Could Popeye Get AMS?

Posted by Jeremy Windsor on Apr 28, 2019

Iron plays an important part in the ability of human cells to sense and respond to low levels of oxygen. Knowing this, two research groups recently set out to explore whether an iron supplement improves the acclimatisation process and therefore reduces the risk of Acute Mountain Sickness (AMS) (1) (2). The trials of both groups had a lot in common - they blinded healthy lowland residents and gave them placebo or a single dose of intravenous iron (III) hydroxide (200mg) at sea level, before transporting them rapidly to high altitude and  measuring their Lake Louise Scores (LLS).

The results of both studies make interesting reading.

In the first trial, a group of UK researchers drove 24 participants from sea level to Cerro de Pasco (4340m) and the next day measured their LLS (1). The mean LLS of the placebo group rose by 3.4 compared to 1.1 in those who received intravenous iron (P<0.05). The incidence of AMS was 67% in the placebo group compared to 42% in those who received intravenous iron (P<0.05).

The Peruvian city of Cerro De Pasco is one of the highest cities in the world. It has a population of approximately 60,000 people. The majority are involved in the mining of silver and other precious metals.

Meanwhile in a more recent trial, Chinese researchers flew 38 participants from Beijing (50m) to Lhasa (4300m) and measured their LLS for the five consecutive days (2). On the day after arrival, 10/19 (53%) in the placebo group had AMS (LLS>3) compared to just 5/19 (26%) who received intravenous iron. Although an obvious numerical difference can be seen this did not reach statistical significance (P>0.05).

Dare I say it, these two small trials may provide the first clues that an iron supplement may help prevent AMS at high altitude. With further research it may be possible to identify the dose, duration and formula of a more practical oral preparation that could offer similar benefits. This might also be the first step in highlighting a potential risk factor for AMS. What if iron deficiency proved to be a risk factor for AMS? A simple blood test could be performed, an oral iron supplement prescribed and the risk of AMS reduced! But before we get ahead of ourselves, is there anyone out there who's willing to do the science? What about conducting a study that takes blood samples from a large population of lowland residents and records their AMS scores following an ascent to high altitude? If a close link could be found, the next step would be to treat those with iron deficiency and see if their LLS was lower than a well matched group receiving a placebo. Of course, there's a much wider set of implications. Could iron deficiency be linked to a higher mortality and morbidity in hypoxic patients on our wards? Could supplemental iron make a difference?

STDZ asked Dr Annabel Nickol, Consultant Respiratory Physician and one of the authors on the Cerro de Pasco study to bring us up to speed...

"There is a really good rationale to believe that iron deficiency exacerbates the deleterious effects of hypoxia. Here are some interesting bits of evidence from Peter Robbins’ laboratory:

Nick Talbot and Tom Smith, who led this interesting bit of work in Cerro de Pasco, previously demonstrated that iron supplementation blunts the hypoxic pulmonary vasoconstrictor response on 8-hour exposure to hypoxia, whereas induced iron deficiency using an infusion of desferrioxamine augments it in health volunteers.  

Differences in hypoxic pulmonary vascular response have also been seen in those with endogenous iron deficiency.  

We also observed that the prevalence of iron deficiency in COPD is high compared to age-matched controls (inflammation increases hepcidin, which reduces iron absorption and use), and the iron deficient patients had lower oxygen saturations. However this last observation was not reproduced in a subsequent study randomising COPD patients to IV iron or placebo, however it was associated with a non-significant improvement in walk-distance. 

So there is every reason to believe that people with iron deficiency could be more susceptible to AMS, and yes a large-scale field study is entirely appropriate!"

Thanks Annabel - There's clearly much to do! 

(1) Talbot NP, et/al. Intravenous iron supplementation may protect against acute mountain sickness: a randomized, double-blinded placebo controlled trial. High Alt Med Biol 2011;12(3):265-269.

(2) Ren et/al. Effect of intravenous iron supplementation on AMS: A preliminary randomised controlled trial. Med Sci Monit 2015:21:2050-2057.

If you'd like a copy of the Talbot et/al study please get in touch!

Note: The long held belief that spinach is a rich source of iron is based upon a transcription error. In 1870 German chemist Erich von Wolf was the first to measure the amount of iron in spinach. Whilst transcribing his notes he accidentally misplaced a decimal point! Instead of recording 3.5 milligrams of iron per 100 gram serving he wrote 35 milligrams instead. The mistake wasn't corrected for almost a century. Today many still believe that spinach is a rich source of iron. Unfortunately Popeye needs other foodstuffs to provide enough iron to maintain his well known physical prowess!

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