High Altitude Sickness and Antioxidant Interventions

Abstract

High altitude sickness (HAS) has been one of the important environmental challenges occurring as a result of the failure of the physiological acclimatization to acute hypobaric hypoxia. The prime bodily retort to hypoxia and adaptation linked to HAS comprises hyperventilation, increased systemic blood pressure together with tachycardia (increased heart rate) and increased hemoglobin concentration. These collective retorts enhance the supply of oxygen to the cells by means of alterations in the respiratory, cardiovascular, and hematologic system, thereby boosting the cellular oxygen uptake together with consumption mechanisms. Additionally, in majority of the cases, these bodily responses may not be sufficient, as a result the mount to high elevations and the associated hypoxia culminate in complex medical condition. Diverse strategies for preventing HAS can be employed categorized mainly into pharmacological and non-pharmacological and miscellaneous. Pharmacological interventions comprise drugs like acetazolamide or dexamethasone which have been found to work effectively but also linked with adverse physical secondary effects. Non-pharmacological and miscellaneous interventions are those which are not founded on the administration of drugs and can be categorized into two sets: pre-acclimatization and supplements. Pre-acclimatization and additional methods founded on pressure comprise the employment of hypobaric air breathing to sham higher elevations, positive end-expiratory pressure, and remote ischemic preconditioning. In addition, non-drug approaches, herbs, and natural supplements have been also tested and found to be promising in combating this challenge. Supplements may contain herbal extracts (like Ginkgo biloba, Rhodiola species, and Coca leaf products), mineral elements (like iron, magnesium), antacids, and hormonal agents (like medroxyprogesterone and erythropoietin). Hypoxia is well known for causing prooxidant/antioxidant disturbances in the cell, thereby resulting in oxidative stress. The key mechanisms through which hypoxia-induced reactive oxygen species (ROS) overgeneration takes place are increased catecholamine manufacture, mitochondrial redox potential diminution together with the stimulation of xanthine oxidase pathway. The scientific observations of a raised risk of ROS and free radical mediated oxidative insult at higher elevation have shown the way to the researchers to suggest nutritional antioxidant interventions such as ascorbic acid, beta-carotene, vitamin E, selenium, alpha-lipoic acid, etc. present in fruits and vegetables and herbal supplements rich in antioxidants like Ginkgo biloba, which may be advantageous in combating the problem of HAS. Several antioxidants and their concoction have been tested and have shown mixed results in relation to the effectiveness of antioxidants in averting HAS. Despite the bulk of scientific investigations exploring the beneficial effects as well as the effectiveness of various antioxidants against HAS in different experimental models, the present state of evidence is unable to substantiate or repudiate the use of any antioxidant or a concoction of antioxidant as a definite prophylactic agent. Additionally, an inadequate number of investigations support the effectiveness of antioxidant supplements at higher elevations in easing the difficulty of HAS. Furthermore, there is a dearth of standardized studies in this regard. The variations in the current investigations with regard to experimental design considerations like altitude reached, rate of ascension, degree of pre-acclimatization; antioxidant employed, purity and quality of the antioxidant, the timing, duration, pretreatment, and dosage administered; individual susceptibility, small sample size, etc. cloud the understanding with respect to their efficacy in bringing out the desirable effects. Another challenge in this regard is to identify the appropriate dosage, timing, or combination of antioxidants which will regulate the induced oxidative stress without any deleterious effects on the body and therefore help the body to ease out the symptoms of HAS. Therefore, given the undesirable side effects associated with pharmacological interventions, non-pharmacological antioxidant interventions which are relatively safer and with minimal side effects need more attention in order to combat this challenge of HAS.