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.
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?

Exogenous ketones are becoming more popular as advancements in scientific research continue to show how they work to improve both health and performance. At first, the only options for delivering exogenous ketones were unpalatable ketone esters; however, exogenous ketones can now be taken in the form of ketone mineral salts that are more palatable and easily blended in water. Making ketone mineral salts involves combining beta-hydroxybutyrate (BHB) with mineral salts such as sodium, calcium, magnesium, or potassium. Before considering whether ketone supplements are a good option, most people immediately look at the salt load, and rightfully so. It is important to take into account the nutritional and health impact of not only the BHB but the minerals that are used to make the product.
Most of the ketone supplements out there are either underdosed or overpriced - some don't even bother to disclose how much BHB (ie ketones) is used in their product. And why would they? BHB is EXTREMELY expensive. So by not disclosing the amount the can get away with putting in as little as they want and still claim it's a ketone supplement while keeping their costs as low as possible.
Other studies have found that fasting was as effective as chemotherapeutic agents in delaying progression of different tumors and increased the effectiveness of chemotherapeutic drugs against melanoma, glioma, and breast cancer cells. Although this research may not apply to your life, it does suggest that intermittent fasting can help support your body in times of toxic stress.
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.
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…

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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?
Increased calcium levels in the bloodstream may contribute to the hardening of arteries (atherosclerosis), which in turn can lead to a heart attack.  Calcium from supplements enters the bloodstream in one bolus, whereas we usually tend to get calcium from foods in small doses from the breakdown process. This might explain why calcium from food doesn’t create the same risk that is introduced by calcium supplements. At first glance, it seems to be the case that high calcium intake –at least from supplements–may not be ideal.
Thank you, Mark! I am an ME/CFS patient, and I have improved quite a bit on a ketogenic diet, which I have been following for the past 3 months. I am slowly losing weight (much needed) and I wondered, does using exogenous ketones inhibit fat loss? I’m trying to balance the benefits of continuing weight loss with benefits in dealing with ME/CFS symptoms. Thank you for any info you can offer!
The CNS cannot use fat as an energy source; hence, it normally utilizes glucose. After 3–4 days without carbohydrate consumption the CNS is ‘forced' to find alternative energy sources, and as demonstrated by the classic experiments of Cahill and colleagues4 this alternative energy source is derived from the overproduction of acetyl coenzyme A (CoA). This condition seen in prolonged fasting, type 1 diabetes and high-fat/low-carbohydrate diets leads to the production of higher-than-normal levels of so-called ketone bodies (KBs), that is, acetoacetate, β-hydroxybutyric acid and acetone—a process called ketogenesis and which occurs principally in the mitochondrial matrix in the liver.6
As repeated KE consumption would be required to maintain nutritional ketosis, we investigated the kinetics of drinks in series and of continuous intra-gastric infusion. During starvation, the accumulation of ketones (>4 mM) reportedly inhibited ketone clearance from the blood, however the underlying mechanism is unknown (Hall et al., 1984; Wastney et al., 1984; Balasse and Fery, 1989). In Study 3, βHB uptake and elimination were identical for the second and third KE drinks, suggesting that βHB may have reached a pseudo-steady state should further identical boluses have been given at similar intervals. Furthermore, when the KE was given at a constant rate via a NG tube, blood ketone concentrations remained ~3 mM. Therefore, repeated KE drinks effectively maintain ketosis at the intervals and doses studied here.

Besides cutting carbs, it's important to increase your fat intake, and be moderate with protein. The fat you eat will keep you feeling energized and support ketone production. Protein is also important but if you go overboard with it, your body could enter into a process called gluconeogenesis. In gluconeogenesis, your body makes glucose from protein, and you want to avoid that.


Some people follow more of an Ultra Low Carb diet approach. This is generally around 50g or less of carbs per day. A ULC is more supportive of reaching a ketogenic state, but again total carbs are not the only variable when it comes to reaching ketosis (other factors such as types of carbs, protein consumption, portion size, ingredients, supplements used etc. all play a role and will be covered in more detail below). 
Whereas ketone esters are 100% D- form, most ketone salts are a 50/50 mix of left and right-handed beta hydroxybutyrate, which is known as a racemic mixture. These beta hydroxybutyrate molecules are linked to a mineral, such sodium (Na), calcium (Ca), potassium (K), or magnesium (Mg). This kind of ketone supplement gets broken down to left and right-handed version of beta hydroxybutyrate along with the mineral.
Even though there is mixed evidence regarding the association between calcium supplementation and cardiovascular events, there may be other reasons to avoid high calcium supplementation. In one of his studies, Dr. Bolland claimed that calcium supplements do not prevent hip fractures. Rather, they may lead to kidney stones, acute gastrointestinal events, and increased risk of myocardial infarction and stroke. Thus, the risks involved with high-calcium supplementation potentially outweigh the benefits[21].
Hey Staci, great to hear you’re getting back into it! To answer your question, it really depends on the individual but there are definitely things you can do to get back into ketosis faster – working out to deplete your glycogen stores or implementing intermittent fasting into your regimen – these are 2 common ways that should kick start you back in the right direction!

