As seen in this exercise, glucose tends to fall quite precipitously following exogenous ketone ingestions. Without exception, every time I ingested these compounds (which I’ve probably done a total of 25 to 30 times), my glucose would fall, sometimes as low as 3 mM (just below 60 mg/dL). Despite this, I never felt symptomatic from hypoglycemia. Richard Veech (NIH) one of the pioneers of exogenous ketones, has suggested this phenomenon is the result of the ketones activating pyruvate dehydogenase (PDH), which enhances insulin-mediated glucose uptake. (At some point I will also write a post on Alzheimer’s disease, which almost always involves sluggish PDH activity —in animal models acute bolus of insulin transiently improves symptoms and administration of exogenous ketones does the same, even without glucose.)
Ketone Esters: Synthetically-made compounds that link an alcohol to a ketone body, which is metabolised in the liver to a ketone. Ketone esters are used primarily in research for testing their efficacy in elevating ketone body levels (below is a generic structure of a BHB ester). Yet, the first commercial Ketone ester drink will be available in 2018 by HVMN. Research esters are reportedly very unpleasant tasting which HVMN hopes to change.

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.
In Summary, I think it’s important to do your own research and draw your own conclusion about the long term risks of ketosis. For some people, a ketogenic diet may be a necessity given their health situation. For those of us who do not suffer from such health conditions I would present the question ‘why do you want to follow a strict ketogenic diet for an extended period’, and then follow this up with ‘are the potential risks and sacrifices worth the benefits?’

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.
Fortunately, you don’t need to be a dietary math savant to cash in on these rewards because the supplement eggheads took the liberty of creating exogenous ketones, which act as direct substitutes to the ones your body creates. Unlike other fat burners that give you the skits jitters, these are actually helping exercisers reach new personal bests while getting leaner, and are totally legal. Here’s what you need to know to get a slice of the action safely.
The benefits of intermittent fasting translate to untrained overweight and obese individuals as well. One study published in Obesity Reviews found that eating fewer calories is effective for fat loss, but it does come with some muscle loss. However, if the subjects fasted for 24 hours and ate as much as they wanted on the next day for a period of 12 weeks, they lost significantly less muscle mass.
Instead of being bound to a mineral (like ketone salts), the ketone molecule (BHB or AcAc) is bound to a ketone precursor (e.g. butanediol or glycerol) via an ester bond. While there aren't as many esters on the market as salts, there is still some variance–especially when looking at the ketone molecule in these products. Before selecting the best one for you, it's important to gather all the necessary information to make your decision.
So, now that we've established that purchasing BHB supplements directly from the manufacturer is the way to go. Now, let's talk about which ketogenic product you should be buying in the stores. Well, if you read our review about the different exogenous ketone supplements, you will also know that Perfect Keto is rated #1 on our list which was a pretty close race but it came out on top after all the tests that we've performed on all the different products.
Individuals who have clinically unregulated blood sugar, such as those with diabetes, are cautioned to consult their trusted healthcare provider before choosing to use exogenous ketones. While it can be done safely, especially in the presence of a well-formulated ketogenic food plan, there may be a risk of blood sugar dropping unexpectedly low. There may be therapeutic value in this application, but close monitoring is key.
Some people follow more of an Ultra Low Carb diet approach. This is generally around 50g or less of carbs per day. A ULC is more supportive of reaching a ketogenic state, but again total carbs are not the only variable when it comes to reaching ketosis (other factors such as types of carbs, protein consumption, portion size, ingredients, supplements used etc. all play a role and will be covered in more detail below). 

