Carotenoids and Flavonoids Contribute to Nutritional Protection against Skin Damage from Sunlight
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- Stahl, W. & Sies, H. Mol Biotechnol (2007) 37: 26. doi:10.1007/s12033-007-0051-z
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The concept of photoprotection by dietary means is gaining momentum. Plant constituents such as carotenoids and flavonoids are involved in protection against excess light in plants and contribute to the prevention of UV damage in humans. As micronutrients, they are ingested with the diet and are distributed into light-exposed tissues, such as skin or the eye where they provide systemic photoprotection. β-Carotene and lycopene prevent UV-induced erythema formation. Likewise, dietary flavanols exhibit photoprotection. After about 10–12 weeks of dietary intervention, a decrease in the sensitivity toward UV-induced erythema was observed in volunteers. Dietary micronutrients may contribute to life-long protection against harmful UV radiation.
The concept of nutritional protection against skin damage from sunlight has recently been reviewed . UV exposure of the skin leads to chemical and biological reactions denoted as photooxidative stress . Primarily, light of an appropriate wavelength interacts with a suitable chromophore, which may be directly damaged or act as a photosensitizer. Short-lived electronically excited species initiate subsequent reactions. In the presence of oxygen, secondary reactive oxygen species are generated extending the range of photodamage. Photooxidative damage affects cellular lipids, proteins, and DNA and is involved in the pathobiochemistry of erythema formation, premature aging of the skin, development of photodermatoses, and skin cancer.
Sunburn is a visible dermal reaction following excessive exposure to sunlight, called UV-induced or solar erythema, and is characterized by tenderness, sometimes painful blistering, and second-degree burns . Direct and indirect damage resulting from photochemical reactions leads to vasodilation of dermal vessels and edema and causes increased blood flow in the affected area. Damage to proteins and DNA accumulates within skin cells, and morphological changes occur in keratinocytes and other skin cells. When a cell becomes irreversibly damaged by UV exposure, cell death follows via apoptotic mechanisms, leading to the appearance of so-called sunburn cells in the epidermis [4, 5].
The UV-B part of solar radiation is highly erythematogenic and is considered as major cause of typical sunburn, which starts to develop a few hours after irradiation, culminating about 18–24 h post-irradiation.
The sensitivity of an individual toward erythematogenic UV exposure is determined by the minimal erythemal dose (MED), defined as the threshold dose required to cause a perceptible reddening of the skin 24 h after exposure . MED values differ between individuals and depend on the endogenous protection by melanin and on skin type. Melanin levels determine the skin color and are related to some extent to the skin type, which is often categorized following the Fitzpatrick scale ranging from type I to VI. Skin type I is assigned to people with white or freckled skin, green or light-blue eyes, red hair and high sensitivity to sun light; skin type VI shows black skin, dark brown eyes, and black hair, almost never experiencing sunburn .
Several strategies are applicable for protection against hazardous light exposure and subsequent impairment of molecular and cellular functions . Avoidance of sun exposure, and protective covering and topical application of sunscreens with a high sun protection factor are recommended during times of intense exposure. A major contribution to endogenous protection of the human skin is provided by melanins, endogenous pigments that scatter and absorb UV light . In epidermal melanocytes, the production of melanin is increased by exposure to sunlight (tanning).
Endogenous or systemic photoprotection may be enhanced by supplying dietary or non-dietary compounds with photoprotective properties. The concept of additional endogenous protection was proposed about 30 years ago  and, as mentioned above, has been reviewed recently [1, 11]. In order to increase the barrier for UV light, the compound should absorb UV light over a broad range of wavelengths with high efficacy. Antioxidants protect molecular targets by scavenging reactive oxygen species, including excited singlet oxygen and triplet state molecules. Compounds that modulate stress-dependent signaling and/or suppress cellular and tissue responses like inflammation are suitable for this purpose.
A number of efficient micronutrients are capable of directly scavenging lipophilic and hydrophilic prooxidants or serving as constituents of antioxidant enzymes. Carotenoids, tocopherols, flavanols, and other polyphenols as well as vitamin C contribute to antioxidant defense and thus contribute to endogenous photoprotection.
