麻豆传媒

MOUNTAINEERS Ralf Dujmovits and Nancy Hansen are no strangers to thin air, having collectively reached the summits of all eight of the world鈥檚 highest mountains. But when they entered the hypoxia chamber at the in May 2018, they were effectively climbing one of the highest peaks of their careers. After a two-week acclimatisation, they spent 16 days breathing air thinner than at Everest base camp 鈥� including four days at the equivalent of 7112 metres. This is just shy of the 鈥渄eath zone鈥� over 8000 metres, where the lack of oxygen impairs climbers鈥� judgement and increases their risk of heart attack and stroke.

Time and again, the two mountaineers 鈥� and those observing them 鈥� questioned whether they should keep going, but they did. If Dujmovits and Hansen could show that humans can tolerate extended periods of low oxygen, known as hypoxia, it would pave the way for an even more ambitious experiment: to test whether, sometimes, it might even be beneficial to starve people of oxygen.

This may sound strange. After all, our organs and tissues need oxygen. Indeed, astonishingly low oxygen levels in people with covid-19 have (See 鈥�Happy hypoxia?鈥�), and treatment . After a heart attack or stroke, people are routinely given oxygen too, to ensure their tissues don鈥檛 die.

Yet, for all this, surprisingly, there are hints that hearts and spinal cord injuries could heal faster if deprived of oxygen. Could it be that, in some cases at least, we have been breathing too much of a good thing?

Our bodies are set up to adapt to variations in oxygen availability. The 2019 Nobel prize for medicine went to the British and US researchers who identified key molecules called hypoxia inducible factors (HIFs) that multiply when oxygen supplies run low. HIFs activate hundreds of genes and biochemical pathways to help cope with oxygen deficiency.

At least some of these adaptations seem to be beneficial. Almost 140 years ago, French physiologist Paul Bert hypothesised that exposure to high altitude increased the number of oxygen-carrying red blood cells. In the 1930s, Russian military pilots prepared for flying planes with open cockpits by undergoing 鈥渁ltitude acclimatisation鈥�. During these sessions, doctors noticed that bouts of hypoxia seemed to help with conditions ranging from asthma to hypertension.

鈥淧eople living at altitude seem to be healthier, on average, than those living near sea level鈥�

That鈥檚 directly at odds with the conventional medical view of hypoxia: when people head into the mountains, their hearts beat faster and their blood pressure increases as their bodies try to cope with the diminished oxygen supply. They may feel nauseous, experience headaches and struggle to concentrate. Severe altitude sickness can be deadly, as the brain swells and lungs fill with fluid.

Even so, people living long-term at altitude seem to be healthier, on average, than those living near sea level. They have lower rates of diabetes, cardiovascular diseases and certain types of cancer like breast cancer and lymphoma.

Now, animal studies are starting to shed light on this paradox. In 2017, Hesham Sadek at the UT Southwestern Medical Center in Dallas, Texas, and his colleagues reported a peculiar finding. They kept mice in a chamber with slowly diminishing oxygen levels and noticed that if they spent two weeks breathing air with 7 per cent oxygen 鈥� roughly equivalent to what each breath delivers on top of Mount Everest 鈥� their . This was surprising because the hearts of adult mammals can鈥檛 usually form enough new tissue to regenerate themselves, which is why heart attacks are so deadly.

Sadek knew that mammalian hearts are able to regenerate themselves in utero, but lose this capacity shortly after birth. He began to wonder if this might be related to the peculiar oxygen environment experienced by embryos. Although they receive oxygen from their mother via the placenta, their heart grows under largely hypoxic conditions. And 鈥渋f you injure it, it regenerates completely鈥�, says Sadek. Babies lose this ability soon after birth, when they start breathing, which floods the body with oxygen. He speculated that this process might be reversible 鈥� that by carefully withholding oxygen, mature heart cells could be prompted to regress to a more embryonic-like state where they start dividing.

Sadek isn鈥檛 alone in spotting that hypoxia may have benefits. For the past few years, a team led by neuroscientist Gordon Mitchell at the University of Florida has been limiting the oxygen intake of people who have had a spinal cord injury. They might, for example, breathe regular air for 1 minute, then air 鈥渢hat鈥檚 as thin as at the summit of Mt Denali 鈥� the highest mountain in Alaska鈥�, the next, says Mitchell.

