The Oxygen Controversy

Hydrogen Peroxide...Oxygen...Free Radicals

Oxygen Emulsion: Inquiring Minds Want to Know

From the Desk of Ted Kalli

The Advanced 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 Emulsion

The traditional 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 peroxide.

How and Why Does it Work

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.

Free Radicals

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.

Oxidative reactions 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 years.

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 killed.[1]

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.[2]

Since antioxidant 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.)[2]

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.[2]

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.[3]

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.[3]

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).[4]

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 control value.[5]

Vitamin E (a-tocopherol) inhibited liquid peroxidation. These results indicate that singlet oxygen may mediate lipid peroxide formation in epidermal microsomes.[6]

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.[6]

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 skin.[6]

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.[7]

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.[8]

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.[9] 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.[10] “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.[11]

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.[11]

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.[12] 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.[13]

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 century.

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 own mind.

References

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.

[6] 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)

Other references.

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: 2403-13 (1990)

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)