We tested the effects of 28-day administration of five ketone supplements on blood glucose, ketones, and lipids in male Sprague–Dawley rats. The supplements included: 1,3-butanediol (BD), a sodium/potassium β-hydroxybutyrate (βHB) mineral salt (BMS), medium chain triglyceride oil (MCT), BMS + MCT 1:1 mixture, and 1,3 butanediol acetoacetate diester (KE). Rats received a daily 5–10 g/kg dose of their respective ketone supplement via intragastric gavage during treatment. Weekly whole blood samples were taken for analysis of glucose and βHB at baseline and, 0.5, 1, 4, 8, and 12 h post-gavage, or until βHB returned to baseline. At 28 days, triglycerides, total cholesterol and high-density lipoprotein (HDL) were measured.
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
Glucose and BHB went down slightly throughout the effort and RQ fell, implying a high rate of fat oxidation. We can calculate fat oxidation from these data. Energy expenditure (EE), in kcal/min, can be derived from the VO2 and VCO2 data and the Weir equation. For this effort, EE was 14.66 kcal/min; RQ gives us a good representation of how much of the energy used during the exercise bout was derived from FFA vs. glucose—in this case about 87% FFA and 13% glucose. So fat oxidation was approximately 12.7 kcal/min or 1.41 g/min. It’s worth pointing out that “traditional” sports physiology preaches that fat oxidation peaks in a well-trained athlete at about 1 g/min. Clearly this is context limited (i.e., only true, if true at all, in athletes on high carb diets with high RQ). I’ve done several tests on myself to see how high I could push fat oxidation rate. So far my max is about 1.6 g/min. This suggests to me that very elite athletes (which I am not) who are highly fat adapted could approach 2 g/min of fat oxidation. Jeff Volek has done testing on elites and by personal communication he has recorded levels at 1.81 g/min. A very close friend of mine is contemplating a run at the 24 hour world record (cycling). I think it’s likely we’ll be able to get him to 2 g/min of fat oxidation on the correct diet.
The USDA guidelines recommend less than 2400 mg of sodium per day for healthy adults, and 1500 mg or less for individuals over the age of 50 or at risk for hypertension[2]. For reference, 2300 mg of sodium is the equivalent of about one teaspoon of salt.  Even though these recommendations are promoted by the American Heart Associated and other health-related organizations, recent research has claimed that there is simply not enough evidence to support these guidelines[5]. Worldwide 24-hour urinary sodium excretion data suggest that the normal range is actually 2500-5000 mg per day, which is what most of us consume daily[6]. Additionally, people with high activity levels or chronically low blood pressure may require more sodium than the average person.
All data are presented as the mean ± standard deviation (SD). Data analysis was performed using GraphPad PRISM™ version 6.0a and IBM SPSS Statistics 22.0. Results were considered significant when p < 0.05. Triglyceride and lipoprotein profile data were analyzed using One-Way ANOVA. Blood ketone and blood glucose were compared to control at the applicable time points using a Two-Way ANOVA. Correlation between blood βHB and glucose levels in ketone supplemented rats was compared to controls using ANCOVA analysis. Organ and body weights were analyzed using One-Way ANOVA. Basal blood ketone and blood glucose levels were analyzed using Two-Way ANOVA. All mean comparisons were carried out using Tukey’s multiple comparisons post-hoc test.
The best time to start a one day fast is in the evening (neither morning nor the night) – preferably, around 6 pm. It won’t make you lose your vital energy during the daytime workouts, nor does it let you sleep with undigested foodstuff in your stomach. Taking late meals and sleeping with undigested food doesn’t allow your body to rest. So the natural healing mechanism of your body fails during the sleep time as the entire resources are busy digesting your food.
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?
The other potentially important distinction between nutritional ketosis and chemically-induced ketosis is the potential metabolic role played by liver AcAc production and redox status. Although the ratio of BOHB to AcAc in venous blood is typically 80% to 20%, classic studies by Cahill (1975) have observed important hepatic vein and peripheral arterio-venous gradients for this ratio in keto-adapted patients. What these observations imply is that the liver produces a higher proportion of AcAc than is found in the peripheral blood, and that this is due to uptake of AcAc in peripheral cells (principally muscle) with re-release as BOHB. In the process, the reduction of AcAc to BOHB produces NAD+, which is beneficial to mitochondrial redox state and mitochondrial function (Verdin 2015, Newman 2017).
Exogenous ketones are not a shortcut to nutritional ketosis, but they do give your body a break from full-time carb usage. They are a tool you can use to get into ketosis if your lifestyle makes it too difficult to do so without them. And they’re also a good way to get an increased edge for those who are very on top of their nutrition and performance.

