Dominic D’Agostino has two in-depth interviews on The Tim Ferriss Show (Part 1, Part 2). Discussion includes exogenous ketones for mitigating the onset of neurodegenerative diseases, using ketones in place of fasting for chemo-protection, benefits of ketone supplementation when consuming carbohydrates, the risks and potential toxicities of ketones.
 “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 chart below shows my ketone and glucose response to consuming 40g of KetoneAid’s ketone esters, which had been calculated to be my optimal serving size based on my weight (170lbs) and type of activity (I am moderately active/athletic, but cognitive experiments are a “low” physical activity). Normally, for increased physical performance ketone esters are consumed along with some glucose, but since I was only focusing on cognitive performance I did not consume any glucose.
Yes. Both producing BHB in your liver as well as supplementing with beta hydroxybutyrate very safe. As we mentioned before, levels of 0.5 – 3.0 mmol measured in a blood test are completely normal. Some people get stressed out when they hear the term “diabetic ketoacidosis” or DKA, which is an entirely different metabolic scenario where your BHB levels skyrocket to 15-25 mmol blood readings.
Because of how effectively exogenous ketones can reduce hunger for those in ketosis, pay attention to the cues your body gives you. It’s possible to extend your fasts longer than necessary because of a decreased appetite cue. While those who have some weight to lose might be tempted to think this is a favorable side effect, there is a difference between fasting and starving for nutrients. Make sure to get enough food to support your activities and maintain your muscle mass.
Proper sleep is important for hormone function and repair of the body. Not getting enough sleep is tough on the adrenals and blood sugar regulation. Try to get at least seven hours of sleep per night. If you struggle with quality sleep, create an environment that is conducive for rest. This could be keeping your room cooler, turning off all electronic devices one to two hours before bedtime or using a sleep mask.
Some general side effects of your body producing beta hydroxybutyrate is essentially the lull in time it takes to switch from carbohydrate metabolism to fat metabolism, which can take 3-4 days. This can lead to mood swings, fatigue, and general low energy. If you want to skip that step, we recommend taking exogenous BHBs to switch your body over effortlessly.
The many roles of magnesium include helping us maintain normal nerve and muscle function, as well as heart rate, supporting a healthy immune system, regulating blood glucose levels, and making energy production and protein synthesis possible[23]. Magnesium is also involved in both aerobic and anaerobic energy production. ATP synthesis (the body’s energy source) depends on enzymes that are activated by magnesium.
If given all as a single salt, 50 grams per day of BOHB would mandate daily intakes of 5.8 g Mg++, 9.6 g Ca++, 11.0 g Na+, or 18.8 g K+. Even if divided up carefully as a mixture of these various salts, it would be problematic getting past 30 grams per day of BOHB intake. And again, most of the currently marketed ketone salt formulations are made with a mix of the D- and L-isomers of BOHB, so the actual delivered dose of the more desirable D-isomer is considerably less. The other concern with the salt formulations is that, as the salts of weak acids, they have an alkalinizing metabolic effect that might have a modest but cumulative effect on blood pH and renal function.
You are probably wondering how there could possibly be a benefit to eating less frequently that goes beyond what you are already getting with a ketogenic diet. Restricting carbs and eating enough fat and protein does come with a plethora of health benefits, but when you add intermittent fasting to your lifestyle you can increase energy and reverse aging by harnessing the power of a nobel prize winning process.
I’m fasting (5 days fast, 2 days food) in an effort to aggressively lose weight. For the most part, I’m not doing the water & salt-only kind of fast… as I will also drink coffee & bone broth… as well as take Perfect Keto Base. Would it be “gilding the lily” to also add MCT powder to my coffee? I’m in nutritional ketosis… ranging from 0.8 to 2.0 or thereabouts.
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.
A typical serving of racemic ketone salts contains around 12g of beta hydroxybutyrate, of which only half is the D- form (6g). Compared to the 40g ketone esters I consumed (which are 100% D- form), I would need to consume somewhere around seven to nine packets of ketone salts to get the same amount of D-β-hydroxybutyrate (some D- form is wasted burning of the L- form), along with the huge amount of salts contained and more than a gallon of water (since the powders must be mixed). Even if one could consume that amount of ketone salts, they will probably suffer from what people often refer as “disaster pants” (aka diarrhea) due to the amount of salt consumed.

