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!
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 
KE consumption decreased FFA from 0.6 to 0.2 mM, TG from 1.0 to 0.8 mM, and glucose from 5.5 to 4.7 mM by the end of the study (4 h). The effect was not altered by a meal (Figures 5A–C). Dextrose drinks also lowered FFA from 0.6 to 0.2 mM and TG from 1.0 to 0.7 mM (Figures 5A, B). This was likely mediated by the transient increase in glucose, which rose from 4.6 to 6.5 mM following the dextrose drink (Figure ​(Figure5C).5C). The anti-lypoytic effect of dextrose drinks was shorter than that of KE drinks as d-βHB concentrations were elevated for longer after KE drinks than glucose after dextrose drinks. Insulin increased to ~ 35 mU.ml−1 after both the meal and the dextrose drink, but also increased to 13 ± 2 mU.ml−1 when KE was consumed whilst fasted owing to the 15 g of glucose in the flavored drink used as a diluent (Figure ​(Figure5D5D).
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.

These studies were approved by external Research Ethics Committees (London Queen's Square: 14/LO/0288 and South West Frenchay: 15/SW/0244) and were conducted in accordance with the Declaration of Helsinki (2008). Studies took place at the University of Oxford between September 2014 and September 2016. Participants were healthy, aged 21–57, non-smokers and had no history of major illness. Female participants were using oral contraception to minimize the effects of menstrual phase on results. Participants provided written informed consent prior to inclusion, and completed a confidential medical screening questionnaire to determine eligibility. Anthropometric characteristics are shown in Table ​Table1.1. Sample sizes were chosen following an estimated power calculation based on the effect size in previous work using KE drinks (Clarke et al., 2012b; Shivva et al., 2016).
How did I do this? Simple, I went into a full fast and exercised. What prevents you from entering ketosis is all the glycogen stored in your liver and muscles. Your body can use this glycogen instead of ketones to fuel your brain, so until you deplete your stores of glycogen, you won’t be able to enter ketosis. By eating nothing, you are going to tap into the glycogen to fuel your brain because you are eating 0 grams of carbs and will also be using that glycogen to walk around all day.
Plasma glucose, free fatty acids (FFA), triglycerides (TG) and urinary d-βHB were assayed using a commercial semi-automated bench-top analyzer (ABX Pentra, Montpellier, France), and insulin was measured using a commercially available ELISA assay (Mercodia, Uppsala, Sweden). Both the pure liquid KS and KE, and a subset of plasma (n = 5) and urine (n = 10) samples from a subset of participants in Study 1 underwent analysis using GC-MS and a chiral column, and the concentrations of l-βHB was calculated using the enzymatically determined concentration of d-βHB and the ratio of the d/l-βHB peaks obtained through GC-MS. Acetoacetate was assayed using an enzymatic method (Bergmeyer, 1965), and breath acetone was measured using GC-MS (Study 1) or with a handheld electrochemical device (Study 2; NTT DOCOMO, Japan) (Toyooka et al., 2013).

Ketosis supplements made in poor quality have proven to lead to side-effects such as constipation and increased levels of cholesterol and triglycerides in men. Women may also experience amenorrhea or other disruptions to the menstrual cycle. This is why it is essential to know what combination of compounds you are consuming while you are on this very strict diet. The wrong balance can mess with you in the long term and won't give you the results that you are looking for.


A growing number of people are giving it a try, thanks to exogenous ketone supplements that claim to launch your body into a state of ketosis within two and a half days—even if you’ve been living on pasta and cookies instead of following a low-carb diet. How can that be, though? And can that kind of rapid transformation actually be safe? Here’s what you should know.
Hi, I still a little confused about when or how to take this. I am trying to get adapted and minimize the flu. Is it most beneficial before eating, after eating, with food or in place of food? I have been keto in the past but this time I am not switching over to fat burning mode even though my macros are good. ( I am thinking it is just too many calories and carbs at this point but I get hungry!) Help please.
The effects of ketone drinks on endogenous insulin secretion are unclear. Whilst the small increase in plasma insulin after KE and KS drinks may have been due to the small quantity of dextrose in the diluent, it has been proposed that ketones could potentiate or even stimulate insulin secretion. Isolated pancreatic islets secreted insulin when stimulated by ketones at glucose concentrations of >5 mM (Biden and Taylor, 1983), and small amounts of insulin are secreted in vivo following exposure to exogenous ketones in animals (Madison et al., 1964; Miles et al., 1981). In response to an intra-venous 10 mM glucose clamp, ketone ester drinks increased glucose uptake and plasma insulin (Holdsworth et al., 2017). The increases in insulin with ketone drinks taken whilst fasted were small compared to the increases seen when the ketone ester drink was consumed with a meal and with consumption of a dextrose drink. Furthermore, the lack of difference in peak plasma insulin between the two latter conditions indicates that nutritional ketosis did not inhibit or increase normal carbohydrate induced insulin production.

