The Crucial Role of Oxygen for Health

Abstract

The human body is dependent upon oxygen for its survival. Yet, various factors such as aging, psychological stress, obstructive sleep apnea, exposure to cigarette smoke, living at high altitude, high-intensity exercise, or a sedentary lifestyle can all lead to a hypoxic state. Hypoxia may be involved in the pathogenesis of a number of disorders including impaired immunity, hormonal imbalances, fibromyalgia, cardiovascular diseases, type 2 diabetes, depression, and anxiety. Hyperbaric oxygen therapy and massage are two means by which to improve oxygen perfusion. Certain dietary supplements such as Ginkgo biloba, coenzyme Q10, and beetroot juice can increase oxygenation through enhanced blood flow while branched-chain amino acids and omega-3 fatty acids can improve maximum oxygen consumption V̇o2max. Additionally, omega-3 fatty acids and vitamin D may reduce the incidence of sleep apnea while N-acetyl cysteine may protect against hypoxia injury related to sleep apnea.

Full text

Journal of Restorative Medicine 2019; e20190106
ABSTRACT
The human body is dependent upon oxygen for its survival. Yet, various factors
such as aging, psychological stress, obstructive sleep apnea, exposure to cigarette
smoke, living at high altitude, high-intensity exercise, or a sedentary lifestyle can all
lead to a hypoxic state. Hypoxia may be involved in the pathogenesis of a number
of disorders including impaired immunity, hormonal imbalances, fibromyalgia,
cardiovascular diseases, type 2 diabetes, depression, and anxiety. Hyperbaric oxygen
therapy and massage are two means by which to improve oxygen perfusion. Certain
dietary supplements such as Ginkgo biloba, coenzyme Q10, and beetroot juice can
increase oxygenation through enhanced blood flow while branched-chain amino
acids and omega-3 fatty acids can improve maximum oxygen consumption

