A Randomized, Double-blinded and Placebo-controlled Study on Super-Oxygenated Water
Phase: NA
Conditions: Adult Subject
Sponsor: Inhale, Inc

Protocol Version 2.0, Dated 16-JAN-2025 
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A randomized, double-blinded and placebo-controlled study on 
super-oxygenated water  
 
 
 
 
 
 
Protocol Number: Inhale-001 
 
 
 
 
 
Principal Investigator: 
 
Dawn DeSylvia, M.D. 
 
3625 Thousand Oaks Blvd 
Building A – Suite 209 
Westlake Village, CA 91362 
 United States 
 
Telephone: +1 (310) 914-3400 
Fax: +1 (424) 293-8901 
 
 
 
 
 
Sponsor: 
 
Inhale, Inc 
 
2501 N Harwood, Suite 2001 
Dallas 75201 
United States 
Telephone: +1 (918) 500-2682 
 
 
 
 
 
Confidentiality Statement  
This document contains trade secrets, commercial and financial information of Inhale, Inc. This document is 
being provided to Clinical Investigators, authorized Research Staff, Institutional Review Board and/or 
Independent Ethics Committee members with an explicit understanding that the information will be utilized 
in the conduct of this designed clinical investigation. The information is being shared under assurance that 
the recipient will maintain confidentiality under applicable statues, regulations, rules, protective orders or 
otherwise without prior written permission from Inhale, Inc. 

Protocol Version 2.0, Dated 16-JAN-2025 
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SYNOPSIS 
 
Oxygenated water is a functional water that contains higher levels of dissolved oxygen than found 
in normal drinking waters. Consumption of oxygenated water has become a growing trend that is 
believed to aid aerobic respiration and offer added health benefits apart from hydration. Several 
animal studies link drinking of oxygenated water to an elevated blood oxygen level, while clinical 
observations suggest a positive association with multitude of metabolic processes involving  post-
exercise recovery, stress endurance, alcohol detoxification, uric acid clearance, immune responses, 
and some benefits in patients with obesity, hypertension, and diabetes. Therapeutic delivery of 
additional oxygen to blood stream via hyperbaric and extracorporeal oxygenation are known to 
induce tissue repair, restore normal body functions and improve survival. The current prospective 
study will evaluate a non-invasive route for oxygen delivery through ingestion of super-
oxygenated water in adult volunteers. The participants will be randomized 1:1 to two treatment 
arms viz. super-oxygenated water and placebo control with source and taste matched normal water. 
Both the participant and investigator will be blinded to the treatment assignment. Participants will 
drink 12 oz of their assigned water and at 1-minute post-ingestion blood oxygen saturation (SpO2) 
level and heart rate will be measured using a pulse oximeter. Response to super-oxygenated water 
will be evaluated in augmenting  blood oxygen saturation (SpO2) level and reducing heart rate 
compared to their pre-ingestion levels.  
 
 

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Table of Contents 
SECTION 1: STUDY SUMMARY ............................................................................................. 4 
SECTION 2: STUDY OBJECTIVE ........................................................................................... 5 
SECTION 3: BACKGROUND AND RATIONALE ................................................................. 5 
SECTION 4: STUDY DESIGN ................................................................................................... 8 
SECTION 5: SUBJECT SELCTION AND ENROLLMENT ................................................ 10 
SECTION 6: STUDY ASSESSMENTS AND PROCEDURE ................................................ 11 
SECTION 7: STUDY ENDPOINTS AND CLINICAL OUTCOMES .................................. 12 
SECTION 8: ADVERSE EVENT REPORTING .................................................................... 12 
SECTION 9: DATA MANAGEMENT AND STATISTICS .................................................. 13 
SECTION 10: DATA COLLECTION AND QUALITY ASSURANCE ............................... 13 
SECTION 11: OPERATIONAL CONSIDERATION ............................................................ 14 
SECTION 12: PUBLICATION ................................................................................................. 14 
SECTION 13: REFERENCES .................................................................................................. 15 
SECTION 14: APPENDICES .................................................................................................... 18 
 
 
 