Even Ben Greenfield Has Thyroid Problems While In Ketosis - “Ben describes one of the main side effects that he encountered being severe hypothyroidism… manifesting as severe sensitivity to cold, poor libido, and poor overall energy. The way they treated this was to eat a lot of liver, desiccated thyroid, and sweetbreads which seemed to fix things for him.”
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].
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.
Once the body is able to generate energy with the help of exogenous ketones which are present in the bloodstream, it would start looking for other sources of ketones. This would encourage the body to tap into the vast reserve of fat which is accumulated in the body. Thus, the process of ketosis is accelerated when you consume extra exogenous ketones. This also leads to quicker weight loss and the body entering ketosis faster.

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.


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.
Ketogenic diets have been successfully used to treat diseases that have an underlying metabolic component, effectively decreasing seizures in recalcitrant pediatric epilepsy (Kossoff et al., 2003), lowering blood glucose concentrations in type 2 diabetes mellitus (Feinman et al., 2015) and aiding weight-loss (Bueno et al., 2013). Emerging evidence supports several clinical uses of ketogenic diets, for example in neurodegenerative diseases (Vanitallie et al., 2005), specific genetic disorders of metabolism (Veech, 2004) and as an adjunct to cancer therapy (Nebeling et al., 1995). Ketone bodies themselves may underlie the efficacy of the ketogenic diet, either through their role as a respiratory fuel, by altering the use of carbohydrate, protein and lipids (Thompson and Wu, 1991; Cox et al., 2016), or through other extra- and intracellular signaling effects (Newman and Verdin, 2014). Furthermore, ketone metabolism may offer a strategy to improve endurance performance and recovery from exercise (Cox et al., 2016; Evans et al., 2017; Holdsworth et al., 2017; Vandoorne et al., 2017). However, achieving compliance to a ketogenic diet can be difficult for both patients and athletes and may have undesirable side effects, such as gastro-intestinal upset (Cai et al., 2017), dyslipidemia (Kwiterovich et al., 2003) or decreased exercise “efficiency” (Edwards et al., 2011; Burke et al., 2016). Hence, alternative methods to raise blood ketone concentrations have been sought to provide the benefits of a ketogenic diet with no other dietary changes.
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.
Interestingly, poly-BOHB has recently been reported to have important roles in mammalian mitochondrial membranes, cell membrane calcium channels, and in exotic functions like protein folding (Dedkova 2014). It exists in a variety of chain lengths, ranging from short to very long. It is not clear if humans can digest and use poly-BOHB consumed in the diet, but in animals, poly-BOHB appears to have probiotic and bowel protective functions. This is a rapidly evolving topic that we will be watching closely.
Blood d-βHB, pH, bicarbonate (HCO3-) and electrolytes measured in arterialized blood samples from resting subjects (n = 7) following a ketone ester or salt drink containing 3.2 mmol.kg−1 of βHB. Shaded areas represent the normal range. Values are means ± SEM. (A) Venous blood d-βHB. (B) Arterialized blood pH. (C) Blood bicarbonate. (D) Blood potassium. (E) Blood sodium. (F) Blood chloride. †p < 0.05 difference between KE and KS, *p < 0.05 difference from baseline value.
My two cents: I wouldn’t take ketone supps if not on some sort of low(ish) carb diet because the idea of high levels of BOTH fuels (ie, ketones AND glucose) doesn’t seem physiologically appropriate… more like a recipe for disaster, and by “disaster,” I mean “out-of-control production of Reactive Oxygen Species” — this might not matter if you’re an athlete looking for a quick performance boost, because the fuels are going to be cleared rather quickly… not so much if you’re a desk jockey.

