Introduction

The multibillion dollar beauty industry in the US continues to flourish, spurred by consumers desire to look and feel forever-young. Several categories exist within the beauty industry, but none more vibrant than the anti-aging segment which includes products to reduce or reverse visible signs of aging such as wrinkles, age

Table 1. Astaxanthin maintains skin health by several methods

Benefits Increase skins ability to resist environmental stripping of skin nutrients. Reduce puffiness and erythema Prevent & reduce presence of UV induced wrinkles. Firmer and elastic skin. Increased moisture. Reduce the risk of skin cancer. Mechanism Restores skins natural antioxidant balance (SOD, CAT, GSH). Protects cell membrane against lipid peroxidation. Suppresses the inflammatory pathway. Protects the dermal layer against oxidative stress dysfunction. Allowing repair process to heal collagen network. Protects against accumulated DNA damage. Topical Dietary Route Route

chemical, physical, and spots, and freckles. While mechanical damage, aging is natural and causing premature aging cannot be avoided, there of the epidermis. are factors such as solar radiation and physical and mechanical damage that accelerate the propensity of visible aging. Today, humans face increasing exposure to chemical pollution, ultraviolet radiation and ozone levels, all of which can damage the skins dermal layer causing wrinkles and enhancing the risk of malignant skin cancer. These negative effects are compounded with increasingly poor diets and lifestyle habits which are not conducive to maintaining the skins natural repair process and antioxidant network. Clearly, there is opportunity for natural ingredients to help improve long term skin health management through topical application and nutritional supplementation.

Skin is exposed to

Protecting the Skins Natural Antioxidant Network and DNA

Oxygen radicals formed from UV radiation attack skin cells in a variety of ways. As demonstrated by OConnor & OBrien (1998), UVA light is capable of producing oxidative stress in living cells in-vitro. By monitoring catalase (CAT), superoxide dismutase (SOD) levels and thiobarbituric acid reactive substances (TBARS), Astaxanthin is capable of reducing oxidative stress (p<0.01, n=6) after UVA light irradiation at very low concentrations (5-10 nM). Astaxanthin has shown to be approximately 100-200 times more effective than other carotenoids, including lutein and beta-carotene (1.0 M). Similar reports by Lyons et al., (2002) demonstrate that UVA irradiated skin cells pretreated with astaxanthin (10 M) suffered significantly less DNA damage. Furthermore, astaxanthin protected the skins endogenous antioxidants SOD and glutathione (GSH) from oxygen radical attack. Topical restoration of the skins natural antioxidant balance is one method to maintaining healthy skin. UV radiation and air borne pollutants tend to strip away the nutrients essential to maintain the skins hydrolipidic barrier. As a result, the skin will become dry and unhealthy in appearance.

In the past, Beta-carotene Astaxanthin is produced (provitamin A) and by Haematococcus in direct Vitamin E have been response to protect cells in extensively studied. vivo against UV induced oxidative stress. Recent focus, however, has switched to other carotenoids such as astaxanthin, (derived from the microalgae Haematococcus pluvialis), which is shown to have potent quenching and anti-lipid-peroxidation properties; a weakness of Beta-carotene and Vitamin E (Miki, 1991). In human trials, astaxanthin has been shown to reduce visible signs of UV-aging through both topical and dietary supplementation within 4 to 6 weeks of use. This data is supported by a number of in-vitro and animal studies. Research suggests potential skin benefits from the use of astaxanthin to maintain a youthful appearance, reverse premature signs of aging and prevent UV induced skin cancer. Naturally, further investigation is necessary to elucidate the mechanism of action and to replicate results using significantly larger clinical trials. To date, the astaxanthin potential is promising.

Topical Wrinkle Reduction

In a study using hairless mice, Arakane (2002) demonstrates astaxanthins ability to suppress the formation of UVB photoinduced wrinkles. UVB doses of 65-95 mJ/cm2 were applied five times per week for 18 weeks on the back skin of the mice. After each UVB treatment, topical application of astaxanthin (350 M) was coated on the exposed areas. After only 5 weeks, the appearance of new wrinkles were significantly reduced up until the end of the study period (P<0.01 at 18 weeks). Concurrently, stained skin sections revealed that astaxanthin preserved the integrity of the dermal layer by protecting the collagen network.

