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).
Ketōnd is an intelligently designed formula containing an industry leading 13,900mg blend of high-powered goBHB™ all packed into a 100% transparent, proprietary blend free formula. Ketōnd is widely known as the most ‘potent’ exogenous ketone supplement available that has been formulated for anyone looking to manage their weight, maximize cognition, or simply feel more energetic in a low carbohydrate environment.
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.

Over the 28-day experiment, ketone supplements administered daily significantly elevated blood ketone levels without dietary restriction (Fig. 2a, b). Naturally derived ketogenic supplements including MCT (5 g/kg) elicited a significant rapid elevation in blood βHB within 30–60 min that was sustained for 8 h. BMS + MCT (5 g/kg) elicited a significant elevation in blood βHB at 4 h, which was no longer significant at 8 h. BMS (5 g/kg) did not elicit a significant elevation in blood βHB at any time point. For days 14–28, BMS + MCT (10 g/kg) and MCT (10 g/kg) elevated blood βHB levels within 30 min and remained significantly elevated for up to 12 h. We observed a delay in the peak elevation of blood βHB: BMS + MCT peaked at 8 h instead of at 4 h and MCT at 4 h instead of at 1 h. Blood βHB levels in the BMS group did not show significant elevation at any time point, even after dose escalation (Fig. 2a). Synthetically derived ketogenic supplements including KE and BD supplementation rapidly elevated blood βHB within 30 min and was sustained for 8 h. For the rats receiving ketone supplementation in the form of BD or the KE, dosage was kept at 5 g/kg to prevent adverse effects associated with hyperketonemia. The Precision Xtra™ ketone monitoring system measures βHB only; therefore, total blood ketone levels (βHB + AcAc) would be higher than measured. For each of these groups, the blood βHB profile remained consistent following daily ketone supplementation administration over the 4-week duration. (Fig. 2b).

The reason for testing after one hour was based on Prüvit’s “59-minute test”, which recommends testing ketones 45-60 minutes after taking the supplement (by the way, saying “59 minutes” instead of 60 minutes or 1 hour just sounds like another marketing gimmick to me). Kegenix Prime also promises “ketosis in 60 minutes” on its packaging. We carried out the testing at more or less the same time each day.
Do I still follow a ketogenic diet? Not anymore. I was strict keto for 12 weeks – enough time to experiment and learn about it. I did enjoy parts (lots of fat!) but I don’t see it as a sustainable way of eating, nor did I benefit from it health or sports performance wise (more on this in an upcoming article). But, I was following a strict keto diet – sans carbs. I think if I were to follow a ketogenic diet AND incorporate a regular carb refeed then the results may be different.
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.
Relationship between blood ketone and glucose levels: a BMS + MCT (5 g/kg) supplemented rats demonstrated a significant inverse relationship between elevated blood ketone levels and decreased blood ketone levels (r2 = 0.4314, p = 0.0203). b At week 4, BMS + MCT (10 g/kg) and MCT (10 g/kg) showed a significant correlation between blood ketone levels and blood glucose levels (r2 = 0.8619, p < 0.0001; r2 = 0.6365, p = 0.0057). Linear regression analysis, results considered significant if p < 0.05

Exogenous Ketones have been shown in performance studies of both humans and animals to improve metabolic efficiency, which in essence means that your body is using better fuel that burns more efficiently over longer periods of time, and decreases the amount of fuel you need while performing. Where glucose fails (glycogen depletion), ketones pick up the slack!


Blood glucose concentrations are decreased during both exogenous and endogenous ketosis, although by different mechanisms. During endogenous ketosis, dietary carbohydrate deficit is the underlying cause of low blood glucose, along with reduced hepatic gluconeogenesis and increased ketone production (Cahill et al., 1966). With exogenous ketosis, carbohydrate stores are plentiful, yet ketones appear to lower blood glucose through limiting hepatic gluconeogenesis and increasing peripheral glucose uptake (Mikkelsen et al., 2015). One clinical use of the ketogenic diet is to improve blood glucose control, yet the elevated blood FFA may increase the risk of heart failure (Holloway et al., 2009). Thus, the ability of exogenous ketones to lower blood glucose without elevating blood FFA concentrations could deliver the desired effect of the diet, whilst also decreasing a potential risk.
Effects of ketone supplementation on organ weight: Data is represented as a percentage of organ weight to body weight. a, b, d, f Ketone supplements did not significantly affect the weight of the brain, lungs, kidneys or heart. c Liver weight was significantly increased as compared to body weight in response to administered MCT ketone supplement compared to control at the end of the study (day 29) (p < 0.001). e Rats supplemented with BMS + MCT, MCT, and BD had significantly smaller spleen percentage as compared to controls (p < 0.05, p < 0.001, p < 0.05). Two-Way ANOVA with Tukey’s post-hoc test; results considered significant if p < 0.05. Error bars represent mean (SD)
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!

