Randy Trumbower and his colleagues in Emory’s Department of Rehabilitation Medicine recently published a study showing that “daily intermittent hypoxia,” combined with walking exercise, can help patients with incomplete spinal cord injury walk for longer times. What is it about being deprived of oxygen for short periods that has a positive effect?

This research was puzzling at first (at least to your correspondent) because “daily intermittent hypoxia” is a good description of the gasping and snorting interruptions of sleep apnea.

Sleep apnea is a very common condition that increases the risk of high blood pressure, diabetes, heart attack and stroke. On the other side of the coin, many endurance athletes have been harnessing the body’s ability to adapt to low oxygen levels — so-called altitude training — to increase their performance for years.

So we have an apparent clash: hypoxia is bad, except when it’s good. Looking closely, there are some critical differences between sleep apnea and therapeutic hypoxia. The dose makes the poison, right?

In the Emory study, participants’ exposure to hypoxia is very limited. By breathing through a mask, they experience 90 seconds of reduced oxygen (9 percent) followed by a minute of normal oxygen, repeated 15 times. That was enough to reduce participants’ blood oxygenation levels down to about 78 percent. Blood oxygenation is usually somewhere between 95 and 100 percent and anything below 90 is considered a clear drop. Still, it’s not on the same level as the effects of sleep apnea, which can lower blood oxygen levels dozens of times a night for years.

With respect to altitude training, Trumbower acknowledged the similarity while discussing the technique with New Scientist:

“If you were to convert 9 per cent oxygen to altitude, you can think of yourself being at about 26,000 feet; at Mount McKinley but not quite Mount Everest. You’re continuously alternating between the summit and base camp,” he said, adding that participants do not experience discomfort because they are not exposed to the hypoxic air for long.

Altitude training’s effects on endurance seem to come from adaptive changes in the body’s ability to carry oxygen: more red blood cells and/or more efficient use of oxygen. In contrast, intermittent hypoxia’s benefits for the spinal cord are thought to come via stimulation of the neurons themselves, via serotonin and the neuron growth factor BDNF. In animal experiments, a similar regimen of hypoxia stimulates BDNF in the spinal cord.

This raises the question whether hypoxia is just simulating or substituting for the effects of aerobic exercise, which is also thought to work by stimulating BDNF. Even if it is, the hypoxia treatment is remarkably efficient, and someone with spinal cord injury literally needs to walk before being able to run. A previous paper by Trumbower and colleagues showed that even a single bout of exposure to hypoxia can put some spring in the step (ie increase ankle strength).

“What was really dramatic in the exercise protocol was that just a single week of breathing with intermittent hypoxia and walking had an effect size that was comparable to, if not in many cases greater than, that shown in previous studies of locomotor training for 4 to 6 weeks,” he told Medscape in November.

Neurologists and rehab specialists who have commented on the study say the therapeutic hypoxia approach looks promising, although safety and applicability to broader ranges of patients are still concerns. Also, the therapeutic effects didn’t last more than a few weeks, but investigators plan to test longer treatment regimens.