of antioxidants on the skin

Photoprotective effect of antioxidants on the skin

Although the skin naturally contains antioxidants, their amount becomes limited during sun exposure. Protective agents applied to the skin have their limitations in protecting the skin, and dietary supplements can help compensate for these deficiencies.

The skin is the largest body organ that plays the role of a biological barrier. It participates in the regulation of body temperature, transmits sensations and prevents harmful substances from entering the body. One of its most important protective functions is to protect against the undesirable effect of solar radiation.

The impact of sunlight on the skin

Sunlight is beneficial for the human body, and one of benefits is stimulation of formation of vitamin D in the skin, which is essential for healthy bones and immunity and increases serotonin level that supports a good mood. But excessive sun exposure, both short and long term, can damage the skin. Besides causing burns, premature skin aging, hyperpigmentation and allergic reactions, it can even lead to serious conditions such as skin cancer. Exposing the skin to the Sun’s UV radiation leads to significant oxidative damage resulting in clinical and histopathological changes, thus contributing to its premature aging. Hyperpigmented lesions, also known as “age spots“, are some of the most noticeable skin changes caused by photoaging.

The vast majority of skin damage caused by the Sun results from UV rays, namely UVA and UVB rays. The skin naturally contains an antioxidant system against UV-generated reactive oxygen metabolites. However, this antioxidant protection is not always fully effective during Sun exposure. Oral antioxidants can help reduce the harmful effects of UV radiation and strengthen the physiological antioxidant defences of the skin.

Various ways of protecting against UV rays include photo protective clothing and applying topical agents that require repeated application due to localized effect. The introduction of useful oral substances is a promising method, providing uniform protection to the whole body. This has led to the development of a market for dietary supplements and products promoted to improve skin health. All these products have in common antioxidant action.

AUTHOR: Daria Šurić, M.Pharm., Darmell Simply explained, antioxidants “fight” against the oxidation process, which over time leads to the destruction of cells. Since oxidative stress is considered to be the main cause of skin aging, nutrients that have antioxidant effects such as carotenoids, flavonoids, plant extracts and omega-3 fatty acids are of interest. Most UV radiation is filtered through the Earth’s atmosphere, and we are exposed mainly to UVA (95%). Primarily, research has focused on the effects of UVB rays, but lately attention has been more shifted to UVA radiation. Its larger wavelengths allow it to penetrate deeper into the skin. Majority of UVB is absorbed in the epidermis, and UVA radiation also affects the dermis, showing carcinogenicity in animal models. UVB rays can also cause burns.

Clinical changes observed in photo aging such as rough structure, wrinkles, spotty hyperpigmentation, vasodilation and loss of elasticity are attributed primarily to the influence of UVA. UVA harms the skin by stimulating the formation of reactive forms of oxygen after they are absorbed by riboflavin, porphyrin and hem-containing proteins. Reactive oxygen molecules can damage import-

ant biomolecules including DNA, proteins and lipids in various parts of the skin, leading to cytotoxicity, mutations and changes in signalling pathways in cells. UVB rays reduce the effectiveness of antioxidant enzymes at the protein level, leading to the accumulation of reactive oxygen radicals (ROS). Since the harmful effects of the sun on the skin provoke oxidative stress, i.e. the formation of free radicals, one way to protect the skin is within, using dietary supplements containing antioxidants. The human body depends on antioxidants that help maintaining balance and healing damaged cellular structures. Although the skin itself naturally contains antioxidants, during Sun exposure their amount becomes limited.

Protection with the products applied to the skin also has its limitations due to e.g. inadequate application (too small amounts, insufficient frequency) or rinsing by sweating. Dietary supplements can help compensate for these shortcomings. Their action is preparing the skin for sun exposure and helping to eliminate the formed free radicals.

Regarding active substances found in the aforementioned dietary supplements, we will describe in more detail several, namely those that have a proven photoprotective effect on the skin.