In a preliminary human study, Seki et al., (2001) demonstrates the same anti-wrinkle observations in female human subjects (n=3) using a topical cream containing astaxanthin. A dermatological assessment revealed significant reduction of wrinkles and puffiness on the lower eye and cheeks after 2 weeks of use. In a separate test using female subjects (n=11), instrument analysis recorded significant moisture improvement (P<0.05) after 3 weeks of use (Figure 1). Figure 1. Cheek moisture retention after 3 weeks application of astaxanthin cream (0.07% of 5% astaxanthin extract; Seki

Figure 3. Magnified Skin Section at start, 2 and 4 weeks (Yamashita, 2002)

Start

2 Weeks

4 Weeks Visible reduction of fine wrinkles

In the second study by Yamashita (2006), female subjects with a variety of skin types (n=49, mean age 47 yrs) were given either 4 mg (2 x 2 mg) astaxanthin or placebo in a single-blind, randomized, controlled study. After six weeks of consuming 4mg astaxanthin per day, the results of a standard questionnaire showed that the treated group of women all felt that their skin condition had improved significantly (Figure 4). Figure 4. Subject response after 6 weeks astaxanthin supplementation (Yamashita, 2006)
80
Astaxanthin Placebo

60

Skin Health that can be Swallowed

Beauty from within or improved skin condition through nutrition and supplementation is a worldwide trend that is on the increase. The market for beauty supplements is currently worth 800 million dollars, and rapid growth in this segment is expected over the next 10 years.
Nutritional factors can modulate photochemical damage, in particular the common carotenoids in food.

40

20

0 Skin Dryness Moisture Content Roughness Elasticity Fine Lines/Wrinkles

Skin improvements seen in all categories after astaxanthin supplementation.

-0.15 -0.2 -0.25 -0.3

Difference Score

Improvement

Two human clinical trials established the use of astaxanthin to improve visible signs of premature aging and general skin health. The first, a double-blind placebo controlled study (Yamashita 2002), showed that astaxanthin in combination with tocotrienol, (a superior form of vitamin E), improved several aspects of overall skin condition. Eight female subjects with dry skin conditions (mean age 40 yrs) received daily doses containing 2 mg astaxanthin and 40 mg natural tocotrienols. Several types of data were collected at 2 and 4 weeks and compared to the initial baseline readings. Measurable differences were observed starting just 2 weeks after supplementation. By the 4th week, the treated subjects with dry skin characteristics exhibited the following: increased moisture levels (P<0.05), (Figure 2); consistent natural oils; reduction of fine wrinkles, (Figure 3); and a reduction in pimples (P<0.01). Figure 2. Beauty supplement results for the cheek and eye region (Yamashita, 2002)
Cheek Moisture Content at 2 and 4weeks
15 10 Variation (microS) 5 0 -5
Astaxanthin Placebo

Instrument analysis proved that the treated group had indeed achieved positive results in hydration (P<0.05) and elasticity (P<0.05). Furthermore, a dermatologists inspection showed wrinkle reduction (P<0.05) and improved elasticity (P<0.05) in the treated group especially between weeks 3 and 6 (Figure 5). The results were significant since skin regeneration usually takes between 4-5 weeks. The greatest improvement seen at week 6 supports the theory that astaxanthin protects and allows skin to regenerate. Figure 5. Dermatologist skin analysis of moisture and elasticity at 3 and 6 weeks astaxanthin supplementation (Yamashita, 2006).
Fine Lines/Wrinkles / Difference from baseline
0 -0.05 Improvement -0.1 Worse

Elasticity- Difference from Baseline

0.6 0.4 0.2 0 -0.2 -0.4

-0.35 -0.4

Week 3

Week 6

Week 3
-0.6

Week 6

Astaxanthin

Placebo

Astaxanthin

Placebo

Eye Region Moisture Content at 2 and 4 weeks

50 40 Variation (microS) 30 20 10 0 -10 -20
Astaxanthin Placebo

Astaxanthin reduced wrinkles and increase elasticity.