I heard a rep from Perfect Keto on a podcast and your Exogenous Ketones. I ordered and received it the other day. I see from this article that I should not do a full scoop at once, but break it up in a day. Good to know. I had about a half scoop before I worked out this morning and could tell I had more energy. Loved that. Just curious….any ideas how long it will take me to get back into ketosis and fat burning?? (I know it depends on what I eat, but a general idea that I promise not to hold you too! (I’m actually missing having ‘keto breath!)


Exogenous ketones have a wide range of benefits that can enhance your fat-burning lifestyle. I personally use them daily as a strategy to heighten my mental performance and give my workouts an extra boost. For these purposes, I have also found it logical to combine exogenous ketones with other known health and performance boosting agents such as branched-chain amino acids and medicinal mushrooms.
Satiety decreased in both cases, slightly less with the supplements than with the placebo: participants reported feeling less hungry after taking the supplements than after taking the placebo. However, we are doubtful whether this would be enough of a difference to impact food intake and therefore induce weight loss indirectly, compared to not taking a supplement at all. Especially since, as noted before, BHB switches off lipolysis.

Beta hydroxybutyrate floats around in your blood, and importantly, can cross different barriers to be able to be turned into energy at all times. One of the most important areas where this happens is in the brain. The blood-brain barrier (BBB) is usually a very tightly regulated interface that doesn’t allow the transfer of many molecules, but since BHB is such a rock star and so hydrophilic, your brain knows to let it in so it can bring energy to the party at any time. This is one of the main reasons why increased levels of ketosis lead to improved mental clarity, focus and reduction in neurodegenerative diseases.


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].
Appetite suppression: Appetite was measured in 10 males and 5 females after consuming a ketone ester (KE) or a dextrose (DEXT) drink . Desire to eat and perception of hunger dropped after both drinks, but the KE was 50% more effective for 1.5-4hrs. Insulin levels rose for both drinks but were 3x less with the KE drink after 30mins (Fig 2). The hunger hormone, ghrelin, was significantly lower between 2 to 4 hours after drinking the KE (Fig 2). In conclusion Ketone esters delay the onset of hunger and lower the desire to eat. 8
The culprit is often restaurant meals or other meals where the nutrition facts are not available with the food itself. Such “ignorance is bliss” situations allow us to avoid dealing with daunting numbers. Many people don’t hesitate to stop and enjoy a meal at a restaurant, but they freak out when they actually see the numbers on a label.  By now, we all know that opting for fatty meat with a side of veggies cooked in butter isn’t that bad after all.  It turns out that what you thought to be the safe, “healthy,” doctor-approved choice might not always be what you think it is.

I started this website because it was hard to find trustworthy, evidence-based information about the ketogenic diet. Information that was published and peer reviewed by respected scientific journals. After years of research, I'm sure you'll achieve great results in a healthy way following my advice. I do my best to translate scientific research jargon into plain English. Remember, it's always a good idea to consult a doctor before starting a new diet!

