Methods and Results: In the first study, 15 participants consumed KE or KS drinks that delivered ~12 or ~24 g of βHB. Both drinks elevated blood D-βHB concentrations (D-βHB Cmax: KE 2.8 mM, KS 1.0 mM, P < 0.001), which returned to baseline within 3–4 h. KS drinks were found to contain 50% of the L-βHB isoform, which remained elevated in blood for over 8 h, but was not detectable after 24 h. Urinary excretion of both D-βHB and L-βHB was <1.5% of the total βHB ingested and was in proportion to the blood AUC. D-βHB, but not L-βHB, was slowly converted to breath acetone. The KE drink decreased blood pH by 0.10 and the KS drink increased urinary pH from 5.7 to 8.5. In the second study, the effect of a meal before a KE drink on blood D-βHB concentrations was determined in 16 participants. Food lowered blood D-βHB Cmax by 33% (Fed 2.2 mM, Fasted 3.3 mM, P < 0.001), but did not alter acetoacetate or breath acetone concentrations. All ketone drinks lowered blood glucose, free fatty acid and triglyceride concentrations, and had similar effects on blood electrolytes, which remained normal. In the final study, participants were given KE over 9 h as three drinks (n = 12) or a continuous nasogastric infusion (n = 4) to maintain blood D-βHB concentrations greater than 1 mM. Both drinks and infusions gave identical D-βHB AUC of 1.3–1.4 moles.min.
If you are having a weight loss plateau and you’ve been at the same weight for 3 or more weeks, try changing something to get back to that stable weight loss rate, like a ketone supplement. It would be exciting to lose more than that each week, but our bodies don’t adjust to dramatic changes well, and a slower rate of loss leads to more of the weight staying off in the future.
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?
Animal procedures were performed in accordance with the University of South Florida Institutional Animal Care and Use Committee (IACUC) guidelines (Protocol #0006R). Juvenile male Sprague–Dawley rats (275–325 g, Harlan Laboratories) were randomly assigned to one of six study groups: control (water, n = 11), BD (n = 11), KE (n = 11), MCT (n = 10), BMS (n = 11), or BMS + MCT (n = 12). Caloric density of standard rodent chow and dose of ketone supplements are listed in Table 1. On days 1–14, rats received a 5 g/kg body weight dose of their respective treatments via intragastric gavage. Dosage was increased to 10 g/kg body weight for the second half of the study (days 15–28) for all groups except BD and KE to prevent excessive hyperketonemia (ketoacidosis). Each daily dose of BMS would equal ~1000–1500 mg of βHB, depending on the weight of the animal. Intragastric gavage was performed at the same time daily, and animals had ad libitum access to standard rodent chow 2018 (Harlan Teklad) for the duration of the study. The macronutrient ratio the standard rodent chow was 62.2, 23.8 and 14 % of carbohydrates, protein and fat respectively.

Dominic D’Agostino has two in-depth interviews on The Tim Ferriss Show (Part 1, Part 2). Discussion includes exogenous ketones for mitigating the onset of neurodegenerative diseases, using ketones in place of fasting for chemo-protection, benefits of ketone supplementation when consuming carbohydrates, the risks and potential toxicities of ketones.

I feel like I should also mention that the GI discomfort is real, people. I would recommend starting this product on a weekend or a day where you’re able to just take it easy. After my first dose, which was only 1/2 scoop, I literally just felt like lying in bed all day due to feelings of nauseousness; however, by the next day I was fine and even bumped my dose to a full scoop.
I eat one meal a day during a one-hour window and fast 23 or more hours every day. I want to use your ketones to get back into ketosis faster after that meal. Will that work? I am confused, because say at the end of my hour eating window I drink your ketones, sure there are lots of ketones suddenly in my body but I also have a big meal in my stomach. My body has to digest and use that food energy, so how do exogenous ketones help me in that case?