Astaxanthin and Skin Cancer

2 weeks 4 weeks

-10 -15 -20 2 weeks 4 weeks

Moisture levels increased in treated groups at 2 and 4 weeks. Control groups got worse.

The risk of skin cancer is increased in skin which is frequently damaged by the sun. Although skin cancer is almost 99% curable if detected early, 1 out of 90 people in the US or 1 out of 150

people in the UK will develop melanomas. Those in the highest risk category are people exposed to frequent short bursts of strong sunlight. Sun screens can block the UV rays, but dietary carotenoids such as astaxanthin can be vital for skin protection as Over the past 60 years, damage to the planet's ozone well.
amount of harmful radiation In another study on that reaches your skin. hairless mice, Black (1998) demonstrates that astaxanthin significantly delays the UV ray formation of skin lesions and tumors (p<0.05). A possible explanation is that astaxanthin is preferentially accumulated over beta-carotene and lycopene. Epidermal analysis determined that the quantity of astaxanthin was 133 times that of lycopene and 28 times that of Beta-carotene. layer has increased the

UV rays induce the production of in situ radical oxygen species (ROS) and matrix metalloproteinases (MMP). These factors are the root of wrinkle formation because they destroy the collagen matrix in the dermis. Fortunately, the skins repair mechanism will rebuild the damage collagen. However, the hindrance of skin renewal by repeated exposure to uncontrolled levels of ROS and MMP leads to the formation of wrinkles. The presence of astaxanthin attenuates the effects of reactive oxygen and MMP and therefore, it allows the skin to regenerate properly (Figure 7). Figure 7. Astaxanthin supports skin renewal by attenuating factors which contribute to wrinkle formation
Environmental factors: solar effect ozone pollution Wrinkle forms because dermal support is insufficient

Further support comes from Savoure et al., (1995) which shows that hairless mice (SKH1) deficient in vitamin A, fed 10 mg/kg/feed astaxanthin alone or in combination with retinol, show enhanced Skin Cancer Facts (2001) skin protection after UVA US: #1 form of cancer. and UVB irradiation. UK: #2 most common cancer. Astaxanthin significantly inhibited accumulation of putrescine (p<0.05) more than retinol and lowered spermidine and spermine.

O2
1

O2

O2

Normal Skin Aging and Life style factors

Singlet oxygen (ROS) disrupts the dermal layer

Elimination and suppression of ROS effects by astaxanthin

Wrinkle reduction Skin Renewed

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O2

Ax

O2

Ax Ax

Ax

Mechanism of Action
Skin is composed of three layers: the epidermis, the dermis, and the subcutaneous fat. The dermis contains collagen, elastin, and other fibers that support the skin's structure. It is these elements that give skin its smooth and youthful appearance and these are the parts of the skin that are damaged by UV radiation (UVR).

Ax

Ax

New Collagen

Astaxanthin helps dermal renewal

1

Astaxanthin continues to defend the skin

O2

Singlet oxygen

Ax

Astaxanthin

Anti-wrinkle
The UVR that affects the skin is composed of two types of waves; UVA and UVB. UVB rays are shorter than UVA rays, and are the main cause behind wrinkle formation and melanin production. However, it is the UVA rays, with their longer wavelength, that are responsible for much of the damage associated with photoaging. UVA rays penetrate deep into the dermis, where they damage collagen fibers, leading to wrinkle formation (Figure 6). Figure 6. Illustration showing effect of UVA, UVB & Ozone on skin
UVB UVA Ozone

Astaxanthin defends against Reactive Oxygen Species (ROS).

Oxygen present in our cells can form harmful radicals known as ROS or active oxygen when sufficient energy from UV rays is applied. ROS include singlet oxygen, superoxides and hydroxyl radicals (leading to peroxyl radicals) and they attempt to steal electrons from neighboring molecules such as DNA, phospholipids, enzymes and protein in order to stabilize. Fortunately, astaxanthin is able to quench singlet oxygen reactions and supress lipid peroxidation much more effectively than other well known antioxidants and thus control the presence of ROS.