V
o2max.
Additionally, omega-3 fatty acids and vitamin D may reduce the incidence of sleep
apnea while N-acetyl cysteine may protect against hypoxia injury related to sleep
apnea.
Keywords: Hypoxia; Oxygenation; Perfusion; Hyperbaric oxygen therapy
The Crucial Role of Oxygen for Health
Chris D. Meletis, ND*
Kimberly WilkesaDOI 10.14200/jrm.2019.0106
*Corresponding author: Associate Professor of Natural Pharmacology, National University of Natural
Medicine, Portland, OR, USA, Tel.: +1-503-466-2722; E-mail: DrMeletis@gmail.com
a15455 NW Greenbrier Parkway Way, Portland, OR 97006, USA.
Copyright © 2019 Chris D. Meletis. This is an open-access article distributed under the terms
of the Creative Commons Attribution NonCommercial-NoDerivatives 4.0 License. The use, distribution or
reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are
credited and that the original publication in this journal is cited, in accordance with accepted academic
practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Journal of Restorative Medicine 2019; e20190106
e Crucial Role of Oxygen for Health
INTRODUCTION
Every tissue and organ in the body is dependent
upon oxygen to function effectively. The human
brain, for example, needs 20% of the oxygen
pumped from the heart while at rest.1,2 The brain’s
oxygen requirement is the highest of any tissue or
organ, even though it accounts for only 2% of the
average person’s body weight.2 Every time we take
a breath in, oxygen is transported via the alveoli
of the lungs to the capillaries and subsequently
into the bloodstream. In the blood, hemoglobin, a
protein in red blood cells (RBC), binds oxygen and
shuttles it to tissues where the oxygen assists with
nutrient breakdown and energy production. This
process of delivering oxygen to tissues is known as
perfusion. If tissues do not receive enough oxygen,
a condition known as hypoxia develops, which
results in pain and suboptimal cellular function.
Tight muscles are reflective of a hypoxic state.
Soreness that occurs after exercising harder than
normal or exercising after a sedentary period is due
to low blood oxygen levels during exercise and the
buildup of lactic acid. Ongoing exercise, on the
other hand, encourages more blood oxygen to be
pumped throughout the body, allowing for greater
ability to move without feeling pain, assuming we
don’t exceed our individual aerobic threshold.
According to the Mayo clinic, 95%–100% oxy-
gen saturation is considered normal blood oxygen
levels.3 However, in clinical practice, many patients
with a 95% oxygen saturation often show signs and
symptoms of hypoxia, such as marginal night time
oxygenation trending towards apnea. This article
describes factors that lead to hypoxia, diseases
associated with hypoxia, and ways to support better
tissue perfusion.
CAUSES OF HYPOXIA
Oxygen levels decline as part of the aging process.
The greatest loss in oxygen levels – up to 10 points
– occurs between 30 and 40 years old.4 Stress
is another factor that can deplete oxygen levels.
During psychological stress, the fight or flight
system is hyperactive, leading to shallower breath-
ing and therefore reduced oxygen supply. Studies
indicate there is decreased oxygen supply and a
greater oxygen demand in the wounds of stressed
animals. Optimal oxygen levels play an important
role in wound healing, while low oxygen levels can
reduce the healing rate.5
In a rodent model of stress-impaired healing, mice
were divided into four groups: controls, controls
with hyperbaric oxygen therapy (HBO), stressed
animals, and stressed animals administered HBO.5
Each of the mice in the four groups was adminis-
tered two cutaneous wounds. The stressed groups
of mice were subjected to restraint stress prior
to and after wounding. The control groups were
deprived of food and water during the same period,
to control for the inability of the stressed animals
to access food and water while restrained. HBO –
which delivers 100% oxygen – was administered
twice per day to one group of stressed mice and
to one control group during early wound repair. In
the stressed mice, the HBO significantly decreased
the detrimental effects of stress on healing, and
increased healing to nearly the level of that of con-
trol animals. HBO did not result in any significant
effect on wound healing in control animals.5
Another study in rodents showed that stress
aggravates periodontitis by decreasing tissue oxy-
genation.6 Gum disease severity was linked to the
level of psychological stress and decreased oxygen-
ation in the periodontal tissue.
Heiden and colleagues studied 24 healthy sub-
jects (12 males and 12 females) who performed
a 45-minute standardized mouse-operated com-
puter task on two occasions. On one occasion, the
subjects were given a deadline to meet and a more
demanding task. On the other occasion, the sub-
jects were told to perform a less demanding task.
Throughout the study, tissue oxygen saturation in
the trapezius and the extensor carpi radialis muscle
of the forearm operating the mouse was measured.
During the more demanding task, oxygen saturation
in the extensor carpi radialis muscle of the forearm
decreased (P<0.05) compared to when the subjects
performed the less demanding task. Females had
lower oxygen saturation than males, during both
rest and the computer tasks (P<0.01). Ratings
of tenseness and fatigue also were higher in the

