Age- and sex-dependent associations between self-reported physical activity levels and self-reported cardiovascular risk factors: a population-based cross-sectional survey.

BACKGROUND: The amount of regular physical activity (PA) can modulate the prevalence of traditional risk factors for cardiovascular disease (CVD) such as obesity, systemic hypertension, hypercholesterolemia, and type 2 diabetes (T2D). However, how different PA levels either below (< 600 MET min/week), within (600-1200 MET min/week), or above (> 1200 MET min/week) the range of the minimal WHO recommendations impact the age- and sex-dependent prevalence of these risk factors remains to be elucidated. METHODS: This cross-sectional study was performed to evaluate these relationships using population-based self-reported data collected in a central European country (Austria, 2019). The sample included a total of 15,461 persons (7166 males: 16-95 + years, BMI 26.6 ± 4.4; 8295 females: 16-95 + years, BMI 25.1 ± 5.0). Besides various lifestyle factors (e.g., dietary habits, smoking, and alcohol consumption), variables of particular interest were the age- and sex-dependent amount of weekly PA and prevalence of risk factors for CVD. Sex-specific logistic regression analyses were applied to estimate adjusted odds ratios (ORs) for the associations between self-reported PA and risk factor prevalence. RESULTS: Relatively small beneficial effects were found regarding the prevalence of risk factors for CVD when achieving PA levels corresponding to 600-1200 MET min/week as compared to those who did not meet these recommendations. However, exceeding the WHO recommendations provided much more pronounced benefits, especially in younger and older age groups. Adjusted ORs revealed that high volumes of PA (> 1200 MET min/week) were associated with a 32-43% reduction in the prevalence of obesity and T2D compared to those who did not achieve the WHO recommendations (< 600 MET min/week), as well as with a lower prevalence of systemic hypertension only in women and a lower prevalence of hypercholesterolemia only in men. CONCLUSIONS: Exceeding minimal WHO recommendations for PA promises large beneficial effects, particularly on the prevalence of obesity and T2D. Demonstrated sex differences in PA levels and their association with cardiovascular risk factors may provide an important basis for preventive health counseling.

Hand-grip strength in recreational downhill skiers: a comparison to normative reference values.

Hand-grip strength was evaluated in 757 recreational downhill skiers and compared to 1021 community-dwellers. Findings are reported for age and sex categories consistent with community-dwelling norms. Effect size (Cohen's d) was calculated to estimate the clinical relevance of strength differences between populations. Most male and half of the female age categories of downhill skiers demonstrated higher grip strength of the dominant hand (moderate to large effect size) compared to the reference population. Hand-grip strength in skiers declined with age at a similar rate as in the reference population. Relative grip strength (per kg body mass) was significantly and positively correlated with physical activity (hours/week), and with the number of ski days per year, and negatively with body mass. Thus, hand-grip strength may be related to the type, volume and intensity of exercise regularly performed. These results can help to assess whether the individual hand-grip strength is above or below average with regard to the normal population and the skier population as well and will support advice for training and/or rehabilitation.

Is it Possible for Individuals with Pre-Existing Mental Disorders to Perform Mountain Sports at High Altitude-First Evidence from a Pilot Cross-Sectional Questionnaire Study.

