Ketone Ester study finds increased capillarization and serum EPO



Why did the experimental group receive the high carb/protein drink in addition to the ketone esters while the control group only received one containing medium-chain triglycerides?

Would’ve been interesting (and pretty easy/cheap) to investigate if that increase in serum EPO leads to a bump in hemoglobin as well.


Haven’t looked into the study yet, but any word on actual performance?

I can also confirm that they will reverse peristaltic wave activity. Similar to the way a sugar mouth rinse can improve TT performance, so to can a ketone mouth rinse reverse peristaltic wave activity.

This study is mostly over my head.

This part:

“Subjects received either 25g of a ketone ester (KE, n = 9) or a control drink (CON, n = 9) immediately after each training session and before sleep. In KE, but not in CON, the training intervention increased number of capillary contacts and capillary-to-fiber perimeter exchange index by 44% and 42%, respectively.”

I understood.

But this part:

“Furthermore, KE also substantially increased VEGF and eNOS expression both at the protein and mRNA level. Serum erythropoietin concentration was concomitantly increased by 26%. Conversely, in CON the training intervention increased only the protein content of eNOS. These data indicate that intermittent exogenous ketosis during endurance overload training stimulates muscular angiogenesis. This likely resulted from a direct stimulation of muscle angiogenesis, which may be at least partly due to stimulation of erythropoietin secretion and elevated VEGF activity, and/or an inhibition of the suppressive effect of overload training on the normal angiogenic response to training. This study provides novel evidence to support the potential of exogenous ketosis to benefit endurance training-induced muscular adaptation.”

All that was lost on me.

My walk away is that ingesting 25g ketone esters, after cycling and before bed, during an overload period that involved 10 sessions/week, has some evidence of increasing endurance adaptations (capillarization and surface area) in muscles.

General comments:

  1. This is an explanatory study, that focuses on surrogate (not performance-based) outcomes.
  2. This appears to be an unplanned analysis of a pre-existing cohort of patients from another study ( The authors do not state which (if any) of their outcomes were prospectively defined before they performed their analysis, so we are left to assume that this is only be data-mining (ie: they are only reporting positive outcomes). ie: this is actually a retrospective observational study in disguise, and is research that is done for the purpose of hypothesis generation and will require subsequent independent validation.
  3. This study used a per-protocol analysis (as they excluded drop-outs). That 10% of patients dropped out and a per-protocol analysis was used, increases the risk of a Type 1 error (ie: a “false positive” result).
  4. Participants were 21 years old on average, with an average VO2 max of 55.7. All participants were male. When you look at the original paper this study is a sub-analysis of, you’ll also note that the average number of hours a week spent on exercise pre-study was ~5h, and none of the participants were regular cyclists.
  5. The study describes itself as double-blind… however, it is unclear how effective their blinding attempts were (was the bitter isocaloric control drink actually indistinguishable from the KE drink?). It’s also unclear how the study conductors who were making these drinks for the athletes were blinded to what was in the drink - the paper does not explain how blinding was achieved. The source study from 2019 also does not explain how blinding of these people was achieved… it just says it was “double blind” with no further explanation.
  6. The study this data comes from describes itself as randomized… but provides absolutely no information on what type of randomization was used, how randomization was conducted, nor how allocation concealment was performed.

Altogether, as is unfortunately the case with the vast majority of exercise research, this paper has a very high risk of bias (ie: poor internal validity) due to its methodology.

If you use something the the Cochrane Risk of Bias Tool, you get the following:

  1. Sequence Generation: Unclear. Likely inadequate.
  2. Allocation Concealment: Unclear. Likely inadequate.
  3. Blinding: Unclear. Likely inadequate.
  4. Incomplete Outcome Data: Unclear.
  5. Selective Outcome Reporting: Unclear.
  6. Other Bias: small study effect, etc.

This high-risk of bias means there is a very high probability that future research on this topic would yield very different results… even among the exact same athletes who participated in the study. As a result, these results need to be prospectively and independently validated.

Independent of this, there are also important issues relating to external validity, such as:

  1. only men were studied.
  2. none of the participants rode a bike regularly.

All that being said, it would nor surprise me if these results were true. Ketones are generated during exercise in response to low energy/glycogen availability. It makes physiological sense that an adaptation to this would be increased capillarization.

And if I really wanted to stir the pot, I would point out that if these results are true, this is more indirect evidence that maybe you shouldn’t be eating 120g/h of carbs during your long z2 rides :wink:


thanks, all interest in ketone esters stopped when I realized you don’t get it from food, the price per dose is outrageous, and it tastes nasty. I’m not big on supplements anyways.

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:metal:t3: Hell yeah!!

I have a 10hour race in 3 weeks and now I’m very interested in this topic

150g/hr for 1 hour z2 rides!


preloading 300g/h of carbs, every hour , 24 hours before z2 ride ride will ensure you go downhill faster :rofl:


in a tailwind

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