Skin Care & Anti-Aging

Brighter Skin and Well-Being Goes Hand-in-Hand

Brighter Skin and Well-Being Goes Hand-in-HandThe multibillion dollar beauty industry 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 spots, and freckles. While aging is natural and cannot be avoided, there 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 skin's 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 skin's 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.
In the past, Beta-carotene (provitamin A) and Vitamin E have been extensively studied. 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.

Table 1. Astaxanthin maintains skin health by several methods Table 1. Astaxanthin maintains skin health by several methods

Protecting the Skin's Natural Antioxidant Network and DNA

Protecting the Skin's Natural Antioxidant Network and DNAOxygen radicals formed from UV radiation attack skin cells in a variety of ways. As demonstrated by O'Connor & O'Brien (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 μM). Similar reports by Lyons et al., (2002) demonstrate that UVA irradiated skin cells pretreated with astaxanthin (10 μM) suffered significantly less DNA damage. Furthermore, astaxanthin protected the skin's endogenous antioxidants SOD and glutathione (GSH) from oxygen radical attack. Topical restoration of the skin's 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 skin's hydrolipidic barrier. As a result, the skin will become dry and unhealthy in appearance.

Topical Wrinkle Reduction

In a study using hairless mice, Arakane (2002) demonstrates astaxanthin's 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 μM) 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 et al., 2001). Figure 1. Cheek moisture retention after 3 weeks application of astaxanthin cream (0.07% of 5% astaxanthin extract; Seki <em>et al.</em>, 2001) Increased moisture content in 8 out of 11 subjects.

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. 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) Figure 2. Beauty supplement results for the cheek and eye region (Yamashita, 2002) Moisture levels increased in treated groups at 2 and 4 weeks. Control groups got worse.
Figure 3. Magnified Skin Section at start, 2 and 4 weeks (Yamashita, 2002) Figure 3. Magnified Skin Section at start, 2 and 4 weeks (Yamashita, 2002) 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) Figure 4. Subject response after 6 weeks astaxanthin supplementation (Yamashita, 2006) Skin improvements seen in all categories after astaxanthin supplementation.

Instrument analysis proved that the treated group had indeed achieved positive results in hydration (P<0.05) and elasticity (P<0.05). Furthermore, a dermatologist's 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). Figure 5. Dermatologist skin analysis of moisture and elasticity at 3 and 6 weeks astaxanthin supplementation (Yamashita, 2006). Astaxanthin reduced wrinkles and increase elasticity.

Astaxanthin and Skin Cancer

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 well.
In another study on 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.
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 protection after UVA and UVB irradiation. Astaxanthin significantly inhibited accumulation of putrescine (p<0.05) more than retinol and lowered spermidine and spermine.

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).

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 inflammation 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 Figure 6. Illustration showing effect of UVA, UVB & Ozone on skin

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 skin's 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 Figure 7. Astaxanthin supports skin renewal by attenuating factors which contribute to wrinkle formation

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. In vitro singlet oxygen quenching activity of Astaxanthin was found to be superior when compared to Catechin, Vitamin C, Alpha Lipoic Acid, Coenzyme Q10, Tocopherol, Lutein and Beta Carotene (Nishida et al., 2007).

Astaxanthin Dominance against Singlet-Oxygen compared to other antioxidants

Singlet oxygen depletes the antioxidant defense system of fibroblasts, especially CAT and SOD. Fibroblasts secrete collagen, a main component of extracellular matrix which provides structural support to the cells. Exposing fibroblasts to singlet oxygen is a widely used technique to model ageing and UV oxidative stress. Furthermore, viability of the fibroblasts remains vital to the maintenance of healthy skin appearance. Tominaga et al (2009a) showed evidence on the ability of Astaxanthin to protect human dermal fibroblasts through in-vitro study. Human dermal fibroblasts were pre-incubated with Astaxanthin and other antioxidants and then exposed to singlet oxygen (Figure 8). Cell viability was restored to more than 80% when the cells were treated with Astaxanthin.
In another study, Camera et al. (2008) compared the photoprotective properties of astaxanthin to other antioxidants on human dermal fibroblasts. After a physiological dose of UVA was applied, roughly equal to a UV dose accumulated within 1-2 hours on a sunny day. Astaxanthin was considerably superior at preventing cell death (reduction of caspase-3 activity at protein level) compared to Canthaxanthin and Beta Carotene (Figure 9).

