The Oxygen Controversy
Inquiring Minds Want to Know
From the Desk of Ted
Dermatologics News, March 1995
You may be aware that
statements are being made in the industry, that the oxygen emulsion
produces free radicals. It has also been implied that the oxygen
emulsion may actually increase the aging effect on the skin. The
following article is intended to address these concerns.
Background of Oxygen
hyperbaric oxygen (HBO) therapy treatment involves intermittent
inhalation of pure oxygen under a pressure greater than one atmosphere.
The oxygen environment we live in is considered to be one atmosphere.
Oxygen pressure greater than one atmosphere is considered to be
hyperbaric. HBO acts both mechanically due to its pressure
component (hyperbaric oxygen chamber), and physiologically, due to its
oxygen component (inhalation of 100% oxygen).
AURA Research’s oxygen
emulsion is an oil-in-water emulsion of hydrogen peroxide. The hydrogen
peroxide emulsion is a mechanical mechanism. It was developed for skin
care, not as a medical treatment. Various ingredients have been combined
with the emulsion; beta-carotene, alpha tocopherol, sodium hyaluronate,
ceramides, salicylic acid, lactic acid, glycolic acid, glucans,
sunscreens, EDTA and other ingredients of known benefit to the skin.
There are some unique
features about the emulsion. One is that the hydrogen peroxide itself,
is isolated from the other ingredients in the emulsion. Another salient
point is that the oxygen emulsion is stable, unlike aqueous hydrogen
How and Why Does it
When hydrogen peroxide
comes in contact with the skin, it always breaks down into water and
oxygen due to the presence of the enzyme, Catalase. Instead of oxygen
being released on the surface of the skin and escaping to the
atmosphere, as with aqueous hydrogen peroxide, the oxygen penetrates the
skin. This is due to the oil phase of the emulsion, which creates a
barrier to the oxygen. The skin becomes the path of least resistance.
When hydrogen peroxide changes from a liquid to a gas (which is
instantaneously), it increases in volume 22.4 times. This instantaneous
increase in volume is what causes the pressure and why the oxygen
penetrates the skin. Simply put, the emulsion is a topically applied,
local hyperbaric oxygen treatment.
Oxygen is a gas only during this instantaneous reaction. As soon as it
penetrates the stratum corneum, it is dissolved in the extracellular
water and in the capillary plasma. Molecular oxygen (gas) can only exist
in the lungs. As the oxygen penetrate the skin, it acts as a vehicle and
takes the water and other ingredients with it.
There are no blood
vessels in the epidermal layers of the skin. Capillaries are responsible
for supplying the skin cells with nutrients. Circulation in the
capillaries is mediocre, at best. As we age, the capillaries become less
permeable and allow little or no oxygen and nutrients pass to the
extracellular fluid, which surrounds the cells. With little oxygen and
nutrients passed to the cells, it is no wonder that the face skin is the
first part of the body to show visible signs of aging.
When discussing free
radicals, it is absolutely necessary to look at the whole picture. It is
difficult to read an article concerning the skin and aging without the
term free radical appearing somewhere in the text.
continuously take place during normal cellular metabolism. A secondary
effect of these reactions the production of free radicals. Free radicals
are a fact of life; life as we know it, could not exist, without oxygen
or free radicals. The oxygen free radical is only one of many free
radicals produced during cellular metabolism. Oxygen free radicals are
short lived, in an optimal oxygen environment, such as our pre-teenage
Oxygen free radical can
be, in fact, beneficial. Activated phagocytes generate large amounts of
superoxide as part of the mechanism by which foreign organisms are
If you want to further
research free radicals and hydrogen peroxide, be prepared to allocate a
tremendous amount of time on this project. In a Medline search, on
January 31, 1995, using the following general keywords there were 1,193
papers on free radicals; 1,291 papers on hydrogen peroxide; 1,132 papers
on catalase; and 177 papers on alpha tocopherol. This search covered
from 1986 to January 16, 1995, a nine year time span, in which a total
of more than one research study was published, per day.
The following are quotes
from just a few of the referenced published papers concerning alpha
tocopherol (vitamin E), antioxidants, EDTA(a chelating agent), and other
factors related to the subject.
