All of the data I’ll present below were from an experiment I did with the help of Dominic D’Agostino and Pat Jak (who did the indirect calorimetry) in the summer of 2013. (I wrote this up immediately, but I’ve only got around to blogging about it now.) Dom is, far and away, the most knowledgeable person on the topic of exogenous ketones. Others have been at it longer, but none have the vast experiences with all possible modalities (i.e., esters versus salts, BHB versus AcAc) and the concurrent understanding of how nutritional ketosis works. If people call me keto-man (some do, as silly as it sounds), they should call Dom keto-king.
Remember how important it is to measure ketone blood levels accurately? Same goes for food tracking. A food tracking app, like MyFitnessPal, provides insight into macronutrient intake and thus the ability to tweak the diet to achieve ketosis. Tracking diet (inputs) and measuring ketones levels (outputs) delivers the best shot at optimizing the keto diet plan.
You see, when someone says ketosis is a natural state, they mean that ketosis is the body’s backup plan for those times when there isn’t any food to eat. It’s an evolutionary adaptation that developed over hundreds of thousands of years and springs from a time when our distant ancestors often had to go many days between decent meals. Fortunately, these days actual starvation is pretty rare so most people will never be in ketosis. But the physiological mechanism is still there, lurking in the background, readily accessible to anyone who is willing to trick their body into thinking it’s starving.
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.

The current recommendation for magnesium is 310-320 mg for adult women and 400-420 mg for adult men. Magnesium deficiencies are common; 2005-2006 data indicates that the majority of Americans’ dietary magnesium intake was less than the Estimated Average Requirement (EAR) for the respective age groups[25]. The EAR for a nutrient is about 20% LESS than the RDA. Current data on magnesium intake and deficiency in the US is not readily available, as magnesium testing is not part of routine electrolyte testing in hospitals and clinics[26].
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.
The two compounds commonly referred to as ‘ketone bodies’ (BOHB and AcAc) are produced and used for multiple purposes across nature from algae to mammals, but seldom in concentrations useful for extraction as human food. For this reason, the source of most exogenous ketones is chemical synthesis. Furthermore, most current research and use of ketone supplements focuses on BOHB. That is because AcAc is chemically unstable – it slowly breaks down to form acetone by releasing of one molecule of CO2.
 “Though the small amount of carbohydrates in the diets may be more than balanced by the potential sugar production from the large amount of protein to keep the ratio of fatty acid to glucose below the generally accepted level of ketogenesis, the respiratory quotient data suggest another mechanism also” ß (most likely the CPT-1A mutation, which had not been discovered at that time)

The protocols carried out in these studies were approved by the the South West Frenchay NHS REC (15/SW/0244) (Study 1) and London Queen's Square REC (14/LO/0288) (Study 2 and 3). The studies were carried out in accordance with the recommendations of the Declaration of Helsinki, apart from pre-registration in a database. All subjects gave written informed consent in accordance with the Declaration of Helsinki.
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’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.
Effects of ketone supplementation on blood βHB. a, b Blood βHB levels at times 0, 0.5, 1, 4, 8, and 12 h post intragastric gavage for ketone supplements tested. a BMS + MCT and MCT supplementation rapidly elevated and sustained significant βHB elevation compared to controls for the duration of the 4-week dose escalation study. BMS did not significantly elevate βHB at any time point tested compared to controls. b BD and KE supplements, maintained at 5 g/kg, significantly elevated βHB levels for the duration of the 4-week study. Two-Way ANOVA with Tukey’s post hoc test, results considered significant if p < 0.05. Error bars represent mean (SD)
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).
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.
Sometimes waiting for your body to make the switch from carbohydrate metabolism to beta hydroxybutyrate metabolism (aka ketosis) can be an uncomfortable and lengthy process. Another way to get beta hydroxybutyrate into your system so your body is using “clean” energy is by taking it supplementally or through nutrition. A betahydroxybutyrate supplement is what can be used in this scenario. This is an exogenous ketone. Exogenous means you get it from outside of your body. Think EX = exit = outside.
Though research involving ketone supplements is still in the early stages, it seems promising. One study published in February 2018 in Obesity suggests exogenous ketone esters lower hunger hormones and act as appetite suppressors. That can lead to weight loss because “if we don’t feel hungry, gosh, we probably aren’t going to eat like we were,” Griffin says.

