Life Extension - Age related disease

Skin Aging - updated: 23 February 2009

ASCORBIC ACID

Double-blind, half-face study comparing topical vitamin C and vehicle for rejuvenation of photodamage

Dermatol Surg. 2002 Mar;28(3):231-6

Fitzpatrick RE, Rostan EF.

BACKGROUND: Aging of the population, in particular the "baby boomers," has resulted in increased interest in methods of reversal of photodamage. Non-invasive treatments are in high demand, and our knowledge of mechanisms of photodamage to skin, protection of the skin, and repair of photodamage are becoming more sophisticated and complex. OBJECTIVE: The objective of this study is to determine if the topical use of a vitamin C preparation can stimulate the skin to repair photodamage and result in clinically visible differences, as well as microscopically visible improvement. METHODS: Ten patients applied in a double-blind manner a newly formulated vitamin C complex having 10% ascorbic acid (water soluble) and 7% tetrahexyldecyl ascorbate (lipid soluble) in an anhydrous polysilicone gel base to one-half of the face and the inactive polysilicone gel base to the opposite side. Clincial evaluation of wrinkling, pigmentation, inflammation, and hydration was performed prior to the study and at weeks 4, 8, and 12. Two mm punch biopsies of the lateral cheeks were performed at 12 weeks in four patients and stained with hematoxylin and eosin, as well as in situ hybridization studies using an anti-sense probe for mRNA for type I collagen. A questionnaire was also completed by each patient. RESULTS: A statistically significant improvement of the vitamin C-treated side was seen in the decreased photoaging scores of the cheeks (P = 0.006) and the peri-oral area (P = 0.01). The peri-orbital area improved bilaterally, probably indicating improved hydration. The overall facial improvement of the vitamin C side was statistically significant (P = 0.01). Biopsies showed increased Grenz zone collagen, as well as increased staining for mRNA for type I collagen. No patients were found to have any evidence of inflammation. Hydration was improved bilaterally. Four patients felt that the vitamin C-treated side improved unilaterally. No patient felt the placebo side showed unilateral improvement. CONCLUSION: This formulation of vitamin C results in clinically visible and statistically significant improvement in wrinkling when used topically for 12 weeks. This clinical improvement correlates with biopsy evidence of new collagen formation

Publication Types:

• double-blind

Topical ascorbic acid on photoaged skin. Clinical, topographical and ultrastructural evaluation: double-blind study vs. placebo

Exp Dermatol. 2003 Jun;12(3):237-44

Humbert PG, Haftek M, Creidi P, Lapière C, Nusgens B, Richard A, Schmitt D, Rougier A, Zahouani H.

Vitamin C is known for its antioxidant potential and activity in the collagen biosynthetic pathway. Photoprotective properties of topically applied vitamin C have also been demonstrated, placing this molecule as a potential candidate for use in the prevention and treatment of skin ageing. A topically applied cream containing 5% vitamin C and its excipient were tested on healthy female volunteers presenting with photoaged skin on their low-neck and arms in view to evaluate efficacy and safety of such treatment. A double-blind, randomized trial was performed over a 6-month period, comparing the action of the vitamin C cream vs. excipient on photoaged skin. Clinical assessments included evaluation at the beginning and after 3 and 6 months of daily treatment. They were performed by the investigator and compared with the volunteer self assessment. Skin relief parameters were determined on silicone rubber replicas performed at the same time-points. Cutaneous biopsies were obtained at the end of the trial and investigated using immunohistochemistry and electron microscopy. Clinical examination by a dermatologist as well as self-assessment by the volunteers disclosed a significant improvement, in terms of the 'global score', on the vitamin C-treated side compared with the control. A highly significant increase in the density of skin microrelief and a decrease of the deep furrows were demonstrated. Ultrastructural evidence of the elastic tissue repair was also obtained and well corroborated the favorable results of the clinical and skin surface examinations. Topical application of 5% vitamin C cream was an effective and well-tolerated treatment. It led to a clinically apparent improvement of the photodamaged skin and induced modifications of skin relief and ultrastructure, suggesting a positive influence of topical vitamin C on parameters characteristic for sun-induced skin ageing.

