Keep these studies in mind as your body tries to play tricks on you during your first day of fasting.  Even after three days of fasting, health complications are highly unlikely. However, it is important to know about the possible issues that can be caused by fasting. If you choose to incorporate fasting into your daily diet, you typically want to eat every day as well. Occasionally going on a longer period of fasting.
In fact this was one of the biggest surprises I had when exploring ketosis. For years I have been following a cyclical lower carb diet. For years I wouldn’t consume a carb until later in the afternoon (ala Carb Backloading style). After eating 5 days without any carbs I tested my ketone levels… they were 0.1 mmol. This reading was done first thing in the morning (10 hours fasted) after 5 days without a carb in my diet.
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).

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.
Ketones are an alternate energy or fuel source for brain and body that our bodies have naturally produced and used for millennia. Ketones have recently leapt to the forefront of health and wellness conversations worldwide as the scientific body of research that seeks to understand their numerous unique properties and profound systemic effects has begun to grow (see below).

Neuroprotective benefits: A natural part of the aging process is neurodegeneration, which is largely responsible for cognitive defects like Alzheimer’s disease. Recent research suggests that exogenous ketone supplementation can drastically slow neurodegeneration and the resulting decrease in mental function.[7] However, the mechanism behind this finding remains to be elucidated; though, researchers suggest exogenous ketones act to reduce brain inflammation. Glucose, on the contrary, may actually accelerate inflammatory response in the brain.[8]
For anyone who wants to get a bit more technical, research by Stubbs and colleagues shows that BHB shuts off lipolysis (fat breakdown). With endogenous ketosis there are many other factors that stimulate lipolysis meaning that a kind of balance is reached and lipolysis stays constant. But with exogenous ketosis those factors stimulating ketosis are not present, so the overall effect of the ingested BHB is to decrease lipolysis.

The way you make an exogenous BHB is by attaching it to some type of other compound (sodium, potassium, calcium, or magnesium) so that your body can process the molecule by cleaving the bond between the salt and the beta hydroxybutyrate. BHB + bound to a salt = BHB salts, which is what most people in the ketosis community call exogenous ketones. There are also things called esters, which are basically unbound BHB molecules. These are really disgusting and cause massive digestive issues, so I like to ignore them until we can produce them in a more appealing way.

For the past few million years, the only way for humans to make use of ketones for fuel was to restrict carbohydrates low enough and long enough to induce the liver to make them. This is admittedly hard for many people to do in a world that still believes that dietary carbs are good and fats are bad. An emerging alternative is to consume ketones as a dietary supplement. The research into how these function in the body and what benefits they can confer remains early stage, but there are already a number of such products available for sale. In this section, we will discuss how exogenous ketones affect blood ketone levels, and how they may influence health and disease compared to ketones produced within the body.
Comments are welcomed and encouraged. The purpose of comments on our site is to expand knowledge, engage in thoughtful discussion, and learn more from readers. Criticism and skepticism can be far more useful than praise and unflinching belief. There’s an art and science to critical thinking and how to conduct yourself. There’s a multitude of fallacious appeals we could spell out, but a good rule of thumb is not to attack the person, attack the ideas. Don’t look for the flaws in the person, look for the flaws in the hypothesis. Let’s keep the brawling to movies depicting minor league hockey teams and political “news” shows. Thank you for adding to the discussion.

