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My experience with exogenous ketones

I wrote this publish at about the same time Germany gained the World Cup in Rio de Janeiro in 2014. There’s been plenty of shifting and shaking on the planet of exogenous ketones since then, to not mention soccer. Wanting back on my submit, I still think about it relevant when it comes to what exogenous ketones probably can (and can’t) do for performance. In this case, to see if exogenous ketone esters present me a “boost” by permitting me to do the identical quantity of labor while expending much less power (and work at a relatively decrease VO2) in comparison with no supplementation.

I’m getting an growing number 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 fast? 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 “smart drug?” What happens if somebody has excessive levels of each glucose and ketones? Are some merchandise higher than others? Salts vs esters? BHB vs AcAc? Can taking exogenous ketones scale back endogenous production on a ketogenic food plan? What’s the difference between racemic mixtures, D-form, and L-form? What’s your experience with MCTs and C8?

Caveat emptor: the following submit doesn’t come near answering most of these questions. I solely 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 should provide you will some context and understanding about what exogenous ketones are, and what they could do for athletic performance. We’ll probably podcast concerning the questions and subjects above and canopy different elements of exogenous ketones in additional element.

—P.A., June 2018

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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 very least be acquainted with the concepts in these posts, which might be discovered here and here.

Within the second of those posts I talk about the Delta G implications of the body using ketones (particularly, beta-hydroxybutyrate, or BHB, and acetoacetate, or AcAc) for ATP era, as an alternative of glucose and free fatty acid (FFA). At the time I wrote that submit I was notably (read: personally) within the Delta G arbitrage. Said merely, per unit of carbon, utilization of BHB presents extra ATP for a similar amount of oxygen consumption (as corollary, era of the same amount of ATP requires less oxygen consumption, when in comparison with glucose or FFA).

I also concluded that publish by discussing the potential of testing this (theoretical) concept in a real individual, with the assistance of exogenous (i.e., synthetic) ketones. I’ve seen this effect in (unpublished) knowledge in world class athletes not on a ketogenic food plan who’ve supplemented with exogenous ketones (more on that, under). Case after case confirmed a small, however vital improve in sub-threshold efficiency (for instance, efforts longer than about 4 minutes all-out).

So I made a decision to seek out out for myself if ketones might, indeed, supply up the same quantity of usable power with less oxygen consumption. Some housekeeping issues earlier than moving into it.

  1. This can be a self-experiment, not real “data”—“N of 1” stuff is suggestive, nevertheless it prevents using nifty little things likes error bars and p-values. Please don’t over interpret these results. My purpose for sharing that is to spark a dialogue and hope that a more systematic and rigorous strategy could be undertaken.
  2. All the knowledge I’ll current under have been from an experiment I did with the help of Dominic D’Agostino and Pat Jak (who did the indirect calorimetry) in the summertime of 2013. (I wrote this up immediately, however I’ve only received round to running a blog about it now.) Dom is, far and away, probably the most knowledgeable individual on the topic of exogenous ketones. Others have been at it longer, however none have the vast experiences with all attainable modalities (i.e., esters versus salts, BHB versus AcAc) and the concurrent understanding of how dietary ketosis works. If individuals call me keto-man (some do, as silly as it sounds), they need to call Dom keto-king.
  3. I have tried the following 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, including 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 each, though, for the sake of time.
  4. The ketone esters are, hands-down, the worst tasting compounds I’ve ever put in my body. The world’s worst scotch tastes like spring water compared to this stuff. The primary time I tried 50 mL of BHB monoester, I failed to mix it with anything (Dom warned me, however I used to be too desperate to attempt them to truly learn his instructions). 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 in the kitchen that I awoke my spouse, who was still 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, but regardless of experimenting with them for months, I used to be unable to persistently ingest them with out experiencing GI side-effects; typically I was superb, however sufficient occasions I was not, which left me concluding that I still needed to work out the kinks. From my discussions with others utilizing the BHB salts, it seems I have a very delicate GI system.

The hypothesis we sought out to test

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

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

The “experiment”

  • A keto-adapted topic (me) completed two 20-minute check rides at roughly 60% of VO2 max on a load generator (CompuTrainer); such a device permits one to “fix” 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 ventilation of oxygen (this was an cardio effort at an influence output of roughly 60% of practical threshold power, FTP, which also corresponded to a minute air flow of approximately 60% of VO2 max)
  • Check set #1—achieved underneath circumstances of delicate nutritional ketosis, while nonetheless fasted
  • Check set #2—60 minutes following ingestion of 15.6 g BHB mineral salt to supply on the spot “artificial ketosis,” which befell instantly following Check set #1
  • Measurements taken included entire blood glucose and BHB (every 5 minutes); VO2 and VCO2 (each 15 seconds); HR (steady); RQ is calculated because the ratio of VO2 and VCO2. In the video of this submit I explain what VO2, VCO2, and RQ tell us about power expenditure and substrate use—very quickly, RQ sometimes varies between about zero.7 and 1.zero—the nearer RQ is to 0.7, the more fat is being oxidized; the reverse is true as RQ approaches 1.0

Outcomes

Check set #1 (control—delicate nutritional ketosis)

