Physical enhancement of older adults using hyperbaric oxygen: a randomized controlled trial.

INTRODUCTION: Aging is associated with a progressive decline in the capacity for physical activity. The objective of the current study was to evaluate the effect of an intermittent hyperbaric oxygen therapy (HBOT) protocol on maximal physical performance and cardiac perfusion in sedentary older adults. METHODS: A randomized controlled clinical trial randomized 63 adults (> 64yrs) either to HBOT (n = 30) or control arms (n = 33) for three months. Primary endpoint included the maximal oxygen consumption (VO2Max) and VO2Max/Kg, on an E100 cycle ergometer. Secondary endpoints included cardiac perfusion, evaluated by magnetic resonance imaging and pulmonary function. The HBOT protocol comprised of 60 sessions administered on a daily basis, for 12 consecutive weeks, breathing 100% oxygen at 2 absolute atmospheres (ATA) for 90 min with 5-minute air breaks every 20 min. RESULTS: Following HBOT, improvements were observed in VO2Max/kg, with a significant increase of 1.91 ± 3.29 ml/kg/min indicated by a net effect size of 0.455 (p = 0.0034). Additionally, oxygen consumption measured at the first ventilatory threshold (VO2VT1) showed a significant increase by 160.03 ± 155.35 ml/min (p < 0.001) with a net effect size of 0.617. Furthermore, both cardiac blood flow (MBF) and cardiac blood volume (MBV) exhibited significant increases when compared to the control group. The net effect size for MBF was large at 0.797 (p = 0.008), while the net effect size for MBV was even larger at 0.896 (p = 0.009). CONCLUSION: The findings of the study indicate that HBOT has the potential to improve physical performance in aging adults. The enhancements observed encompass improvements in key factors including VO2Max, and VO2VT1. An important mechanism contributing to these improvements is the heightened cardiac perfusion induced by HBOT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02790541 (registration date 06/06/2016).

Hyperbaric oxygen therapy in children with post-concussion syndrome improves cognitive and behavioral function: a randomized controlled trial.

Persistent post-concussion syndrome (PPCS) is a common and significant morbidity among children following traumatic brain injury (TBI) and the evidence for effective PPCS treatments remains limited. Recent studies have shown the beneficial effects of hyperbaric oxygen therapy (HBOT) in PPCS adult patients. This randomized, sham-control, double blind trial evaluated the effect of hyperbaric oxygen therapy (HBOT) on children (age 8-15) suffering from PPCS from mild-moderate TBI events six months to 10 years prior. Twenty-five children were randomized to receive 60 daily sessions of HBOT (n = 15) or sham (n = 10) treatments. Following HBOT, there was a significant increase in cognitive function including the general cognitive score (d = 0.598, p = 0.01), memory (d = 0.480, p = 0.02), executive function (d = 0.739, p = 0.003), PPCS symptoms including emotional score (p = 0.04, d = - 0.676), behavioral symptoms including hyperactivity (d = 0.244, p = 0.03), global executive composite score (d = 0.528, p = 0.001), planning/organizing score (d = 1.09, p = 0.007). Clinical outcomes correlated with significant improvements in brain MRI microstructural changes in the insula, supramarginal, lingual, inferior frontal and fusiform gyri. The study suggests that HBOT improves both cognitive and behavioral function, PPCS symptoms, and quality of life in pediatric PPCS patients at the chronic stage, even years after injury. Additional data is needed to optimize the protocol and to characterize the children who can benefit the most.

Effects of Hyperbaric Oxygen Therapy on Mitochondrial Respiration and Physical Performance in Middle-Aged Athletes: A Blinded, Randomized Controlled Trial.