And now, you can take ketone supplements (salts and esters), known as exogenous ketones, without actually restricting anything. According to those promoting this nasty-tasting supplement, that means you can have a brain and body fuelled by ketones, along with all of the supposed health benefits that come with running on fat. Well, don't fall for it.
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.
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.
If you’re somebody who isn’t already a keto-goer, then you might be wondering why? Why do I need to limit my carbohydrate intake to get my body into a state of ketosis? Simply put, and without getting to technical; you want your body to be in a constant state where fat is the is the primary source of fuel for the body rather than glucose. You see, once you eat carbs, the body will break this down into glucose which it will then use for fuel before tapping into your fat reserves for energy. If you limit the amount of glucose that is in your system by restricting your carbohydrate intake, the body has no choice but to tap into your fat stores for energy. Fats are metabolised in the liver where ketones are then produced for your physical and cognitive needs.
Onnit is an incredible company that’s making a massive impacts in the lives of athletes in nearly every sport. From Olympic Gold Medalists, to NFL middle linebackers, Onnit has taken athletic performance to a new level. Providing supplements, food, and training equipment, Onnit was an early adopter of the elite performance booster that is exogenous ketones!
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?
In a subset of participants (n = 7) the effect of 3.2−1 of βHB as KE and KS on blood pH and electrolytes after ketone drinks was investigated. Blood d-βHB kinetics were similar to those in the initial experiment (Figure ​(Figure3A).3A). After 60 min, blood pH declined from 7.41 to 7.31 following a KE drink (p < 0.001, Figure ​Figure3B).3B). Bicarbonate fell significantly from 23.6 ± 0.7 to 17.0 ± 0.8 mM following KE drinks (p < 0.001), but remained within the normal range (Figure 3C). Both ketone drinks significantly decreased blood potassium concentrations by 0.7 mM (both drinks p < 0.05, Figure 3D) and increased sodium and chloride concentrations (Sodium: both drinks p < 0.05, Chloride: KE = p < 0.05, KS = p < 0.005, Figures 3E,F).
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)

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.

Animal research findings report that BHB supplementation also enhances oxygen utilization, especially in the central nervous system (CNS).[11] While molecular oxygen is a crucial molecule for health and longevity, too much of it can be potentially toxic and speed the effects of aging in tissues throughout the body.Therefore, using a BHB supplement can effectively mitigate the toxic buildup of molecular oxygen, particularly in the CNS/brain.

With single doses of the D-BHB ester as a sports drink, gastrointestinal (GI) side effects are rare. Some studies have reported mild GI side-effects of HVMN Ketone drinks at extremely high doses (4x serving size) or when given in a thick, meal replacement formulation.10,13 However, other studies of athletes reported there were no side-effects of ketone ester drinks hindering sport performance.11,14

Hi Mark, sorry this is off topic but not sure where to send a question for a future Ask Mark. I’m about to go into my yearly physical and I am wondering if there is any specific bloodwork that you like to do for your annual check up. I’m 47 year’s old and the than the basic blood work like lipid panel, etc..I’m going to ask my doctor to test my testosterone, HbA1C, fasting insulin, and Vitamin D levels. I’m also going to ask my doctor to do a stool test to check for parasites or other infections I may have picked up from open water swimming for triathlons. Can you recommend any other blood work that might be useful? Thanks!
But some people chose to use supplements to benefit from ketosis (Therapeutic Ketosis), and finally there is the MCT Ketogenic Diet – which in a form of nutritional ketosis (ULC, limited protein, high fat) with a twist – about 30-60% of the fat intake in the diet comes from MCT (Medium Chain Triglyceride) fats. Sources of MCT fats include Pure MCT Oil, Coconut oil and coconut products. The MCT Ketogenic Diet is often used with epilepsy suffers, as the high levels MCT oil create a higher level of ketones in the blood – which helps prevent seizures.
Blood, urine, plasma, and breath ketone concentrations following mole-matched ketone ester or isocaloric dextrose drinks in fed and fasted subjects (n = 16) at rest. Data from both of the two study visits in each condition (fed and fasted) completed by an individual are included in the analysis. Values are means ± SEM. (A) Blood d-βHB. (B) AUC of blood d-βHB. (C) Urine d-βHB excretion. (D) Plasma acetoacetate (AcAc). (E) Measured breath acetone (ppm = parts per million). (F,G) Mean d-βHB Cmax and difference between βHB Cmax over two visits when subjects separately consumed two ketone ester drinks in both the fed (F) and fasted (G) state. X axis = mean d-βHB Cmax of the 2 visits (mM), Y axis = difference between d-βHB Cmax in each visit. 95% confidence limits are shown as dotted lines. Significance denoted by: *p < 0.05 fed vs. fasted.
Because of how effectively exogenous ketones can reduce hunger for those in ketosis, pay attention to the cues your body gives you. It’s possible to extend your fasts longer than necessary because of a decreased appetite cue. While those who have some weight to lose might be tempted to think this is a favorable side effect, there is a difference between fasting and starving for nutrients. Make sure to get enough food to support your activities and maintain your muscle mass.

