PHYSIOLOGY

The body implements a number of adaptive changes (acclimatization) which include a higher ventilation (respiratory or breathing) rate and a higher blood lactate level for any level of sub-maximal exercise to offset the lower blood oxygen levels as the elevation above sea level increases. Both of these increase an individual's sensation of dyspnea (shortness of breath) and fatigue. Acclimatization responses begin immediately and may take 4 to 6 weeks to reach their maximal effectiveness - specifically an increase in red blood cell mass.

In addition to a decrease in maximal aerobic capacity, the symptoms of acute mountain sickness (AMS) affect, to varying degrees, all travelers to elevations greater than 5280 feet. In a small percentage of those climbing to this altitude, AMS can lead to high-altitude pulmonary edema (HAPE) and/or high-altitude cerebral edema (HACE). Symptoms of AMS range from a combination of headache, insomnia, anorexia, nausea, and dizziness,to more serious manifestations, such as vomiting, dyspnea, muscle weakness, oliguria, peripheral edema, and retinal hemorrhage.

Although the primary cause of symptoms at altitude is the reduced oxygen content (of the air and as a result the blood) at high altitudes, the physiologic pathway leading from hypoxia to AMS (and its sequelae) remains unclear. Tips on self-diagnosis and symptom recognition are critical elements to include in educating those who are contemplating a trip to high altitudes.

Short term (days) physiologic adjustments to altitude

The most immediate response to altitude is the hyperventilation that occurs in response to the decrease in blood (arterial) oxygen levels (a significant symptom above 2000 meters). This increased respiratory rate can remain elevated for up to a year at altitude. The degree of this hyperventilation response varies from individual to individual - those with a strong hypoxic drive will perform exercise tasks better at altitude than those with a blunted ventilatory response.

A second is an increase in resting heart rate and, as a result, cardiac output. The increase in blood flow at the muscle cell level compensates for the decrease in blood oxygen concentration with the total amount of oxygen being delivered to the muscles in a resting state being unchanged. However, the fact that there is always a lower blood oxygen concentration means that even with the compensatory increase in heart rate and blood flow, the level of exercise at which oxygen demands are unmet and metabolism shifts to anaerobic (VO2 max. has been reached) will always be less than at sea level.

Long term (weeks) adjustments to altitude

Hyperventilation and an increased cardiac output are the immediate response to limit the effects of altitude on physical performance.

With time, a change in the body's acid-base balance counters the effects of a chronically lower blood CO2 from hyperventilation (respiratory alkalosis), but does not affect physical performance to any significant degree.

An increase in the blood hemoglobin (hematocrit) level over 3 to 4 weeks increases the oxygen carrying capacity of the blood and is the most important of all the performance adaptations to altitude. The result is that every milliliter of blood that moves through the muscle capillaries will be able to deliver an increased amount of oxygen compared to the same volume of blood with a sea level hematocrit.

Finally, there are cellular changes that favor oxygen delivery to the muscle cell. The capillary concentration (very small blood vessels) in skeletal muscle is increased in animals living at altitude compared to those at sea level, and muscle biopsies in acclimatized men have shown an increase in myoglobin, mitochondria, and the metabolic enzymes necessary for aerobic energy production. Taken together, these changes improve the efficiency of oxygen delivery to the muscle cell as well as the extraction of blood oxygen at the muscle cell level.

These adaptations are sufficient to restore maximum aerobic exercise capacity (VO2max) to NEAR sea level values at altitudes up to 2500 meters (7500 feet). At higher elevations, acclimatization will never restore VO2 max. to what is possible at sea level.

Not all the changes that occur with acclimatization are favorable to improve athletic performance in the face of a decrease in available oxygen. One notable negative is the loss of lean body mass and body fat that occurs with long term exposure to high altitudes. The result is a decreased maximum potential for athletic performance because of decreased muscle mass.

The time course of acclimatization

• As mentioned, the ventilatory response begins immediately upon climbing to altitude from sea level.
• Hyperventilation changes the blood acid base balance (with a respiratory alkalosis) which in turn stimulates the kidneys to excrete bicarbonate to compensate. This renal compensatory response takes about a week.
• The sympathetic nervous system is activated almost immediately with an increase in both sympathetic nerve activity and an increase in blood epinephrine levels - resulting in an increase in heart rate and cardiac output to maintain tissue oxygen delivery at near sea level values. By two to three weeks, blood flow returns toward sea level values as muscle oxygen delivery improves as a result of the other compensatory mechanisms.
• The hematocrit level begins to increase within 24 to 48 hours as a result of a reduction in plasma volume, not an increase in overall red cell mass. Erythropoietin levels increase within hours, peak at about 48 hours, and remain elevated for 1 to 2 weeks. They in turn stimulate the bone marrow to increase production and the total circulating red cell mass increases slowly (and may take several years to reach levels equal to natives living permanently at these altitudes).

