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]
Exogenous ketones cause the body to rely less on fat as fuel (see Fig 3). Fat takes longer to metabolise for energy than muscle glycogen. This is why fatty acids are not the preferred fuel under heavy exercise. This could be useful for keto-adapted athletes performing high-intensity cardiovascular or strength training.12 This is particularly useful for the Keto-adapted athlete who wants to undergo high-intensity cardiovascular or strength training.

Let’s briefly discuss some organic chemistry. Two molecules that are “the same” but mirror images of each other (like your hands) are known as enantiomers, a type of spatial isomer. Beta hydroxybutyrate comes in two forms, D-β-hydroxybutyrate (“right-handed”) and L-β-hydroxybutyrate (“left-handed”). D-β-hydroxybutyrate is the form that is naturally produced in the body and is most bioavailable when taken exogenously.

Plecko B., Stoeckler-Ipsiroglu S., Schober E., Harrer G., Mlynarik V., Gruber S., et al. . (2002). Oral beta-hydroxybutyrate supplementation in two patients with hyperinsulinemic hypoglycemia: monitoring of beta-hydroxybutyrate levels in blood and cerebrospinal fluid, and in the brain by in vivo magnetic resonance spectroscopy. Pediatr. Res. 52, 301–306. 10.1203/01.PDR.0000019439.27135.2B [PubMed] [CrossRef]
Hello! I’m planning on taking a short vacation and will be having “kept friendly” drinks, mostly vodka and water with lemon and stevia. When should I take my exogenous ketones? That night before bed or early the next morning or after the 3 day vacation is completely over? I’m unsure how to manage this to have the best odds of staying in ketosis and get back to burning FAT. Also, I just purchased Instaketones from Julian Bakery, what are your thoughts on this brand? Thanks for what you do!
Personally, I do this on Friday night to Saturday night, so if something happens and my hunger hasn’t crashed by Sunday morning, I have another day that I can go zero carb to keep the momentum going. While the body will trigger ketosis as soon as you run out of glycogen, hunger is attached to your triglyceride and insulin levels, which might take an extra day to normalize.
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.
Zenwise Health Keto BHB is an exogenous ketone supplement that features goBHB, an innovative beta-hydroxybutyrate complex that supports the body's fueling processes through nutritional ketosis to promote peak mental and physical performance. Great for reaching ketosis fast, to max out your pre-workout routine, while also promoting overall high-performance, brain function, and maximum endurance. This Keto powder formula features a Raspberry Lemonade flavor that will mix and shake well with any water based drink. Best of all, this BHB is formulated with absolutely no carbs or caffeine for clean energy. Simply mix this BHB powder with water-based drinks or your favorite fruit flavored drink or smoothie, and enjoy.
Unless otherwise stated, statistical analysis was conducted using Prism 6™ software. Values, expressed as means ± SEM, were considered significantly different at p < 0.05. Initial tests were undertaken to ensure that normality and sphericity assumptions were not violated. Subsequently, either one or two way repeated measures ANOVA, or Freidman's test with post-hoc Tukey or Dunnet's correction were performed, to compare changing concentrations of substrates, electrolytes, pH, insulin, breath and urinary βHB: both over time and between study interventions. In Study 2, data from each of the two study visits in each condition (fed and fasted) completed by an individual were included in the analysis.

Even though endurance athletes can train in a carb depleted state, they will generally consume carbohydrates in the lead up to a race (the athlete is seeking to increase the ability to run off fats by training in a carb depleted state, then benefiting from both fats AND carbs come race day). Likewise, with the brain, even though the brain can function off ketones, does it mean it’s the best state for brain function?
The table below shows the same measurements and calculations as the above table, but under the test conditions. You’ll note that BHB is higher at the start and falls more rapidly, as does glucose (for reasons I’ll explain below). HR data are almost identical to the control test, but VO2 and VCO2 are both lower. RQ, however, is slightly higher, implying that the reduction in oxygen consumption was greater than the reduction in carbon dioxide production.

If the goal is to deplete glucose levels so that we can start producing ketone bodies, then forcibly exerting physical energy through exercise is a great way to go about it. Keeping it relatively low intensity to begin with and working out in the morning is recommended as this helps to keep down your cortisol (stress hormone) levels. This only applies at the beginning of your keto adaptation process, as intense workouts such as HIIT once already keto-adapted will be completely fine.

Let’s briefly discuss some organic chemistry. Two molecules that are “the same” but mirror images of each other (like your hands) are known as enantiomers, a type of spatial isomer. Beta hydroxybutyrate comes in two forms, D-β-hydroxybutyrate (“right-handed”) and L-β-hydroxybutyrate (“left-handed”). D-β-hydroxybutyrate is the form that is naturally produced in the body and is most bioavailable when taken exogenously.
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.
Ketone Salts: While the body uses and makes BHB ketones salts naturally, in supplement form ketone salts are synthetically (lab) made compounds that combine sodium (and/or potassium, calcium, or magnesium) with BHB. The salt is used to raise the pH and make things less acidic. Currently, all ketone supplements on the market are made from ketone salts. While they raise ketone levels, most people will only experience mild nutritional ketosis (~0.6-1.0 mmol/L).