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e Crucial Role of Oxygen for Health
subjects who performed the more demanding task.7
The effects of stress on oxygen supply has implica-
tions that extend beyond acute stressors to chronic
stress, as many individuals in modern society are in
a near perpetual fight-or-flight state due to vari-
ous perceived threats such as traffic jams, job and
relationship stress, and feeling overburdened with
too many daily tasks.
In addition to being a result of chronic and acute
stress, hypoxia can also cause psychological stress
through a mechanism that may involve alterations
in the hypothalamic-pituitary-adrenal (HPA) axis
and elevation of cortisol levels.8 Subjects with
obstructive sleep apnea (OSA) were shown to have
substantially higher 24-hour cortisol levels compared
with controls, whereas treatment with a continuous
positive airway pressure (CPAP) device dramatically
reduced cortisol levels similar to those of controls.8
Chronic obstructive sleep apnea is a common
cause of hypoxia. According to The American
Sleep Apnea Association9 and the National Sleep
Foundation, an estimated 18 million Americans
have sleep apnea. Many individuals who have the
disorder go undiagnosed, suggesting this number
may actually be much higher.9 Hypoxia caused by
obstructive sleep apnea (OSA) has been shown to
exacerbate the effects of air pollution by prevent-
ing the clearance of particulate matter from the
lungs.10 It may be a vicious cycle as air pollution
itself can deprive the body of oxygen. This may
lead to the development of sleep apnea, which has
a greater prevalence in poor urban environments,
where pollution is more common. Furthermore, in
patients with post-traumatic stress disorder (PTSD),
the presence of severe OSA was related to suicidal
ideation, indicating that hypoxia can exacerbate the
negative consequences of chronic stress.11
Even in the absence of OSA, pollution is a common
cause of hypoxia. Although the harmful effects of
pollution are mostly attributed to the presence of
toxic substances such as polycyclic aromatic hydro-
carbons (PAHs) and other organic components
such as endotoxins, its potential to deplete oxygen
levels is an important concern. A study of 32 elderly
subjects found that greater exposure to air pollu-
tion (both traffic and non-traffic industrial sources)
reduced oxygen saturation. The study authors
suggested this was the result of an inflammation
response in the lungs or vascular dysfunction due
to exposure to airborne particles.12 Cigarette smoke
and secondhand smoke,13 weight gain,14,15 drinking
alcohol,16,17 living at high altitude, or too much or
too little exercise18,19 are other factors that deprive
the body of optimal oxygen levels.
CELLULAR REACTION TO OXYGEN
DEPLETION
Two of the primary cellular consequences of low
oxygen levels involve the mitochondria and the
switch from aerobic to anaerobic respiration.
LOW OXYGEN AND MITOCHONDRIA
The mitochondria require oxygen to manufacture
ATP. Oxygen serves as a fuel for cytochrome
oxidase, the final enzyme in the electron trans-
port chain that generates ATP.18 Because diffusion
would be an inefficient means of supplying cells
with oxygen, hemoglobin and myoglobin act as
oxygen-carrying molecules to perfuse the tissues.20
As blood circulates through capillaries, oxygen
bound to hemoglobin diffuses via a steep pressure
gradient into tissues and subsequently into the mito-
chondria.20 This oxygen delivery to cells is tightly
regulated with only enough myoglobin present to
deliver the optimal amount of oxygen.20
One group of researchers described the mitochon-
dria’s role as “rheostats within a cell to orchestrate
cellular responses to various stimuli, including
hypoxia.”21 Oxygen concentrations are an impor-
tant contributor to such responses. However,
carbon monoxide and nitric oxide also compete for
oxygen-binding sites on enzymes such as cyto-
chrome C oxidase and thus may also play a role in
oxygen signaling.22 Improvement in mitochondrial
function can parallel increases in oxygen saturation.
After hyperbaric oxygen administration, improved
mitochondrial complex IV activity has been recog-
nized as a marker of recovery from acute carbon
monoxide poisoning.23
AEROBIC VS. ANAEROBIC RESPIRATION
Cells exposed to oxygen undergo aerobic metabo-
lism whereas oxygen-deficient cells switch to