Gstir, Claudia, Timo Schurr, Roxana Ehlers, Johannes Burtscher, Barbara Sperner-Unterweger, and Katharina Hüfner. Is it possible for individuals with pre-existing mental disorders to perform mountain sports at high altitude-First evidence from a pilot cross-sectional questionnaire study. High Alt Med Biol. 00:00-00, 2024. Introduction: Mountain sports at high altitude (HA) are gaining increasing popularity, but little is known about the effect of such activities on mental health, despite a great prevalence of mental disorders. Methods: Data were collected using an online self-report questionnaire assessing mental and somatic disorders in individuals performing mountain sports at HA (>2,500 m above sea level [ASL]) as well as their symptom change. Nonparametric tests were used for analyses. Results: 251 individuals without pre-existing disorders (noD), 34 with somatic disorders (somaD), and 38 with mental disorders (mentalD; mainly depressive, eating, and anxiety disorders) participated in this study. Overall, 44.7% of the mentalD group compared with 14.7% of somaD experienced ameliorated symptoms during mountain sports at HA, while 2.6% and 8.8%, respectively, reported a worsening (χ2[2] =8.13, p = 0.017). People in the mentalD compared with somaD group significantly less frequently inform tour partners (41.9% vs. 90.9%; χ2[2]=16.69, p < 0.001) about their condition or consult their physician (2.6% vs. 26.5%; χ2[1]=8.53, p = 0.003) regarding their plans to perform mountain sports at HA. 14.5% of all participants reported mental symptoms at 2,500-3,500 m ASL, 23.5% between >3,500-5,500 m ASL and 31.8% >5,500 m ASL. Conclusion: Individuals with mental disorders often report improved mental health during mountain sports at HA, possibly due to a combination of physical activity, the alpine natural environment, and/or moderate hypoxia. The fact that tour partners and physicians are rarely informed shows the need to reduce the stigma of mental disorders in the mountain sports community. The study was prospectively registered with the German Clinical Trials Registry (DRKS00024949).

Tolerability and first hints for potential efficacy of motor-cognitive training under inspiratory hypoxia in health and neuropsychiatric disorders: A translational viewpoint.

Hypoxia is more and more perceived as pivotal physiological driving force, allowing cells in the brain and elsewhere to acclimate to lowered oxygen (O2), and abridged metabolism. The mediating transcription program is induced by inspiratory hypoxia but also by intensive motor-cognitive tasks, provoking a relative decrease in O2 in relation to the acutely augmented requirement. We termed this fundamental, demand-dependent drop in O2 availability "functional hypoxia." Major players in the hypoxia response are hypoxia-inducible factors (HIFs) and associated prolyl-hydroxylases. HIFs are transcription factors, stabilized by low O2 accessibility, and control expression of a multitude of genes. Changes in oxygen, however, can also be sensed via other pathways, among them the thiol-oxidase (2-aminoethanethiol) dioxygenase. Considering the far-reaching biological response to hypoxia, hitherto mostly observed in rodents, we initiated a translational project, combining mild to moderate inspiratory with functional hypoxia. We had identified this combination earlier to benefit motor-cognitive attainment in mice. A total of 20 subjects were included: 13 healthy individuals and 7 patients with depression and/or autism spectrum disorder. Here, we show that motor-cognitive training under inspiratory hypoxia (12% O2) for 3.5 h daily over 3 weeks is optimally tolerated. We present first signals of beneficial effects on general well-being, cognitive performance, physical fitness and psychopathology. Erythropoietin in serum increases under hypoxia and flow cytometry analysis of blood reveals several immune cell types to be mildly modulated by hypoxia. To obtain reliable information regarding the "add-on" value of inspiratory on top of functional hypoxia, induced by motor-cognitive training, a single-blind study-with versus without inspiratory hypoxia-is essential and outlined here.

Healthy Aging at Moderate Altitudes: Hypoxia and Hormesis.

BACKGROUND: Aging is associated with cellular and tissue responses that collectively lead to functional and structural deterioration of tissues. Poor tissue oxygenation, or hypoxia, is involved in such responses and contributes to aging. Consequently, it could be speculated that living at higher altitude, and therefore in hypoxic conditions, accelerates aging. This assumption is indeed supported by evidence from populations residing at very high altitudes (>3,500 m). In contrast, accumulating evidence suggests that living at moderate altitudes (1,500-2,500 m) is protective rather than injurious, at least for some body systems. SUMMARY: In this review, we critically evaluate the hypothesis that the physiological responses to mild hypoxic stress associated to life at moderate altitudes provide protection from many hypoxia-related diseases through hormesis. Hormesis means that a low dose of a stressor (here hypoxia) elicits beneficial outcomes, while a higher dose can be toxic and might explain at least in part the dose-dependent contrasting effects of hypoxia on the aging processes. The lack of well-designed longitudinal studies focusing on the role of the altitude of residence, and difficulties in accounting for potentially confounding factors such as migration, ethnicity/genetics, and socioeconomic and geoclimatic conditions, currently hampers translation of related research into uncontroversial paradigms. KEY MESSAGES: Deeper investigations are required to understand the impact of altitude-related hypoxia on age-related diseases and to develop molecular markers of ageing/senescence in humans that are linked to hypoxia. However, the presented emerging evidence supports the view that hypoxia conditioning has the potential to improve life quality and expectancy.

