Blood glucose concentrations are decreased during both exogenous and endogenous ketosis, although by different mechanisms. During endogenous ketosis, dietary carbohydrate deficit is the underlying cause of low blood glucose, along with reduced hepatic gluconeogenesis and increased ketone production (Cahill et al., 1966). With exogenous ketosis, carbohydrate stores are plentiful, yet ketones appear to lower blood glucose through limiting hepatic gluconeogenesis and increasing peripheral glucose uptake (Mikkelsen et al., 2015). One clinical use of the ketogenic diet is to improve blood glucose control, yet the elevated blood FFA may increase the risk of heart failure (Holloway et al., 2009). Thus, the ability of exogenous ketones to lower blood glucose without elevating blood FFA concentrations could deliver the desired effect of the diet, whilst also decreasing a potential risk.

Too low of sodium intake can be just as dangerous as getting too much. As with all essential nutrients, the graph for risk associated with sodium and health problems is actually u-shaped, such that both low and high quantities of sodium are associated with risk of cardiovascular disease and all-cause mortality[8]. Evidence also suggests that restricting sodium to the recommendations may rapidly increase plasma levels of renin, angiotensin II, and aldosterone, which can lead to complications in itself[9].
Participants consumed 13.2 mmol.kg−1 of βHB (6.6 mmol.kg−1 or 1,161 mg/kg of KE) over 9 h, either as 3 drinks of 4.4 mmol.kg−1 of βHB at 3 h intervals (n = 12), or as an initial bolus of 4.4 mmol.kg−1 of βHB given through a nasogastric tube, followed by an infusion of 1.1 mmol.kg.h−1, beginning 60 min after the initial bolus, for 8 h (n = 4). Two participants completed both conditions (total n = 14). In both conditions, the KE was diluted to 1.5 L using the same citrus water as used in Study 2.
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.
Ketogenic Diets and Physical Performance – Impaired physical performance is a common but not obligate result of a low carbohydrate diet. Lessons from traditional Inuit culture indicate that time for adaptation, optimized sodium and potassium nutriture, and constraint of protein to 15–25 % of daily energy expenditure allow unimpaired endurance performance despite nutritional ketosis.
Pruvit v Perfect Keto: One of the more popular brands for BHB salts is Pruvit (Keto OS). Pruvit is a good brand, but they do use some additives. Also, Pruvit is an MLM company that has tons of people pushing their products as the best weight loss product in the world. And you have to use one of their representatives’ referral codes to buy it. Learn more about the two in this Pruvit vs Perfect Keto comparison article.
A meal high in carbohydrate and calories significantly decreased peak d-βHB by ~ 1 mM (Figure ​(Figure4A)4A) and reduced the d-βHB AUC by 27% (p < 0.001, Figure ​Figure4B).4B). There were no significant changes in d-βHB Tmax (fed = 73 ± 6 min vs. fasted 66 ± 4 min). Despite the differences in d-βHB kinetics after the meal, there were no effects of food on urinary ketone excretion (Figure ​(Figure4C),4C), plasma AcAc (Figure ​(Figure4D)4D) or breath acetone (Figure ​(Figure4E)4E) following KE ingestion. Plasma AcAc kinetics followed a similar time course to d-βHB, with the ratio of blood d-βHB: AcAc being 6:1 when KE drinks were consumed whilst fasted, and 4:1 following the meal. As observed in Study 1, breath acetone concentrations rose more slowly than blood ketone concentrations, reaching a plateau at 150 min and remaining elevated for at least 4 h (Figure ​(Figure4E4E).
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!

Hi. Thanks for the informative article! I have fallen down the exogenous ketone rabbit hole for the last 2 days trying to figure everything out. I am currently on a nutritional ketonic diet but after 8 months, I am finding it difficult to stay on it 100%. I would like to remain on a low-carb diet, but also have a little more flexibility in my food choices. If you take the expense out of the equation, which product would you recommend for someone who wants to use ketosis as a method of weight loss? Thank you so much.

