- Siegesbeckia
Orientalis Extract
- Emblica
- Palmitoyl
Pentapeptide-3
- Palmitoyl
Tetrapeptide-3
- Acetyl
Hexapeptide-3
- Scientific rationale for alpha lipoic acid (ALA)
as a skin anti-aging agent
- Clinical evidence for the anti-aging
effects of topical DMAE
- Laboratory evidence for the anti-aging
effects of topical antioxidants
Siegesbeckia
Orientalis Extract
Siegesbeckia Orientalis Extract is obtained from the herb
Siegesbeckia orientalis. This herb has been used for centuries externally
to soothe inflammation and stimulate wound healing, which it does
through tissue regeneration by way of collagen matrix build-up.
A now expired patent by Pierre Fabre Medicaments describes its
ability to stimulate wound healing, to promote more regular tissue
renewal, to increase the normal appearance of scars and to fully
restore elasticity to damaged skin with collagen fibers arranged
in regular fashion.
Extracts of Siegesbeckia orientalis have shown anti-inflammatory
properties, inhibition of collagenase and protection from UV induced
erythema.
This initial research led to an investigation of Siegesbeckia Orientalis
Extract ability to restructure stretch marks. Stretch marks are
caused by abnormal stretching of the dermis (pregnancy, change in
weight), from a linear scar or from some endocrine disorders. In
each case the stretch mark affects the elastin fibers in the middle
dermis, which are diminished or disappear. Any effective treatment
for stretch marks thus must restore normal quantities of collagen
and elastin fibers.
The effects shown in a four-week clinical study where a crème
containing 1.5% of Siegesbeckia Orientalis Extract was applied by
volunteers twice daily are listed below.
Results
Length of Streaks -- Reduced 52.15%
Surface Smoothness -- Increased 13.7%
Indented Surfaces -- Reduced 55.4%
Length of Irregularities -- Reduced 52.2%
These results correspond to restructuring of the tissue. At the
end of treatment the surface of the skin was more regular in appearance
and the global profile was more uniform with stretch marks tending
to fade. These results show Siegesbeckia Orientalis Extract to possess
exciting characteristics for the treatment of stretch marks. In
addition, Siegesbeckia Orientalis Extract is shown to possess excellent
tolerance and non-toxicity.
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Emblica
Emblica is the trade name for a tannin-rich extract
from the herb Phyllanthus emblica. This herb has been used for thousands
of years in India and is a cornerstone within the traditional healing
system of Ayurveda.
As a skincare ingredient Emblica has been shown to have great multifunctionality.
Though its primary applications within the skincare industry are
as a photoprotective agent and a skin lightener, Emblica offers
a host of benefits for the skin.
Studies have shown Emblica to possess powerful, broad-spectrum
antioxidant properties. In addition, Emblica is extremely stable
and is not subject to photodegradation. While vitamins C, and E,
and antioxidants from pine bark and rosemary lose over 50% of their
antioxidant activity in an aqueous solution after only three months,
Emblica remains stable for over a year. Research has shown Emblica
to increase skin hydration and skin lipids, to reduce collagenase
activity, to reduce UV-induced erythema, to reduce inflammation
and to help preserve skin tone and integrity.
One of Emblica’s most exciting applications is as a skin
lightener. While most skin lighteners such as Hydroquinone, Arbutin,
and Kojic Acid have toxicity issues or can cause negative reactions
on the skin, Emblica is well tolerated with no side effects. Magnesium
Ascorbyl Phosphate has been the best-tolerated skin lightener up
to this point, however Emblica is more stable and does not generate
pro-oxidant activity.
Skin lightening agents are used to either lighten or depigment
the skin. Skin lighteners are generally used in Europe and the United
States to treat age spots and freckles whereas the Asian market
uses them to change or modify skin color. Excessive pigmentation
of the skin can be caused by UV-radiation, hormonal imbalance, inflammation,
drugs or aging. A number of studies have demonstrated Emblica’s
ability to lighten and even-tone normal, hyper-pigmented and UV-induced
pigmented skin color. In two studies Emblica showed comparable results
to an equal concentration of Hydroquinone for skin lightening with
Hispanic and Asian skin over a nine-week period. Another study showed
Emblica to provide significant lightening of freckle spots after
8 weeks.
Though there has not been a specific study of Emblica’s potential
to normalize the uneven skin tone caused by stretch marks, its ability
to lighten both normal and hyper-pigmented skin is perhaps an indication
that Emblica could also play a role in helping to normalize the
appearance of stretch-marked skin.