Spatial orientation (also known as sense of direction) involves being aware of the surrounding environment. The game involves navigating a penguin through a two-dimensional maze (up, down, left, right) to get to a fish. As the penguin moves through the maze, the entire screen periodically rotates to another orientation, so “up” for the penguin then becomes, say, “left” to the player, who must quickly adapt to the navigation controls.
One other thing I must point out is also that we are talking about being in ketosis and not being fully keto adapted. You enter ketosis when your body starts producing ketones above a specified level, being fully keto adapted means that your body is full adapted to  use fat as your primary energy source and that the production of certain enzymes in your body is fully adapted. This doesn’t happen in one day and it takes about 1 month on average to be fully keto adapted. But we are not looking for this as we just want to end the most unpleasant period and to start losing weight.
After a few days of fasting, or of drastically reduced carbohydrate consumption (below 50 g/day), glucose reserves become insufficient both for normal fat oxidation via the supply of oxaloacetate in the Krebs cycle (which gave origin to the phrase ‘fat burns in the flame of carbohydrate') and for the supply of glucose to the central nervous system (CNS).4
The current USDA recommendations reflect “unachievable goals” that do not match what research suggests our normal physiological ranges might be[10]. There is not enough evidence to show that sodium restriction is associated with less mortality or cardiovascular morbidity in healthy individuals or individuals with high blood pressure, and there is evidence that sodium restriction might actually be harmful to individuals with heart failure[11]. For serious athletes, and individuals who are active daily, the current recommendations might not only be unwise but unsafe. If you are eating a carbohydrate-restricted diet, this applies to you even more. Don’t stress about the high amounts of sodium in a lot of these ketone supplements, being that they allow for a fast delivery of ketones to the body, which has unique benefits that will be discussed in a separate article.  Instead, change out the frozen dinner and experiment with an effective dose of exogenous ketones.
Weight loss benefits ushered the keto diet into the spotlight. That’s how most people have likely heard about ketones, a fuel source created naturally by the body when burning fat. But more and more research points to diverse applications of ketones in the blood outside of just fat loss, from improved endurance performance to the treatment of medical conditions like epilepsy.
[1] Shannon L. Kesl, corresponding author Angela M. Poff, Nathan P. Ward, Tina N. Fiorelli, Csilla Ari, Ashley J. Van Putten, Jacob W. Sherwood, Patrick Arnold, and Dominic P. D’Agostino (2016). Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and lipoprotein levels in Sprague–Dawley rats. Nutrition & Metabolism, 13(9)
That’s exactly what ketones do: inhibit lipolysis, the breakdown of body fat into triglycerides and free fatty acids for burning. In normal conditions where ketones are produced endogenously, this is expected and beneficial. If homemade ketones increased lipolysis, you’d end up with ketoacidosis. You’d make ketones which released more body fat which got turned into more ketones which released more body fat which became more ketones. And on and on. It simply wouldn’t stop.

You see, when someone says ketosis is a natural state, they mean that ketosis is the body’s backup plan for those times when there isn’t any food to eat. It’s an evolutionary adaptation that developed over hundreds of thousands of years and springs from a time when our distant ancestors often had to go many days between decent meals. Fortunately, these days actual starvation is pretty rare so most people will never be in ketosis. But the physiological mechanism is still there, lurking in the background, readily accessible to anyone who is willing to trick their body into thinking it’s starving.

The many roles of magnesium include helping us maintain normal nerve and muscle function, as well as heart rate, supporting a healthy immune system, regulating blood glucose levels, and making energy production and protein synthesis possible[23]. Magnesium is also involved in both aerobic and anaerobic energy production. ATP synthesis (the body’s energy source) depends on enzymes that are activated by magnesium.


