Harry R. Elden, Ph.D., consultant, Elden Associates, Inc., Miami, FL
Ted Kalli, AURA Research, Ltd., Marmora, NJ
at the end of blood circulation and in vivo oxygen delivery even though
epidermal cells are exposed to the atmosphere. A few cosmetic class
products have proposed to improve hypoxic shin condition that increases
with age. An efficient formulation concept is that based on dilute
hydrogen peroxide, but skeptics hastily rally caution against dangers of
lipoperoxidation they envision accompanying topical hydrogen peroxide.
article briefly reviews the need to improve skin oxygenation to overcome
intermittent and progressive hypoxia. Published studies (Oak Ridge
National Laboratory) show that dilute hydrogen peroxide is not a major
threat to epidermal cell integrity when compared to benzoyl peroxide.
been known for some time that oxygen uptake decreases with aging (Dobeln
et al., 1967) at submaximal and maximal work loads. A mathematical
equation relates maximal oxygen uptake (V) to work load (L), Heart rate
(H) and age (A):
1.29 [ L / (H - 60) ] exp ( -0.00884 A )
(1967) also showed that aerobic work capacity and many co-related
physiological functions all decline with increasing age beyond peak
performances attained post-adolescence. Generally, the human body
improves its aerobic competence until late teens/early twenties, then
Impediments to oxygenation exist at several points between lungs and
cells. While blood is a hydraulic conductance for oxygen, transfer of
oxygen to and from red blood cells is impeded by plasma constituents.
Navari, Gainer and Hall (1970) showed that plasma proteins and other
constituents generate liquid structures that slow down oxygen
free-diffusion. Oxygen, glucose and carbon dioxide have impaired
diffusion through human plasma with normal range of protein
concentrations. Chisolm et al. (1970), then showed that free-diffusion
of oxygen in plasma decreases linearly with aging, while concentration
of cholesterol increases with aging.
vulnerable to hypoxia because it is the terminal organ for oxygen
delivery, its metabolic rate is transient due to environmental
temperature and autonomic system responses to stress deprive skin
Functional perfusion reserve, i.e., reactive hyperemia following release
of occlusion, is less for older than for younger human subjects.
Xakellis et al. (1993) showed that compression prompts a compensatory
increased circulation in skin which increases with duration of
compression. Older persons show impaired compensation to compression of
blood flow. Findings are of importance to understanding mechanisms of
decubitus ulcer formation in compressed and compromised skin.
Transcutaneous oxygen and carbon dioxide have been measured in situ in
human skin. Dowd et al. (1983) showed a statistical distribution of
partial pressure oxygen for normal and ischaemic skin. Low end of normal
skin overlaps upper end of ischaemic skin, suggesting that human skin in
situ has a wide range of ortho/hypoxia under ordinary conditions.
al. (1982) showed that elevation of upper limbs against gravity markedly
decreased skin oxygen while breathing ambient atmosphere. Evans and
Nalyor (1967) showed, however, that inhaling oxygen markedly raised skin
tissue oxygen at top and base of an induced blister. Thus, skin
circulation and oxygen are highly sensitive to environmental factors.
insidious impairment of skin oxygenation is due to cigarette smoking;
Soffer (1986). Inhalation of nicotine-containing smoke, either primary
or second-hand causes the release of vasopressin, a powerful
vasoconstrictor. Waeber et al. (1984) showed that cigarette smoking
markedly decreased skin blood flow and oxygenation.
early studies amply show that skin blood flow and oxygenation declines
with aging, depends on limb position/occlusion and is impaired further
by environmental pollutants (cigarette smoking). Consequences lead to
exacerbation of decubitus ulcers and impaired wound healing.
relevant further observation is that cigarette smoking increases the
perception of agedness, based upon aesthetic perceptions of the human
face. Studies done by Borkan and Norris (1980) at the Gerontology
Research Center, National Institute of Aging indicated that faces judged
to look functionally older were accompanied by numerous older
sub-systems in the body. Circulation and oxygenation of skin are vital
to physiological health and to aesthetic perceptions of wellness,
fitness, vitality and beauty. Clearly, there is a need to enhance
otherwise compromised oxygen tension of mature adult and aging human
Scientific evidence strongly encourages the development of ways to
enhance oxygenation of skin, and perhaps all other organs as well.