As mentioned above, Emblica also possesses exciting photoprotective
properties. Of particular importance is Emblica’s ability
to reduce collagenase activity (a protein that attacks the dermis),
which is increased by UV light. Collagenase is one of the key factors
in aging of the skin.
Another extremely important feature of Emblica is that it can chelate
iron and copper.
While iron and copper are necessary for many biological activities,
their toxicity threatens cellular integrity. Emblica seems a particularly
good ingredient to add to sun protection products, as it is clear
that UV radiation causes the release of iron in skin firbroblasts
and that sun-damaged skin contains significantly higher levels of
iron.
While antioxidants are the chief defense against free radical damage,
vitamins C and E as well as glutathione all function as pro-oxidants
when in the presence of iron and copper, causing additional oxidative
stress. Emblica may play an increasing role in UV protective products
because it can help reduce oxidative stress by scavenging free radicals
while simultaneously chelating iron and copper, stopping their harmful
effects.
Emblica is extremely well tolerated with no adverse side effects.
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Palmitoyl
Pentapeptide-3
Palmitoyl Pentapeptide-3 is a synthetic protein that is a fragment
of the C-terminal portion of collagen I (the most common type of
the nineteen forms of collagen) combined with palmitic acid to make
it more lipophillic, to improve its stability and to enhance its
affinity towards human skin. One could look at Palmitoyl Pentapeptide-3
as a man-made precursor to collagen I. When this protein is added
to cultured human fibroblasts it enhances the synthesis of collagen
I, collagen III and fibronectin.
The research behind Palmitoyl Pentapeptide-3 was begun to find
specific solutions to address aging factors in the skin, particularly
the thinning of the sinusoidal layer between the dermis and the
epidermis. The goal was to find a short peptide that would stimulate
fibroblasts in the skin to produce key components of the extra-cellular
matrix such as collagen and hyaluronic acid. The reasons for this
follow.
As we age, the skin gets thinner. Part of this process is that
the sinusoidal dermo-epidermal interface layer between the dermis
and the epidermis gets flatter. It is this layer that allows nutrients
to flow from the dermis to the epidermis. As we age this layer gets
flatter and this reduces the area of exchange interface between
the dermis and the epidermis. This can significantly affect the
quality of the epidermis. The loss of adhesion between these two
structures, which is normally provided by collagen IV and collagen
VII, results in nutritional exchange deficiencies and a slowing
of biological processes in the skin.
Collagen is the main constituent of the skin’s extra-cellular
matrix. In fact, collagen as a whole makes up approximately 25%
of all protein found in the human body. In young skin, the collagen
fibers are held in place by orderly bonds, to form a sort of net.
The “holes” of this net are filled by proteoglycans
and glycosaminoglycans forming the glycan network. The glycan network
is a water-saturated gel in which water-soluble molecules and ions
are able to circulate. It is this water that gives skin its visco-elasticity
and its turgidity. A key molecule in this process is hyaluronic
acid, as it can hold up to 1000 times its weight in water. A reduction
in the quantity of interstitial glycans (including hyaluronic acid)
leads to a loss of water retention and the glycan network collapses
onto itself. With age, this gel tends to sag, hindering cell migration
and mitosis. As the number of fibroblasts, mastocytes and blood
vessels falls, the dermis atrophies.
Studies were carried out to see if Palmitoyl Pentapeptide-3 would
affect the sinusoidal dermo-epidermal interface layer and if it
would help to stimulate factors making up the glycan network. As
mentioned above, collagen IV and collagen VII are the primary constituents
of the sinusoidal dermo-epidermal interface layer between the dermis
and the epidermis that allows nutrients to flow from the dermis
to the epidermis. In vitro, Palmitoyl Pentapeptide-3 was found to
stimulate collagen IV synthesis by 100-327% and to stimulate hyaluronic
acid synthesis by 267%. In vivo Palmitoyl Pentapeptide-3 was found
to stimulate collagen synthesis by 30-117%. The next step was to
use image analysis to determine the affect Palmitoyl Pentapeptide-3
had on wrinkled skin. The six-month results are listed below, though
significant results were seen in two months.
Results
Mean wrinkle depth -- Reduced 17%
Surface area – deep wrinkles -- Reduced 68%
Surface area – moderate wrinkles -- Reduced 51%
Mean density of wrinkled area -- Reduced 47%
Skin roughness -- Reduced 16%
Main wrinkle volume -- Reduced 24%
These results show that Palmitoyl Pentapeptide-3 had a dramatic
effect on reducing the quantity and depth of wrinkles. It also improved
surface smoothness. The studies behind Palmitoyl Pentapeptide-3
give a clear description of the mechanism for how this is accomplished
and also indicate that Palmitoyl Pentapeptide-3 is stimulating natural
biological processes to reverse the aging process of the skin. In
addition, Palmitoyl Pentapeptide-3 is very well tolerated by the
skin. Palmitoyl Pentapeptide-3 is a very exciting ingredient and
is becoming more and more popular as its results are becoming more
widely known.
