Venous blood samples (2 ml) were obtained during all visits using a 22 G catheter inserted percutaneously into an antecubital vein. The catheter was kept patent using a saline flush following each sample collection. Additionally, during Study 1, arterialized blood from a catheter inserted into a heated hand (Forster et al., 1972) was collected into heparinized blood gas syringes (PICO 100, Radiometer, Copenhagen) from a subset of participants (n = 7) and immediately analyzed for pH and electrolytes using a clinical blood gas analyser (ABL, Radiometer, Copenhagen).

The major determinant of whether the liver will produce ketone bodies is the amount of liver glycogen present (8). The primary role of liver glycogen is to maintain normal blood glucose levels. When dietary carbohydrates are removed from the diet and blood glucose falls, glucagon signals the liver to break down its glycogen stores to glucose which is released into the bloodstream. After approximately 12-16 hours, depending on activity, liver glycogen is almost completely depleted. At this time, ketogenesis increases rapidly. In fact, after liver glycogen is depleted, the availability of FFA will determine the rate of ketone production. (12)
Recently, two published studies investigated the effects of ketone salts in athletes (total n = 22).8,9 Performance over a four-minute cycling time-trial and a 150 kJ ( ~11 mins) cycling time trial were compared between ketone salts vs. carbohydrate. In the four-minute trial there was no change in performance, and in the 150 kJ test, performance decreased by 7%. Blood BHB levels peaked at 0.6 and 0.8 mM in these studies.
Intellectual property covering uses of dietary ketone and ketone ester supplementation is owned by BTG Ltd., the University of Oxford, the National Institute of Health and TΔS Ltd. Should royalties ever accrue from these patents, KC and PC, as inventors, will receive a share of the royalties under the terms prescribed by the University of Oxford. KC is a director of TΔS Ltd., a company spun out of the University of Oxford to develop and commercialize products based on the science of ketone bodies in human nutrition. At the time of data collection and manuscript preparation, BS was an employee of TΔS Ltd., funded by the Royal Commission for the Exhibition of 1851. SH is an employee of NTT DOCOMO, Inc. (Japan). The other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Studies show that exercising depletes both liver and muscle glycogen faster than fasting [4]. For example, swimming for an hour and a half depletes the same amount of glycogen as a 24-hour fast. However, it's a good idea to eat a tiny amount of carbs and protein before and after a workout to prevent muscle damage. Your body can break down proteins in your muscles if glycogen stores get depleted during workouts.
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.
There are several ways to approach the “intermittent” part of food restriction. One of the most common is limiting the window in which food is consumed to about eight hours a day. Another is fasting for a full 24 hours once a week, or once a month. Fasting beyond three days can be stressful on the body and should be done with medical advice and supervision.
I bought this because I didn't want to be sucked into an autoshipment for a ketone supplement like KetoOS, which is HOT right now. I did the comparison on the ingredient list between this product and KetoOS and they are quite similar. I think one of the big differences is that KetoOS has the option of caffeinated or non-caffeinated powders. For the cost and the free shipping (I'm a Prime member), it's something I could easily fit into my budget, rather than the $114 canister you'd get with KetoOS.
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 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.
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.
Long-Term Effects of a Ketogenic Diet in Obese Patients – The present study shows the beneficial effects of a long-term ketogenic diet. It significantly reduced the body weight and body mass index of the patients. Furthermore, it decreased the level of triglycerides, LDL cholesterol and blood glucose, and increased the level of HDL cholesterol. Administering a ketogenic diet for a relatively longer period of time did not produce any significant side effects in the patients. Therefore, the present study confirms that it is safe to use a ketogenic diet for a longer period of time than previously demonstrated.
While the KetoneAid folks have been seeing tremendous success working with elite athletes to improve athletic performance, I thought it would be interesting to quantify the effects of ketone esters on cognitive performance. For the week prior to taking the ketones, I re-established baseline scores in a number of cognitive testing areas using Lumosity*:
Hybrid strategy: A hybrid strategy is to follow a low-carb/high-fat ketogenic diet to induce nutritional ketosis and use ketone supplements strategically. Supplements like Ketone salts or MCT oil can help ease the transition into ketosis, they can be an effective tool when we are knocked out of nutritional ketosis and they can help push ketone levels higher in the body for added benefit.
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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!
Ketogenic diets have been successfully used to treat diseases that have an underlying metabolic component, effectively decreasing seizures in recalcitrant pediatric epilepsy (Kossoff et al., 2003), lowering blood glucose concentrations in type 2 diabetes mellitus (Feinman et al., 2015) and aiding weight-loss (Bueno et al., 2013). Emerging evidence supports several clinical uses of ketogenic diets, for example in neurodegenerative diseases (Vanitallie et al., 2005), specific genetic disorders of metabolism (Veech, 2004) and as an adjunct to cancer therapy (Nebeling et al., 1995). Ketone bodies themselves may underlie the efficacy of the ketogenic diet, either through their role as a respiratory fuel, by altering the use of carbohydrate, protein and lipids (Thompson and Wu, 1991; Cox et al., 2016), or through other extra- and intracellular signaling effects (Newman and Verdin, 2014). Furthermore, ketone metabolism may offer a strategy to improve endurance performance and recovery from exercise (Cox et al., 2016; Evans et al., 2017; Holdsworth et al., 2017; Vandoorne et al., 2017). However, achieving compliance to a ketogenic diet can be difficult for both patients and athletes and may have undesirable side effects, such as gastro-intestinal upset (Cai et al., 2017), dyslipidemia (Kwiterovich et al., 2003) or decreased exercise “efficiency” (Edwards et al., 2011; Burke et al., 2016). Hence, alternative methods to raise blood ketone concentrations have been sought to provide the benefits of a ketogenic diet with no other dietary changes.
Many of us avoid foods like processed meats and cheeses or salted nuts because of their high sodium content. However, processed carbohydrate sources can have equal or higher amounts of sodium per serving. An ounce of salted pretzels[3] has over four times as much sodium as an ounce of salted peanuts[4]. Just because we can’t taste the sodium doesn’t mean it isn’t in there. Flavors from other ingredients like sugar and spices can make it difficult to identify salt as a dominant flavor.