Ketone monoester and diester compounds may circumvent the problems associated with inorganic ion consumption in KS drinks. KE ingestion rapidly increased blood ketone concentrations to >5 mM in animals (Desrochers et al., 1995a,b; Clarke et al., 2012a) and the first oral, non-racemic KE for human consumption, (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, raised blood βHB concentrations to 3–5 mM in healthy adults (Clarke et al., 2012b; Shivva et al., 2016) and athletes (Cox et al., 2016; Holdsworth et al., 2017; Vandoorne et al., 2017). However, the pharmacokinetics and pharmacodynamics of this KE with confounding factors, such as prandial state or multiple KE drinks, have not been characterized.
Ketone Esters: These are not normally found in the body, but exogenous ketone esters convert into BHB once it is in the body. They are also synthetically (lab) made compounds that link an alcohol to a ketone body, which can then be metabolized by the liver into a ketone. They are like ketone salts on steroids as they have 5-10 time more BHB per serving/maximum daily intake than ketone salts. To date, pure ketone esters have been very expensive to produce and have only been available to researchers, elite athletes (Tour de France cyclists), and the US Department of Defense (people have spent more than $20,000 to have an independent lab produce a single serving!).
Besides cutting carbs, it's important to increase your fat intake, and be moderate with protein. The fat you eat will keep you feeling energized and support ketone production. Protein is also important but if you go overboard with it, your body could enter into a process called gluconeogenesis. In gluconeogenesis, your body makes glucose from protein, and you want to avoid that.
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.
Whereas ketone esters are 100% D- form, most ketone salts are a 50/50 mix of left and right-handed beta hydroxybutyrate, which is known as a racemic mixture. These beta hydroxybutyrate molecules are linked to a mineral, such sodium (Na), calcium (Ca), potassium (K), or magnesium (Mg). This kind of ketone supplement gets broken down to left and right-handed version of beta hydroxybutyrate along with the mineral.
Not only is Ketōnd considered one of the best on ketone supplements the market it also currently holds favorable ratings, reaching numbers as high as 98 percent in customer reviews. They absolutely love this product and you will too if you give it a try. You will get some incredible results. Whether you are a busy professionals, athlete, on-the-go moms or dads, or college students you too will love this product.
As I mentioned before, this was by no means a scientific experiment carried out under lab conditions, and this means we can only draw tentative conclusions from any of the data. Nonetheless, carrying out the testing in the way described above should give most people a good idea of how well the ketone supplements show the noticeable benefits they are marketed to have and provide a clear enough basis for a decision on whether or not to buy them.
One thing to remember here is that even if your calculated daily ‘keto approved’ protein allowance is (let’s say) 150g, that doesn’t mean you can eat 150g in one meal and still be in ketosis. You may find that you can’t eat more than 40g of protein at a time, otherwise you will drop out of ketosis. OR, you may find you can eat 50g of protein but you need a LOT of fat. Whereas a small serve of 15g of protein without fat might knock you out of ketosis. 
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.
After a minimal amount of internet "research," I decided to try my first exogenous ketones. I have used the ketogenic diet off and on for at 15 years and my body is pretty efficient at fat adapting. (Usually by the end of 2 strict days, I am in ketosis, but not without symptoms and intense cravings.) I can consistently fast from carbs for 20 - 24 hours and do this consistently. However, around hour 20, my mind begins to negotiate that intermittent fasting is advantageous too and that I can afford to have some carbs once a day. Hence the yo-yo effect.

For the past few million years, the only way for humans to make use of ketones for fuel was to restrict carbohydrates low enough and long enough to induce the liver to make them. This is admittedly hard for many people to do in a world that still believes that dietary carbs are good and fats are bad. An emerging alternative is to consume ketones as a dietary supplement. The research into how these function in the body and what benefits they can confer remains early stage, but there are already a number of such products available for sale. In this section, we will discuss how exogenous ketones affect blood ketone levels, and how they may influence health and disease compared to ketones produced within the body.