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.
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.
Several studies have investigated the safety and efficacy of ketone supplements for disease states such as AD and Parkinson’s disease, and well as for parenteral nutrition [40, 48–50, 100–103]. Our research demonstrates that several forms of dietary ketone supplementation can effectively elevate blood ketone levels and achieve deleted: therapeutic nutritional ketosis without the need for dietary carbohydrate restriction. We also demonstrated that ketosis achieved with exogenous ketone supplementation can reduce blood glucose, and this is inversely associated with the blood ketone levels. Although preliminary results are encouraging, further studies are needed to determine if oral ketone supplementation can produce the same therapeutic benefits as the classic KD in the broad-spectrum of KD-responsive disease states . Additionally, further experiments need to be conducted to see if the exogenous ketone supplementation affects the same physiological features as the KD (i.e. ROS, inflammation, ATP production). Ketone supplementation could be used as an alternative method for inducing ketosis in patients uninterested in attempting the KD or those who have previously had difficulty implementing the KD because of palatability issues, gall bladder removal, liver abnormalities, or intolerance to fat. Additional experiments should be conducted to see if ketone supplementation could be used in conjunction with the KD to assist and ease the transition to nutrition ketosis and enhance the speed of keto-adaptation. In this study we have demonstrated the ability of several ketone supplements to elevate blood ketone levels, providing multiple options to induce therapeutic ketosis based on patient need. Though additional studies are needed to determine the therapeutic potential of ketone supplementation, many patients that previously were unable to benefit from the KD may now have an alternate method of achieving therapeutic ketosis. Ketone supplementation may also represent a means to further augment ketonemia in those responsive to therapeutic ketosis, especially in those individuals where maintaining low glucose is important.
If you are trying to lose weight, following a ketogenic diet can help you burn fat fast. However, trying to get into ketosis can be a frustrating experience. Am I eating too many carbs, not enough fat, too much protein? Getting into ketosis usually takes 3 to 5 days at least, and can take people up to two weeks. Recently I have discovered a simple and easy way to get into ketosis very quickly. I went from eating lots of carbs one night, to in ketosis 24 hours later.
Ketones naturally exist in the body, being created during the process of fat metabolism and are therefore safe to consume even during pregnancy or breastfeeding. Supplements such as Ketologie’s PROBHB are simply providing ketones from an external (exogenous means literally ‘outside of the body’) source. However, if you suffer from any medical conditions and/or are on medications, it is always advisable to consult your health care provider prior to starting any new nutritional or dietary supplement.  
Divided attention involves processing multiple streams of information. The game involves observing a pond full of koi fish swimming around, and tapping each fish only once to feed it a pellet without feeding any fish previously fed. Each level adds more fish with increasing speed and redirection. It’s similar to pretending to be an air-traffic controller who must keep track of every plane on their radar.
While exogenous ketones (EK) are a newer supplement, having entered the market for consumers in just the past few years, scientists have been synthesizing ketone bodies in a lab since the 1960’s. They were useful for scientists studying their use for specific disease conditions, most notably childhood seizure disorders, though they were prohibitively expensive for consumers (1, 2).
Effects of ketone supplementation on triglycerides and lipoproteins: Ketone supplementation causes little change in triglycerides and lipoproteins over a 4-week study. Graphs show concentrations at 4-weeks of total cholesterol (a), Triglycerides (b), LDL (c), and HDL (d). MCT supplemented rats had signfiicantly reduced concentration of HDL blood levels compared to control (p < 0.001) (b). One-Way ANOVA with Tukey’s post hoc test, results considered significant if p < 0.05. Error bars represent mean (SD)

Unless otherwise stated, statistical analysis was conducted using Prism 6™ software. Values, expressed as means ± SEM, were considered significantly different at p < 0.05. Initial tests were undertaken to ensure that normality and sphericity assumptions were not violated. Subsequently, either one or two way repeated measures ANOVA, or Freidman's test with post-hoc Tukey or Dunnet's correction were performed, to compare changing concentrations of substrates, electrolytes, pH, insulin, breath and urinary βHB: both over time and between study interventions. In Study 2, data from each of the two study visits in each condition (fed and fasted) completed by an individual were included in the analysis.
“Consumption of KETO//OS before exercise can result in significant decreases in oxygen demand and increases in performance. We recommend 30 minutes before a workout. Note: Pre-workout use is recommended after building up to a full dose. The best way to maximize energy, appetite control and sustain energy is to take KETO//OS first thing in morning. To maximize benefits, build up to 1 serving 3 times daily – morning, afternoon and early evening. May be used with carbohydrate supplements if desired or by itself as a non-carb, highly efficient energy source.”

