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.
For the ketone esters, on the other hand, repeated doses of 20-30 grams in any one day may be possible. Thus these products may be able to maintain a modest level of ketonemia without dietary carbohydrate restriction. Thus some of the cardiac and brain fueling benefits may follow, not to mention the epigenetic effects limiting oxidative stress and inflammation. But given the recent observation that administered ketone esters markedly reduce circulating free fatty acids (Myette-Cote 2018) — possibly due to an insulin-tropic effect or direct suppression of lipolysis (Taggart 2005) — their sustained use in people with underlying insulin resistance may compromise their long-term benefits by promoting weight gain unless combined with carbohydrate restriction.
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.
I’m often asked if it’s necessary to buy and use keto products like urine sticks. They’re small test strips that you dip in urine to see if your body is producing ketones (and therefore indicate if you’ve entered ketosis.) There's very little information on how to know that you are in ketosis other than using these ketones supplements because they are as accurate as can be in determining your current state. Outside of that, you can only guess if you are in it or not by your body's performance.

Those of you who have tried this form of weight loss before are probably more than aware of how hard it can be to first get your body to adapt to such a dramatic change in your daily intake of food, let alone without the help of a single exogenous ketone supplement. And the situation isn’t made any easier if you use a poor quality ketosis supplement because the wrong ketone product may actually do you more harm than good.
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).

Despite the recent growth of the ketone salt market, there is very little published work analyzing the effects of these products on any biomarkers or performance measurements in humans. Several studies have been carried out in rats,6,7 with blood BHB levels being relatively low (<0.5 mM) post-consumption of salt drinks. In humans, ketone salts provided peak D-BHB levels of 1 mM, whereas the same amount of BHB in a ketone ester (BD-BHB) raised blood BHB to 2.8 mM.5

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.)
I I started off interested in this product because it was cheaper than another popular Keto drink that I have known people to loose weight on. I have been drinking this about 2 weeks every morning on my way to work and I have never gotten the shakes jitters or felt a crash. I have also noticed my clothes to fit more comfortably as well. I do feel somewhat better taking this product I don’t know if it’s a mental thing but I will definitely purchase more and keep drinking it to hopefully see more difference
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.

A recent study, Ketone Bodies Mimic the Life Span Extending Properties of Caloric Restriction, showed the effects of exogenous ketones on longevity (ketone esters, specifically) and concluded that ketones should be labeled as an “anti-aging” compound (suggesting that the real reason caloric restriction has been shown to extend life span is actually due to resulting ketosis).
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.
In a keto-adapted individual where ketone metabolism is brisk with up to 100 grams or more being oxidized (i.e., ‘burned for energy’) daily, the small amount lost in breath and urine as acetone is minor. But because this breakdown occurs spontaneously without needing the help of enzymes, it also happens to AcAc in a stored beverage or food (even in an air-tight container), making the shelf-life of AcAc-containing products problematic. Thus all current ketone supplements consist of BOHB in some form rather than the naturally occurring mix of BOHB and AcAc produced by the liver.
Ketōnd discloses everything right there on their label so you know EXACTLY what you are getting. I have tried numerous ketone supplements and I can tell you I was not surprised that Ketōnd gave me more energy, mental clarity and improved my training more than any other ketone supplement. But take a few minutes and look at the product comparisons. You will see that Ketōnd has more ketones per serving and comes in at a fraction of the cost of every other product out there.
The year before last I somehow full on Rocked at the keto diet lost 100lb, and was taking adderall. I am transitioning back into it again also back on the adderall, but i seem to have no energy and last time my doc did my blood work i was only 16% hydrated. Obviously it’s a huge problem for me, staying hydrated and trying to lift the fogginess. I am type 2 diabetic and my doctor is on board with me trying all to keep my sugars down YEAH!!! I have never tried any exogenous product. My body seems to not absorb much vitamins. Can anyone make a or any suggestion to me as to how to get this under control?
Over five visits, participants (n = 16) consumed either 4.4−1 of βHB (2.2−1 or 395 mg/kg of KE; 1 mole of KE delivered 2 moles of d-βHB equivalents): twice whilst fasted, and twice following a standardized meal, or an isocaloric dextrose drink without a meal. To improve palatability, drinks were diluted to 500 ml with a commercially available, citrus flavored drink containing 65 kCal (5 g of carbohydrate) (Glaceau, UK). The dextrose drink was taste-matched using a bitterness additive (Symrise, Holzminden, Germany). The standard meal consisted of porridge oats (54 g), semi-skimmed milk (360 ml) and banana (120 g), giving 600 kCal per person, with a macronutrient ratio of Carbohydrate: Protein: Fat of 2:1:1.
I don’t think we even need a drumroll here… Based on my background research into ketone-supplement companies, the survey of Diet Doctor users and the experiment itself, we cannot recommend taking these supplements. I can personally think of many more beneficial ways to invest money in my health, such as buying grass-fed meat and organic vegetables, or even buying a bicycle and riding it outside in the sunshine.
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.
Another source of the D-BOHB isomer is an evolutionarily ancient energy source for micro-organisms. Poly-BOHB is a long chain of D-BOHB molecules strung end-to-end. It functions in many single-cell organisms as a concentrated energy source similar to glycogen in mammals, but whereas glycogen breakdown releases individual glucose molecules, poly-BOHB hydrolysis releases single D-BOHB molecules.
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.
Possible GI distress (flatulence) at exceptionally high doses –  In the studies referenced in this article, exogenous ketones taken in large doses occasionally resulted in GI distress, especially flatulence. However, the cause of this is hypothesized to be due to the fact that ketones were mixed in a milky fluid that wasn’t very palatable. If you’re taking a nominal dose of exogenous ketones the likelihood of GI distress is rather low. Moreover, if some GI distress is prevalent, it should improve as you become accustomed to taking ketones.
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.