The metabolic phenotype of endogenous ketosis is characterized by lowered blood glucose and elevated FFA concentrations, whereas both blood glucose and FFA are lowered in exogenous ketosis. During endogenous ketosis, low insulin and elevated cortisol increase adipose tissue lipolysis, with hepatic FFA supply being a key determinant of ketogenesis. Ketone bodies exert negative feedback on their own production by reducing hepatic FFA supply through βHB-mediated agonism of the PUMA-G receptor in adipose tissue, which suppresses lipolysis (Taggart et al., 2005). Exogenous ketones from either intravenous infusions (Balasse and Ooms, 1968; Mikkelsen et al., 2015) or ketone drinks, as studied here, inhibit adipose tissue lipolysis by the same mechanism, making the co-existence of low FFA and high βHB unique to exogenous ketosis.
Ketoacidosis is driven by a lack of insulin in the body.  Without insulin, blood sugar rises to high levels and stored fat streams from fat cells.  This excess amount of fat metabolism results in the production of abnormal quantities of ketones. The combination of high blood sugar and high ketone levels can upset the normal acid/base balance in the blood and become dangerous.  In order to reach a state of ketoacidosis, insulin levels must be so low that the regulation of blood sugar and fatty acid flow is impaired.

Of course, there may be some people who choose to take these supplements because they genuinely do feel they benefit from them. This is of course your choice and this article in no way aims to shame or criticize anybody. However, I do think that, for most people, eating a low-carb diet based on real foods is a lot more likely to be associated with the benefits that the supplements claim to provide than the supplements themselves.
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).
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.

Is keto safe? Putting yourself through this type of therapy isn't always easy and the process can take some getting used to, in particular during the initial stages when people must go through a period of fasting in order to raise ketone bodies faster. Of course, by doing this, it can put your body through a bit of shock and may cause a person to experience some short-term side effects until their bodies begin to adapt to the lifestyle and any BHB supplement they may be taking.
Good question. There have been many tests and studies that have been conducted to see if ketogenic supplements genuinely do work and many of these studies have shown that ketosis theories are correct. Adding ketones to your body and using fats as a resource of energy has some fantastic effects and if done right can help your body fight all sorts of ailments such as cancer, heart disease, diabetes and many other illnesses that can only be cured by chemical therapy. Keto therapy or nutritional ketosis is paving the way for more natural solutions, and it's a good thing that scientists have created these exogenous ketone supplements that help us induce more ketones in our body.
When taken as a drink, the ester bonds are broken down to release butanediol (BDO) and D-BHB into the blood. BDO is easily metabolized by the liver to form D-BHB. Then, both molecules of D-BHB reach the blood, as the liver is unable to use ketones. Consumption of this ketone ester elevates blood ketone levels in humans safely, with few side effects.10 HVMN Ketone is WADA compliant and safe to use in all levels of sports. It is designated as a foodstuff and is FDA GRAS. Each lot is 3rd party certified and batch tested for banned substances. 
The liver is always producing ketones to some small degree and they are always present in the bloodstream. Under normal dietary conditions, ketone concentrations are simply too low to be of any significant benefit. A ketogenic diet and exogenous ketone supplements will increase the amount of ketone in your body. The idea that  ketones are “toxic” is ridiculous. Ketones are a normal physiological substance that play many important roles in the human body.
Fortunately, you don’t need to be a dietary math savant to cash in on these rewards because the supplement eggheads took the liberty of creating exogenous ketones, which act as direct substitutes to the ones your body creates. Unlike other fat burners that give you the skits jitters, these are actually helping exercisers reach new personal bests while getting leaner, and are totally legal. Here’s what you need to know to get a slice of the action safely.
At baseline, 4 h after intragastric gavage, the elevation of blood ketones was inversely related to the reduction of blood glucose compared to controls following the administration of MCT (5 g/kg) (p = 0.008) and BMS + MCT (5 g/kg) (p = 0.039) . There was no significant correlation between blood ketone levels and blood glucose levels compared to controls for any other ketone supplemented group at baseline (Fig. 4a). At week 4, 4 h after intragastric gavage, there was a significant correlation between blood ketone levels and blood glucose levels compared to controls in MCT (10 g/kg) and BMS + MCT (10 g/kg) (p < 0.0001, p < 0.0001) (Fig. 4b).
Exercise or performing an extensive workout during the day is a perfect way to burn all those glycogen reserves in your body. Performing a HIIT or High Intensity Interval Training is a perfect type of exercise to do this. So, the next morning when you are awake, get set on an intense exercise session (remember, in the morning, not the afternoon). This will keep the cortisol level lowered during the evening when you wish to have some rest.
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.
BHB supplementation can drastically enhance your insulin sensitivity, resulting in better shuttling of blood glucose into cells.[10] With type-2 diabetes and insulin resistance becoming growing concerns, BHB supplementation may provide a promising alternative for healthy blood glucose regulation in the coming years.Even for everyday gym goers and fitness enthusiasts, increasing insulin sensitivity via BHB supplementation can be a great benefit as this puts your body in a better position for partitioning nutrients/carbohydrates to energetically demanding, glycolytic tissues, such as skeletal muscle.
Ketones are also a cleaner-burning fuel than carbs. They’re burned for energy in the mitochondria, and fewer free radicals (a highly-reactive, short-lived uncharged molecule) are generated when compared to burning glucose.15 What’s more, ketone molecules themselves cause a decrease in production of free radicals,21,22 while also increasing glutathione–a powerful antioxidant protecting against mitochondrial damage induced by free radicals.23
Ketogenesis is the metabolism of fatty acids by β-oxidation. 4 This process gives acetyl CoA which then leads to β-hydroxy-β-methyglutaryl-CoA (HMG-CoA) as seen below5. HMG-CoA converts into Acetoacetone which can switch back and forth to BHB. Acetoacetone to Acetone conversion is irreversible (on the left below). Acetoacetate and BHB (via acetoacetate) are used to produce energy when converted back into acetyl-CoA within a cell’s mitochondria whilst Acetone is excreted in the breath and urine.4
Recently, a friend of mine’s dad had high blood pressure. His doctor told him to stop consuming eggs and to avoid adding extra salt to his foods. That’s it. His recommendation was to rid a good, high-quality protein source, yet French fries, chicken nuggets, and even chicken noodle soup were all presumably okay. I’ll never understand some of these recommendations; nonetheless, they happen day in and day out, all over the world.
Getting into a state of ketosis normally involves eating a ketogenic diet consisting of around 80 percent fat, 15 percent protein, and 5 percent carbs. Over time, the body transitions from burning carbs for fuel to burning ketones—an alternative fuel source that the liver makes by breaking down fat, explains keto diet expert Amy Davis, RD, LDN. Since advocates say that ketosis can help you lose weight fast, think more clearly, and feel more energized, it’s tempting to try.
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!