Instead of being bound to a mineral (like ketone salts), the ketone molecule (BHB or AcAc) is bound to a ketone precursor (e.g. butanediol or glycerol) via an ester bond. While there aren't as many esters on the market as salts, there is still some variance–especially when looking at the ketone molecule in these products. Before selecting the best one for you, it's important to gather all the necessary information to make your decision.
Taking exogenous ketones not only eliminates the need to follow a strict ketogenic diet to achieve ketosis (so you can have your high carb cake and eat it too), it can also help users get there faster. “They can expedite the process of getting into ketosis and becoming fat adapted,” Davis explains. “They can also help people push past the keto flu and potentially experience more mental energy and clarity than from diet alone.”
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.
Intellectual property covering uses of dietary ketone and ketone ester supplementation is owned by BTG Ltd., the University of Oxford, the National Institute of Health and TΔS Ltd. Should royalties ever accrue from these patents, KC and PC, as inventors, will receive a share of the royalties under the terms prescribed by the University of Oxford. KC is a director of TΔS Ltd., a company spun out of the University of Oxford to develop and commercialize products based on the science of ketone bodies in human nutrition. At the time of data collection and manuscript preparation, BS was an employee of TΔS Ltd., funded by the Royal Commission for the Exhibition of 1851. SH is an employee of NTT DOCOMO, Inc. (Japan). The other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Exogenous ketones are powerful. They will get you into ketosis whether keto-adapted or not. The benefits of this range from weight loss to sustained mental and physical energy. The benefits are the same as those from nutritional ketosis, however, they’re not a substitute for nutritional ketosis. More on that below before we get into the top 5 exogenous ketones for 2018.


When your body transitions from using energy from carbohydrates to ketones, there can be a lot of nasty and unwanted side effects. These include low energy, bloating, irritability, headaches and fatigue. This is because your body is “in between” burning carbs and burning ketones and hasn’t become efficient at burning ketones and producing them from your fat stores yet.
Background and aims: Currently there is considerable interest in ketone metabolism owing to recently reported benefits of ketosis for human health. Traditionally, ketosis has been achieved by following a high-fat, low-carbohydrate “ketogenic” diet, but adherence to such diets can be difficult. An alternative way to increase blood D-β-hydroxybutyrate (D-βHB) concentrations is ketone drinks, but the metabolic effects of exogenous ketones are relatively unknown. Here, healthy human volunteers took part in three randomized metabolic studies of drinks containing a ketone ester (KE); (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, or ketone salts (KS); sodium plus potassium βHB.
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.
I stumbled onto this trend before it even blew up, I have read just about every peer-review journal of the topic, I have trialed as well as tested different methods and keto products (exogenous ketones, MCT oils, pills, etc), and lastly, I have reported and analyzed my performance to share with you all. It hasn't been an easy task, but I have also seen the fruits of the labor, and the fruit is sweet.
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.
Your brain has a very tight barrier so not everything in the blood can get through. This is called the blood brain barrier. Because your brain uses 25% of the energy that your entire body uses throughout the day, you need to make sure it is fueled appropriately. Glucose can’t directly cross the blood brain barrier. When you eat carbs, you get swings in energy that is available to cross the blood brain barrier which leads to mental fog.
When your body is done using up a certain substrate to create energy (acetyl-CoA) after eating carbohydrates, it will start to find creative ways to get the job done. This is something that you want to happen. This is the switch to ketosis. If you didn’t do this, you’d be dead after fasting for a very short period of time. Under normal circumstances, the liver will start making beta-hydroxybutyrate from long chain and medium chain fatty acids that are liberated from your fat tissue. You are turning fat into fuel. Good work. This is why people can fast for months at a time and still function like normal humans.
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.

2. Shimazu, T., Hirschey, M.D., Newman, J., He, W., Shirakawa, K., Le Moan, N., Grueter, C.A., Lim, H., Saunders, L.R., Stevens, R.D., Newgard, C.B., Farese Jr, R.V., De Cabo, R., Ulrich, S., Akassoglou, K., and Verdin, E. (2013). Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science 339, 211-214.
We will go deep in the science behind this fascinating diet and then review some of the best exogenous ketone supplements out there in the market. Because without the knowledge and the right information about exogenous ketones that you can properly follow, you might never reach your goals and you may as well keep eating that mashed potato for dinner and club sandwich for lunch.

