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My experience with exogenous ketones

My experience with exogenous ketones

I wrote this submit at about the identical time Germany gained the World Cup in Rio de Janeiro in 2014. There’s been numerous shifting and shaking on the earth of exogenous ketones since then, to not point out soccer. Wanting again on my publish, I nonetheless think about it related when it comes to what exogenous ketones probably can (and can’t) do for efficiency. On this case, to see if exogenous ketone esters present me a “increase” by permitting me to do the identical quantity of labor whereas expending much less power (and work at a comparatively decrease VO2) in comparison with no supplementation.

I’m getting an growing variety of questions on exogenous ketones. Are they good? Do they work for efficiency? Is there a dose-response curve? If I’m fasting, can I eat them with out “breaking” the quick? Am I in ketosis if my liver isn’t producing ketones, however my BOHB is 1.5 mmol/L after ingesting ketones? Can they “ramp-up” ketogenesis? Are they a “sensible drug?” What occurs if somebody has excessive ranges of each glucose and ketones? Are some merchandise higher than others? Salts vs esters? BHB vs AcAc? Can taking exogenous ketones scale back endogenous manufacturing on a ketogenic weight loss plan? What’s the distinction between racemic mixtures, D-form, and L-form? What’s your expertise with MCTs and C8?

Caveat emptor: the next submit doesn’t come near answering most of those questions. I solely doc my expertise with BHB salts (and a non-commercial model at that), however say little to nothing about my expertise with BHB esters or AcAc esters. However it’ll present you’ll some context and understanding about what exogenous ketones are, and what they could do for athletic efficiency. We’ll possible podcast concerning the questions and subjects above and canopy different elements of exogenous ketones in additional element.

—P.A., June 2018


Unique publication date: August 14, 2014

Final yr I wrote a few posts on the nuances and complexities of ketosis, with an emphasis on dietary ketosis (however some dialogue of different states of ketosis—hunger ketosis and diabetic ketoacidosis, or DKA). To know this submit, you’ll need to at the least be acquainted with the concepts in these posts, which may be discovered right here and right here.

Within the second of those posts I talk about the Delta G implications of the physique utilizing ketones (particularly, beta-hydroxybutyrate, or BHB, and acetoacetate, or AcAc) for ATP era, as an alternative of glucose and free fatty acid (FFA). On the time I wrote that publish I used to be notably (learn: personally) within the Delta G arbitrage. Said merely, per unit of carbon, utilization of BHB presents extra ATP for a similar quantity of oxygen consumption (as corollary, era of the identical quantity of ATP requires much less oxygen consumption, when in comparison with glucose or FFA).

I additionally concluded that publish by discussing the potential for testing this (theoretical) concept in an actual individual, with the assistance of exogenous (i.e., artificial) ketones. I’ve seen this impact in (unpublished) knowledge in world class athletes not on a ketogenic weight loss plan who’ve supplemented with exogenous ketones (extra on that, under). Case after case confirmed a small, however vital improve in sub-threshold efficiency (for instance, efforts longer than about four minutes all-out).

So I made a decision to seek out out for myself if ketones might, certainly, supply up the identical quantity of usable power with much less oxygen consumption. Some housekeeping points earlier than stepping into it.

  1. This can be a self-experiment, not actual “knowledge”—“N of 1” stuff is suggestive, however it prevents using nifty little issues likes error bars and p-values. Please don’t over interpret these outcomes. My cause for sharing that is to spark a dialogue and hope that a extra systematic and rigorous strategy could be undertaken.
  2. All the knowledge I’ll current under have been from an experiment I did with the assistance of Dominic D’Agostino and Pat Jak (who did the oblique calorimetry) in the summertime of 2013. (I wrote this up instantly, however I’ve solely obtained round to running a blog about it now.) Dom is, far and away, probably the most educated individual on the subject of exogenous ketones. Others have been at it longer, however none have the huge experiences with all attainable modalities (i.e., esters versus salts, BHB versus AcAc) and the concurrent understanding of how dietary ketosis works. If individuals name me keto-man (some do, as foolish because it sounds), they need to name Dom keto-king.
  3. I’ve tried the next preparations of exogenous ketones: BHB monoester, AcAc di-ester, BHB mineral salt (BHB mixed with Na+, Okay+, and Ca2+). I’ve consumed these at totally different concentrations and together with totally different mixing brokers, together with MCT oil, pure caprylic acid (C8), branch-chained amino acids, and lemon juice (to decrease the pH). I gained’t go into the small print of every, although, for the sake of time.
  4. The ketone esters are, hands-down, the worst tasting compounds I’ve ever put in my physique. The world’s worst scotch tastes like spring water in comparison with this stuff. The primary time I attempted 50 mL of BHB monoester, I failed to combine it with something (Dom warned me, however I used to be too wanting to attempt them to truly learn his directions). Strategic error. It tasted as I think about jet gasoline would style. I assumed I used to be going to go blind. I didn’t cease gagging for 10 minutes. (I did this earlier than an early morning bike experience, and I used to be gagging so loudly within the kitchen that I awoke my spouse, who was nonetheless sleeping in our bed room.) The style of the AcAc di-ester is a minimum of masked by the truth that Dom was capable of put it into capsules. However they’re nonetheless categorically horrible. The salts are undoubtedly higher, however regardless of experimenting with them for months, I used to be unable to persistently ingest them with out experiencing GI side-effects; typically I used to be high quality, however sufficient occasions I used to be not, which left me concluding that I nonetheless wanted to work out the kinks. From my discussions with others utilizing the BHB salts, it appears I’ve a very delicate GI system.