However, it's important to NEVER overlook the power of exercise and of course sticking to a proper routine to get the most optimized results. The most common mistake people make is by treating any keto supplement like a "wonder drug" that will help them shed weight in their sleep. Seriously... how is that even scientifically possible. So if you are thinking about trying out a particular keto supplement, I would suggest two things:
While ketone salts are widely available, unfortunately in the near-term ketone esters are in short supply and the only people who will be able to afford taking them several times per day will be elite athletes, the military, corporate CEO-types, and professional poker players. Even with economies of scale and ramping up production, the cost of raw materials to produce pure ketone esters will keep their price tag prohibitively high for most people, but could realistically get down to a few dollars per gram.
Slowly ramp up your ketone intake. Be patient! 🙂 For many of us, our bodies aren’t used to running on ketones, so you can expect an adjustment period. Try ¼ scoop first. Transitioning to ketosis removes water from our bodies, so getting lots of water will help with any dehydration and stomach issues. Ramp up from there, trying ½ scoop the second week or when you feel it’s appropriate, and then try a whole scoop 1-2 weeks in. You can use it for extra energy or to help get into ketosis if you aren’t there already. Most people use it 0-3 times per day.
Bottom line: EK isn't the magic pill for instant weight loss. EK triggers ketosis which is a metabolic state where your body burns fat for fuel. EK increases satiety and feeling full, and boosts energy for exercise which helps you lose weight for the long term. You should always aim for the long term and sustainable weight loss and keep the weight off for good instead of looking for a quick fix.

Relationship between blood ketone and glucose levels: a BMS + MCT (5 g/kg) supplemented rats demonstrated a significant inverse relationship between elevated blood ketone levels and decreased blood ketone levels (r2 = 0.4314, p = 0.0203). b At week 4, BMS + MCT (10 g/kg) and MCT (10 g/kg) showed a significant correlation between blood ketone levels and blood glucose levels (r2 = 0.8619, p < 0.0001; r2 = 0.6365, p = 0.0057). Linear regression analysis, results considered significant if p < 0.05