To be in ketosis, you need to get very specific about the macronutrient ratios hanging off your fork. This means eating 75% fats, 20% protein and 5% carbohydrates. It’ll see you getting 5-10% of your total calories from carbohydrates, which is roughly 25-30g of carbs per day, and diligently keeping this below the 50g threshold creates the ketosis that burns stored fat. Unlike the no-limit-protein option on the table when going low carb, eating more than 0.67-0.81g of protein per pound of bodyweight can hoof you out of ketosis because too much of it can be converted into glucose, blunting the benefits of the ketones. On the plus side, you will have a high fat intake, making your energy levels more balanced so you can train at higher intensities.
Next, BHB salts are the only supplement that elevates BHB levels while muscle glycogen remains at capacity (low muscle glycogen can drastically impede long-duration athletic performance). In short, athletes who consume carb-based diets, and those on low-carb diets, stand to benefit from exogenous ketone supplements taken prior to training/exercise.
Every 7 days, animals were briefly fasted (4 h, water available) prior to intragastric gavage to standardize levels of blood metabolites prior to glucose and βHB measurements at baseline. Baseline (time 0) was immediately prior to gavage. Whole blood samples (10 μL) were taken from the saphenous vein for analysis of glucose and βHB levels with the commercially available glucose and ketone monitoring system Precision Xtra™ (Abbott Laboratories, Abbott Park, IL). Blood glucose and βHB were measured at 0, 0.5, 1, 4, 8, and 12 h after test substance administration, or until βHB returned to baseline levels. Food was returned to animals after blood analysis at time 0 and gavage. At baseline and week 4, whole blood samples (10 μL) were taken from the saphenous vein immediately prior to gavage (time 0) for analysis of total cholesterol, high-density lipoprotein (HDL), and triglycerides with the commercially available CardioChek™ blood lipid analyzer (Polymer Technology Systems, Inc., Indianapolis, IN). Low-density lipoprotein (LDL) cholesterol was calculated from the three measured lipid levels using the Friedewald equation: (LDL Cholesterol = Total Cholesterol - HDL - (Triglycerides/5)) [51, 52]. Animals were weighed once per week to track changes in body weight associated with hyperketonemia.
Look around your grocery store, and you’ll soon start to see “Fortified with Calcium” on a variety of different labels, along with calcium supplements everywhere you look. Calcium is essential for cardiovascular health, but several studies have found too much calcium to be associated with cardiovascular events and even death.  One study found that consumption of 1000+ mg of supplemental calcium per day was associated with an increased risk of death from cardiovascular disease in men but not women[13]. Dietary calcium intake (i.e., calcium from incorporated foods such as milk, etc.), on the other hand, was not associated with death from cardiovascular disease in men or women. Additionally, a different study found 1000 mg of supplemental calcium to be associated with an increase in rates of cardiovascular events in women[14].

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.  


I think almost everyone agrees with me when I say that the ketogenic diet is probably one of the most complex and difficult eating plans out there. Even when you’re not on a diet or trying to lose weight you still have to bring a lot of attention to detail. Getting into ketosis isn’t as important as we would think, but there are still 5 simple steps we can make to get into a ketotic state.
Hello! I’m planning on taking a short vacation and will be having “kept friendly” drinks, mostly vodka and water with lemon and stevia. When should I take my exogenous ketones? That night before bed or early the next morning or after the 3 day vacation is completely over? I’m unsure how to manage this to have the best odds of staying in ketosis and get back to burning FAT. Also, I just purchased Instaketones from Julian Bakery, what are your thoughts on this brand? Thanks for what you do!

For anyone who wants to get a bit more technical, research by Stubbs and colleagues shows that BHB shuts off lipolysis (fat breakdown). With endogenous ketosis there are many other factors that stimulate lipolysis meaning that a kind of balance is reached and lipolysis stays constant. But with exogenous ketosis those factors stimulating ketosis are not present, so the overall effect of the ingested BHB is to decrease lipolysis.

As seen in this exercise, glucose tends to fall quite precipitously following exogenous ketone ingestions. Without exception, every time I ingested these compounds (which I’ve probably done a total of 25 to 30 times), my glucose would fall, sometimes as low as 3 mM (just below 60 mg/dL). Despite this, I never felt symptomatic from hypoglycemia. Richard Veech (NIH) one of the pioneers of exogenous ketones, has suggested this phenomenon is the result of the ketones activating pyruvate dehydogenase (PDH), which enhances insulin-mediated glucose uptake. (At some point I will also write a post on Alzheimer’s disease, which almost always involves sluggish PDH activity —in animal models acute bolus of insulin transiently improves symptoms and administration of exogenous ketones does the same, even without glucose.)

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