Ketostix are very unreliable. There are many factors which can alter results such as hydration level, if you’ve worked out recently and the amount of unused ketones in your body to name just a few. Never rely of Ketostix to determine whether you are in ketosis or not. The Precision Xtra blood ketone monitor is the gold standard for testing for ketones in your body. After following a ketogenic diet for a while, you should be able to tell if you are in ketosis or not by the way you feel.
Before the Nobel Prize was awarded to Yoshinori Ohsumi, other researchers were making groundbreaking discoveries about autophagy. In 2009, an article was published in Cell Metabolism entitled Autophagy Is Required to Maintain Muscle Mass. In this article, researchers described how deactivating an important autophagy gene resulted in a profound loss in muscle mass and strength.
The way you make an exogenous BHB is by attaching it to some type of other compound (sodium, potassium, calcium, or magnesium) so that your body can process the molecule by cleaving the bond between the salt and the beta hydroxybutyrate. BHB + bound to a salt = BHB salts, which is what most people in the ketosis community call exogenous ketones. There are also things called esters, which are basically unbound BHB molecules. These are really disgusting and cause massive digestive issues, so I like to ignore them until we can produce them in a more appealing way.
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.

Exogenous ketones can lower appetite during a fast. After an overnight fast, normal weight human subjects either drank a ketone ester supplement or a calorie-matched glucose drink. Compared to the glucose drinkers, the ketone drinkers had lower insulin, lower ghrelin, greater satiety, and less hunger. This can be useful for people trying to extend their fast who don’t want to or can’t yet deal with the hunger. You’re still taking in energy, but the metabolic profile remains similar to that of a fasted person.
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.
After a minimal amount of internet "research," I decided to try my first exogenous ketones. I have used the ketogenic diet off and on for at 15 years and my body is pretty efficient at fat adapting. (Usually by the end of 2 strict days, I am in ketosis, but not without symptoms and intense cravings.) I can consistently fast from carbs for 20 - 24 hours and do this consistently. However, around hour 20, my mind begins to negotiate that intermittent fasting is advantageous too and that I can afford to have some carbs once a day. Hence the yo-yo effect.
A meal high in carbohydrate and calories significantly decreased peak d-βHB by ~ 1 mM (Figure ​(Figure4A)4A) and reduced the d-βHB AUC by 27% (p < 0.001, Figure ​Figure4B).4B). There were no significant changes in d-βHB Tmax (fed = 73 ± 6 min vs. fasted 66 ± 4 min). Despite the differences in d-βHB kinetics after the meal, there were no effects of food on urinary ketone excretion (Figure ​(Figure4C),4C), plasma AcAc (Figure ​(Figure4D)4D) or breath acetone (Figure ​(Figure4E)4E) following KE ingestion. Plasma AcAc kinetics followed a similar time course to d-βHB, with the ratio of blood d-βHB: AcAc being 6:1 when KE drinks were consumed whilst fasted, and 4:1 following the meal. As observed in Study 1, breath acetone concentrations rose more slowly than blood ketone concentrations, reaching a plateau at 150 min and remaining elevated for at least 4 h (Figure ​(Figure4E4E).
For the first part of my experiment, I would simply record my blood ketone and glucose levels over a period of two hours after taking the ketone esters. While I am already fairly keto-adapted and can attain nutritional ketosis fairly easily (> 0.5 mmol/L), it wasn’t until the end of my Five-day Fasting Mimicking Diet that I was even close to reaching therapeutic ketosis levels (>5.0 mmol/L).

Patrick Arnold is an organic chemist who is notorious for being the creator of several performance-enhancing steroids. He is arguably one of the strongest influencers on the advancement of sports supplementation. Currently he is focused on developing products under the KetoSports brand, which includes two exogenous ketone products – KetoForce and KetoCaNa.
Intermittent fasting will significantly help the body transition into ketosis as limiting your consumption of food for that many hours will help deplete the system of any excess glucose. It’s a shock to the system and research has shown that daily fasting can have other profound effects aside from weight control such as autophagy, lowering risks of heart disease and diabetes, as well as an improvement in cognitive function. So if you’re still wondering how to get into ketosis in 24 hours, then fasting will surely kick things into gear!