To determine the reason for the differences in blood d-βHB concentration, the KE and KS drinks were analyzed for enantiomeric purity. The KE contained >99% of the d-isoform, whereas ~50% of the KS βHB was the l-isoform (Figure ​(Figure1D).1D). Plasma samples from participants who consumed the high dose KS drink (n = 5) were analyzed to reveal higher l-βHB than d-βHB, the total βHB Cmax being 3.4 ± 0.2 mM (Figure ​(Figure1E),1E), with a total βHB AUC of 549 ± 19 mmol.min. After 4 h, plasma l-βHB remained elevated at 1.9 ± 0.2 mM; differences in urinary excretion of the two isoforms could not explain this observation as both d- and l-βHB were excreted in proportion to their blood AUCs (Figure ​(Figure1F).1F). Therefore, in order to determine the time required for l-βHB elimination, a follow-up experiment was undertaken in which subjects (n = 5) consumed 3.2 mmol.kg−1 of βHB as KE and KS with hourly blood and breath sample collection up to 4 h, plus additional samples at 8 h and 24 h post-drink. l-βHB was found to be 1.1 ± 0.1 mM at 4 h, and 0.7 ± 0.2 mM after 8 h, but undetectable after 24 h (Figure 1G). Low amounts of d-βHB (0.3 ± 0.1 mM) were present at 24 h, presumably due to endogenous production. Both ketone drinks significantly increased breath acetone concentration, but at a slower rate than blood d-βHB, reaching a peak after 3 h that was twice as high following the KE (87 ± 9 ppm) than the KS (44 ± 10 ppm), suggesting that d-βHB was readily converted to acetone, but l-βHB was not (p < 0.005, Figure ​Figure1H1H).


Nutritional ketosis induced with the KD has proven effective for the metabolic management of seizures and potentially other disorders [1–26]. Here we present evidence that chronic administration of ketone supplements can induce a state of nutritional ketosis without the need for dietary carbohydrate restriction and with little or no effect on lipid biomarkers. The notion that we can produce the therapeutic effects of the KD with exogenous ketone supplementation is supported by our previous study which demonstrated that acutely administered KE supplementation delays central nervous system (CNS) oxygen toxicity seizures without the need for dietary restriction [29]. We propose that exogenous ketone supplementation could provide an alternative method of attaining the therapeutic benefits of nutritional ketosis, and as a means to further augment the therapeutic potential of the KD.
Taking MCT oil (medium chain triglyceride) or coconut oil (contains 60% MCT) can help boost ketone production. This is because your body absorbs MCT very quickly as it bypasses the gallbladder and into the liver to be processed into ketone bodies. Make sure you’re getting unprocessed versions of coconut oil that is labelled as ‘organic’ or ‘extra virgin’. This, along with grass-fed butter, is what I add into my ‘bulletproof’ coffees.

