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.
Currently, we lack enough evidence to change the recommendations for calcium intake. The Tolerable Upper Intake Level (UL) for adults 19-50 years old is 2500 mg. This is well over the RDA of 1000 mg for the same age group. Calcium supplements commonly contain 600-1200 mg. When assessing your own calcium intake, keep in mind that calcium from food sources and calcium from supplements may have different outcomes.
 “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)
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.
“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.”

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.


When your body is done using up a certain substrate to create energy (acetyl-CoA) after eating carbohydrates, it will start to find creative ways to get the job done. This is something that you want to happen. This is the switch to ketosis. If you didn’t do this, you’d be dead after fasting for a very short period of time. Under normal circumstances, the liver will start making beta-hydroxybutyrate from long chain and medium chain fatty acids that are liberated from your fat tissue. You are turning fat into fuel. Good work. This is why people can fast for months at a time and still function like normal humans.

Some think so because higher ketone levels imply increased fuel for the brain and heart (that prefer ketones), and increased protection against inflammation and oxidation. But are the health benefits coming from the ketones themselves, or are they coming from the state you have to put your body in to actually produce them? And if you're kicking yourself out of ketosis by ingesting ketones would you still get the same benefits?
Studies show that exercising depletes both liver and muscle glycogen faster than fasting [4]. For example, swimming for an hour and a half depletes the same amount of glycogen as a 24-hour fast. However, it's a good idea to eat a tiny amount of carbs and protein before and after a workout to prevent muscle damage. Your body can break down proteins in your muscles if glycogen stores get depleted during workouts.
So if you really want to jump start ketosis, do what the prehistoric humans did; don’t eat for 3 to 5 days. Keep the water bottle and multivitamins close and go on a strict fast. It might seem extreme and to a degree it is, but starving yourself will put you into ketosis. No ifs, ands, or buts about it. And it will cause you to lapse into a ketogenic state faster than if you tried to do so by manipulating the foods you eat (replacing carbs with fats). Once starvation has caused your body to transition to a ketogenic state, you can begin to introduce your low carb, high fat keto-friendly foods.
Great question. We can’t see any reason this can’t be a part of a successful weight loss program on the ketogenic diet. In the morning with coffee is a very popular way to raise ketone levels in the morning. See if you are on pace with your goals and perhaps try a week with a different breakfast to see what feels best. Also – new article might be helpful here too: https://perfectketo.com/exogenous-ketones-for-weight-loss/ Good luck! 🙂
Miriam, Thank you for the questions. I am going to do my best here to provide you with answers: Q: The manufacture of BHB salts involves ionic bonding of an anion (beta-hydroxybutyrate) with a cation (Na+, K+, Ca+, Mg+). At least one of the exogenous ketone products you listed does in fact contain potassium ions. People taking potassium-sparing drugs need to know this and that raises concerns about leaving it off your chart. A: The table lists the BHB and the mineral content from the BHB salts (no added minerals). Therefore, since potassium BHB is not in any of the… Read more »
This fasting process will not only activate autophagy in your cells, it will also increase your ketones much more quickly than if you were just eating a standard ketogenic diet. If you start implementing intermittent fasting and activities (like walking, cycling, or lifting weights) together, you can raise ketone levels and increase autophagy more than you would with intermittent fasting alone. This suggests that intermittent fasting would be a great addition to your life, but it is important to be familiar with the negative symptoms that can arise before you start.
Another effect of the ketone drinks was to lower blood glucose, free fatty acids, and triglyceride levels. This sounds great. Elevated levels of all those markers are harbingers of disease, particularly if they remain chronically elevated. But think about what this means. If free fatty acids go down, that means adipose tissue isn’t being liberated for burning.
Appetite suppression: Appetite was measured in 10 males and 5 females after consuming a ketone ester (KE) or a dextrose (DEXT) drink . Desire to eat and perception of hunger dropped after both drinks, but the KE was 50% more effective for 1.5-4hrs. Insulin levels rose for both drinks but were 3x less with the KE drink after 30mins (Fig 2). The hunger hormone, ghrelin, was significantly lower between 2 to 4 hours after drinking the KE (Fig 2). In conclusion Ketone esters delay the onset of hunger and lower the desire to eat. 8
Exogenous ketones provide the body with another fuel to employ. Think about it like an electric car that runs on both gas and electricity: by consuming ketones along with carbohydrates, the body will preferentially burn the ketones first, saving the carbohydrates for later. Exogenous ketones allow us to enter a metabolic state that wouldn't occur naturally: the state of having full carbohydrate stores, as well as elevated ketones in the blood. This could be advantageous to athletes looking to boost their physical performance. 