Biopeptide-CL
Like Palmitoyl Pentapeptide-3, Biopeptide-CL is a synthetic protein
that is a fragment of collagen combined with palmitic acid to make
it more lipophillic, to improve its stability and to enhance its
affinity towards human skin. As with Palmitoyl Pentapeptide-3, one
could look at Biopeptide-CL as a man-made precursor to collagen.
Biopeptide-CL was developed through research to identify a substance
that would behave similarly to retinoic acid but without its drawbacks,
especially in regards to synthesizing collagen.
The reported results are as follows:
In vitro:
Increases collagen production by the fibroblasts by as much as 350%.
Increases hyaluronic acid production by the fibroblasts by as much
as 146%.
In vivo:
The following statistics were gathered using image analysis of
volunteers who used crèmes containing a 3% concentration
of Biopeptide-CL for 28 days.
Surface roughness -- Reduced 17%
Mean depth of wrinkles -- Reduced 23%
Depth of main wrinkle -- Reduced 39%
Skin thickness -- Increased 4%
The increase in skin thickness was considered especially notable
and contrasts with the 6% reduction of the skin thickness that occurs
after 10 years of aging. The study concludes to state that Biopeptide-CL
is a potent active cosmetic ingredient without the adverse effects
(including irritation, dehydration or long-term toxicity and instability)
characteristic of retinoids.
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Palmitoyl
Tetrapeptide-3
Palmitoyl Tetrapeptide-3 is a synthetic peptide
that is a fragment of immunoglobulin G that has been combined with
palmitic acid to make it more lipophillic and thus enhance its affinity
towards human skin. Palmitoyl Tetrapeptide-3 was discovered through
research to learn how to suppress the body’s production of
interleukins, particularly IL6, since these are the chemical messengers
that trigger the body’s acute inflammatory response.
Inflammation is a function of immunity and is a protective response
to injury or destruction of tissue. This is the body’s way
of walling off the injurious agent and the injured tissue. Under
normal circumstances, very little IL6 is secreted and its secretion
is strictly controlled. However, as we age this regulation system
develops defects, and significant levels of IL6 appear in the plasma
even when there is no inflammatory stimulus. This results in high
levels of inflammatory proteins in the tissues and a loss of healing
potential. This process has been linked with breast cancer, osteoporosis,
anemia, autoimmunity and slower tissue regeneration.
The hormone DHEA is directly responsible for maintaining the regulation
of the production of IL6. This has even been demonstrated in the
skin: when DHEA is present in sufficient amounts it is converted
into a steroid hormone, androstenediol, which is directly responsible
for maintaining IL6 production and for maintaining local homeostasis
of cytokine and interleukin production. As we age, DHEA is reduced
and this directly leads to cytokine deregulation and the over-production
of some interleukins and the under production of others. As mentioned
above, IL6 production is increased with negative consequences. Since
UV radiation can increase IL6 production by five times, this process
can significantly impact the skin.
The researchers’ goal thus became to find a peptide that
would mimic the effects of DHEA without DHEA’s potential for
being converted into estrogen, since estrogen is a hormone that
is not licensed for cosmetic purposes. Specifically they wanted
to find a peptide that would target IL6 and inhibit its production.
The results:
1.) At concentrations from 10 ppm, Palmitoyl Tetrapeptide-3 induces
a marked reduction in the secretion of the cytokine IL6. This reduction
is progressive and depends on the concentration of the peptide:
baseline secretion may be inhibited by up to 40%.
2.) Palmitoyl Tetrapeptide-3 reduced levels of IL6 after cells
were exposed to UV radiation by up to 86% even though IL6 had been
increased by about 20 fold by the UV.
These results show that Palmitoyl Tetrapeptide-3 is able to affect
baseline levels of IL6 as well as modulate the effects of UV-stimulated
over-production of IL6. IL6 is marketed by Sederma as a molecule
that can restore cytokine equilibrium, which characterizes youthful
skin. Cosmedical Aesthetics has chosen to use Palmitoyl Tetrapeptide-3as
a synergistic support ingredient to create a more optimum environment
for other active ingredients to help restore youthful skin appearance.
