Animal procedures were performed in accordance with the University of South Florida Institutional Animal Care and Use Committee (IACUC) guidelines (Protocol #0006R). Juvenile male Sprague–Dawley rats (275–325 g, Harlan Laboratories) were randomly assigned to one of six study groups: control (water, n = 11), BD (n = 11), KE (n = 11), MCT (n = 10), BMS (n = 11), or BMS + MCT (n = 12). Caloric density of standard rodent chow and dose of ketone supplements are listed in Table 1. On days 1–14, rats received a 5 g/kg body weight dose of their respective treatments via intragastric gavage. Dosage was increased to 10 g/kg body weight for the second half of the study (days 15–28) for all groups except BD and KE to prevent excessive hyperketonemia (ketoacidosis). Each daily dose of BMS would equal ~1000–1500 mg of βHB, depending on the weight of the animal. Intragastric gavage was performed at the same time daily, and animals had ad libitum access to standard rodent chow 2018 (Harlan Teklad) for the duration of the study. The macronutrient ratio the standard rodent chow was 62.2, 23.8 and 14 % of carbohydrates, protein and fat respectively.
It comes in a small bottle that usually contains 50-100 strips depending on the type you choose. It’s very thin, and on one end there’s a small square of paper (this is the end you dip in the urine). If there are ketones in your urine, the little paper will change color. The darker it is (light pink up to a purple color) the more it is in your urine. On the bottle, there’s a picture you compare the color of the paper with that can be a very good indication of your current ketone state. 
In a subset of participants (n = 7) the effect of 3.2 mmol.kg−1 of βHB as KE and KS on blood pH and electrolytes after ketone drinks was investigated. Blood d-βHB kinetics were similar to those in the initial experiment (Figure ​(Figure3A).3A). After 60 min, blood pH declined from 7.41 to 7.31 following a KE drink (p < 0.001, Figure ​Figure3B).3B). Bicarbonate fell significantly from 23.6 ± 0.7 to 17.0 ± 0.8 mM following KE drinks (p < 0.001), but remained within the normal range (Figure 3C). Both ketone drinks significantly decreased blood potassium concentrations by 0.7 mM (both drinks p < 0.05, Figure 3D) and increased sodium and chloride concentrations (Sodium: both drinks p < 0.05, Chloride: KE = p < 0.05, KS = p < 0.005, Figures 3E,F).
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 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.
88. Yost T, Erskine J, Gregg T, Podlecki D, Brass E, Eckel R. Dietary substitution of medium chain triglycerides in subjects with non-insulin-dependent diabetes mellitus in an ambulatory setting: impact on glycemic control and insulin-mediated glucose metabolism. J Am Coll Nutr. 1994;13(6):615–22. doi: 10.1080/07315724.1994.10718457. [PubMed] [CrossRef]

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.
Thank you, Mark! I am an ME/CFS patient, and I have improved quite a bit on a ketogenic diet, which I have been following for the past 3 months. I am slowly losing weight (much needed) and I wondered, does using exogenous ketones inhibit fat loss? I’m trying to balance the benefits of continuing weight loss with benefits in dealing with ME/CFS symptoms. Thank you for any info you can offer!
If you ever wondered how to get into ketosis, know that getting into ketosis is easy and completely natural for your body. All you need to do is follow the ketogenic diet which involves cutting down on carbs and eating lots of fat. You can also get into ketosis through fasting. But if your goal is weight-loss and reaping all the benefits of ketosis, the ketogenic diet is a must.
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.

Again, there are very interesting animal studies plus some single case reports and small uncontrolled trials of humans with neurodegenerative disease and cancer given ketogenic diets and/or exogenous ketones (Murray 2016, Poff 2015, Roberts 2017, Newport 2015, Cunnane 2016). In some cases where the patient does not have the cognitive resources to comply with a well-formulated ketogenic diet, or where target blood levels of BOHB that work in animals are hard to achieve in humans by diet alone, supplemental ketones may have an important role to play in the prevention, management, or reversal of these disease categories.

 Effects of beta-hydroxybutyrate on cognition in memory-impaired adults. – Glucose is the brain’s principal energy substrate. In Alzheimer’s disease (AD), there appears to be a pathological decrease in the brain’s ability to use glucose. Neurobiological evidence suggests that ketone bodies are an effective alternative energy substrate for the brain. Elevation of plasma ketone body levels through an oral dose of medium chain triglycerides (MCTs) may improve cognitive functioning in older adults with memory disorders. On separate days, 20 subjects with AD or mild cognitive impairment consumed a drink containing emulsified MCTs or placebo. Significant increases in levels of the ketone body beta-hydroxybutyrate (beta-OHB) were observed 90 min after treatment (P=0.007) when cognitive tests were administered. beta-OHB elevations were moderated by apolipoprotein E (APOE) genotype (P=0.036). For 4+ subjects, beta-OHB levels continued to rise between the 90 and 120 min blood draws in the treatment condition, while the beta-OHB levels of 4- subjects held constant (P<0.009). On cognitive testing, MCT treatment facilitated performance on the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-cog) for 4- subjects, but not for 4+ subjects (P=0.04). Higher ketone values were associated with greater improvement in paragraph recall with MCT treatment relative to placebo across all subjects (P=0.02). Additional research is warranted to determine the therapeutic benefits of MCTs for patients with AD and how APOE-4 status may mediate beta-OHB efficacy.


