OBJECTIVE: This study aimed to systematically review the effect of nitrate supplementation on blood oxygen saturation.
METHODS: We searched PubMed, Scopus, and Cochrane Library databases from their inception up to October 2022. Two reviewers independently conducted two stages of the screening process to include a randomized controlled trial with nitrate supplementation versus placebo intervention assessing oxygen saturation among lowlanders going to either real or simulated high altitude environments. We used the Cochrane Risk of Bias 2.0 tool to assess the risk of bias in the included studies. Fixed-effect model meta-analyses were conducted for laboratory-based studies. Random-effect meta-analyses were conducted for real-world studies.
RESULTS: We found 7 trials that met the eligibility criteria. A meta-analysis of studies with some bias concerns showed an increase of 1.26 % in the SpO2 with 44 % I2 during submaximal exercise at simulated high altitudes (GRADE: low). On the contrary, a meta-analysis of studies without heterogeneity showed that nitrate supplementation aggravated oxygen saturation decline (-2.64 %, p = 0.03, GRADE: high) during rest in real high-altitude environments. A meta-analysis also showed that nitrate supplementation did not affect Acute Mountain Sickness (AMS) symptoms (GRADE: high).
CONCLUSIONS: Our results suggest that nitrate supplementation did not provide benefits for AMS prevention during rest at high altitudes. The low-quality evidence showing small beneficial effects of nitrate supplementation during exercise calls for further studies.

Nitric oxide was first identified as a novel and effective treatment for persistent pulmonary hypertension of the newborn (PPHN), and has since been found to be efficacious in treating acute respiratory distress syndrome (ARDS) and pulmonary hypertension. Physicians and researchers have also found it shows promise in resource-constrained settings, both within and outside of the hospital, such as in high altitude pulmonary edema (HAPE) and COVID-19. The treatment has been well tolerated in these settings, and is both efficacious and versatile when studied across a variety of clinical environments. Advancements in inhaled nitric oxide continue, and the gas is worthy of investigation as physicians contend with new respiratory and cardiovascular illnesses, as well as unforeseen logistical challenges.

Mateikaitė-Pipirienė, Kastė, Dominique Jean, Peter Paal, Lenka Horakova, Susi Kriemler, Alison J. Rosier, Marija Andjelkovic, Beth A. Beidleman, Mia Derstine, Jacqueline Pichler Hefti, David Hillebrandt, and Linda E. Keyes for the UIAA MedCom writing group on Women\'s Health in the Mountains. Menopause and high altitude: A scoping review-UIAA Medical Commission Recommendations. High Alt Med Biol. 25:1-8, 2024. Background: Older people are an important fraction of mountain travelers and climbers, many of them postmenopausal women. The aim of this work was to review health issues that older and postmenopausal women may experience at high altitude, including susceptibility to high-altitude illness. Methods: We performed a scoping review for the UIAA Medical Commission series on Women\'s Health in the mountains. We searched PubMed and Cochrane libraries and performed an additional manual search. The primary search focused on articles assessing lowland women sojourning at high altitude. Results: We screened 7,165 potential articles. The search revealed three relevant articles, and the manual search another seven articles and one abstract. Seven assessed menopausal low-altitude residents during a high-altitude sojourn or performing hypoxic tests. Four assessed high-altitude residents. We summarize the results of these 11 studies. Conclusions: Data are limited on the effects of high altitude on postmenopausal women. The effects of short-term, high-altitude exposure on menopause symptoms are unknown. Menopause has minimal effect on the physiological responses to hypoxia in physically fit women and does not increase the risk of acute mountain sickness. Postmenopausal women have an increased risk of urinary tract infections, which may be exacerbated during mountain travel. More research is needed on the physiology and performance of older women at high altitude.

Pichler Hefti, Jacqueline, Dominique Jean, Alison Rosier, Mia Derstine, David Hillebrandt, Lenka Horakova, Linda E. Keyes, Kastė Mateikaitė-Pipirienė, Peter Paal, Marija Andjelkovic, Beth Beidlemann, and Susi Kriemler. High-altitude pulmonary edema in women: a scoping review-UIAA Medical Commission Recommendations. High Alt Med Biol. 24:268-273, 2023. Background: High-altitude pulmonary edema (HAPE) can occur >2,500-3,000 m asl and is a life-threatening medical condition. This scoping review aims to summarize the current data on sex differences in HAPE. Methods: The International Climbing and Mountaineering Federation (UIAA) Medical Commission convened an international author team to review women\'s health issues at high altitude. Pertinent literature from PubMed and Cochrane was identified by keyword search combinations (including HAPE), with additional publications found by hand search. The primary search focus was for original articles that included minimum one woman and at least a rudimentary subgroup analysis. Results: The literature search yielded 7,165 articles, 416 of which were relevant for HAPE, and 7 of which were ultimately included here. Six were case series, consistently reporting a lower HAPE prevalence in women. The one retrospective case-control study reported male HAPE prevalence at 10/100,000 and female at 0.74/100,000. No studies were identified that directly compared sex differences in the prevalence of HAPE. No published data was found for topics other than epidemiology. Conclusions: Few studies and associated methodological limitations allow few conclusions to be drawn. Incidence of HAPE may be lower in women than in men. We speculate that besides physiological aspects, behavioral differences may contribute to this potential sex difference.