 
 
 
 

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Section 1: STUDY SUMMARY 
 
TITLE 
A randomized, double-blinded and placebo-controlled study 
on super-oxygenated water  
RATIONALE 
Therapeutic effects of oxygen supplementation have been long 
known to improve health and wellness. In addition to the 
pulmonary gaseous exchange, oxygen has been shown to be 
absorbed from the gastric and intestinal surfaces. Oral delivery 
of dissolved oxygen with oxygenated beverage appears as a 
practical route to raise blood oxygen. This study will evaluate 
ingestion of water supersaturated with oxygen in comparison 
with normal water. 
TARGET 
POPULATION 
Adult volunteers 
NUMBER OF 
PARTICIPANTS 
60 divided into two treatment arms with 30 each 
INTERVENTION 
Subjects will drink 12oz of their assigned water (blinded) 
PRIMARY 
OBJECTIVE 
To demonstrate an improvement in blood oxygen saturation 
(SpO2) and reduction in heart rate following ingestion of 
super-oxygenated water  
PRIMARY 
ENDPOINT 
Pre- and post-ingestion SpO2 and heart rate will be measured 
using a pulse oximeter.  
STUDY DESIGN 
Randomized double blinded study with two treatment arms  
 
 
 
 
 
 
 
 
 
 

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Section 2: STUDY OBJECTIVE 
To evaluate the efficacy of super-oxygenated water ingestion in augmenting blood Oxygen 
saturation (SpO2) level and reducing heart rate in adult volunteers. 
 
Section 3: BACKGROUND AND RATIONALE 
Gaseous oxygen remains central to aerobic metabolism that acts as the final electron acceptor in 
cellular respiration to generate energy1. Essentially, oxygen is an indispensable element for 
sustenance of aerobic life and is primarily acquired from the atmosphere. In terrestrial organisms, 
oxygen is made available to the tissues via three interdependent processes; 1) ventilation, the 
process by which air moves in and out of the lungs, 2) diffusion, the spontaneous exchange of 
gases across air-blood barrier between the air sacs or alveoli and the blood capillaries in the lungs, 
and 3) perfusion, the process by which the cardiovascular system pumps blood throughout the 
body. Oxygenated blood from lungs travels to peripheral tissues to deliver oxygen and returns to 
lungs as de-oxygenated blood to be re-oxygenated in their circulatory journey2. The oxygenation 
and de-oxygenation of blood are reversible processes facilitated by hemoglobin, an oxygen carrier 
protein in red blood cells. Hemoglobin chemically couples with oxygen during gaseous exchange 
in lungs and releases it in response to high levels of carbon dioxide prevalent in peripheral tissues. 
Cells have built-in oxygen sensors and any impairment in oxygen transport resulting in lower 
tissue oxygen levels induces cellular hypoxia that may lead a multitude of signaling events, cell 
injury and pathophysiologic outcomes3,4. 
 
Therapeutic benefits from oxygen supplementation have been long achieved. Hyperbaric 
oxygenation therapy that involves breathing of pure oxygen in a pressurized environment is a well-
established treatment for decompression sickness, carbon dioxide poisoning, sepsis, hard to heal 
wounds, and COVID-195,6. Delivery of supersaturated oxygen therapy via extra corporeal 
oxygenation is a recently approved treatment for acute myocardial infarction following 
percutaneous coronary intervention with stenting to reduce infarct size7. A long-term clinical 
benefit of supersaturated oxygen therapy has also been observed in an open-label study where 
patients who received intracoronary supersaturated oxygen therapy had an improved survival, 
lower rates of new-onset heart failure and hospitalization for the entire one year of follow-up study 
compared to those who did not receive the supersaturated oxygen therapy8. Despite clinical 
benefits,  these interventions of oxygen supplementation are not amenable for everyday use and 

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are rather medically involved requiring specialized equipment including hyperbaric chambers, 
cardiac catheterization laboratory, and extracorporeal oxygenators.  
 