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.)
About the only other negative thing I have heard about the company is that if you are placing an order over the phone, they don’t answer too many questions. Instead, they refer you to their website. Their website is very informative and pretty much answers any question you might have. Ketōnd has gotten too popular, and the company had to hire an answering service like they are selling George Forman Grills or something to take calls from around the world 24-7. I know it’s popular all over Europe and Australia too. My buddies that compete in Crossfit swear that this stuff gives them the edge.

Calories do matter, even on a ketogenic diet. If you consume more calories than your body uses, you’re going to gain weight. Period. What you mean to say is that it’s very difficult to eat your entire day’s worth of calories on a ketogenic diet because fats are so satiating. This distinction is important to keep in mind for those who generally have a voracious appetite (like me).
Follow our simple tips to get into ketosis and speed up the process. Our tips are scientifically-proven to work and are completely safe for everyone. If you need more guidance to achieve ketosis safely and effectively, enroll in our free Ketocademy course. The course will teach you everything there is to know about entering ketosis in less than 3 hours. Try it out today!

If given all as a single salt, 50 grams per day of BOHB would mandate daily intakes of 5.8 g Mg++, 9.6 g Ca++, 11.0 g Na+, or 18.8 g K+. Even if divided up carefully as a mixture of these various salts, it would be problematic getting past 30 grams per day of BOHB intake. And again, most of the currently marketed ketone salt formulations are made with a mix of the D- and L-isomers of BOHB, so the actual delivered dose of the more desirable D-isomer is considerably less. The other concern with the salt formulations is that, as the salts of weak acids, they have an alkalinizing metabolic effect that might have a modest but cumulative effect on blood pH and renal function.
1 – If you’re not looking to spend a ton of money up front while testing the ketogenic lifestyle – no problem! For starters, you need to try nutritional ketosis before ever worrying about exogenous supplementation. If you don’t like the diet, it’s not going to matter how many supplements you by. However, if you want to get an idea if exogenous ketones are for you, we would suggest a simple MCT Oil, or a great beginner exo keto like Keto CaNa.
Hypoglycemia: why not to be concerned – Taking exogenous ketones can drive blood glucose levels quite low, but you are not likely to feel the typical symptoms of hypoglycemia. This is because when ketone levels are high enough, they dominate as fuel in the brain; hence, you will feel just fine despite having low blood glucose. A highly-cited study by George Cahill, found elevated ketone levels could protect fasted participants when they were administered insulin to induce hypoglycemia.
I interviewed Dr. Brianna Stubbs, a ketone researcher with a Ph.D. in Metabolic Physiology from the University of Oxford who is now Research Lead at HVMN, specializing in developing ketone esters. She told me that in terms of science on the ketone salts and their effect on physical performance, one of the most-cited benefits of ketone salts, the scientific studies that have been done show at best no effect on physical performance and that, currently, there is no peer-reviewed scientific research on the ketone salt products on the market.
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.
I interviewed Dr. Brianna Stubbs, a ketone researcher with a Ph.D. in Metabolic Physiology from the University of Oxford who is now Research Lead at HVMN, specializing in developing ketone esters. She told me that in terms of science on the ketone salts and their effect on physical performance, one of the most-cited benefits of ketone salts, the scientific studies that have been done show at best no effect on physical performance and that, currently, there is no peer-reviewed scientific research on the ketone salt products on the market.
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1 – If you’re not looking to spend a ton of money up front while testing the ketogenic lifestyle – no problem! For starters, you need to try nutritional ketosis before ever worrying about exogenous supplementation. If you don’t like the diet, it’s not going to matter how many supplements you by. However, if you want to get an idea if exogenous ketones are for you, we would suggest a simple MCT Oil, or a great beginner exo keto like Keto CaNa.
We designed a test for each of the chosen benefit claims and enlisted the help of four of our Diet Doctor teammates to try out the supplements and go through the testing. They were Jonatan and Giorgos from the video team, Emőke from the recipe team and Erik from the IT team. We had a mix of people who were naturally in endogenous ketosis during testing, and people who were not.
In terms of getting back into Ketosis, Keto//OS would most likely be a better choice (and a change back to a low-carb diet, of course) because it not only has MCTs, but also provides beta-hydroxybutyrate, which is the product that comes from your liver after it synthesizes acetoacetate. However, since this product also has caffeine (great for workouts), you might want to go with the decaf if you’re strictly looking for a ketosis jumpstart.
This may have been mentioned, I haven’t checked all comments, but glutamine causes gluconeogenesis so that may explain why it affects Ketosis. Whenever I took a glutamine powder supplement for gut healing, I noticed I would “feel” less Ketogenic and I knew it was affecting me adversely. Glycine (which is also in bone broth) also has this effect I believe. Apparently some amino acids are just more easily converted to glucose.