Publication Types:

• double-blind study

Clinical, biometric and structural evaluation of the long-term effects of a topical treatment with ascorbic acid and madecassoside in photoaged human skin

Exp Dermatol. 2008 Nov;17(11):946-52.

Haftek M, Mac-Mary S, Le Bitoux MA, Creidi P, Seité S, Rougier A, Humbert P.

Skin ageing is a complex process determined by the genetic endowment of individual and environmental factors, such as sun exposure. The effects of skin ageing are mostly encountered in the superficial dermis and in the epidermis. We have previously demonstrated in vivo the beneficial effect of a topically applied formula of 5% vitamin C in the treatment of skin ageing. Another active compound, madecassoside extracted from Centella asiatica, known to induce collagen expression and/or to modulate inflammatory mediators, might thus prevent and correct some signs of ageing. A randomized double-blind study was carried out on photoaged skin of 20 female volunteers to investigate the effects of topically applied 5% vitamin C and 0.1% madecassoside on the clinical, biophysical and structural skin properties. After 6 months of treatment, we observed a significant improvement of the clinical score for deep and superficial wrinkles, suppleness, firmness, roughness and skin hydration. These results were corroborated by measurements of skin elasticity and semi-quantitative histological assessment of the elastic fibre network in the papillary dermis. Two-thirds of the subjects showed an improvement. The re-appearance of a normally structured elastic fibre network was observed. Our results revealed a functional and structural remodelling of chronically sun-damaged skin.

Publication Types:

• Randomized Controlled Trial

Topical ascorbic acid on photoaged skin. Clinical, topographical and ultrastructural evaluation: double-blind study vs. placebo

Exp Dermatol. 2003 Jun;12(3):237-44

Humbert PG, Haftek M, Creidi P, Lapière C, Nusgens B, Richard A, Schmitt D, Rougier A, Zahouani H.

Vitamin C is known for its antioxidant potential and activity in the collagen biosynthetic pathway. Photoprotective properties of topically applied vitamin C have also been demonstrated, placing this molecule as a potential candidate for use in the prevention and treatment of skin ageing. A topically applied cream containing 5% vitamin C and its excipient were tested on healthy female volunteers presenting with photoaged skin on their low-neck and arms in view to evaluate efficacy and safety of such treatment. A double-blind, randomized trial was performed over a 6-month period, comparing the action of the vitamin C cream vs. excipient on photoaged skin. Clinical assessments included evaluation at the beginning and after 3 and 6 months of daily treatment. They were performed by the investigator and compared with the volunteer self assessment. Skin relief parameters were determined on silicone rubber replicas performed at the same time-points. Cutaneous biopsies were obtained at the end of the trial and investigated using immunohistochemistry and electron microscopy. Clinical examination by a dermatologist as well as self-assessment by the volunteers disclosed a significant improvement, in terms of the 'global score', on the vitamin C-treated side compared with the control. A highly significant increase in the density of skin microrelief and a decrease of the deep furrows were demonstrated. Ultrastructural evidence of the elastic tissue repair was also obtained and well corroborated the favorable results of the clinical and skin surface examinations. Topical application of 5% vitamin C cream was an effective and well-tolerated treatment. It led to a clinically apparent improvement of the photodamaged skin and induced modifications of skin relief and ultrastructure, suggesting a positive influence of topical vitamin C on parameters characteristic for sun-induced skin ageing.

Publication Types:

• Randomized Controlled Trial

Use of topical ascorbic acid and its effects on photodamaged skin topography

Arch Otolaryngol Head Neck Surg. 1999 Oct;125(10):1091-8

Traikovich SS.