Astaxanthin

Astaxanthin belongs to the group of carotenoids found in nature. It is also called the “king of carotenoids” because it is one of the strongest natural antioxidants. Its rich burgundy pigment gives color to krill, salmon and shrimps. There are different sources of astaxanthin (food, bacteria, synthesized and natural from microalgae) that can also have different bio-availability. The best source of astaxanthin for dietary supplements is obtained from a natural source, the microalgae Haematococcus pluvialis, which contains about 40 grams of astaxanthin per kilogram. For comparison, salmon meat contains 5 mg of astaxanthin per kilogram. Nowadays, astaxanthin from microalgae can be produced in industrial quantities. Microalgae produce it to protect against the stressful influences of the environment. Hence, when the drying out begins during the summer, it allows them to preserve DNA from damage. In this way, they remain ready for regrowth when the rains come, and even if it will take several years. This astonishing ability shows the effectiveness of astaxanthin. It manifests its antioxidant action by collecting free radicals. Its ability to eliminate free radicals has been proven to be 1,000 times greater than that of coenzyme Q10 (Mori J.) A wide range of clinical studies in several different health areas has proven its multiple positive effects on the human body, in the following areas: • joint and tendon health; • skin health; • cardiovascular health; • eye and brain health; • protection at the cellular level; • recovery after sport activity. rocytes to the brain where it crosses the bloodbrain barrier, and also into the skin, including the dermis and epidermis. This unique antioxidant is bioavailable throughout the organism. In addition to the skin, it can be found in the muscles, ligaments, tendons, eyes, cardiovascular system, nervous system and internal organs.

These soft tissues work better thanks to the presence of the antioxidant power of astaxanthin. The human organism cannot synthesize it on its own, so it is necessary to introduce it in food and dietary supplements. The protective role of astaxanthin on the skin concerning damage caused by UV radiation has been proven on cell cultures, rodents and in humans. Taking astaxanthin prevented UV-induced photo aging and improved the healing of burns in rodents (Komatsu T.). In addition to astaxanthin, several other carotenoids, such as beta-carotene and lycopene, showed a protective role in UV-induced skin damage (Sies H.).

In a randomized, double blinded, placebo-controlled clinical trial (Ito N.), 23 healthy individuals were divided over 10 weeks into a group that was given 4 mg of astaxanthin in capsules and into a placebo group. To prove the protective role of astaxanthin on UV-induced skin damage, a minimum erythema dose (MED) was established and UV-induced transepidermal moisture loss (TEWL) was analysed at the beginning and after 9 weeks of supplementation.

Thanks to the results achieved, it has been proven that astaxanthin acts protectively on UV-induced skin aging and helps maintaining healthy skin in healthy individuals. Side effects or significant changes in biochemical parameters in the blood and hematological tests were also monitored. Side effects associated with taking astaxanthin have not been observed.

FIGURE 1 Impact of astaxanthin supplementation on minimal erythema dose

Dietary supplements with astaxanthin increase the minimum erythema dose (MED). (a) Image of the irradiated area in the placebo group (left) and astaxanthin group (right) before and after supplementation; (b) Changes in the MED baseline in the placebo group (black) and astaxanthin group (red). * p < 0.05 with Mann-Whitney U-test. Error bars indicate a standard deviation (SD). Taken from: The Protective Role of Astaxanthin for UV-Induced Skin Deterioration in Healthy People-A Randomized, Double-Blind, Placebo-Controlled Trial - PubMed (nih.gov)

In dietary supplements on Croatian market, doses of astaxanthin range from 4 to 8 mg. According to EFSA, a daily intake of up to 8 mg is safe for adults even in combination with a high intake of astaxanthin from food (salmon, shrimps). For adolescents up to 14 years of age and younger children are it is recommended 4 mg per day (EFSA Journal). Astaxanthin has a unique molecular structure among carotenoids. It has hydroxyl and keto parts of the molecule, which allows it to stretch through the two-layer cell membrane from the outer wall to the inner side, and also to eliminate oxidized fats from the surface of the membrane. It is a lipophilic molecule that is well absorbed when taken with food. One of the leading manufacturers of astaxanthin is the company Algatech. They have developed a protected process of cultivation of microalgae, which lasts approximately three months and mimics the accumulation of astaxanthin in natural conditions. Cultivation begins in the “green stage”. Algae are provided with optimal growing conditions and biomass is allowed to grow to its maximum over time.