Individuals at higher altitudes may experience a decrease in blood oxygen levels, which can result in a variety of clinical illnesses, such as high-altitude pulmonary edema, high-altitude cerebral edema, and milder but more common acute mountain sickness (AMS).
This study aims to review the current state of knowledge related to motion sickness, the risk of AMS, and pharmacological and non-pharmacological treatments for AMS.
Several databases, including PubMed, Bentham Science, Elsevier, Springer, and Research Gate, were used to compile the data for the article following a thorough analysis of the various research findings connected to acute mountain sickness and motion sickness, along with treatments and prevention.
This article covers the research on mountain sickness as well as every imaginable form of conventional and alternative medicine. It contains ten medicinal plants that are useful in treating mountain sickness and various other remedies. Additionally, case studies are provided.
Therefore, the information in the paper will help travel medicine specialists better personalize their appropriate care for patients who travel to high-altitude locations. Additionally, all available antiemetic medications, serotonin agonists, nonsteroidal anti-inflammatory drugs, and herbal treatments for motion sickness were discussed. The prevention and consequences of acute mountain sickness are also covered in this study.

Derstine, Mia, Dominique Jean, Beth A. Beidleman, Jacqueline Pichler Hefti, David Hillebrandt, Lenka Horakova, Susi Kriemler, Kasté Mateikaité-Pipiriené, Peter Paal, Alison Rosier, Marija Andjelkovic, and Linda E. Keyes. Acute mountain sickness and high altitude cerebral edema in women: A scoping review-UIAA Medical Commission recommendations. High Alt Med Biol. 24:259-267, 2023. Background: Acute mountain sickness (AMS) and high-altitude cerebral edema (HACE) are illnesses associated with rapid ascent to altitudes over 2,500 m in unacclimatized lowlanders. The aim of this scoping review is to summarize the current knowledge on sex differences in the epidemiology, pathophysiology, symptomatology, and treatment of AMS and HACE, especially in women. Methods and Results: The UIAA Medical Commission convened an international author team to review women\'s health issues at high altitude and to publish updated recommendations. Pertinent literature from PubMed and Cochrane was identified by keyword search combinations (including AMS, HACE, and high altitude), with additional publications found by hand search. The primary search focus was for articles assessing lowland women sojourning at high altitude. Results: The literature search yielded 7,165 articles, 37 of which were ultimately included. The majority of publications included did not find women at increased risk for AMS or HACE. There was extremely limited sex-specific data on risk factors or treatment. Conclusions: There is a limited amount of data on female-specific findings regarding AMS and HACE, with most publications addressing only prevalence or incidence with regard to sex. As such, general prevention and treatment strategies for AMS and HACE should be used regardless of sex.

Poudel, Sangeeta, Sandesh Gautam, Purushottam Adhikari, and Ken Zafren. Physiological effects of sildenafil versus placebo at high altitude: a systematic review. High Alt Med Biol. 25:16-25, 2024. Introduction: High altitude pulmonary edema (HAPE), a life-threatening condition that affects individuals ascending to high altitude, requires the development of pulmonary hypertension. Sildenafil can be used to prevent and treat HAPE, presumably by decreasing pulmonary artery pressure (PaP). We compared the physiological effects of sildenafil versus placebo at high altitude (above 2,500 m), including the effects on PaP. Methods: We performed a systematic search of PubMed, EMBASE, and Cochrane CENTRAL for randomized controlled studies of the physiological effects of sildenafil in hypoxia in healthy individuals. We conducted a systematic review of all studies meeting our criteria. Results: Of the 14 studies that met the inclusion criteria, 8 were hypobaric hypoxia studies. Six studies reported data at rest at altitudes from 3,650 to 5,245 m. Two were simulations reporting exercise data at equivalent altitudes of 2,750-5,000 m. Nine studies used normobaric hypoxia corresponding to altitudes between 2,500 and 6,400 m. One reported only rest data, two reported rest and exercise data, and the others reported only exercise data. Sildenafil significantly reduced PaP at rest and exercise in hypobaric or normobaric hypoxia. There were no significant differences between arterial oxygen saturation (SpO2) with sildenafil in hypobaric or normobaric hypoxia at rest or exercise. There were no significant differences in heart rate or mean arterial pressure (MAP) at rest or exercise and cardiac output during exercise in hypobaric or normobaric hypoxia. Conclusions: Sildenafil significantly reduces PaP at rest and exercise in normobaric or hypobaric hypoxia. Sildenafil has no significant effects on SpO2, heart rate, cardiac output (during exercise), or MAP at rest or exercise in hypobaric or normobaric hypoxia.

