Ketones and Performance II: Post-Exercise Beneficial Effects

Last week's blog (read here: https://www.thethreshold.coach/single-post/optimizing-fitness-with-ketones-science-backed-insights) discussed the different types of ketones on the market, and its benefits during exercise looking at a well-designed double-blind placebo study.

This week we continue on that road to look at Ketone use after exercise and some of the interesting studies that have come out showing significant POTENTIAL performance benefits

Questions we will answer:

1.What is Erythropoietin (EPO)?

-Physiology of Red Blood cells and Hemoglobin

2.Acute EPO production and Ketone use

-A study recently published on the short-term use of the impact of ketones and EPO production

3.Chronic Ketone use and its impact on performance benefits

-EPO and muscle capillary density increases

-Nutritional Intervention

4.Summary

1.What is Erythropoietin (EPO)?

First some physiology

Within the cycling community, EPO is widely known for its association with boosting performance and engaging in a prohibited method known as blood doping, (the classic method involves the reinfusion of red blood cells through intravenous means). This practice typically utilizes recombinant DNA technology to stimulate the production of red blood cells in the bone marrow, leading to an increase in red blood numbers (known as hematocrit) and hemoglobin levels. The concentration of hemoglobin (Hb) is closely linked to oxygen transport (O2), a relationship quantifiable through the CaO2 equation of (Hb) x 1.34ml O2 per gram of Hb. In males, normal hemoglobin levels range from 130 to 180 grams per liter of blood; in females, the range is approximately 120 to 150 grams per liter. Refer to Figure 1 for an illustration depicting the structure of a red blood cell with its hemoglobin component.

Fig 1. Red Blood Cell with hemoglobin molecule

Now we understand why red blood cells are so important, especially in endurance sports (and using oxygen to create energy). Let's look at a study that shows using ketones significantly boosts EPO production.

2.Acute EPO production and Ketone use

Let's have a look at a study published by Evans et al. 2023. that looked at the impact ketones have on EPO production

Results summarized below:

9 Cyclists (Age 25 years old, VO2max +-55)	First Lab visit: Ingestion of Ketones (0.29 g.kg of body mass each hour) for 3 hours post-exercise	Second Lab Visit: Control (No ketones)
Performed a high intensity training session with 2mins at 90% of VO2max and 2mins at 50% of VO2max until failure (total volume around 90mins)	Average Power output (APO): 220w	APO: 220w
EPO concentration (at 4 hours post-exercise)	+20% (+-9 UI.L)	+-7 UI.L

See Fig 2. below for the EPO production between the ketone and control group. The asterisk * denotes statistical significance which means that the chance that the results obtained are NOT by randomness but by a specific cause.

Fig 2. Acute EPO production from post exercise Ketone consumption

• Highlighting the significance of this being a single exercise intervention is important to note. The primary concern to tackle is the lasting impact of ketone consumption post-exercise. Presently, carrying out such research would be expensive, posing a challenge for those lacking support from a ketone producer or a funding entity willing to finance ketone supplements.

3.Chronic Ketone use and its impact on performance benefits

Let's examine a study conducted by a team of researchers that were mentioned in the previous post about ketones, once again led by Poffe et al in 2023.

Results summarized below:

20 Cyclists (21 years old VO2max 55)	Ingestion of Ketones (25 g of ketone ester immediately after training and 30min pre-sleep)	Control (no ketones but the drink was matched for ketone ester calories)
3 weeks of 8-13 hours of training per week (with 4-6 high-intensity sessions in that week). Increase in load each consecutive week	Week 3 training load was higher in the Ketone group	The control group had to reduce the week 3 training load to finish the training
Muscle Capillarization	40% increase	NO change
EPO	25% increase	NO change

Nutritional Intervention

Currently, ketones are not cost-effective when compared to established ergogenic aids like using maltodextrin, protein, etc during and after exercise. Therefore, the focus shifts to increasing hemoglobin levels in red blood cells, with one approach being monitoring iron intake.

In their 2019 study, Sim and colleagues conducted a narrative review focusing on iron supplementation. Iron plays a crucial role in hemoglobin production, and it is recommended to assess ferritin (the protein that stores iron), as well as hemoglobin and hematocrit levels in a blood panel as an initial step in enhancing red blood cells among athletes. The review revealed that Ferritin levels below 35 ug/L were considered low, even though the lower limit on lab tests is 12 ug/L. In South Africa, measurements are in ng/ml with a reference range of 20-250 ng/ml, which represents a significant range. It is important to note that ug/L is equivalent to ng/ml. See Fig 3. to understand where iron fits into the hemoglobin molecule.

Fig 3. Hemoglobin consisting of Heme groups made up of iron molecule critical for oxygen transport

4.Summary

Key concepts to take from the above results are as follows:

• The Poffe et al. study showed Ketone intake was associated with increased capillary. This increased capillary density allows greater extraction of oxygen due to an increased ability to hold greater blood volume levels, decreased diffusion distance to the energy powerhouse of the cell, as well as slowed blood flow through muscle to allow greater diffusion of oxygen (Holloszy and Coyle. 1984).

• Ketones seem to allow a greater ability to handle high training loads (4-6 high-intensity sessions in a week is well above recommendations of any coaching manual or what would be prescribed by a diligent coach) and could be useful to use during a heavy loading period or as we have seen during a 3-week grand tour to cope with the massive physical demands.

• Increased EPO production can possibly increase red blood cell mass (and hemoglobin) however, red blood cell mass is tightly regulated within individual physiology and may or may not increase.
  

Any help with further questions, discussions, consultations, or coaching? Please don't hesitate to reach out to darrin@thethreshold.coach

@darrinjordaan

@wattfarming

Train Hard and Prosper!

Darrin Jordaan

MSc (Med) Biokinetics WITS

HMS (Hons) Sports Science UP

BK 0016934

CSCS

UCI Level 1 Cycle Certified Coach

IronMan Certified Coach

WADA Coaches of High-Performance Education Program Certified

References

Scott, WC. 1990. The abuse of Erythropoietin to enhance athletic performance. Journal of American Medical Association 264:1660

Evans E, Walhin JP, Hengist A, Betts JA, Dearlove DJ, Gonzalez JT. Ketone Monoester ingestion increases postexercise serum erythropoietin concentrations in healthy men. American Journal Endocrinology Metabolism. 2023. Jan 1: 324 (1): E56-E61

Poffe C, Robberechts R, Van Thienen R, Hespel P. Exogenous Ketosis elevates circulating erythropoietin and stimulates muscular angiogenesis during endurance training overload. Journal of Physiology. 2023 Jun, 601 (12):2345-2358

Holloszy, JO and Coyle EF. Adaptations of skeletal muscle to endurance and their metabolic consequences. Journal of Applied Physiology. Respiratory, Environmental and Exercise Physiology 56:831-28. 1984.

Sim M, Garvican-Lewis L, Cox GR, Govus A, McKay AKA, Stellingwerff T, Peeling P. Iron considerations for the athlete: a narrative review. European Journal Of Applied Physiology. July 119 (7) 1463:1478. 2019.