Effect of Lumenato a Tomato derived oral supplement on improving skin barrier strength.

INTRODUCTION: Improvement of skin barrier strength could lead to healthy and youthful appearance. "Beauty inside-out" approach using nutraceuticals such as tomato derived carotenoids to support skin barrier strength could be of benefit to the ageing population. METHOD: A panel of 60 female subjects were provided with the Lumenato capsules (containing carotenoids) or placebo capsules as nutritional supplements for 3 months. Skin health and barrier function were observed using evaporimeter which measures trans epidermal water loss (TEWL). Barrier strength was determined by study of the number of strippings required to disrupt skin barrier and barrier repair was observed in terms of TEWL a few hours after barrier disruption. Cutometer was used to observe skin firmness and elasticity. Measurements were obtained before treatment and after 4 and 12 weeks of use. RESULTS: Results indicated a statistically significant improvement (p < 0.05) in skin barrier strength; a higher number of strippings were required to disrupt skin barrier after 12 weeks of supplement use. There was also a significant improvement in skin firmness and elasticity as observed with a cutometer. CONCLUSION: Based on the confines and conditions of this study, oral supplementation with Lumenato resulted in significant improvement in skin barrier as well as skin firmness and elasticity.

Effect of Lumenato oral supplementation on plasma carotenoid levels and improvement of visual and experiential skin attributes.

BACKGROUND: Cellular metabolism and exposure to solar irradiation result in generation of free radicals which are destructive and can lead to premature aging. Antioxidants and free radical scavengers such as carotenoids successfully protect from these free radicals by quenching and neutralizing them thereby strengthening skin barrier which leads to improved skin moisturization, desquamation, and a more youthful look. This study was designed to evaluate the consumer-perceived efficacy of an oral supplement (Lumenato™) containing a mix of tomato carotenoids and oil-soluble vitamins in improving skin appearance after 12 weeks of supplement use. MATERIALS AND METHODS: Plasma levels of phytoene, phytofluene, zeta-carotene, and lycopene were quantitated before and after 1-, 2-, 3-, and 4-week administration of Lumenato by 24 healthy volunteers. Part II of the study addressed skin visual attributes as assessed by validated tools (questionnaires). A total of 60 females, aged 35 to 55 years, completed part II of the study. The subjects answered questionnaires pertaining to their assessment of skin appearance before and after 12 weeks of taking the supplement. RESULTS: There was a significant increase (p < 0.001) in plasma levels of phytoene, phytofluene, and zeta-carotene after 1- to 4-week treatment with Lumenato. After 12 weeks of using the supplement, the score of different skin parameters was reported to significantly improve (p < 0.001). Improvement was recorded in skin elasticity, firmness, brightness, skin tone, reduction in dark spots and periorbital dark circles, skin hydration, texture and fine lines and wrinkles. A significant (p < 0.001) improvement in overall skin condition after using the supplement was observed. The subjects noticed statistically significant (p < 0.001) improvement in skin elasticity, firmness, brightness, skin tone, reduction in dark spots and periorbital dark circles, skin hydration, texture and fine lines and wrinkles after 12 weeks of using the supplement. The overall skin condition also exhibited a significant improvement (p < 0.001). Self-assessed improvement of the face was identified at the first time point (4 weeks) and improved significantly (p < 0.001) for the 12 weeks of use. Interestingly, these improvements persisted even after treatment was stopped. CONCLUSION: Based on the confines and conditions of this study, the use of oral supplement containing a mix of tomato carotenoids significantly increased plasma levels of phytoene, phytofluene, and zeta-carotene, and continuous use resulted in improved facial skin attributes which were palpable by the consumers and continued even after treatment was stopped.

Beauty from within: Oral administration of a sulfur-containing supplement methylsulfonylmethane improves signs of skin ageing.