Testing BHB levels in the blood is simple but can get pricey if you are doing it many times a day.  The Precision Xtra blood glucose and ketone meter is a good buy at $28-$30.   The expensive part is the ketone test strips here which can cost $4 each.   If you are looking at testing yourself every day it is going to cost you $120 a month and the $30 meter.  Here is a starter kit you can get on Amazon.

The salts typically utilize sodium, potassium, calcium, or magnesium as the cation. Because these cations vary in molecular weight and valence (1+ or 2+), the amount of mineral delivered per gram of BOHB varies from 10% for the magnesium salt to 27% for potassium. Given that recommended daily intakes of these various minerals range from a few hundred milligrams up to 5 grams, whereas the daily ketone intake goal to mimic nutritional ketosis blood levels would need to be on the order of 50 grams, achieving this goal with ketone salts would severely challenge human dietary mineral tolerance.
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]
LDL is the lipoprotein particle that is most often associated with atherosclerosis. LDL particles exist in different sizes: large molecules (Pattern A) or small molecules (Pattern B). Recent studies have investigated the importance of LDL-particle type and size rather than total concentration as being the source for cardiovascular risk [56]. Patients whose LDL particles are predominantly small and dense (Pattern B) have a greater risk of cardiovascular disease (CVD). It is thought that small, dense LDL particles are more able to penetrate the endothelium and cause in damage and inflammation [82–85]. Volek et al. reported that the KD increased the pattern and volume of LDL particles, which is considered to reduce cardiovascular risk [73]. Though we did not show a significant effect on LDL levels for ketone supplements, future chronic feeding studies will investigate the effects of ketone supplementation on lipidomic profile and LDL particle type and size.
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.
It's also important to note that you probably should follow a low carb diet or ketosis diet when using this product. Your brain prefers glucose as fuel because it's easier for the body to metabolize from food, so if you are eating a standard American diet of 100g+ carbs per day, or excessive protein, this won't help you lose weight, even with exercise because you'll have more than enough glucose to power your brain. Carbohydrate restriction, moderate protein, and lots of good healthy fat is what puts your body into ketosis.
Let me introduce myself. My name is Mark Sisson. I’m 63 years young. I live and work in Malibu, California. In a past life I was a professional marathoner and triathlete. Now my life goal is to help 100 million people get healthy. I started this blog in 2006 to empower people to take full responsibility for their own health and enjoyment of life by investigating, discussing, and critically rethinking everything we’ve assumed to be true about health and wellness...