Given that blood βHB after identical ketone drinks can be affected by factors such as food or exercise (Cox et al., 2016), the accuracy of tools for non-invasive monitoring of ketosis should be investigated. Breath acetone and urinary ketone measurements provide methods to approximate blood ketosis without repeated blood sampling (Martin and Wick, 1943; Taboulet et al., 2007). However, breath acetone did not change as rapidly as blood βHB following KE and KS drinks. Acetone is a fat-soluble molecule, so may have been sequestered into lipids before being slowly released, resulting in the differences observed here. Similarly, significant differences in blood d-βHB between study conditions were not reflected in the urinary d-βHB elimination. As the amount of d-βHB excreted in the urine (≈0.1–0.5 g) represented ~1.5% of the total consumed (≈23.7 g), it appears that the major fate of exogenous d-βHB was oxidation in peripheral tissues. These results suggest that neither breath acetone nor urinary ketone measurements accurately reflect the rapid changes in blood ketone concentrations after ketone drinks, and that blood measurement should be the preferred method to quantitatively describe ketosis. That said, it should be noted that although commercial handheld monitors are the most practical and widely available tool for measuring blood ketones, they can overestimate blood D-βHB compared to laboratory measures (Guimont et al., 2015) and these monitors do not measure L-βHB and so may not provide accurate total blood ketone concentrations, especially if a racemic ketone salt has been consumed.


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.

As ketone drinks can deliver nutritional ketosis without fasting, we investigated the effect of food on KE uptake and metabolism. It is well documented that food in the gut can slow, or prevent, the uptake of small hydrophilic hydrocarbons, such as βHB (Melander, 1978; Toothaker and Welling, 1980; Horowitz et al., 1989; Fraser et al., 1995), so decreased gut βHB uptake is probably the cause of lower blood βHB following the meal. Despite higher blood βHB concentrations in the fasted state, the meal did not alter plasma AcAc. This suggests that the rate of conversion of βHB to AcAc may not match the rate of appearance of βHB following KE consumption. Alternatively, meal-induced changes in the hepatic ratio of NAD+:NADH may have altered the conversion of βHB to AcAc (Himwich et al., 1937; Desrochers et al., 1992).


That said, there also remains the question of the relative benefits of AcAc versus BOHB, both as independent signaling molecules and as redox modulators in peripheral (aka non-hepatic) tissues. Seen from this perspective, AcAc generated in the liver acts as a NAD+ donor for the periphery, whereas pure BOHB taken orally, to the extent that it is retro-converted to AcAc (Sherwin 1975), potentially deprives the periphery of NAD+.
Instead of being bound to a mineral (like ketone salts), the ketone molecule (BHB or AcAc) is bound to a ketone precursor (e.g. butanediol or glycerol) via an ester bond. While there aren't as many esters on the market as salts, there is still some variance–especially when looking at the ketone molecule in these products. Before selecting the best one for you, it's important to gather all the necessary information to make your decision.
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!

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].

Now onto the best ketone supplements. All of these 5 are great products with good customer experiences and reviews. The list contains 3 MCT oil powders and 2 BHB salts. Since it’s just 5 products, there’s no room for bad quality. If you see a lower rating it may be due to price/value, the taste or perhaps a lack of third-party inspection certificates.


Venous blood samples (2 ml) were obtained during all visits using a 22 G catheter inserted percutaneously into an antecubital vein. The catheter was kept patent using a saline flush following each sample collection. Additionally, during Study 1, arterialized blood from a catheter inserted into a heated hand (Forster et al., 1972) was collected into heparinized blood gas syringes (PICO 100, Radiometer, Copenhagen) from a subset of participants (n = 7) and immediately analyzed for pH and electrolytes using a clinical blood gas analyser (ABL, Radiometer, Copenhagen).
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.

When your body is done using up a certain substrate to create energy (acetyl-CoA) after eating carbohydrates, it will start to find creative ways to get the job done. This is something that you want to happen. This is the switch to ketosis. If you didn’t do this, you’d be dead after fasting for a very short period of time. Under normal circumstances, the liver will start making beta-hydroxybutyrate from long chain and medium chain fatty acids that are liberated from your fat tissue. You are turning fat into fuel. Good work. This is why people can fast for months at a time and still function like normal humans.

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