Several means exist to accomplish this objective, but one with the
longest history of safety is to apply stabilized hydrogen peroxide
lotions to the skin.
of this cosmetic formulation concept raise a cry against adding
(hydrogen) peroxide to the skin, but say nothing about the widespread
use of (benzoyl) peroxide. This article addresses benefits vs. risks of
hydrogen peroxide cosmetic formulation, and cites evidence that strongly
supports immediate and longer term safety.
a beneficial response to topical hydrogen peroxide? The first step in
benefit is to determine extent to which oxygen tension is raised by
topical hydrogen peroxide. Extensive unreported studies clearly show
that topical hydrogen peroxide is decomposed by contact with skin;
closed and open wounds. Oxygen tension rises to a peak and descends
slowly to baseline. Time course for this event is on the order of
100-minutes for an FDA cosmetic class formulation.
does not dissipate immediately upon release from hydrogen peroxide.
Lipid solubility of molecular oxygen favors retention in non-aqueous
PHYSIOLOGICAL AND BIOCHEMICAL MODELS
Biochemical studies of skin oxygenation can be standardized by two
physiological treatment modalities. It is well known that inhaling
orthobaric oxygen raises concentrations of oxygen in plasma and thereby
elevates concentrations of oxygen in end-organ skin. By extension,
exposure of a limb or entire body to hyperbaric oxygen further elevates
plasma oxygen and that of the skin. Responses to topical cosmetic
formulation can be compared with skin oxygenated at ortho and hyperbaric
method illustrates the rapidity which dilute stabilized hydrogen
peroxide cosmetic lotions reacts with the skin. It has been reported
that white spots appear at pressure sites when subjects recline on
sunbeds for UVA photo tanning; Tegner (1990).White spots due to
cutaneous hypoxia are prevented by pre-treating sites with 1% hydrogen
peroxide cream just minutes prior to UVA exposure.
comment is not intended to encourage artificial tanning, but refers to
studies that can be confirmed using standard solar simulators and
pressure on skin. Clearly, oxygen is delivered rapidly and it becomes
involved immediately in cellular biochemical reactions.
Laboratory measurements can be done conveniently with transcutaneous
oxygen meter as used in respiratory physiology skin oxygen tension
increases with topical application of oxygen delivery cosmetic
formulations. Few studies exist in the literature, however, on benefits
of topical oxygenation. They are anticipated by numerous testimonial,
anecdotal and clinical perceptions of improvement.
of formal study is not due to the difficulty in measuring skin oxygen.
Nor, is there uncertainty about stability of up to 4% hydrogen peroxide
cosmetic formulations. There is skepticism, perhaps cynicism, regarding
safety attending topical hydrogen peroxide. And there is general lack of
appreciating the physiology of mature, adult and aging skin. Otherwise,
there would be a major effort to improve blood circulation and
oxygenation in adult skin.
balance, it is necessary to evaluate the risk-potential of topical
hydrogen peroxide, since free radical reactions are possible and
PROTECTION IN PLACE
systems are protected in vivo to a substantial degree against free
radicals generated by cellular basal metabolism. Catalase, superoxide
dismutase, glutathione, vitamin E and vitamin C are part of the body's
natural protective system. Skin cells are particularly well protected
against hydrogen peroxide mediated free radicals because topical
hydrogen peroxide does not exist very long in situ.
application of stabilized hydrogen peroxide cosmetic products, catalase
breaks up hydrogen peroxide releasing oxygen which dissolves in lipid
regions of skin surface. Oxygen then equilibrates with aqueous phase and
is dispersed by blood and lymphatic circulations.