Enteric delivery of gaseous oxygen has been demonstrated to raise blood oxygen level 
experimentally in cats and rats as well as clinically in humans9-11. It was observed that  
administration of enteral oxygen in patients undergoing upper abdominal operations showed nearly 
20% increase in oxygen saturation of the portal blood11. In another preclinical experiment 
oxygenated water was administered into stomach of anesthetized rabbits12. Following the 
intragastric delivery, an elevated oxygen content was noted in the abdominal cavity as well as in 
the portal vein indicating enteric absorption of the dissolved oxygen. Notably, effective oxygen 
absorption was noticeable when the level of dissolved oxygen was at least 45 mg/L. Till today 
numerous animal studies have been conducted that link drinking of oxygenated water to improved 
metabolism, stress responses and protective immunity. In a placebo-controlled study with rats, 
pretreatment with oxygenated water for four weeks or longer prevented hyperuricemia and 
significantly attenuated experimental hyperuricemia induction in a dose dependent manner13. 
Drinking of oxygenated water for 25 days induced greater cellular and humoral immune responses 
in pigs to an experimental infection by Salmonella producing significantly higher levels of white 
blood cells, lymphocytes and cytokines compared to control pigs who drank tap water14. Benefits 
of drinking oxygenated water has also been reported in broiler chickens where an increased level 
of serum lysozyme, a potent anti-bacterial component, and greater infection-fighting peripheral 
blood mononuclear cell proliferation were observed compared to control chickens who drank tap 
water15. In the same study, chickens experimentally infected with Salmonella showed a marked 
alleviation in disease symptoms and registered an increased survival of over 20% over the control 
by drinking oxygenated water. Additional effects of oxygenated water ingestion have been noted 
to accelerate alcohol detoxification in monkeys16, and protect rats from epileptic seizures17. 
 
Given that an adult human body is composed of 50-70% of water, the U.S. National Academies of 
Sciences, Engineering, and Medicine determined that necessary daily fluid intake is approximately 
2.7 liters (91 ounces) for women and approximately 3.7 liters (125 ounces) for men to maintain 
adequate hydration. The daily fluid requirement is generally higher for physically active 
individuals, and those living in warmer climate and with other physiologic needs such as breast-

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feeding. Nearly 80% of the daily fluid requirement is met by ingestion of water or beverages. In 
this context, targeting drinking water as a vehicle for oxygen supplementation emerges as a 
practical route. 
 
Normal drinking waters contains low amounts of dissolved oxygen (5-7 mg/L) whereas  
commercially available oxygen-enriched drinking waters may contain 30 mg to 120 mg of 
dissolved oxygen per liter13. Ingestion of oxygenated water showed a faster recovery from an 
intense exercise regimen18. The placebo-controlled study evaluated male collegiate distance 
runners that were given oxygen-supplemented water before, during and after a 5000-meter 
treadmill run where serum lactate clearance was significantly higher in runners receiving oxygen-
supplemented water compared to those receiving taste matched control water. In another double-
blind placebo-controlled diabetes study, patients with type 2 diabetes ingested 21L of water stably 
enriched with oxygen every fortnight for 24 weeks19. Remarkably, the glycosylated hemoglobin 
level in patients on oxygen enriched water was significantly lower at weeks 6 and 12 with respect 
to their baseline values whereas no such reduction was noted in glycosylated hemoglobin in 
placebo drinking water. Dissolved oxygen has been shown to reduce blood alcohol  levels20. 
Alcoholic drinks that had greater dissolved oxygen content  (20, and 25 mg/L) had a faster 
elimination from the body evidenced by lower blood alcohol level compared to  alcohol drink that 
had normal level of dissolved oxygen (8 mg/L). In a related study, oxygen enriched water was 
supplemented with alcoholic drinks that had varied levels of dissolved oxygen21. Even after 
consuming a large amount of alcohol, the blood alcohol concentration was markedly lower in 
group that received the oxygenated alcohol drink along with oxygenated water.  
 
