Carotenoids and Skin
5.5 Dietary Carotenoids Protect Skin Against Some of the Damaging Effects of UV Exposure
5.5.1 Damaging Effects of UV on Skin
Ultraviolet radiation present in sunlight represents one of the most important environmental hazardous physical agents that the skin encounters on a daily basis throughout a person’s lifetime. Depending on the amount and form of the UV radiation and the skin type of the individual exposed, UV irradiation may cause tissue injury and cutaneous inflammation signifying sunburn (Clydesdale et al.
2001; Cavallo and DeLeo 1986), immune suppression (Ullrich 2005; Moodycliffe et al. 2000), premature aging of the skin called photoaging (Helfrich et al. 2008), and skin cancer (Melnikova and Ananthaswamy 2005; Matsumura et al. 2004).
Chronic exposure to solar UV is considered the major etiological factor for the development of nonmelanoma skin cancer, which occurs primarily on sun-exposed areas of the body.
Sunburn is a term applied to the marked erythema and pain that commonly follows sun overexposure. A sunburn is delayed UV-induced erythema caused by an increase in blood flow to the affected skin that begins about 4 h after exposure and peaks at 8–24 h (Andersen et al. 1991; Ramsay and Challoner 1976). The underlying cause of sunburn is direct and indirect damage to specific cellular targets from photochemical reactions and the generation of reactive oxygen species (Hruza and Pentland 1993). Damage to DNA, the activation of several inflammatory pathways,
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and the release of inflammatory mediators by keratinocytes are thought to trigger this reaction, ultimately leading to vasodilation and edema (Clydesdale et al. 2001;
Cavallo and DeLeo 1986; Roshchupkin et al. 1979). The development of erythema therefore implies that enough ultraviolet damage has occurred that inflammatory pathways have been activated. Erythema is probably best thought of as a total failure of sun protection and is a marker for severe UV damage. It is now appreci- ated that there is a linkage between a history of repeated, severe sunburn and an increased risk for melanoma (Whiteman and Green 1994; MacKie and Aitchison 1982) and nonmelanoma skin cancer (Kricker et al. 1995; Gallagher et al. 1995;
Kennedy et al. 2003; Naylor 1997).
Various strategies are followed for the protection of skin against UV-dependent damage. Limiting sun exposure, protective clothing, and the use of sunscreens are generally recommended. Systemic photoprotection through endogenous supply of nutritional bioactive agents such as carotenoids also provides important protection of the skin against the damaging effects of UV irradiation. However, far more research into the protective mechanisms of action of nutritional molecules on skin health is needed to fully appreciate and understand the long-term benefits of systemic photoprotection. In this chapter, we review the available evidence supporting a role for dietary carotenoids in systemic photoprotection.
5.5.2 Carotenoids are Scavengers of UV-Induced Reactive Oxygen Species that Damage DNA
Upon UV exposure, reactive oxygen species (ROS), which are constantly generated in skin, may be rapidly neutralized by nonenzymatic and enzymatic antioxidant substances. In consequence, cellular macromolecules (i.e., lipids, proteins, DNA) are protected from oxidation and a pro-oxidant/antioxidant balance is maintained, resulting in cell and tissue stabilization. If the antioxidant defense is exhausted, these ROS oxidize lipids, proteins, or DNA, leading to the formation of oxidized products such as lipid hydroperoxides, protein carbonyls, or 8-hydroxyguanosine, respectively (Beehler et al. 1992; Hu and Tappel 1992; Podda et al. 1998) and result in cell damage.
In recent years, carotenoids have gained considerable attention as a means to neutralize ROS (Mukhtar and Ahmad 1999). Because of their 11 conjugated double bonds, carotenoids such as b-carotene, lycopene, zeaxanthin, and lutein have potent antioxidant functionality and are among the most effective naturally occur- ring scavengers of single oxygen and peroxyl radicals (Cantrell et al. 2003;
Di Mascio et al. 1989; Stahl and Sies 2003). Carotenoids are efficiently distrib- uted to skin and, in consequence, might participate to the antioxidant capacity of the skin. Supplementation with lutein and zeaxanthin significantly decreases skin lipid peroxidation, as measured by malondialdehyde levels (Palombo et al. 2007;
Morganti et al. 2002).
