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*:
In conclusion, drinks containing exogenous ketones, in either ester or salt form, can raise concentrations of blood βHB in humans, although elevation of l-βHB lasts longer after racemic KS consumption. Both KE and KS drinks mildly altered acid-base balance. Exogenous ketones lowered blood glucose and lipids without inhibiting endogenous insulin secretion. The KE delivered highly repeatable blood concentrations of d-βHB, although ketosis was decreased by a meal. Uptake and elimination of d-βHB were similar when several drinks were consumed in succession. The dietary KE could maintain ketosis using drinks taken regularly around a normal meal pattern, or using a continuous infusion via a nasogastric tube. Therefore, ketone drinks are a viable and practical alternative to dietary strategies to achieve ketosis.
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.
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.
Glucose and BHB went down slightly throughout the effort and RQ fell, implying a high rate of fat oxidation. We can calculate fat oxidation from these data. Energy expenditure (EE), in kcal/min, can be derived from the VO2 and VCO2 data and the Weir equation. For this effort, EE was 14.66 kcal/min; RQ gives us a good representation of how much of the energy used during the exercise bout was derived from FFA vs. glucose—in this case about 87% FFA and 13% glucose. So fat oxidation was approximately 12.7 kcal/min or 1.41 g/min. It’s worth pointing out that “traditional” sports physiology preaches that fat oxidation peaks in a well-trained athlete at about 1 g/min. Clearly this is context limited (i.e., only true, if true at all, in athletes on high carb diets with high RQ). I’ve done several tests on myself to see how high I could push fat oxidation rate. So far my max is about 1.6 g/min. This suggests to me that very elite athletes (which I am not) who are highly fat adapted could approach 2 g/min of fat oxidation. Jeff Volek has done testing on elites and by personal communication he has recorded levels at 1.81 g/min. A very close friend of mine is contemplating a run at the 24 hour world record (cycling). I think it’s likely we’ll be able to get him to 2 g/min of fat oxidation on the correct diet.
Some think so because higher ketone levels imply increased fuel for the brain and heart (that prefer ketones), and increased protection against inflammation and oxidation. But are the health benefits coming from the ketones themselves, or are they coming from the state you have to put your body in to actually produce them? And if you're kicking yourself out of ketosis by ingesting ketones would you still get the same benefits?
Neuroprotective benefits: A natural part of the aging process is neurodegeneration, which is largely responsible for cognitive defects like Alzheimer’s disease. Recent research suggests that exogenous ketone supplementation can drastically slow neurodegeneration and the resulting decrease in mental function.[7] However, the mechanism behind this finding remains to be elucidated; though, researchers suggest exogenous ketones act to reduce brain inflammation. Glucose, on the contrary, may actually accelerate inflammatory response in the brain.[8]

No this is wrong. Your body will use your own fat and any fat you eat as fuel. This counts as exogenous ketones. It won’t stop burning your fat. The same logic would say that if eating any fat your fat loss would stall and that is not true. It can help get you back into ketosis because you have certain monocarboxylic acid transporters that are upregulated when ketones are present. The evidence is physiology.

Measurements taken included whole blood glucose and BHB (every 5 minutes); VO2 and VCO2 (every 15 seconds); HR (continuous); RQ is calculated as the ratio of VO2 and VCO2. In the video of this post I explain what VO2, VCO2, and RQ tell us about energy expenditure and substrate use—very quickly, RQ typically varies between about 0.7 and 1.0—the closer RQ is to 0.7, the more fat is being oxidized; the reverse is true as RQ approaches 1.0


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/)
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).
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.
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).
Exogenous ketones drinks are growing in popularity as a method to elevate blood ketone concentrations and mimic a ketogenic diet without the need for dietary changes (Ari et al., 2016; Cox et al., 2016; Kesl et al., 2016; Caminhotto et al., 2017; Evans et al., 2017). The present study describes the pharmacokinetic and pharmacodynamics properties of ketone ester and salt drinks in humans at rest, and characterizes the effects of a prior meal, which is pertinent to use as a dietary supplement. The main findings were that KE drinks elevated blood d-βHB > 50% higher than KS drinks, the latter significantly increasing blood l-βHB, which was metabolized more slowly by the body. Both drinks had similar effects on FFA, TG, glucose and electrolyte concentrations, although with disparate effects on pH. A prior meal decreased total blood d-βHB appearance after a KE drink. Finally, either three KE drinks or nasogastric feeding effectively maintained nutritional ketosis over 1 mM for 9 h.
Good question. There have been many tests and studies that have been conducted to see if ketogenic supplements genuinely do work and many of these studies have shown that ketosis theories are correct. Adding ketones to your body and using fats as a resource of energy has some fantastic effects and if done right can help your body fight all sorts of ailments such as cancer, heart disease, diabetes and many other illnesses that can only be cured by chemical therapy. Keto therapy or nutritional ketosis is paving the way for more natural solutions, and it's a good thing that scientists have created these exogenous ketone supplements that help us induce more ketones in our body.
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.*
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).
Although several studies have linked calcium supplementation with an increased risk of heart attack and heart disease[18], other studies have not found the same association. For example, a study on calcium supplementation (1000 mg/day) in postmenopausal women indicated a reduced risk of hip fracture, but no increase in cardiovascular disease or mortality in the supplement group, compared to the placebo group[19]. Another study found no effect from calcium supplementation (600 or 1200 mg/day) on abdominal aortic calcification[20].

