I came across a new company called KetoneAid that has begun producing small batches of ketone monoesters (KMEs). The main molecule in their product (D-β-hydroxybutyrate / D 1,3-butanediol) is based on a five-year, $10M study commissioned by the Defense Advanced Research Projects Agency (DARPA), looking to create the most powerful source of energy for special operations soldiers such as Navy SEALs, when undertaking very physically and cognitively challenging missions. In fact, the main researcher of the DARPA study is Dr. Richard Veech, the same person that authored the longevity study I just mentioned. Very cool.
Ketone supplements contain exogenous ketones—synthetic ketones made in a lab. Most use a type of ketone called beta-hydroxybutyrate (BHB), which is the same as the ketones the body produces naturally. “We’re literally biohacking," says Amie Heverly, who began taking a ketone supplement called Prüvit last year and now works as a promoter selling Prüvit products. "You’re not adding a foreign substance to your body, because BHB is identical to what your body would naturally produce,” she explains.
Although most of the research has been done utilizing ketone esters, ketone salt supplementation has the potential to provide additional benefits through the extra electrolytes/nutrients that are required to make the ketones. While ketone esters are expensive due to the manufacturing process involved in making them, ketone salts might be a more convenient option for both inducing a state of ketosis and elevating blood ketone levels for various reasons we will discuss in another article.
I simply use this to attempt to reduce the symptoms of the "keto-flu" when I'm entering ketosis after blowing my carbs out. The holidays are particularly bad for falling off the keto band-wagon. I've used this three times now to transition back into ketosis and I can report that it does seem to reduce the effects of the keto flu (headache, weakness) that I'd normally experience transitioning back into a low-carbohydrate diet. I typically take it for 3 days and then stop because by that time I'm in ketosis again, but I'd imagine you could take it longer.
If you’re wondering how to get into ketosis in 24 hours, and whether it’s even possible with such a short turnaround time, then combining a keto diet with intermittent fasting is a must. I am a massive advocate of not only the ketogenic diet but also the practice of daily fasting – I swear by it! It’s not for everyone as it does require a lot of discipline to pull off. But if you can commit to it, the benefits in my opinion are well worth it. So you may be wondering what intermittent fasting is? Well, it’s the practice of performing a daily fast from food and (caloric) drinks for at least 16 hours of the day.
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).
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.
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].
Intense exercise — more than just fidgeting or pacing — uses ketones, when glucose is in short supply, which means the body has to create more ketones to replace what you use. This is great for those who are used to a moderate to intense activity level, but intensity is a fine dance between encouraging ketone production and elevating cortisol for the rest of us.
If you have been reading the science behind the ketogenic diet, you know there can be a lot of benefits associated with choosing this way of eating. There is usually a transition period from when someone chooses to go on a ketogenic diet and implements the changes to their menu to when they actually get into ketosis and are able to produce and burn ketones for fuel.
There are many places where you can buy ketone supplements especially online. You have Amazon, Craigslist, and eBay to name a few but the thing with that is, they are often over-priced compared to the actual costs from the direct manufacturer. If you buy ketones directly from the official website of the product or brand, you are likely to get a way better deal than buying from any third-party seller that you might bump into on the internet. 
Second, take a look back at table 2. Kegenix Prime scored as the “winning brand” for 4 out of the 7 markers tested: mental performance, satiety, mental clarity and energy. Compared to the other supplements, it also scored highest for physical performance, although none of the supplements were listed as a “winner” since the placebo outperformed them all for that marker.
We carried out the testing across five different days, leaving at least two days between the different testing days so that my teammates had time to recover from the physical performance test each time. The reason we needed five days was that we included a placebo (an artificially flavored drink with no caffeine content) alongside the four brands we tested. Our teammates didn’t know that one of the supplements was a placebo. We also gave everyone a different supplement each time, to rule out any improvement in the tests being a result of people simply getting better at those tests over time.