From the review of available anecdotal reports and controlled studies, drinking of oxygenated 
waters appear beneficial even though deciphering these findings is an arduous task  due to lack of 
a defined study endpoint, lack of understanding of an optimal oral dose of dissolved oxygen and 
multitude of commercially available products with unique chemistry and varied dissolved oxygen 
levels. The functional water that encompasses oxygenated water is an emerging concept whose 
market size for year 2022 was valued at $4.2 billion US dollars. Due to the inherent variability 
with the manufacturing process and oxygen content, it is imperative that each oxygenated water 
product is evaluated for the benefit claim. 

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Section 4: STUDY DESIGN 
 
The study will be conducted by Dr Dawn DeSylvia at the provider’s clinic/office and/or at 
surrounding business locations in Westlake Village, CA. A total of 60 adult volunteers will be 
enrolled who will provide written informed consent on the IRB approved form before study 
participation. 
 
The study subjects will sign informed consent form and will be randomized at 1:1 ratio between 
two study arms to receive either INHALE super-oxygenated water or a source and taste-matched 
normal water by a randomization software (Randomizer,  https://www.randomizer.at/). This is a 
double blinded study where neither the subject nor the investigator will know the assigned 
treatment arm. An unblinded research staff will perform the randomizations and prepare the 
blinded waters for use by blinded investigator. The randomized subjects will be stratified based on 
the gender (Male or Female) to ensure proportionate participation.  Water in both treatment arms 
will be served chilled (4oC) to the study subjects.    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fig 1: Study design schema 
Informed Consent
Randomization 
(1:1)
Baseline 
Measurement
(SpO2, HR)
Endpoint 
Measurement
(SpO2, HR)
INHALE Superoxygenated 
Water, (n=40)
Source and taste 
matched normal Water, 
(n=40)
12 oz Water 
Ingestion
1-min post-ingestion

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The study will evaluate ingestion of 12 oz of water (about 10% of daily fluid intake and is similar 
to an average beverage size) in one administration. The test article, INHALE super-oxygenated 
water contains dissolved oxygen at ~56 mg/L without any added sodium, sugar, protein or fat 
(Table 1, Fig 2).  
The test articles INHALE super-oxygenated water, and a taste matched normal water will be 
provided at no cost to the subjects by the research team. The preparation, supply, storage and 
handling of the waters will be according to the manufacturer’s guidelines. 
 
Only one dose (12 oz) of water will be ingested. This amount is based upon available literature 
which is a reasonable amount to drink and not to cause any dilution effect on blood oxygen 
saturation. No overdose is expected since there is only one serving size per container. Subjects will 
not be allowed to crossover from one arm to the other. 
 
Subjects receiving medications and supportive therapies necessary to maintain general health are 
allowed other those listed in the exclusion criteria.  
 
Table 1: Nutrition facts for INHALE super-oxygenated water 
 
 
Ingredients: Water 
 
Serving Size 12 fl oz 
 
1 Serving per container 
 
Amount per serving 
 
Calories 
0 
                                                                                  % Daily Value* 
Total Fat, 0g 
 
0% 
Sodium, 0g 
0% 
Total Carbohydrate, 0g 
0% 
Total Sugars, 0g 
 
Includes 0g Added Sugars 
0% 
Protein 0g 
 
 
* The % Daily Value tells you how much a nutrient in a serving of food contributes to a daily 
diet. 2000 calories a day is used for general nutrition advice. 

Protocol Version 2.0, Dated 16-JAN-2025 
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Section 5: SUBJECT SELCTION AND ENROLLMENT 
 
Subject eligibility must be reviewed and documented by the Investigator before study enrolment. 
Sponsor may be consulted for an eligibility review on a case-by-case basis.  No exceptions to the 
subject eligibility requirements set in the protocol will be granted by the Sponsor. 
 
