– THE USE OF NUTRACEUTICAL INGREDIENTS IN THE COSMETIC INDUSTRY

IN THE COSMETIC INDUSTRY

Author

Qi Jia

Chief Science Officer

Unigen Inc. 3005 First Avenue, Seattle, WA 98121

ABSTRACT

Skin conditions are not only related to environmental conditions such as UV exposure, temperature, humidity, and chemical and mechanical wear and tear, but they are also associated with age, gender, and the nutritional history of individuals.1 Since introduction of the terms nutraceuticals and cosmeceuticals2 separately in the 1980s, the term nutricosmetics was proposed in conjunction with the launch of the first oral ingredient for a beauty product called “Imedeen” in the late 1980s. This chapter provides an extensive introduction to the rapidly growing area of nutraceuticals in cosmetics and personal care. What was once a beauty industry that focused on topical treatments has now emerged in an expanded form that acknowledges and provides documentation and ingredients for the enhancement of beauty and well-being based on internal nutricosmetics as well as the synergy between both topical and internal ingredients. It is also pointed out that the beauty-from-within concept has long been known and accepted in the Asian world and that the path to individualized approaches is now being embarked upon for future product enhancements.

TABLE OF CONTENTS

9.1.1 Introduction

9.1.2 Nutraceutical ingredients that are suitable for cosmetic usage

9.1.3 Characterization of nutracosmetic ingredients based
on biological function

e. Supporting healthy skin-cell renewal and
rebuilding dermal structure

f. Anti-skin aging

9.1.4 Bioavailability and clinical considerations

“You are what you eat” is a phrase that can be found in almost every culture. Traditional Chinese Medicine (TCM) has taught for thousands of years that optimal health and well-being are related to the intake of certain ingestables, which are designed by practitioners to balance the body and, in Western terms, to achieve homeostasis. TCM thinking and practice, in terms of ingestion of proper foods and herbs have, in fact, gone far ahead of the Western thinking only now emerging, that each individual is different and therefore, to achieve homeostasis and optimal health requires personalized ingestion of selected “nutraceuticals.”

Achieving beauty from within is a well-accepted concept in Asia and Europe. This concept and its growing global acceptance go far deeper than the “traditional” definition of achieving the appearance of beauty by means of topical “cosmetics.” Although not yet accepted from a regulatory point of view, the concept is strikingly appealing in that what is ingested will have a significant impact on health, well-being, and the appearance of the largest organ of the body: skin. The nutritional approach to improving appearance and beauty has an enormous market potential. Orally supplemented nutritional products for skin care grew into a multi-billion-dollar segment and enjoyed double-digit growth in the middle and late 2000s.3 Looking ahead, since our intention is not only to discuss current approaches in this field, we foresee the potential for individualized nutritional approaches to beauty and the opportunity for incredible leaps forward in humanity’s common need to be, look, and feel beautiful and young as we all move into healthy (and beautiful) aging.

There are three fundamental forces behind the use of nutraceutical ingredients in the cosmetic industry. This industry needs cutting-edge, competitive advantages for their products that can offer unique claims and beauty benefits to grow business. The nutraceutical industry is looking to expand applications and claims for their ingredients;4 and consumers—especially baby boomers—are eager to do anything, and everything, to slow down the inevitable aging process and maintain a youthful, healthy appearance and feeling.

The extraordinary growth rate of nutricosmetics in the past ten years has been fueled by new product introductions and a strong marketing push from big-name players. Unfortunately, a lack of scientific evidence and marginal beauty benefits from many nutricosmetics has turned consumers away. Fortunately, the consumer pull has encouraged the technology push that has continued to pursue the holy grail of finding, demonstrating, and proving that the concept of “beauty from within” is an idea whose time has come.