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

Glucose and BHB went down slightly throughout the trouble and RQ fell, implying a high fee of fats oxidation. We will calculate fat oxidation from these knowledge. Power expenditure (EE), in kcal/min, might be derived from the VO2 and VCO2 knowledge and the Weir equation. For this effort, EE was 14.66 kcal/min; RQ provides us an excellent representation of how a lot of the power used through the train bout was derived from FFA vs. glucose—in this case about 87% FFA and 13% glucose. So fat oxidation was approximately 12.7 kcal/min or 1.41 g/min. It’s value stating that “traditional” sports physiology preaches that fats oxidation peaks in a well-trained athlete at about 1 g/min. Clearly that is context limited (i.e., solely true, if true at all, in athletes on excessive carb diets with high RQ). I’ve completed a number of exams on myself to see how high I might push fat oxidation fee. Thus far my max is about 1.6 g/min. This means to me that very elite athletes (which I am not) who’re highly fats adapted might strategy 2 g/min of fats oxidation. Jeff Volek has completed testing on elites and by personal communication he has recorded levels at 1.81 g/min. A very close good friend of mine is contemplating a run at the 24 hour world report (cycling). I feel it’s doubtless we’ll have the ability to get him to 2 g/min of fat oxidation on the right food plan.

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 table under exhibits the same measurements and calculations because the above desk, but beneath the check circumstances. You’ll word that BHB is larger at the beginning and falls extra rapidly, as does glucose (for causes I’ll clarify under). HR knowledge are virtually equivalent to the management check, but VO2 and VCO2 are both lower. RQ, nevertheless, is barely greater, implying that the reduction in oxygen consumption was higher than the reduction in carbon dioxide production.

In case you do the same calculations as I did above for estimating fats oxidation, you’ll see that EE on this case was roughly 13.92 kcal/min, whereas fat 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 body did about 5% much less mechanical work, whereas oxidizing about 25% much less of my own fats. Nearly all of this distinction, I assume, is from the utilization of the exogenous BHB, and not glucose (again, I will handle under what I feel is occurring with glucose ranges).

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

Aspect-by-side difference

The ultimate graph, under, exhibits the continual knowledge for less than VO2 side-by-side for the 20 minute period. The upper (blue) line represents oxygen consumption underneath control circumstances, whereas the decrease line (pink) represents oxygen consumption following the BHB ingestion. In principle, provided that the same load was being overcome, and the identical amount of mechanical work was being executed, these strains must be equivalent.

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

Limitations

The most obvious limitation of this endeavor is the fact that it’s not an appropriately managed experiment. Putting that apart, I need to concentrate on the nuanced limitations—which don’t impression the first consequence of oxygen consumption—even when one have been appropriately doing a real experiment.

  1. It’s not clear that the Weir coefficients used to estimate EE are relevant for someone in ketosis, not to mention somebody ingesting exogenous BHB. (The Weir formulation states that EE is approximated by three.94 * VO2 + 1.11 * VCO2, where 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 influence the primary remark—much less oxygen was consumed with greater ketones—it does impression the estimation of EE and substrate use.
  2. In addition to 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 seems quite believable—larger fat oxidation once I had to make my ketones; less once I obtained my ketones for “free.”

Observations from this “experiment” (and my experience, normally)

Animal models (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 appears to have been the case in my anecdotal train.

The power necessary to carry out the mechanical work did not seem to vary much between checks, although the amount of oxygen utilization and fat oxidation did go down measurably. The latter discovering is no surprise because the body was not sitting on an ample and out there source of BHB—there was much less have to make BHB “the old fashioned way.”

As seen in this exercise, glucose tends to fall quite precipitously following exogenous ketone ingestions. With out exception, each time I ingested these compounds (which I’ve in all probability achieved a total of 25 to 30 occasions), my glucose would fall, typically as little as three mM (slightly below 60 mg/dL). Despite this, I never felt symptomatic from hypoglycemia. Richard Veech (NIH) one of the pioneers of exogenous ketones, has instructed this phenomenon is the results of the ketones activating pyruvate dehydogenase (PDH), which reinforces insulin-mediated glucose uptake. (Sooner or later I may even write a publish on Alzheimer’s disease, which just about all the time includes sluggish PDH activity —in animal fashions acute bolus of insulin transiently improves signs and administration of exogenous ketones does the same, even without glucose.)

In addition, the physique regulates ketone manufacturing by way of ketonuria (peeing out excess ketones) and ketone-induced insulin release, which shuts off hepatic ketogenesis (the liver making extra ketones when you’ve gotten sufficient).   The insulin from this process could possibly be growing glucose disposal which, when coupled with PDH activation, might drive glucose ranges quite low.

If that explains the hypoglycemia, it will appear the absence of signs may be explained by the work of George Cahill (again in the day; see backside determine in this submit)—when ketone ranges are excessive sufficient they will dominate brain gasoline, even ahead of glucose.

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

Open inquiries to be tested in actual experiments

  1. Are these results reproducible? In that case, how variable are the outcomes throughout people (by baseline metabolic state, weight-reduction 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 larger at greater plasma levels of BHB (e.g., 5 to 7 mM), which is “easily” achievable with exogenous ketones?
  4. Would the noticed effect be the same or totally different at greater 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 efficiency proceed if the exercise bout was longer in period (say, larger than 2 hours)?
  6. How will exogenous ketones influence exercise period and lactate buffering?
  7. Why do exogenous ketones (each BHB and AcAc it seems) scale back blood glucose ranges so much, and may this function be exploited to treat sort 2 diabetes?
  8. Are there deleterious results from utilizing exogenous ketones, apart from GI side-effects?
  9. What are the differences 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 shown other differences in metabolic response and medical software, together with their relative impression on neurons.)

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