Inclusion Criteria 
1. Legally adult (³18 years) and either gender (Male or Female) will qualify 
2. Subject must be willing to review and provide an informed consent to participation 
3. Subject must agree to the study procedures including water ingestion, and SPO2 and 
heart rate measurements 
 
Exclusion Criteria 
1. Any active and life-threatening medical condition involving hepatic, renal, cardiac, 
respiratory, endocrinal, or gastrointestinal systems, or any blood disorder in view of the 
Principal Investigator to confound the study  
2. Female subjects those are pregnant, nursing or planning to become pregnant 
3. Subjects receiving any experimental medications or have undergone a major surgical 
procedure in last 30 days 
 
  
 
 
 
Fig 2: Test article, INHALE Superoxygenated water 

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4. Subjects are excluded if they have previously utilized the test article (INHALE super-
oxygenated water) within the last 24 hours, have undergone bariatric surgery or have 
received weight-loss medication 
5. Subjects with known anemia, hemoglobinopathies or other comorbidities necessitating 
fluid restriction would be excluded 
 
Section 6: STUDY ASSESSMENTS AND PROCEDURE 
Voluntary, written, dated, and signed IRB-approved informed consent form must be obtained from 
the subject before any study specific procedures are performed. Participants not with active life-
threatening medical conditions and not on medications interfering with oxygen metabolism are 
eligible for enrollment. The subjects will complete a demographics and brief medical history form 
(Appendix 1). 
As this is a randomized study with two (2) treatment arms, the subjects will be assigned their 
treatment group using Randomizer, (https://www.randomizer.at/). Neither the subject nor the 
investigator will know the treatment assignment (as they are blinded in the study) and an unblinded 
study staff will perform the randomization and dispense the blinded water for the subject. 
The subjects will provide an Energy level and Brain clarity assessment (Appendix 2) at pre-dose. 
Pre-ingestion or baseline measurements of blood oxygen saturation (SpO2) and heart rate will be 
measured with a pulse oximeter attached to index or middle finger of either hand. The subjects are 
expected to ingest their assigned water within 30 sec. At 1-minute post ingestion, SpO2 and heart 
rate will be recorded. Subjects will again provide the Energy level and Brain clarity assessment 
(Appendix 2) at post-dose.  Super-oxygenated water is marketed as functional water and is 
generally considered safe for human consumption. The sponsor is not aware of any health events 
related to drinking of super-oxygenated water. The production cycle of INHALE super-
oxygenated water encompasses a closed and aseptic cycle that ensures consistency and sterility of 
the product.  
 
The study treatment would require only one session/visit and no follow-up visits will be necessary. 
The participants will be asked for an optional 30-min post-ingestion observation. Patients may 
discontinue from study treatment at any time at their own request, or they may be discontinued at 

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any time at the discretion of the Investigator or Sponsor for safety, behavioral reasons, or the 
inability of the patient to comply with the protocol or procedures. 
Section 7: STUDY ENDPOINTS AND CLINICAL OUTCOMES 
 
Primary efficacy endpoint for the study will be an increase in blood oxygen saturation and decrease 
in heart rate at post-ingestion compared with that at pre-ingestion baseline. A medical grade pulse 
oximeter will be utilized in the measurement. 
Section 8: ADVERSE EVENT REPORTING 
An adverse event (AE) is any reaction, side effect or other unfavorable medical event that occurs 
during participation in a clinical trial regardless of treatment group or suspected causal relationship 
with the treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or 
disease in the enrolled subjects. All AEs that occur prior to the study treatment are considered as 
medical history unless the AE develops or worsens during or after the study treatment. Assessment 
of AEs will include type, incidence, severity, timing, seriousness, and relatedness to study 
treatment. A treatment emergent AE (TEAE) is an AE that occurs after the first dose of any study 
treatment or any preexisting condition that increases in severity should be reported as AEs. The 
AE is classified as a serious adverse event (SAE) when the untoward medical occurrence results 
in death, becomes life threatening, causes persistent/significant disability or results inpatient 
hospitalization. 
Every AE will be assessed by the investigator with regard to evaluation of its Severity (Grade 1 
[mild], Grade 2 [moderate], Grade 3 [severe], Grade 4 [life-threatening] and Grade 5 [death]; 
Causality (Related- when there is a reasonable chance that the AE is connected to or is caused by 
the water ingestion, Not related- when there is a reasonable chance that the AE is connected to or 
is caused by something else other than the water ingestion); and Outcome (Recovered/Resolved, 
Recovered/Resolved with sequelae, Ongoing, Fatal/results in death). 
The active reporting period for SAEs begins from the time that the patient provides informed 
consent and until completion of the study (post-ingestion endpoint measurement). All SAEs must 
be reported to the sponsor (emailed or faxed) within 24 hours of Investigator being aware about 
occurrence about the event. Sponsor will report the collected SAE events to the IRB following 
their reporting guidelines. 