Background: Methylsulfonylmethane (MSM) is an organosulfur compound with known benefits for joint health, sports nutrition, immune function, and anti-aging formulations and is gaining popularity as a nutritional supplement for the support of hair, skin and nails. Methods: The study was conducted in two steps; in Part I (pilot study) a panel of 20 participants ingested either 3 g a day of MSM or placebo capsules for 16 weeks. Visual and subject self assessment of wrinkles and skin texture as the predominant sign of ageing was observed. In Part II (dose-response study), 63 participants ingested either 1 g or 3 g per day of MSM for 16 weeks. Expert clinical grading, instrumental measurements and consumer perception was used to evaluate skin conditions like lines and wrinkles. Additionally, instrumentational analysis was conducted using corneometer and cutometer for investigation of skin hydration, firmness and elasticity. Results: Part I of the study clearly indicates that oral ingestion of MSM (3 g/d) reduces signs of ageing like facial wrinkles (p < 0.05) and skin roughness (p < 0.05) as compared to placebo. Detailed analysis in Part II instrumentation assessments showed a significant (p < 0.05) improvement from baseline in the severity of facial wrinkles, as well as improved skin firmness, elasticity and hydration with MSM. Some of these parameters exhibited a good dose-response indicating that the higher (3 g/d) of the supplement was more effective than the lower dose of 1 g/d, but generally the lower dose of 1 g/d appeared to be sufficiently effective in reducing the facial signs of ageing. Conclusion: This study indicated that MSM is effective in reducing visual signs of skin ageing even at a low dose of 1 g/d.

Omeprazole, a gastric proton pump inhibitor, inhibits melanogenesis by blocking ATP7A trafficking.

Omeprazole is a proton pump inhibitor used in the treatment of peptic ulcer disease and gastrosophageal reflux disease and acts by irreversibly blocking ATP4A, a P-type H+/K+ ATPase in gastric parietal cells. We found that omeprazole and its closely related congeners inhibited melanogenesis at micromolar concentrations in B16 mouse melanoma cells, normal human epidermal melanocytes, and in a reconstructed human skin model. Omeprazole topically applied to the skin of UV-irradiated human subjects significantly reduced pigment levels after 3 weeks compared with untreated controls. Omeprazole had no significant inhibitory effect on the activities of purified human tyrosinase or on the mRNA levels of tyrosinase, dopachrome tautomerase, Pmel17, or MITF mRNA levels. Although melanocytes do not express ATP4A, they do express ATP7A, a copper transporting P-type ATPase in the trans-Golgi network that is required for copper acquisition by tyrosinase. ATP7A relocalization from the trans-Golgi network to the plasma membrane in response to elevated copper concentrations in melanocytes was inhibited by omeprazole. Omeprazole treatment increased the proportion of EndoH sensitive tyrosinase, indicating that tyrosinase maturation was impaired. In addition, omeprazole reduced tyrosinase protein abundance in the presence of cycloheximide, suggestive of increased degradation. Our findings are consistent with the hypothesis that omeprazole reduces melanogenesis by inhibiting ATP7A and by enhancing degradation of tyrosinase.

Effect of seasonal and geographical differences on skin and effect of treatment with an osmoprotectant: Sorbitol.

Human skin maintains an optimal permeability barrier function in a terrestrial environment that varies considerably in humidity. Cells cultured under hyperosmotic stress accumulate osmolytes including sorbitol. Epidermal keratinocytes experience similar high osmolality under dry environmental conditions because of increased transepidermal water loss (TEWL) and concomitant drying of the skin. This study was designed to determine if epidermal keratinocytes, in vitro, could be protected from high osmotic stress, with the exogenous addition of sorbitol. In addition, we evaluated the effect of a formulation containing topical sorbitol on skin barrier and moisturization of subjects living in arid and humid regions in summer as well as in winter. Results from in vitro experiments showed that 50 mM sorbitol protected epidermal keratinocytes from osmotic toxicity induced by sodium chloride. Clinical studies indicated that skin chronically exposed to hot, dry environment appeared to exhibit stronger skin barrier and a lower baseline TEWL. In addition, skin barrier was stronger in summer than in winter. Sorbitol exhibited significant improvement in both barrier repair and moisturization, especially in individuals subjected to arid environmental conditions.