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Acetyl
Hexapeptide-3(Argelline)
Acetyl Hexapeptide-3 is used in our formulationsas a wrinkle
reducer and as alternative to injections. It is also an effective
wrinkle preventive.
Acetyl Hexapeptide-3 is a mimic of the N-terminal end of SNAP-25,
one of three proteins (known as the SNARE complex) that are essential
for neurotransmitter release at the synapse, which is the chemical
signal for a muscle to contract.
As a wrinkle reducer, studies have shown that Acetyl Hexapeptide-3
at a 10% concentration was able to significantly decrease the depth
of wrinkles after 30 days of treatment. The mechanism by which Acetyl
Hexapeptide-3 is able to accomplish this is related to the ways
in which Acetyl Hexapeptide-3 is able to assist wrinkle prevention.
Acetyl Hexapeptide-3 performs this activity in two distinct ways:
The first way Acetyl Hexapeptide-3 acts as a wrinkle prevenyive
is by competing with SNAP-25 for a position in the SNARE complex.
This destabilizes the SNARE complex, preventing the vesicle from
releasing neurotransmitters efficiently, and therefore attenuating
muscle contraction. This causes a reduction in facial muscle contraction,
which is believed to help prevent the long-term formation of lines
and wrinkles.
The second way that Acetyl Hexapeptide-3 acts as a wrinkle preventive
is by reducing the release of catecholamines the overproduction
of which is known to induce the formation of wrinkles and fine lines
in the skin).
Acetyl Hexapeptide-3 is non-toxic and well tolerated by the skin.
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Scientific
rationale for alpha lipoic acid (ALA) as a skin anti-aging agent
The scientific evidence cited below demonstrates why topical and
dietary alpha lipoic acid (ALA) is effective for reducing oxidation/inflammation
in human and animal skin. Both delivery methods (oral and topical)
make good scientific sense as a safe way to reduce oxidation/inflammation
in the skin, which most researchers agree to be a primary cause
of wrinkles.
Current research reveals four things about topical and supplemental
use of ALA:
ALA is shown to protect skin against free radicals and inflammation
in the skin.
Meewes C, Brenneisen P, Wenk J, Kuhr L, Ma W, Alikoski J, Poswig
A, Krieg T, Scharffetter- Kochanek K. Adaptive antioxidant response
protects dermal fibroblasts from UVA-induced phototoxicity. Free
Radic Biol Med. 2001 Feb 1;30(3):238-47.
Pertinent Excerpt: "Here we report that, in addition to the
previously published induction of manganese superoxide dismutase
(MnSOD) activity, single and, to a higher extent, repetitive low-dose
UVA irradiation also leads to a substantial upregulation of glutathione
peroxidase (GPx) activity. .... Collectively, these data indicate
that the concomitant induction of MnSOD and GPx activity is related
to the optimal adaptive protection from photooxidative damage."
[Note: This finding supports the importance of ALA as a recycler
of MnSOD and GPx in protecting skin against oxidative stress.]
Taborda V, Baumann L. A randomized, double-blind, placebo-controlled
trial of alpha-lipoic acid cream in facial aging skin. Lauro de
Souza Lima Institute & University of Miami.
http://www.dermato.med.br/iacd/congress/papers/papers-b.htm
Pertinent Excerpt: "Alpha lipoic acid (ALA) has been proposed
as a new antioxidant agent to treat and prevent aging skin. In order
to evaluate the effectiveness of topical application of alpha-lipoic
acid cream to the face as an adjunct therapy in the management of
aging skin, the authors compared the application of topical alpha-lipoic
acid cream on the face with a placebo cream and with glycolic acid.
Pertinent Excerpt: "In summary, alpha lipoic acid is a potent
antioxidant which represents a promising option in the treatment
of aging skin and, therefore, should achieve maximum importance
in our future cosmetics practice."
ALA reduces (i.e., recycles to full potency) oxidized glutathione,
vitamin E, and ascorbatethe body's other key antioxidantsand it
boosts the cell's ability to synthesize glutathione. This provides
the bodyincluding its largest organ-an enhanced antioxidant network
with which to reduce ROS and inflammation in the skin.
Han D, Handelman G, Marcocci L, Sen CK, Roy S, Kobuchi H, Tritschler
HJ, Flohe L, Packer L. Lipoic acid increases de novo synthesis of
cellular glutathione by improving cystine utilization. Biofactors.
1997;6(3):321-38.
Podda M, Tritschler HJ, Ulrich H, Packer L. Alpha-lipoic acid supplementation
prevents symptoms of vitamin E deficiency. Biochem Biophys Res Commun.