OBJECTIVE: To determine the efficacy of topical ascorbic acid application in treating mild to moderate photodamage of facial skin using an objective, computer-assisted image analysis of skin surface topography and subjective clinical, photographic, and patient self-appraisal questionnaires. DESIGN: A 3-month, randomized, double-blind, vehicle-controlled study. SETTING: Facial plastic surgery private practice. PATIENTS: Nineteen evaluable volunteer sample patients aged between 36 and 72 years with Fitzpatrick skin types I, II, and III who were in good physical and mental health with mild to moderately photodamaged facial skin were considered for analysis. INTERVENTION: Coded, unmarked medications were randomly assigned to the left and right sides of each subject's face, one containing the active agent, topical ascorbic acid (Cellex-C high-potency serum; Cellex-C International, Toronto, Ontario), the other, the vehicle serum (Cellex-C International). Three drops (0.5 mL) of each formulation were applied daily to the randomly assigned hemifaces over the 3-month study period. Treatment assignments were not disclosed to subjects, clinicians, or personnel involved in analyzing skin replicas. MAIN OUTCOME MEASURES: Specific clinical parameters were evaluated and graded on a 0- to 9-point scale (0, none; 1-3, mild; 4-6, moderate; and 7-9, severe). Reference photographs were used to standardize grading criteria. Overall investigator scores were compared with baseline and graded as excellent (much improved), good (improved), fair (slightly improved), no change, or worse. Patient self-appraisal questionnaires rated the degree of improvement (much improved, improved, slightly improved, no change, or worse) and reported adverse effects (burning, stinging, redness, peeling, dryness, discoloration, itching, and rash). Standard photographs were taken at baseline, including anteroposterior and left and right oblique views to facilitate subsequent clinical evaluations, and at the end of therapy for comparison. Optical profilometry analysis was performed on the skin surface replicas of the lateral canthal (crow's feet) region, comparing baseline to end-of-study specimens. Using this computer-based system, the resulting image was digitally analyzed, and numeric values were assigned to reflect surface features. The parameters obtained included Rz, Ra, and shadows. These values provided objective data that document pretreatment and posttreatment texture changes proportional to the degree of wrinkling, roughness, and other surface irregularities. RESULTS: Optical profilometry image analysis demonstrated a statistically significant 73.7% improvement in the Ra and shadows north-south facial axis values with active treatment greater than vehicle control, as well as a trend for improvement in the Rz north-south facial axis parameter, showing a 68.4% greater improvement of active treatment vs vehicle control. Clinical assessment demonstrated significant improvement with active treatment greater than control for fine wrinkling, tactile roughness, coarse rhytids, skin laxity/tone, sallowness/yellowing, and overall features. Patient questionnaire results demonstrated statistically significant improvement overall, active treatment 84.2% greater than control. Photographic assessment demonstrated significant improvement, active treatment 57.9% greater than control. CONCLUSIONS: A 3-month daily regimen of topical ascorbic acid provided objective and subjective improvement in photodamaged facial skin. Skin replica optical profilometry is an objective method for quantification of the skin surface texture changes.

Publication Types:

• 3-month, randomized, double-blind

RESVERATROL

Anti-aging properties of resveratrol: review and report of a potent new antioxidant skin care formulation

J Cosmet Dermatol. 2008 Mar;7(1):2-7

Baxter RA.

Resveratrol, an antioxidant polyphenol from red wine, has been the subject of intense interest in recent years due to a range of unique anti-aging properties. These include cardiovascular benefits via increased nitric oxide production, down-regulation of vasoactive peptides, lowered levels of oxidized low-density lipoprotein, and cyclooxygenase inhibition; possible benefits on Alzheimer's disease by breakdown of beta-amyloid and direct effects on neural tissues; phytohormonal actions; anticancer properties via modulation of signal transduction, which translates into anti-initiation, antipromotion, and antiprogression effects; antimicrobial effects; and sirtuin activation, which is believed to be involved in the caloric restriction-longevity effect. Here we report a resveratrol-based skin care formulation, with 17 times greater antioxidant activity than idebenone. The role of resveratrol in prevention of photoaging is reviewed and compared with other antioxidants used in skin care products.