All the hydrogen peroxide
emulsions manufactured by AURA Research, Ltd., include alpha tocopherol
and EDTA as ingredients.
About 1-3% of the oxygen
we breathe in is used to make superoxide. Since human beings consume a
lot of oxygen, we may produce over 2 kg of superoxide in the body every
year; people with chronic infections may make much more.
defenses are not completely effective, repair enzymes exist that destroy
free-radical-damaged proteins, remove oxidized fatty acids form
membranes and repair free-radical damage to DNA (some of the oxidized
bases removed are excreted in urine.)
Some antioxidant defenses
are located both intracellularly and extracellulary. [alpha]-tocopherol
(TH) occurs in membranes and lipoproteins. It blocks the chain reaction
of lipid peroxidation by scavenging intermediate peroxyl radicals.
Oxygen gas is able to
diffuse through body tissue and skin, and it is possible to detect it by
means of an electrochemical oxygen sensor applied to the skin
surface (Kontron Cutaneous Oxygen Monitor). In order to create local
arterialization, the sensor is heated to a constant temperature which is
higher than normal body surface temperature. The sensor allows a
quantitative determination of the oxygen partial pressure at the level
of the arterialized cutaneous tissue.
The cutaneous pO2 is of
particular value in detecting any pathological change in the patients
state which ultimately results in low tissue oxygenation. A low
cutaneous pO2 generally indicates a critical situation which e.g. may be
due to insufficient oxygen supply, respiratory distress, low cardiac
output or impaired peripheral circulation.
H2O2 has no unpaired
electrons and does not qualify as a radical. Hence the term reactive
oxygen species has been introduced to describe collectively not only O2
and .OH (radicals) but also H2O2 (non-radical).
The use of a number of
cosmetic ingredients including alpha tocopherol acetate and beta
carotene were effective in reducing the MDA value by 40 to 80% of the
Vitamin E (a-tocopherol)
inhibited liquid peroxidation. These results indicate that singlet
oxygen may mediate lipid peroxide formation in epidermal microsomes.
Vitamin E (a-tocopherol)
which interrupts free radical chain reactions, caused a 60% decrease in
lipid peroxide formation when added at a concentration of 10 uM.
Addition of EDTA, Mn+3,
cytochrome c+3, and catalase to the NADPH-supported enzynic peroxidation
system resulted in strong inhibition of lipid peroxide formation in
Vitamin E is now
considered to be essential for the stabilization of biological
membranes, particular those containing large amounts of polyunsaturated
fatty acids. The oxidation of unsaturated fats produces lipid peroxides,
which interfere with the structure and function of biological membranes.
It is now known that vitamin E acts as an antioxidant, and can inhibit
the formation of lipid peroxides. It might thus play a role against
aging--particularly of the skin--since lipidperoxidation in tissues
maybe on of the causes of skin aging.
The following is an
abstract taken from an early paper by Barry Halliwell. In this article,
several of his papers on free radicals have been cited.
“Oxygen radicals” are now
popular subjects for research papers; several hundred are published each
year. Many of these pass rapidly into oblivion, joining the great mass
of unread scientific literature that clogs library shelves and dilutes
important research findings to an increasingly great extent. The basic
chemistry of oxygen-derived species was established years ago by
radiation chemists, but “superoxide” is still endowed with miraculous
properties by the uninitiated. Demonstration that the action of a
disease or toxin in vivo produces increased lipid peroxidation (a
currently-popular scientific activity) means nothing more than the fact
that its action produces increased lipid peroxidation: it does not
automatically follow that the lipid peroxidation causes the damaging
effects of the drug or disease.
Active oxygen species
produced in the body are usually rendered harmless by endogenous
enzymatic and nonenzymatic antioxidative defenses. Such antioxidative
enzymes as superoxide dismutase (SOD), glutathione peroxidase and
catalase help maintain low levels of oxidants that are normally produced
by, for example, a respiring mitochondria and by neutrophils stimulated
to undergo a respiratory burst. Free radicals, possessing an unpaired
electron, wreak major damage by oxidizing—robbing an electron from—a
protein or other nearby molecule. They also threaten to set in motion a
self-perpetuating chain reaction as each electron they rob transforms a
molecule into an electron-hungry radical itself. Vitamin E, the body’s
premier antioxidant, stops this destructive chain of oxidizing reactions
by donating an electron. In the process, vitamin E also becomes a
radical, but a relatively nonreactive and benign one. Vitamin E radical
was thought to just decay away, but studies over the past decade have
suggested otherwise. To resolve the issue, Lester Packer and his
coworkers at Lawrence Berkeley (Calif.) Laboratory recently fed high
vitamin-E diets to rats for three weeks, enriching tocopherol levels in
their mitochondrial membranes to 20 times normal. These membranes are
the main site of oxygen consumption—and therefore, Packer reasoned, a
likely site of vitamin-E rejuvenators.