1994 Oct 14;204(1):98- 104.
Packer L, Witt EH, Tritschler HJ alpha-Lipoic acid as a biological
antioxidant. Free Radic Biol Med. 1995 Aug;19(2):227-50. Review.
ALA possesses the ability to block protein glycationa key factor
in skin aging, due to the protein cross-linking and free radicals
it produces. ALA produces an indirect antioxidant effect in this
context, since the glycation bond generates free radicals continuously.
In addition, ALA increases cellular glucose uptake through recruitment
of the glucose transporter-4 to plasma membranes, thus reducing
the amount of free glucose available for glycation reactions.
Podda M, Zollner TM, Grundmann-Kollmann M, Thiele JJ, Packer L,
Kaufmann R. Activity of alpha-lipoic acid in the protection against
oxidative stress in skin. Curr Probl Dermatol. 2001;29:43-51.
Bierhaus A, et al. Advanced glycation end product-induced activation
of NF-kappaB is suppressed by alpha-lipoic acid in cultured endothelial
cells. Diabetes. 1997 Sep;46(9):1481- 90.
Kunt T, et al. Alpha-lipoic acid reduces expression of vascular
cell adhesion molecule-1 and endothelial adhesion of human monocytes
after stimulation with advanced glycation end products. Clin Sci
(Lond). 1999 Jan;96(1):75-82.
Melhem MF, Craven PA, Liachenko J, DeRubertis FR. alpha-Lipoic Acid
Attenuates Hyperglycemia and Prevents Glomerular Mesangial Matrix
Expansion in Diabetes. J Am Soc Nephrol. 2002 Jan;13(1):108-16.
ALA blocks key inflammation signals in body cells. As people age,
cumulative damage by free radicals lowers the activation thresholds
of redox-modulated transcription factors. The system that activates
genes deteriorates, producing inflammation, immunosenescence, cancer,
and degenerative disease. Alpha lipoic acid, (ALA) has special properties
and functions within the antioxidant network that contribute to
its impressive anti-aging properties. ALA helps control inflammation
by regulating the redox-sensitive nuclear transcription factors
known as Activator Protein 1 (AP-1) and Nuclear Factor kappa-B (NF-jB).
Meyer M, Pahl HL, Baeuerle PA. Regulation of the transcription
factors NF-kappa B and AP-1 by redox changes. Chem Biol Interact.
1994 Jun;91(2-3):91-100.
Packer L, Roy S, Sen CK. a-Lipoic acid: a metabolic antioxidant
and potential redox modulator of transcription. Advances in Pharmacology
1996; 38: 79-101.
Lavrovsky Y, Chatterjee B, Clark RA, Roy AK. Role of redox-regulated
transcription factors in inflammation, aging and age-related diseases.
Exp Gerontol. 2000 Aug;35(5):521-32. Review.
Pertinent Excerpt: "Chronic oxidative stress and inflammatory
reaction also lead to many age- associated diseases such as atherosclerosis
and arthritis. Transcription factors that are directly influenced
by ROS and proinflammatory cytokines include nuclear factor kappa
B (NF-kappaB), activator protein 1 (AP-1), specificity protein 1
(Sp1), peroxisome proliferator- activated receptors (PPARs) and
other members of the nuclear receptor superfamily."
- Meyer M, Pahl HL, Baeuerle PA. Regulation of the transcription
factors NF-kappa B and AP-1 by redox changes. Chem Biol Interact.
1994 Jun;91(2-3):91-100.
- Meyer M, Schreck R, Baeuerle PA. H2O2 and antioxidants have
opposite effects on activation of NF-kappa B and AP-1 in intact
cells: AP-1 as secondary antioxidant-responsive factor. EMBO J.
1993 May;12(5):2005-15.
- Saliou C, Kitazawa M, McLaughlin L, Yang JP, Lodge JK, Tetsuka
T, Iwasaki K, Cillard J, Okamoto T, Packer L. Antioxidants modulate
acute solar ultraviolet radiation-induced NF- kappa-B activation
in a human keratinocyte cell line. Free Radic Biol Med. 1999 Jan;26(1-
2):174-83.
- Sen CK, Packer L. Antioxidant and redox regulation of gene transcription.
FASEB J. 1996; 10: 709-720.
- Suzuki YJ, Aggarwal BB, Packer L. Alpha-lipoic acid is a potent
inhibitor of NF-kappa B activation in human T cells. Biochem Biophys
Res Commun. 1992 Dec 30;189(3):1709-15.
- Suzuki YJ, Mizuno M, Tritschler HJ, Packer L. Redox regulation
of NF-kappa B DNA binding activity by dihydrolipoate. Biochem
Mol Biol Int. 1995 Jun;36(2):241-6.