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Section 9: DATA MANAGEMENT AND STATISTICS 
Privacy of research subjects and confidentiality of their personal information will be maintained 
to the maximum limit possible under applicable regulations and international guidelines. Subjects 
will be assigned with anonymized identifiers to minimize such risks. A detailed methodology for 
summary and statistical analyses of the collected data will be developed and maintained by the 
Sponsor. Each eligible subject will be assigned with a unique combination of alphanumeric 
characters. Initials for First and Last names of the subject and gender and a sequence number will 
be assigned to each subject. For example, subject 1, Jane Doe will be denoted as JDW-001. 
Similarly subject 2, John Doe, will be denoted as JDM-002. These subject number will be utilized 
in randomization for treatment assignment. At no time, the protected health information (PHI) will 
be collected, shared or stored during the study.  
 
The hypothesis being tested here is that INHALE super-oxygenated water will significantly 
increase SpO2 levels and decrease heart rate following a single ingestion. The study aims to enroll 
30 subjects per treatment arm that will further be stratified between male and female. The sample 
size is selected to support analysis for an expected <1% increase in SpO2 and an anticipated 1% 
decrease in heart rate as continuous measures in the experimental group with an alpha level of 0.05 
powered at 80%. Statistical analysis of this study will be the responsibility of the Sponsor and 
Investigators. All tests of treatment effects will be conducted at a 2-sided, unless otherwise stated. 
Continuous variables will be summarized using descriptive statistics (i.e., number of participants, 
mean, median, standard deviation, minimum, and maximum). Categorical variables will be 
summarized by frequency and its corresponding percentage. 
 
At study conclusion all datasets will be utilized to construct a comparative analysis. The data will 
be analyzed by JMP Pro and GraphPad Prism software for statistical comparisons. Principles of 
intent-to-treat analysis will be applied where every piece of collected data will be processed 
without any bias or selection and no enrolled subjects will be excluded from the analysis. 
 
Section 10: DATA COLLECTION AND QUALITY ASSURANCE 
All data entries will be conducted by the study investigator or trained study staff. No PHI data will 
be utilized as subject identifier, and every subject will be assigned an anonymized alphanumeric 

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character described in Section 9. All study personnel and sub-investigators will be trained by the 
Principal Investigator with regard to study protocol and subsequent data collection.  
 
Section 11: OPERATIONAL CONSIDERATION 
 
This study will be conducted in accordance with International Ethical Guidelines for Biomedical 
Research Involving Human Subjects (Council for International Organizations of Medical 
Sciences), Guidelines for Good Clinical Practice (GCP) (International Council for Harmonization 
[ICH] 1996), ICH E6 (R2) and concepts that have their origin in the Declaration of Helsinki. The 
study will be conducted under a protocol reviewed and approved by an Institutional Review Board 
(IRB) and the study will be conducted by scientifically and medically qualified persons; the 
benefits of the study are in proportion to the risks; the rights and welfare of the patients will be 
respected; the physicians conducting the study do not find the hazards to outweigh the potential 
benefits; and each patient will give his or her written informed consent before any protocol-driven 
procedures or evaluations are performed. 
 
The Investigator or designee is responsible for informing the subject of all available information 
relevant to his/her safety and obtaining signed, written consent from all participating subjects. 
Additionally, the Investigator is responsible for monitoring subject safety and providing periodic 
and requested reports to the IRB/EC. The Investigator is responsible for the accuracy and 
completeness of all study records including source documents and/or case report forms (CRFs). 
Section 12: PUBLICATION  
Results from this study may be considered for publication in an appropriate scientific platform 
upon study completion. 
 
