Increased EPO

Increased Erythropoietin (EPO) Naturally

EPO is a naturally-occurring hormone produced in the kidneys that stimulates the bone marrow to release more red blood cells into circulation. Because red blood cells carry oxygen from the lungs to the muscles, having a higher concentration in the circulation can greatly improve an athlete’s aerobic capacity.

EPO that is produced in a lab (sometimes used in doping) is almost identical to the naturally occurring hormone that is produced in the body.

The Science

1. Increase EPO by 24%

Results showed that EPO concentration increased by 24%, which peaked at three hours after the final breath hold and returned to baseline two hours later.

Exercise: “Three sets of five maximum duration breath holds, with each set separated by ten minutes of rest.”

See: de Bruijn R, Richardson M, Schagatay E. “Increased erythropoietin concentration after repeated apneas in humans.” Eur J Appl Physiol 2008; 102:609–13. Epub 2007 Dec 19.

2. Increase EPO by 24 to 36% by lowering blood oxygen saturation to lower than 91% for 24 seconds and 26 seconds respectively

Researchers from the Human Performance Laboratory, University of Calgary, Canada, conducted a study to investigate the relationship between a decrease of oxygen concentration during exercise and erythropoietin (EPO) production. Five athletes cycled for three minutes at an intensity greater than maximal (supramaximal) at two different elevations: 1,000m and 2,100m.

Oxygen saturation of hemoglobin was lower than 91 percent for approximately 24 seconds during exercise at 1,000 meters and for 136 seconds during exercise at 2,100 meters, with EPO levels increasing by 24 percent and 36 percent, respectively following the exercise.

Roberts D, Smith DJ, Donnelly S, Simard S. Plasma-volume contraction and exercise-induced hypoxaemia modulate erythropoietin production in healthy humans. Clinical Science.2000 ;(Jan;98(1):39-45

3. Breath Holding Increases EPO Naturally

Korean researchers Choi et al. carried out a study on 263 subjects to determine the relationship between hematocrit levels and obstructive sleep apnea (involuntary holding of the breath during sleep). Patients with severe sleep apnea had significantly higher levels of hematocrit than mild and moderate OSA.

Study findings showed that hematocrit levels were significantly correlated with per cent of time spent at oxygen saturation of below 90 percent, as well as average oxygen saturation.

See: Jong Bae Choi, José S. Loredo, Daniel Norman, Paul J. Mills, Sonia Ancoli-Israel, Michael G. Ziegler and Joel E. Dimsdale. Does obstructive sleep apnea increase haematocrit?. Sleep and Breathing.2006 ;(Sep;10(3)):155-60

Simulate High Altitude Training

A major determinant of aerobic performance is the capacity to deliver oxygen to the tissues. Breath holding to lower oxygen saturation of the blood causes the spleen to release red blood cells into circulation and generates erythropoietin (EPO).

The spleen is an organ that acts as a blood bank; when the body signals an increased demand for oxygen, the spleen releases stores of red blood cells. It therefore plays a very important role in regulating blood hematocrit (the percentage of red blood cells in the blood), as well as hemoglobin concentration.

EPO stimulates the proliferation and maturation of red blood cells in the bone marrow, increasing the maximum volume of oxygen that an athlete can use, known as your VO2 max. (Saunders et al concluded that 1% Hb mass increase eventually results in the 0.6- 0.7% VO2 max increase)

There are simple strategies that will allow you to access the benefits of living at a high altitude with reduced oxygen intake: keeping your mouth closed while you are exercising and practicing the various exercises outlined in the Oxygen Advantage®program. This is a challenge during intense exercise, due to air hunger, but this is when most of the benefit actually occurs.

Some papers have showed no improvements to red blood cell count resulting from breath hold training. I have included these in references 9 and 10 below.

The Science

1. 10.79% increase to VO2 max, 5.35% increase to hemoglobin

Research was conducted to establish the effects of 8 week hypercapnic-hypoxic training program in elite male swimmers, 30 to 45 minutes, three times a week. Each test subject has withheld breath individually, by a subjective feeling, for as long as possible. The condition is that each breath hold must be above the minimum values which describe hypercapnia, that is, the values of carbon dioxide in the exhaled breath had to be over 45 mmHg, which was controlled by a capnometer.