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.
The product does not work. I have taken one scoop daily and for last two days two scoops (once in the morning and once in the night). I also do intermittent fast i.e. no food from 8 pm - next day 2 pm other than this powder in the morning. My food is 1500 calories with 60% fat, 30% protein and 5% carbs. I used to achieve ketosis naturally prior to using the powder. But now, there is no ketosis. This product does not work. I am wondering how on earth did they pick up so many reviews, unless it is faked marketing.

Despite the recent growth of the ketone salt market, there is very little published work analyzing the effects of these products on any biomarkers or performance measurements in humans. Several studies have been carried out in rats,6,7 with blood BHB levels being relatively low (<0.5 mM) post-consumption of salt drinks. In humans, ketone salts provided peak D-BHB levels of 1 mM, whereas the same amount of BHB in a ketone ester (BD-BHB) raised blood BHB to 2.8 mM.5
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?
Before that though, I do want to touch on MCT oil and it’s impact on ketone levels. MCT – or Medium Chain Triglyceride – are fatty acids that bypass the liver – and become quick energy for the brain and muscles. As they are a fat based energy source (and not a carbohydrate) they are quickly converted into ketones. This means MCT oil is a great way to boost ketone levels in the body.
Here we investigated the effects of KE and KS consumption on blood βHB and metabolite concentrations. As we found that KE ingestion delivered a >50% higher plasma concentrations of d-βHB alone, we subsequently determined the reliability and repeatability of ketosis following KE consumption and the effects of concomitant meal ingestion on blood ketone and substrate kinetics. Finally, we determined whether nasogastric infusion could be used for KE administration, given that some patients require feeding in this manner.

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?
In terms of epigenetic signaling, initial studies of the effects of BOHB on class-1 histone deacetylase activity against oxidative stress (Schimazu 2013), NLRP3 inflammasome suppression (Youm 2015), mouse longevity (Roberts 2017), and other epigenetic regulatory effects suggest that levels as low as 1 mM have potent effects. Furthermore, the association between very mild ketonemia and reduced coronary mortality with SGLT2 inhibitor use in patients with type 2 diabetes (Ferranini 2016) suggests that there might be clinical benefits with chronic BOHB levels as low as 0.3 mM (Gormsen 2017. Vetter 2017).

Anti-cancer potential: Recent research suggests that ketogenic diets can blunt malignant tumor growth.[5] This is due to the fact cancer cells can’t metabolize ketones effectively to nourish their growth and replication. Astonishingly, one study found that supplementing with BHB salts increases odds of survival in mice with systemic cancer by up to 70% in comparison to mice who didn’t receive exogenous ketones.[6]
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.
When your body is done using up a certain substrate to create energy (acetyl-CoA) after eating carbohydrates, it will start to find creative ways to get the job done. This is something that you want to happen. This is the switch to ketosis. If you didn’t do this, you’d be dead after fasting for a very short period of time. Under normal circumstances, the liver will start making beta-hydroxybutyrate from long chain and medium chain fatty acids that are liberated from your fat tissue. You are turning fat into fuel. Good work. This is why people can fast for months at a time and still function like normal humans.
88. Yost T, Erskine J, Gregg T, Podlecki D, Brass E, Eckel R. Dietary substitution of medium chain triglycerides in subjects with non-insulin-dependent diabetes mellitus in an ambulatory setting: impact on glycemic control and insulin-mediated glucose metabolism. J Am Coll Nutr. 1994;13(6):615–22. doi: 10.1080/07315724.1994.10718457. [PubMed] [CrossRef]
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.
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)

You are probably wondering how there could possibly be a benefit to eating less frequently that goes beyond what you are already getting with a ketogenic diet. Restricting carbs and eating enough fat and protein does come with a plethora of health benefits, but when you add intermittent fasting to your lifestyle you can increase energy and reverse aging by harnessing the power of a nobel prize winning process.
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).
Ketones are also a cleaner-burning fuel than carbs. They’re burned for energy in the mitochondria, and fewer free radicals (a highly-reactive, short-lived uncharged molecule) are generated when compared to burning glucose.15 What’s more, ketone molecules themselves cause a decrease in production of free radicals,21,22 while also increasing glutathione–a powerful antioxidant protecting against mitochondrial damage induced by free radicals.23