High-altitude (HA) affects sensory organ response, but its effects on the inner ear are not fully understood. The present scoping review aimed to collect the available evidence about HA effects on the inner ear with focus on auditory function.
The scoping review was conducted following the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis extension for scoping reviews. PubMed, Scopus, and Web of Science electronic databases were systematically searched to identify studies conducted in the last 20 years, which quantified in healthy subjects the effects of HA on auditory function.
The systematic search identified 17 studies on a total population of 888 subjects (88.7% male, age: 27.8 ± 4.1 years; median sample size of 15 subjects). Nine studies were conducted in a simulated environment and eight during real expeditions at HA. To quantify auditory function, six studies performed pure tone audiometry, four studies measured otoacoustic emissions (OAE) and eight studies measured auditory evoked responses (AER). Study protocols presented heterogeneity in the spatio-temporal patterns of HA exposure, with highly varying maximal altitudes and exposure durations.
Most studies reported a reduction of auditory function with HA in terms of either elevation of auditory thresholds, lengthening of AER latencies, reduction of distortion-product and transient-evoked OAEs. Future studies in larger populations, using standardized protocols and multi-technique auditory function evaluation, are needed to further characterize the spatio-temporal pattern of HA effects along the auditory pathways and clarify the pathophysiological implications and reversibility of the observed changes.

Kharel, Sanjeev, Suraj Shrestha, Samriddha Raj Pant, Suman Acharya, Amit Sharma, Santosh Baniya, and Sanjeeb S. Bhandari. High-altitude exposure and cerebral venous thrombosis: an updated systematic review. High Alt Med Biol. 24:167-174, 2023. Background: High altitude (HA) may increase the risk of cerebral venous thrombosis (CVT). Differentiating it from other HA illnesses is crucial for prompt treatment and better outcomes. We aimed to summarize the clinical data, etiology, and risk factors of this poorly understood entity at an HA. Materials and Methods: A systematic literature search of various databases, including PubMed, Embase, and Google Scholar, was done using relevant keywords; cerebral venous thrombosis; HA, up to May 1, 2022. Results: A total of nine studies, including 75 cases of CVT at HA (3,000-8,848 m), with 66 males and 9 females, were included in this review. Headache and seizure were the most common clinical presentations. Smoking, drinking habits, and the use of oral contraceptive pills (OCP) were the most common risk factors for the development of CVT. Similarly, various underlying hypercoagulable states were also present among cases of CVT associated with HA exposure. Conclusion: Our review concludes that HA exposure can predispose individuals with risk factors such as preexisting hypercoagulable states, smoking, drinking habits, and use of OCP to an increased risk of CVT.

This report aims to summarise the scientific knowledge around hydration, nutrition, and metabolism at high altitudes and to transfer it into the practical context of extreme altitude alpinism, which, as far as we know, has never been considered before in the literature. Maintaining energy balance during alpine expeditions is difficult for several reasons and requires a deep understanding of human physiology and the biological basis for altitude acclimation. However, in these harsh conditions it is difficult to reconcile our current scientific knowledge in sports nutrition or even for mountaineering to high-altitude alpinism: extreme hypoxia, cold, and the logistical difficulties intrinsic to these kinds of expeditions are not considered in the current literature. Requirements for the different stages of an expedition vary dramatically with increasing altitude, so recommendations must differentiate whether the alpinist is at base camp, at high-altitude camps, or attempting the summit. This paper highlights nutritional recommendations regarding prioritising carbohydrates as a source of energy and trying to maintain a protein balance with a practical contextualisation in the extreme altitude environment in the different stages of an alpine expedition. More research is needed regarding specific macro and micronutrient requirements as well as the adequacy of nutritional supplementations at high altitudes.