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.
In terms of epigenetic signaling, initial studies of the effects of BOHB on class-1 histone deacetylase activity against oxidative stress (Schimazu 2013), NLRP3 inflammasome suppression (Youm 2015), mouse longevity (Roberts 2017), and other epigenetic regulatory effects suggest that levels as low as 1 mM have potent effects. Furthermore, the association between very mild ketonemia and reduced coronary mortality with SGLT2 inhibitor use in patients with type 2 diabetes (Ferranini 2016) suggests that there might be clinical benefits with chronic BOHB levels as low as 0.3 mM (Gormsen 2017. Vetter 2017).
Hybrid strategy: A hybrid strategy is to follow a low-carb/high-fat ketogenic diet to induce nutritional ketosis and use ketone supplements strategically. Supplements like Ketone salts or MCT oil can help ease the transition into ketosis, they can be an effective tool when we are knocked out of nutritional ketosis and they can help push ketone levels higher in the body for added benefit.
Hi Rob thanks so much, many people experience inconclusive results from the pee strips, as the ketone concentration in our pee is a measure of ketones not being used by the body. Basically the overflow or unused ketones. As our body becomes more adapted to using ketones, there will be less in our urine. It’s tough to keep the variable constant of how hydrated you are across many pee tests. Don’t be discouraged by pee test results. We have had many times where our blood tests show 1-3mmol/dl BHB but our pee test showed no results. Definitely keep testing (consider using a precision Xtra) and changing the dose to suit your needs. Hope this is helpful!
Getting into a state of ketosis normally involves eating a ketogenic diet consisting of around 80 percent fat, 15 percent protein, and 5 percent carbs. Over time, the body transitions from burning carbs for fuel to burning ketones—an alternative fuel source that the liver makes by breaking down fat, explains keto diet expert Amy Davis, RD, LDN. Since advocates say that ketosis can help you lose weight fast, think more clearly, and feel more energized, it’s tempting to try.
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.
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.
And now, you can take ketone supplements (salts and esters), known as exogenous ketones, without actually restricting anything. According to those promoting this nasty-tasting supplement, that means you can have a brain and body fuelled by ketones, along with all of the supposed health benefits that come with running on fat. Well, don't fall for it.

Individuals who have clinically unregulated blood sugar, such as those with diabetes, are cautioned to consult their trusted healthcare provider before choosing to use exogenous ketones. While it can be done safely, especially in the presence of a well-formulated ketogenic food plan, there may be a risk of blood sugar dropping unexpectedly low. There may be therapeutic value in this application, but close monitoring is key.
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.
With oral ketone supplementation, we observed a significant elevation in blood βHB without dietary restriction and with little change in lipid biomarkers (Fig. 1). Over the 4 week study, MCT-supplemented rats demonstrated decreased HDL compared to controls. No significant changes were observed in any of the triglycerides or lipoproteins (HDL, LDL) with any of the remaining exogenously applied ketone supplements. It should be noted that the rats used for this study had not yet reached full adult body size [79]. Their normal growth rate and maturation was likely responsible for the changes in triglyceride and lipoprotein levels observed in the control animals over the 4 week study (baseline data not shown, no significant differences) [80, 81]. Future studies are needed to investigate the effect of ketone supplementation on fully mature and aged animals. Overall, our study suggests that oral ketone supplementation has little effect on the triglyceride or lipoprotein profile after 4 weeks. However, it is currently unknown if ketone supplementation would affect lipid biomarkers after a longer duration of consumption. Further studies are needed to determine the effects of ketone supplements on blood triglyceride and lipoproteins after chronic administration and as a means to further enhance the hyperketonemia and improve the lipid profile of the clinically implemented (4:1) KD.
Ketone supplements contain exogenous ketones—synthetic ketones made in a lab. Most use a type of ketone called beta-hydroxybutyrate (BHB), which is the same as the ketones the body produces naturally. “We’re literally biohacking," says Amie Heverly, who began taking a ketone supplement called Prüvit last year and now works as a promoter selling Prüvit products. "You’re not adding a foreign substance to your body, because BHB is identical to what your body would naturally produce,” she explains.