That’s not to say that the supplements don’t work. They very well might. But they could also be useless—or even dangerous, says Christine Palumbo, RDN, Nominating Committee member for the Academy of Nutrition and Dietetics. As of right now, there’s no way to know. “Currently, there’s just not enough evidence from research studies to answer those questions,” Barnes adds.


For whatever reason, many patients won’t attempt a ketogenic diet—even if the evidence is clear that it could help. Doctors are often hesitant to recommend dramatic dietary shifts—even if they believe in their efficacy—to patients who are already dealing with difficult health issues. If you’ve got a picky kid with epilepsy, a pickier adult with Alzheimer’s, or a cancer patient who refuses to give up the familiar-yet-non-ketogenic foods that give him some small manner of comfort in this trying ordeal, exogenous ketones could make a big difference.
Exogenous ketones are ketones that come in the form of a powder that you mix with water to drink them. Exogenous ketones are controversial in the keto world. The problem is the marketing of them have made some people believe that all they have to do is use this product to get into ketosis. If your blood glucose is too high your body will not use the ketones and they will go to waste.
Plasma glucose, free fatty acids (FFA), triglycerides (TG) and urinary d-βHB were assayed using a commercial semi-automated bench-top analyzer (ABX Pentra, Montpellier, France), and insulin was measured using a commercially available ELISA assay (Mercodia, Uppsala, Sweden). Both the pure liquid KS and KE, and a subset of plasma (n = 5) and urine (n = 10) samples from a subset of participants in Study 1 underwent analysis using GC-MS and a chiral column, and the concentrations of l-βHB was calculated using the enzymatically determined concentration of d-βHB and the ratio of the d/l-βHB peaks obtained through GC-MS. Acetoacetate was assayed using an enzymatic method (Bergmeyer, 1965), and breath acetone was measured using GC-MS (Study 1) or with a handheld electrochemical device (Study 2; NTT DOCOMO, Japan) (Toyooka et al., 2013).
Getting enough sleep not only helps in the production of growth hormones vital for muscle growth, but it plays a particular role as already discussed. If you’re intermittently fasting then sleep is crucial is helping you sustain the fast. 6-10 hours of your day will be dedicated to sleep, helping you to reboot and not think about food during this time. That means less time for you to actually be fasting! Stress is another factor – if we don’t get enough sleep, we’ll tend to feel more stress and agitation throughout the day. Ensuring that we’re well rested plays a huge part in keeping down cortisol levels so that are insulin and blood sugar levels don’t spike.
We will go deep in the science behind this fascinating diet and then review some of the best exogenous ketone supplements out there in the market. Because without the knowledge and the right information about exogenous ketones that you can properly follow, you might never reach your goals and you may as well keep eating that mashed potato for dinner and club sandwich for lunch.
Long-Term Effects of a Ketogenic Diet in Obese Patients – The present study shows the beneficial effects of a long-term ketogenic diet. It significantly reduced the body weight and body mass index of the patients. Furthermore, it decreased the level of triglycerides, LDL cholesterol and blood glucose, and increased the level of HDL cholesterol. Administering a ketogenic diet for a relatively longer period of time did not produce any significant side effects in the patients. Therefore, the present study confirms that it is safe to use a ketogenic diet for a longer period of time than previously demonstrated.
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)
Ketosis supplements made in poor quality have proven to lead to side-effects such as constipation and increased levels of cholesterol and triglycerides in men. Women may also experience amenorrhea or other disruptions to the menstrual cycle. This is why it is essential to know what combination of compounds you are consuming while you are on this very strict diet. The wrong balance can mess with you in the long term and won't give you the results that you are looking for.

Currently, we lack enough evidence to change the recommendations for calcium intake. The Tolerable Upper Intake Level (UL) for adults 19-50 years old is 2500 mg. This is well over the RDA of 1000 mg for the same age group. Calcium supplements commonly contain 600-1200 mg. When assessing your own calcium intake, keep in mind that calcium from food sources and calcium from supplements may have different outcomes.


I’m not sure whether I am leto-adapted but have been following the keto program for about 6 weeks. The scale and the eye confirm I have been burning fat. I’ve been using ketostix to keep track of ketones as I don’t prefer to prick my fingers to get blood measurements. I have reached my weight loss goal and planning to transition to maintenance in the next couple of weeks. I’m curious if exogenous ketones will be aid in maintaining my weight.