levels of tissue oxygen attained by topical cosmetic formulations
approximates that produced desirably by orthobaric inhalation and
hyperbaric treatment. An added safety feature of cosmetic application is
that only skin surface is exposed, allowing dilution by distribution to
PROTECTION BY FORMULATIONS - VITAMINS E AND C
class formulations of hydrogen peroxide should contain vitamin E and C
to block free radical production. This does not interfere with direct
production and utilization of oxygen. Anti-oxidant agents add protection
to epidermal cells beyond that intended for unreacted hydrogen peroxide.
Another feature of cosmetic formulations is that the formula pH should
be near that of the acid mantle. This protects skin and also stabilizes
hydrogen peroxide against spontaneous decomposition.
peroxide (3%) is distributed to mass market consumers as an
acid-stabilizes solution. These solutions are safe and effective
disinfectant and cleansing agents for open wounds in human subjects.
Topical hydrogen peroxide remains safe and effective for open wounds and
also for use in dental products, even thought the same hydrogen peroxide
is capable of generating free radicals.
SUBSTANTIATION OF SAFETY
and C effectively block free radical mediated lipoperoxidation in vivo
and in vitro. An outstanding in vitro study by Nike et al. (1984) shows
that oxidation of methyl linoleate in solution is inhibited by vitamins
E and C. Kinetic mechanisms of initiation, propagation and termination
have been delineated and measured in this detailed study.
Literature distributed by Hoffman-La Roche, Inc., shows about a 50%
reduction in lipoperoxidation by TBA assay of MDA produced by
irradiating mouse epidermal cells: see report by Pugliese (1985).
Hoffman-La Roche report, Elden (1988), shows distribution of topical
vitamin E linoleate into lipid components of the epidermis; viz.,
ceramide, cholesterol and cholesterol ester fractions.
reports amply demonstrate protection against excessive lipoperoxidation
by vitamins E and C at concentrations used to formulate topical
stabilized hydrogen peroxide emulsions; see AURA research, Ltd.
PRODUCTION - PEROXIDES
evidence favoring safety of topical hydrogen peroxide is that provided
by Biology Division, Oak Ridge National Laboratory. Klien-Szanto and
Slaga (1982) studied tumor protection in mouse skin treated with benzoyl,
lauroyl and hydrogen peroxides at 10, 20 and 40 mg. doses for 25 weeks.
peroxides were incomplete carcinogens, but benzoyl and lauroyl peroxide
were effective tumor promoters in a two-stage (DMBA) carcinogenesis
protocol. Hydrogen peroxide was ineffective as complete carcinogen and
inducer. Thus, hydrogen peroxide was not observed to be a potent tumor
promoter. Benzoyl peroxide, while not a complete carcinogen or inducer
is well known as a tumor promoter.
class hydrogen peroxide emulsions are an economical and effective source
of oxygen for hypoxic adult skin. Oxygen is released rapidly upon
topical application which decreases remaining hydrogen peroxide.
Solubility of oxygen in lipid domains of epidermal cells does not raise
concentrations higher than attained by ortho and hyperbaric
oxygenations. vitamins E and C protect epidermal cells against
lipoperoxidation, and are included in hydrogen peroxide cosmetic
peroxide is FDA safe and effective as and anti-infective and cleansing
agent for open wounds. It is used extensively in dental products. Years
of use by mass market consumers have not revealed dangerous side effects
that would prohibit continues application to skin surface.
comparison with benzoyl peroxide, hydrogen peroxide is much less a risk
for tumor induction and promotion of epidermal skin cells. Benzoyl
peroxide is of such far greater risk that the FDA Anti-Acne Final
Monograph removed benzoyl peroxide from safe and effective
classification. Efficacy is not the issue; safety is being reviewed
extensively with animal studies to determine its risk for long term
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Astrand and A. Bergstrom. An Analysis of Age and Other Factors Related
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