Blood, breath, and urine ketone kinetics following mole-matched ketone ester (KE) and ketone salt (KS) drinks, at two amounts, in 15 subjects at rest. Values are means ± SEM. (A) Blood d-βHB. (B) Tmax of blood d-βHB. (C) AUC of blood d-βHB. (D) Isotopic abundance (%) of d- and l-chiral centers in pure liquid KE and KS. (E) Blood d-βHB and l-βHB concentrations in subjects (n = 5) consuming 3.2 mmol.kg−1 of βHB in KS drinks. (F) d-βHB and l-βHB concentrations in urine samples from subjects (n = 10) consuming 3.2 mmol.kg−1 of βHB in KS drinks. (G) Blood d- and l-βHB after 4, 8, and 24 h in subjects (n = 5) consuming 3.2 mmol.kg−1 of βHB in KS drinks. (H) Breath acetone over 24 h in subjects (n = 5) consuming 3.2 mmol.kg−1 of βHB in KE and KS drinks (ppm = parts per million). (I) Urine d-βHB excreted over 4 h after KE and KS drinks (n = 15). (J) Urine pH 4 h after drink, dotted line indicates baseline. †p < 0.05 KE vs. equivalent amount of KS, *p < 0.05 difference between 1.6 vs. 3.2 mmol.kg−1 of βHB, §p < 0.05 difference between amounts of d- and l-βHB, p < 0.05 difference between baseline and post-drink level.
At baseline, 4 h after intragastric gavage, the elevation of blood ketones was inversely related to the reduction of blood glucose compared to controls following the administration of MCT (5 g/kg) (p = 0.008) and BMS + MCT (5 g/kg) (p = 0.039) . There was no significant correlation between blood ketone levels and blood glucose levels compared to controls for any other ketone supplemented group at baseline (Fig. 4a). At week 4, 4 h after intragastric gavage, there was a significant correlation between blood ketone levels and blood glucose levels compared to controls in MCT (10 g/kg) and BMS + MCT (10 g/kg) (p < 0.0001, p < 0.0001) (Fig. 4b).
If Prüvit’s Keto OS-Max is “not a weight loss supplement” as stated in their disclaimer, why is the official website full of success stories of people who claim to have lost huge amounts of weight from taking the supplements? Ketōnd also feature a number of weight loss success stories on their site. I will get to why there is a problem with weight loss claims later on.

Serial drinks or a continuous NG infusion of KE effectively kept blood ketone concentrations >1 mM for 9 h (Figure ​(Figure6).6). With drinks every 3 h, blood d-βHB rose and then fell, but had not returned to baseline (~ 0.1 mM) when the next drink was consumed. There was no significant difference in d-βHB Cmax between drinks 2 and 3 (3.4 ± 0.2 mM vs. 3.8 ± 0.2 mM p = 0.3), as the rate of d-βHB appearance fell slightly with successive drinks (0.07 ± 0.01 mmol.min−1 and 0.06 ± 0.01 mmol.min−1 p = 0.6). d-βHB elimination was the same after each bolus (142 ± 37 mmol.min, 127 ± 45 mmol.min; and 122 ± 54 mmol.min). When KE was given via a nasogastric tube, the initial bolus raised blood d-βHB to 2.9 ± 0.5 mM after 1 h, thereafter continuous infusion maintained blood d-βHB between 2–3 mM. Total d-βHB appearance in the blood was identical for both methods of administration (Serial drinks AUC: 1,394 ± 64 mmol.min; NG infusion AUC: 1,305 ± 143 mmol.min. p = 0.6).