Menopause increases the iron storage protein ferritin in skin.

Menstruation and desquamation are important routes for humans to excrete iron. Because menstruation is no longer available in postmenopausal women, in the present study, we examined whether iron accumulates more in postmenopausal skin than in premenopausal skin. Skin biopsy samples were obtained from six pre- and six postmenopausal Caucasian women. Iron levels in the form of ferritin were 42% higher, but vascular endothelial growth factor and total antioxidant capacity were 45% and 34% lower in postmenopausal skin (58.8 ± 1.3 years old) than in premenopausal skin (41.6 ± 1.7 years old), respectively. Moreover, in vitro cultured normal human epidermal keratinocytes had surprisingly high levels of ferritin when compared to immortalized human breast epithelial MCF-10A cells or human liver HepG2 cancer cells. Our results indicate that skin is a cellular repository of iron and that menopause increases iron in skin and, thus, may contribute to the manifestation of accelerated skin aging and photo aging after menopause.

Enzymatically generated hydrogen peroxide reduces the number of acne lesions in acne vulgaris.

A major component to the etiology of acne is the growth and invasion by Propionibacterium acnes. Hydrogen peroxide is an excellent antimicrobial agent but is unstable in most formulations. We have developed a hydrogen peroxide generation system using the enzyme glucose oxidase and glucose. This system is stable in a simple formulation and nonirritating. In a short-term clinical study (4 days), this formulation was effective in reducing the individual lesion size and total number of inflammatory acne lesions. There was a 68% reduction in acne-induced inflammation and 61% reduction in acne size within 4 days of treatment. A long-term clinical study (6 weeks in use) displayed 56% reduction in total number of inflamed lesions and a 45% reduction in noninflamed lesions after 6 weeks. This suggests that topical enzymatically generated hydrogen peroxide may help alleviate acne.

Physiological effect of a probiotic on skin.

INTRODUCTION AND OBJECTIVE: Normal human skin can produce a range of antimicrobial chemicals that play an important part in eliminating potential cutaneous pathogens. Lactobacillus plantarum is a gram-positive bacteria that produces antimicrobial peptides, which when applied to the skin can act like an anti-inflammatory as well as enhance the antimicrobial properties of the skin. Clinical studies were conducted to determine the effect of lactobacillus extract on improvement of skin barrier and reduction of erythema from chemical irritant, skin microflora, and acne. Results show that lactobacillus extract was effective in reducing skin erythema, repairing skin barrier, and reducing skin microflora, thereby exhibiting an effective reduction in acne lesion size and erythema at 5%, but not at 1%. CONCLUSION: Based on the results of these studies, lactobacillus extract (5%) can be used to treat mild acne lesions.

Two fluorescent wavelengths, 440(ex)/520(em) nm and 370(ex)/440(em) nm, reflect advanced glycation and oxidation end products in human skin without diabetes.

BACKGROUND: Advanced glycation end products (AGEs) and oxidation products (OPs) play an important role in diabetes complications, aging, and damage from sun exposure. Measurement of skin autofluorescence (SAF) has been promoted as a noninvasive technique to measure skin AGEs, but the actual products quantified are uncertain. We have compared specific SAF measurements with analytically determined AGEs and oxidative biomarkers in skin collagen and determined if these measurements can be correlated with chronological aging and actinic exposure. METHODS: SAF at four excitation (ex)/emission (em) intensities was measured on the upper inner arm ("sun protected") and dorsal forearm ("sun exposed") in 40 subjects without diabetes 20-60 years old. Skin collagen from the same sites was analyzed by liquid chromatography-tandem mass spectrometry for three AGEs-pentosidine, carboxymethyllysine (CML), and carboxyethyllysine (CEL)-and the OP methionine sulfoxide (MetSO). RESULTS: There was poor correlation of AGE-associated fluorescence spectra with AGEs and OP in collagen, with only pentosidine correlating with fluorescence at 370(ex)/440(em) nm. A little-studied SAF (440(ex)/520(em) nm), possibly reflecting elastin cross-links, correlated with all AGEs and OPs. Levels of CML, pentosidine, and MetSO, but not SAF, were significantly higher in sun-exposed skin. These AGEs and OPs, as well as SAF at 370(ex)/440(em) nm and 440(ex)/520(em) nm, increased with chronological aging. CONCLUSIONS: SAF measurements at 370(ex)/440(em) nm and 335(ex)/385(em) nm, except for pentosidine, which correlated with fluorescence at 370(ex)/440(em), correlate poorly with glycated and oxidatively modified protein in human skin and do not reflect actinic modification. A new fluorescence measurement (440(ex)/520(em) nm) appears to reflect AGEs and OPs in skin.