First, there’s something unnatural about having elevated levels of ketones and glucose together. It’s really hard to make that happen using traditional whole foods. The closest natural approximation you could get to it would be the traditional coconut-rich diets of the Kitava people in the South Pacific, where the medium chain triglycerides (MCT) in the coconut fat increased ketone production alongside the carbs in the fruit and tubers they ate. They had excellent metabolic health, but they weren’t anywhere close to a ketogenic diet. Coconut fat isn’t as ketogenic as purified MCT oil, let alone exogenous ketones.

BS, KC, and PC designed the research studies. BS, PC, RE, SM, and PS carried out the studies. SH provided the gas analyser used in the study on behalf of NTT DOCOMO Inc. BS, MS, and SM analyzed the data and performed statistical analysis in collaboration with JM. BS wrote the paper with help from KC, PC, and OF. KC had primary responsibility for final content. All authors read and approved the final manuscript.


When the results for the supplement and the placebo were within 0.2 (either % or mmol/L) of each other, we classed the supplement as neither “better” nor “worse” than the placebo. We gave a “winning brand” sticker to the brand that scored highest against the placebo for each marker, but not for physical performance, since none of the supplements performed better than the placebo for that marker.
Compared to our other cellular gasoline (carbs), we can store an unlimited supply of energy from ketones in our body within our fat. When you’re reliant on carbohydrates, you’re forced to keep your tank partly full as we can only store just over 2,000 calories of glycogen from carbs. An empty carb tank results in carb-withdrawal symptoms from not being able to switch into a ketone or fat burning metabolism.
LDL is the lipoprotein particle that is most often associated with atherosclerosis. LDL particles exist in different sizes: large molecules (Pattern A) or small molecules (Pattern B). Recent studies have investigated the importance of LDL-particle type and size rather than total concentration as being the source for cardiovascular risk [56]. Patients whose LDL particles are predominantly small and dense (Pattern B) have a greater risk of cardiovascular disease (CVD). It is thought that small, dense LDL particles are more able to penetrate the endothelium and cause in damage and inflammation [82–85]. Volek et al. reported that the KD increased the pattern and volume of LDL particles, which is considered to reduce cardiovascular risk [73]. Though we did not show a significant effect on LDL levels for ketone supplements, future chronic feeding studies will investigate the effects of ketone supplementation on lipidomic profile and LDL particle type and size.

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