We sampled each of the 3 flavors and also mixed in the available Ketōstax and this supplement tasted better than any other we had tried. Ketōnd costs $79.95 for 30 servings which is about $2.67 per serving – which is less than half the price of the leading competitor. Ketōnd’s label and ingredients are 100% transparent, so they disclose everything that is in the supplement – which is only ketones. What we really liked about Ketōnd is that it isn’t part of some Multi Level Marketing company so there are no obligations.
Increased calcium levels in the bloodstream may contribute to the hardening of arteries (atherosclerosis), which in turn can lead to a heart attack.  Calcium from supplements enters the bloodstream in one bolus, whereas we usually tend to get calcium from foods in small doses from the breakdown process. This might explain why calcium from food doesn’t create the same risk that is introduced by calcium supplements. At first glance, it seems to be the case that high calcium intake –at least from supplements–may not be ideal.
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].
International Patent # PCT/US2014/031237, University of South Florida, D.P. D’Agostino, S. Kesl, P. Arnold, “Compositions and Methods for Producing Elevated and Sustained Ketosis”. P. Arnold (Savind) has received financial support (ONR N000140610105 and N000140910244) from D.P. D’Agostino (USF) to synthesize ketone esters. The remaining authors have no conflicts of interest.
Increased calcium levels in the bloodstream may contribute to the hardening of arteries (atherosclerosis), which in turn can lead to a heart attack.  Calcium from supplements enters the bloodstream in one bolus, whereas we usually tend to get calcium from foods in small doses from the breakdown process. This might explain why calcium from food doesn’t create the same risk that is introduced by calcium supplements. At first glance, it seems to be the case that high calcium intake –at least from supplements–may not be ideal.
Ketosis is a metabolic state where most of the body’s energy supply comes from ketone bodies in the blood, in contrast to a state of glycolysis where blood glucose provides most of the energy. Ketosis is characterised by serum blood concentrations of ketone bodies over 0.5 millimolar with low and stable levels of insulin and blood glucose. However, with ketone supplementation (as you’ll learn about later in this article) ketosis can actually be induced even when there are high levels of blood glucose
This research is a good reminder to discuss with your doctor before taking any supplements. Given the widespread use of calcium supplements, more research is required before any final conclusions can be drawn. Several ketone companies have tried to avoid the large sodium loads but instead relied on a bump in the calcium content from the BHB ketone salts, seemingly without consideration for the aforementioned results. Calcium BHB will likely absorb slower compared to sodium BHB due to digestion and absorption kinetics.  For those looking to optimize brain uptake of ketones, this probably isn’t the best strategy (as uptake is directly proportional to the levels in the blood).   Be cautious of supplements running from the sodium and chasing the calcium BHB instead, and make sure you factor that into your overall daily needs.
Will taking exogenous slow down my fat loss? Since now before digging into my body for energy/ketones, I will first use up the exogenous ketones I ingest. Also do exogenous ketones somehow help get even more keto adapted, keeping in mind I have been on a strict keto diet without a problem and don’t mind it at all. Outside of performance improvements, do you think exogenous ketones is for someone like me who is primarily looking for fat loss.
Athletic performance benefits: The use of exogenous ketone supplements for bettering physical/athletic performance is promising for several reasons. Firstly, taking exogenous ketones (particularly BHB salts) induces acute nutritional ketosis for upwards of eight hours, mimicking fasting physiology (e.g. increases fat burning, insulin sensitivity, etc.).[3]
Elliot received his BS in Biochemistry from the University of Minnesota and has been a freelance writer specializing in nutritional and health sciences for the past 5 years. He is thoroughly passionate about exercise, nutrition, and dietary supplementation, especially how they play a role in human health, longevity, and performance. In his free time you can most likely find him lifting weights at the gym or out hiking through the mountains of Colorado. He will also host the upcoming BioKeto podcast. You can connect with him on Facebook (https://www.facebook.com/elliot.reimers) and Instagram (@eazy_ell)
A small side effect for some people is “ketosis breath”. Many people on a ketogenic diet have experienced this temporary phenomenon, and those taking exogenous ketones can experience it as well. The smell of your breath when you are early in the ketogenic diet can have a hint of acetone to it, and it might be mildly unpleasant, but it’s also harmless. Most gum is pretty low in carbohydrates and is a great option while your keto breath fades.

