Abstract
Nitric oxide (NO) production plays a central role in conferring tolerance to hypoxia. Tibetan highlanders, successful high-altitude dwellers for millennia, have higher circulating nitrate and exhaled NO (ENO) levels than native lowlanders. Since nitrate itself can reduce the oxygen cost of exercise in normoxia it may confer additional benefits at high altitude. Xtreme Alps was a double-blinded randomised placebo-controlled trial to investigate how dietary nitrate supplementation affects physiological responses to hypoxia in 28 healthy adult volunteers resident at 4559 m for 1 week; 14 receiving a beetroot-based high-nitrate supplement and 14 receiving a low-nitrate ‘placebo’ of matching appearance/taste. ENO, vital signs and acute mountain sickness (AMS) severity were recorded at sea level (SL) and daily at altitude. Moreover, standard spirometric values were recorded, and saliva and exhaled breath condensate (EBC) collected. There was no significant difference in resting cardiorespiratory variables, peripheral oxygen saturation or AMS score with nitrate supplementation at SL or altitude. Median ENO levels increased from 1.5/3.0 mPa at SL, to 3.5/7.4 mPa after 5 days at altitude (D5) in the low and high-nitrate groups, respectively (p = 0.02). EBC nitrite also rose significantly with dietary nitrate (p = 0.004), 1.7–5.1 μM at SL and 1.6–6.3 μM at D5, and this rise appeared to be associated with increased levels of ENO. However, no significant changes occurred to levels of EBC nitrate or nitrosation products (RXNO). Median salivary nitrite/nitrate concentrations increased from 56.5/786 μM to 333/5,194 μM with nitrate supplementation at SL, and changed to 85.6/641 μM and 341/4,553 μM on D5. Salivary RXNO rose markedly with treatment at SL from 0.55 μM to 5.70 μM. At D5 placebo salivary RXNO had increased to 1.90 μM whilst treatment RXNO decreased to 3.26 μM. There was no association with changes in any observation variables or AMS score. In conclusion, dietary nitrate supplementation is well tolerated at altitude and significantly increases pulmonary NO availability and both salivary and EBC NO metabolite concentrations. Surprisingly, this is not associated with changes in hemodynamics, oxygen saturation or AMS development.
Highlights
The partial pressure of oxygen decreases on ascent to high altitude as a result of a decline in barometric pressure; at 5300 m it is approximately half the value at sea level [1]
There was no significant difference in resting cardiorespiratory variables, peripheral oxygen saturation or acute mountain sickness (AMS) score with nitrate supplementation at sea level (SL) or altitude
These results demonstrate that dietary nitrate supplementation with a beetroot/fruit juice mixture at altitude successfully increases nitrate availability; these increases are associated with markedly enhanced levels of exhaled Nitric oxide (NO) (ENO), and nitrate and nitrite levels in saliva as well as nitrite concentrations in exhaled breath condensate (EBC) throughout the duration of altitude exposure
Summary
The partial pressure of oxygen decreases on ascent to high altitude as a result of a decline in barometric pressure; at 5300 m (the height of Everest base camp) it is approximately half the value at sea level [1] This hypobaric hypoxia causes hypoxaemia (a lack of oxygen in the blood) resulting in significant physiological challenges. Native lowlanders seem to rely heavily on increased erythropoiesis to maintain oxygen content at altitude [1], whilst this response is much less pronounced in native highlanders such as the Sherpas (supremely adapted after living at high altitude for over 500 generations) [4] Another notable difference that is remarkably conserved across different high altitude populations (including the Tibetan populations and the Bolivian Aymara) is that mountain dwellers exhale higher concentrations of nitric oxide (NO) compared to individuals living at sea level [5,6]. During graded exposure to altitude, NO production increases in lowlanders suggesting that NO production and respiratory NO availability might play an important role in offsetting the effect of hypoxia and improve performance [8]
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