Carotenoids in Photoprotection
Carotenoids as accessory light-harvesting pigments play an essential role in the protection of plants against excess light and photooxidative stress [12, 13]. Carotenoids exhibit a long central chain of conjugated double bonds carrying acyclic or cyclic substituents. Xanthophylls, also called oxocarotenoids, contain functional oxygen groups . The extended system of conjugated double bonds is crucial for the antioxidant properties of carotenoids [15–17]. Carotenoids are among the most efficient natural scavengers of singlet molecular oxygen [16, 18]. It has been suggested that UVA-dependent skin aging is mainly associated with singlet oxygen formation and that the effects of β-carotene on signaling are at least in part related to singlet oxygen-quenching properties . At low oxygen tension, carotenoids also scavenge peroxyl radicals , inhibiting the process of lipid peroxidation.
The most abundant carotenoids in the human organism are β-carotene, α-carotene, and lycopene, as well as the xanthophylls lutein, zeaxanthin, α- and β-cryptoxanthin [21, 22]. Carotenoid levels in human skin are in the range of 0.2–0.6 nmol/g wet tissue ; however, there are significant differences regarding the level of single carotenoids and distribution of carotenoids within different skin areas .
β-Carotene supplements are applied as oral sun protectants. Data from human studies on the photoprotective effects of orally applied β-carotene are contradictory. In some of the studies, moderate photoprotection was determined, while no effects were found in others (see ). It has been noted that the efficacy of β-carotene in systemic photoprotection is dependent on the duration of treatment before light exposure and on the dose. In studies in which protection was observed, treatment with carotenoids was for at least 10 weeks, and the dose was higher than 20 mg of carotenoids per day [10, 25–27]. In studies reporting no protective effects, carotenoids were applied for only 3–8 weeks [28, 29]. Based on these findings, it has been concluded that the application of moderate doses of β-carotene alone is not sufficient to obtain sustained photoprotection .
The use of high doses of β-carotene in supplements for photoprotection has been discussed controversially, as a result of safety concerns . In two intervention trials with individuals at a high risk for lung cancer, a higher cumulative index for lung cancer was observed in the groups that received β-carotene [31–33]. Therefore, other carotenoids or dietary sources providing considerable amounts of other carotenoids may be suitable for endogenous photoprotection. Supplementation with a daily dose of 24 mg of carotenoid mix comprising the three main dietary carotenoids, β-carotene, lutein, and lycopene (8 mg each/d) provides protection against UV-induced erythema; the effect was comparable to that of β-carotene alone applied at 24 mg/d .
More than 80% of lycopene consumed in the United States is derived from tomato products, although apricots, papaya, pink grapefruit, guava, and watermelon also contribute to dietary intake. Lycopene content of tomatoes can vary significantly, depending on type of tomato and ripening. In the reddest strains of tomatoes, lycopene levels are close to 50 mg per kg compared with only 5 mg per kg in the yellow strains. In most cases, bioavailability of lycopene from dietary sources is increased by thermal processing and by co-ingestion of dietary lipids [35, 36]. Processing of food helps to release lycopene from the food matrix, thus improving accessibility of the lipophilic compound for the formation of lipid micelles together with dietary lipids and bile acids. Cooking and food processing enhance the bioavailability of carotenoids; e.g., lycopene uptake is higher after ingestion of processed tomatoes (tomato paste) as compared to fresh tomatoes .
Many of the reported health benefits of lycopene are attributed to its ability to protect cells against oxidative damage. Although there has been less research focused on lycopene compared to other carotenoids, in vitro studies show that lycopene is a very efficient quencher of singlet oxygen and a potent scavenger of oxygen radicals [18, 38, 39].
In the following paragraphs, we describe a series of studies performed in our laboratory investigating the photoprotective effects in human intervention trials.
Data from human intervention studies have been published, and methodological details have been described [40, 41]. Volunteers who participated in the studies were of skin type II, which was evaluated based on the coloration of skin, hair and eyes and the history of sensitivity to sun exposure . Further criteria for inclusion were healthy condition, body mass index (BMI) of 18–25 kg/m2, no pregnancy or lactation, no supplementation with vitamins, and no medication during the study.
