Clinical Trial: Anti-Oxidant Supplementation for the Prevention of Acute Mountain Sickness
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: Randomized Double-Blind Placebo-Controlled Trial of Oral Anti-Oxidant Supplementation for the Prevention of Acute Mountain Sickness.
Brief Summary:
Acute mountain sickness (AMS), high altitude pulmonary edema (HAPE), and high altitude cerebral edema (HACE) are complications of rapid ascent to high altitude. Several features suggest that raised intracranial pressure (ICP) may be an important factor in the pathogenesis of AMS. Magnetic resonance imaging of HACE patients has demonstrated that the oedema in HACE is of the vasogenic, rather that cytotoxic, type. Thus it is likely that cerebrovascular permeability has an important role in the development of AMS and HACE.
Reactive oxygen species (ROS) have been shown to alter the permeability of the blood-brain barrier in severe ischaemia, causing vasogenic cerebral oedema. Endogenous antioxidant systems may have some capacity to respond to oxidative stress in hypoxia. The plasma concentration of urate, a powerful endogenous antioxidant, rises on acute exposure to high altitude and may play a crucial antioxidant role in systemic hypoxia. This antioxidant prevents free-radical induced cerebral oedema in animal models.
There are numerous sources of ROS in hypoxia, including the mitochondrial electron transfer chain, haemoglobin (Hb) autoxidation and xanthine oxidase activity. There have been several reports of raised markers of oxidative stress in humans at moderate altitude (<3000m).
Oral antioxidant supplementation with preparations containing vitamins C and E in humans at altitude has been shown to decrease breath pentanes (a marker of oxidative stress), and improve erythrocyte filterability. In a small randomised controlled trial, Bailey and Davies demonstrated a significant reduction in symptoms of AMS in subjects taking an oral antioxidant cocktail.
The antioxidants alpha-lipoic acid, vitamin C and vitamin E act synergi
Detailed Summary:
Acute mountain sickness (AMS), high altitude pulmonary edema (HAPE), and high altitude cerebral edema (HACE) are complications of rapid ascent to high altitude. By definition, AMS is a benign condition, but it is likely that the same pathology underlies high altitude cerebral oedema (HACE). In contrast, HAPE occurs in the context of pathologically elevated pulmonary artery pressures and uneven distribution of hypoxic pulmonary vasoconstriction across the pulmonary vascular bed.
Several features suggest that raised intracranial pressure (ICP) may be an important factor in the pathogenesis of AMS. Magnetic resonance imaging of HACE patients has demonstrated that the oedema in HACE is of the vasogenic, rather that cytotoxic, type. Thus it is likely that cerebrovascular permeability has an important role in the development of AMS and HACE.
Reactive oxygen species (ROS) have been shown to alter the permeability of the blood-brain barrier in severe ischaemia, causing vasogenic cerebral oedema. Endogenous antioxidant systems may have some capacity to respond to oxidative stress in hypoxia. The plasma concentration of urate, a powerful endogenous antioxidant, rises on acute exposure to high altitude and may play a crucial antioxidant role in systemic hypoxia. This antioxidant prevents free-radical induced cerebral oedema in animal models.
The pathogenesis of HAPE is understood to have two components: (i) increased pulmonary arterial pressures secondary to hypoxic pulmonary vasoconstriction and; (ii) an increase in endothelial permeability, possibly due to stress rupture of pulmonary capillaries. There is much debate surrounding the cellular mechanisms of hypoxic pulmonary vasoconstriction, but it is likely that ROS have an important role.
Same as current
Current Secondary Outcome: Pulmonary artery systolic pressure [ Time Frame: Day 6 ]
Original Secondary Outcome: Same as current
Information By: Altitude Physiology Expeditions
Dates:
Date Received: April 7, 2008
Date Started: March 2003
Date Completion:
Last Updated: April 21, 2008
Last Verified: April 2008