Obviously, cutting carbs is much easier than not eating anything at all for days on end. It's also safer for people with diabetes as it leads to a gradual decline in blood glucose [2]. The carbs you have to reduce are known as net carbs. Those are the carbs that your body uses to make glucose. You calculate them by subtracting the grams of fiber from total carbs in a food item.
The other option – which is the superior option – is the breakdown of fat into a fuel that can be used by the brain. This is a beautiful solution, because even the leanest individual will have weeks and weeks’ worth of energy stored as body fat. The body breaks down this fat in the liver and converts it into ketone bodies. The brain can then utilise these ketones as a fuel source – forgoing the need for stored glucose or constant consumption of carbohydrates. These ketones can also be used to make ATP.
It is a good idea to weigh the pros and cons before deciding to add a calcium supplement to your diet. This includes exogenous ketone supplements. If you have any risk factors for osteoporosis, have low bone density, or have issues that prevent you from consuming a nutrient-rich diet, then the benefits of calcium supplements will likely outweigh the risks. But don’t forget that there are other avenues to improving your bone density, like strength training, and, more importantly, a well-balanced diet.
When you restrict carbs, the kidneys excrete a lot of sodium. Not replacing this sodium can leave you feeling light headed. I recommend having a big glass of spring water with ½ teaspoon of Celtic sea salt twice a day (first thing in the morning and midafternoon are two times that work well). A long with this, make sure you use a lot of salt on your meals.
You must realise that our bodies are lazy and switching to a new energy source means hard work, that means that your body will not do this easily and you basically have to force it. One way to speed up this process is to put your body into fight or flight mode. My preferred  controlled exercise to do this is to have a high intensity workout followed immediately by a  cold shower.  I am describing it in the article to go slowly, but in this case it will actually be beneficial if you can force your self to go straight into a cold shower and try to stay there at least 2 minutes. One of the benefits of this that your body will produce the hormone noradrenaline. Obviously this is something for people in perfect health. Please advice your doctor before you want to take cold showers.
Taking MCT oil (medium chain triglyceride) or coconut oil (contains 60% MCT) can help boost ketone production. This is because your body absorbs MCT very quickly as it bypasses the gallbladder and into the liver to be processed into ketone bodies. Make sure you’re getting unprocessed versions of coconut oil that is labelled as ‘organic’ or ‘extra virgin’. This, along with grass-fed butter, is what I add into my ‘bulletproof’ coffees.
Intermittent fasting is using the same reasoning – instead of using the fats we are eating to gain energy, we are using our stored fat. That being said, you might think it’s great – you can just fast and lose more weight. You have to take into account that later on, you will need to eat extra fat in order to hit your daily macros (the most important thing). If you’re overeating on fats here, you will store the excess.
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.
In Study 2 a Student's unequal variance t-test with equal SD was used to compare urine βHB concentrations. Additionally, a linear mixed effects model was constructed to estimate partitions of variance in R, using the lme4 and blme packages (Chung et al., 2013; Bates et al., 2015). Feeding state and visit number were fixed effects in this model, and inter-participant variability was a random effect. Inter-participant variability was calculated according to the adjusted generalized R2 metric (as proposed by Nakagawa and Schielzeth, 2013), to partition variance between the fixed effects of feeding, inter-participant variability, and residual variability. The coefficient of variation for βHB Cmax and AUC were calculated using the method of Vangel (1996).
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. (http://www.ncbi.nlm.nih.gov/pubmed/15123336)
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!

Plecko B., Stoeckler-Ipsiroglu S., Schober E., Harrer G., Mlynarik V., Gruber S., et al. . (2002). Oral beta-hydroxybutyrate supplementation in two patients with hyperinsulinemic hypoglycemia: monitoring of beta-hydroxybutyrate levels in blood and cerebrospinal fluid, and in the brain by in vivo magnetic resonance spectroscopy. Pediatr. Res. 52, 301–306. 10.1203/01.PDR.0000019439.27135.2B [PubMed] [CrossRef]
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.
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.  

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.


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.
Hi, I still a little confused about when or how to take this. I am trying to get adapted and minimize the flu. Is it most beneficial before eating, after eating, with food or in place of food? I have been keto in the past but this time I am not switching over to fat burning mode even though my macros are good. ( I am thinking it is just too many calories and carbs at this point but I get hungry!) Help please.

It was explained to me that exogenous ketones inhibit lipolysis (breaking down of fat cells), therefore triglycerides should be expected to go down. They theorize that ketones may promote transfer of triglycerides from blood into cells, which primes the pump for fat burning, but to verify would require conducting biopsies to measure blood versus tissue.
Caveat emptor: the following post doesn’t come close to answering most of these questions. I only document my experience with BHB salts (and a non-commercial version at that), but say little to nothing about my experience with BHB esters or AcAc esters. But it will provide you will some context and understanding about what exogenous ketones are, and what they might do for athletic performance. We’ll likely podcast about the questions and topics above and cover other aspects of exogenous ketones in more detail.

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