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.

Patrick Arnold is an organic chemist who is notorious for being the creator of several performance-enhancing steroids. He is arguably one of the strongest influencers on the advancement of sports supplementation. Currently he is focused on developing products under the KetoSports brand, which includes two exogenous ketone products – KetoForce and KetoCaNa.


Let me introduce myself. My name is Mark Sisson. I’m 63 years young. I live and work in Malibu, California. In a past life I was a professional marathoner and triathlete. Now my life goal is to help 100 million people get healthy. I started this blog in 2006 to empower people to take full responsibility for their own health and enjoyment of life by investigating, discussing, and critically rethinking everything we’ve assumed to be true about health and wellness...
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!
In addition to the Weir coefficients being potentially off (which impacts EE), the RQ interpretation may be incorrect in the presence of endogenous or exogenous ketones. As a result, the estimation of fat and glucose oxidation may be off (though it’s directionally correct). That said, the current interpretation seems quite plausible—greater fat oxidation when I had to make my ketones; less when I got my ketones for “free.”
Her clients have had similar success. One woman, for instance, has gone from around 170 pounds to 140 pounds since April without making any initial dietary changes. She’s started to gravitate towards more keto foods over time, but still eats her favorite high-carb treats. As for exercise? Her routine consists of a couple of walks each week, Heverly says.
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.
In a subset of participants (n = 7) the effect of 3.2 mmol.kg−1 of βHB as KE and KS on blood pH and electrolytes after ketone drinks was investigated. Blood d-βHB kinetics were similar to those in the initial experiment (Figure ​(Figure3A).3A). After 60 min, blood pH declined from 7.41 to 7.31 following a KE drink (p < 0.001, Figure ​Figure3B).3B). Bicarbonate fell significantly from 23.6 ± 0.7 to 17.0 ± 0.8 mM following KE drinks (p < 0.001), but remained within the normal range (Figure 3C). Both ketone drinks significantly decreased blood potassium concentrations by 0.7 mM (both drinks p < 0.05, Figure 3D) and increased sodium and chloride concentrations (Sodium: both drinks p < 0.05, Chloride: KE = p < 0.05, KS = p < 0.005, Figures 3E,F).
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).
Some people follow more of an Ultra Low Carb diet approach. This is generally around 50g or less of carbs per day. A ULC is more supportive of reaching a ketogenic state, but again total carbs are not the only variable when it comes to reaching ketosis (other factors such as types of carbs, protein consumption, portion size, ingredients, supplements used etc. all play a role and will be covered in more detail below). 