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If you read about ketosis in magazine or heard about it in a podcast and wanted to jump on the bandwagon, then I think you should avoid it. Remember, it is a strict diet, and the potential health downsides may not be worth the upsides, unless you are working with a medical professional and or you are tracking your labs to see what’s going on with your health (thyroid).
Exercising is undoubtedly important when it comes to losing weight. An added bonus of being in a state of ketosis is the ability to improve your exercise performance, but you should also remember that entering ketosis for the first time can be a bit of a challenge for a lot of people. The body is still adjusting to such a dramatic diet change, so exercising may prove to be difficult at first. The key here is to keep going.
Hi- Thank you for this super helpful post. I’m new to Keto and supplementing Keytones. I just got the Julian Bakery Keytones and am curious about how to take them as there are no instructions on the packaging. Indeed the website has a diet plan to follow with the keytones but I am very suspicious of it because it is 0 fat which I believe is not healthy for brain or body and given that I have soft tissue and joint issues, I try to eat enough fat daily. I want to lose weight and I crossfit 5 days per week. So how do I best start with using the keytone supplements? I took a scoop full yesterday when they arrived (in the early afternoon) but hadn’t yet eaten and I think that was a mistake because I had immediate diarrhea which lasted a few hours, even after eating.
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.
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.
No the main reason to enter ketosis fast is because it is not pleasent to be glycogen depleted and not yet be in the state of ketosis. You feel sleepy, without energy, some people even have headaches or mild flu symptoms. However you look at this it is not pleasant until your body starts producing ketones and you can effectively start using fat as the primary energy source. So you want to breakthrough this period as fast as possible and not be stuck in this middle place for days or even weeks.
I followed 30g carbs as my limit each day, moderate protein, increased fat intake (avocado at each main meal plus carefully chosen oils, eggs and nuts) and have upped green veg to the bucket load and incorporated a juiced lemon in water to my morning, as well as my usual water consumption. I also did intermittent fasting Mon to Thur, 18 hours fasting each day.
The “BHB salt” is simply a compound that consists of sodium (Na+), potassium (K+), and the ketone body β-hydroxybutyrate.  In supplements like Pruvit’s Keto OS  these individual components are being held together by ionic bonds; however, when you consume the product, it is absorbed into the blood where it dissociates into free Na+, K+, and BHB since it is a water-based solution.  Thus, consuming the product directly and immediately puts more ketones into your blood.
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).
The “BHB salt” is simply a compound that consists of sodium (Na+), potassium (K+), and the ketone body β-hydroxybutyrate. In supplements like Pruvit’s Keto OS these individual components are being held together by ionic bonds; however, when you consume the product, it is absorbed into the blood where it dissociates into free Na+, K+, and BHB since it is a water-based solution. Thus, consuming the product directly and immediately puts more ketones into your blood.
Recently, a friend of mine’s dad had high blood pressure. His doctor told him to stop consuming eggs and to avoid adding extra salt to his foods. That’s it. His recommendation was to rid a good, high-quality protein source, yet French fries, chicken nuggets, and even chicken noodle soup were all presumably okay. I’ll never understand some of these recommendations; nonetheless, they happen day in and day out, all over the world.
The USDA guidelines recommend less than 2400 mg of sodium per day for healthy adults, and 1500 mg or less for individuals over the age of 50 or at risk for hypertension[2]. For reference, 2300 mg of sodium is the equivalent of about one teaspoon of salt.  Even though these recommendations are promoted by the American Heart Associated and other health-related organizations, recent research has claimed that there is simply not enough evidence to support these guidelines[5]. Worldwide 24-hour urinary sodium excretion data suggest that the normal range is actually 2500-5000 mg per day, which is what most of us consume daily[6]. Additionally, people with high activity levels or chronically low blood pressure may require more sodium than the average person.
Once you hit the bed, the adrenal glands will be off and the body will enter the anabolic stage. This will allow your body to repair itself. If you stay up late for long periods of time your body will enter the hypercatabolic state. In this state, the levels of cortisol in your body increase significantly. This also increases the insulin resistance of the body which would again increase the blood sugar levels.

An effective ketosis program requires that you control your appetite. Caffeine has been proven to be an excellent appetite suppressant. It can curb your appetite and reduce your cravings for food. If you are finding it hard to implement intermittent fasting, try to introduce coffee into the equation. If you are not into coffee drinks, try to take tea or use caffeine pills. Both of them contain caffeine, which can help you to adjust smoothly into fasting.
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!
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.