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Clinical evidence
for the anti-aging effects of topical DMAE
The natural bodily compound known as DMAE is a probable precursor
to the neurotransmitter acetycholine, responsible for maintaining
muscle tone. This is one reason why DMAE is a key topical ingredient
in my program. (It also enhances the skin penetration of alpha lipoic
acid and other ingredients.)
The efficacy of DMAE in improving skin tone and firmnessand the
long-term safety of topical DMAEwere confirmed in two clinical
studies by researchers at the Johnson & Johnson company (see
"Cole AC, Gisoldi EM, Grossman RM," below). Their positive
findings, including before and after photos, were presented at a
scientific conference (American Academy of Dermatology, Feb. 22-26,
2002, New Orleans), and were confirmed in 2002 by researchers at
the University Medical Center of Liege, Belgium (see "Uhoda
I," below).
Cole AC, Gisoldi EM, Grossman RM. Clinical and consumer evaluations
of improved facial appearance after 1 month use of topical dimethylaminoethanol.
Poster presentation, American Academy of Dermatology, Feb. 22-26,
2002, New Orleans USA.
Grossman RM, Gisoldi EM, Cole AC. Long term safety and efficacy
evaluation of a new skin firming technology: dimethylaminoethanol.
Poster presentation, American Academy of Dermatology, Feb. 22-26,
2002, New Orleans USA.
Uhoda I, Faska N, Robert C, Cauwenbergh G, Pierard GE. Split face
study on the cutaneous tensile effect of 2-dimethylaminoethanol
(deanol) gel. Skin Res Technol. 2002 Aug;8(3):164-7.
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Laboratory
evidence for the anti-aging effects of topical antioxidants
Laboratory evidence for topical vitamin C and vitamin C
ester
The plain vitamin C found in foods (and used in most vitamin-infused
cosmetics) is called ascorbic acid. Vitamin C ester is a term describing
any of the uncommon, fat-soluble forms of vitamin C, such as ascorbyl
palmitatethe vitamin C ester used in N.V. Perricone, M.D. Cosmeceuticals
products-or acylated ascorbate.
The majority of published research results suggest that vitamin
C ester offers very substantial advantages over ascorbic acid in
terms of its absorption, potency per gram, and ability to stimulate
repair of skin structures (collagen).
Note: In the only peer-reviewed human clinical trial published
to date, the proprietary vitamin C dietary supplement known as Ester-C(r)
(which, despite its name, is not an este) showed no bodily absorption
advantage over ascorbic acid. Nor is there any evidenceor scientific
reason to supposethat it is superior to ascorbic acid or true vitamin
C esters as a topical antioxidant.
Rosenblat G, et al. Acylated ascorbate stimulates collagen synthesis
in cultured human foreskin fibroblasts at lower doses than does
ascorbic acid. Connect Tissue Res. 1998;37(3- 4):303-11.
Pertinent Excerpt: "Cells treated with 10 microM palmitoyl
ascorbate for 36 h exhibited a production of collagen threefold
greater than those in the presence of 10 microM ascorbic acid, and
it was about the same as in cells treated with 100 microM ascorbic
acid."
Rosenblat G, Willey A, Zhu YN, Jonas A, Diegelmann RF, Neeman I,
Graham MF. Palmitoyl ascorbate: selective augmentation of procollagen
mRNA expression compared with L- ascorbate in human intestinal smooth
muscle cells. J Cell Biochem 1999 Jun 1;73(3):312- 20.
Pertinent Excerpt: "Palmitoyl ascorbate augments HISM cell
procollagen synthesis and mRNA levels more efficiently than L-ascorbate.
This property may be due to the greater resistance of the ascorbate
ester to oxidation and suggests that palmitoyl ascorbate could be
an important agent for studies of collagen synthesis in vitro."
Ross D, Mendiratta S, Qu ZC, Cobb CE, May JM. Ascorbate 6-palmitate
protects human erythrocytes from oxidative damage. Free Radic Biol
Med. 1999 Jan;26(1-2):81-9.
Pertinent Excerpt: "These results show that an amphipathic
ascorbate derivative is retained on the exterior cell surface of
human erythrocytes, where it helps to protect the membrane from
oxidant damage originating outside the cells."
Perricone N, Nagy K, Horvath F, Dajko G, Uray I, Zs-Nagy I. The
hydroxyl free radical reactions of ascorbyl palmitate as measured
in various in vitro models. Biochem Biophys Res Commun. 1999 Sep
7;262(3):661-5.