Skin Layers
Stratum Corneum Epidermis Papillary Dermis+ Dermis

Damage
Ozone damages stratum corneum which potentiate moisture loss. UVA & UVB Dermal damage increases premature wrinkle formation.

Anti-inflammatory Action
Inflammation that normally follows sun exposure can be modulated by a powerful antioxidant. Yamashita (1995) shows in healthy male subjects (n=7), that topical natural astaxanthin significantly reduces burn level (erythema) by 60% at 98 hours after

Subcutaneous Fat

UVB exposure. We now know that astaxanthin works by suppressing the proinflammatory mediators and cytokines via the I B kinase dependant NF- B activation pathway (Lee et al., 2003).

Safety for Topical & Nutritional Use

Astaxanthin is determined safe for topical use. A total of forty-five subjects (males and females) were exposed to the Standard Japanese Patch test and results were reported 24 and 48 hours after application. Dermatitis was only induced by the adhesive plaster and not astaxanthin itself (Seki et al. 2002). Furthermore, Koura (2005) reports no adverse topical reactions in animal sensitization models. Astaxanthin is listed in the JP Cosmetics and INCI name as Haematococcus pluvialis extract.

7. Lyons, N.M., & OBrien, N.M., et al., (2002), Modulatory effects of an algal extract containing astaxanthin on UVA-irradiated cells in culture. Journal of Dermatological Science 30:73-84. 8. Yamashita, E., (2002), Cosmetic benefit of the supplement health food combined astaxanthin and tocotrienol on human skin. Food Style 21 6(6):112-117. 9. Seki, T., et al., (2001), Effects of astaxanthin from haematococcus pluvialis on human skin. Fragrance Journal 12:98-103. 10. Black, H. S., (1998), Radical Interception by carotenoids and effects on UV carcinogenesis. Nutrition Cancer 31(3):212-217. 11. O'Connor, I., & O'Brian, N., (1998), Modulation of UVA light induced oxidative stress by beta-carotene, lutein and astaxanthin in cultured fibroblasts. Journal of Dermatological Science 16:226-230. 12. Savoure, N., et al., (1995), Vitamin A status and metabolism of cutaneous polyamines in the hairless mouse after UV irradiation: action of beta-carotene and astaxanthin. International Journal of Vitamin and Nutrition Research 65(2):79-86. 13. Yamashita, E., (1995), Suppression of post UVB hyperpigmentation by topical astaxanthin from krill. Fragrance Journal 14:180-185. 14. Miki, W., (1991), Biological functions and activities of animal carotenoids. Pure & Appl. Chem., 63(1):141-146.

Patent
Method of inhibitating the expression of inflammatory cytokines and chemokines, US7078040.

Outlook
Naturally, the best way to avoid photo-aging is through prevention of the solar effects on skin by applying sunscreen to areas vulnerable to increased exposure. However, recent surveys reveal that people in general are not doing enough to protect their skin. The use of powerful carotenoids like astaxanthin in topical and nutritional skin products can help deliver the benefits against the risk of accelerated photo-aging and skin cancer.

References
1. www.skincancer.org/ 2. www.skincancerfacts.org.uk/facts.asp 3. Yamashita, E., (2006), The Effects of a Dietary Supplement Containing Astaxanthin on Skin Condition. Carotenoid Science, 10:91-95. 4. Koura, S., (2005). Skin sensitization study of Astaxanthin in Guinea Pigs. Study No. 05035. New Drug Research Center Inc., Hokkaido Japan. Fuji Sponsored Study. 5. Lee, S.J. et al., (2003), Astaxanthin Inhibits Nitric Oxide Production and Inflammatory Gene Expression by Suppressing I B Kinase-dependent NF- B Activation. Molecules and Cells, Vol. 16, No. 1, pp. 97-105. 6. Arakane (2002), Superior Skin Protection via Astaxanthin. Carotenoid Science April 5:21-24.

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