9.1.2 NUTRACEUTICAL INGREDIENTS THAT
ARE SUITIBLE FOR COSMETIC USE

One of the challenges in selecting appropriate nutritional ingredients to achieve skin care benefits is to translate existing nutritional knowledge into a science-based beauty claim and to achieve believable results in complex biological systems that vary from person to person.5 The following general guidelines shall be considered:

• Chemical profile and active components are well characterized.
• The mechanism of action of the active components in the ingredients has direct correlations with perceived skin benefits.
• Nutritional, biological, and functional evidence available from the use of the ingredients is well established.
• Bioavailability data are available to support the oral administration and delivery of the functional components systemically—and preferably into dermis and/or epidermis.
• Optimum dosages assure efficacious levels of the active components.
• Products should be suitable for long-term use without significant safety concerns.
• Regulatory concerns for oral consumption should be addressed.
• Relevant human clinical results should substantiate the usage and skin-functional claims.
• The question needs to be dealt with as to whether one “active” ingredient or the typical multiplicity of ingredients found in nature are the causes of the observed results.

9.1.3 CHARACERIZATION OF NUTRACOSMETIC
INGREDIENTS BASED ON BIOLOGICAL FUNCTION

a. Antioxidation

UV-induced skin damage such as wrinkles, skin aging, and skin cancers has been well documented. However, before such long-term damage appears, complicated structural and functional compromise has occurred at the molecular level, in skin cells, skin tissues, and even at systemic levels after exposure to solar radiation generated at both UVA and UVB wavelengths.

The changes described above include: generation of reactive oxygen species (ROS), modification of proteins and lipids, damage to DNA, and compromises of the integrity of skin-cell membranes.6 Free radicals are produced by normal physiological processes in the body to perform critical functions of cellular defense, inflammation process, and immune responses. Damage, both genetic and epigenetic types, can also be generated from environmental sources such as ultraviolet radiation, tobacco smoke, food additives, and many other pollutants. Cells have specific mechanisms to maintain homeostasis that keeps free radical levels in check. However, if this process is out of balance, free radicals become dangerous, highly reactive, and unstable molecules that damage DNA, proteins, and components of cell membranes. Eventually this type of damage will lead to cellular damage throughout the body and play a primary role in the skin aging process. Physiological changes that occur as we age result in the loss of a homeostatic balance between the generation of reactive oxygen species (ROS) that cause oxidative damage and the production of naturally occurring antioxidants such as glutathione (GSH) or other regulatory enzymes (superoxide dismutase, catalase, and peroxidases).

Antioxidant defense mechanisms are species specific and heavily influenced by nutrition, since important antioxidants such as ascorbic acid and α-tocopherol cannot be synthesized by humans and therefore must be obtained from one’s diet. Antioxidants are popular dietary supplements in the nutritional and functional food industries.7 Nutritional ingredients promoted as antioxidants include vitamins (i.e., VC, VE, VB, β-carotene), minerals (i.e., selenium), amino acids (i.e., lysine, cysteine, n-acetyl cysteine, lipoic acid), polyphenols (i.e., anthocyanidines pycnogenol, tannins, curcumin, resveratrol,), flavonoids (i.e., catechins, EGCG, rutin, quercetine, etc.), coumarine derivatives, and many different types of botanical extracts.8

Even though antioxidants may reduce free radicals in vitro generated by radiotherapy and chemotherapy, there is limited clinical evidence suggesting that a dramatic improvement in systemic oxidative stress in vivo can be achieved from the oral administration of common antioxidants such as alpha-lipoic acid9 and vitamin E even at very high dosages.10 The failure to deliver the perceived reduction of systemic oxidative stress from supplements of simple antioxidants may be due to the sub-optimum dosages, poor bioavailability, and lack of organ/tissue specificity from the antioxidants. Another factor that has to be taken into consideration is how to better control the macronutrients such as fat and sugar, which induce oxidative stress.11 Only considering the food selection based on total antioxidant capacity, without standardization, was another factor cited as a possible reason that reductions of oxidative stress markers could not be achieved in a crossover two-week intervention study.12 Polyphenols are classes of natural antioxidants that exist in fruits, vegetables, nuts, and different plant parts. These exist as free radical scavengers by neutralizing existing free radicals and/or maintaining a reducing environment around the cells and thereby preventing the formation of undesirable “aging” free radicals.13 Natural polyphenols have a great structural diversity with antioxidation capacities higher than vitamin C and E.14 Delivering natural polyphenols in order to meet distinctive nutritional requirements for the managing of oxidative stress phenomena has a unique advantage over the “simple” administration of classical antioxidation vitamins,15 especially at levels approved by regulatory agencies but which may not be optimal for individuals at each stage of their aging process. One of the specific benefits for oral supplement of polyphenols is protection from UV-induced skin erythema, the increase of skin hydration,16 and reduction of hyperpigmentation17 with procyanidins found in apples, pine bark, and grape seeds.