Publication Types:

• Review

Resveratrol imparts photoprotection of normal cells and enhances the efficacy of radiation therapy in cancer cells

Photochem Photobiol. 2008 Mar-Apr;84(2):415-21

Reagan-Shaw S, Mukhtar H, Ahmad N.

Solar radiation spans a whole range of electromagnetic spectrum including UV radiation, which are potentially harmful to normal cells as well as ionizing radiations which are therapeutically beneficial towards the killing of cancer cells. UV radiation is an established cause of a majority of skin cancers as well as precancerous conditions such as actinic keratosis. However, despite efforts to educate people about the use of sunscreens and protective clothing as preventive strategies, the incidence of skin cancer and other skin-related disorders are on the rise. This has generated an enormous interest towards finding alternative approaches for management of UV-mediated damages. Chemoprevention via nontoxic agents, especially botanical antioxidants, is one such approach that is being considered as a plausible strategy for prevention of photodamages including photocarcinogenesis. In this review, we have discussed the photoprotective effects of resveratrol, an antioxidant found in grapes and red wine, against UVB exposure-mediated damages in vitro and in vivo. In addition, we have also discussed studies showing that resveratrol can act as a sensitizer to enhance the therapeutic effects of ionizing radiation against cancer cells. Based on available literature, we suggest that resveratrol may be useful for (1) prevention of UVB-mediated damages including skin cancer and (2) enhancing the response of radiation therapies against hyperproliferative, precancerous and neoplastic conditions.

Publication Types:

• Review

DMAE

The role of dimethylaminoethanol in cosmetic dermatology

Am J Clin Dermatol. 2005;6(1):39-47

Grossman R.

Skincare formulations for the improvement of aging skin are increasingly important consumer products. Here, we review available data on one such agent - 2-dimethylaminoethanol (DMAE) or deanol - that has recently been evaluated in a placebo-controlled trial. DMAE is an analog of the B vitamin choline and is a precursor of acetylcholine. Although the role of acetylcholine as a neurotransmitter is well known, growing evidence points to acetylcholine as a ubiquitous cytokine-like molecule that regulates basic cellular processes such as proliferation, differentiation, locomotion, and secretion in a paracrine and autocrine fashion. Indeed, this modulatory role may contribute to the cutaneous activity of DMAE.In a randomized clinical study, 3% DMAE facial gel applied daily for 16 weeks has been shown to be safe and efficacious (p < 0.05) in the mitigation of forehead lines and periorbital fine wrinkles, and in improving lip shape and fullness and the overall appearance of aging skin. These effects did not regress during a 2-week cessation of application. Beneficial trends (p > 0.05 but

Publication Types:

• Review

The antiwrinkle effect of topical concentrated 2-dimethylaminoethanol involves a vacuolar cytopathology

Br J Dermatol. 2007 Mar;156(3):433-9

Br J Dermatol. 2007 Mar;156(3):433-9

BACKGROUND: The 'cosmeceutical' agent 2-dimethylaminoethanol (DMAE) is a tertiary amine found in high concentration in numerous topical antiwrinkle preparations. OBJECTIVES: We hypothesized that a 337 mmol L(-1) (3%) DMAE reservoir applied to the skin could reproduce the cytopathology induced by other amines by maintaining a millimolar drug concentration within a certain depth of the skin layers, and that vacuolar cell expansion could account for the very rapid effect on the apparent skin fullness. METHODS: Morphological and functional assays were applied to cultured rabbit dermal fibroblasts treated with tertiary amines in vitro. A morphological verification of the vacuolization caused by topical DMAE was also attempted in vivo using the inner skin of the rabbit ear and in vitro using primary cultures of human cutaneous epithelial cells. RESULTS: Fibroblasts responded to DMAE (2.5-10 mmol L(-1)) by massive vacuolization (0.5-4 h; phase contrast observations). Triethanolamine, another chemical frequently used topically, was also active in this respect (10 mmol L(-1)). The vacuolar adenosine triphosphatase inhibitor bafilomycin A1 prevented DMAE- or triethanolamine-induced vacuolization; adding bafilomycin A1 or cell washout slowly reversed the established vacuolization induced by DMAE. Further effects of DMAE in cultured fibroblasts included a moderate cytotoxicity (10 mmol L(-1)) that was abated by bafilomycin A1 cotreatment, a concentration-dependent mitotic arrest (2.5 mmol L(-1)) and transient and mild effects on cell ploidy. The epidermis of the rabbit external ear was significantly thickened and exhibited clear perinuclear swelling indicative of vacuolization in response to 3% DMAE (1 h; paraffin tissue sections). Cultured human cutaneous epithelial cells responded to DMAE by vacuolization (inhibited by bafilomycin A1 cotreatment). CONCLUSIONS: The vacuolar cytopathology induced by concentrated organic amines may be the cellular basis of the antiwrinkle effect of DMAE.