EK use can be compared to the nootropics that have been developed for optimizing focus, memory creation, and faster cognitive performance. While you may not notice this effect on a minute to minute basis if you keep a journal of “forgetful moments” you’ll find that you have fewer of them as time goes on. You’ll also find that you’re able to come up with better ideas, and your workflow is more efficient through the day (10, 11).


I eat one meal a day during a one-hour window and fast 23 or more hours every day. I want to use your ketones to get back into ketosis faster after that meal. Will that work? I am confused, because say at the end of my hour eating window I drink your ketones, sure there are lots of ketones suddenly in my body but I also have a big meal in my stomach. My body has to digest and use that food energy, so how do exogenous ketones help me in that case?
Hello, I’ve tried several different Exogenous Ketone supplements and I believe Perfect Keto may be the best I’ve tried. Thus far I’ve had Keto//OS from Pruvitt, Kegenix, KetoForce, KetoCaNa and Ketond. Out of all these brands both Perfect Keto and Ketond have been the products that hack me into Ketosis quick and for longer periods of time. Perfect Keto is less expensive that Ketones from Pruvitt mainly because Pruvitt and their Network Marketing is all about making money. The flavors of Perfect Keto are much better than Pruvitt.
Most of the information regarding the effects of ketosis come from studies on the ketogenic diet, wherein ketones are made by the liver and become a major fuel source for the body. The ketogenic diet is currently under investigation for its potential therapeutic effects in a number of healthy and disease states. More recently, studies are beginning to reveal that many of the effects observed with the ketogenic diet are mechanistically attributable to ketones, which is a primary reason that exogenous ketones are being developed and studied. However, because they are such a new technology, there’s not a lot of data on exogenous ketones themselves. In a few pre-clinical studies, exogenous ketones have mimicked the therapeutic effects of the ketogenic diet”
I heard a rep from Perfect Keto on a podcast and your Exogenous Ketones. I ordered and received it the other day. I see from this article that I should not do a full scoop at once, but break it up in a day. Good to know. I had about a half scoop before I worked out this morning and could tell I had more energy. Loved that. Just curious….any ideas how long it will take me to get back into ketosis and fat burning?? (I know it depends on what I eat, but a general idea that I promise not to hold you too! (I’m actually missing having ‘keto breath!)
Once you hit the bed, the adrenal glands will be off and the body will enter the anabolic stage. This will allow your body to repair itself. If you stay up late for long periods of time your body will enter the hypercatabolic state. In this state, the levels of cortisol in your body increase significantly. This also increases the insulin resistance of the body which would again increase the blood sugar levels.

The same question posed in a different way can be, what’s better, getting protein from powder or from a grass-fed steak or wild salmon? Omega-3 from supplements or from a variety of healthy wild fish? Just like with health supplements where you consume an isolated nutrient instead of the whole food where it comes from, if it’s possible to get what you need from whole food or nutrition, then that’s probably the best choice.
If you have been reading the science behind the ketogenic diet, you know there can be a lot of benefits associated with choosing this way of eating. There is usually a transition period from when someone chooses to go on a ketogenic diet and implements the changes to their menu to when they actually get into ketosis and are able to produce and burn ketones for fuel.
Anti-cancer potential: Recent research suggests that ketogenic diets can blunt malignant tumor growth.[5] This is due to the fact cancer cells can’t metabolize ketones effectively to nourish their growth and replication. Astonishingly, one study found that supplementing with BHB salts increases odds of survival in mice with systemic cancer by up to 70% in comparison to mice who didn’t receive exogenous ketones.[6]
Why is this desirable? Think about energy production in your body much like macro energy consumption on a planetary level. Coal is gross and dirty and messes tons of different things up. You need to continue to burn it to get energy. Solar power is free, clean and pretty much limitless. This is pretty much the same story when you are burning carbs (coal) versus fats (solar) for energy.

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Medical Disclaimer: The material on this site is provided for informational purposes only and is not medical advice. Always consult your physician before beginning any diet or exercise program.

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