Flying to high-altitude destinations.

Every year millions of people fly to high-altitude destinations. They thereby expose themselves to specific high-altitude conditions. The hypoxic environment (low ambient oxygen availability) constitutes a major factor affecting health and well-being at high altitude. While the oxygen availability is already moderately reduced inside the aircraft cabin, this reduction becomes aggravated when leaving the plane at high-altitude destinations. Especially if not pre-acclimatized, the risk of suffering from high-altitude illnesses, e.g., acute mountain sickness, high-altitude cerebral or pulmonary edema, increases with the level of altitude. In addition, diminished oxygen availability impairs exercise tolerance, which not only limits physical activity at high altitude but may also provoke symptomatic exacerbation of pre-existing diseases. Moreover, the cold and dry ambient air and increased levels of solar radiation may contribute to adverse health effects at higher altitude. Thus, medical pre-examination and pre-flight advice, and proper preparation (pre-acclimatization, exercise training, and potentially adaptation of pharmacological regimes) are of utmost importance to reduce negative health impacts and frustrating travel experiences.

Controlled Hypoxia Acutely Prevents Physical Inactivity-Induced Peripheral BDNF Decline.

Brain-derived neurotrophic factor (BDNF) is a crucial mediator of neuronal plasticity. Here, we investigated the effects of controlled normobaric hypoxia (NH) combined with physical inactivity on BDNF blood levels and executive functions. A total of 25 healthy adults (25.8 ± 3.3 years, 15 female) were analyzed in a randomized controlled cross-over study. Each intervention began with a 30 min resting phase under normoxia (NOR), followed by a 90 min continuation of NOR or NH (peripheral oxygen saturation [SpO2] 85-80%). Serum and plasma samples were collected every 15 min. Heart rate and SpO2 were continuously measured. Before and after each exposure, cognitive tests were performed and after 24 h another follow-up blood sample was taken. NH decreased SpO2 (p < 0.001, ηp2 = 0.747) and increased heart rate (p = 0.006, ηp2 = 0.116) significantly. The 30-min resting phase under NOR led to a significant BDNF reduction in serum (p < 0.001, ηp2 = 0.581) and plasma (p < 0.001, ηp2 = 0.362). Continuation of NOR further significantly reduced BDNF after another 45 min (p = 0.018) in serum and after 30 min (p = 0.040) and 90 min (p = 0.005) in plasma. There was no significant BDNF decline under NH. A 24 h follow-up examination showed a significant decline in serum BDNF, both after NH and NOR. Our results show that NH has the potential to counteract physical inactivity-induced BDNF decline. Therefore, our study emphasizes the need for a physically active lifestyle and its positive effects on BDNF. This study also demonstrates the need for a standardized protocol for future studies to determine BDNF in serum and plasma.

Hyperoxic recovery interferes with the metabolic imprint of hypoxic exercise.

Supplemental oxygen (hyperoxia) improves physical performance during hypoxic exercise. Based on the analysis of metabolome and iron homeostasis from human athlete blood samples, we show that hyperoxia during recovery periods interferes with metabolic alterations following hypoxic exercise. This may impair beneficial adaptations to exercise and/or hypoxia and highlights risks of oxygen supplementation in hypoxia.

Brain-Periphery Interactions in Huntington's Disease: Mediators and Lifestyle Interventions.