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.
Getting into a state of ketosis normally involves eating a ketogenic diet consisting of around 80 percent fat, 15 percent protein, and 5 percent carbs. Over time, the body transitions from burning carbs for fuel to burning ketones—an alternative fuel source that the liver makes by breaking down fat, explains keto diet expert Amy Davis, RD, LDN. Since advocates say that ketosis can help you lose weight fast, think more clearly, and feel more energized, it’s tempting to try.
Fortunately a new way to test ketosis has been developed - and that is by measuring acetone levels in the breath. This is rather new technology but based on the reports I have seen it does look reasonably reliable. The testing process is simple, you use a device like that made by Ketonix, you breathe into it, wait a minute or so and it will give you a color indicating the state of ketosis you are in. However, there are numerous downsides:
Exogenous ketones have become a popular nutritional supplement since their introduction in 2014. Unfortunately there is a lot of inaccurate information and marketing you have to read through to find the truth about them. This article does the hard work for you. It gets right to the true benefits and drawbacks of exogenous ketones supported by research studies.
For whatever reason, many patients won’t attempt a ketogenic diet—even if the evidence is clear that it could help. Doctors are often hesitant to recommend dramatic dietary shifts—even if they believe in their efficacy—to patients who are already dealing with difficult health issues. If you’ve got a picky kid with epilepsy, a pickier adult with Alzheimer’s, or a cancer patient who refuses to give up the familiar-yet-non-ketogenic foods that give him some small manner of comfort in this trying ordeal, exogenous ketones could make a big difference.
Ketone supplements contain exogenous ketones—synthetic ketones made in a lab. Most use a type of ketone called beta-hydroxybutyrate (BHB), which is the same as the ketones the body produces naturally. “We’re literally biohacking," says Amie Heverly, who began taking a ketone supplement called Prüvit last year and now works as a promoter selling Prüvit products. "You’re not adding a foreign substance to your body, because BHB is identical to what your body would naturally produce,” she explains.

At day 29 of the study, animals were euthanized and brain, lungs, liver, kidneys, spleen and heart were harvested and weighed. Organ weights were normalized to body weight. Ketone supplementation did not significantly change brain, lung, kidney, or heart weights compared to controls (Fig. 5a, b, d, f). MCT supplemented animals had significantly larger livers compared to their body weight (p < 0.05) (Fig. 5c). Ketone supplements BMS + MCT, MCT and BD caused a significant reduction in spleen size (BMS + MCT p < 0.05, MCT p < 0.001, BD p < 0.05) (Fig. 5e). Rats administered KE gained significantly less weight over the entire study compared to controls. BMS + MCT, BMS, and BD supplemented rats gained significantly less weight than controls during weeks 2 – 4, and MCT animals gained less weight than controls at weeks 3 – 4 (Fig. 6). Increased gastric motility (increased bowel evacuation and changes to fecal consistency) was visually observed in rats supplemented with 10 g/kg MCT, most notably at the 8 and 12-h time points. All animals remained in healthy weight range for their age even though the rate of weight gain changed with ketone supplementation [53–54]. Food intake was not measured in this study. However, there was not a significant change in basal blood glucose or basal blood ketone levels over the 4 week study in any of the rats supplemented with ketones (Fig. 7).
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.
Our mission at Ketologie is to help educate and assist people in transitioning to a ketogenic way of eating for life. Primarily, we support people achieving this via adopting a VLCHF or ketogenic way of eating. Exogenous ketones can however play a useful role in transitioning to and maintaining a ketogenic lifestyle, and so we have exhaustively researched and developed a unique, “next level” ketone supplement that focuses specifically on optimizing health via the gut-brain axis.
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.