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)


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. 


So if your high-fat diet includes a high amount of roasted seeds or roasted nuts, nut butters, heated oils such as heated coconut oil or heated extra virgin olive oil, barbecued meats or meats cooked at very high temperatures, then your triglyceride count is going to go up. You should have triglycerides that are less than 150mg/dL, and a triglyceride to HDL ratio that is no more than 4:1, and in most of the healthiest people I’ve worked with, triglycerides are under 100 and the triglyceride to HDL ratio is less than 2:1. If your ratio is whacked, your ketogenic diet isn’t doing you any favors.’
Bottom line: EK isn't the magic pill for instant weight loss. EK triggers ketosis which is a metabolic state where your body burns fat for fuel. EK increases satiety and feeling full, and boosts energy for exercise which helps you lose weight for the long term. You should always aim for the long term and sustainable weight loss and keep the weight off for good instead of looking for a quick fix.
If you are not on a vigorous exercise plan, I wouldn't go more than about a scoop a day (if you are a 30min/day, low carb person like me) because some of the research available says that if you get into ketosis using diet only and supplement with extra ketones, you may experience a slower rate of weight loss since you are getting your ketones from a supplement rather than the body transforming fat to ketones. As I progress, I will probably move up to 2 scoops per day.

 “Though the small amount of carbohydrates in the diets may be more than balanced by the potential sugar production from the large amount of protein to keep the ratio of fatty acid to glucose below the generally accepted level of ketogenesis, the respiratory quotient data suggest another mechanism also” ß (most likely the CPT-1A mutation, which had not been discovered at that time)
Participants refrained from alcohol and caffeine for 24 h prior to each visit AND were asked to consume a similar meal the night before each visit. All studies were carried out at the University of Oxford Human Physiology Laboratories and started at 0800 h following an overnight (>8 h) fast, with a minimum of 72 h between visits. Visit order was randomized prior to commencement by an administrative investigator using a pseudo-random number generator to produce a list of combinations of visit order, which were then allocated based on order of enrolment by a different investigator.
Task switching is the process of adapting to changing circumstances (switching from one goal to another). Two cards are shown one above the other, and a combination of letter and a number (i.e., “A4”) will appear on one of the two cards. If it appears on top, the task is to indicate whether the number is an even number, and if on the bottom the task is to indicate whether the letter is a vowel.
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?
In a keto-adapted individual where ketone metabolism is brisk with up to 100 grams or more being oxidized (i.e., ‘burned for energy’) daily, the small amount lost in breath and urine as acetone is minor. But because this breakdown occurs spontaneously without needing the help of enzymes, it also happens to AcAc in a stored beverage or food (even in an air-tight container), making the shelf-life of AcAc-containing products problematic. Thus all current ketone supplements consist of BOHB in some form rather than the naturally occurring mix of BOHB and AcAc produced by the liver.
Participants refrained from alcohol and caffeine for 24 h prior to each visit AND were asked to consume a similar meal the night before each visit. All studies were carried out at the University of Oxford Human Physiology Laboratories and started at 0800 h following an overnight (>8 h) fast, with a minimum of 72 h between visits. Visit order was randomized prior to commencement by an administrative investigator using a pseudo-random number generator to produce a list of combinations of visit order, which were then allocated based on order of enrolment by a different investigator.
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.
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.
So if you really want to jump start ketosis, do what the prehistoric humans did; don’t eat for 3 to 5 days. Keep the water bottle and multivitamins close and go on a strict fast. It might seem extreme and to a degree it is, but starving yourself will put you into ketosis. No ifs, ands, or buts about it. And it will cause you to lapse into a ketogenic state faster than if you tried to do so by manipulating the foods you eat (replacing carbs with fats). Once starvation has caused your body to transition to a ketogenic state, you can begin to introduce your low carb, high fat keto-friendly foods.