Figure 8. Astaxanthin's cell protection ability comparison with other anti-oxidants (Tominaga 2009a) Figure 8. Astaxanthin's cell protection ability comparison with other anti-oxidants (Tominaga 2009a) Study showed that astaxanthin had the highest ability to protect cells.
Figure 9. UVA-induced activation of caspase-3, detected by annexin V staining, 24h after irradiation (Camela et al., 2008) Figure 9. UVA-induced activation of caspase-3, detected by annexin V staining, 24h after irradiation (Camela <em>et al.</em>, 2008)

Gaining Customers' Hearts with Tangible Results - Astaxanthin Inner and Outer Treatment

Complementing astaxanthin oral administration with astaxanthin topical treatment (dual treatment) can have enhanced synergistic effects against premature skin aging since astaxanthin is effective at all layers of skin, the skin surface, epidermis and dermis.
According to studies conducted by Tominaga et al. (2009b), astaxanthin "dual treatment" was found to be effective in all layers of skin. In a study with 28 subjects aged 20-55 years, astaxanthin effectively reduced wrinkles as well as improved skin elasticity. Replica analysis after 6 mg of astaxanthin supplementation combined with topical application for 8 weeks showed a reduction in the overall average wrinkle depth.
Furthermore, a reduction in wrinkle width by 9% (p<0.05) and depth by 14% (P<0.01) of the largest wrinkle were also observed. Astaxanthin treatment also showed significant improvement in skin elasticity (p<0.01) (Figure 10). These results were substantiated through in vitro studies. In vitro studies with fibroblasts pre treated with astaxanthin (10 μM) before singlet oxygen exposure showed collagen production restored up to 80%. This evidence suggests that astaxanthin protect fibroblasts and support collagen production thereby exerting wrinkle reduction and enhancing skin elasticity (Figure 11).
Astaxanthin was effective in reducing skin roughness. The study showed that after 4 weeks of treatment, the mean depth of roughness significantly improved (p<0.05). Before and after the clinical trials, cells from the stratum corneum from the cheek area were collected by tape stripping. The cells were stained and cell area was measured and quantified by image analysis. The size of cells in the stratum corneum was found to be significantly increased (p<0.05). At the start of the clinical trials, signs of desquamation were extensively observed. At the end of the 8-week clinical trial, many of these cornified layer cells were healthier or showed a better arrangement.
Astaxanthin was also found effective in reducing age spot (p<0.05). An objective evaluation rated improvement in condition of age spot and freckles for 59% of the subjects. In vitro studies using human epidermis models, showed that astaxanthin at very low concentration (0.0006 mg/ml) inhibited melanogenesis. This inhibitory effect is superior to that induced by vitamin C (5 mg/ml) and comparable to that induced by tranexamic acid (5mg/ml) or L-cysteine (0.1 mg/ml) which are agents commonly used in dermatological therapy.

Figure 10. Effects of Astaxanthin on skin elasticity after extended intake/external application (Tominaga 2009b) Figure 10. Effects of Astaxanthin on skin elasticity after extended intake/external application (Tominaga 2009b)
Figure 11. Stimulatory effects of Astaxanthin on collagen production and maintenance (Tominaga 2009b) Figure 11. Stimulatory effects of Astaxanthin on collagen production and maintenance (Tominaga 2009b)

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

Safety for Topical & Nutritional Use

Natural astaxanthin is determined safe for topical and nutritional 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 astaxanthin.

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

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Patent

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