We tested the effects of 28-day administration of five ketone supplements on blood glucose, ketones, and lipids in male Sprague–Dawley rats. The supplements included: 1,3-butanediol (BD), a sodium/potassium β-hydroxybutyrate (βHB) mineral salt (BMS), medium chain triglyceride oil (MCT), BMS + MCT 1:1 mixture, and 1,3 butanediol acetoacetate diester (KE). Rats received a daily 5–10 g/kg dose of their respective ketone supplement via intragastric gavage during treatment. Weekly whole blood samples were taken for analysis of glucose and βHB at baseline and, 0.5, 1, 4, 8, and 12 h post-gavage, or until βHB returned to baseline. At 28 days, triglycerides, total cholesterol and high-density lipoprotein (HDL) were measured.
Personally, I think it is wise to include a regular carb meal in your diet if you are going to follow a ketogenic diet. Long term ketogenic diets do seem to downregulate your thyroid and metabolism, and a weekly carb meal (or carb day) can help avoid this. The Carb Nite diet by J. Kiefer is a good example of this. And BJJCaveman posted his labs showing how a weekly carb meal helped his thyroid HERE.
Meanwhile Brinkworth, et al., in their 2009 paper "Long-term Effects of a Very Low-Carbohydrate Diet and a Low-Fat Diet on Mood and Cognitive Function" looked at the effects on ketogenic diet on cognitive function and mood. The study participants ate a ketogenic diet for a year and the researchers found that mood levels decreased when compared to a group eating a high carb/low fat diet. They go on to remark “there was no evidence that the dietary macronutrient composition of LC and LF diets affected cognitive functioning over the long term, as changes in cognitive function were similar for both diets”.

Blood d-βHB, pH, bicarbonate (HCO3-) and electrolytes measured in arterialized blood samples from resting subjects (n = 7) following a ketone ester or salt drink containing 3.2 mmol.kg−1 of βHB. Shaded areas represent the normal range. Values are means ± SEM. (A) Venous blood d-βHB. (B) Arterialized blood pH. (C) Blood bicarbonate. (D) Blood potassium. (E) Blood sodium. (F) Blood chloride. †p < 0.05 difference between KE and KS, *p < 0.05 difference from baseline value.

Let’s take a look at some of the facts and misconceptions about three of the minerals used to make ketone mineral salts: sodium, calcium, and magnesium. Potassium is very hygroscopic, meaning that it absorbs water very easily. Therefore, it is only feasible that it can be utilized in liquid formulations.  Thus, one should be cautious if companies say they have potassium BHB salt powder in their product. I’d be very surprised if that’s actually the case.
Even though there is mixed evidence regarding the association between calcium supplementation and cardiovascular events, there may be other reasons to avoid high calcium supplementation. In one of his studies, Dr. Bolland claimed that calcium supplements do not prevent hip fractures. Rather, they may lead to kidney stones, acute gastrointestinal events, and increased risk of myocardial infarction and stroke. Thus, the risks involved with high-calcium supplementation potentially outweigh the benefits[21].
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 not a magical fat-loss supplement, and to suggest otherwise is both factually incorrect and deliberately misleading. In fact, consuming ketones to excess can hinder rather than help fat loss! Aggressive marketing of exogenous BHB’s has helped to create a myth being believed now by millions – that simply drinking ketones each day will somehow magically melt away the pounds. The metabolic fact that unscrupulous marketers do not point out is that dietary fat (plate fat; or fat/ketones you ingest) will be burned before stored fat (body fat). So, whilst exogenous ketones can help you to mitigate hunger (and therefore help you achieve a caloric deficit) – and although they also have many other benefits (detailed below); they are not a magic wand that you can wave to achieve weight or fat loss and should not be marketed as such.
The effects of ketone drinks on endogenous insulin secretion are unclear. Whilst the small increase in plasma insulin after KE and KS drinks may have been due to the small quantity of dextrose in the diluent, it has been proposed that ketones could potentiate or even stimulate insulin secretion. Isolated pancreatic islets secreted insulin when stimulated by ketones at glucose concentrations of >5 mM (Biden and Taylor, 1983), and small amounts of insulin are secreted in vivo following exposure to exogenous ketones in animals (Madison et al., 1964; Miles et al., 1981). In response to an intra-venous 10 mM glucose clamp, ketone ester drinks increased glucose uptake and plasma insulin (Holdsworth et al., 2017). The increases in insulin with ketone drinks taken whilst fasted were small compared to the increases seen when the ketone ester drink was consumed with a meal and with consumption of a dextrose drink. Furthermore, the lack of difference in peak plasma insulin between the two latter conditions indicates that nutritional ketosis did not inhibit or increase normal carbohydrate induced insulin production.