After isolating these
membranes, the researchers scanned them spectroscopically and for the
first time directly observed vitamin-E radicals in biological materials.
Next, they subjected their soup of membranes and vitamin-E radicals to
an electron-donating chemical and watched as the membranes’ “respiratory
system” began shunting electrons around. Before long, enzymes in this
system transformed the radicals back to vitamin E. “Right now, as
you are breathing air, about 5 percent of the oxygen is breaking down
into free radicals,” said Helaine M Alessio, associate professor of
exercise physiology at Miami University in Oxford, Ohio.
To an extent, free
radicals are good because they work as part of the white blood cell’s
defenses against infection and injury, said Lester Packer, Professor of
Molecular and Cell Biology at the University of California, Berkeley.
But they can get out of hand, he said.
Smokers incur a sustained
free radical load that may increase their vitamin E requirement.
Erythrocytes of male smokers from a Scottish population with a
habitually low vitamin E intake were more susceptible to hydrogen
peroxide-stimulated peroxidation than were those from nonsmokers (P <
0.001). Plasma concentrations of lipid peroxides, thiobarbituric acid
reactive substances, and conjugated dienes were also elevated in smokers
compared with nonsmokers (P < 0.05). These indexes of oxidative stress
were markedly decreased (P < 0.001) in the smokers and nonsmokers after
consumption of 280 mg dl-[alpha] tocopherol acetate/d for 10 wk.
Platelet numbers in serum of both smokers and nonsmokers were also
decreased by vitamin E supplementation
< 0.02). Although the
clinical significance of the results is unclear, elevated indexes of
lipid peroxidation are associated with the pathogenesis of
atherosclerosis, and platelets are involved with fibrinolysis.
Therefore, both smokers and non-smokers may benefit from increased
vitamin E intakes. As an antioxidant, vitamin E (alpha tocopherol) is
one of the ways we can fight free radicals. We can’t live without
oxygen, of course, but we need protection to assure that life-giving
oxygen won’t cause our cells to deteriorate by means of oxidation.
Vitamin E can offer that protection.
This journal lacks the
space to cite all the references. It must also be pointed out that
hydrogen peroxide is readily available, as a 3% aqueous solution for use
as an antiseptic, on broken skin and is used orally for periodontal
conditions. Since the gums and lining of the mouth, are soft tissue
mucosa, if hydrogen peroxide, was in any way detrimental, it would have
been a well-published fact, decades ago and its use would have been
restricted by the FDA. Hydrogen peroxide has been in use for over a
Controversy will always
exist. Like the AHA’s, varying opinions always abound concerning
formulations, buffers, pH, percentages, benefits, disadvantages, etc.
The number of papers published on oxygen, free radicals and alpha
hydroxy acids proves that there is great scientific interest in these
subjects and the emerging technologies behind such products. In addition
to the scientific interests in these subject matters, there are also
financial and legal issues.
As with everything in
life, use some commonsense. Review the available information; test the
products or the technology; evaluate the results, and then make up your
1. Babior BM, Woodman RC. “Chronic
granulomatous disease,” Semin Herarol 1990;27:247-59.
2. Halliwell, Barry. “Free radicals,
antioxidants, and human disease: curiosity, cause, or consequence?” The
Lancet, Sept. 10, 1994 v344 n8924 p721(4)
3. “Cutaneous pO2 Monitor, Operating
Manual,” Roche Bio-Electronics, 1979, Basle, Switzerland.