 
 
 

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Section 13: REFERENCES 
 
 
1. 
Babcock GT. How oxygen is activated and reduced in respiration. Proc Natl Acad Sci U S A. 
Nov 09 1999;96(23):12971-3. doi:10.1073/pnas.96.23.12971 
2. 
Popel AS. Theory of oxygen transport to tissue. Crit Rev Biomed Eng. 1989;17(3):257-321.  
3. 
Semenza GL. Oxygen sensing, hypoxia-inducible factors, and disease pathophysiology. Annu 
Rev Pathol. 2014;9:47-71. doi:10.1146/annurev-pathol-012513-104720 
4. 
Semenza GL. Oxygen sensing, homeostasis, and disease. N Engl J Med. Aug 11 
2011;365(6):537-47. doi:10.1056/NEJMra1011165 
5. 
Ortega MA, Fraile-Martinez O, García-Montero C, et al. A General Overview on the 
Hyperbaric Oxygen Therapy: Applications, Mechanisms and Translational Opportunities. 
Medicina (Kaunas). Aug 24 2021;57(9)doi:10.3390/medicina57090864 
6. 
Oliaei S, SeyedAlinaghi S, Mehrtak M, et al. The effects of hyperbaric oxygen therapy 
(HBOT) on coronavirus disease-2019 (COVID-19): a systematic review. Eur J Med Res. Aug 
19 2021;26(1):96. doi:10.1186/s40001-021-00570-2 
7. 
TherOx DownStream System (2019). 
8. 
Chen S, David SW, Khan ZA, et al. One-year outcomes of supersaturated oxygen therapy in 
acute anterior myocardial infarction: The IC-HOT study. Catheter Cardiovasc Interv. May 
01 2021;97(6):1120-1126. doi:10.1002/ccd.29090 
9. 
Gelman S, Paz M, Levy E. Influence of enteral oxygen administration on the slow electrical 
activity of the intestine and stomach. Arch Surg. May 1976;111(5):566-74. 
doi:10.1001/archsurg.1976.01360230066014 
10. Gelman SI. The effect of enteral oxygen administration on the hepatic circulation during 
halothane anaesthesia: experimental investigations. Br J Anaesth. Dec 1975;47(12):1253-9. 
doi:10.1093/bja/47.12.1253 
11. Gelman SI. The effect of enteral oxygen administration on the hepatic circulation during 
halothane anaesthesia: clinical observations. Br J Anaesth. Dec 1975;47(12):1261-4. 
doi:10.1093/bja/47.12.1261 
12. Forth W, Adam O. Uptake of oxygen from the intestine-- experiments with rabbits. Eur J Med 
Res. Nov 20 2001;6(11):488-92.  