International Patent # PCT/US2014/031237, University of South Florida, D.P. D’Agostino, S. Kesl, P. Arnold, “Compositions and Methods for Producing Elevated and Sustained Ketosis”. P. Arnold (Savind) has received financial support (ONR N000140610105 and N000140910244) from D.P. D’Agostino (USF) to synthesize ketone esters. The remaining authors have no conflicts of interest.

There are many different variations of intermittent fasting as well. Dr. Dom D’Agostino, the well-known ketogenic diet researcher, suggests doing a longer intermittent fast for 3 days, 3 times a year. This means not eating for 3 days, and eating normally until the next fast. Daily intermittent fasts are recommended as well. He says that it is ideal to have one to two meals after fasting for most of the day to reap the benefits of intermittent fasting every day.

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.
All data are presented as the mean ± standard deviation (SD). Data analysis was performed using GraphPad PRISM™ version 6.0a and IBM SPSS Statistics 22.0. Results were considered significant when p < 0.05. Triglyceride and lipoprotein profile data were analyzed using One-Way ANOVA. Blood ketone and blood glucose were compared to control at the applicable time points using a Two-Way ANOVA. Correlation between blood βHB and glucose levels in ketone supplemented rats was compared to controls using ANCOVA analysis. Organ and body weights were analyzed using One-Way ANOVA. Basal blood ketone and blood glucose levels were analyzed using Two-Way ANOVA. All mean comparisons were carried out using Tukey’s multiple comparisons post-hoc test.
d-βHB was measured immediately on whole blood using a handheld monitor and enzyme-based reagent strips (Precision Xtra, Abbott Diabetes Care, UK). Samples were stored on ice, centrifuged and duplicate plasma aliquots stored at −80°C. All urine passed during the visit was collected, the total volume recorded, and 1 ml aliquots taken, frozen and retained for analysis.

Over the past couple years, I’ve tried a number of ketone supplements, generally to enhance a longer fast or to offer an edge before one of my Ultimate Frisbee evenings. This Kegenix variety is one I’d recommend. I’ve also used Quest Nutrition MCT oil powder with good results as well, but there are plenty of other solid formulations to choose from.

So long long does it take to get into ketosis? This transition could take anywhere from 48 hours to one week. The length in time will vary depending upon your activity level, lifestyle, body type and carbohydrate intake. There are several ways you can speed up this process, like intermittent fasting, drastically decreasing your carb intake and supplementation.

One thing to remember here is that even if your calculated daily ‘keto approved’ protein allowance is (let’s say) 150g, that doesn’t mean you can eat 150g in one meal and still be in ketosis. You may find that you can’t eat more than 40g of protein at a time, otherwise you will drop out of ketosis. OR, you may find you can eat 50g of protein but you need a LOT of fat. Whereas a small serve of 15g of protein without fat might knock you out of ketosis. 
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.
About the only other negative thing I have heard about the company is that if you are placing an order over the phone, they don’t answer too many questions. Instead, they refer you to their website. Their website is very informative and pretty much answers any question you might have. Ketōnd has gotten too popular, and the company had to hire an answering service like they are selling George Forman Grills or something to take calls from around the world 24-7. I know it’s popular all over Europe and Australia too. My buddies that compete in Crossfit swear that this stuff gives them the edge.
Zhou Nutrition’s MCT Powder is another great quality MCT powder to try out. Taking a note from Perfect Keto, Zhou uses only Acacia Fiber during its manufacturing process and avoids all use of the common additives and fillers you see in most MCT powders. Zhou’s MCT Powder is made with the patented “goMCT” MCTs. While you don’t get the delicious flavors Perfect Keto have perfected, Zhou’s MCT Powder is a proven product pushing a 4 digit tally in positive reviews. Hundreds have attested to its true lack of flavor and positive ketone results.
No additives: Perfect Keto BASE is a bhb supplement keto drink that provides keto salts, contains ZERO carbs, ZERO gums or fillers, and ZERO sugars. Check the labels of other exogenous ketone products and you'll find plenty of gums, binders, fillers and other junk. Not here. Nothing but pure, effective exogenous ketones supplement designed to optimize your ketogenic state
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 read about ketosis in magazine or heard about it in a podcast and wanted to jump on the bandwagon, then I think you should avoid it. Remember, it is a strict diet, and the potential health downsides may not be worth the upsides, unless you are working with a medical professional and or you are tracking your labs to see what’s going on with your health (thyroid).
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.

Beta-Hydroxybutyrate (BHB) is a ketone body produced by the liver, from fat, for energy when glucose isn’t available. It ultimately becomes the body and brain’s primary source of energy. Since the liver naturally produces BHB during ketosis, the process can take quite some time, often resulting in symptoms of fatigue, hunger (cravings for sugar, a faster energy source), and mental cloudiness. That’s why supplementing BHB on a keto diet can have a profound positive impact.

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