I eat one meal a day during a one-hour window and fast 23 or more hours every day. I want to use your ketones to get back into ketosis faster after that meal. Will that work? I am confused, because say at the end of my hour eating window I drink your ketones, sure there are lots of ketones suddenly in my body but I also have a big meal in my stomach. My body has to digest and use that food energy, so how do exogenous ketones help me in that case?

There are things you can do to get into ketosis faster. We explain how to get into ketosis and ways to make transitioning into ketosis easier. But first, we go over some facts about ketosis you need to understand before you start your keto journey. We will also explain the science behind ketosis, including how long it realistically takes for your body to make the switch.

There are things you can do to get into ketosis faster. We explain how to get into ketosis and ways to make transitioning into ketosis easier. But first, we go over some facts about ketosis you need to understand before you start your keto journey. We will also explain the science behind ketosis, including how long it realistically takes for your body to make the switch.
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.
We’ve all been taught that high sodium intake is bad for us, similar to how we’ve been told for decades that fat is the driver of coronary heart disease, and consuming large amounts will kill us.  Sodium has been thought to increase blood pressure, and therefore increase the risk of heart disease, kidney disease, stroke, osteoporosis, and stomach cancer. Thus, many of us tend to avoid consuming foods or supplements with labels that have high amounts of sodium.

Keto-adaption is a complex set of metabolic processes in which the body shifts from using primarily glucose for energy to using largely ketones and fat for energy. Achieving ketosis doesn’t mean the body is maximizing the use of these ketones; it takes longer than a few days for the body to get used to burning fat and ketones as its predominant fuels.
An effective ketosis program requires that you control your appetite. Caffeine has been proven to be an excellent appetite suppressant. It can curb your appetite and reduce your cravings for food. If you are finding it hard to implement intermittent fasting, try to introduce coffee into the equation. If you are not into coffee drinks, try to take tea or use caffeine pills. Both of them contain caffeine, which can help you to adjust smoothly into fasting.
One common concern regarding the KD is its purported potential to increase the risk of atherosclerosis by elevating blood cholesterol and triglyceride levels [55, 56]. This topic remains controversial as some, but not all, studies have demonstrated that the KD elevates blood levels of cholesterol and triglycerides [57–62]. Kwitervich and colleagues demonstrated an increase in low-density lipoprotein (LDL) and a decrease in high-density lipoprotein (HDL) in epileptic children fed the classical KD for two years [27]. In this study, total cholesterol increased by ~130 %, and stabilized at the elevated level over the 2-year period. A similar study demonstrated that the lipid profile returned to baseline in children who remained on the KD for six years [63]. Children typically remain on the diet for approximately two years then return to a diet of common fat and carbohydrate ingestion [64]. The implications of these findings are unclear, since the influence of cholesterol on cardiovascular health is controversial and macronutrient sources of the diet vary per study. In contrast to these studies, the majority of recent studies have suggested that the KD can actually lead to significant benefits in biomarkers of metabolic health, including blood lipid profiles [65–72]. In these studies, the KD positively altered blood lipids, decreasing total triglycerides and cholesterol while increasing the ratio of HDL to LDL [68–77]. Although, the KD is well-established in children, it has only recently been utilized as a strategy to control seizures in adults. In 2014, Schoeler and colleagues reported on the feasibility of the KD for adults, concluding that 39 % of individuals achieved > 50 % reduction in seizure frequency, similar to the results reported in pediatric studies. Patients experienced similar gastrointestinal adverse advents that have been previously described in pediatric patients, but they did not lead to discontinuation of the diet in any patient [78].
Since beta hydroxybutyrate is transported throughout the body via the blood, the best way to check your true BHB levels is through a blood test. The good news is that you can just use a simple finger prick and an at home method that is very similar to how diabetics check their glucose. The bad news is that it can be pretty expensive. Each strip and time you test can be around $4-6.
The human studies aren’t quite there yet, but it seems likely that they’d help. A recent human case study found that ketone esters added to the regular diet improved Alzheimer’s symptoms. Animal studies indicate that adding exogenous ketones to a regular lab (read: not ketogenic) diet can reduce seizure activity and improve overall symptoms in epilepsy animal models, reverse early neuronal hyperactivity in Alzheimer’s animal models, and reduce anxiety in rats.