Keep these studies in mind as your body tries to play tricks on you during your first day of fasting.  Even after three days of fasting, health complications are highly unlikely. However, it is important to know about the possible issues that can be caused by fasting. If you choose to incorporate fasting into your daily diet, you typically want to eat every day as well. Occasionally going on a longer period of fasting.
Effects of beta-hydroxybutyrate on cognition in memory-impaired adults. – Glucose is the brain’s principal energy substrate. In Alzheimer’s disease (AD), there appears to be a pathological decrease in the brain’s ability to use glucose. Neurobiological evidence suggests that ketone bodies are an effective alternative energy substrate for the brain. Elevation of plasma ketone body levels through an oral dose of medium chain triglycerides (MCTs) may improve cognitive functioning in older adults with memory disorders. On separate days, 20 subjects with AD or mild cognitive impairment consumed a drink containing emulsified MCTs or placebo. Significant increases in levels of the ketone body beta-hydroxybutyrate (beta-OHB) were observed 90 min after treatment (P=0.007) when cognitive tests were administered. beta-OHB elevations were moderated by apolipoprotein E (APOE) genotype (P=0.036). For 4+ subjects, beta-OHB levels continued to rise between the 90 and 120 min blood draws in the treatment condition, while the beta-OHB levels of 4- subjects held constant (P<0.009). On cognitive testing, MCT treatment facilitated performance on the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-cog) for 4- subjects, but not for 4+ subjects (P=0.04). Higher ketone values were associated with greater improvement in paragraph recall with MCT treatment relative to placebo across all subjects (P=0.02). Additional research is warranted to determine the therapeutic benefits of MCTs for patients with AD and how APOE-4 status may mediate beta-OHB efficacy. (http://www.ncbi.nlm.nih.gov/pubmed/15123336)
For example, the popular Raspberry Ketones supplement is far different than what we have been discussing in this article. Raspberry ketones are unrelated to the ketones that are produced in the body and are not the same as the ketone salts that have been covered above. There are some limited studies that indicate raspberry ketones may be helpful for weight loss, but they are inconsistent. Raspberry ketones are the molecules that give raspberries their scent and flavor, and in some cases, aren’t even derived from raspberries at all.
Hi- Thank you for this super helpful post. I’m new to Keto and supplementing Keytones. I just got the Julian Bakery Keytones and am curious about how to take them as there are no instructions on the packaging. Indeed the website has a diet plan to follow with the keytones but I am very suspicious of it because it is 0 fat which I believe is not healthy for brain or body and given that I have soft tissue and joint issues, I try to eat enough fat daily. I want to lose weight and I crossfit 5 days per week. So how do I best start with using the keytone supplements? I took a scoop full yesterday when they arrived (in the early afternoon) but hadn’t yet eaten and I think that was a mistake because I had immediate diarrhea which lasted a few hours, even after eating.

But there have also been studies done showing that the Inuit Eskimo’s do not actually reach a state of ketosis. This is due to numerous factors. One being that the diet the eskimo’s eat ‘would not be expected to cause ketosis, because the calculated anti-ketogenic effect of the large protein ingestion was somewhat more than enough to offset the ketogenic effect of fat plus protein.” 
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.
However, with the ketone esters, the effects are nearly immediate, and my entire body was humming throughout the entire day, but not in a jittery way. I was full of mental and physical energy that lasted without any sort of crash (it was a gradual taper). During my cognitive tests, things felt almost effortless as I played the various games. After my experiment was complete I continued writing code for several hours, then went to the gym to work out. I did forget to each lunch though, so there must be some suppressive effect on appetite.

At day 29 of the study, animals were euthanized and brain, lungs, liver, kidneys, spleen and heart were harvested and weighed. Organ weights were normalized to body weight. Ketone supplementation did not significantly change brain, lung, kidney, or heart weights compared to controls (Fig. 5a, b, d, f). MCT supplemented animals had significantly larger livers compared to their body weight (p < 0.05) (Fig. 5c). Ketone supplements BMS + MCT, MCT and BD caused a significant reduction in spleen size (BMS + MCT p < 0.05, MCT p < 0.001, BD p < 0.05) (Fig. 5e). Rats administered KE gained significantly less weight over the entire study compared to controls. BMS + MCT, BMS, and BD supplemented rats gained significantly less weight than controls during weeks 2 – 4, and MCT animals gained less weight than controls at weeks 3 – 4 (Fig. 6). Increased gastric motility (increased bowel evacuation and changes to fecal consistency) was visually observed in rats supplemented with 10 g/kg MCT, most notably at the 8 and 12-h time points. All animals remained in healthy weight range for their age even though the rate of weight gain changed with ketone supplementation [53–54]. Food intake was not measured in this study. However, there was not a significant change in basal blood glucose or basal blood ketone levels over the 4 week study in any of the rats supplemented with ketones (Fig. 7).

Should We Use Exogenous Ketones? Ketosis serves a purpose, and it’s probably why we’re able to survive on this planet. Being able to go without eating and use stored fats for energy is a survival tool and possibly far more as we’re now seeing with the keto diet. But it’s probably not a good idea to constantly take exogenous ketones and eat a high carb diet (high blood glucose levels). It’s not natural for the body to have high blood glucose and use ketones. This is a personal opinion, so 


Usually, you’ll find exogenous ketones in the form of powdered ketone salts. Less common are ketone esters, which are the purest form of ketones. Griffin says they work quickly (in 10 to 15 minutes, as opposed to an hour for the salts) and effectively, but they’re more expensive, have a more-revolting taste, and are harder to find (HVMN is one U.S. company that sells them). People also use medium-chain triglyceride (MCT) oil — or partially manmade fats — to put the body into a state of ketosis.
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.
Next, BHB salts are the only supplement that elevates BHB levels while muscle glycogen remains at capacity (low muscle glycogen can drastically impede long-duration athletic performance). In short, athletes who consume carb-based diets, and those on low-carb diets, stand to benefit from exogenous ketone supplements taken prior to training/exercise.
Ketogenic Diets and Physical Performance – Impaired physical performance is a common but not obligate result of a low carbohydrate diet. Lessons from traditional Inuit culture indicate that time for adaptation, optimized sodium and potassium nutriture, and constraint of protein to 15–25 % of daily energy expenditure allow unimpaired endurance performance despite nutritional ketosis.