Besides the swimming training sessions the control group was subjected to additional aerobic training sessions on a treadmill. The program was conducted three times a week for eight weeks.

Experiment Control

Pre: Hb (g/L)

144.63

147.75

Post: Hb (g/L)

152.38

145.38

The above shows a 5.35% increase to hemoglobin in the group that practiced breath holding after an exhalation.

Furthermore, there was a 10.79% increase to VO2 max as shown below:

Experiment Control

VO2 Max Pre:

63.80

59.46

VO2 Max Post:

70.38

60.81

*See: “THE EFFECTS OF HYPERCAPNIC-HYPOXIC TRAINING PROGRAM ON HEMOGLOBIN CONCENTRATION AND MAXIMUM OXYGEN UPTAKE OF ELITE SWIMMERS”

Dajana Zoretic, Nada Grcic-Zubcevic and Katarina Zubcic
Faculty of Kinesiology, University of Zagreb, Croatia

2. Hematocrit (Hct) increase by 6.4% and hemoglobin concentration (Hb) increase by 3.3%

Results found that the volunteers with spleens showed a 6.4 percent increase in hematocrit (Hct) and a 3.3 percent increase in hemoglobin concentration (Hb) following the breath holds. This means that after just five breath holds, the oxygen-carrying capacity of the blood was significantly improved.

However, for the individuals who had their spleens removed (due to prior medical reasons), there were no recorded changes to the blood resulting from breath holding.

Schagatay E, Andersson JP, Hallén M, Pålsson B.. Selected contribution: role of spleen emptying in prolonging apneas in humans. Journal of Applied Physiology.2001;(Apr;90(4)):1623-9

3. Hematocrit (Hct) increase by 4%

Seven male volunteers performed two sets of five breath holds to near maximal duration; one in air and the other with their faces immersed in water. Each breath hold was separated by two minutes of rest and each set separated by twenty minutes.

Both Hct and Hb concentration increased by approximately 4 percent across both series of breath holds – in air and in water. This study in particular provides pertinent information about the consequence of breath holding: since there was no visible increase in the results of breath holding with the subject’s faces immersed in water, the authors concluded that “the breath hold, or its consequences, is the major stimulus evoking splenic contraction.”

See: Schagatay E, Andersson JP, Nielsen B. Hematological response and diving response during apnea and apnea with face immersion. European Journal of Applied Physiology.2007;(Sep;101(1):):125-32

4. Spleen size decreased by a total of 20 percent

A study by Baković et al from University of Split School of Medicine, Croatia, was conducted to investigate spleen responses resulting from five maximal breath holds. Ten trained breath hold divers, ten untrained volunteers and seven volunteers who had their spleen removed were recruited. The subjects performed five maximum breath holds with their face immersed in cold water, and each breath hold was separated by a two-minute rest.

The duration of the breath holds peaked at the third attempt, with breath hold divers reaching 143 seconds, untrained divers reaching 127 seconds and splenectomised persons achieving 74 seconds. Spleen size decreased by a total of 20 percent in both breath hold divers, and the untrained volunteers.

Researchers concluded that the “results show rapid, probably active contraction of the spleen in response to breath hold in humans. Rapid spleen contraction and its slow recovery may contribute to prolongation of successive, briefly repeated breath hold attempts.”

See: Darija Baković, Zoran Valic, Davor Eterović, Ivica Vuković, Ante Obad, Ivana Marinović-Terzić, Zeljko Dujić. Spleen volume and blood flow response to repeated breath-hold apneas. Journal of Applied Physiology.2003;(vol. 95 no. 4):1460-1466

5. Longer breath holds causes greater splenic contraction

In a paper by Dr Espersen and colleagues from Herlev Hospital, University of Copenhagen, Denmark, splenic contraction was found to take place even with very short breath holds of 30 seconds.

However, the strongest contraction of the spleen was as it released blood cells into circulation, occurring when a subject held their breath for as long as possible.