Carotenoids are the most extensively studied and utilized antioxidants in nutricosmetic products. Carotenoids include different types of lipophilic natural compounds such as α, β, λ, and δ-carotenes; lycopene found in fruits such as tomato, watermelon, grapefruit, and red bell pepper;18 lutein found in green leafy vegetables such as kale and spinach; retinoids (vitamin A, retinal, retinol, and retinoic acid); zeaxanthin from marine microalgae; and Astaxanthin. The concentrations of cutaneous carotenoids have been considered as sensitive biomarkers of oxidative stress of skin. Human skin is relatively enriched with high levels of lipophilic carotenoids such as lycopene and beta-carotene compared to dihydroxycarotenoids, lutein, and zeaxanthin.19 Carotenoids in skin are strongly associated with the influence of stress factors such as fatigue, illness, smoking, alcohol consumption, and daily dietary intake.20 Carotenoids have an excellent capacity to quench singlet oxygen (1O2) and inhibit lipid peroxidation. However, they cannot scavenge superoxide anion radicals (O2−), hydroxy radicals (OH·), or hydrogen peroxide (H2O2).2122

Oral supplementation of carotenoid-enriched diets can quickly increase the measured carotenoid level in skin.23 Oral supplementation of isotretinoin for photo-aging has also been documented.24 Many parameters of the epidermal defense against UV-induced damage were significantly improved after seven weeks of oral intake of an antioxidant complex that contained lycopene, α & β-carotene, α-tocopherol, and organic selenium.25 The significant reductions of UV-induced peroxides T-BARs and two markers of UV-induced genotoxicity, p53 expression, and photodyskeratotic cell number demonstrated the efficacy resulting from the combination of protection by diminishment of oxidative stress, and reduction of both UV-induced DNA damage and cell damage.26

Astaxanthin is a marine carotenoid that is distributed in marine bacteria, algae, crustaceans, and fish. This carotenoid is an excellent antioxidant with a unique mechanism that neutralizes oxidative free radicals in both polar and nonpolar zones of phospholipid aggregates. Out of five different carotenoids, only astaxanthin reduces peroxidation and preserves cell membrane structure. In human dermal fibroblasts under UVA exposure, astaxanthin can reduce the level of reactive oxygen species, increase antioxidant enzyme activities, reduce the expression of heme oxygenase, and reduce apoptosis.27 Astaxanthin also shows biological functions including protection of human LDL against oxidative damage; reduction of oxidative stress marker MDA, increase in SOD and TAC, protection against oxidative DNA damage, anti-carcinogenesis, anti-inflammatory benefits, promotion of immune response, protection of nerve cells, relief of eye fatigue, anti-diabetic properties, and anti-obesity activities.28 Recently, in two human clinical trials, orally and in combination with topically administration of astaxanthin for eight weeks at a daily dose of 6 mg significantly improved skin conditions measured by skin elasticity, trans-epidermal water loss, sebum oil level, and crow’s feet wrinkle.29

Human clinical trials have shown clear evidence of photo-protection through oral administration of antioxidants, especially in combining multiple nutritional ingredients with antioxidation properties from different mechanisms of action. The protection of skin from UV and especially long wavelengths of light by lutein and zeaxanthin was reviewed by Roberts in 2009. Lutein and zeaxanthin are found in human skin as a result of dietary intakes. Multiple human ingestion studies showed reduced skin edema, erythema, and hyperplasia caused by UV exposure.30 In a randomized, placebo-controlled 12-week clinical trial, 40 healthy women were divided into four groups to evaluate the effects of lutein and zeaxanthin administrated orally and/or topically. The lutein and zeaxanthin combination significantly decreased lipid peroxidation of skin and increased photoprotective activity, with the best performance from the combination of oral and topical treatment. Oral administration of lutein and zeaxanthin showed the same effects in skin hydration though topical application, which yielded a better improvement of skin elasticity than oral administration.31