The culprit is often restaurant meals or other meals where the nutrition facts are not available with the food itself. Such “ignorance is bliss” situations allow us to avoid dealing with daunting numbers. Many people don’t hesitate to stop and enjoy a meal at a restaurant, but they freak out when they actually see the numbers on a label.  By now, we all know that opting for fatty meat with a side of veggies cooked in butter isn’t that bad after all.  It turns out that what you thought to be the safe, “healthy,” doctor-approved choice might not always be what you think it is.
The second ketone ester compound was developed at the University of South Florida. This is a diester of AcAc and BDO. In rodents, this ketone ester raises blood D-BHB to 1-4 mM and blood AcAc to up to 5 mM.19 There is one published study of this ketone ester in humans; results showed a 2% decrease in 31 km cycling time trial performance.16 This may be due to the high rate of side effects of this ester studied. Other factors may have been low levels of BHB (<2 mM), the short, high-intensity time trial used, or the use of AcAc vs. BHB.
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?
Satiety decreased in both cases, slightly less with the supplements than with the placebo: participants reported feeling less hungry after taking the supplements than after taking the placebo. However, we are doubtful whether this would be enough of a difference to impact food intake and therefore induce weight loss indirectly, compared to not taking a supplement at all. Especially since, as noted before, BHB switches off lipolysis.
At day 29 of the study, animals were euthanized and brain, lungs, liver, kidneys, spleen and heart were harvested and weighed. Organ weights were normalized to body weight. Ketone supplementation did not significantly change brain, lung, kidney, or heart weights compared to controls (Fig. 5a, b, d, f). MCT supplemented animals had significantly larger livers compared to their body weight (p < 0.05) (Fig. 5c). Ketone supplements BMS + MCT, MCT and BD caused a significant reduction in spleen size (BMS + MCT p < 0.05, MCT p < 0.001, BD p < 0.05) (Fig. 5e). Rats administered KE gained significantly less weight over the entire study compared to controls. BMS + MCT, BMS, and BD supplemented rats gained significantly less weight than controls during weeks 2 – 4, and MCT animals gained less weight than controls at weeks 3 – 4 (Fig. 6). Increased gastric motility (increased bowel evacuation and changes to fecal consistency) was visually observed in rats supplemented with 10 g/kg MCT, most notably at the 8 and 12-h time points. All animals remained in healthy weight range for their age even though the rate of weight gain changed with ketone supplementation [53–54]. Food intake was not measured in this study. However, there was not a significant change in basal blood glucose or basal blood ketone levels over the 4 week study in any of the rats supplemented with ketones (Fig. 7).
Effects of beta-hydroxybutyrate on cognition in memory-impaired adults. – Glucose is the brain’s principal energy substrate. In Alzheimer’s disease (AD), there appears to be a pathological decrease in the brain’s ability to use glucose. Neurobiological evidence suggests that ketone bodies are an effective alternative energy substrate for the brain. Elevation of plasma ketone body levels through an oral dose of medium chain triglycerides (MCTs) may improve cognitive functioning in older adults with memory disorders. On separate days, 20 subjects with AD or mild cognitive impairment consumed a drink containing emulsified MCTs or placebo. Significant increases in levels of the ketone body beta-hydroxybutyrate (beta-OHB) were observed 90 min after treatment (P=0.007) when cognitive tests were administered. beta-OHB elevations were moderated by apolipoprotein E (APOE) genotype (P=0.036). For 4+ subjects, beta-OHB levels continued to rise between the 90 and 120 min blood draws in the treatment condition, while the beta-OHB levels of 4- subjects held constant (P<0.009). On cognitive testing, MCT treatment facilitated performance on the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-cog) for 4- subjects, but not for 4+ subjects (P=0.04). Higher ketone values were associated with greater improvement in paragraph recall with MCT treatment relative to placebo across all subjects (P=0.02). Additional research is warranted to determine the therapeutic benefits of MCTs for patients with AD and how APOE-4 status may mediate beta-OHB efficacy. (http://www.ncbi.nlm.nih.gov/pubmed/15123336)

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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