If the color is close to the original beige of the test strip, it means there are few if any ketones in your urine and you’ll need to make some dietary tweaks. This may include eating less fat. That’s because if you have doubled down on the healthy fats your body may be rebelling. One way to tell is if you are constipated. If you think this is the case, ratchet back the fats by 50% and see if it makes a difference. 
Ketone monoester and diester compounds may circumvent the problems associated with inorganic ion consumption in KS drinks. KE ingestion rapidly increased blood ketone concentrations to >5 mM in animals (Desrochers et al., 1995a,b; Clarke et al., 2012a) and the first oral, non-racemic KE for human consumption, (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, raised blood βHB concentrations to 3–5 mM in healthy adults (Clarke et al., 2012b; Shivva et al., 2016) and athletes (Cox et al., 2016; Holdsworth et al., 2017; Vandoorne et al., 2017). However, the pharmacokinetics and pharmacodynamics of this KE with confounding factors, such as prandial state or multiple KE drinks, have not been characterized.
If given all as a single salt, 50 grams per day of BOHB would mandate daily intakes of 5.8 g Mg++, 9.6 g Ca++, 11.0 g Na+, or 18.8 g K+. Even if divided up carefully as a mixture of these various salts, it would be problematic getting past 30 grams per day of BOHB intake. And again, most of the currently marketed ketone salt formulations are made with a mix of the D- and L-isomers of BOHB, so the actual delivered dose of the more desirable D-isomer is considerably less. The other concern with the salt formulations is that, as the salts of weak acids, they have an alkalinizing metabolic effect that might have a modest but cumulative effect on blood pH and renal function.
I noticed for myself that it helps if I add some highly nutritional foods to my diet before I go into ketogenic diet. Adding minerals and vitamins will aid your body in this difficult process and on top of that if you have a deficiency of some sort you will be even more hungry and it will make your transition more difficult, so why make it harder on your self if you can just add some leafy greens to your diet.
The keto-esters are more appropriate for delivering higher doses of BOHB, but with repeated dosing can push the limits of taste and GI tolerance. There has been fairly extensive research on a compound 3-hydroxybutyl 3-hydroxybutyrate that is converted via hydrolysis and liver metabolism to yield 2 molecules of ketones, presumably mostly D-BOHB (Clarke 2012 and 2014). In a study involving lean athletes, an approximate 50 gram dose raised blood BOHB levels to 3 mM after 10 min and reached 6 mM by 20 min. Submaximal exercise resulted in increased ketone disposal from 2 to 3 hours and contributed significantly to whole body energy use during exercise (Cox 2016). This product has been shown to significantly reduce appetite after a single dose (Stubbs 2018) but its effect on body weight in humans over a longer period of time has not been studied, nor has its effect on blood glucose control been reported in humans with type 2 diabetes. However a single dose prior to a glucose tolerance test in healthy humans reduced blood glucose area-under-curve by 11% and non-esterified fatty acid area-under-curve by 44% (Myette-Cote 2018).
Plus, take a look at this promotional video from Prüvit. It claims that “ketones make the fat melt off your body”, which is simply not true (I’ll get back to this later). It also claims that if you wanted to reach ketosis naturally, you would either need to work out 10x harder and longer or be like one of the “extreme people” who “biohack their bodies” to get into ketosis, which “can take weeks or months”. For me, this is irresponsible. A keto diet can be simple and enjoyable, but this video makes switching to a healthy, real food, keto diet sound extreme and difficult while promoting an easy way out in the form of a drink. And that’s just bad advice.
There are a couple factors that will make this look much more viable and achievable. For example, if you were to skip breakfast and have your first meal at 12PM, you could eat up until 8PM. This will also mean that dinner needs to be eaten slightly earlier. But let’s not forget about the fact that if we were to combine this with the 6-10 hours of sleep that you would normally have each night, that’ll take up the majority of your fasting period. Obviously, you’re not restricted to these hours, as everyone has a different schedule. Doesn’t sound as bad as you initially thought? Well let’s make it even more enticing! During your fasting hours, and this is extremely helpful during mornings up until you can have your first meal, non-caloric beverages such as tea and coffee can help starve away those hung pangs. Just make sure you’re taking these drinks on it’s own, without any added sugar or milk. There are many variations of intermittent fasting with the most common being 16/8. But depending on your schedule, there are other options advocated such as 20/4, 22/2, and if you’re crazy enough and can eat a full day’s worth of calories in one sitting then there is also OMAD (one meal a day).
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.

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