70 S.K. Thakkar et al.
Considering that carotenoids exhibit high antioxidant activity in vitro, this property may be promising in neutralizing the ROS generated in vivo upon UV exposure. Although this effect is promising, it needs to be investigated in depth in human intervention studies with carotenoids and with validated markers of peroxidation (i.e., F-2 isoprostane for lipid peroxidation or the Comet assay for DNA peroxidation).
5.5.3 Dietary Carotenoids Reduce Sunburn Development
The sensitivity of an individual to erythematogenic UV exposure is determined by two methods: (1) the minimum erythema dose (MED), defined as the threshold dose required to cause perceptible reddening of the skin 24 h after exposure (Orentreich et al. 2001); or (2) the change of skin color assessed by chromametry (Stahl et al.
2006). With the latter technique, erythema is assessed by a change of chromametry a-values after and before irradiation (in daltons, or Da).
Decreasing Da values in comparison to those at week 0 (set to 100%) reflects protection against UV-induced erythema. In human intervention studies, the photo- protective effect of a nutritional intervention refers to UV-induced erythema as an early observable immediate response. It is measured either as increased MED or as a reduction of erythema intensity after UV exposure compared to baseline and to that of an unsupplemented group.
The efficacy of b-carotene in systemic photoprotection was investigated in seven human intervention studies (Garmyn et al. 1995; Mathews-Roth et al. 1972; McArdle et al. 2004; Lee et al. 2000; Stahl et al. 2000a; Heinrich et al. 2003; GOLLNICK et al. 1996). A meta-analysis (Kopcke and Krutmann 2008) of these seven studies demonstrated that b-carotene supplementation is efficient in providing protection against the development of sunburn (Table 5.1). The effect size is 0.8 SD [95%
confidence interval (CI) 0.2–1.4]. The photoprotective effect is observed only in studies providing a daily dose of 20 mg for a minimum of 10 weeks of supplementation.
The efficacy of lycopene in systemic photoprotection was also investigated but to a lesser extent. Tomato paste provided a daily dietary intake of 16 mg lycopene.
After 10 weeks of supplementation, dorsal erythema formation was 40% lower in the group that consumed tomato paste compared to the control group, although no difference between the groups was found after 4 weeks of treatment (Stahl et al.
2001). Results of another intervention study (Aust et al. 2005) supported this lycopene photoprotective effect. Daily intake of 10 mg of lycopene was provided from three sources: a synthetic lycopene, a tomato extract (Lyc-o-Mato), or a drink containing solubilized Lyc-o-Mato (Lyc-o-Guard-Drink). After 12 weeks of supple- mentation, erythema formation induced by UV exposure was significantly lower with each of the three lycopene treatments. Compared to week 0, the reductions were of 25%, 38%, and 48% for the synthetic lycopene, the tomato extract, and the drink, respectively. Stahl and coworkers (Stahl et al. 2006) also demonstrated this effect in a study where four lycopene sources—tomato paste, lycopene-rich carrot juice, lycopene drink, synthetic lycopene—were used to supply lycopene
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(8.2–16.0 mg/day) to volunteers over a period of 10–12 weeks. The paste, juice, and drink induced efficient photoprotection by 40%, 45%, and 50%, respectively.
The synthetic lycopene showed a trend but it did not reach statistical significance (Stahl et al. 2006). Supplements derived from tomato-based products contain a number of other constituents, including other carotenoids such as phytofluene and phytoene, which are precursors of lycopene in the biosynthetic pathway. These compounds may well contribute to the photoprotective effects as they absorb in the UV range. This, then, may explain the absence of a photoprotective effect with the synthetic lycopene, as lycopene absorption into blood and its distribution to skin was good for the four products.