The speculation we sought out to check

A keto-adapted topic (who might already profit from some Delta G arbitrage) will, beneath fastened work load, require much less oxygen when ingesting exogenous ketones than when not.

Posed as a query: At a given price of mechanical work, would the addition of exogenous ketones scale back a topic’s oxygen consumption?

The “experiment”

  • A keto-adapted topic (me) accomplished two 20-minute check rides at roughly 60% of VO2 max on a load generator (CompuTrainer); such a tool permits one to “repair” the work requirement by fixing the facility demand to pedal the bike
  • This fastened load was chosen to be 180 watts which resulted in roughly three L/min of VO2—minute air flow of oxygen (this was an cardio effort at an influence output of roughly 60% of useful threshold energy, FTP, which additionally corresponded to a minute air flow of roughly 60% of VO2 max)
  • Check set #1—accomplished beneath circumstances of delicate dietary ketosis, whereas nonetheless fasted
  • Check set #2—60 minutes following ingestion of 15.6 g BHB mineral salt to supply immediate “synthetic ketosis,” which befell instantly following Check set #1
  • Measurements taken included entire blood glucose and BHB (each 5 minutes); VO2 and VCO2 (each 15 seconds); HR (steady); RQ is calculated because the ratio of VO2 and VCO2. Within the video of this submit I clarify what VO2, VCO2, and RQ inform us about power expenditure and substrate use—in a short time, RQ sometimes varies between about zero.7 and—the nearer RQ is to zero.7, the extra fats is being oxidized; the reverse is true as RQ approaches


Check set #1 (management—delicate dietary ketosis)

The desk under exhibits the info collected over the primary 20 minute effort. The 20 minute effort was steady, however for the aim of presenting the info, I’ve proven the segmental values—finish of phase for glucose and BHB; phase common for HR, minute air flow (in mL per min), and RQ; and phase complete for minute air flow (in liters).

Glucose and BHB went down barely all through the trouble and RQ fell, implying a excessive price of fats oxidation. We will calculate fats oxidation from these knowledge. Power expenditure (EE), in kcal/min, could be derived from the VO2 and VCO2 knowledge and the Weir equation. For this effort, EE was 14.66 kcal/min; RQ provides us a very good illustration of how a lot of the power used in the course of the train bout was derived from FFA vs. glucose—on this case about 87% FFA and 13% glucose. So fats oxidation was roughly 12.7 kcal/min or 1.41 g/min. It’s value mentioning that “conventional” sports activities physiology preaches that fats oxidation peaks in a well-trained athlete at about 1 g/min. Clearly that is context restricted (i.e., solely true, if true in any respect, in athletes on excessive carb diets with excessive RQ). I’ve carried out a number of checks on myself to see how excessive I might push fats oxidation price. Thus far my max is about 1.6 g/min. This means to me that very elite athletes (which I’m not) who’re extremely fats tailored might strategy 2 g/min of fats oxidation. Jeff Volek has accomplished testing on elites and by private communication he has recorded ranges at 1.81 g/min. A really shut pal of mine is considering a run on the 24 hour world report (biking). I feel it’s possible we’ll have the ability to get him to 2 g/min of fats oxidation on the right eating regimen.

The graph, under, exhibits the continual knowledge for VO2, VCO2 (measured), and RQ (calculated).

Check set #2 (ingestion of 15.6 g BHB salt 60 minutes prior)

The desk under exhibits the identical measurements and calculations because the above desk, however underneath the check circumstances. You’ll notice that BHB is larger firstly and falls extra quickly, as does glucose (for causes I’ll clarify under). HR knowledge are virtually equivalent to the management check, however VO2 and VCO2 are each decrease. RQ, nevertheless, is barely greater, implying that the discount in oxygen consumption was higher than the discount in carbon dioxide manufacturing.

In case you do the identical calculations as I did above for estimating fats oxidation, you’ll see that EE on this case was roughly 13.92 kcal/min, whereas fats oxidation was solely 67% of this, or 9.28 kcal/min, or 1.03 g/min. So, for this second effort (the check set) my physique did about 5% much less mechanical work, whereas oxidizing about 25% much less of my very own fats. Nearly all of this distinction, I assume, is from the utilization of the exogenous BHB, and never glucose (once more, I’ll tackle under what I feel is occurring with glucose ranges).

The graph as soon as once more exhibits the continual knowledge for VO2, VCO2 (measured), and RQ (calculated).

Aspect-by-side distinction

The ultimate graph, under, exhibits the continual knowledge for less than VO2 side-by-side for the 20 minute interval. The higher (blue) line represents oxygen consumption underneath management circumstances, whereas the decrease line (purple) represents oxygen consumption following the BHB ingestion. In principle, provided that the identical load was being overcome, and the identical quantity of mechanical work was being completed, these strains ought to be similar.