See: Kurt Espersen, Hans Frandsen, Torben Lorentzen, Inge-Lis Kanstrup,Niels J. Christensen. The human spleen as an erythrocyte reservoir in diving-related interventions . Journal of Applied Physiology.2002;(May;92(5)):2071-9

6. Long Term Effects of Breath Holding

French researcher Lematires wrote a very interesting paper entitled ‘Apnea – A new training method in sport’ in which he noted that resting Hb mass in trained breath hold divers was 5 percent higher than in untrained divers.

In addition, breath hold divers showed a larger relative increase to Hb after three apneas. The paper noted that, “the long-term effect of apnea training on Hb mass might be implicated in elite divers’ performance.”

See: Lemaître F, Joulia F, Chollet D. Apnea: a new training method in sport? Med Hypotheses.2010;(Mar;74(3)):413-5

7. Increase of hemoglobin concentration after maximal apneas in divers, skiers, and untrained humans

Matt Richardson investigated the haematological responses to maximal apneas performed by three groups: elite apnoeic divers, elite cross country skiers and untrained subjects. Pre-test hemoglobin tended to be higher in the diver group than both skiers and untrained individuals.

Each subject was required to perform three maximal breath holds separated by two minutes of rest and normal breathing. Following the breath holds, all groups responded with increased hemoglobin, with divers showing the largest increase. The duration of the third breath hold time was 187 seconds in divers, 111 seconds in skiers, and 121 seconds in untrained individuals.

The authors observed that the higher Hb concentration in divers “suggests that regular apnea practice could impart a specific training effect, effecting haematological responses to apnea in a manner that differs from that of exercise training.”

See: Richardson M, de Bruijn R, Holmberg HC, Björklund G, Haughey H, Schagatay E. Increase of hemoglobin concentration after maximal apneas in divers, skiers, and untrained humans. Canadian Journal Applied Physiology.2005;(Jun;30(3)):276-81

8. Hematocrit increased 9.5 percent

Splenic size was measured before and after repetitive breath hold dives to approximately 6 meters in ten Korean ama (diving women) and in three Japanese males who were not experienced in breath holding. Following the breath holds, splenic size and hematocrit were unchanged in the Japanese male divers.

In the ama, splenic volume decreased 19.5 percent, hemoglobin increased by 9.5 percent, and hematocrit increased 9.5 percent. The study showed that long-term repeated apneas induce a stronger spleen contraction and resultant hematological response.

See: Hurford WE, Hong SK, Park YS, Ahn DW, Shiraki K, Mohri M, Zapol WM. Splenic contraction during breath-hold diving in the Korean ama. Journal Applied Physiology.1990;(Sep;69(3)):932-6

9. Nonhematological mechanisms of improved sea-level performance after hypoxic exposure

Specific beneficial nonhematological factors include improved muscle efficiency probably at a mitochondrial level, greater muscle buffering, and the ability to tolerate lactic acid production.

This review explores evidence of factors other than accelerated erythropoiesis that can contribute to improved athletic performance at sea level after living and/or training in natural or artificial hypoxia. We describe a range of studies that have demonstrated performance improvements after various forms of altitude exposures despite no increase in red cell mass.

In addition, the multifactor cascade of responses induced by hypoxia includes angiogenesis, glucose transport, glycolysis, and pH regulation, each of which may partially explain improved endurance performance independent of a larger number of red blood cells.

Specific beneficial nonhematological factors include improved muscle efficiency probably at a mitochondrial level, greater muscle buffering, and the ability to tolerate lactic acid production. Future research should examine both hematological and nonhematological mechanisms of adaptation to hypoxia that might enhance the performance of elite athletes at sea level.

Gore CJ, Clark SA, Saunders PU. Nonhematological mechanisms of improved sea-level performance after hypoxic exposure. Med Sci Sports Exerc. 2007 Sep;39(9):1600-9.

10. Not all researchers have reported improvements to aerobic capacity. More research is required.

No change in Hb after training

Xavier Woorons , Pascal Mollard, Aur´elien Pichon, Alain Duvallet, Jean-Paul Richalet, Christine Lamberto. Effects of a 4-week training with voluntary hypoventilation carried out at low pulmonary volumes. Respiratory Physiology & Neurobiology 160 (2008) 123–130