INTRODUCTION: Hyperbaric oxygen therapy (HBOT) has been used to increase endurance performance but has yet to be evaluated in placebo-controlled clinical trials. The current study aimed to evaluate the effect of an intermittent HBOT protocol on maximal physical performance and mitochondrial function in middle-aged master athletes. METHODS: A double-blind, randomized, placebo-controlled study on 37 healthy middle-aged (40-50) master athletes was performed between 2018 and 2020. The subjects were exposed to 40 repeated sessions of either HBOT [two absolute atmospheres (ATA), breathing 100% oxygen for 1 h] or SHAM (1.02ATA, breathing air for 1 h). RESULTS: Out of 37 athletes, 16 HBOT and 15 SHAM allocated athletes were included in the final analysis. Following HBOT, there was a significant increase in the maximal oxygen consumption (VO2Max) (p = 0.010, effect size(es) = 0.989) and in the oxygen consumption measured at the anaerobic threshold (VO2AT)(es = 0.837) compared to the SHAM group. Following HBOT, there were significant increases in both maximal oxygen phosphorylation capacity (es = 1.085, p = 0.04), maximal uncoupled capacity (es = 0.956, p = 0.02) and mitochondrial mass marker MTG (p = 0.0002) compared to the SHAM sessions. CONCLUSION: HBOT enhances physical performance in healthy middle-age master athletes, including VO2max, power and VO2AT. The mechanisms may be related to significant improvements in mitochondrial respiration and increased mitochondrial mass. Trial Registration ClinicalTrials.gov Identifier: https://clinicaltrials.gov/ct2/show/NCT03524989 (May 15, 2018).

The effect of hyperbaric oxygen therapy on the pathophysiology of skin aging: a prospective clinical trial.

INTRODUCTION: Skin biopsies can be used to evaluate physiological effects of aging targeted intervention at the tissue/cellular levels. Recent clinical trials have shown that hyperbaric oxygen therapy (HBOT) can target aging hallmarks, including telomere shortening, senescent cells clearance and angiogenesis. The aim of this study was to evaluate the effects of HBOT on the skin of a normal, non-pathological, aging population. METHODS: The study was performed as a prospective clinical trial. After signing informed consent and undergoing baseline evaluations, the subjects were assigned to a three-month control period followed by three months of HBOT daily sessions. Skin biopsies were taken at baseline, after three months of no intervention (control) and 1-2 weeks following the last HBOT session. Trichrome, Orecin, lipofuscin and CD31 staining were used to evaluate collagen fibers, elastic fibers, senescent cells and blood vessels, respectively. RESULTS: Out of the cohort of 70 participants in the normal aging population study, thirteen male patients (age 68.07±2.5y) gave consent for repeated skin biopsies. Following HBOT, there was a significant increase in collagen density (p<0.001, effect size(es)=1.10), elastic fiber length (p<0.0001, es=2.71) and the number of blood vessels (p=0.02, es=1.00). There was a significant decrease in fiber fragmentation (p=0.012) and in tissue senescent cells (p=0.03, es=0.84) post-HBOT. No changes were noted in elastic fiber density or thickness. CONCLUSIONS: The study indicates, for the first time in humans, that HBOT can significantly modulate the pathophysiology of the skin aging in a healthy aging population. The demonstrated mechanisms include angiogenesis and senescent cell clearance.

Hyperbaric oxygen therapy induces transcriptome changes in elderly: a prospective trial.

INTRODUCTION: Aging is characterized by the progressive loss of physiological capacity. Changes in gene expression can alter activity in defined age-related molecular pathways leading to cellular aging and increased aging disease susceptibility. The aim of the current study was to evaluate whether hyperbaric oxygen therapy (HBOT) affects gene expression in normal, non-pathological, aging adults. METHODS: Thirty-five healthy independently living adults, aged 64 and older, were enrolled to receive 60 daily HBOT exposures. Whole blood samples were collected at baseline, at the 30th and 60th HBOT session, and 1-2 weeks following the last session. Differential gene expression analysis was performed. RESULTS: Following 60 sessions of HBOT, 1342 genes and 570 genes were differently up- and downregulated (1912 total), respectively (p < 0.01 FDR), compared to baseline. Out of which, five genes were downregulated with a >1.5-fold change: ABCA13 (FC = -2.28), DNAJ6 (FC = -2.16), HBG2 (FC = -1.56), PDXDC1 (FC = -1.53), RANBP17 (FC = -1.75). Two weeks post-HBOT, ABCA13 expression was significantly downregulated with a >1.5fold change (FC = -1.54, p = 0.008). In conclusion, for the first time in humans, the study provides direct evidence of HBOT is associated with transcriptome changes in whole-blood samples. Our results demonstrate significant changes in gene expression of normal aging population.

Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells: a prospective trial.

