In Study 2 a Student's unequal variance t-test with equal SD was used to compare urine βHB concentrations. Additionally, a linear mixed effects model was constructed to estimate partitions of variance in R, using the lme4 and blme packages (Chung et al., 2013; Bates et al., 2015). Feeding state and visit number were fixed effects in this model, and inter-participant variability was a random effect. Inter-participant variability was calculated according to the adjusted generalized R2 metric (as proposed by Nakagawa and Schielzeth, 2013), to partition variance between the fixed effects of feeding, inter-participant variability, and residual variability. The coefficient of variation for βHB Cmax and AUC were calculated using the method of Vangel (1996).

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.
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. (
Exogenous ketones have become a popular nutritional supplement since their introduction in 2014. Unfortunately there is a lot of inaccurate information and marketing you have to read through to find the truth about them. This article does the hard work for you. It gets right to the true benefits and drawbacks of exogenous ketones supported by research studies.
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.
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.
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.
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).
I heard a rep from Perfect Keto on a podcast and your Exogenous Ketones. I ordered and received it the other day. I see from this article that I should not do a full scoop at once, but break it up in a day. Good to know. I had about a half scoop before I worked out this morning and could tell I had more energy. Loved that. Just curious….any ideas how long it will take me to get back into ketosis and fat burning?? (I know it depends on what I eat, but a general idea that I promise not to hold you too! (I’m actually missing having ‘keto breath!)
This process can be used as a way to get you into ketosis more quickly, so you can transition gracefully into a ketogenic lifestyle or as a way to stimulate autophagy and fat loss. If you can’t go without fat for the full 3 day fast — it’s okay — you will still illicit many of the benefits of fasting by limiting your protein and carbohydrate intake.

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.(
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.
Fasting blood samples were collected prior to all interventions. Following consumption of study drinks (details below), blood, expired gas and urine samples were collected at regular intervals for 4 h. Water was freely permitted and participants remained sedentary at the test facility throughout the visit. A subset of participants returned for samples 8 and 24 h after the ketone drinks (Study 1).

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.
They’ve got enough science behind them to suggest they do work very well indeed, but watch out for the online ads featuring the raspberry ketone fat burners. Their name is little more than a parlour trick because this is not related in any way to ketones, a ketogenic diet or nutritional ketosis. They are merely the natural substance that gives raspberries their sweet aroma and flavour. Just because they’re marketed at the must-have fat burner, doesn’t mean they work and are one of the most widely spread Internet scams. There aren’t any human studies to back up raspberries claims so exercise a handful of caution when choosing your ketone supplier. Make sure they’re reputable, can be held accountable and are Australian made to set yourself up to become leaner while increasing your stamina.
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.
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.
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.

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).

In addition, the body regulates ketone production via ketonuria (peeing out excess ketones) and ketone-induced insulin release, which shuts off hepatic ketogenesis (the liver making more ketones when you have enough).   The insulin from this process could be increasing glucose disposal which, when coupled with PDH activation, could drive glucose levels quite low.

Exogenous ketones provide the body with another fuel to employ. Think about it like an electric car that runs on both gas and electricity: by consuming ketones along with carbohydrates, the body will preferentially burn the ketones first, saving the carbohydrates for later. Exogenous ketones allow us to enter a metabolic state that wouldn't occur naturally: the state of having full carbohydrate stores, as well as elevated ketones in the blood. This could be advantageous to athletes looking to boost their physical performance. 
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
Too much cortisol tells the liver that you are in physical danger and need a lot of energy fast. The brain doesn't understand the difference between physical danger and emotional stress. When emotionally stressed, the brain thinks you're in a life-and-death situation, so the liver comes to your rescue and gives you the glucose you need to fight off your attacker.

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)

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.
I’m just getting back into an active lifestyle after being sedentary for a few years.. Rough start I must admit but I’m focused.. Objective is to lose 80lbs. I’ve previously had my body in ketosis when I was dieting and working out so I can attest to the benefits I’ve felt before.. Now that I see Exogenous Ketones are available, I’m wondering if it’s recommended to start taking them to help jumpstart my body into ketosis since that is the goal for burning fat…

A common question is why BHB is the go-to ketone body for exogenous ketone supplements. The likely reason is a combination of its efficient conversion into energy and its ease of formulation. In other words, that it is easier to formulate BHB into a nutritional supplement. And the body efficiently converts BHB to acetoacetic acid, which effectively raises blood ketone levels.
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.
 “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)
The other option – which is the superior option – is the breakdown of fat into a fuel that can be used by the brain. This is a beautiful solution, because even the leanest individual will have weeks and weeks’ worth of energy stored as body fat. The body breaks down this fat in the liver and converts it into ketone bodies. The brain can then utilise these ketones as a fuel source – forgoing the need for stored glucose or constant consumption of carbohydrates. These ketones can also be used to make ATP.
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.
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.
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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