Publication Types:

• Laboratory Test

Split face study on the cutaneous tensile effect of 2-dimethylaminoethanol (deanol) gel

Skin Res Technol. 2002 Aug;8(3):164-7

Uhoda I, Faska N, Robert C, Cauwenbergh G, Piérard GE.

BACKGROUND/AIMS: Beyond subjective assessments, the effect of skin tensors is difficult to assess. The present 2-phase randomized double-blind split face study was designed to compare the effect of a gel containing 3% 2-dimethylaminoethanol (deanol, DMAE) with the same formulation without DMAE. METHODS: In a first pilot study, sensorial assessments and measures of the skin distension under suction were performed in eight volunteers. In a second study conducted in 30 volunteers, shear wave propagation was measured. RESULTS: Large interindividual variations precluded any significant finding in the first study. The DMAE formulation showed, however, a significant effect characterized by increased shear wave velocity in the direction where the mechanical anisotropy of skin showed looseness. CONCLUSION: The DMAE formulation under investigation increased skin firmness.

Publication Types:

• 2-phase randomized double-blind

ANTIOXIDANTS

Photoprotection of UV-irradiated human skin: an antioxidative combination of vitamins E and C, carotenoids, selenium and proanthocyanidins

Skin Pharmacol Appl Skin Physiol. 2002 Sep-Oct;15(5):307-15

Greul AK, Grundmann JU, Heinrich F, Pfitzner I, Bernhardt J, Ambach A, Biesalski HK, Gollnick H.

Endogenous antioxidants are decreased in skin and blood during UV exposure. Combined supplementation of beta-carotene, alpha-tocopherol and ascorbic acid in addition to topical sunscreens may help to lower the risk of sunburning. Acute UV erythema with sunburn reaction are the most important factors in conjunction with the cumulative life-long UV dose for inducing skin damage resulting in photoageing and precancerous and cancerous lesions. Therefore, a clinical, randomized, double-blind, parallel group, placebo-controlled study was conducted in healthy young female volunteers (skin type II) investigating the preventive, photoprotective effect of supplementation with Seresis, an antioxidative combination containing both lipid and water-soluble compounds: carotenoids (beta-carotene and lycopene), vitamins C and E, selenium and proanthocyanidins. In this study, the oral administration of Seresis appeared to be well tolerated. The preparation contains antioxidant compounds in quantities occurring at physiological levels and can therefore be used safely over a long period of time. Despite the fact that the assessment of the light sensitivity (minimal erythemal dose, chromametry) of the skin did not show any statistically significant differences between the Seresis and the placebo group, a clear statistical trend, however, could be demonstrated, i.e. Seresis was able to slow down the time of the development and grade of UVB-induced erythema. The primary efficacy parameter matrix metalloproteinases 1 (MMP-1) between treatment and placebo group following UV irradiation showed a significant difference (p < 0.05), which occurred due to the fact that after a 2-week UV irradiation, MMP-1 slightly increased (p < 0.03) in the placebo group and decreased (p < 0.044) in the treated group. The MMP-9 changes showed a clear tendency of decrease in the Seresis group (p < 1.393) and increase (p < 0.048) in the placebo group. These data emphasise that supplementation with Seresis decreases the UV-induced expression of MMP-1 and 9, which might be important in photoprotective processes. From our data, we thus finally draw the conclusion that by the combination of antioxidants, such as in the formulation of Seresis, a selective protection of the skin against irradiation can be achieved. This might be important for future recommendations for immediate suppression of the early phase of UV-induced erythema, that means pharmacological prevention of sunburn reaction as well as subsequent chronic skin damage.