Hi Mark, sorry this is off topic but not sure where to send a question for a future Ask Mark. I’m about to go into my yearly physical and I am wondering if there is any specific bloodwork that you like to do for your annual check up. I’m 47 year’s old and the than the basic blood work like lipid panel, etc..I’m going to ask my doctor to test my testosterone, HbA1C, fasting insulin, and Vitamin D levels. I’m also going to ask my doctor to do a stool test to check for parasites or other infections I may have picked up from open water swimming for triathlons. Can you recommend any other blood work that might be useful? Thanks!
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.
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!
Those new to keto should be testing to see if their bodies are in ketosis, regardless of method. Testing, in general, is the most objective way to know if you’re in ketosis. There can be some subjective benefits of ketosis: appetite suppression, fat loss, low blood sugar, improvement in mental cognition and focus. But before recognizing these subjective benefits, it’s important to track and measure the level of ketones in the blood to ensure ketosis on a physical level.
Great question. So if you are already in nutritional ketosis from your diet, exogenous ketones would still help raise ketone (energy) levels when you want that (maybe for focus at work or energy at the gym. They also help get you back into ketosis after cheat meals and skip the “keto flu” which is the period when your body is using up stored glycogen.
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.
Second, there are inherent metabolic differences between boosting ketones via diet and boosting ketones via supplements. On a ketogenic diet, ketones go up because you’re converting body and dietary fat into ketone bodies. A rise in endogenous ketones means you’re burning fat and building the requisite machinery to metabolize the new energy source. On exogenous ketones, ketones go up because you ate some ketones; conversion of body and dietary fat into ketone bodies goes down if anything.
That’s not to say that the supplements don’t work. They very well might. But they could also be useless—or even dangerous, says Christine Palumbo, RDN, Nominating Committee member for the Academy of Nutrition and Dietetics. As of right now, there’s no way to know. “Currently, there’s just not enough evidence from research studies to answer those questions,” Barnes adds.
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, and women may also experience amenorrhea or other disruptions to the menstrual cycle. This is why it is really important to know what combination of compounds you are consuming, particularly while you are on this very strict diet because the wrong balance can really mess with you in the long term and won't give you the high performance that you are looking for. 

Hey Staci, great to hear you’re getting back into it! To answer your question, it really depends on the individual but there are definitely things you can do to get back into ketosis faster – working out to deplete your glycogen stores or implementing intermittent fasting into your regimen – these are 2 common ways that should kick start you back in the right direction!


On day 29, rats were sacrificed via deep isoflurane anesthesia, exsanguination by cardiac puncture, and decapitation 4–8 h after intragastric gavage, which correlated to the time range where the most significantly elevated blood βHB levels were observed. Brain, lungs, liver, kidneys, spleen and heart were harvested, weighed (AWS-1000 1 kg portable digital scale (AWS, Charleston, SC)), and flash-frozen in liquid nitrogen or preserved in 4 % paraformaldehyde for future analysis.
Athletic performance benefits: The use of exogenous ketone supplements for bettering physical/athletic performance is promising for several reasons. Firstly, taking exogenous ketones (particularly BHB salts) induces acute nutritional ketosis for upwards of eight hours, mimicking fasting physiology (e.g. increases fat burning, insulin sensitivity, etc.).[3]
That’s exactly what ketones do: inhibit lipolysis, the breakdown of body fat into triglycerides and free fatty acids for burning. In normal conditions where ketones are produced endogenously, this is expected and beneficial. If homemade ketones increased lipolysis, you’d end up with ketoacidosis. You’d make ketones which released more body fat which got turned into more ketones which released more body fat which became more ketones. And on and on. It simply wouldn’t stop.

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.


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

d-βHB was measured immediately on whole blood using a handheld monitor and enzyme-based reagent strips (Precision Xtra, Abbott Diabetes Care, UK). Samples were stored on ice, centrifuged and duplicate plasma aliquots stored at −80°C. All urine passed during the visit was collected, the total volume recorded, and 1 ml aliquots taken, frozen and retained for analysis.
If you do the same calculations as I did above for estimating fat oxidation, you’ll see that EE in this case was approximately 13.92 kcal/min, while fat oxidation was only 67% of this, or 9.28 kcal/min, or 1.03 g/min. So, for this second effort (the test set) my body did about 5% less mechanical work, while oxidizing about 25% less of my own fat. The majority of this difference, I assume, is from the utilization of the exogenous BHB, and not glucose (again, I will address below what I think is happening with glucose levels).

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