OZON Emma Adriana1, NIȚULESCU Georgiana1*, BALACI Teodora Dalila1, LUPULIASA Dumitru1
1 Pharmaceutical Technology Department, Faculty of Pharmacy, ”Carol Davila” University of Medicine and Pharmacy, 6, Traian Vuia Street, 020956, Bucharest (ROMANIA)
*corresponding author, firstname.lastname@example.org
The beauty industry is constantly developing and nutricosmetics represent the newest trend based on beauty from within principle. In this review an analyze of some product components such as hyaluronic acid, omega‐3 fatty acids, vitamins and minerals and natural compounds is reported.
Keywords: beauty from within; nutricosmetics, omega‐3 fatty acids, hyaluronic acid
The combination between nutrition and cosmetic in the same word opened a new field to be explored by various industries: food, cosmetic, and even pharmaceutical. Currently the legislation of nutricosmetics is not well establish because these products represent a border category. In Europe, the nutricosmetic supplements have to comply with the Directive 2002/46/EC of the European Parliament and of the Council establishing that ”food supplements’ mean foodstuffs, the purpose of which is to supplement the normal diet . In the United States, the Food and Drug Administration regulates the nutricosmetic market under the Dietary Supplement Health and Education Act (1994) . However, the nutricosmetic market has grown significantly in the last years, thus the need for methods to prove their effectiveness. This review examines clinical data for some of the ingredients used in nutricosmetics regarding their impact on skin and general health.
Hyaluronic acid (HA), also known as Hyaluronan, is an anionic, non-sulfated glycosaminoglycan unfold wide throughout the connective and epithelial tissues. This molecule is built of an energetically stable oligosaccharide that is composed of D-glucuronic acid and N-acetyl-glucosamine groups through interchanging β-1,4 and β-1,3 glycoside bonds. These individual disaccharides bind along and arrange in different forms from a curl to a coiling. The chain structure can have varied length and relative molecular mass ranging from 10 to 1000 kDa with length up to 10 nm. With such a large range in its molecular weight, HA has acquired different elastic properties which can be employed for various medicinal uses . HA plays important roles in our body such as cell and organ development, the response to tissue injury and inflammation, cell migration, cancer formation and resistance .
For the cosmetic purposes HA is used in topical delivery systems which localize the compounds in the skin such as creams, gels, or transdermal formulations which deliver the active compounds through the skin into the bloodstream. In topical formulations HA is able to hydrate both the stratum corneum and the dermis due to its exceptionally strong water-absorption property. It was observed that the low molecular weight HA (5 kDa) displayed higher stratum corneum hydration capacity as compared with medium (100 kDa) and high (1 MDa) molecular weight ones. That is because the high molecular weight HA increase the viscosities of formulations, providing lower diffusion rate of drugs from the formulation onto the skin surface, which eventually leads to the permeation retardation . As a biocompatible, biodegradable and non-immunogenic biomaterial, HA can be easily delivered by minimally invasive injections in aesthetic procedures . Although HA fillers may seem to be similar, they actually each have different physical properties that differentiate them, making proper product choice important when used for facial rejuvenation. Factors such as HA concentration, amount of cross-linking, particle size, extrusion force, and elastic modulus influence product selection and indications . Several trials studied the effects of HA fillers on correction of nasolabial folds [6,7], facial wrinkles [8-10] or lip enhancement[11-14] with positive results. Although this method is well supported it is not without complications such as nodules, granulomas, prolonged edema, Tyndall effect – blue-grey hue, infection, biofilm (nonischemic complications) or skin ischemia/necrosis, blindness/visual compromise (ischemic complications) . Kawada and colab. reviewed the studies ran until 2012 that observed the effects on skin of ingested hyaluronan and concluded that a consumption of 35 to 240 mg of HA daily for at least a month would significantly increase the skin moisture .
In the in vitro studies, the physiological activities of HA in the body vary with its MW , so several types of HA manufactured by Kewpie Corporation (Tokyo, Japan) were studied in double-blinded, placebo-controlled clinical trials. In the first one, the effects obtained using HA with MWs of 800 k (Hyaluronsan HA-F) and 300 k (Hyabest® (S) LF-P) were studied. The study confirmed that daily ingestion of 120 mg of HA (MWs: 800 k and 300 k) for 6 weeks increased the skin moisture content and improved the facial aging symptoms such as luster and suppleness, in subjects with dry skin. There were no differences in the effects of ingesting HA of various MWs, which we confirmed by using HAs with MWs of 800 k and 300 k as they had the same moisturizing and skin improvement effects . In the second one, Hyabest® (A) – MW 2 k and Hyabest® (S) LF-P – MW 300 k were studied. Sixty Japanese male and female subjects received 120 mg HA of MW 2 k or 300 k per day for 12 weeks. The HA 300 k group and the HA 2 k group shown suppressed wrinkles compared with the placebo group . Even though the hyaluronan polymers have a vast range of activities which vary with their MW in clinical trials the efficacy of oral HA on wrinkles could not be different depending on the MW of HA, one possible cause can be that the HA is decomposed to low MW by intestinal bacteria then absorbed into the body. The effects on skin of different combination with HA were studied in several trials. In an uncontrolled monocentric study, the test product was a HA of biotechnological origin (NUTRIHYL) with a molecular weight of ≥ 1 MDa, designed for nutritional use, diluted in in a cascade-fermented organic wholefood concentrate supplemented with biotin, vitamin C, copper, zinc, and natural silica. Intake of the HA solution led to a significant increase in skin elasticity, skin hydration, and to a significant decrease in skin roughness and wrinkle depths . A multicomponent nutraceutical containing 200 mg of HA, 500 mg of L-carnosine, and 400 mg of methylsulfonylmethane was tested in a randomized, placebo-controlled study for the effects on facial skin and wellbeing. It was observed a statistically significant decrease in sebum secretion in the glabella area, and an overall increased hydration and elasticity in the facial skin . Even though HA has the best results on skin when is administrated by an invasive method, the oral intake showed that it can be a promising ingredient in nutricosmetics.