The speculation being examined on this “experiment” is that they might not be the identical. Past visible inspection, the distinction between the strains seems to develop because the check goes on, which is captured within the tabular knowledge displaying 5 minute segmental knowledge.


The obvious limitation of this endeavor is the truth that it’s not an appropriately managed experiment. Placing that apart, I need to concentrate on the nuanced limitations—which don’t influence the first end result of oxygen consumption—even when one have been appropriately doing an actual experiment.

  1. It’s not clear that the Weir coefficients used to estimate EE are related for somebody in ketosis, not to mention somebody ingesting exogenous BHB. (The Weir components states that EE is approximated by three.94 * VO2 + 1.11 * VCO2, the place VO2 and VCO2 are measured in L/min; three.94 and 1.11 are the Weir coefficients, and they’re derived by tabulating the stoichiometry of lipid synthesis and oxidation of fats and glucose and calculating the quantity of oxygen consumed and carbon dioxide generated.) Whereas this doesn’t impression the primary remark—much less oxygen was consumed with larger ketones—it does impression the estimation of EE and substrate use.
  2. Along with the Weir coefficients being probably off (which impacts EE), the RQ interpretation could also be incorrect within the presence of endogenous or exogenous ketones. Consequently, the estimation of fats and glucose oxidation could also be off (although it’s directionally right). That stated, the present interpretation appears fairly believable—larger fats oxidation once I needed to make my ketones; much less once I obtained my ketones for “free.”

Observations from this “experiment” (and my expertise, generally)

Animal fashions (e.g., utilizing rat hearts) and unpublished case stories in elite athletes recommend supplemented BHB produces extra ATP per unit carbon and per unit oxygen consumed than glycogen and FFA. This seems to have been the case in my anecdotal train.

The power essential to carry out the mechanical work didn’t seem to vary a lot between exams, although the quantity of oxygen utilization and fats oxidation did go down measurably. The latter discovering is no surprise because the physique was not sitting on an ample and obtainable supply of BHB—there was much less have to make BHB “the quaint method.”

As seen on this train, glucose tends to fall fairly precipitously following exogenous ketone ingestions. With out exception, each time I ingested these compounds (which I’ve in all probability carried out a complete of 25 to 30 occasions), my glucose would fall, typically as little as three mM (slightly below 60 mg/dL). Regardless of this, I by no means felt symptomatic from hypoglycemia. Richard Veech (NIH) one of many pioneers of exogenous ketones, has steered this phenomenon is the results of the ketones activating pyruvate dehydogenase (PDH), which reinforces insulin-mediated glucose uptake. (Sooner or later I may also write a publish on Alzheimer’s illness, which just about all the time includes sluggish PDH exercise —in animal fashions acute bolus of insulin transiently improves signs and administration of exogenous ketones does the identical, even with out glucose.)

As well as, the physique regulates ketone manufacturing by way of ketonuria (peeing out extra ketones) and ketone-induced insulin launch, which shuts off hepatic ketogenesis (the liver making extra ketones when you have got sufficient).   The insulin from this course of might be growing glucose disposal which, when coupled with PDH activation, might drive glucose ranges fairly low.

If that explains the hypoglycemia, it might appear the absence of signs could be defined by the work of George Cahill (again within the day; see backside determine on this submit)—when ketone ranges are excessive sufficient they will dominate mind gasoline, even forward of glucose.

Lastly, these compounds appeared to have a profound impression on my urge for food (they produced a robust tendency in the direction of urge for food suppression). I feel there are at the very least two good explanations for this, which I plan to put in writing about in a devoted submit. This specific matter—urge for food regulation—is just too fascinating to warrant something much less.

Open inquiries to be examined in actual experiments

  1. Are these outcomes reproducible? In that case, how variable are the outcomes throughout people (by baseline metabolic state, food plan, health)?
  2. Would the distinction in oxygen consumption be bigger (or smaller) in an athlete not already keto-adapted (i.e., not producing endogenous ketones)?
  3. Would the noticed impact be higher at larger plasma ranges of BHB (e.g., 5 to 7 mM), which is “simply” achievable with exogenous ketones?
  4. Would the noticed impact be the identical or totally different at larger ranges of ATP demand (e.g., at FTP or at 85-95% of VO2 max)?
  5. Would the development in the direction of improved power effectivity proceed if the train bout was longer in period (say, larger than 2 hours)?
  6. How will exogenous ketones impression train period and lactate buffering?
  7. Why do exogenous ketones (each BHB and AcAc it appears) scale back blood glucose ranges a lot, and may this function be exploited to deal with sort 2 diabetes?
  8. Are there deleterious results from utilizing exogenous ketones, in addition to GI side-effects?
  9. What are the variations between exogenous BHB and AcAc (which in vivo exist in a reversible equilibrium) on this specific phenomenon? (Work by Dom D’Agostino’s group and others have proven different variations in metabolic response and medical software, together with their relative influence on neurons.)