For subjects completing the initial experiment (n = 15), the amount of d-βHB excreted in the urine increased with d-βHB intake, but was <1.5% of the total βHB ingested and was not different between matched doses of KE vs. KS (Figure ​(Figure1I).1I). There was no change in urine volume produced in different study conditions. Baseline urinary pH (5.7 ± 0.1) was unchanged by KE ingestion (pH 6.4 ± 0.2. p = 0.8 vs. baseline) but was significantly alkalinized by KS consumption (pH 8.5 ± 0.1. p < 0.001 vs. baseline) (Figure ​(Figure1J1J).
Exogenously delivered ketone supplements significantly altered rat weight gain for the duration of the study (Fig. 6). However, rats did not lose weight and maintained a healthy range for their age. Rats have been shown to effectively balance their caloric intake to prevent weight loss/gain [97–99]. Due to the caloric density of the exogenous ketone supplements (Table 1) it is possible for the rats to eat less of the standard rodent chow and therefore less carbohydrates while maintaining their caloric intake. Food intake was not measured for this study. However, if there was a significant carbohydrate restriction there would be a signifcant change in basal blood ketone and blood glucose levels. As the hallmark to the KD, carbohydrate restriction increases blood ketone levels and reduces blood glucose levels. Neither an increase in basal blood ketone levels nor a decrease in basal blood glucose levels was observed in this study (Fig. 7). Additionally, if there were an overall blood glucose decrease due to a change in food intake, this would not explain the rapid reduction (within 30 min) in blood glucose correlated with an elevation of blood ketone levels after an intragastric bolus of ketone supplement (Figs. 2, ​,33 and ​and44).
Selective attention involves focusing only on relevant information while suppressing the impulse to pay attention to irrelevant distractions. A v-shaped flock of birds are displayed. The center (target) bird points in one direction and is surrounded by birds that either match the target’s direction or do not. The task is to rapidly identify which direction the target bird is pointing.
The chart below shows my ketone and glucose response to consuming 40g of KetoneAid’s ketone esters, which had been calculated to be my optimal serving size based on my weight (170lbs) and type of activity (I am moderately active/athletic, but cognitive experiments are a “low” physical activity). Normally, for increased physical performance ketone esters are consumed along with some glucose, but since I was only focusing on cognitive performance I did not consume any glucose.
As Dr. Ryan Lowery pointed out to me, ketone supplements could play an important role in the future for elite sports performance, for example, or for people with brain injuries who cannot metabolize glucose properly. I am encouraged that scientists are working to develop these possibilities and, as long as plenty of peer-reviewed scientific research is done into the products being developed, I could feel more positive about the ketone salts in the future. For now, that scientific support is lacking.
Hi Rob thanks so much, many people experience inconclusive results from the pee strips, as the ketone concentration in our pee is a measure of ketones not being used by the body. Basically the overflow or unused ketones. As our body becomes more adapted to using ketones, there will be less in our urine. It’s tough to keep the variable constant of how hydrated you are across many pee tests. Don’t be discouraged by pee test results. We have had many times where our blood tests show 1-3mmol/dl BHB but our pee test showed no results. Definitely keep testing (consider using a precision Xtra) and changing the dose to suit your needs. Hope this is helpful!

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.

Your body uses the energy source that is the easiest to use, in our case this is glucose. Glucose is just a type of sugar. As our body cannot store glucose as such it stores the extra glucose in form of glycogen that is stored in our liver and muscles. To initiate production of ketones in your body as fast as possible you must deplete your body of glycogen reserves. The best way to do this is a simple 24 hours fast. This will deplete your glycogen stores as fast as possible. If you don’t over eat for dinner or you even skip it all together you will already wake up in state of mild ketosis the next morning due to the overnight fast. Here are also described some signs that you are in Ketosis already.
A typical serving of racemic ketone salts contains around 12g of beta hydroxybutyrate, of which only half is the D- form (6g). Compared to the 40g ketone esters I consumed (which are 100% D- form), I would need to consume somewhere around seven to nine packets of ketone salts to get the same amount of D-β-hydroxybutyrate (some D- form is wasted burning of the L- form), along with the huge amount of salts contained and more than a gallon of water (since the powders must be mixed). Even if one could consume that amount of ketone salts, they will probably suffer from what people often refer as “disaster pants” (aka diarrhea) due to the amount of salt consumed.
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.

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