Beta-hydroxybutyrate (BHB): Nutrition strategies that rely on carbohydrates always leave us needing more food. On the other hand, the ketogenic diet relies on and taps into your body’s stored fat for longer, more stable energy with no bonking. Many keto-lovers adopt this lifestyle because they love the mental clarity, focus, and productivity that they experience while in ketosis. Whether you’re full-time keto or not, our Perfect Keto is designed to support ultimate mental performance.


There’s some support that exogenous ketones can be helpful for people already dutifully following the keto diet — but research has been limited. One thing we know for sure: These aren’t a get-thin-quick solution. “I think people are drawn to a quick, easy fix, kind of a magic bullet supplement, and it’s not that this won’t contribute to weight loss, but it’s not that magic bullet,” Griffin says.
I am a little confused. I can see how EK’s can help up the state of ketosis, but as far is weight loss is concerned, aren’t the ketones you produce naturally created by the breaking down of your own fat? If I supplement with exogenous ketones, will that slow the natural creation of ketones? Especially if I am eating a higher amount of carbs. Would exogenous ketones speed fat loss, or slow it?
The metabolic phenotype of endogenous ketosis is characterized by lowered blood glucose and elevated FFA concentrations, whereas both blood glucose and FFA are lowered in exogenous ketosis. During endogenous ketosis, low insulin and elevated cortisol increase adipose tissue lipolysis, with hepatic FFA supply being a key determinant of ketogenesis. Ketone bodies exert negative feedback on their own production by reducing hepatic FFA supply through βHB-mediated agonism of the PUMA-G receptor in adipose tissue, which suppresses lipolysis (Taggart et al., 2005). Exogenous ketones from either intravenous infusions (Balasse and Ooms, 1968; Mikkelsen et al., 2015) or ketone drinks, as studied here, inhibit adipose tissue lipolysis by the same mechanism, making the co-existence of low FFA and high βHB unique to exogenous ketosis.

Unless otherwise stated, statistical analysis was conducted using Prism 6™ software. Values, expressed as means ± SEM, were considered significantly different at p < 0.05. Initial tests were undertaken to ensure that normality and sphericity assumptions were not violated. Subsequently, either one or two way repeated measures ANOVA, or Freidman's test with post-hoc Tukey or Dunnet's correction were performed, to compare changing concentrations of substrates, electrolytes, pH, insulin, breath and urinary βHB: both over time and between study interventions. In Study 2, data from each of the two study visits in each condition (fed and fasted) completed by an individual were included in the analysis.

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
We are told by our parents, doctors, and the media that milk builds strong bones and that we should take calcium supplements to help protect against osteoporosis. Indeed, calcium deficiency can lead to a plethora of health problems[12]. However, those of us who take calcium supplements or consume calcium-fortified foods and beverages may, in fact, be consuming above the Recommended Dietary Allowance (RDA) of calcium.

The keto-esters are more appropriate for delivering higher doses of BOHB, but with repeated dosing can push the limits of taste and GI tolerance. There has been fairly extensive research on a compound 3-hydroxybutyl 3-hydroxybutyrate that is converted via hydrolysis and liver metabolism to yield 2 molecules of ketones, presumably mostly D-BOHB (Clarke 2012 and 2014). In a study involving lean athletes, an approximate 50 gram dose raised blood BOHB levels to 3 mM after 10 min and reached 6 mM by 20 min. Submaximal exercise resulted in increased ketone disposal from 2 to 3 hours and contributed significantly to whole body energy use during exercise (Cox 2016). This product has been shown to significantly reduce appetite after a single dose (Stubbs 2018) but its effect on body weight in humans over a longer period of time has not been studied, nor has its effect on blood glucose control been reported in humans with type 2 diabetes. However a single dose prior to a glucose tolerance test in healthy humans reduced blood glucose area-under-curve by 11% and non-esterified fatty acid area-under-curve by 44% (Myette-Cote 2018).


Your body is trained to use glucose as its main energy source, but when you decrease your consumption of carbs, your body turns to another source of energy that is naturally produced by our own bodies--fat. Therefore, a great way to lose weight faster is to consume low-carb fruits, vegetables and other food that are specially designed for a low-carb 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.
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.
They’ve got enough science behind them to suggest they do work very well indeed, but watch out for the online ads featuring the raspberry ketone fat burners. Their name is little more than a parlour trick because this is not related in any way to ketones, a ketogenic diet or nutritional ketosis. They are merely the natural substance that gives raspberries their sweet aroma and flavour. Just because they’re marketed at the must-have fat burner, doesn’t mean they work and are one of the most widely spread Internet scams. There aren’t any human studies to back up raspberries claims so exercise a handful of caution when choosing your ketone supplier. Make sure they’re reputable, can be held accountable and are Australian made to set yourself up to become leaner while increasing your stamina.
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.
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.
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.
While it usually takes 2-7 days for your body to enter into a state of ketosis on a ketogenic diet, there are a few things you can do to kickstart this process. It isn’t guaranteed but it will assist in the process, and may work in extreme cases. Intermittent fasting, exercise, proper sleep, a strict high-fat-low-carb diet, and supplementation can all help fastened the transition process. Whether you’ve fallen out of ketosis after a cheat weekend or maybe you’re somebody who have just started out on your keto journey – here is how to get into ketosis in 24 hours.