First and foremost, one of the most important factors is to be discipline when following the ketogenic diet. This means heavily restricting your carbohydrate intake, while switching to high-fat foods and moderate proteins. The general rule of thumb when it comes to splitting your macros out should look something like this: 5% (carbs)/ 80% (fats)/ 15% (proteins). Although if you’re just starting out, I wouldn’t focus too heavily on macros but rather place more importance in restricting your carbohydrate intake to 20 grams or less. Depending on the individual, most keto diets will allow approximately 20g-70g of net carbs as part of your overall daily intake, but if you’re asking the extreme question of ‘how to get into ketosis in 24 hours?’ then let’s focus on the absolute limit. For a more detailed breakdown, please see my keto shopping list article.
I carried out a survey among Diet Doctor users as background research to the experiment (a big thank you to the 638 people who responded!). In the survey, 28% of the respondents reported that they do take ketone supplements. The top four benefits that these respondents reported experiencing were increased energy, improved focus/cognition, reduced hunger and weight loss.
A sound sleep is highly associated with the dark. Also, studies have proven that our body’s natural defense mechanisms against cancer cells get activated in the absence of light (that’s why sleeping is the best way to natural healing). So turn off all the lights, TV screen, lamps, and all other light emitting devices at least 30 minutes before going to sleep. With this trick, you are actually preparing yourself to fall asleep.
We tested the effects of 28-day administration of five ketone supplements on blood glucose, ketones, and lipids in male Sprague–Dawley rats. The supplements included: 1,3-butanediol (BD), a sodium/potassium β-hydroxybutyrate (βHB) mineral salt (BMS), medium chain triglyceride oil (MCT), BMS + MCT 1:1 mixture, and 1,3 butanediol acetoacetate diester (KE). Rats received a daily 5–10 g/kg dose of their respective ketone supplement via intragastric gavage during treatment. Weekly whole blood samples were taken for analysis of glucose and βHB at baseline and, 0.5, 1, 4, 8, and 12 h post-gavage, or until βHB returned to baseline. At 28 days, triglycerides, total cholesterol and high-density lipoprotein (HDL) were measured.
Also, it’s important to remember that just because something may be SAFE (and to reiterate, I’m not saying a long term ketogenic diet is safe), it doesn’t mean it’s good for you or beneficial. Running Marathons could be considered safe (especially if it’s on a closed race circuit), but does this mean it’s good for you? Or should you be out running marathons every day?
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.
“Imagining that everyone is going to go on a ketogenic diet is very unlikely. I’ve done it myself, and it is hard as a diet to sustain for a long period of time,” said Verdin. “The interest for us in BHB is [if] can we recapitulate all the beneficial effects that we are seeing from the ketogenic diet simply by administering BHB as a food or as a drug, whatever you want to call it.”
Ketogenic diets have been successfully used to treat diseases that have an underlying metabolic component, effectively decreasing seizures in recalcitrant pediatric epilepsy (Kossoff et al., 2003), lowering blood glucose concentrations in type 2 diabetes mellitus (Feinman et al., 2015) and aiding weight-loss (Bueno et al., 2013). Emerging evidence supports several clinical uses of ketogenic diets, for example in neurodegenerative diseases (Vanitallie et al., 2005), specific genetic disorders of metabolism (Veech, 2004) and as an adjunct to cancer therapy (Nebeling et al., 1995). Ketone bodies themselves may underlie the efficacy of the ketogenic diet, either through their role as a respiratory fuel, by altering the use of carbohydrate, protein and lipids (Thompson and Wu, 1991; Cox et al., 2016), or through other extra- and intracellular signaling effects (Newman and Verdin, 2014). Furthermore, ketone metabolism may offer a strategy to improve endurance performance and recovery from exercise (Cox et al., 2016; Evans et al., 2017; Holdsworth et al., 2017; Vandoorne et al., 2017). However, achieving compliance to a ketogenic diet can be difficult for both patients and athletes and may have undesirable side effects, such as gastro-intestinal upset (Cai et al., 2017), dyslipidemia (Kwiterovich et al., 2003) or decreased exercise “efficiency” (Edwards et al., 2011; Burke et al., 2016). Hence, alternative methods to raise blood ketone concentrations have been sought to provide the benefits of a ketogenic diet with no other dietary changes.
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
Animal research findings report that BHB supplementation also enhances oxygen utilization, especially in the central nervous system (CNS).[11] While molecular oxygen is a crucial molecule for health and longevity, too much of it can be potentially toxic and speed the effects of aging in tissues throughout the body.Therefore, using a BHB supplement can effectively mitigate the toxic buildup of molecular oxygen, particularly in the CNS/brain.
Long-Term Effects of a Ketogenic Diet in Obese Patients – The present study shows the beneficial effects of a long-term ketogenic diet. It significantly reduced the body weight and body mass index of the patients. Furthermore, it decreased the level of triglycerides, LDL cholesterol and blood glucose, and increased the level of HDL cholesterol. Administering a ketogenic diet for a relatively longer period of time did not produce any significant side effects in the patients. Therefore, the present study confirms that it is safe to use a ketogenic diet for a longer period of time than previously demonstrated.(http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2716748/)

Nutritional ketosis induced with the KD has proven effective for the metabolic management of seizures and potentially other disorders [1–26]. Here we present evidence that chronic administration of ketone supplements can induce a state of nutritional ketosis without the need for dietary carbohydrate restriction and with little or no effect on lipid biomarkers. The notion that we can produce the therapeutic effects of the KD with exogenous ketone supplementation is supported by our previous study which demonstrated that acutely administered KE supplementation delays central nervous system (CNS) oxygen toxicity seizures without the need for dietary restriction [29]. We propose that exogenous ketone supplementation could provide an alternative method of attaining the therapeutic benefits of nutritional ketosis, and as a means to further augment the therapeutic potential of the KD.