INTRODUCTION: Aging is characterized by the progressive loss of physiological capacity. At the cellular level, two key hallmarks of the aging process include telomere length (TL) shortening and cellular senescence. Repeated intermittent hyperoxic exposures, using certain hyperbaric oxygen therapy (HBOT) protocols, can induce regenerative effects which normally occur during hypoxia. The aim of the current study was to evaluate whether HBOT affects TL and senescent cell concentrations in a normal, non-pathological, aging adult population. METHODS: Thirty-five healthy independently living adults, aged 64 and older, were enrolled to receive 60 daily HBOT exposures. Whole blood samples were collected at baseline, at the 30th and 60th session, and 1-2 weeks following the last HBOT session. Peripheral blood mononuclear cells (PBMCs) telomeres length and senescence were assessed. RESULTS: Telomeres length of T helper, T cytotoxic, natural killer and B cells increased significantly by over 20% following HBOT. The most significant change was noticed in B cells which increased at the 30th session, 60th session and post HBOT by 25.68%±40.42 (p=0.007), 29.39%±23.39 (p=0.0001) and 37.63%±52.73 (p=0.007), respectively. There was a significant decrease in the number of senescent T helpers by -37.30%±33.04 post-HBOT (P<0.0001). T-cytotoxic senescent cell percentages decreased significantly by -10.96%±12.59 (p=0.0004) post-HBOT. In conclusion, the study indicates that HBOT may induce significant senolytic effects including significantly increasing telomere length and clearance of senescent cells in the aging populations.

Cognitive enhancement of healthy older adults using hyperbaric oxygen: a randomized controlled trial.

More than half of community-dwelling individuals sixty years and older express concern about declining cognitive abilities. The current study's aim was to evaluate hyperbaric oxygen therapy (HBOT) effect on cognitive functions in healthy aging adults.A randomized controlled clinical trial randomized 63 healthy adults (>64) either to HBOT(n=33) or control arms(n=30) for three months. Primary endpoint included the general cognitive function measured post intervention/control. Cerebral blood flow (CBF) was evaluated by perfusion magnetic resonance imaging.There was a significant group-by-time interaction in global cognitive function post-HBOT compared to control (p=0.0017). The most striking improvements were in attention (net effect size=0.745) and information processing speed (net effect size=0.788).Voxel-based analysis showed significant cerebral blood flow increases in the HBOT group compared to the control group in the right superior medial frontal gyrus (BA10), right and left supplementary motor area (BA6), right middle frontal gyrus (BA6), left middle frontal gyrus (BA9), left superior frontal gyrus (BA8) and the right superior parietal gyrus (BA7).In this study, HBOT was shown to induce cognitive enhancements in healthy aging adults via mechanisms involving regional changes in CBF. The main improvements include attention, information processing speed and executive functions, which normally decline with aging.

Hyperbaric oxygen therapy improves neurocognitive functions of post-stroke patients - a retrospective analysis.

BACKGROUND: Previous studies have shown that hyperbaric oxygen therapy (HBOT) can improve the motor functions and memory of post-stroke patients in the chronic stage. OBJECTIVE: The aim of this study is to evaluate the effects of HBOT on overall cognitive functions of post-stroke patients in the chronic stage. The nature, type and location of the stroke were investigated as possible modifiers. METHODS: A retrospective analysis was conducted on patients who were treated with HBOT for chronic stroke (>3 months) between 2008-2018. Participants were treated in a multi-place hyperbaric chamber with the following protocols: 40 to 60 daily sessions, 5 days per week, each session included 90 min of 100% oxygen at 2 ATA with 5 min air brakes every 20 minutes. Clinically significant improvements (CSI) were defined as > 0.5 standard deviation (SD). RESULTS: The study included 162 patients (75.3% males) with a mean age of 60.75±12.91. Of them, 77(47.53%) had cortical strokes, 87(53.7%) strokes were located in the left hemisphere and 121 suffered ischemic strokes (74.6%).HBOT induced a significant increase in all the cognitive function domains (p < 0.05), with 86% of the stroke victims achieving CSI. There were no significant differences post-HBOT of cortical strokes compared to sub-cortical strokes (p > 0.05). Hemorrhagic strokes had a significantly higher improvement in information processing speed post-HBOT (p < 0.05). Left hemisphere strokes had a higher increase in the motor domain (p < 0.05). In all cognitive domains, the baseline cognitive function was a significant predictor of CSI (p < 0.05), while stroke type, location and side were not significant predictors. CONCLUSIONS: HBOT induces significant improvements in all cognitive domains even in the late chronic stage. The selection of post-stroke patients for HBOT should be based on functional analysis and baseline cognitive scores rather than the stroke type, location or side of lesion.