BHB supplementation can drastically enhance your insulin sensitivity, resulting in better shuttling of blood glucose into cells.[10] With type-2 diabetes and insulin resistance becoming growing concerns, BHB supplementation may provide a promising alternative for healthy blood glucose regulation in the coming years.Even for everyday gym goers and fitness enthusiasts, increasing insulin sensitivity via BHB supplementation can be a great benefit as this puts your body in a better position for partitioning nutrients/carbohydrates to energetically demanding, glycolytic tissues, such as skeletal muscle.


It’s sometimes the case that a person has been attempting to transition to a state of ketosis, but in spite of their best efforts, they seem stuck in a kind of limbo where they’re eating hardly any carbs, but they don’t seem to be losing weight or experiencing the other benefits of the keto diet. But the science is the science, which means if you’re doing everything right you should be in ketosis. If you’re not, or you seem to be drifting in and out of a keto state, it’s not your body’s fault, it’s your diet.
2. Shimazu, T., Hirschey, M.D., Newman, J., He, W., Shirakawa, K., Le Moan, N., Grueter, C.A., Lim, H., Saunders, L.R., Stevens, R.D., Newgard, C.B., Farese Jr, R.V., De Cabo, R., Ulrich, S., Akassoglou, K., and Verdin, E. (2013). Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science 339, 211-214.

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.
I bought this because I didn't want to be sucked into an autoshipment for a ketone supplement like KetoOS, which is HOT right now. I did the comparison on the ingredient list between this product and KetoOS and they are quite similar. I think one of the big differences is that KetoOS has the option of caffeinated or non-caffeinated powders. For the cost and the free shipping (I'm a Prime member), it's something I could easily fit into my budget, rather than the $114 canister you'd get with KetoOS.
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 year before last I somehow full on Rocked at the keto diet lost 100lb, and was taking adderall. I am transitioning back into it again also back on the adderall, but i seem to have no energy and last time my doc did my blood work i was only 16% hydrated. Obviously it’s a huge problem for me, staying hydrated and trying to lift the fogginess. I am type 2 diabetic and my doctor is on board with me trying all to keep my sugars down YEAH!!! I have never tried any exogenous product. My body seems to not absorb much vitamins. Can anyone make a or any suggestion to me as to how to get this under control?
Funding. This work supported by an Industrial DPhil Fellowship to BS from the Royal Commission for the Exhibition of 1851. JM was supported by the EPSRC Doctoral Training Centre and Prize Fellowship; Ref: EP/M508111/1. The funding sources were not involved in the design, conduct or analysis of this study. TΔS Ltd. provided the ketone ester, ΔG®, and NTT DOCOMO Inc. provided the acetone meter for the study.
-       Take ketone supplements (therapeutic ketosis): A second option is to consume ketones in the form of a supplement. Supplements like Perfect Keto Ketone Salts that provide the exact same ketone bodies that are produced naturally in the body. And while supplements are not a complete replacement for the benefits of ketones produced through diet, they do lower the barrier by allowing anyone to start benefiting from therapeutic ketones.
Geek note: Technically speaking, beta hydroxybutyrate is NOT a legitimate ketone body. Ketone bodies, or ketones are technically molecules with carbonyl carbons which are bonded to two additional carbon atoms. One carbon has four available bonds. When that carbon is double bonded to oxygen and also has two single bonds to carbon, we have a ketone body. If you have a carbon atom that is double bonded to an oxygen (carbonyl group), which is also bound to an -OH group instead of two different carbon atoms, that would be a carboxylic acid, but that really doesn’t matter in this case. For all intents and purposes of the ketogenic diet, betahydroxybutyrate should be considered one of the three ketone bodies and a “ketone” nonetheless. Your body uses BHB pimarily for energy in the state of ketosis, so it’s a ketone, okay?

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