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).


Electrolyte Imbalance – The physiological reasoning behind electrolytes becoming depleted during a state of ketosis is due to lack of water retention and frequent urination. When supplementing with exogenous ketones, the acute state of ketosis will likely increase the frequency of urination, but it won’t deplete glycogen stores. Therefore, it may be useful to drink an electrolyte solution if you are urinating a lot after taking exogenous ketones, but it’s dependent upon how you feel.
Lots of good info but some things are just plain wrong. It takes 2 days max to get into ketosis if you stop eating carbs. Your body can only store roughly 2 days worth of glycogen. When those stores are exhausted your body will immediately turn to fat. It may take a week or several weeks to get “keto adapted” but it simply won’t ever take you more than 2 days to get into a state of ketosis.

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.
I’m fasting (5 days fast, 2 days food) in an effort to aggressively lose weight. For the most part, I’m not doing the water & salt-only kind of fast… as I will also drink coffee & bone broth… as well as take Perfect Keto Base. Would it be “gilding the lily” to also add MCT powder to my coffee? I’m in nutritional ketosis… ranging from 0.8 to 2.0 or thereabouts.

The challenge for me is what 80% fat looks like. If I eat 1500 calories a day – mostly veggies and protein – how do I best get the fat? I can eat an avocado with my meals, olive oil on my salads, cook my eggs in coconut oil, but I am not clear on how to eat so much fat the healthy way while keeping calories at a lower amount. I eat once – twice a day. I am not a fan of eating tons of saturated fat – bacon on everything is bad advice I have seen pushed out on other pages. Eating Keto does not mean eating high fat meats for your fat. Healthy is the focus. How to eat a heavy veggie, low protein, high fat diet the most healthy way? The calculations are challenging on a tight schedule for one trying to get started :)I would love some solid advice.
It is important to define what it means to be “in ketosis”. If being “in ketosis” means having ketones in your blood, then of course ketone supplements get you into ketosis. But that is different from being in an endogenous ketogenic, fat-burning state as a result of following a ketogenic diet. Getting this distinction right will go a long way towards stopping ketone salts companies from using misleading marketing about the issue. We need to reach a consensus about what being “in ketosis” means and then force companies to use that definition.
Individuals who have clinically unregulated blood sugar, such as those with diabetes, are cautioned to consult their trusted healthcare provider before choosing to use exogenous ketones. While it can be done safely, especially in the presence of a well-formulated ketogenic food plan, there may be a risk of blood sugar dropping unexpectedly low. There may be therapeutic value in this application, but close monitoring is key.
As repeated KE consumption would be required to maintain nutritional ketosis, we investigated the kinetics of drinks in series and of continuous intra-gastric infusion. During starvation, the accumulation of ketones (>4 mM) reportedly inhibited ketone clearance from the blood, however the underlying mechanism is unknown (Hall et al., 1984; Wastney et al., 1984; Balasse and Fery, 1989). In Study 3, βHB uptake and elimination were identical for the second and third KE drinks, suggesting that βHB may have reached a pseudo-steady state should further identical boluses have been given at similar intervals. Furthermore, when the KE was given at a constant rate via a NG tube, blood ketone concentrations remained ~3 mM. Therefore, repeated KE drinks effectively maintain ketosis at the intervals and doses studied here.

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*:
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 
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.

The fate of excess ketones: In the event someone has an excessive amount of ketones in the blood, the body (specifically the kidneys) will work as quickly as possible to filter out ketones via urine rather than converting them to adipose tissue.9 This is not to say that you can’t gain fat if you consume an exorbitant amount of exogenous ketones, but that they are less prone to be converted to fat than other nutrients.


Response inhibition is the ability to suppress inappropriate responses that interfere with goal-directed actions. Two cards are shown, one above the other, each containing the name of a color in a certain color. The goal is to rapidly indicate if the meaning of the color on top (i.e. “yellow”) matches the color of the color on the bottom (i.e., card says “red” but is colored yellow).
Two ground-breaking studies have recently been published on the effects of intermittent fasting on males. One group of researchers studied the effects that 16 hours of intermittent fasting had on males that lift weights. They found that muscle mass stayed the same, fat mass decreased significantly, and the males who fasted for 16 hours a day burned more fat for fuel compared to the control group that only fasted for 12 hours.