Structural and functional differences in barrier properties of African American, Caucasian and East Asian skin.

BACKGROUND: Differences in structural and functional skin characteristics have been linked with ethnical background. But racial differences in skin have not been thoroughly investigated by objective methods and the data are often contradictory. OBJECTIVES: This study was undertaken to compare skin barrier-related parameters of the stratum corneum on African American, Caucasian and East Asian skin by objective measurements. METHODS: Baseline values of trans epidermal water loss were collected on the face. Consecutive stratum corneum D-squame tape strippings were collected on the panelist's ventral forearm and face to evaluate skin barrier strength and cohesion. Stratum corneum ceramides, maturation, measured as the transglutaminase-mediated cross-linking of stratum corneum proteins, and stratum corneum trypsin like enzyme activity were measured on the D-squame tape strippings. RESULTS: East Asian and to some extent Caucasian skin was characterized by low maturation and relatively weak skin barrier. African American skin was characterized by low ceramide levels and high protein cohesion in the uppermost layers of the stratum corneum. These data can be interpreted in terms of the high prevalence of xerosis in black skin and increased skin sensitivity in East Asian skin. CONCLUSION: These results demonstrate that skin properties at the level of the stratum corneum vary considerably among these ethnic groups. This contributes to an improved understanding of physiological differences between these study populations.

Modification of skin discoloration by a topical treatment containing an extract of Dianella ensifolia: a potent antioxidant.

Skin hyperpigmentation, and the reactions that precipitate it, have been linked to free radicals by the fact that free radical scavengers or antioxidants can slow that hyperpigmentation. We have screened several hundred plant extracts for antioxidants and discovered one that is both a strong antioxidant and can reduce skin hyperpigmentation. Extracts of Dianella ensifolia contain 1-(2,4-dihydrophenyl)-3-(2,4-dimethoxy-3-methylphenyl) propane (DP), which was found to inhibit the free radical 1-1-diphenyl-2-picryl-hydrazyl (DPPH) with an EC(50) value of 78 mum. DP was also found to inhibit Ultraviolet (UV)C-induced lipid oxidation with an EC(50) of about 30 mum. We next investigated the effects of this antioxidant on skin hyperpigmentation. The reduction of discoloration by different topical treatments has been assessed in human volunteers using an in vivo assay for the rate of fading of UVB-induced tan. Two pharmaceutical formulas containing 4% hydroquinone (HQ) were used as positive controls, and we tested the ability of DP, a plant-derived amphoteric antioxidant, to increase performance of non-HQ cosmetic formulations. We found that the cosmetic formula containing DP produced an increase in the rate of fading compared to the two pharmaceutical treatments containing HQ.

A novel method to study the skin-lightening effect of topical materials.

Skin without significant dyschromia is an aesthetic requirement for people worldwide. There are several in vitro methods to determine the whitening potential of actives; however, the in vivo testing of skin whiteners is a long and expensive process. We have designed a rapid clinical method to screen potential skin whiteners using a UV-induced skin tan as a model. Small areas of identical suntan are repeatably induced on the skin, and treatment of these sites allows rapid screening of several skin whiteners within the course of a month. The method provides reproducible results and valuable information about the potential skin-lightening activity of topical preparations.