Table 5.1 Carotenoids and skin erythema Intervention
dose (source)
Duration
(weeks) Results Reference
b-Carotene
90 mg/day 3 No protection Garmyn et al. (1995)
15 mg/day (supplement) 8 No effect McArdle et al. (2004)
180 mg/day 10 MED increased Mathews-Roth et al.
(1972)
24 mg/day (D. salina) 12 Erythema less
pronounced
Stahl et al. (2000c)
24 mg/day (D. salina) 12 Erythema less
pronounced
Heinrich et al. (2003) 30 mg/day (supplement) 12 Erythema less
pronounced
Gollnick et al. (1996)
30 mg/day (D. salina) 8 MED increased Lee et al. (2000)
60 mg/day (D. salina) 8 90 mg/day (D. salina) 8 Lycopene
16 mg/day (tomato paste) 10–12 Erythema less pronounced
Stahl et al. (2001) 10 mg/day (synthetic lycopene) 12 Erythema less
pronounced
Aust et al. (2005) 10 mg/day (tomato extract:
Lyc-o-Mato) 10 mg/day (beverage:
Lyc-o-Guard-Drink)
16 mg/day (tomato paste) 12 Erythema less pronounced except for synthetic lycopene
Stahl et al. (2006) 10.2 mg/day (synthetic
lycopene) Carotenoid mix
60 mg/day (b-carotene) + 90 mg/day (canthaxanthin)
4 No protection Wolf et al. (1988) 8 mg/day (b-carotene) + 8 mg/day
(lycopene) + 8 mg/day lutein
12 Erythema less pronounced
Heinrich et al. (2003) 5.1 mg/day (b-carotene,
carrot juice) + 10 mg (lycopene, synthetic)
10 Erythema less pronounced except for synthetic lycopene
Stahl et al. (2006)
D. salina, Dunaliella salina (alga); MED minimum erythema dose
72 S.K. Thakkar et al.
Human intervention studies with a mix of carotenoids (i.e., b-carotene, lycopene, lutein) confirmed the photoprotective effect of carotenoids (Heinrich et al. 2003).
Erythema development was diminished in subjects whose diets were supplemented with b-carotene (24 mg/day) or a carotenoid mixture consisting of b-carotene, lutein, and lycopene (8 mg each/day) for 12 weeks (Stahl et al. 2001).
5.5.4 Dietary Carotenoids and Skin Cancer
Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most com- monly occurring skin cancers in white populations, and incidence rates have increased in Europe, the United States, and Australia (Christenson et al. 2005; de Vries et al.
2004; Staples et al. 2006). More than 1 million new cases of nonmelanoma skin cancers per year are being reported in the United States. According to estimates of the National Cancer Institute, 40–50% of Americans who live to age 65 develop skin cancer at least once, and the risk of developing additional tumors is high.
Since the 1980s, b-carotene has been proposed as a possible dietary preventive agent against cancer. In animal studies, b-carotene protects against skin cancer induced by chemicals and UV radiation (Krinsky 1989; Bollag 1970). At present, however, there is no clear evidence that carotenoids protect humans against skin cancer. Based on epidemiological studies, no association was found between dietary carotenoids and BCC (Fung et al. 2002; McNaughton et al. 2005) or SCC (Fung et al. 2003). In intervention studies, b-carotene supplementation failed to decrease the risk of nonmelanoma skin cancer among men with low baseline plasma b-caro- tene (Green et al. 1999; Greenberg et al. 1990; Darlington et al. 2003; Schaumberg et al. 2004). Moreover, b-carotene (30 mg/day) had no effect on the incidence of solar keratosis, a premalignant skin cancer, in a randomized controlled study in 1,600 participants (Darlington et al. 2003). These results were supported by another study showing that daily use of b-carotene (30 mg/day, n = 1621) for 4.5 years did not reduce the incidence of BSC or SCC (Green et al. 1999).