Some people follow more of an Ultra Low Carb diet approach. This is generally around 50g or less of carbs per day. A ULC is more supportive of reaching a ketogenic state, but again total carbs are not the only variable when it comes to reaching ketosis (other factors such as types of carbs, protein consumption, portion size, ingredients, supplements used etc. all play a role and will be covered in more detail below). 
The problem? Exogenous ketone supplements work by flooding your bloodstream with ketones. But unless you’re also eating a ketogenic diet (and producing a steady stream of ketones naturally), those supplemental ketones won’t stick around forever. “The benefit of exogenous ketones is limited due to their excretion through the urine,” explains Madge Barnes, MD, family medicine specialist with Texas Health Family Care. In other words? They’ll only work for a few hours until you pee them out. As a result, you need to keep on supplementing—which can get expensive. Twenty single-serving packets of Prüvit’s Keto//OS MAX Pure Therapeutic Ketones, for example, cost $130. (The company doesn’t specify how often you should take them.)
The ketone supplements were associated with a 5.4% decrease in physical performance while the artificially-sweetened, non-caffeinated beverage I used as a placebo was associated with a 20.3% increase: a big difference in favour of the placebo. Before you go rushing out to buy some, remember that this experiment was not performed under fully-controlled, laboratory conditions, and we were working with too small a group to prove that the placebo caused an increase in physical performance. But what we can say is that we couldn’t find any correlation between ketone supplements and an increase in physical performance in this experiment. According to Brianna Stubbs, some of the work currently being done on new kinds of ketone salts is starting to show more promise in relation to physical performance, so there may be better news on this down the line.

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 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).
 “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)

Recently, two published studies investigated the effects of ketone salts in athletes (total n = 22).8,9 Performance over a four-minute cycling time-trial and a 150 kJ ( ~11 mins) cycling time trial were compared between ketone salts vs. carbohydrate. In the four-minute trial there was no change in performance, and in the 150 kJ test, performance decreased by 7%. Blood BHB levels peaked at 0.6 and 0.8 mM in these studies.
For the past few million years, the only way for humans to make use of ketones for fuel was to restrict carbohydrates low enough and long enough to induce the liver to make them. This is admittedly hard for many people to do in a world that still believes that dietary carbs are good and fats are bad. An emerging alternative is to consume ketones as a dietary supplement. The research into how these function in the body and what benefits they can confer remains early stage, but there are already a number of such products available for sale. In this section, we will discuss how exogenous ketones affect blood ketone levels, and how they may influence health and disease compared to ketones produced within the body.
As KE drinks achieved a significantly higher d-βHB concentrations than KS, we investigated factors that may be important in the use of ketone drinks to achieve nutritional ketosis. Initially we determined the repeatability of blood ketosis following KE drinks and found little variation in kinetic parameters between individuals. Variability between participants was less than within the population, and accurate individual prediction of the d-βHB Cmax following a body-weight adjusted KE drink was achieved. Variability within individuals was likely due to normal daily changes in GI function, including gastric emptying, portal blood flow or intestinal transit time, which may alter KE hydrolysis and absorption.
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?
Working memory involves temporarily storing and manipulating information. The game involves seeing three cards – a top card with a symbol that then moves along a track and is flipped over, exposing a new card above. The goal is to remember the symbol of the cards two cards back and indicate whether it matches the visible card or not. If you have ever played dual n-back games, this is very similar.

An alternative to the ketogenic diet is consumption of drinks containing exogenous dietary ketones, such as ketone esters (KE) and ketone salts (KS). The metabolic effects of KS ingestion have been reported in rats (Ari et al., 2016; Kesl et al., 2016; Caminhotto et al., 2017), in three extremely ill pediatric patients (Plecko et al., 2002; Van Hove et al., 2003; Valayannopoulos et al., 2011) and in cyclists (O'Malley et al., 2017; Rodger et al., 2017). However, the concentrations of blood βHB reached were low (<1 mM) and a high amount of salt, consumed as sodium, potassium and/or calcium βHB, was required to achieve ketosis. Furthermore, dietary KS are often racemic mixtures of the two optical isoforms of βHB, d-βHB, and l-βHB, despite the metabolism of l-βHB being poorly understood (Webber and Edmond, 1977; Scofield et al., 1982; Lincoln et al., 1987; Desrochers et al., 1992). The pharmacokinetics and pharmacodynamics of KS ingestion in healthy humans at rest have not been reported.


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.
It’s not clear that the Weir coefficients used to estimate EE are relevant for someone in ketosis, let alone someone ingesting exogenous BHB. (The Weir formula states that EE is approximated by 3.94 * VO2 + 1.11 * VCO2, where VO2 and VCO2 are measured in L/min; 3.94 and 1.11 are the Weir coefficients, and they are derived by tabulating the stoichiometry of lipid synthesis and oxidation of fat and glucose and calculating the amount of oxygen consumed and carbon dioxide generated.) While this doesn’t impact the main observation—less oxygen was consumed with higher ketones—it does impact the estimation of EE and substrate use.

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