At a later stage, algae are transferred to advanced glass photobioreactors where they grow rapidly under the Sun of the Arava Desert. When fully developed, the “red stage” begins, in which algae are subjected to stressful conditions that sample the natural response - the production of astaxanthin for protection. This method of production ensures high purity of astaxanthin, with more than 95% of total carotenoids. Nutrex Hawaii is also a world-renowned manufacturer of astaxanthin, founded by Dr. Gerald Cysewski, an expert in microalgae and carotenoid, in Hawaii in 1990. Their production is located on the unpolluted Kona Coast in Hawaii, where natural resources are used in production.

Studies have proven that after two weeks of consumption of this astaxanthin, the time it takes to form a burn caused by exposure of the skin to the Sun is significantly extended. The inflammatory reaction of the skin and subcutaneous tissue, which arises as a reaction to excessive exposure to UV radiation, is also reduced.

Other carotenoids

Beta-carotene belongs to the group of carotenoid micronutrients found primarily in fruits and vegetables. Besides the specific antioxidant effect, they also act on impulse transmission and gene expression at the cellular level. Together with lycopene, beta-carotene is a pigment that gives color to carrots and tomatoes and they are the dominant carotenes in the blood and tissues as well. Both substances affect the skin resistance when taken as a FIGURE 2 Haematococcus pluvialis

TAKEN FROM: https://www.nutrex-hawaii.com/blogs/learn/ what-is-astaxanthin

dietary supplement.

They have been proven to protect the skin from burns caused by solar radiation (solar erythema) by increasing the basal ability to protect the skin from UV damage (Stahl W.). Data collected by in vitro studies show that other carotenoids also have a photoprotective effect. One of them is lutein.

For successful carotenoid driven protection of the skin, it is recommended to take them at least ten weeks. Increased carotenoid intake can help protecting the skin from UV radiation.

Beta-carotene is a precursor of vitamin A, converted into vitamin A in the liver. Natural beta-carotene increases skin hydration. Vitamin A was approved to contributing to the maintenance of normal skin.

In one study, 30 healthy male volunteers were given beta-carotene at a dose of 180 mg/day, or placebo during 10 weeks, followed by exposing to sunlight in the Arizona desert for 2 hours. Beta-carotene had a small but statistically significant effect, by increasing the minimal erythema dose (MED) of solar radiation (Mathews-Roth MM).

In another, placebo-controlled study, in which 30 mg/day of beta-carotene was used for 10 weeks, a significant decrease in the intensity of Sun-induced erythema (Gollnick H.P.M.) was observed.

Dunaliella salina, a microalga that lives in the oceans, produces a large concentration of beta-carotene and other carotenoids to protect against intense UV radiation. Similarly, beta-carotene exhibits an antioxidant effect on the human body and protects the skin from the Sun. Dunaliella salina is a natural source of other mixed carotenoids, cryptoxanthin, zeaxanthin and lutein. It is considered as one of the highest quality sources of beta-carotene for use in dietary supplements.

It is important that people who have sensitive skin prone to rashes, eczema or psoriasis increase their intake of beta-carotene to increase skin protection from the Sun. Beta-carotene is best taken in its natural form (along with other carotenoids) for at least 12 weeks.

Lutein and zeaxanthin - Lutein is a stereoisomer of zeaxanthin, also belonging to the carotenoids. Its role in preserving healthy vision is well known, while in protecting the skin it is somewhat less mentioned. Lutein is also found in the skin, in the epidermis and dermis. It contributes to its color and protects it by

blocking blue light. In this way, it reduces the appearance of melasma, a pigmentation disorder that manifests itself as the appearance of dark spots, especially facial (Souyoul SA; Balić A.). Lutein also manifests its protective role from blue light on the retina of the eye by filtering blue light and acting as an antioxidant.

To protect the skin, recommended dose is 10-20 mg/day. It is often combined with zeaxanthin. Since lutein is fat-soluble, like other carotenoids, taking a dietary supplement is recommended with a meal.