Calculation of apparent age by linear combination of facial skin parameters: a predictive tool to evaluate the efficacy of cosmetic treatments and to assess the predisposition to accelerated aging.

The estimated apparent age (EAA) was estimated by a panel of trained experts, for the individuals in a cohort. Twelve independent clinical, biophysical and biochemical parameters measured on facial skin, have been identified by multiple regression analysis, which influence the EAA of a person of chronological age (CA) (under eye lines, clinically assessed crow's feet, age spots, clinically evaluated firmness, forehead lines, pores, lip lines, instrumentally evaluated firmness, instrumentally evaluated crow feet, skin texture, in vivo fluorescence related to proliferation and glycation). An algorithm has been devised to obtain the calculated age score (CAS) in a cohort of 452 female volunteers, as CAS(n) = ∑RCiPi(n) (i = 1-13, n = 1-452 and P13 = 1) where the coefficients Ci are obtained by minimizing the difference EAA - CAS, and Pi(n) are the experimental values of the i-th parameter for the n-th volunteer. The determination of CAS before and after a specific cosmetic or pharmacological anti-aging treatment can be used to objectively assess the efficacy of the treatment. The comparison of EAA(n) and of CAS(n) with CA(n) allows one to predict the susceptibility of an individual's face to undergo aging. It has been observed that the biophysical and biochemical parameters play a relevant role in the assessment of the predisposition of skin to undergo accelerated aging.

A rapid method to clinically assess the effect of an anti-acne formulation.

Historically, clinical evaluation of acne treatment has been based on direct visual assessment and the counting of lesions over a period of several weeks of treatment. However, with advancing technology there has been ever-increasing speed in the effectiveness of these treatments. To successfully assess these faster treatments, acne pathology needs to be evaluated in a shorter time frame. The object of these studies was to develop techniques to evaluate individual acne lesions in a shorter time frame and to assess speedier treatment technologies. Ten healthy volunteers with acne lesions on their upper backs were recruited for the study. Two inflamed acne lesions were selected for each treatment, along with lesions to be left untreated, on each volunteer. Each lesion was marked, photographed, and visually graded. A skin surface microscope (Scopeman) was used to visualize size and to grade the lesions by two experts every day for five days. The sites were treated once a day for the course of the study. There was a remarkable reduction in the size and erythema of acne lesions after treatment with the acne formulation as compared to the untreated and vehicle-treated lesions. Individual lesions, both treated and untreated, appeared resolved in 14 days. This resolution can be noticeably accelerated by topical treatments. We have developed a simple and faster clinical method to evaluate the effects of topical anti-acne technology.

Morphological changes associated with aging: age spots and the microinflammatory model of skin aging.

Affymetrix gene-expression analysis was performed on mRNAs from involved and noninvolved skin biopsies from three volunteers with Lentigo senilis. Of the 42,000 transcripts scanned, 17 were downregulated (<1.4 times below the control level) and 23 were upregulated (>1.9 times above the control level). A serine peptidase gene was downregulated in keeping with the suggestion that age spots are associated with impaired melanin degradation. Three genes involved in the keratinization and synthesis and the organization of fibers in the basement membrane were downregulated, two metalloproteinase genes were upregulated, as were six genes associated with the inflammatory response, in keeping with the postulate that the visible aspects of aged skin are causally linked with a microinflammatory response. The regulation of five genes associated with the Wnt family was altered. Antiapoptotic genes were downregulated, and six genes associated with transmembrane transport were upregulated.

Effect of systemic hormonal cyclicity on skin.