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13. Fang CH, Tsai CC, Shyong YJ, et al. Effects of Highly Oxygenated Water in a Hyperuricemia 
Rat Model. J Healthc Eng. 2020;2020:1323270. doi:10.1155/2020/1323270 
14. Jung BG, Lee JA, Lee BJ. Oxygenated drinking water enhances immune activity in pigs and 
increases immune responses of pigs during Salmonella typhimurium infection. J Vet Med Sci. 
Dec 2012;74(12):1651-5. doi:10.1292/jvms.12-0051 
15. Jung BG, Lee JA, Nam KW, Lee BJ. Oxygenated drinking water enhances immune activity 
in broiler chicks and increases survivability against Salmonella Gallinarum in experimentally 
infected broiler chicks. J Vet Med Sci. Mar 2012;74(3):341-6. doi:10.1292/jvms.11-0316 
16. Hyvärinen J, Laakso M, Sippel H, et al. Alcohol detoxification accelerated by oxygenated 
drinking water. Life Sci. Feb 1978;22(7):553-9. doi:10.1016/0024-3205(78)90333-8 
17. Kwon HH, Jung SY, Park H, et al. Oxygenated Water Increases Seizure Threshold in Various 
Rodent Seizure Models. Int J Mol Sci. Nov 16 2022;23(22)doi:10.3390/ijms232214124 
18. Fleming N, Vaughan J, Feeback M. Ingestion of oxygenated water enhances lactate clearance 
kinetics in trained runners. J Int Soc Sports Nutr. 2017;14:9. doi:10.1186/s12970-017-0166-
y 
19. Khoo J, Hagemeyer CE, Henstridge DC, et al. Effects of water stably-enriched with oxygen 
as a novel method of tissue oxygenation on mitochondrial function, and as adjuvant therapy 
for type 2 diabetes in a randomized placebo-controlled trial. PLoS One. 2021;16(7):e0254619. 
doi:10.1371/journal.pone.0254619 
20. Baek IH, Lee BY, Kwon KI. Influence of dissolved oxygen concentration on the 
pharmacokinetics of alcohol in humans. Alcohol Clin Exp Res. May 2010;34(5):834-9. 
doi:10.1111/j.1530-0277.2010.01155.x 
21. Rhee SJ, Chae JW, Song BJ, Lee ES, Kwon KI. Effect of dissolved oxygen in alcoholic 
beverages and drinking water on alcohol elimination in humans. Alcohol. Feb 2013;47(1):27-
30. doi:10.1016/j.alcohol.2012.08.007 
22. Wilkinson D, Chapman IM, Heilbronn LK. Hyperbaric oxygen therapy improves peripheral 
insulin sensitivity in humans. Diabet Med. Aug 2012;29(8):986-9. doi:10.1111/j.1464-
5491.2012.03587.x 
23. Vera-Cruz P, Guerreiro F, Ribeiro MJ, Guarino MP, Conde SV. Hyperbaric Oxygen Therapy 
Improves Glucose Homeostasis in Type 2 Diabetes Patients: A Likely Involvement of the 
Carotid Bodies. Adv Exp Med Biol. 2015;860:221-5. doi:10.1007/978-3-319-18440-1_24 

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24. Schoenberg MH, Hierl TC, Zhao J, Wohlgemuth N, Nilsson UA. The generation of oxygen 
radicals after drinking of oxygenated water. Eur J Med Res. Mar 28 2002;7(3):109-16.  
25. Pakravan N, Abbasi A, Hassan ZM. Immunotherapy Using Oxygenated Water and Tumor-
Derived Exosomes Potentiates Antitumor Immune Response and Attenuates Malignancy 
Tendency in Mice Model of Breast Cancer. Oxid Med Cell Longev. 2021;2021:5529484. 
doi:10.1155/2021/5529484 
26. Masik MG, Danilishina VS. [Enteric oxygen therapy in the treatment of obesity]. Vopr Pitan. 
1972;31(4):56-9.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Section 14: APPENDICES 
 
APPENDIX 1: 
 
 
 
 
Subject #:_____________________                    Date:____________________ 
(dd -Mmm- yyyy) 
 
 
1. Age (Years):___________________ 
 
 
2. Gender (Choose one): 
 
 Male 
 Female 
 Not Reported 
 
 
3. Medical History: 
 
 
# 
Condition/Disease 
(one item per line) 
Start Date 
(dd/Mmm/yyyy) 
Status 
 
 
 
 Current 
 Resolved 
 
 
 
 Current 
 Resolved 
 
 
 
 Current 
 Resolved 
 
 
 
 Current 
 Resolved 
 
 
 
Demographics and Brief Medical History 

Protocol Version 2.0, Dated 16-JAN-2025 
19 
APPENDIX 2: 
 
 
 
 
 
 
Subject #:_____________________       
 Before Dosing        
 After Dosing 
 
 
 
 
 
 
 
 
(Choose one) 
 
 
 
 
1. How would you score your Energy Level? 
 
10= Very High, 1= Very Low 
 
 
        
        
        
        
        
        
        
        
        
 
10 
9 
8 
7 
6 
5 
4 
3 
2 
1 
Very High                                                                                                                                    Very Low 
 
 
 
2. How would you score your Brain Clarity? 
 
10= Very High, 1= Very Low 
 
 
        
        
        
        
        
        
        
        
        
 
10 
9 
8 
7 
6 
5 
4 
3 
2 
1 
Very High                                                                                                                                    Very Low 
 
 
 
Energy Level and Brain Clarity Assessment