Regarding well-known brands found as raw materials in food supplements, Omniactive Lutemax 2020 lutein® and zeaxanthin and Kemin FloraGLO® lutein are often mentioned. FloraGLO® lutein is a natural ingredient derived from marigold flower (Tagetes erecta), and has results from 25 years of research. It’s the most tested lutein brand in the world. It has excellent absorption, since it contains a form of lutein equal to that of vegetables and other foods. Lutemax 2020® is an ingredient that contains premium lutein and zeaxanthin isomers in a ratio of 5:1, as found in nature.

Red orange extract

Red orange (Citrus sinensis var Moro, Tarocco and Sanguinello) has great healing potential. Namely, in fruits, leaves, juice and roots it contains a whole wealth of active molecules that contribute to pharmacological activity: flavonoids, steroids, coumarins, peptides, carotenoids and nutrients such as potassium, magnesium, calcium and sodium. Proving the in vitro antioxidant effect, it was assumed that it has also a photoprotective effect. A study was conducted by supplementation with red orange extract in relation to photoprotective action in UV-induced skin erythema and in relation to the production of melanin in solar lentigo. The test was done on healthy volunteers using the appropriate instrumental method. The dose was 100 mg of extract per day, for 15 days. A significant decrease in the degree of erythema was shown, and pigmentation spots on the skin (melanin content) decreased from 27% to 7%. It was concluded that a dietary supplement containing red orange extract can increase the antioxidant protective capacity of the skin, protecting it from the harmful processes involved in photo aging thereby improving its appearance and pigmentation (Puglia C.).

FIGURE 3 Chemism of the red orange fruit

SOURCE: Molecules | Free Full-Text | Chemistry and Pharmacology of Citrus sinensis (mdpi.com)

Fatty acids

Important factors for skin health are fatty acids found in unrefined Evening primrose, Borage and Hemp (GLA) oils, and blue fish and algae (omega-3). Fatty acids play a key role in creating the skin lipid barrier and affect the response of skin cells to UV radiation.

Omega-3 fatty acids also showed photoprotective action at a dose of 2.8 g of EPA and 1.2 g of DHA during 4 weeks (Orengo IF). The mechanism of action is associated with anti-inflammatory properties so that it reduces the UV-induced release of cytokines and other mediators from different types of skin cells.

Polyphenols

Polyphenols are antioxidants present in fruits, vegetables, cereals, olive oil, chocolate, but also in beverages like coffee, tea and wine. Polyphenolic compounds suppress local and systemic immunosuppression caused by UVB rays, and mediate the reduction of reactive forms of oxygen in the skin.

Green tea - Epigalocatechin-3-gallate (EGCG) is the most prevalent polyphenol in green tea, being primarily responsible for its positive effects on health. EGCG has two triphenol chemical groups in its composition. These groups are significant for the antioxidant effect that also protects against UV-induced DNA damage.

People who do not tolerate well large amounts of green tea, it is recommended to take dietary supplements containing its extract, standardized to the content of EGCG.

Quercetin

Quercetin is a flavonoid native to vegetables, fruits or ginkgo. In several studies, he has shown anti-inflammatory and antioxidant properties. In the skin, it prevents the breakdown of collagen induced by UV radiation. Quercetin also affects the slowdown of skin photo aging, supports growth and prolongs the life of skin cells, and fibroblast resistance.

Resveratrol

Resveratrol is a substance found in red wine, associated with its positive effects ion health. It is found in the fruits of grapes, more precisely in the skin and seeds of the fruit, as a protection against toxins. Red grapes are fermented together with the skin so that they contain resveratrol. It is also found in white wine, but in an amount 10 times less than in red. Like other bioflavonoids, it has a proven antioxidant effect (Brasnyó P.).

Polypodium leucotomos extract

Fern extract Polypodium leucotomos has been used in folk medicine of South American Indians to treat skin inflammation since ancient times. It has an antioxidant effect that has been proven by clinical trial during which a significant decrease in erythema has been observed.

The conclusion of the conducted research is that oral intake of a dietary supplement containing the extract of this fern has a chemophotoprotective effect, thus exhibiting a significant ability to protect

the skin from UV radiation (Middlekamp-Hup MA). Among other ingredients that could play a significant role in dietary supplements to protect the skin from solar radiation, oral intake of hyaluronic acid shows promising potential.

Overall, conclusion is that taking described substances in a form of food supplements has significant beneficial effect on protection of the skin from harmful impact of the Sun radiation.