Journal of Restorative Medicine 2019; e20190106
e Crucial Role of Oxygen for Health
anaerobic metabolism. The goal of both aerobic
and anaerobic metabolism is to transform nutrients
into ATP. Aerobic metabolism is as much as 15
times more efficient than anaerobic metabolism
at producing ATP. Aerobic metabolism generates
approximately 29–30 ATP molecules per one mole-
cule of glucose. Conversely, anaerobic metabolism,
yields only two ATP molecules per one molecule
of glucose.24 Another negative consequence of
anaerobic metabolism is that it produces lactic acid
in muscles, which is responsible for post-exercise
pain. The lactic acid is produced as a result of fer-
mentation that occurs under anaerobic conditions.
When the body switches to anaerobic metabolism
for a short duration, such as during intense exer-
cise, no long-term adverse consequences result.
However, when anaerobic metabolism is utilized
most of the time, this can lead to adverse effects.
DISORDERS ASSOCIATED WITH
HYPOXIA
HORMONAL IMBALANCES
Hypoxia can interfere with hormone metabolism. In
individuals with chronic low oxygen due to chronic
obstructive airway disease or pulmonary fibrosis,
testosterone concentrations are often low.25 Low
testosterone levels also are frequently observed
in patients with obstructive sleep apnea. In men
with excessive abdominal fat and who also suf-
fered from sleep apnea, hypoxia severity during
sleeping hours was associated with lower testos-
terone levels, independent of body mass index and
abdominal fat.26 Furthermore, in men with chronic
obstructive airways disease, the severity of arterial
hypoxia was inversely correlated with testosterone
concentrations.27
Additionally, administering testosterone can
have profound effects on oxygen levels. In rab-
bits fed a high-fat diet, hypoxic fat accumulated
in the visceral tissue.28 When researchers admin-
istered testosterone to the rabbits, it restored the
proper oxygenation level in the visceral fat tissue.
However, in the conventional medical model, tes-
tosterone administration to men with severe OSA is
contraindicated due to concerns that it may exacer-
bate the OSA.
Passavanti and associates investigated the effect
of hyperbaric oxygen therapy on 14 male patients
(23–72 years old) who were suffering from a
variety of injuries and conditions including leg
fractures, diabetic foot wounds, firearm injuries,
or underwater diving embolism.29 The effect of
hyperbaric oxygen on six healthy male volunteers
(37–51 years old) was also studied. The study
authors measured plasma testosterone immediately
before the first hyperbaric oxygen session and the
day after the last session. At the end of hyperbaric
oxygen treatment, 12 patients fully recovered and
two diabetic patients with foot wounds experienced
a marked improvement. Both patients and controls
had a pronounced rise in their testosterone levels
after hyperbaric oxygenation therapy.
EFFECTS ON IMMUNE FUNCTION
Inflamed, infected, or injured tissue is character-
ized by hypoxia. Immune cells are able to infiltrate
and perform their functions in tissues with reduced
levels of nutrients and oxygen.30 Most bacteria and
viruses thrive in low-oxygen environments. The
ability of hyperbaric oxygen therapy to improve
immune cell function is due to a resolution of that
low-oxygen state. The increased oxygen pro-
vided by hyperbaric oxygen therapy enhances the
bacteria-killing ability of white blood cells, reduces
edema, and allows new blood vessels to grow more
rapidly into affected areas.31
In one study, 331 patients who had typhoid, diph-
theria, meningococcal infection, or viral hepatitis
were treated with hyperbaric oxygen therapy while
363 controls did not receive hyperbaric oxygen.32
The patients who underwent hyperbaric oxygen-
ation experienced improved oxygen saturation of
blood compared to controls. Other improvements
were observed, including a more favorable course
and outcome of their disease process. In an animal
experiment, ozone treatment caused a pronounced
reduction of bacterial counts in rats with MRSA.33
When combined with the antibiotic vancomycin,
the ozone was associated with an even greater
decline in bacterial counts.33
Hyperbaric oxygen therapy increases the production
of reactive oxygen intermediates (ROIs) throughout
the body. ROIs are known to eliminate enveloped
viruses, such as the human immunodeficiency