b. Anti-inflammation

Sunlight has a significant effect on the skin, causing premature aging, skin cancer, and a host of other skin changes such as erythema and tanning. Exposure of skin to UV radiation induces biphasic reactions. Thus, upon initial exposure, an immediate erythema reaction occurs, a weak reaction that fades within 30 minutes. A delayed erythema reaction occurs after 2–5 hours of exposure and peaks at around 10–24 hours. Enhanced prostaglandin (PGE2) and leukotriene (LTB4) is the major mechanism of action for UV-, sun-, and chemical/thermal-caused erythema.32 Prostaglandins and leukotrienes also play important roles in the physiological and pathological processes of wounds, burns, scalds, acne, microbial infections, dermatitis, and many other diseases and conditions of the skin.33 Many natural nutritional ingredients contain the active components that can be utilized in dermatology by inhibiting the pro-inflammatory pathways related to prostaglandin and leukotriene production.34

It is not surprising that dietary polyunsaturated fatty acids inhibit COX and LOX enzymes due to their structural similarities to arachidonic acid. Polyunsaturated fatty acids also can be metabolized by skin epidermal enzymes to convert into anti-inflammatory and anti-proliferative metabolites.35 The source of the dietary polyunsaturated fatty acids are plant-based 18-carbon fatty acids with three to nine double bonds such as α-linolenic acid (n-3) from canola and flaxseed oil; linoleic acid (n-6) from soy, corn, and sunflower oils; and oleic acid (n-9) from olive oil. Fish oil contains 20 and 22 carbon n-3 fatty acids—eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Dietary polyunsaturated fatty acids not only can decrease PGE–2 and LTB4 production, but also reduce the pro-inflammatory cytokines like TNF-α, IL-1β, and IL-6.36 Dietary polyunsaturated fatty acids have diverse dermatological functions, including maintenance of the stratum corneum permeability barrier, maturation and differentiation of the stratum corneum, formation and secretion of lamellar bodies, inhibition of pro-inflammatory eicosanoids, elevation of the sunburn threshold, inhibition of pro-inflammatory cytokines (tumor necrosis factor-alpha, interferon-gamma, and interleukin-12), inhibition of lipoxygenase, promotion of wound healing, and promotion of apoptosis in malignant cells, including melanoma.37

Human clinical trials showed that dietary omega-3 polyunsaturated fatty acids (omega-3 PUFA) reduce sunburn, which is an acute inflammatory response in humans, by reduction of ultraviolet-B (UV-B) induction of prostaglandin (PGE2) in healthy skin after oral supplement 4 g daily of 95% ethyl esters of eicosapentaenoic acid (EPA) for three months. Abundant clinical evidence also showed that omega-3 polyunsaturated fatty acids, especially EPA, can offer protection against photo-aging, photosensitivity, photo-immune suppression, and photo-carcinogenesis.38 Omega-6 essential fatty acid from borage oil has been studied in 11 clinical trials for dermatitis. Though the efficacy is relatively moderate, an 8- to 12-week oral supplement of 2–4 g per day borage oil showed benefit in controlling the dermatitis and preventing flare-up in mild to moderate disease.39 Oral supplement omega-3 and -6 fatty acid with vitamin C, vitamin E, and zinc can improve the symptoms and reduce severity scores of atopic dermatitis.40

Polyphenols are a widely distributed group of natural products that have been reported to have anti-inflammatory, antiallergic, antimutagenic, antibacterial, antiviral, antineoplastic, antithrombic and vasodilatory activity. Fruits and vegetables such as berries, green tea, grape seed, and soy are the primary sources of polyphenols. In the United States, the level of polyphenol intake is low due to the small amounts of fruits and vegetables consumed by Americans.41 The anti-inflammatory effects from polyphenols are well documented at both systemic and cutaneous levels with clearly defined molecular targets, for example, by the inactivating of reactive oxygen and nitrogen species, inhibiting pro-inflammatory enzymes (COX/LOX/iNOS), and modulating inflammatory signaling pathways at gene expression levels through NF-κB and mitogen-activated protein kinase (MAPK).42 Plant-derived polyphenols interacting with phase II detoxification enzymes plus repairing UV-induced DNA damage are also proposed as the basic mechanism of action for skin photoprotection.43

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