Publication Types:

• Review

GREEN TEA

Green tea and the skin

J Am Acad Dermatol. 2005 Jun;52(6):1049-59

Hsu S.

Plant extracts have been widely used as topical applications for wound-healing, anti-aging, and disease treatments. Examples of these include ginkgo biloba, echinacea, ginseng, grape seed, green tea, lemon, lavender, rosemary, thuja, sarsaparilla, soy, prickly pear, sagebrush, jojoba, aloe vera, allantoin, feverwort, bloodroot, apache plume, and papaya. These plants share a common character: they all produce flavonoid compounds with phenolic structures. These phytochemicals are highly reactive with other compounds, such as reactive oxygen species and biologic macromolecules, to neutralize free radicals or initiate biological effects. A short list of phenolic phytochemicals with promising properties to benefit human health includes a group of polyphenol compounds, called catechins, found in green tea. This article summarizes the findings of studies using green tea polyphenols as chemopreventive, natural healing, and anti-aging agents for human skin, and discusses possible mechanisms of action

Publication Types:

• Review

Consumption of functional fermented milk containing borage oil, green tea and vitamin E enhances skin barrier function

Exp Dermatol. 2008 Aug;17(8):668-74

Puch F, Samson-Villeger S, Guyonnet D, Blachon JL, Rawlings AV, Lassel T.

As emerging studies show that skin functioning can be improved with orally imbibed ingredients, we decided to investigate a mixture of borage oil, catechins, vitamin E and probiotics, all known for their reported effects on epidermal function, in a fermented dairy product, for the first time. Gamma-linolenic acid (GLA) and catechins bioavailability and their effects on skin functionality have not been previously investigated from a fermented dairy product. Firstly, we assessed the bioavailability of GLA and catechins mixed in a fermented dairy matrix by measuring their levels in chylomicrons and plasma samples respectively. For the GLA contained in the dairy matrix, the area under the curve and time for maximal absorption were significantly different to the same kinetic parameters compared with absorption from the free oil indicating improved oral bioavailability. However, the overall absorption of catechins over the 6-h period was identical for both product forms. These results were sufficiently promising to warrant a 24 week skin nutrition intervention study in female volunteers having dry and sensitive skin. The product improved stratum corneum barrier function compared with a control product as early as 6 weeks after the consumption which continued throughout the rest of the study. The reduction in transepidermal water loss relative to control was maintained throughout the trial despite seasonal changes. Moreover, as a result of the enhanced bioavailability, a much greater effect on skin barrier function occurred than reported previously for the individual ingredients. Nevertheless, body mass index significantly influenced various outcome measurements of this study

Publication Types:

• Randomized Controlled Trial

Double-blinded, placebo-controlled trial of green tea extracts in the clinical and histologic appearance of photoaging skin

Dermatol Surg. 2005 Jul;31(7 Pt 2):855-60

Chiu AE, Chan JL, Kern DG, Kohler S, Rehmus WE, Kimball AB.