Journal of Restorative Medicine 2019; e20190106
e Crucial Role of Oxygen for Health
virus (HIV). This is likely the mechanism by which
hyperbaric oxygen has been used effectively in
acquired immune deficiency syndrome (AIDS)
patients.34 Hyperbaric oxygen in cell culture studies
also has been shown to have viricidal actions. In
one study, researchers found that in HIV-infected
cells exposed to hyperbaric oxygen, HIV viral load
was decreased.35 In uninfected cells exposed to
hyperbaric oxygen and then to HIV, only a small
amount of the HIV virus entered the cells.
The hepatitis virus is also vulnerable to oxygen
therapy. Researchers administered hyperbaric oxy-
gen therapy to 30 male subjects who had hepatitis
B, whereas another 30 male subjects were treated
with conventional therapy alone.36 The partici-
pants treated with hyperbaric oxygen recovered
faster, gained appetite, and improved their sense of
well-being more quickly than the control subjects.
Additionally, the hyperbaric oxygen resulted in a
faster improvement in symptoms such as itching
and normalization of liver function. Moreover,
hepatitis B virus surface antigen became negative
more quickly in patients in the hyperbaric oxygen
group. These patients also had an overall shorter
duration of hospital stay and convalescence com-
pared to controls.
FIBROMYALGIA
Fibromyalgia (FM) is a common chronic pain con-
dition affecting approximately 10 million people in
the United States and an estimated 3%–6% of the
global population.37
Evidence indicates that the muscle pain and
fatigue that occurs in fibromyalgia may be associ-
ated with impaired muscle tissue microcirculation
and oxygen metabolism.38 A number of studies
have observed lower skin/muscle blood flow or
oxygen consumption in fibromyalgia patients.39–42
Moreover, recovery times for oxygen levels after
muscle ischemia or aerobic exercise are longer in
individuals with fibromyalgia.43,44 Another study
found evidence of low tissue oxygenation in
fibromyalgia patients as evidenced by abnormal or
low muscle oxygenation in the trigger point area of
painful muscles.45
Furthermore, studies have demonstrated that
fibromyalgia symptoms are exacerbated in lower
atmospheric pressure climates where there is
decreased oxygen pressure.46 Fibromyalgia patients
respond successfully to the increased oxygen pres-
sure in hyperbaric chamber treatment as well as to
coenzyme Q10 supplementation, which enhances
the body’s use of oxygen.46
CARDIOVASCULAR DISEASE
Heart disease and high blood pressure are linked
to sleep apnea, which has a higher prevalence in
patients with cardiac disorders compared to healthy
controls.47 Even mild sleep apnea is associated with
an increased risk for cardiovascular disease due to
apnea-induced arterial stiffness.48 In one study, 91%
(51 of 56) of subjects who had suffered a stroke
had sleep apnea.49 The combination of strokes and
sleep apnea was associated with an increased risk of
silent strokes and white matter lesions, increasing
the risk of disability at hospital discharge. There is
also a higher risk of cardiac arrhythmia in people
who have sleep apnea.50,51
Sleep apnea is associated with hypertension and
45% of individuals who have sleep apnea also have
high blood pressure.52 The severity of the sleep
apnea often correlates with severity of daytime
hypertension.53 Sleep apnea is also associated with
treatment-resistant hypertension.54
Hyperbaric oxygen has been shown to have other
cardiovascular applications. In one randomized,
controlled study, researchers investigated the effects
of hyperbaric oxygen therapy on patients undergoing
first-time elective coronary artery bypass graft sur-
gery (CABG).55 Prior to surgery, 41 subjects received
hyperbaric oxygen therapy twice for 30-minutes, with
a five minute interval between treatments, whereas
40 subjects received no hyperbaric oxygen before
surgery. Although not statistically significant, the
researchers found that the group treated with hyper-
baric oxygen prior to CABG surgery experienced
less postoperative heart injury, an 18% reduction
(P=0.05) in length of stay in the intensive care unit
(ICU), a 57% reduction in intraoperative blood loss
(P=0.02) as well as 11.6% reduced blood loss post-
surgery (P=0.09). Fewer patients in the hyperbaric
oxygen group required a blood transfusion compared
to untreated controls (P=0.4) and there was an 11%
reduction in atrial fibrillation (P=0.6), a 12.7% reduc-
tion in pulmonary complications (P=0.8), and a 7.6%