The “BHB salt” is simply a compound that consists of sodium (Na+), potassium (K+), and the ketone body β-hydroxybutyrate. In supplements like Pruvit’s Keto OS these individual components are being held together by ionic bonds; however, when you consume the product, it is absorbed into the blood where it dissociates into free Na+, K+, and BHB since it is a water-based solution. Thus, consuming the product directly and immediately puts more ketones into your blood.
A lot of people who use ketogenic diets will include a regular (i.e. weekly) carb refeed meal. There are various reasons behind doing this. If you are doing a lot of glycolic based training, then the carb refeed can help bump up muscle glycogen levels and in turn boost performance. Others use these refeeds as a way to keep their thyroid health in check, and finally some people use these refeeds as a ‘cheat day’ – so that they can still enjoy the pleasures from carbohydrates!

The famous keto-breath is powerful enough to throw shade on your increasingly ripped rig. The mouth-based ketones are released when your body scalds fat are responsible for the pong. Going into ketosis by changing your diet means your body doesn’t have carbs as a fuel source, so you’re using fats and proteins for energy, which fuels the potency of the fireworks seeping from your grill. The same can happen when taking supplements, but not by the same degree – proving that changing your diet it obviously a more potent fat burning tool. A lot of people also report gastric distress, so you could offend those you’re co-habituating with. What’s more, they can have a slight diuretic effect, which can deplete your magnesium, potassium and sodium stores, so make sure your levels are topped up when you’re out for a extra long exercise stint. Research in Nutrition and Metabolism on animals, found there were no negative side effects, but whether this extends to humans is still up for discussion. Fortunately, you’re more likely benefit from the upsides such as improved endurance, appetite suppression and fat burning.

Getting enough sleep not only helps in the production of growth hormones vital for muscle growth, but it plays a particular role as already discussed. If you’re intermittently fasting then sleep is crucial is helping you sustain the fast. 6-10 hours of your day will be dedicated to sleep, helping you to reboot and not think about food during this time. That means less time for you to actually be fasting! Stress is another factor – if we don’t get enough sleep, we’ll tend to feel more stress and agitation throughout the day. Ensuring that we’re well rested plays a huge part in keeping down cortisol levels so that are insulin and blood sugar levels don’t spike.

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?
Long-Term Effects of a Ketogenic Diet in Obese Patients – The present study shows the beneficial effects of a long-term ketogenic diet. It significantly reduced the body weight and body mass index of the patients. Furthermore, it decreased the level of triglycerides, LDL cholesterol and blood glucose, and increased the level of HDL cholesterol. Administering a ketogenic diet for a relatively longer period of time did not produce any significant side effects in the patients. Therefore, the present study confirms that it is safe to use a ketogenic diet for a longer period of time than previously demonstrated.(http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2716748/)
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]
This may have been mentioned, I haven’t checked all comments, but glutamine causes gluconeogenesis so that may explain why it affects Ketosis. Whenever I took a glutamine powder supplement for gut healing, I noticed I would “feel” less Ketogenic and I knew it was affecting me adversely. Glycine (which is also in bone broth) also has this effect I believe. Apparently some amino acids are just more easily converted to glucose.
Ketosis supplements made in poor quality, have proven to lead to side-effects such as constipation and increased levels of cholesterol and triglycerides in men, and women may also experience amenorrhea or other disruptions to the menstrual cycle. This is why it is really important to know what combination of compounds you are consuming, particularly while you are on this very strict diet because the wrong balance can really mess with you in the long term and won't give you the high performance that you are looking for. 
Besides cutting carbs, it's important to increase your fat intake, and be moderate with protein. The fat you eat will keep you feeling energized and support ketone production. Protein is also important but if you go overboard with it, your body could enter into a process called gluconeogenesis. In gluconeogenesis, your body makes glucose from protein, and you want to avoid that.
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.

If you truly want to optimize health and performance, magnesium should not be neglected. There is still more research to be done on its potential. Good sources of magnesium include whole grains, nuts, seeds, legumes, green leafy vegetables, and supplements. However, be careful about taking too much magnesium at one time, or else you might end up running to the bathroom in a hurry.
It's also important to note that you probably should follow a low carb diet or ketosis diet when using this product. Your brain prefers glucose as fuel because it's easier for the body to metabolize from food, so if you are eating a standard American diet of 100g+ carbs per day, or excessive protein, this won't help you lose weight, even with exercise because you'll have more than enough glucose to power your brain. Carbohydrate restriction, moderate protein, and lots of good healthy fat is what puts your body into ketosis.
Im very excited about this product! I received it about a week ago and it helped me break my month+ plateau! I've been on a keto diet since mid-April and had lost 10 lbs but stalled out. Ill be honest, the after taste is not pleasant but I'll take it since it's working. I've lost 12.5 lbs and going strong. Feeling better than ever. Would recommend and buy again!

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