Altitude sickness update

DNC News

Jacob Schor, ND, FABNO

June 2013


My first review about altitude sickness was posted online in 2004 and a second in 2009.  I receive more emails in response to these ‘altitude’ than about any other topic. Knowledge about altitude sickness and how we should treat it keeps shifting and yesterday’s answers are often discarded. It’s time to visit the subject again


Two things prompted me to review the new literature today.  The first is that a good many of my fellow naturopathic physicians will arrive in Colorado July 10th for our annual conference, which this year will be held at Keystone Resort.  Rena and I are looking forward to seeing a many friends and getting out of the city for a few days.


The second thing that had me thinking about altitude sickness was an article in the June 18th issue of New Scientist by Ed Douglas. The article brought a different perspective to the discussion.  The adjustments that the human body makes at high altitudes have generally been considered adjustments to the lower air pressure.  Douglas suggests, as many researchers seem to be suggesting, that the changes might better be seen as compensations to low blood oxygen levels, what is called hypoxia.  Oxygen pressure decreases with decreasing air pressure as elevation increases.  People accustomed to sea level air pressure will notice the difference when they come to visit us.  At first heart rate and blood pressure increases.  With Himalayan high altitudes this can lead to life-threatening illnesses, notably high-altitude pulmonary and cerebral edema.  Such a reaction is rare in Colorado, but discomfort isn’t.


The body slowly responds to this lack of oxygen by making extra red blood cells and extra hemoglobin.  This allows the heart rate and blood pressure to fall, increasing ability to do athletic sorts of things without feeling instantly short of breath.


A new perspective:

At least this has been the accepted understanding.  Recently researchers have questioned these ideas.  The assumption was that these responses had evolved over time to aid humans, but really what percentage of human beings have needed to climb Mt. Everest in evolutionary history?  Not enough to influence the evolution of a “High Altitude Response.”  The making of more hemoglobin at high altitude may just be a response to hypoxia and not really even the best way to compensate for it.  Our evolution was more likely driven to respond to injuries that cause blood loss than a need to climb mountains.  With sudden blood loss, say after an injury, our blood becomes hypoxic, that is low in oxygen, and the best way to fix this is to produce new red blood cells as fast as possible.  Thus the increase in RBCs and hemoglobin seen at high altitude may only be your body thinking it has lost blood suddenly.


Increasing hemoglobin is not the best strategy for responding to altitude-induced hypoxia.  More blood cells do not really increase oxygen transfer efficiency, which is dependent on atmospheric pressure, not the amount of hemoglobin.



According to one researcher that Douglas quotes, this response is actually a dumb idea. "It turns your blood to porridge…..This is not good for you. It knackers your microcirculatory system." Thicker blood, means more viscous blood, and this increases your risk of clots, stroke, and death.  


This thinking stems from research on the Chinese who have moved to the Tibetan plateau. Lowland Chinese living in Tibet exhibit very different responses to the high elevations than the people whose families have lived there for thousands of years.  This is particularly evident in pregnant women.  Women from China, as would be expected, produce extra hemoglobin during pregnancy putting them at high risk for stroke, thrombosis and eclampsia.  Tibetan women do not make extra hemoglobin when pregnant.


In fact all Tibetans have low levels of oxygen in their blood all of the time.  It doesn’t appear to slow them down though.  Rather than living with porridge blood, they have evolved a way to live with less oxygen.


It isn’t just Tibetans who have evolved the ability to function on low oxygen.  Another high altitude people, the Amhara in Ethiopia, have evolved a similar adaptation (though via different genes).  Both populations limit the production of extra hemoglobin in response to hypoxia. 


Increasing hemoglobin while a common response to high altitude and hypoxia, isn’t a solution. We can list no shortage of illnesses that trigger hypoxia in the body, resulting in ‘porridge blood’ that in turn increases risk of stroke, thrombosis etc.  One person in five will, at some point in their lives, suffer from hypoxia unrelated to high altitude or blood loss.  Thus understanding how to trigger better ways for the body to respond to hypoxia may be potentially useful knowledge.