How about iron?

First, the original article which, I feel, misrepresents the conclusions of the referenced study: Iron Levels and Altitude. Taking supplements may increase the benefits of thin-air training. Which it was then reprinted for cyclists in Bicycling: This Common Supplement Could Help You Ride Better at Altitude"

This was a pretty strong claim so I thought I'd look for more details in the original article in PLOS. Although the PLOS article was quoted as supporting improved athletic performance at altitude with iron supplements, as far as I can determine it only found that IRON DEFICIENT athletes incorporate more substrate (iron) into their blood cells if they were given supplements - which makes sense. They need iron (even at sea level as they are iron deficient), so given iron plus the stimulus of altitude, it is only reasonable to assume that they will absorb more of it. And as iron is in many enzymes (along with iron in blood cells), one might also expect some performance improvement (non heme level related) in the iron deficient athletes as well. And of course there is no evidence that the iron deficient group actually improved performance - only that the blood cell mass increased and thus it was assumed they would perform better as well.

So unless you are iron deficient (have a low ferritin), iron will not help your performance (at altitude or sea level), and if you have adequate iron stores, there are risks of iron overload and toxicity with unneeded supplements.

Viagra (sildenafil)- a reasonable option for a subset of athletes who suffer from altitude.

Viagra increase the effects of NO in erectile dysfunction by increasing the sensitivity to NO released with sexual stimulation from nerve endings and endothelial cells in the corpus cavernosum of the penis. The NO then stimulates an enzyme to convert guanosine triphosphate (GTP) into cyclic guanosine monophosphate (cGMP). And it is the cGMP that causes the smooth muscle of the arteries in the penis to relax, in turn allowing an inflow of blood leading to an erection. cGMP is broken down and back to the inactive GMP by a second enzyme - phosphodiesterase type 5 (PDE5). Men who suffer from erectile dysfunction often produce too little endogenous NO and the small amount of cGMP they subsequently produce is eliminated quickly (the same absolute rate of degradation, but less total cGMP to be metabolized so the level of total cGMP decreases at a faster rate). Thus it doesn't accumulate and lead to the hoped for vasodilation effect. Sildenafil (Viagra) works by inhibiting the enzyme PDE5. This means that cGMP is not hydrolyzed as fast, accumulates to higher levels, and as a result is present for a longer time to act to allow the smooth muscle to relax. Sildenafil is a potent and highly selective inhibitor of PDE5.

If you suffer disproportionately from the effects of altitude (nausea, headaches), Viagra may eliminate the metabolic changes that are putting you at a performance disadvantage. And may "level the playing field" for a competitive event.

ALTITUDE AS A TRAINING AID

Does anaerobic (i.e. hypoxic) exercise at altitude provide a training benefit? This is controversial, but controlled studies in trained athletes have not confirmed a benefit for hypoxic exercise WITHOUT CONCOMITANT ACCLIMATIZATION.

And the direct effects of interval training to stress and improve an athlete's maximum aerobic capacity (VO2 max.) at altitude deteriorate with training at elevation as a result of the inability to achieve a VO2 max. that is comparable to what is possible at sea level. During interval work outs, speed, oxygen uptake, heart rate, and lactate levels are all lower than those from lower altitudes suggesting that interval training is best performed as near sea level as possible.

Does exercise training at altitude improve sea level performance?

Many scientists, athletes, and coaches have been intrigued by the similarities of altitude acclimatization and training effects. Does living and training at altitude (with the associated changes in red cell mass and cellular changes in mitochondria, etc.) lead to an increase in the maximal aerobic exercise capacity (VO2 max.) upon return to sea level? The answer is "it depends". It is the net balance of the benefits of the acclimatization effects countered by the negatives of a reduction in training intensity and resulting deconditioning (in an oxygen limited environment) that are the ultimate determinate of the outcome of altitude training in endurance athletes. Controlled studies have NOT shown any advantage of TRAINING at altitude compared to a similar TRAINING program (the same absolute VO2 max. being achieved at both altitudes) at sea level.

Are there any strategies that can use altitude to benefit a training program?

The answer to this question is YES. But it requires balancing the acclimatization benefits of an increased red cell mass from living at altitude (one must be at altitude for more than 12 hours a day to maintain an increase erythropoietin level) while maximizing the VO2 max. achievable in training equivalent to that possible at sea level.

How high must one live to maximize acclimatization? An altitude of 2500 to 2800 meters maintains a balance between stimulating erythropoietin and minimizing the effects of acute mountain sickness that occur with increasing frequency at higher elevations.

How long should one live at altitude to maximize benefits?? At least 3 to 4 weeks.

How long will the acclimatization effects last? Based on actual performance studies, 2 to 3 weeks at most before they begin to reverse.

And the optimal training altitude? Although this should be individualized as some athletes do quite well maintaining a high VO2 max training at high altitudes, the general rule is to train as close to sea level as possible, preferably below 1500 meters.