Erythema Prevention and Measurement of Skin Color
Prior to the start of the study, the minimal erythemal dose (MED) was determined for each subject. At the time points of blood sampling, dorsal skin was irradiated with UV light (1.25–fold the MED) to induce erythema; for irradiation a blue-light solar simulator (Hönle, Munich, Germany) was applied. The test for photoprotection is based on the recommendations of the COLIPA work group “Sun-Protection-Measurement” . At each time point, skin color was evaluated before and 24 h after irradiation. Skin color was determined by chromametry (Chromameter Minolta CR 200, Ahrensburg, Germany) using the three-dimensional color system (L, a, b -values). L-values are a parameter for lightness of skin and b-values (blue/yellow axis) are indicative for pigmentation. a-Values (red/green-axis) are a measure for skin reddening. Δ-a values were calculated subtracting the a-value measured before irradiation from the a-value determined after irradiation. They are directly related to UV-induced erythema formation and were used to quantify skin responses to UV irradiation. Upon successful intervention, Δ-a values at the end of the study should be lower than at the beginning. The a-values differ between individuals due to skin sensitivity and basal skin color. For better comparison, the Δ-a values at the beginning of the study were set at 100% and the others calculated as the percentage of basal numbers.
Photoprotective Effects Following the Consumption of Lycopene-Rich Products
The difference between chromametry a-values after and before irradiation (Δ a-value) were taken as a measure for UV-response of the skin, namely erythema formation. Decreasing Δ-avalues in comparison to week 0 (set to 100%) reflect a protection against UV-induced erythema. Following the ingestion of tomato paste, a decrease in the Δa-values from week 0 to week 4 and week 10 was determined. The difference was most pronounced and statistically significant on week 10. In comparison to baseline, the Δ-avalue was lowered by about 40% .
Treatment with synthetic lycopene for a period of 12 week led to a decrease in the Δ a-value after 12 week. However, the difference was statistically not significant.
Four different sources were used to supply lycopene to volunteers and investigate UV-protective effects over a period of 10–12 week [see 11]. The daily dose of lycopene was comparable between groups, ranging from 8.2 to 16 mg/d. In one of the groups (lycopene synthetic), only lycopene and no other carotenoid was present . The supplements derived from tomato-based products contain a number of other constituents including further carotenoids such as phytofluene and phytoene, which are precursors of lycopene in the biosynthetic pathway. These compounds may well contribute to the photoprotective effects, since they absorb in the UV-range.
Photoprotection by High-Flavanol Cocoa
Following the studies with carotenoids, we examined the question whether high-flavanol cocoa provides photoprotection against UV-induced erythema . In that study, two groups of volunteers consumed either a high flavanol (326 mg/d) or low flavanol (27 mg/d) cocoa powder dissolved in 100 ml water over a period of 12 weeks. Photoprotective effects and parameters of skin condition were measured before and during the intervention. Following exposure of selected skin areas toward 1.25 minimal erythemal dose (MED), UV-induced erythema was significantly decreased in the high-flavanol group, by 50% and 70%, after 6 and 12 week of treatment, respectively, whereas no change was found in the low-flavanol group. Ingestion of high flavanol cocoa led to an increase in blood flow of cutaneous and subcutaneous tissues, and to a significant increase in skin density, thickness, and skin hydration. These parameters were not affected in the low flavanol group. Evaluation of the skin surface showed a significant decrease of skin roughness and scaling in the high flavanol cocoa group, whereas again no change was found in the low flavanol cocoa group, comparing the starting values with week 6 and 12. The presented data  show that ingestion of dietary flavanols from cocoa contributes to endogenous photoprotection and improves dermal blood circulation. Cocoa flavanols further affect cosmetically relevant parameters of skin surface and hydration. Recently, a short-term study was completed, showing that dermal blood flow was increased 1.7-fold at 2 h and oxygen saturation of dermal hemoglobin was elevated 1.8-fold upon intake of high flavanol cocoa .
Carotenoids are suitable compounds for photoprotection in the human. In addition to β-carotene, other carotenoids like lycopene or lutein can be used as photoprotectants. Photoprotective effects can be achieved with a diet rich in carotenoids. However, it should be noted that other components of the diet such as further carotenoids (phytoene, phytofluene) or non-carotenoid constituents contribute to photoprotection. Notably, this applies to flavanols as evidenced by protective effects observed with cocoa rich in flavanols.
Endogenous protection associated with dietary means is to be considered complementary to the topical use of a sunscreen with a high-sun protection factor. Increasing the basal protection systemically contributes to life-long defense against UV-dependent skin damage.
The lycopene project was supported in part by the Bundesministerium für Bildung und Forschung, Bonn (Project: 0312248C). The flavanol project was supported by Mars Inc. (Hackettstown, NJ) and by Krebsforschung International e.V. (Düsseldorf, Germany). H.S. is a Fellow of the National Foundation for Cancer Research (NFCR), Bethesda, MD.