Tibetans live their whole lives with low levels of blood oxygen.  Perhaps our treatments for hypoxia should mirror their chemistry.  One thing unique about native Tibetans is that they produce unusually high levels of nitric oxide that dilates their blood vessels letting larger volumes of blood move through their bodies in a shorter time.  Perhaps this allows them to live comfortably with less oxygen?  Thus drugs or supplements that increase nitric oxide or impact blood flow have been suggested as possible treatments.  So far though the results have been mixed.



A few years ago, sildenafil caused a stir of excitement and jokes among high-altitude researchers.  Silfenafil is the generic name for Viagra.  Recall that this drug increases nitric oxide and blood flow. In 2005 a study announced that by improving pulmonary circulation, sildenafil safely protects against the high altitude-induced pH changes and improves gas exchange.   It was assumed that this would alleviate symptoms of altitude sickness.  Unfortunately this hope was dashed by recent papers that found no significant difference in most latitude related symptoms in those taking Viagra from those who received placebo.  One study actually reported worse symptoms with the drug.   The most recent paper we come across is a 2011 paper by Kressler et al that concluded, “… that sildenafil is unlikely to exert beneficial effects at altitudes <4,000 m for a majority of the population.”

Not what we had hoped.



Ginkgo biloba extracts were also the big thing for treating altitude sickness a decade ago.  One good clinical trial was followed by a second trial that yielded disappointment.  The researchers tried to explain away this inconsistency by blaming the, “source or composition of the… products” they used in their trials. While it is true that there is great inconsistency in herbal products, a problem that may only be getting worse as supplement sales expand, this does not seem like an adequate an explanation.  A 2013 study that compared gingko with acetazolamide, the drug commonly prescribed for altitude sickness, found no effect from the ginkgo.   Acetazolamide, while it helps altitude sickness is not without drawbacks.  A 2012 meta-analysis of multiple studies confirmed that, “ acetazolamide is effective for the prevention of acute mountain sickness but may be associated with paresthesias.”   



The Asian botanical medicine Rhodiola has long been suggested as a treatment for altitude sickness.  The recent research is mixed.  A 2013 report tells us that a particular subspecies of the herb, Rhodiola crenulata, is useful in treating hypoxic pulmonary edema in rats.    Unfortunately or fortunately we are not rats, and what helps a rat may not help us.  Rhodiola does, according to an April 2013 paper, protect red blood cells from death by suffocation in low oxygen conditions.  While this also sounds good, this study was talking about cells in a test tube.   We are not rats and we don’t live in test tubes.  In a study of Chinese railroad employees who were working in Tibet, no lessening of symptoms of altitude sickness was seen in those taking rhodiola preparations.   A 2011 paper that compares three common Chinese preparations used to prevent altitude sickness reported that, “Shenqi Pollen Capsule was more effective than Rhodiola Rosea Capsule and Sankang Capsule.”   What exactly Shenqi pollen capsules are and where to find them is a great question for which I don’t have an answer. 



A few new studies of interest suggest that several far more common supplements may be of help.  Seabuckthorn (Hippophae rhamnoides) has long been used as a traditional treatment for altitude sickness.   We sometimes use extracts of this plant to treat damage from the radiation therapy used in cancer treatment, particularly of the mucous membranes and bladder.  Zhou et al in a 2012 paper tell us that seabuckthorn prevents the increase in red blood cells in rats, the porridge effect (or in more medical terms, polycythemia), caused by high altitude.   Another 2012 paper describes a traditional concoction used to treat altitude sickness made of seabuckthorn, apricots and rhodiola.   This mixture provides a number of different phytonutrients and antioxidants, in particular a chemical called quercetin.



We’ve written at length about quercetin’s impact on antioxidant status, athletic performance and anticancer effects.  We frequently use it to treat allergies and asthma.


In January 2012, Zhou et al reported that quercetin given to rats under high altitude conditions had a protective action improving cardiac function because it improves arterial blood gas levels and nitric oxide metabolism.   In August 2012, Patir et al reported that pre-treatment with quercetin protected rats from cerebral edema when exposed to simulated high altitude conditions.