Journal of Restorative Medicine 2019; e20190106
e Crucial Role of Oxygen for Health
reduction in wound infections (P=0.4) in the hyper-
baric oxygen group.
EFFECTS ON BLOOD SUGAR
There is an increased risk of developing insulin
resistance and type 2 diabetes in individuals with
sleep apnea.56,57 Additionally, enhancement of
oxygen levels is associated with an improvement
in blood sugar. For example, a study showed that
treatment with a positive airway pressure device
(CPAP) in people who had sleep apnea and type 2
diabetes caused an increase in insulin sensitivity
and a decline in HbA1c levels.58
MOOD DISORDERS
Oxygen levels play an important role in maintaining
mood and mental health. Veterans with sleep apnea
have a pronounced increase in depression, anxiety,
psychosis, and post-traumatic stress disorder.59
Moreover, in one study of 32 newly diagnosed sleep
apnea patients who also suffered from depression,
researchers found a connection between the severity
of depression and the degree of hypoxia; the severity
of depression correlated to the degree of sleepiness
and to low oxygen saturation.60 After treatment for
sleep apnea, the patients’ depression improved.
OTHER CONDITIONS
Low oxygen levels have been associated with a
number of other health concerns. The hypoxia that
occurs at high altitude may be a trigger for inflam-
matory bowel disease (IBD) flare ups.61 Learning
and memory is also affected by oxygen levels. In
animal models of Alzheimer disease, hyperbaric
oxygen combined with Ginkgo biloba protected
rats against damage to brain cells.62 Compared to
untreated animals, Ginkgo combined with hyper-
baric oxygen also improved the rats’ ability to find
their way through a water maze, increased levels
of antioxidant enzymes in the brain, and lowered
markers of oxidant damage. Hyperbaric oxygen and
Ginkgo administered separately protected against
cell death; however, the combination of both
enhanced the beneficial effects. In another study,
rats with vascular dementia experienced increased
neurogenesis as well as improved blood supply to
the brain after hyperbaric oxygen treatment.63
One of the few human studies on the topic inves-
tigated 64 patients with vascular dementia. The
study authors compared hyperbaric oxygen used
together with the drug donepezil to the use of
donepezil alone. Patients receiving hyperbaric
oxygen plus donepezil had significantly better
cognitive function than the donepezil-only group
after 12 weeks.64
A review of nine trials including 201 patients
indicates headaches are another health disorder
linked to hypoxia.65 Five of the trials compared
hyperbaric oxygen therapy to placebo therapy in
acute migraine,65 two studies compared the effects
of hyperbaric oxygen to a placebo on cluster head-
aches, and two studies measured the effects of one
atmosphere oxygen breathing (NDOT) on cluster
headaches.65 Pooling of data from three of the trials
indicated that although hyperbaric oxygen did not
prevent migraine attacks or reduce the incidence of
nausea, it relieved migraine headaches compared
with the placebo (P=0.01). These data indicated
that more than 70% of individuals with migraines
who are treated with HBO may achieve relief of
pain within about 40 minutes. One trial included
in the review found a significantly greater number
of subjects with cluster headaches achieved relief
after 15 minutes of NBOT compared to a placebo
therapy with air. Of the patients treated with NBOT,
9 of 16 subjects (56%) reported complete relief or
significant reduction in headache intensity (P=0.04)
compared to only 1 of 14 (7%) in the control group
reporting improvement.65
MEASURING OXYGEN LEVELS
An oximeter is the device normally used to deter-
mine oxygen levels (Spo2). However, this standard
device can vary in accuracy depending on a num-
ber of factors. It has a number of limitations that
can result in inaccurate readings in some cases.66
In a survey of 551 critical care nurses, 37% were
unaware that patient motion compromises the
accuracy of oximeters, 15% did not know that
poor signal quality can affect reading accuracy,
and 30% thought that Spo2 readings could be
a replacement for arterial blood gas samples
when managing ICU patients.67,68 Values are

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e Crucial Role of Oxygen for Health
also inaccurate when the patient’s finger is cold.
Although arterial blood gas analysis is a more
accurate means of determining oxygen concentra-
tion, for most clinical purposes, pulse oximetry
is considered sufficiently accurate, as long as the
clinician recognizes its limitations.69
IMPROVING OXYGEN PERFUSION
A number of strategies can be employed to
increase blood flow to tissues and thus improve
oxygenation. The many benefits of massage
therapy including reducing pain and improving
functionality in patients with osteoarthritis and
fibromyalgia,70,71 relieving low back pain,72 reduc-
ing blood pressure73 and the incidence of chronic
tension headaches,74 and improving mitochondrial
function75 may all be associated with increased
oxygen perfusion to tissues. Studies have shown
that massage can increase muscle blood flow and
oxygenation in people with low back pain who
drive frequently,76 individuals with restless legs
syndrome,77 and after exercise-induced muscle
injury,78 among other applications. However, ben-
efits of massage can be short term and disappear
after treatment stops.70 Bad posture, stress, and
other factors can eliminate the beneficial effects.
Therefore, it has been proposed by some clinicians
that administering oxygen during a massage could
extend the benefits.
Evidence indicates that increased oxygen perfu-
sion can also be achieved with certain nutrients
and botanicals that have been shown to increase
blood flow and oxygenate the tissues. Coenzyme
Q10 (CoQ10) is one such nutrient. Patients with
fibromyalgia, who suffer from musculoskeletal
oxygenation alterations, were successfully treated
with CoQ10, which improved their oxygen usage.46
In a rodent study, CoQ10 reduced the hypoxic dam-
age that occurred when the animals were exposed
to the organophosphate pesticide mevinphos.79
Furthermore, CoQ10 reduced hypoxia-reperfusion
damage in neural stem cells in part by inhibiting
free radical formation and by increasing the expres-
sion of survival-related proteins.80
Ginkgo biloba is another dietary supplement known
for its ability to increase blood flow, thus increasing
oxygen perfusion to tissues. As noted earlier in this
article, Ginkgo has been found to work synergistically
with hyperbaric oxygen in reducing amyloid-beta
protein burden in rodents.62 The mechanism of action
of these two synergistic treatments involved reduc-
ing cell toxicity and oxidative stress by inhibiting
mitochondria-controlled apoptosis signaling.62 In a
human study, Ginkgo biloba combined with hyper-
baric oxygen either resolved or improved tinnitus in
approximately 80% of the patients (P=0.046).81
In vitro, Ginkgo biloba has been shown to pro-
tect human vascular endothelial cells and retinal
pigment epithelial cells against injury from
hypoxia.82,83 Ginkgo biloba also has been shown
to increase ocular and cerebral blood flow.84–86
Cerebral injury related to low oxygen perfusion
after surgery is one of the main causes of post-
surgery disability and death.87 Ginkgo biloba
extract has been shown to enhance cerebral oxygen
supply, lower cerebral oxygen extraction rate
and consumption, and help regulate the balance
between cerebral oxygen supply and consumption
after surgery.87
Beetroot (Beta vulgaris) juice is another substance
that has beneficial effects due to its ability to
increase levels of nitric oxide, which is involved
in improving blood flow.88 Hypoxia can impair
exercise performance in athletes while the use of
beetroot juice may reduce this hypoxia-induced
effect on cardiorespiratory endurance.88
SUPPLEMENTS TO IMPROVE MAXIMUM
OXYGEN CONSUMPTION (