Because of their injuries, these patients need ventilators to help them breathe, but consuming thin air seems to make them less reliant on them. Their ability to walk and grasp objects also improves. Mitchell鈥檚 team has been investigating why this happens. One discovery is that hypoxia triggers the release of growth factors that fortify neural connections. 鈥淭he ,鈥� says Mitchell. Clinical trials are under way to test this further.

There is also . That may help explain why living at high altitude seems to reduce the risk of cardiovascular disease.

too, according to a review of several early-stage trials published in May. 鈥淲e are beginning to see efforts in other clinical disorders including ALS, MS and stroke, although none of these initial pilot studies have been published yet,鈥� says Mitchell.

Proponents believe the benefits may go further still. One area of interest is weight loss. This is rooted in research showing that people who live in mountainous areas are less likely to be obese, and that lowlanders who frequently go mountaineering often lose weight. Is that because people who prefer to live in the mountains tend to be more physically active, or simply that climbing a mountain is strenuous work? Partly, perhaps. But researchers say there is more to the story.

In 1985, the US Army simulated a 40-day mountaineering expedition in a hypoxia chamber. Six volunteers were kept warm and provided with unlimited snacks and meals. They could also exercise, but only if they felt like it. As with Dujmovits and Hansen鈥檚 stay at the DLR, oxygen levels were gradually reduced until . On average, the participants lost 7.5 kilograms during the 40 days.

Something similar was observed when researchers . Although they did no exercise and ate as much as they desired, each slimmed down by around 1.3 kilograms.

Researchers believe that hypoxia induces weight loss in two ways. First, it seems to make people less hungry. The reason is as yet unclear as yet, but in this study, researchers found that participants produced more of the satiety hormone leptin at altitude. By the end, they ate 730 fewer calories than usual per day.

Second, hypoxia also seems to trigger hormonal changes that boost our metabolic rate, so we burn more calories. It can increase energy expenditure by 30 per cent or more.

That鈥檚 not to say everyone should head to the mountains if they want to lose weight. For one thing, the effects of hypoxia seem to fade when people are no longer exposed to it: a weekend at a ski resort is unlikely to produce lasting weight loss. It is also not clear how much oxygen should be withheld, and if the same amount would apply to everyone.

Ultimately, hypoxia is probably a double-edged sword: beneficial in some situations, undeniably harmful in others. For people with sleep apnoea, for instance, it is surely the latter. The condition causes breathing to repeatedly stop for up to several minutes at night, and many people with sleep apnoea go on to develop diabetes. That may be because hypoxia triggers changes in glucose metabolism that make them more susceptible to the disease.

鈥淗ypoxia seems to make people less hungry and boost metabolic rate, so we burn more calories鈥�

More experiments are clearly needed, which is where Dujmovits and Hansen come in. Inspired by Sadek鈥檚 mouse studies suggesting that hypoxia strengthens the heart, Ulrich Limper and his colleagues at the DLR wanted to test the effect of prolonged hypoxia on healthy individuals, before eventually trying it on people recovering from a heart attack.

Breathing thin air : their heartbeats became irregular, blood thickened from the extra red blood cells churned out by their bone marrow, veins in the brain swelled and their hearts shrank while its walls grew thicker. .

For their part, Dujmovits and Hansen seemed relieved when they stepped out of the windowless chamber, back into normal air. 鈥淭he first thing I noticed about being outside after five weeks is that outside is BIG! And busy,鈥� reported Hansen on her blog. 鈥淲ith lots of oxygen. It tastes good.鈥�

Further studies had been held up by the pandemic. But if things go according to plan, the work should resume soon. 鈥淣ow that we know that healthy individuals can tolerate this kind of hypoxia without real risk, we need to show that heart patients can, too,鈥� says Limper. He and his team have recruited volunteers who have had a heart attack and are willing to spend several weeks in the low-oxygen chamber.

Like the mountaineers, they will be slowly starved of oxygen, that irreplaceable stuff that cells need to function, to produce energy, to live. Limper hopes that precisely because oxygen is so essential, the body will find a way to fight back 鈥� and people will emerge fitter and healthier, out of thin air.