Lipids: ω-3 and ω-6 polyunsaturated fatty acids
The two major classes of polyunsaturated fatty acids (PUFAs) are the ω-3 and ω-6 fatty acids. Because they cannot be synthesized in human body, the ω-3 (alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA)) and ω-6 (linoleic acid (LA) and arachidonic acid (AA)) are known as essential fatty acids. Due to their contributions in cardiovascular disease , metabolic syndrome  neurodevelopment , neurological disorders, and also their roles in skin health the ω-3 FAs represent an important source for health industry. The stratum corneum is formed by corneocytes that are embedded in a lipid-rich matrix comprising a large number of ceramide species, cholesterol and free fatty acids. The epidermal keratinocytes have a poor ability to form long chain PUFAs, this highlights the importance of systemic long chain PUFA supplementation for skin health, and the role of dermal-epidermal cross talk for the efficient structure and function of the epidermis. The implication of ω-6 and ω-3 PUFAs in the skin health are distinct. The LA (ω-6) contributes to the formation of ceramides essential for the structure of the epidermal barrier, and the absence of LA-containing ceramides in the stratum corneum results in barrier permeability problems. Derivatives of ALA (ω-3) can modulate the immune response of the epidermis that influence many inflammatory dermatoses, including acne vulgaris, psoriasis, atopic dermatitis, systemic lupus erythematosus and skin cancer. They also can prevent UV‐induced inflammation and hyperpigmentation and speed up skin wound healing .
Even though the products with PUFAs are mainly indicated for cardiovascular protection their promising in vitro effects on skin conducted to further researchers in the field. The effects on skin elasticity, TEWL, and skin roughness of a liquid product (Eskimo® Skin Care) was tested in a single-blind randomized trial on 24 healthy women. It contains the natural stable fish oil Eskimo-3 (70%), evening primrose oil (20%), canola oil (10%) and vitamin D 40 IU/mL. It contains 12.7% EPA, 8.1% DHA and 2.1% gamma-linolenic acid (GLA) . There was a 10% increase in skin elasticity in the Eskimo® Skin Care group after 12 weeks of treatment, but without a difference in skin roughness or TEWL values. Morse and colab. proved in an open-label clinical trial that a supplement (Bend Skincare Anti-Aging Formula) administrated for 8 weeks significantly improved tolerance to UV exposure. The daily intake was 1400 mg of EPA+DHA, 120 mg of GLA, 5 mg of lutein, 2.5 mg of zeaxanthin, and 1000 IU of vitamin D3 . These studies represent a proof that ω-3 fatty acids can be useful for preventing an aged-induced decrease in skin elasticity and provides skin photoprotection that increases with continued use and should be further explored. The PUFAs sources for the dietary supplement formulations include fish oil, krill oil, cod liver oil, and vegetarian products that contain algal oil. Usually the products provide omega-3 fatty acids in one of three forms: triglycerides, ethyl esters, or free fatty acids. As liposoluble ingredients PUFAs are sensitive to oxidative reactions giving rise to a range of new compounds with the development of undesirable flavors and loss of nutritive value.
Researchers are focused to improve the stability and bioavailability of the commercial products. The microencapsulation technology has been explored to overcome the ω-3 FAs oxidation that can lead to off flavors and odors, which are deemed undesirable by consumers.
Various methods are used for microencapsulation of ω-3 oils, such as: spray drying of emulsions, freeze dried emulsions, fluidized bed drying, extrusion, melt injection, complex coacervation, inclusion complexation, liposome entrapment and also some emerging microencapsulation methods (electrospraying for ultrathin coating, spray granulation and fluid bed film coating and encapsulation using ultrasonic atomizer) .