As we are already familiar with using quercetin for a wide range of conditions and consider it well tolerated and safe, we will likely add this to our list of supplements to consider for prevention altitude sickness.  Experience suggests that it is more effective when taken in combination with fish oil, green tea and bromelain.  Researchers typically have dosed it at 1,000 mg/day in human trials.  We have not found a human clinical trial on altitude sickness yet. In earlier studies conducted on endurance runners in Leadville, Colorado, endpoints related to altitude sickness were not reported.



Studies on two other supplements deserve our attention.  N-acetyl-cysteine, improves mental function under high altitude conditions, at least in rats.  We don’t know if it will work as well in people but it is certainly worth a try.   Typical oral doses used for other applications are usually in the range of 1,000 to 2,000 mg/day.

Actyl-l-carnitine has also been reported to have a similar benefit, improving spatial working memory during exposure to a simulated high altitude that causes hypoxia.   This is often dosed in a range of 1,000 to 2,500 mg/day.


Water and Alcohol:

As far as diet, we don’t know much, well aside from encouraging people to drink as much fluid, in particular water, as possible.  Aggressive fluid intake continues to be considered protective.   Increasing carbohydrate intake has been suggested as useful.  It may help increase hemoglobin saturation but it hasn’t been shown to relieve symptoms.   Thus it’s not clear what to say.   Alcohol consumption at higher altitudes has a bigger impact than at lower altitudes; people get a lot drunker a lot easier and a lot faster. This is so well known that we won’t even bother finding a citation.



So that’s where we are this summer.  There is no doubt that this information will change in the near future, but for today we have evidence that some of the older treatments, in particular seabuckthorn and rhodiola might work along with the hint that NAC, quercetin and acetyl-l-carnitine might be worth a try.






2009 article:

2004 article:

Quercetin in NMJ:





Ed Douglas. Everest's final frontier: Life without oxygen

New Scientist. 18 June 2013


Expert Opin Pharmacother. 2005 May;6(5):835-7.

Sildenafil for the treatment of altitude-induced hypoxaemia.

Perimenis P.


High Alt Med Biol. 2011 Fall;12(3):207-14. doi: 10.1089/ham.2011.0007.

Sildenafil citrate for the prevention of high altitude hypoxic pulmonary hypertension: double blind, randomized, placebo-controlled trial.

Bates MGThompson AABaillie JKSutherland AIIrving JBHirani NWebb DJ.


Eur J Appl Physiol. 2011 Dec;111(12):3031-40. doi: 10.1007/s00421-011-1930-3. Epub 2011 Mar 31.

Sildenafil does not improve steady state cardiovascular hemodynamics, peak power, or 15-km time trial cycling performance at simulated moderate or high altitudes in men and women.

Kressler JStoutenberg MRoos BAFriedlander ALPerry ACSignorile JFJacobs KA.


Wilderness Environ Med. 2009 Spring;20(1):66-71. doi: 10.1580/08-WEME-BR-247.1.

Ginkgo biloba does--and does not--prevent acute mountain sickness.

Leadbetter GKeyes LEMaakestad KMOlson STissot van Patot MCHackett PH.


High Alt Med Biol. 2009 Spring;10(1):33-43. doi: 10.1089/ham.2008.1085.

Ginkgo biloba for prevention of acute mountain sickness: does it work?

van Patot MCKeyes LELeadbetter G 3rdHackett PH.

High Alt Med Biol. 2013 Jun;14(2):162-7. doi: 10.1089/ham.2012.1099.

Effect of acetazolamide and gingko biloba on the human pulmonary vascular response to an acute altitude ascent.

Ke TWang JSwenson ERZhang XHu YChen YLiu MZhang WZhao FShen XYang QChen J,Luo W.


Ann Emerg Med. 2012 Apr;59(4):307-317.e1. doi: 10.1016/j.annemergmed.2011.10.015. Epub 2011 Dec 7.

Pharmacologic prophylaxis for acute mountain sickness: a systematic shortcut review.

Seupaul RAWelch JLMalka STEmmett TW.


Chin Med J (Engl). 2012 Apr;125(8):1393-400.