Eating around 20 grams of net carbs a day is as a foolproof way to get you into ketosis a quickly as is humanly possible. However, having 50 grams of total carbs will also get you into ketosis within three days [3]. This amount of carbs is enough to deplete glucose reserves. It's also low enough to prevent fat being used to make glucose and, instead, the body is forced to make ketones.
How BHB turns into energy is a fairly simple process. As we’ve mentioned, beta hydroxybutryate eventually leads to energy production after you consume it or after your body breaks stored body fat down. It does this by going into the cell, entering the mitochondria (energy factories) at which stage it cleaves the carboxyl acid group and becomes acetoacetate (another “ketone body”). Acetoacetate turns into acetoacetyl-CoA, which then is cleaved to acetone (another “ketone body”) and acetyl-CoA. Acetyl-CoA is the whole reason we want BHB in the first place. This jumps into what is called the Kreb’s cycle (don’t you remember any of your biochemistry classes?) and is churned into ATP — the energy currency of your cells!
I heard a rep from Perfect Keto on a podcast and your Exogenous Ketones. I ordered and received it the other day. I see from this article that I should not do a full scoop at once, but break it up in a day. Good to know. I had about a half scoop before I worked out this morning and could tell I had more energy. Loved that. Just curious….any ideas how long it will take me to get back into ketosis and fat burning?? (I know it depends on what I eat, but a general idea that I promise not to hold you too! (I’m actually missing having ‘keto breath!)
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.
So if you really want to jump start ketosis, do what the prehistoric humans did; don’t eat for 3 to 5 days. Keep the water bottle and multivitamins close and go on a strict fast. It might seem extreme and to a degree it is, but starving yourself will put you into ketosis. No ifs, ands, or buts about it. And it will cause you to lapse into a ketogenic state faster than if you tried to do so by manipulating the foods you eat (replacing carbs with fats). Once starvation has caused your body to transition to a ketogenic state, you can begin to introduce your low carb, high fat keto-friendly foods.
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!
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.
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.
Exogenous Ketones have been shown in performance studies of both humans and animals to improve metabolic efficiency, which in essence means that your body is using better fuel that burns more efficiently over longer periods of time, and decreases the amount of fuel you need while performing. Where glucose fails (glycogen depletion), ketones pick up the slack!
I just read your comment and was wondering the same thing. I can see how exogenous ketones can be a great energy boost to people on the ketogenic diet, but I don’t see how they can speed fat loss. Keto OS claims you can eat higher carbs and still see the benefits of ketosis. I don’t see how that is possible. the whole point of weight loss through ketosis is the breaking down of your own fat to create energy. I don’t see how exogenous energy will increase natural fat breakdown. I wish I could get a straight answer to this from somebody.
As KE drinks achieved a significantly higher d-βHB concentrations than KS, we investigated factors that may be important in the use of ketone drinks to achieve nutritional ketosis. Initially we determined the repeatability of blood ketosis following KE drinks and found little variation in kinetic parameters between individuals. Variability between participants was less than within the population, and accurate individual prediction of the d-βHB Cmax following a body-weight adjusted KE drink was achieved. Variability within individuals was likely due to normal daily changes in GI function, including gastric emptying, portal blood flow or intestinal transit time, which may alter KE hydrolysis and absorption.

If you’ve done any reading about ketosis, you no doubt read at some point that ketosis is a “natural” state. You may have read on a bit more and learned what is meant by that statement or you may have simply skipped ahead to the keto success stories and decided to give it a try. But we’d like to direct your attention back to that little tidbit of information about keto being “natural” for a moment.
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.

If you’re somebody who isn’t already a keto-goer, then you might be wondering why? Why do I need to limit my carbohydrate intake to get my body into a state of ketosis? Simply put, and without getting to technical; you want your body to be in a constant state where fat is the is the primary source of fuel for the body rather than glucose. You see, once you eat carbs, the body will break this down into glucose which it will then use for fuel before tapping into your fat reserves for energy. If you limit the amount of glucose that is in your system by restricting your carbohydrate intake, the body has no choice but to tap into your fat stores for energy. Fats are metabolised in the liver where ketones are then produced for your physical and cognitive needs.
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!

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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