The final graph, below, shows the continuous data for only VO2 side-by-side for the 20 minute period. The upper (blue) line represents oxygen consumption under control conditions, while the lower line (red) represents oxygen consumption following the BHB ingestion. In theory, given that the same load was being overcome, and the same amount of mechanical work was being done, these lines should be identical.
Fortunately, you don’t need to be a dietary math savant to cash in on these rewards because the supplement eggheads took the liberty of creating exogenous ketones, which act as direct substitutes to the ones your body creates. Unlike other fat burners that give you the skits jitters, these are actually helping exercisers reach new personal bests while getting leaner, and are totally legal. Here’s what you need to know to get a slice of the action safely.
The classical KD consists of a 4:1 ratio of fat to protein and carbohydrate, with 80–90 % of total calories derived from fat [27]. The macronutrient ratio of the KD induces a metabolic shift towards fatty acid oxidation and hepatic ketogenesis, elevating the ketone bodies acetoacetate (AcAc) and β-hydroxybutyrate (βHB) in the blood. Acetone, generated by decarboxylation of AcAc, has been shown to have anticonvulsant properties [28–32]. Ketone bodies are naturally elevated to serve as alternative metabolic substrates for extra-hepatic tissues during the prolonged reduction of glucose availability, suppression of insulin, and depletion of liver glycogen, such as occurs during starvation, fasting, vigorous exercise, calorie restriction, or the KD. Although the KD has clear therapeutic potential, several factors limit the efficacy and utility of this metabolic therapy for widespread clinical use. Patient compliance to the KD can be low due to the severe dietary restriction - the diet being generally perceived as unpalatable - and intolerance to high-fat ingestion. Maintaining ketosis can be difficult as consumption of even a small quantity of carbohydrates or excess protein can rapidly inhibit ketogenesis [33, 34]. Furthermore, enhanced ketone body production and tissue utilization by the tissues can take several weeks (keto-adaptation), and patients may experience mild hypoglycemic symptoms during this transitional period [35].
The same question posed in a different way can be, what’s better, getting protein from powder or from a grass-fed steak or wild salmon? Omega-3 from supplements or from a variety of healthy wild fish? Just like with health supplements where you consume an isolated nutrient instead of the whole food where it comes from, if it’s possible to get what you need from whole food or nutrition, then that’s probably the best choice.
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Effects of ketone supplementation on blood βHB. a, b Blood βHB levels at times 0, 0.5, 1, 4, 8, and 12 h post intragastric gavage for ketone supplements tested. a BMS + MCT and MCT supplementation rapidly elevated and sustained significant βHB elevation compared to controls for the duration of the 4-week dose escalation study. BMS did not significantly elevate βHB at any time point tested compared to controls. b BD and KE supplements, maintained at 5 g/kg, significantly elevated βHB levels for the duration of the 4-week study. Two-Way ANOVA with Tukey’s post hoc test, results considered significant if p < 0.05. Error bars represent mean (SD)


There are many different variations of intermittent fasting as well. Dr. Dom D’Agostino, the well-known ketogenic diet researcher, suggests doing a longer intermittent fast for 3 days, 3 times a year. This means not eating for 3 days, and eating normally until the next fast. Daily intermittent fasts are recommended as well. He says that it is ideal to have one to two meals after fasting for most of the day to reap the benefits of intermittent fasting every day.