Safety Warning — KEEP OUT OF REACH OF CHILDERN. This product is only intended to be consumed by healthy adults 18 years of age or older. Do not use if you are pregnant, trying to become pregnant, breast feeding, have known medical conditions (including but not limited to diabetes, kidney, heart, or liver disease) or are taking prescription or OTC medication(s). Consult with your health care practitioner before using this product These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. —

In Summary, I think it’s important to do your own research and draw your own conclusion about the long term risks of ketosis. For some people, a ketogenic diet may be a necessity given their health situation. For those of us who do not suffer from such health conditions I would present the question ‘why do you want to follow a strict ketogenic diet for an extended period’, and then follow this up with ‘are the potential risks and sacrifices worth the benefits?’

The benefits of intermittent fasting translate to untrained overweight and obese individuals as well. One study published in Obesity Reviews found that eating fewer calories is effective for fat loss, but it does come with some muscle loss. However, if the subjects fasted for 24 hours and ate as much as they wanted on the next day for a period of 12 weeks, they lost significantly less muscle mass.
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.
Exogenous ketones are ketones that come in the form of a powder that you mix with water to drink them. Exogenous ketones are controversial in the keto world. The problem is the marketing of them have made some people believe that all they have to do is use this product to get into ketosis. If your blood glucose is too high your body will not use the ketones and they will go to waste.
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).
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.

MCT oil has recently been used to induce nutritional ketosis although it produces dose-dependent gastrointestinal (GI) side effects in humans that limit the potential for its use to significantly elevate ketones (>0.5 mM). Despite these limitations, Azzam and colleagues published a case report in which a 43-year-old-man had a significant decrease in seizure frequency after supplementing his diet with 4 tablespoons of MCT oil twice daily [96]. An attempt to increase his dosage to 5 tablespoons twice daily was halted by severe GI intolerance. Henderson et al. observed that 20 % of patients reported GI side effects with a 20 g dose of ketogenic agent AC-1202 in a double blind trial in mild to moderate Alzheimer’s patients [24]. We visually observed similar gastrointestinal side effects (loose stools) in the rats treated with MCT oil in our study. Rats were closely monitored to avoid dehydration, and gastric motility returned to normal between 12–24 h. Interestingly, the BMS + MCT supplement elevated βHB similarly to MCT oil alone, without causing the adverse gastrointestinal effects seen in MCT-supplemented rats. However, this could be due to the fact in a 10 g/kg dose of BMS + MCT, only 5 g/kg is MCT alone, which is less than the 10 g/kg dose that elicits the GI side effects. This suggests that this novel combination may provide a more useful therapeutic option than MCT oil alone, which is limited in its ability to elevate ketones in humans.
In conclusion, drinks containing exogenous ketones, in either ester or salt form, can raise concentrations of blood βHB in humans, although elevation of l-βHB lasts longer after racemic KS consumption. Both KE and KS drinks mildly altered acid-base balance. Exogenous ketones lowered blood glucose and lipids without inhibiting endogenous insulin secretion. The KE delivered highly repeatable blood concentrations of d-βHB, although ketosis was decreased by a meal. Uptake and elimination of d-βHB were similar when several drinks were consumed in succession. The dietary KE could maintain ketosis using drinks taken regularly around a normal meal pattern, or using a continuous infusion via a nasogastric tube. Therefore, ketone drinks are a viable and practical alternative to dietary strategies to achieve ketosis.
Great question. We can’t see any reason this can’t be a part of a successful weight loss program on the ketogenic diet. In the morning with coffee is a very popular way to raise ketone levels in the morning. See if you are on pace with your goals and perhaps try a week with a different breakfast to see what feels best. Also – new article might be helpful here too: Good luck! 🙂
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 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.
Neuroprotection: As humans age, the brain becomes more susceptible to neurodegeneration and subsequent conditions such as Alzheimer’s and Parkinson’s disease. Exogenous ketone supplementation appears to ameliorate the typical decline in cognitive function that comes with aging. The likely mechanism for this neuroprotective property is that ketone bodies reduce the inflammation and hyperexcitability that is normally exhibited as glucose metabolism declines in the brain.18, 19
There is so much talk about the benefits of a ketogenic diet and its ability to improve fat burning, brain health, energy and anti-aging.  The main units of energy on a ketogenic diet are ketone bodies, of which beta hydroxybutyrate (BHB) is the main player!  This article will go over the health benefits of BHB and exogenous ketones. Additionally, this article will cover strategies on using exogenous ketones in your daily life.
Halitosis (bad breath) – If you’re on a ketogenic diet you are probably aware that as the body starts to metabolize fat, ketones can cause poor breath. There is very little one can do about this, it’s just the nature of the beast. Unfortunately, this can also arise when using exogenous ketones, but it’s not as lasting as when on a ketogenic diet. Chewing gum or mints is about the best option if it becomes a noticeable issue. This maybe caused by over consumption of the ketone supplement, tailoring the quantity consumed may prevent excess BHB being converted to acetone, which is likely excreted by the lungs.
You may wonder why we are emphasizing on using these specific oils. Well, this is because the extra virgin oil is an unprocessed form, and contains lauric acid that is antimicrobial in nature and is good for brain health. (This is the same lauric acid that is naturally found in breast milk as well.) Its antibacterial property also indirectly supports the growth of Candida that keep your gut healthy.
There is one viable explanation for consuming ketones. If you're in a calorie or carb-restricted state, then maybe during a workout it would make sense. But even then, that really only applies to endurance activities, since it has more to do with enhancing aerobic performance (where oxygen is required), than it does with enhancing high-intensity efforts (where it's not).
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?

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