Who are more at risk for acute mountain sickness: a prospective study in Qinghai-Tibet railroad construction workers on Mt. Tanggula.

Wu TYDing SQLiu JLJia JHChai ZCDai RC.


J Nat Prod. 2012 Apr 27;75(4):531-7. doi: 10.1021/np200555s. Epub 2012 Apr 6.

Salidroside protects human erythrocytes against hydrogen peroxide-induced apoptosis.

Qian EWGe DTKong SK.


Chin Med J (Engl). 2012 Apr;125(8):1393-400.

Who are more at risk for acute mountain sickness: a prospective study in Qinghai-Tibet railroad construction workers on Mt. Tanggula.

Wu TYDing SQLiu JLJia JHChai ZCDai RC.


Zhong Xi Yi Jie He Xue Bao. 2011 Apr;9(4):395-401.

[Three preparations of compound Chinese herbal medicines for de-adaptation to high altitude: a randomized, placebo-controlled trial].

[Article in Chinese]

Shi ZFZhou QQXiang LMa SDYan CJLuo H.


Molecules. 2012 Sep 28;17(10):11585-97.

Protective effect of total flavonoids of seabuckthorn (Hippophae rhamnoides) in simulated high-altitude polycythemia in rats.

Zhou JYZhou SWDu XHZeng SY.


J Food Sci. 2012 Feb;77(2):C156-61. doi: 10.1111/j.1750-3841.2011.02523.x. Epub 2012 Jan 6.

Antioxidant capacities and total polyphenol contents of hydro-ethanolic extract of phytococktail from trans-Himalaya.

Dhar PTayade ABBajpai PKSharma VKDas SKChaurasia OPSrivastava RBSingh SB.


Eur J Pharmacol. 2012 Jan 15;674(2-3):450-4. doi: 10.1016/j.ejphar.2011.11.028. Epub 2011 Nov 25.

Modulatory effects of quercetin on hypobaric hypoxic rats.

Zhou JZhou SGao YZeng S.


Free Radic Biol Med. 2012 Aug 15;53(4):659-68. doi: 10.1016/j.freeradbiomed.2012.06.010. Epub 2012 Jun 26.

Quercetin as a prophylactic measure against high altitude cerebral edema.

Patir HSarada SKSingh SMathew TSingh BBansal A.


Nieman DC, Henson DA, Davis JM, Dumke CL, Gross SJ, Jenkins DP, Murphy EA, Carmichael MD, Quindry JC, McAnulty SR, McAnulty LS, Utter AC, Mayer EP. Quercetin ingestion does not alter cytokine changes in athletes competing in the Western States Endurance Run. J Interferon Cytokine Res. 2007 Dec;27(12):1003-11. doi: 10.1089/jir.2007.0050.


Physiol Behav. 2007 Nov 23;92(4):643-50. Epub 2007 May 24.

N-acetyl cysteine supplementation prevents impairment of spatial working memory functions in rats following exposure to hypobaric hypoxia.

Jayalakshmi KSingh SBKalpana BSairam MMuthuraju SIlavazhagan G.


Eur J Pharmacol. 2007 Sep 10;570(1-3):97-107. Epub 2007 Jun 13.

Acetyl-L-carnitine ameliorates hypobaric hypoxic impairment and spatial memory deficits in rats.

Barhwal KSingh SBHota SKJayalakshmi KIlavazhagan G.


Wilderness Environ Med. 2006 Winter;17(4):215-20.

Acute mountain sickness: influence of fluid intake.

Nerín MAPalop JMontaño JAMorandeira JRVázquez M.


Aviat Space Environ Med. 1999 Sep;70(9):874-8.

Improvement in hypoxemia at 4600 meters of simulated altitude with carbohydrate ingestion.

Lawless NPDillard TATorrington KGDavis HQKamimori G.


Aviat Space Environ Med. 1997 Jun;68(6):499-503.

Acute mountain sickness is not altered by a high carbohydrate diet nor associated with elevated circulating cytokines.

Swenson ERMacDonald AVatheuer MMaks CTreadwell AAllen RSchoene RB.