The classical KD consists of a 4:1 ratio of fat to protein and carbohydrate, with 80–90 % of total calories derived from fat [27]. The macronutrient ratio of the KD induces a metabolic shift towards fatty acid oxidation and hepatic ketogenesis, elevating the ketone bodies acetoacetate (AcAc) and β-hydroxybutyrate (βHB) in the blood. Acetone, generated by decarboxylation of AcAc, has been shown to have anticonvulsant properties [28–32]. Ketone bodies are naturally elevated to serve as alternative metabolic substrates for extra-hepatic tissues during the prolonged reduction of glucose availability, suppression of insulin, and depletion of liver glycogen, such as occurs during starvation, fasting, vigorous exercise, calorie restriction, or the KD. Although the KD has clear therapeutic potential, several factors limit the efficacy and utility of this metabolic therapy for widespread clinical use. Patient compliance to the KD can be low due to the severe dietary restriction - the diet being generally perceived as unpalatable - and intolerance to high-fat ingestion. Maintaining ketosis can be difficult as consumption of even a small quantity of carbohydrates or excess protein can rapidly inhibit ketogenesis [33, 34]. Furthermore, enhanced ketone body production and tissue utilization by the tissues can take several weeks (keto-adaptation), and patients may experience mild hypoglycemic symptoms during this transitional period [35].
Proponents like Heverly say that taking exogenous ketones can transform your body—and your life. (Her before-and-after shots below were taken just 10 days apart.) “Within 10 days, my body had this shift. My midsection wasn’t as bloated or fluffy. And I don’t have that cellulite on my legs now,” she says. Heverly also credits Prüvit with giving her a much-needed energy boost and improved mental clarity.
I started this website because it was hard to find trustworthy, evidence-based information about the ketogenic diet. Information that was published and peer reviewed by respected scientific journals. After years of research, I'm sure you'll achieve great results in a healthy way following my advice. I do my best to translate scientific research jargon into plain English. Remember, it's always a good idea to consult a doctor before starting a new diet!
Why is this desirable? Think about energy production in your body much like macro energy consumption on a planetary level. Coal is gross and dirty and messes tons of different things up. You need to continue to burn it to get energy. Solar power is free, clean and pretty much limitless. This is pretty much the same story when you are burning carbs (coal) versus fats (solar) for energy.
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).
However, with the ketone esters, the effects are nearly immediate, and my entire body was humming throughout the entire day, but not in a jittery way. I was full of mental and physical energy that lasted without any sort of crash (it was a gradual taper). During my cognitive tests, things felt almost effortless as I played the various games. After my experiment was complete I continued writing code for several hours, then went to the gym to work out. I did forget to each lunch though, so there must be some suppressive effect on appetite.
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.
I also chatted to some Prüvit reps, who told me that it might be necessary to keep taking the supplements for a couple of months to start to see more elevated ketones. Well, the proof is in the pudding (or in this case, in the fluorescent-coloured, artificial-tasting pink drink). But I would hesitate before spending money on a two-month supply just to find out if that’s true. Real Ketones’ Kegenix Prime was associated with a decrease blood ketones. Not a good start, and we’ll get back to this point later.
In terms of getting back into Ketosis, Keto//OS would most likely be a better choice (and a change back to a low-carb diet, of course) because it not only has MCTs, but also provides beta-hydroxybutyrate, which is the product that comes from your liver after it synthesizes acetoacetate. However, since this product also has caffeine (great for workouts), you might want to go with the decaf if you’re strictly looking for a ketosis jumpstart.
However, we will not be commenting on ketone esters since there are big differences between them and ketone salts, and the ketone salts are the ones that have been heavily commercialized and marketed to the public over recent years. Ketone esters may be more difficult to market due to their having an unpleasant taste. We may look more deeply into the esters in the future.
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:
Recent studies suggest that many of the benefits of the KD are due to the effects of ketone body metabolism. Interestingly, in studies on T2D patients, improved glycemic control, improved lipid markers, and retraction of insulin and other medications occurred before weight loss became significant. Both βHB and AcAc have been shown to decrease mitochondrial reactive oxygen species (ROS) production [36–39]. Veech et al. have summarized the potential therapeutic uses for ketone bodies [28, 40]. They have demonstrated that exogenous ketones favorably alter mitochondrial bioenergetics to reduce the mitochondrial NAD couple, oxidize the co-enzyme Q, and increase the ΔG’ (free enthalpy) of ATP hydrolysis [41]. Ketone bodies have been shown to increase the hydraulic efficiency of the heart by 28 %, simultaneously decreasing oxygen consumption while increasing ATP production [42]. Thus, elevated ketone bodies increase metabolic efficiency and as a consequence, reduce superoxide production and increase reduced glutathione [28]. Sullivan et al. demonstrated that mice fed a KD for 10–12 days showed increased hippocampal uncoupling proteins, indicative of decreased mitochondrial-produced ROS [43]. Bough et al. showed an increase of mitochondrial biogenesis in rats maintained on a KD for 4–6 weeks [44, 45]. Recently, Shimazu et al. reported that βHB is an exogenous and specific inhibitor of class I histone deacetylases (HDACs), which confers protection against oxidative stress [38]. Ketone bodies have also been shown to suppress inflammation by decreasing the inflammatory markers TNF-a, IL-6, IL-8, MCP-1, E-selectin, I-CAM, and PAI-1 [8, 46, 47]. Therefore, it is thought that ketone bodies themselves confer many of the benefits associated with the KD.
I wrote this post at about the same time Germany won the World Cup in Rio de Janeiro in 2014. There’s been a lot of moving and shaking in the world of exogenous ketones since then, not to mention soccer. Looking back on my post, I still consider it relevant in terms of what exogenous ketones possibly can (and cannot) do for performance. In this case, to see if exogenous ketone esters provide me a “boost” by allowing me to do the same amount of work while expending less energy (and work at a relatively lower VO2) compared to no supplementation.

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