Pertinent Excerpt: "AP [ascorbyl palmitate] inhibits carbonyl
formation very efficiently, indicating that AP may be utilized as
a biological OH(*) free radical scavenger in human therapy."
Tebbe B, Wu S, Geilen CC, Eberle J, Kodelja V, Orfanos CE. L-ascorbic
acid inhibits UVA- induced lipid peroxidation and secretion of IL-1alpha
and IL-6 in cultured human keratinocytes in vitro. J Invest Dermatol.
1997 Mar;108(3):302-6.
Pertinent Excerpt: "These findings indicate a major cell-protective
effect of L-ascorbic acid on UVA-induced lipid peroxidation and
the secretion of pro-inflammatory cytokines by UVA- irradiated human
keratinocytes [skin protein cells]."
Lin JY, Selim MA, Shea CR, Grichnik JM, Omar MM, Monteiro-Riviere
NA, Pinnell SR. UV photoprotection by combination topical antioxidants
vitamin C and vitamin E. J Am Acad Dermatol. 2003 Jun;48(6):866-74.
Pertinent Excerpt: "Appreciable photoprotection can be obtained
from the combination of topical vitamins C and E. We suggest that
these natural products may protect against skin cancer and photoaging."
Laboratory evidence for topical alpha lipoic acid (ALA)
Podda M, Zollner TM, Grundmann-Kollmann M, Thiele JJ, Packer
L, Kaufmann R. Activity of alpha-lipoic acid in the protection against
oxidative stress in skin. Curr Probl Dermatol. 2001;29:43-51.
Pertinent Excerpt: "....based on our in vivo and in vitro studies
we suggest that alpha lipoic acid could be a good candidate antioxidant
for the protection of skin against oxidative damage."
Perricone N, Nagy K, Horvath F, Dajko G, Uray I, Zs-Nagy I. Alpha
lipoic acid (ALA) protects proteins against the hydroxyl free radical-induced
alterations: rationale for its geriatric topical application, Archives
of Gerontology and Geriatrics 29 (1) (1999) pp. 45-56. Author's
Summary: "Two studies were performed to test the effectiveness
of ALA as a topical application to protect proteins, such as the
collagen in human skin. One test used gamma radiation to produce
free radicals in cow-tissue proteins; a second test used a 'Fenton'
reaction caused by the presence of iron to produce free radicals.
The cow protein was protected by the Na-ALA in both cases. Note:
The ALA was modified to make it water soluble, which makes the study
applicable to N.V. Perricone, M.D. Cosmeceutical products.
Pertinent Excerpt: "Na-ALA [water-soluble alpha lipoic acid]
may be considered a potential biologically useful free-radical scavenger
for human therapy, explaining also the beneficial effects of its
topical application against certain age-dependent skin alterations
[i.e., wrinkles]."
Podda M, Rallis M, Traber MG, Packer L, Maibach HI. Kinetic study
of cutaneous and subcutaneous distribution following topical application
of [7,8-14C]rac-alpha-lipoic acid onto hairless mice. Biochem Pharmacol.
1996 Aug 23;52(4):627-33.
Pertinent Excerpt: "In conclusion, alpha-lipoic acid topically
applied to skin penetrated readily, and was reduced to dihydrolipoic
acid. Thus, alpha-lipoic acid could potentiate skin antioxidant
protection."
Laboratory evidence for topical vitamin E
Vitamin E consists of eight related compounds called tocopherols
and tocotrienols, and they are perhaps the key protective antioxidants
occurring naturally in human skin. Topical vitamin E reduces the
damaging effects of ultraviolet radiation, quickly penetrates skin
to the subcutaneous fat layer, helps preserve existing vitamin E
levels in skin cells, and significantly increases vitamin E levels
in the skin. N.V. Perricone, M.D. Cosmeceuticals topical products
employ tocotrienol forms of vitamin E, because they offer superior
antioxidant capacity and penetrate skin tissues very quickly (30
minutes) and deeply (into the subcutaneous layers).
Packer L, Weber SU, Rimbach G. Molecular aspects of alpha-tocotrienol
antioxidant action and cell signalling. J Nutr. 2001 Feb;131(2):369S-73S.
Review.
Pertinent Excerpt: "Tocopherols and tocotrienols are part of
an interlinking set of antioxidant cycles, which has been termed
the antioxidant network. Although the antioxidant activity of tocotrienols
is higher than that of tocopherols, tocotrienols have a lower bioavailability
after oral ingestion. Tocotrienols penetrate rapidly through skin
and efficiently combat oxidative stress induced by UV or ozone."