4. Halliwell, Barry. “Reactive oxygen
species in living systems: source, biochemistry, and role in human
disease,” American Journal of Medicine, Sept. 30, 1991 v91 n3C p14S(9)
5. Peter T. Pugliese, M.D., Cheryl B.
Lampley, B.A. - Xienta Institute for Skin Research. “A new look at old
skin: A challenge to cosmetology,” Presented at the International
Meeting, March 7-9, 1985 Rome, Italy.
 Rakesh Dixit, Ph.D., Hassan Mukhtar,
Ph.D. and David R. Bickers, M.D. “Studies on the role of reactive oxygen
species in mediating lipid peroxide formation in epidermal microsomes of
rat skin,” The Journal of Investigative Dermatology, 81:369-375, 1983.
7. Idson, Bernard. “Vitamins and the skin,”
Cosmetics and Toiletries, Dec. 1993 v108 n12 p79(11)
8. B. Halliwell. Oxygen radicals: “A
commonsense look at their nature and medical importance,” Medical
Biology 62:71-77, 1984
9. Oksana M. Gecha, Julie M. Fagan.
“Protective effect of ascorbic acid on the breakdown of proteins exposed
to hydrogen peroxide in chicken skeletal muscle,” American Institute of
Nutrition, June 25, 1992.
10. Raloff, J. “Vitamin E fights radicals -
again and again,” Science News, May 27, 1989 v135 n21 p327(1) 11. Miami
University. “Vitamin E may counteract effect of free radicals,” Cancer
Weekly, March 22, 1993 p8(2)
12. Brown, Katrina M.; Morrice, Phillip, C.;
Duthie, Garry G. “ Vitamin E supplementation suppressed indexes of lipid
peroxidation and platelet counts in blood of smokers and nonsmokers but
plasma lipoprotein concentrations remain unchanged,” American Journal of
Clinical Nutrition, Sept 1994 v60 n3 p383(5)
13. Scheer, James. “Fight free radicals with
vitamin E; research shows that vitamin E offers protection from cellular
oxidation, nitrosamines and artheroscierosis,” Better Nutrition, April
1990 v52 n4 p8(2)
14. Urbano S; Kitahara M; Kato Y; Hasegawa
Y; Matsuo M. “Membrane stabilizing effect of vitamin E: existence of a
hydrogen bond between alpha-tocopherol and phospholipids in bilayer
liposomes,” Tokyo Metropolitan Institute of Gerontology, Japan. J Nutr
Sci Vitaminol (Tokyo) 36:513-9 (1990)
15. Gplring CE; Rice-Evans CA; Burton RH;
Rao R; Haq I; Diplock AT. “Alpha-tocopherol uptake and its influence on
cell proliferation and lipid peroxidation transformed and nontransformed
baby kidney cells,” UMDS Guy’s Hospital, University of London, United
Kingdom. Arch Biochem Biophys 303: 429-35 (1993)
16. Kaiser S; Di Mascio P; Murphy ME; Sies
H. “Physical and chemical scavenging of singlet oxygen by tocopherols,”
Institut fur Physiologische Chemie I, Universitat Dusseldorf, Federal
Republic of Germany. Arch Biochem Fiophts 277: 101-8 (1990)
17. Salgado J; Villalain J; Gomez-Fernandez
JC. “Alpha-tocopherol interacts with natural micelle-forming
single-chain phospholipids stabilizing the bilayer phase,” Universidad
de Murcia, Spain. Arch Biochem Biophys 306: 368-76 (1993)
18. Hornsby PJ; Harris SE. “Oxidative damage
to DNA and replicative lifespan in culture adrenocortical cells,” Exp
Cell Res 168: 203-17 (1987)
19. Kagan VE; Serbinova EA; Bakalova RA;
Stoytchev TS; Erin AN; Prilipko LL; Evstigneeva RP. “Mechanisms of
stabilization of biomembranes by alpha-tocopherol. The role of the
hydrocarbon chain I the inhibition of lipid peroxidation,” Institute of
Physiology, Bulgarian Academy of Science, Sofia. Biochem Pharmacol 40:
20. Weringhaus K; Handjani RM; Gilchrest BA.
“Positive effect of alpha-tocopherol in carrier liposomes of
ultraviolet-mediated human epidermal cell damage in vitro,” USDA Human
Nutritional Research Center on Aging, Tufts University, Boston
Massachusetts. Photodematol Photoimmunol Photomed 8: 236-42 (1991)