Now that you have fasted for quite a long time, you can break your fast at around 4 to 5 pm. Try having some good fat for this purpose, such as coconut oil or MCT oil, butter, or any other healthy fat. MCT oil might come in as a better option in this case since it gets quickly absorbed by the body. It swiftly bypasses the gallbladder and reaches the liver where it is transformed to ketones rapidly.
Over the past couple years, I’ve tried a number of ketone supplements, generally to enhance a longer fast or to offer an edge before one of my Ultimate Frisbee evenings. This Kegenix variety is one I’d recommend. I’ve also used Quest Nutrition MCT oil powder with good results as well, but there are plenty of other solid formulations to choose from.
I came across a new company called KetoneAid that has begun producing small batches of ketone monoesters (KMEs). The main molecule in their product (D-β-hydroxybutyrate / D 1,3-butanediol) is based on a five-year, $10M study commissioned by the Defense Advanced Research Projects Agency (DARPA), looking to create the most powerful source of energy for special operations soldiers such as Navy SEALs, when undertaking very physically and cognitively challenging missions. In fact, the main researcher of the DARPA study is Dr. Richard Veech, the same person that authored the longevity study I just mentioned. Very cool.
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.

Another factor to consider is that in nutritional ketosis the liver makes a steady supply of ketones and continuously releases them into the circulation. In contrast, most ketone supplement protocols involve bolus intakes that don’t mimic the endogenous release pattern. The extent to which this impacts metabolic and signaling responses across different tissues remains unclear.


Getting enough sleep not only helps in the production of growth hormones vital for muscle growth, but it plays a particular role as already discussed. If you’re intermittently fasting then sleep is crucial is helping you sustain the fast. 6-10 hours of your day will be dedicated to sleep, helping you to reboot and not think about food during this time. That means less time for you to actually be fasting! Stress is another factor – if we don’t get enough sleep, we’ll tend to feel more stress and agitation throughout the day. Ensuring that we’re well rested plays a huge part in keeping down cortisol levels so that are insulin and blood sugar levels don’t spike.

A lot of people who use ketogenic diets will include a regular (i.e. weekly) carb refeed meal. There are various reasons behind doing this. If you are doing a lot of glycolic based training, then the carb refeed can help bump up muscle glycogen levels and in turn boost performance. Others use these refeeds as a way to keep their thyroid health in check, and finally some people use these refeeds as a ‘cheat day’ – so that they can still enjoy the pleasures from carbohydrates!
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 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.

Although several studies have linked calcium supplementation with an increased risk of heart attack and heart disease[18], other studies have not found the same association. For example, a study on calcium supplementation (1000 mg/day) in postmenopausal women indicated a reduced risk of hip fracture, but no increase in cardiovascular disease or mortality in the supplement group, compared to the placebo group[19]. Another study found no effect from calcium supplementation (600 or 1200 mg/day) on abdominal aortic calcification[20].
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.
North Americans typically live pro-inflammatory, pro-disease lives (think about your everyday: likely sitting in a flexed position for hours on end, not enough natural sunlight, not enough movement, artificial food stuffs, artificial colouring, going to bed late, blue light exposure, less in-person contact with our loved ones, late night snacks, the list goes on and on).

The human studies aren’t quite there yet, but it seems likely that they’d help. A recent human case study found that ketone esters added to the regular diet improved Alzheimer’s symptoms. Animal studies indicate that adding exogenous ketones to a regular lab (read: not ketogenic) diet can reduce seizure activity and improve overall symptoms in epilepsy animal models, reverse early neuronal hyperactivity in Alzheimer’s animal models, and reduce anxiety in rats.
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.
BHB isn’t just an energy source for the brain–it has other effects which promote brain health. BHB can trigger the release of chemicals called neurotrophins, which support neuron function and synapse formation. One of these neurotrophins is called BDNF (brain-derived neurotrophic factor), which is a protein in the brain associated with cognitive enhancement, alleviation of depression and reduction of anxiety.10

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