Ricciarelli R, Maroni P, Ozer N, Zingg JM, Azzi A. Age-dependent
increase of collagenase expression can be reduced by alpha-tocopherol
via protein kinase C inhibition. Free Radic Biol Med. 1999 Oct;27(7-8):729-37.
Pertinent Excerpt: "Our in vitro experiments with skin fibroblasts
suggest that alpha- tocopherol may protect against skin aging by
decreasing the level of collagenase expression, which is induced
by environmental insults and by aging."
Traber MG, Rallis M, Podda M, Weber C, Maibach HI, Packer L. Penetration
and distribution of alpha-tocopherol, alpha- or gamma-tocotrienols
applied individually onto murine skin. Lipids. 1998 Jan;33(1):87-91.
Pertinent Excerpt: " .... the largest fraction of skin vitamin
E following topical application was found in the deeper subcutaneous
layers--the lowest layers, PD (40 +/- 15%) and D (36 +/- 15%), contained
the major portion of the applied vitamin E forms. .... Hence, applied
vitamin E penetrates rapidly through the skin, but the highest concentrations
are found in the uppermost 5 microns."
Traber, MG, Podda M, Weber C, et al. Diet derived topically applied
tocotrienols accumulate in skin and protect the tissue against UV
light-induced oxidative stress. Asia Pacific Journal of Clinical
Nutrition. 1997;6:63-67.
Pertinent Excerpt: "The unique distribution of tocotrienols
in skin suggested that they might have superior protection against
environmental stressors."
Weber C, Podda M, Rallis M, Thiele JJ, Traber MG, Packer L. Efficacy
of topically applied tocopherols and tocotrienols in protection
of murine skin from oxidative damage induced by UV-irradiation.
Free Radic Biol Med. 1997;22(5):761-9.
Pertinent Excerpt: "Thus, UV-irradiation of skin destroys its
antioxidants: however, prior application of TRF [tocotrienols fraction
of vitamin E] to mouse skin results in preservation of vitamin E."
Lin JY, Selim MA, Shea CR, Grichnik JM, Omar MM, Monteiro-Riviere
NA, Pinnell SR. UV photoprotection by combination topical antioxidants
vitamin C and vitamin E. J Am Acad Dermatol. 2003 Jun;48(6):866-74.
Pertinent Excerpt: "Appreciable photoprotection can be obtained
from the combination of topical vitamins C and E. We suggest that
these natural products may protect against skin cancer and photoaging."
Literature review articles on the anti-aging effects of
topical antioxidants
Thiele JJ, Schroeter C, Hsieh SN, Podda M, Packer L. The
antioxidant network of the stratum corneum. Curr Probl Dermatol.
2001;29:26-42. Review.
Pertinent Excerpt: "Taken together, the presented data suggest
that, under conditions of environmentally challenged skin or during
prooxidative dermatological treatment, topical and/or systemic application
of antioxidants could support physiological mechanisms to maintain
or restore a healthy skin barrier. Growing experimental evidence
should lead to the development of more powerful pharmaceutical and
cosmetic strategies involving antioxidant formulations to prevent
UV-induced carcinogenesis and photoaging as well as to modulate
desquamatory skin disorders."
Dreher F, Maibach H. Protective effects of topical antioxidants
in humans. Curr Probl Dermatol. 2001;29:157-64. Review.
Pertinent Excerpt: "Human studies have convincingly demonstrated
pronounced photoprotective effects of 'natural' and synthetic antioxidants
when applied topically before UVR [sun] exposure. .... In conclusion,
regular application of skin care products containing antioxidants
may be of the utmost benefit in efficiently preparing our skin against
exogenous oxidative stressors occurring during daily life."
- Perricone NV. Topical vitamin C ester (ascorbyl palmitate).
Adapted from the first annual symposium on aging skin, San Diego,
CA, February 21-23, 1997. J Geriatric Dermatol 1997; 5(4):162-170.
- Perricone NV. Aging: prevention and intervention part I: Antioxidants.
J Geriatr Dermatol 1997;5(1):1-2.
- Perricone NV. Topical vitamin c ester (ascorbyl palmitate).
Adapted from the first annual symposium on aging skin, San Diego,
CA, February 21-23, 1997. J Geriatric Dermatol 1997; 5(4):162-170.
- Kleinsmith DM, Perricone NV. Common skin problems in the elderly.
Clin Geriatr Med 1989, Feb;5(1):189-211. Review.
- Kleinsmith DM, Perricone NV. Common skin problems in the elderly.
Dermatol Clin. 1986 Jul;4(3):485-99. Review.
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