BACKGROUND: Green tea extracts have gained popularity as ingredients in topical skin care preparations to treat aging skin. Green tea polyphenolic compounds have significant antioxidant and anti-inflammatory activities, and studies suggest that these extracts help mediate ultraviolet radiation damage. OBJECTIVE: To evaluate the effects of a combination regimen of topical and oral green tea supplementation on the clinical and histologic characteristics of photoaging. METHODS: Forty women with moderate photoaging were randomized to either a combination regimen of 10% green tea cream and 300 mg twice-daily green tea oral supplementation or a placebo regimen for 8 weeks. RESULTS: No significant differences in clinical grading were found between the green tea-treated and placebo groups, other than higher subjective scores of irritation in the green tea-treated group. Histologic grading of skin biopsies did show significant improvement in the elastic tissue content of treated specimens (p<.05). CONCLUSION: Participants treated with a combination regimen of topical and oral green tea showed histologic improvement in elastic tissue content. Green tea polyphenols have been postulated to protect human skin from the cutaneous signs of photoaging, but clinically significant changes could not be detected. Longer supplementation may be required for clinically observable improvements.

Publication Types:

• Double-blinded, placebo-controlled trial

Q10

Aging skin is functionally anaerobic: importance of coenzyme Q10 for anti aging skin care

Biofactors. 2008;32(1-4):245-55

Prahl S, Kueper T, Biernoth T, Wöhrmann Y, Münster A, Fürstenau M, Schmidt M, Schulze C, Wittern KP, Wenck H, Muhr GM, Blatt T.

The functional loss of mitochondria represents an inherent part in modern theories trying to explain the cutaneous aging process. The present study shows significant age-dependent differences in mitochondrial function of keratinocytes isolated from skin biopsies of young and old donors. Our data let us postulate that energy metabolism shifts to a predominantly non-mitochondrial pathway and is therefore functionally anaerobic with advancing age. CoQ10 positively influences the age-affected cellular metabolism and enables to combat signs of aging starting at the cellular level. As a consequence topical application of CoQ10 is beneficial for human skin as it rapidly improves mitochondrial function in skin in vivo

Publication Types:

• vivo

VITAMIN E

Protective effect against sunburn of combined systemic ascorbic acid (vitamin C) and d-alpha-tocopherol (vitamin E).

J Am Acad Dermatol. 1998 Jan;38(1):45-8

Eberlein-König B, Placzek M, Przybilla B.

BACKGROUND: UV radiation causes acute adverse effects like sunburn, photosensitivity reactions, or immunologic suppression, as well as long-term sequelae like photoaging or malignant skin tumors. UV radiation induces tissues to produce reactive oxygen species, eicosanoids and cytokines. Inhibition of these mediators might reduce skin damage. Antioxidants such as ascorbic acid and d-alpha-tocopherol have been found to be photoprotective in some in vitro studies and animal experiments. OBJECTIVE: Our purpose was to assess the protective effect of systemic vitamins C and E against sunburn in human beings. METHODS: In a double-blind placebo-controlled study, each of 10 subjects took daily either 2 gm of ascorbic acid (vitamin C) combined with 1000 IU of d-alpha-tocopherol (vitamin E) or placebo. The sunburn reaction before and after 8 days of treatment was assessed by determination of the threshold UV dose for eliciting sunburn (minimal erythema dose [MED]) and by measuring the cutaneous blood flow of skin irradiated with incremental UV doses against that of nonirradiated skin. RESULTS: The median MED of those taking vitamins increased from 80 to 96.5 mJ/cm2 (p < 0.01), whereas it declined from 80 to 68.5 mJ/cm2 in the placebo group. Cutaneous blood flow changed significantly (p < 0.05) for most irradiation doses with decreases in those given vitamins and increases in the placebo group. CONCLUSION: Combined vitamins C and E reduce the sunburn reaction, which might indicate a consequent reduced risk for later sequelae of UV-induced skin damage. The increase of sunburn reactivity in the placebo group could be related to "priming" by the previous UV exposure.

Publication Types:

• double-blind placebo-controlled study

VITAMIN A

Improvement of naturally aged skin with vitamin A (retinol).

Arch Dermatol. 2007 May;143(5):606-12

Kafi R, Kwak HS, Schumacher WE, Cho S, Hanft VN, Hamilton TA, King AL, Neal JD, Varani J, Fisher GJ, Voorhees JJ, Kang S.