Fluctuations in estrogen and progesterone during the menstrual cycle can cause changes in body systems other than the reproductive system. We conducted several studies to determine a possible correlation between phases of the menstrual cycle and specific skin properties. Healthy Caucasian women (ages 21-48), who had a typical 26-29 day menstrual cycle, participated in the studies. Measurements of skin barrier strength, dryness, response to lactic acid stinging, skin surface lipids, and microflora were obtained every week for two to three months. Ultraviolet B susceptibility in terms of minimal erythemal dose was also studied. The skin barrier was the weakest between days 22 and 26 of the cycle. Elevated neuronal response (lactic acid sting) was not observed to vary much with the cycle. Skin was driest between day 1 and day 6, while skin surface lipid secretion appeared to be highest on days 16-20 of the hormonal cycle. The highest microbial count was around days 16-22, and there was a high UV-B susceptibility between days 20 and 28 of the menstrual cycle.

Normal human epidermal keratinocytes treated with 7-dehydrocholesterol express increased levels of heat shock protein.

Human skin, and its isolated cells, respond to insults with a variety of repair and protective mechanisms. One such mechanism is the production of heat shock proteins (HSPs). Heat shock proteins help the other cellular proteins fold correctly into their active three-dimensional structures. Therefore, they can enhance the survival of cells under harsh, denaturing conditions. In order to develop a means of promoting the heat shock response to prepare the skin to withstand insult, we are investigating materials that appear to protect the skin biologically. One such material is vitamin D3 and its precursors. We have observed that keratinocytes treated with 7-dehydrocholesterol (7-DHC), a precursor of vitamin D3, have increased levels of protein and mRNA for heat shock proteins. In addition, we observed that topically applied 7-DHC increases the minimal dose of UVB required to induce erythema. These data suggest that 7-DHC can induce heat shock proteins in skin keratinocytes and that they will be more resistant to UVB insult.

Evidence and utility of melanin degrading enzymes.

The biochemical synthesis of human melanin is understood in some detail. However, little is known about melanin degradation and catabolism of melanin. We hypothesize that human skin contains enzymes that degrade melanin and these enzymes can be used to reduce skin color. To test this hypothesis, HaCaT keratinocytes and normal human keratinocytes in culture were pulse labeled for one hour with radiolabeled synthetic melanin. This melanin was synthesized in vitro using tyrosinase enzyme from mushrooms and using radiolabeled [14C]3,4-dihydroxyphenylalanine (DOPA) as a substrate. After the initial pulse labeling, samples of both the cells and media were taken at 2, 4, 6 and 18 hours. Over these time periods the counts remaining in the media and cell fraction were significantly decreased. This data suggests the need for new protein synthesis and the lysosome organelle function for the degradation. Melanin degrading extracts isolated from Aspergillus fumigatus and Saccharomyces cerevisiae were applied to human skin. These extracts cause significant reduction in UVB induced pigmentation. These extracts may be useful in developing new whitening products to even skin color and tone.

Impact of stress of marital dissolution on skin barrier recovery: tape stripping and measurement of trans-epidermal water loss (TEWL).

BACKGROUND: Psychological stress of marital disruption is associated with significant increases in a variety of psychological and physical disorders. The effect of stress on the immune system is well documented and skin disorders have been reported to exacerbate during stressful situations. This study was designed to observe the effects of stress on skin barrier strength and recovery. Twenty-eight healthy females age 21-45 who were in the process of marital separation were tested for skin barrier strength and recovery. The panel was chosen on the basis of the intensity of self perceived stress. The control group was an age-matched group of self perceived 'happy' subjects. Servomed evaporimeter was used to measure trans-epidermal water loss (TEWL) from cheek area of the face, before and after removing stratum corneum layers with tape strippings. Skin barrier strength was defined as the number of tape strippings required to disrupt skin barrier, which is a TEWL of 18 g/m2/h or more. Barrier recovery was denoted by the level of TEWL, 3 h and 24 h after barrier disruption. RESULTS: There was no correlation between the degree of stress and barrier strength. However, individuals with high stress recovered slower than the individuals with low stress after 3 h (R = 0.64) and 24 h (R = 0.74). CONCLUSIONS: Psychological stress of marital dissolution does not appear to change skin barrier strength but has a negative impact on skin barrier recovery.