Prominent pathological features of Huntington's disease (HD) are aggregations of mutated Huntingtin protein (mHtt) in the brain and neurodegeneration, which causes characteristic motor (such as chorea and dystonia) and non-motor symptoms. However, the numerous systemic and peripheral deficits in HD have gained increasing attention recently, since those factors likely modulate disease progression, including brain pathology. While whole-body metabolic abnormalities and organ-specific pathologies in HD have been relatively well described, the potential mediators of compromised inter-organ communication in HD have been insufficiently characterized. Therefore, we applied an exploratory literature search to identify such mediators. Unsurprisingly, dysregulation of inflammatory factors, circulating mHtt, and many other messenger molecules (hormones, lipids, RNAs) were found that suggest impaired inter-organ communication, including of the gut-brain and muscle-brain axis. Based on these findings, we aimed to assess the risks and potentials of lifestyle interventions that are thought to improve communication across these axes: dietary strategies and exercise. We conclude that appropriate lifestyle interventions have great potential to reduce symptoms and potentially modify disease progression (possibly via improving inter-organ signaling) in HD. However, impaired systemic metabolism and peripheral symptoms warrant particular care in the design of dietary and exercise programs for people with HD.

Intermittent Hypoxic Training Increases and Prolongs Exercise Benefits in Adult Untrained Women.

Alba Camacho-Cardenosa, Marta Camacho-Cardenosa, Johannes Burtscher, Pedro R. Olivares, Guillermo Olcina, and Javier Brazo-Sayavera. Intermittent hypoxic training increases and prolongs exercise benefits in adult untrained women. High Alt Med Biol. 00:00-00, 2024. Background: Exercising in hypoxia may confer multiple health benefits, but the evidence for specific benefits is scarce. Methods: We investigated effects of intermittent hypoxic training (IHT) on the quality of life and functional fitness of healthy adult women, in a double-blind, randomized, placebo-controlled study. Subjects performed 36 sessions of IHT (experimental group, n = 41; fraction of inspired oxygen [FIO2]: 0.17) or the same training in normoxia (control group, n = 41; FIO2: 0.21). Health-related quality of life, fitness tests, and hemoglobin levels were assessed before (T1), directly after (T2), and 4 weeks after (T3) cessation. Results: At T2, upper body strength (+14.96%), lower body strength (+26.20%), and agility (-4.94%) increased significantly in the experimental group compared to baseline but not in controls. The experimental group improved lower body strength more (by 9.85%) than controls at T2 and performed significantly better in walking (by 2.92%) and upper body strength testing (by 16.03%), and agility (by 4.54%) at T3. Perceived general health and vitality was significantly greater in the experimental group at T2 and T3 compared with T1. None of these improvements were observed in the control group. Conclusions: IHT is a promising strategy to induce long-lasting fitness benefits in healthy adult women.

Hypoxia Sensing and Responses in Parkinson's Disease.

Parkinson's disease (PD) is associated with various deficits in sensing and responding to reductions in oxygen availability (hypoxia). Here we summarize the evidence pointing to a central role of hypoxia in PD, discuss the relation of hypoxia and oxygen dependence with pathological hallmarks of PD, including mitochondrial dysfunction, dopaminergic vulnerability, and alpha-synuclein-related pathology, and highlight the link with cellular and systemic oxygen sensing. We describe cases suggesting that hypoxia may trigger Parkinsonian symptoms but also emphasize that the endogenous systems that protect from hypoxia can be harnessed to protect from PD. Finally, we provide examples of preclinical and clinical research substantiating this potential.

Women at Altitude: Sex-Related Physiological Responses to Exercise in Hypoxia.