Vitamins and minerals
Vitamins are almost ubiquitous ingredients in nutricosmetic formulations. The most common are vitamins C, D and E. Vitamin C may promote fibroblast proliferation, migration, and replication-associated base excision repair of potentially mutagenic DNA lesions. Also, vitamin C plays an important role in the synthesis and release of type IV collagen . Vitamin E is the most important lipid-soluble membrane-bound antioxidant in the body and works synergistically with vitamin C. Topical vitamin E showed photoprotective effects when is applied before UVA and UVB-exposure and oral supplementation of vitamin combined with topical application may have implications for conditions of dry skin such as atopic dermatitis .
Minerals with important roles in skin function are copper, zinc and selenium. Copper promotes keratinocyte and fibroblast proliferation and is an important cofactor in enzymatic reactions during collagen crosslinking with lysyl oxidase and skin pigmentation with tyrosinase. Selenium has an important role in DNA synthesis and repair, cell apoptosis, and guarding against oxidative damage . As antioxidant selenium may have effects on skin photoaging, but more studies are needed to determine the ideal daily dose of selenium to achieve maximal skin benefit. Zinc is an important cofactor for cellular activity and defense. It protects against lipid peroxidation, UV-induced cytotoxicity, and oxidative stress induced by reactive oxygen species (ROS) made and distributed within the cytosol by macrophages. It plays a major role in wound healing and keratinocyte cell survival and also has an anti-inflammatory effect by hindering intercellular adhesion molecule 1, a pro-inflammatory marker of keratinocytes, and decreasing the production of nitric oxide . The most important sources for minerals are the foods that contain them, such as nuts, seeds, seafood, meat and whole grains, however oral supplementations represent a convenient method to achieve daily recommended doses.
As part of diet, plants represent an important source of nutrients, not only vitamins and minerals, but also various compounds with signifyingly roles in human health.
Carotenoids are isoprenoid metabolites synthesized by all photosynthetic organisms (including plants, algae and cyanobacteria) and for humans are essential nutrients because they do not synthesize carotenoids de novo, the exogen intake is necessary for the production of retinoids such as vitamin A . They are the most efficient singlet oxygen (1O2) quencher in biological systems and they protect against oxidative damage from UV light the tissues in which they accumulate: β-carotene in skin and lutein and zeaxanthin in the macula lutea . Several studies proved that supplementations with carotenoids protect the skin from UV-induced erythema. Beside the photoprotective effect, Balić and colab. reviewed the studies that proved their beneficial effects in prevention and improvement of skin aging (improved skin elasticity and hydration, skin texture, wrinkles, and age spots) . Consider all of that, the inclusion of carotenoids as antioxidant ingredients in nutricosmetics is justified by their effects and their accumulation in the target tissue, the skin.
A widely distributed class of compounds in the plant kingdom are polyphenols, with more than 8000 structures identified until now. This highly diverse group of natural products contains three main sub-groups: phenolic acids, flavonoids and nonflavonoids . These compounds are extremely studied as anti-aging agents due to their antioxidant and antiradical activities. Normal cellular function involves an oxidative metabolism that generates ROS. The photo-aging cause dermal damage via he impact of ROS production and oxidative stress mechanisms and it is responsible for a majority of the pathological changes in human skin such as: damage to DNA, the inflammatory response, reduced production of antioxidants and activation/inhibition of various signaling factors which lead to collagen and elastin degradation. A specific study regarding the nutricosmetics and cosmeceutical potentials of polyphenolic bark extracts from Canadian forest species was conducted by Royer and colab. and their results shown that the extracts had antiradical activities and capacity to inhibit enzymes involved in loss of skin elasticity and hyperpigmentation and could act as anti-aging agents . As their antioxidant activities are well established, a multitude of natural extracts rich in polyphenols are included in nutricosmetic formulations, the most frequently used for increasing lifespan are: resveratrol, quercetin, curcumin and catechins/ epigallocatechin 3-O-gallate (EGCG) . The inclusion of polyphenols in nutricosmetic products may raise formulation issues regarding their stability and bioavailability. The polyphenolic profile of a product is very easy influenced by a range of acidity, heat, light and enzymatic reactions that can occur during the processing of fresh fruits and vegetables such as washing and refrigerating, grain milling, fermentation, roasting, blanching, juicing and thermal processing . Relatively low water solubility represents a disadvantage that influence the bioavailability. Due to all that reasons the formulation of polyphenols require some methods to protect them. Liposomes coated with various polymers are used to enhance the stability, local bioavailability and even to bypasses the stomach if the coating material is insoluble at gastric pH, such as different types of eudragit . The most common polymers are: hydroxypropyl methylcellulose, carboxymethyl cellulose or biopolymers such as chitosan, lysozyme, arabic gum, whey protein.
The aging process, and implicitly the general health conditions are influenced by three main factors: genetics and family history; lifestyle choices and exercise, and finally diet and nutrition. The last one is, possibly, the most approachable solution to aging and associated morbidity . Clinical proofs are an advantage for manufacturers because they increase consumer confidence in the product and therefore sales. Currently, studies on the effectiveness of nutricosmetic ingredients are constantly evolving and their results are promising, but because the ingredients of interest are also found in food, rigorous working protocols are needed to achieve solid results.
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