OBJECTIVE: To evaluate the effectiveness of topical retinol (vitamin A) in improving the clinical signs of naturally aged skin. DESIGN: Randomized, double-blind, vehicle-controlled, left and right arm comparison study. SETTING: Academic referral center. PATIENTS: The study population comprised 36 elderly subjects (mean age, 87 years), residing in 2 senior citizen facilities. INTERVENTION: Topical 0.4% retinol lotion or its vehicle was applied at each visit by study personnel to either the right or the left arm, up to 3 times a week for 24 weeks. MAIN OUTCOME MEASURES: Clinical assessment using a semiquantitative scale (0, none; 9, most severe) and biochemical measurements from skin biopsy specimens obtained from treated areas. RESULTS: After 24 weeks, an intent-to-treat analysis using the last-observation-carried-forward method revealed that there were significant differences between retinol-treated and vehicle-treated skin for changes in fine wrinkling scores (-1.64 [95% CI, -2.06 to -1.22] vs -0.08 [95% CI, -0.17 to 0.01]; P<.001). As measured in a subgroup, retinol treatment significantly increased glycosaminoglycan expression (P = .02 [n = 6]) and procollagen I immunostaining (P = .049 [n = 4]) compared with vehicle. CONCLUSIONS: Topical retinol improves fine wrinkles associated with natural aging. Significant induction of glycosaminoglycan, which is known to retain substantial water, and increased collagen production are most likely responsible for wrinkle effacement. With greater skin matrix synthesis, retinol-treated aged skin is more likely to withstand skin injury and ulcer formation along with improved appearance.

Publication Types:

• Randomized Controlled Trial

The mechanism of action of topical retinoids

Cutis. 2005 Feb;75(2 Suppl):10-3; discussion 13

Kang S.

UV irradiation of human skin sets in motion a complex sequence of events that causes damage to the dermal matrix. When topical tretinoin is applied to human skin, any collagen deficiency existing in photoaged skin is remedied at least partially, and the skin is primed to prevent further matrix degradation induced by solar UV. Retinoids, therefore, have become essential in the treatment and prevention of photoaging. This article describes the mechanism of action of retinoids, including how they are mediated through retinoic acid receptors (RARs) and retinoid X receptors (RXRs), how they block inflammation mediators, and how production of procollagen is increased to augment the formation of types I and III collagen. Three naturally occurring retinoids are reviewed

Publication Types:

• Review

Treatment of photodamage with topical tretinoin: an overview

J Am Acad Dermatol. 1997 Mar;36(3 Pt 2):S27-36

Gilchrest BA.

Topical administration of tretinoin has proved to be effective in treating clinical signs of photodamaged skin. In large-scale, double-blind, placebo-controlled, 6-month trials, 0.05% tretinoin emollient cream (Renova, Retinova) reduced fine wrinkles and skin roughness, and it produced histologic changes such as epidermal thickening, increased granular layer thickness, stratum comeum compaction, and decreased melanin content. Smaller changes were also observed at lower tretinoin concentrations. Continued for another 6 months, 0.05% tretinoin emollient cream produced some additional clinical improvement but the histologic changes observed in the epidermis (with the exception of melanin content) regressed toward baseline, raising questions as to what was responsible for the clinical improvement. After 12 months of treatment, there were additional signs of tissue normalization including deposition of new collagen in the papillary dermis and ultrastructural evidence of dermal reconstruction with improvement in the dermoepidermal junction and correction of keratinocyte degeneration, changes that presumably relate directly to tretinoin's mechanism of action. There was no suggestion of cytologic atypia in these studies or in biopsy specimens obtained after up to 4 years of continued use. Mild to moderate dermatitis was the only common adverse reaction to tretinoin use. Percutaneous tretinoin absorption is low, raising plasma levels by amounts that are negligible compared with the normally low endogenous tretinoin levels. No teratogenic effects have been observed in retrospective studies of topical tretinoin application during the first trimester of pregnancy. Thus, topical tretinoin is safe and effective in the treatment of photodamage.

Publication Types:

• Review

Publication Types:

• Review

Publication Types:

• Review