Sex differences in physiological responses to various stressors, including exercise, have been well documented. However, the specific impact of these differences on exposure to hypoxia, both at rest and during exercise, has remained underexplored. Many studies on the physiological responses to hypoxia have either excluded women or included only a limited number without analyzing sex-related differences. To address this gap, this comprehensive review conducted an extensive literature search to examine changes in physiological functions related to oxygen transport and consumption in hypoxic conditions. The review encompasses various aspects, including ventilatory responses, cardiovascular adjustments, hematological alterations, muscle metabolism shifts, and autonomic function modifications. Furthermore, it delves into the influence of sex hormones, which evolve throughout life, encompassing considerations related to the menstrual cycle and menopause. Among these physiological functions, the ventilatory response to exercise emerges as one of the most sex-sensitive factors that may modify reactions to hypoxia. While no significant sex-based differences were observed in cardiac hemodynamic changes during hypoxia, there is evidence of greater vascular reactivity in women, particularly at rest or when combined with exercise. Consequently, a diffusive mechanism appears to be implicated in sex-related variations in responses to hypoxia. Despite well-established sex disparities in hematological parameters, both acute and chronic hematological responses to hypoxia do not seem to differ significantly between sexes. However, it is important to note that these responses are sensitive to fluctuations in sex hormones, and further investigation is needed to elucidate the impact of the menstrual cycle and menopause on physiological responses to hypoxia.

Exercise and gait/movement analyses in treatment and diagnosis of Parkinson's Disease.

Cardinal motor symptoms in Parkinson's disease (PD) include bradykinesia, rest tremor and/or rigidity. This symptomatology can additionally encompass abnormal gait, balance and postural patterns at advanced stages of the disease. Besides pharmacological and surgical therapies, physical exercise represents an important strategy for the management of these advanced impairments. Traditionally, diagnosis and classification of such abnormalities have relied on partially subjective evaluations performed by neurologists during short and temporally scattered hospital appointments. Emerging sports medical methods, including wearable sensor-based movement assessment and computational-statistical analysis, are paving the way for more objective and systematic diagnoses in everyday life conditions. These approaches hold promise to facilitate customizing clinical trials to specific PD groups, as well as personalizing neuromodulation therapies and exercise prescriptions for each individual, remotely and regularly, according to disease progression or specific motor symptoms. We aim to summarize exercise benefits for PD with a specific emphasis on gait and balance deficits, and to provide an overview of recent advances in movement analysis approaches, notably from the sports science community, with value for diagnosis and prognosis. Although such techniques are becoming increasingly available, their standardization and optimization for clinical purposes is critically missing, especially in their translation to complex neurodegenerative disorders such as PD. We highlight the importance of integrating state-of-the-art gait and movement analysis approaches, in combination with other motor, electrophysiological or neural biomarkers, to improve the understanding of the diversity of PD phenotypes, their response to therapies and the dynamics of their disease progression.

Recommendations for Women in Mountain Sports and Hypoxia Training/Conditioning.

The (patho-)physiological responses to hypoxia are highly heterogeneous between individuals. In this review, we focused on the roles of sex differences, which emerge as important factors in the regulation of the body's reaction to hypoxia. Several aspects should be considered for future research on hypoxia-related sex differences, particularly altitude training and clinical applications of hypoxia, as these will affect the selection of the optimal dose regarding safety and efficiency. There are several implications, but there are no practical recommendations if/how women should behave differently from men to optimise the benefits or minimise the risks of these hypoxia-related practices. Here, we evaluate the scarce scientific evidence of distinct (patho)physiological responses and adaptations to high altitude/hypoxia, biomechanical/anatomical differences in uphill/downhill locomotion, which is highly relevant for exercising in mountainous environments, and potentially differential effects of altitude training in women. Based on these factors, we derive sex-specific recommendations for mountain sports and intermittent hypoxia conditioning: (1) Although higher vulnerabilities of women to acute mountain sickness have not been unambiguously shown, sex-dependent physiological reactions to hypoxia may contribute to an increased acute mountain sickness vulnerability in some women. Adequate acclimatisation, slow ascent speed and/or preventive medication (e.g. acetazolamide) are solutions. (2) Targeted training of the respiratory musculature could be a valuable preparation for altitude training in women. (3) Sex hormones influence hypoxia responses and hormonal-cycle and/or menstrual-cycle phases therefore may be factors in acclimatisation to altitude and efficiency of altitude training. As many of the recommendations or observations of the present work remain partly speculative, we join previous calls for further quality research on female athletes in sports to be extended to the field of altitude and hypoxia.