One monk, for example, set out to do a 40 day fast with medical supervision while maintaining his daily activities in the monastery. After 36 days, the medical professionals had to step in due to “profound weakness” and low blood pressure when standing. Although the monk fasted for 15 days longer than Ghandi, the medical professionals were able to stop the fast in time so that he could recover.
This was a big surprise. We were at the very least expecting that drinking a ketone supplement would cause blood ketones to rise, but an average increase of 0.33 mmol/L is very small. The supplement associated with the highest average increase in blood ketones was Prüvit’s Keto-OS Max, but it was only an increase of 0.6 mmol/L. Brianna Stubbs, the ketone researcher I consulted with, agrees that an increase of below 2.0-3.0 mmol/L is unlikely to be of much use.
Over five visits, participants (n = 16) consumed either 4.4 mmol.kg−1 of βHB (2.2 mmol.kg−1 or 395 mg/kg of KE; 1 mole of KE delivered 2 moles of d-βHB equivalents): twice whilst fasted, and twice following a standardized meal, or an isocaloric dextrose drink without a meal. To improve palatability, drinks were diluted to 500 ml with a commercially available, citrus flavored drink containing 65 kCal (5 g of carbohydrate) (Glaceau, UK). The dextrose drink was taste-matched using a bitterness additive (Symrise, Holzminden, Germany). The standard meal consisted of porridge oats (54 g), semi-skimmed milk (360 ml) and banana (120 g), giving 600 kCal per person, with a macronutrient ratio of Carbohydrate: Protein: Fat of 2:1:1.
The fate of excess ketones: In the event someone has an excessive amount of ketones in the blood, the body (specifically the kidneys) will work as quickly as possible to filter out ketones via urine rather than converting them to adipose tissue.9 This is not to say that you can’t gain fat if you consume an exorbitant amount of exogenous ketones, but that they are less prone to be converted to fat than other nutrients.
There’s debate raging about which dietary tactic is the god particle for making you leaner, faster and healthier. How the ketogenic diet option squares off against the low carb route is vital for understanding the ways in which exogenous ketone supplements work. To get into ketosis the natural way, you need to keep your carb intake low enough for long enough for your body to begin using use fat as fuel. Your liver then converts a portion of that fat into energy molecules called ketones. These work together with glucose as a fuel source, but can actually kick in faster, allowing your body to operate more economically during lengthy, high-energy exercise efforts.
I don’t think we even need a drumroll here… Based on my background research into ketone-supplement companies, the survey of Diet Doctor users and the experiment itself, we cannot recommend taking these supplements. I can personally think of many more beneficial ways to invest money in my health, such as buying grass-fed meat and organic vegetables, or even buying a bicycle and riding it outside in the sunshine.
Been using yur stuff for the last week and tyere is absolutely no change in the amount of ketones based on the ketone strips i use to monitor ketone levels. I use another product as well and switched back and have sustained higher levels of ketones most of the day. Is there a reason that your product doesnot produce the results based on the strip test? I am a larger guy, 260 possibly need more? I have 2 tubs to go through and am not overly optimistic about whats going on.
If you are not on a vigorous exercise plan, I wouldn't go more than about a scoop a day (if you are a 30min/day, low carb person like me) because some of the research available says that if you get into ketosis using diet only and supplement with extra ketones, you may experience a slower rate of weight loss since you are getting your ketones from a supplement rather than the body transforming fat to ketones. As I progress, I will probably move up to 2 scoops per day.
Let’s take a look at some of the facts and misconceptions about three of the minerals used to make ketone mineral salts: sodium, calcium, and magnesium. Potassium is very hygroscopic, meaning that it absorbs water very easily. Therefore, it is only feasible that it can be utilized in liquid formulations.  Thus, one should be cautious if companies say they have potassium BHB salt powder in their product. I’d be very surprised if that’s actually the case.
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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