So it is the balance between acclimatization and deconditioning that gives the personalized answer for each individual athlete. A few can maintain a high training VO2 max. even while training at altitude enabling them to live at altitude and train there as well. But the vast majority need to descend to train several times a week or face a competitive disadvantage from deconditioning.

THE BOTTOM LINE

Altitude can be used to improve sea level performance. But it needs to be used correctly. Its advantages are related to acclimatization effects i.e. an increase in the red cell mass from 2 to 3 weeks at altitude. The same benefits could be gained from using injections of erythropoietin if it were not a banned substances (and one with some health risks as well from overzealous use and exceedingly high hematocrits). Blood doping has the same effects. And it has been suggested that living (or sleeping for more than 12 hours a day) in a high altitude chamber or using nitrogen houses as the Scandinavians have proposed (and utilized) may have the same beneficial effect.

But to maximize the benefits of the altitude effect, training (i.e. absolute VO2 max. achievable) should be near sea level. Some athletes can train at altitude and pull this off, but the majority will need to do interval training at least twice a week at sea level oxygen levels to avoid the disadvantages of deconditioning (and a lower personal VO2max with time).

Altitude effects on performance are a complex issue, but are best summarized in the simple mantra:

Is there any way to avoid the hassles of traveling to a lower elevation to train - gaining the advantages of the hypoxia of altitude to acclimatize during the majority of your day (and while sleeping at night) while maintaining a high level training program?

The Scandinavians reportedly live in a "nitrogen" house which lowers the ambient oxygen level during sleep and the portion of the day they spend there (and training is as easy as stepping out the door), while others have suggested sleeping in an altitude chamber. Another option that seemed to make sense to the author was living at altitude and using supplemental oxygen while training to raise the amount of oxygen available to the alveoli in the lung and maximizing VO2max achievable during training sessions. This question was addressed to Dr. Ben Levine who has done the majority of the work leading up to the high-low theory of training.

His response:

Dear Dr. Rafoth,

Thanks for your note. You are absolutely right that an alternative to travel for high-low is training high with supplemental O2. In fact, this is exactly the tack taken by US Cycling and US Swimming at Colorado Springs. It is a bit cumbersome, but as long as the workouts can be reproduced, will work fine.

Ben Levine

COMPETITION AT ALTITUDE

What should an athlete do to prepare for competition at altitude ?

For endurance events, if it is possible, adequate time should be allowed to complete acclimatization - 2 to 3 weeks. The longer one waits, the more deconditioning of the VO2 max. that occurs. Returning to sea level to do interval training several times a week to minimize the deconditioning effect would be a definite advantage but is usually impractical.

Is it worth it, three weeks at altitude if one cannot return to sea level to maintain their conditioning? One article suggests the benefit (aside from acclimatization to avoid acute mountain sickness) gets one very little - maybe a 1% improvement. Thus it is very possible that for the majority of us mortals, 3 to 5 days is just enough to balance the positives of acclimatization against the negatives of detraining while waiting to acclimate.

For sprints (400 meters or less) most of the energy for muscular activity is oxygen independent (anaerobic) and acclimatization will not be of any benefit. But the lower air resistance at altitude will decease race times - which is why the 400 meter events were very fast in Mexico City in 1968 but the longer 1500 meter results were slower than at sea level.

THE RECREATIONAL RIDER GOING TO ALTITUDE

A major concern would be Acute Mountain Sickness. The rider needs to accept that there will be an inevitable decrease in VO2max (see above) and no special training program that will blunt this effect of altitude on performance.

Preventive strategies might include allowing 2 days of acclimatization before engaging in strenuous exercise at high altitudes, avoiding alcohol, and increasing fluid intake. A high-carbohydrate, low-fat, low-salt diet may aid in preventing the onset of AMS.

Although slow ascent is the preferred approach to avoiding AMS, there are times when this is impractical (plane connections to the start of a ride, emergency situations). In those cases, there are medications available that can decrease the chances of developing AMS. Acetazolamide (250 mg twice daily or 500 mg slow release once daily), taken before and during, ascent is recommended by many physicians although dexamethasone (4 mg, 4 times daily) has been shown to be of equal effectiveness. And in one study, those on acetazolamide actually had more symptoms of nausea at low altitudes (where AMS was not an issue) than a placebo group. Nausea was not a problem for those using dexamethasone, and indeed a mild euphoria was often reported. The usual recommendation for both medications is to start 24 hours before going to altitude and then continuing for 48 hours after starting the ascent. By that time, normal adaptive mechanisms should have had time to take over.

As dexamethasone is faster acting than acetazolamide, some authorities suggest taking the dexamethasone along, but starting it only when and if symptoms develop. As severe AMS is uncommon, this eliminates the inconvenience (and possible drug allergy or intolerance) of a medication that might not be needed.