V
o2max)

V
o2max is the maximum amount of oxygen used by
the lungs during one minute of strenuous exercise.
Increasing oxygen levels can increase

V
o2max by
11% or more.89 It is thought that improved

V
o2max
is responsible for the enhanced exercise tolerance
that occurs after oxygen administration during
exercise. Certain dietary supplements are known to
improve

V
o2max. For example, supplementation of
overweight women with omega-3 fatty acids com-
bined with lifestyle alteration that included healthy
diet education and aerobic exercise significantly
improved

V
o2max outcome (P=0.03).90 Branched-
chain amino acid supplementation has also been
known to improve endurance exercise capacity in
part by increasing

V
o2max in trained male subjects
(P<0.05).91

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e Crucial Role of Oxygen for Health
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SUPPLEMENTS FOR SLEEP APNEA
Use of a CPAP machine is the standard treatment for
obstructive sleep apnea patients. Certain dietary sup-
plements can be administered concurrently with use
of a CPAP machine or used proactively to possibly
inhibit the development of obstructive sleep apnea
(OSA). Vitamin D insufficiency is associated with an
increased risk for OSA.92 The relationship of reduced
vitamin D levels with the development of OSA is
thought to be due to the relationship between vitamin
D insufficiency and immune system modulation,
myopathy, and inflammation.92 Insufficient intake
of omega-3 fatty acids may also be linked to sleep
apnea. Ladesich and colleagues observed the asso-
ciation between RBC levels of docosahexaenoic acid
(DHA) and OSA severity in 350 patients involved in
sleep studies.93 The authors noted an inverse relation-
ship between RBC, DHA, and OSA severity. For
each 1-standard deviation (SD) of increase in DHA
concentrations, the study subjects were 53% less
likely to be diagnosed with severe OSA. Antioxidant
therapy may be beneficial in individuals diagnosed
with obstructive sleep apnea. For example, compared
with a placebo control, N-acetyl cysteine (NAC) sup-
plementation led to a decline in muscle sympathetic
nerve activity in 16 human subjects in response to
intermittent hypoxia (P<0.02), suggesting it may
have therapeutic potential in OSA.94
CONCLUSION
Proper perfusion of oxygen to tissues and organs
throughout the body is crucial for optimal health.
Hypoxia has been associated with a number of
health concerns, whereas administering oxygen in
a hyperbaric chamber or improving sleep apnea
has been beneficial in cardiovascular health,
immunity, cognitive function, and other disorders.
Improvement in oxygen perfusion can be achieved
through the utilization of dietary supplements such
as CoQ10, Ginkgo biloba, beetroot juice, omega-3
fatty acids, and branched-chain amino acids.
Furthermore, individuals diagnosed with sleep
apnea or at risk of sleep apnea should be tested for
vitamin D insufficiency and supplementation be
implemented accordingly. Omega-3 fatty acids and
NAC may also be beneficial in this population.
COMPETING INTERESTS
The authors declare they have no competing
interests.
ACKNOWLEDGMENTS AND FUNDING
No funding was received for the preparation or
writing of this article.

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