Exogenous ketones don’t seem to improve high-intensity, glucose-intensive exercise, increasing fat burning during steady state exercise but dropping top-end high-intensity performance. Another study found that ketone dieters reduced 50-minute time trial performance in cyclists, though another group of researchers have criticized the methods. Even when a ketone ester didn’t improve performance in the shuttle run to exhaustion and 15 meter sprint repeats, it did reduce the drop in brain function following the exercise.


While ketone salts are widely available, unfortunately in the near-term ketone esters are in short supply and the only people who will be able to afford taking them several times per day will be elite athletes, the military, corporate CEO-types, and professional poker players. Even with economies of scale and ramping up production, the cost of raw materials to produce pure ketone esters will keep their price tag prohibitively high for most people, but could realistically get down to a few dollars per gram.
Keto dieters love exogenous ketones because they help fight the keto flu and get you quickly into ketosis. One study found that taking drinks with exogenous ketones lowers blood levels of glucose, free fatty acid, and triglycerides [8]. The study concluded that exogenous ketones are a practical and effective way to achieve ketosis. Taking exogenous ketones longer will also speed up the process of keto-adaptation.
This is an excellent resource. Thank you for all the work and resources you found. i had never even heard of Adkins 72. I am keto but I always let Sunday be my high Carb cheat day.So im learning from this blog how to get back in ketosis in 24 hours after my 4pm meal on Sunday The Lords & family day. So im 25hr fasting. I would like to reference this article on my blog, thanks for helping me on my 100 lb lost journey.
2. Shimazu, T., Hirschey, M.D., Newman, J., He, W., Shirakawa, K., Le Moan, N., Grueter, C.A., Lim, H., Saunders, L.R., Stevens, R.D., Newgard, C.B., Farese Jr, R.V., De Cabo, R., Ulrich, S., Akassoglou, K., and Verdin, E. (2013). Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science 339, 211-214.
Effects of ketone supplementation on organ weight: Data is represented as a percentage of organ weight to body weight. a, b, d, f Ketone supplements did not significantly affect the weight of the brain, lungs, kidneys or heart. c Liver weight was significantly increased as compared to body weight in response to administered MCT ketone supplement compared to control at the end of the study (day 29) (p < 0.001). e Rats supplemented with BMS + MCT, MCT, and BD had significantly smaller spleen percentage as compared to controls (p < 0.05, p < 0.001, p < 0.05). Two-Way ANOVA with Tukey’s post-hoc test; results considered significant if p < 0.05. Error bars represent mean (SD)
I wrote this post at about the same time Germany won the World Cup in Rio de Janeiro in 2014. There’s been a lot of moving and shaking in the world of exogenous ketones since then, not to mention soccer. Looking back on my post, I still consider it relevant in terms of what exogenous ketones possibly can (and cannot) do for performance. In this case, to see if exogenous ketone esters provide me a “boost” by allowing me to do the same amount of work while expending less energy (and work at a relatively lower VO2) compared to no supplementation.

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