References:

Mori J., Yokoyama H., Sawada T., Miyashita Y., Nagata K. Anti-oxidative properties of astaxanthin and related compounds. Mol. Cryst. Liq. Cryst. 2013;580:52–57. doi: 10.1080/15421406.2013.804380. [CrossRef] [Google Scholar] Ito N, Seki S, Ueda F. The Protective Role of Astaxanthin for UV-Induced Skin Deterioration in Healthy People-A Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients. 2018 Jun 25;10(7):817. doi: 10.3390/nu10070817. PMID: 29941810; PMCID: PMC6073124.

Satoh A., Mitarai A., Kanno T., Hori Y., Takeda R. Effects of the Intake of Astaxanthin on the Reduction of Skin Darkling Induced by UV Irradiation in adult women. Pharmacometrics. 2011;80:7–11.

Komatsu T., Sasaki S., Manabe Y., Hirata T., Sugawara T. Preventive effect of dietary astaxanthin on UVA-induced skin photoaging in hairless mice. PLoS ONE. 2017;12:e171178. doi: 10.1371/journal.pone. 0171178. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Sies H., Stahl W. Carotenoids and UV protection. Photochem. Photobiol. Sci. 2004;3:749–752. doi: 10.1039/b316082c. [PubMed] [CrossRef] [Google Scholar] https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2020.5993 Stahl W, Sies H. Photoprotection by dietary carotenoids: concept, mechanisms, evidence and future development. Mol Nutr Food Res. 2012 Feb;56(2):287-95. doi: 10.1002/mnfr.201100232. Epub 2011 Sep 23. PMID: 21953695. Mathews-Roth MM, Pathak MA, Parrish J, Fitzpatrick TB, Kass EH, Toda K, Clemens W. A clinical trial of the effects of oral beta-carotene on the responses of human skin to solar radiation. J Invest Dermatol. 1972 Oct;59(4):349-53. doi: 10.1111/1523-1747.ep12627408. PMID: 4569104. Gollnick H.P.M., Hopfenmuller W., Hemmes C., Chun S.C., Schmid C., Sundermeier K., Biesalski H.K. Systemic beta-carotene plus topical UV-sunscreen are an optimal protection against harmful effects of natural UV-sunlight: results of the Berlin-Eilath study. Eur. J. Dermatol. 1996;6:200–205. [Google Scholar] [Ref list]

Souyoul SA, Saussy KP, Lupo MP. Nutraceuticals: a review. Dermatol Ther (Heidelb). 2018;8(1):5–16. doi:10.1007/s13555-018-0221-x [PMC free article] [PubMed] [CrossRef] [Google Scholar] Balić A, Mokos M. Do we utilize our knowledge of the skin protective effects of carotenoids enough? Antioxidants. 2019;8(8):259. doi: 10.3390/antiox8080259 [PMC free article] [PubMed] [CrossRef] [Google Scholar] Puglia C, Offerta A, Saija A, Trombetta D, Venera C. Protective effect of red orange extract supplementation against UV-induced skin damages: photoaging and solar lentigines. J Cosmet Dermatol. 2014 Jun;13(2):151-7. doi: 10.1111/jocd.12083. PMID: 24910279.

Orengo IF, BlackHS, WolfJE. Influence of fish oil supplementation on the minimal erythema dose in humans. ArchDermatolRes1992; 284:219–21. Brasnyó P, Molnár GA, Mohás M, Markó L, Laczy B, Cseh J, Mikolás E, Szijártó IA, Mérei A, Halmai R, Mészáros LG, Sümegi B, Wittmann I. Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients. Br J Nutr. 2011 Aug;106(3):383-9. doi: 10.1017/S0007114511000316. Epub 2011 Mar 9. PMID: 21385509. Middelkamp-Hup MA, Pathak MA, Parrado C, Goukassian D, Rius- Díaz F, Mihm MC, Fitzpatrick TB, González S. Oral Polypodium leucotomos extract decreases ultraviolet-induced damage of human skin. J Am AcadDermatol. 2004 Dec;51(6):910-8. doi: 10.1016/j.jaad. 2004.06.027. PMID: 15583582.