Although if you’re just starting out, I wouldn’t focus too heavily on macros but rather place more importance in restricting your carbohydrate intake to 20 grams or less. Depending on the individual, most keto diets will allow approximately 20g-70g of net carbs as part of your overall daily intake, but if you’re asking the extreme question of ‘how to get into ketosis in 24 hours?’ then let’s focus on the absolute limit. For a more detailed breakdown, please see my keto shopping list article.
Getting into a state of ketosis normally involves eating a ketogenic diet consisting of around 80 percent fat, 15 percent protein, and 5 percent carbs. Over time, the body transitions from burning carbs for fuel to burning ketones—an alternative fuel source that the liver makes by breaking down fat, explains keto diet expert Amy Davis, RD, LDN. Since advocates say that ketosis can help you lose weight fast, think more clearly, and feel more energized, it’s tempting to try.
Another effect of the ketone drinks was to lower blood glucose, free fatty acids, and triglyceride levels. This sounds great. Elevated levels of all those markers are harbingers of disease, particularly if they remain chronically elevated. But think about what this means. If free fatty acids go down, that means adipose tissue isn’t being liberated for burning.
Over four visits, participants (n = 15) consumed 1.6 and 3.2 mmol.kg−1 of βHB as KE (141 mg/kg and 282 mg/kg of R-3-hydroxybutyl-R-1,3-hydroxybutyrate) or as KS (KetoForce, KetoSports, USA) sodium and potassium βHB, containing 1.6–3.2 g of each cation), plus 6 g of sweetener containing 19 kCal (4 g of carbohydrate) (Symrise, Holzminden, Germany), diluted to 300 ml using water. Drink blinding was not possible due to unmaskable differences in taste (bitter vs. salty).
The fate of excess ketones: In the event someone has an excessive amount of ketones in the blood, the body (specifically the kidneys) will work as quickly as possible to filter out ketones via urine rather than converting them to adipose tissue.9 This is not to say that you can’t gain fat if you consume an exorbitant amount of exogenous ketones, but that they are less prone to be converted to fat than other nutrients.
There is a great deal of positive speculation that exogenous ketones can be beneficial for inflammation, cognitive enhancement, and even protection against certain types of cancer. There is mounting evidence that the ketogenic way of eating can help many people, and when used appropriately with realistic expectations, exogenous ketone supplementation can enhance these positive effects (25).

Beta-Hydroxybutyrate (BHB) is naturally ketone body that is produced when free fatty acids are broken down in the liver. The other two types of Ketone bodies are acetoacetate (AcAc) and acetone. Ketones provide pure energy to fuel the human brain and other tissues. The elevation in ketones in your blood have been a rapidly emerging area of research and studies are continuing to show improvements in performance, brown adipose tissue, and several other possible applications.

The ketogenic journey should be more of a lifestyle than one that acts like a fad. So taking more than a day for your body to enter ketosis should not be the greatest of concern. It’s more important to stay discipline and to consistently keep your body in a fat-burning state. Although, if you are someone who has fallen out of ketosis after a cheat day, or rather somebody who is just starting out and finding it longer than expected to enter ketosis, then this article can definitely help in that respect. It’s nothing new, and it’s definitely no secret but strict dieting, fasting, exercise, controlling stress levels, sleep, and certain supplements can help you boost ketogenesis!

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.


Your brain has a very tight barrier so not everything in the blood can get through. This is called the blood brain barrier. Because your brain uses 25% of the energy that your entire body uses throughout the day, you need to make sure it is fueled appropriately. Glucose can’t directly cross the blood brain barrier. When you eat carbs, you get swings in energy that is available to cross the blood brain barrier which leads to mental fog.
Is keto safe? Putting yourself through this type of therapy isn't always easy and the process can take some getting used to, in particular during the initial stages when people must go through a period of fasting in order to raise ketone bodies faster. Of course, by doing this, it can put your body through a bit of shock and may cause a person to experience some short-term side effects until their bodies begin to adapt to the lifestyle and any BHB supplement they may be taking.
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.
Considering both the broad therapeutic potential and limitations of the KD, an oral exogenous ketone supplement capable of inducing sustained therapeutic ketosis without the need for dietary restriction would serve as a practical alternative. Several natural and synthetic ketone supplements capable of inducing nutritional ketosis have been identified. Desrochers et al. elevated ketone bodies in the blood of pigs (>0.5 mM) using exogenous ketone supplements: (R, S)-1,3 butanediol and (R, S)-1,3 butanediol-acetoacetate monoesters and diester [48]. In 2012, Clarke et al. demonstrated the safety and efficacy of chronic oral administration of a ketone monoester of R-βHB in rats and humans [49, 50]. Subjects maintained elevated blood ketones without dietary restriction and experienced little to no adverse side effects, demonstrating the potential to circumvent the restrictive diet typically needed to achieve therapeutic ketosis. We hypothesized that exogenous ketone supplements could produce sustained hyperketonemia (>0.5 mM) without dietary restriction and without negatively influencing metabolic biomarkers, such as blood glucose, total cholesterol, HDL, LDL, and triglycerides. Thus, we measured these biomarkers during a 28-day administration of the following ketone supplements in rats: naturally-derived ketogenic supplements included medium chain triglyceride oil (MCT), sodium/potassium -βHB mineral salt (BMS), and sodium/potassium -βHB mineral salt + medium chain triglyceride oil 1:1 mixture (BMS + MCT) and synthetically produced ketogenic supplements included 1, 3-butanediol (BD), 1, 3-butanediol acetoacetate diester/ ketone ester (KE).

KE was synthesized as previously described [29]. BMS is a novel agent (sodium/potassium- βHB mineral salt) supplied as a 50 % solution containing approximately 375 mg/g of pure βHB and 125 mg/g of sodium/potassium. Both KE and BMS were developed and synthesized in collaboration with Savind Inc. Pharmaceutical grade MCT oil (~65 % caprylic triglyceride; 45 % capric triglyceride) was purchased from Now Foods (Bloomingdale, IL). BMS was formulated in a 1:1 ratio with MCT at the University of South Florida (USF), yielding a final mixture of 25 % water, 25 % pure βHB mineral salt and 50 % MCT. BD was purchased from Sigma-Aldrich (Prod # B84785, Milwaukee, WI).
The ‘carb-sparing’ effect from BHB suppresses the break down of muscle glycogen. This leads to lower lactate levels. When increasing exercise intensity, fat oxidation (burning) reaches a limit. At that point the muscle burns carbohydrates as fuel. But when consuming Ketone esters, the body does not make this switch. This suggests Ketones are being used instead. 11
Hi! My question is, how low must my current daily carb count be in order to benefit from taking your exogenous ketones? I am a 33 year old female, keeping total carbs at 100-125 grams per day. My priority is fat loss, and I do HIIT training 4-5 days a week. I’ll soon be adding in heavier strength training. I don’t function well eating less than 100 total carbs a day. Could this even benefit me? And if it will benefit me, would the befits outweigh the sodium content? I keep my sodium at 2,000 mg a day, as I’m trying to avoid water weight.

If you have tried other ketone supplements that haven’t worked as promised or tasted terrible. Have no fear. This stuff is what a ketone supplement should be. It’s incredible what customers tell me. How it’s given them more energy, focus, drive. Helped them lose weight and suppress their appetite. Help them train harder at the gym and all kinds of great stories.*
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