Skin care regimens tailored toward specific skin types and conditions have garnered interest among consumers who are leaning toward a more personalized approach in caring for their skin.

In an increasingly competitive marketplace, manufacturers are seeking the newest active ingredients, delivery systems and results that differentiate their products from the competition. The hot button resides in the most current research on amino acids and specific components of the skin, providing new opportunities and outlets for addressing pervasive skin conditions. Interestingly, the latest dermatologic research pulls back the layers and delves deep into the physiology and anatomy of skin. Instead of looking at solutions to these problems, researchers are uncovering the root causes behind dryness, dermatitis, allergies and reactions.

A FLESHY FOUNDATION

Skin consists of two main structural layers: the epidermis, the outer protective layer of the skin; and the deeper layer known as the dermis, which provides the skin’s structural support. The epidermis is made up of layers of cells in various stages of development, connected by protein bridges called desmosomes. At the base of the epidermis are reproductive cells known as basal cells. When these cells evolve and mature they move toward the outer skin layer, making room for new cells. As they reach the stratum corneum, the top layer of skin, the cells turn into corneocytes, cells that lack a nucleus and cellular structure. "Corneocytes are flat, hexagonal-shaped cells filled with water-retaining keratin proteins surrounded by a protein envelop and lipids," said Christina Marino, M.D., in a Washington State Department of Labor and Industries report, "Skin Physiology, Irritants, Dry Skin and Moisturizers." "The cellular shape and the orientation of the keratin proteins add strength to the stratum corneum. There are 10 to 30 layers of stacked corneocytes." She added stacked bilayers of lipids surround the cells in the extracellular space, which helps form the natural physical and water-retaining barrier of the skin.

Filaggrin, an essential protein in skin barrier function, is gaining attention as a vital component of healthy skin. It serves a key role in the process of forming a protective layer in the stratum corneum, and helps keep water in and foreign organisms out. As aging cells move toward the stratum corneum, the cells clump proteins into granules, which are then filled with filaggrin. Afterward, a complex of keratin proteins and filaggrin is produced to protect the filaggrin from proteolytic breakdown. As old cells move toward the stratum corneum, enzymes break down this complex, causing the filaggrin to reside outside of corneocytes, and the keratin inside the corneocytes, Marino explained, noting, "When the moisture content of the skin is decreased, specific proteolytic enzymes in the stratum corneum are triggered to further break down filaggrin into free amino acids."

exCel Cosmeuticals, manufacturer of the patented AFA™ formulation based on the body’s natural acid amino acids, added, "Filaggrin is metabolized in the epidermis into several acidic amino acids and these amino acids are the primary agents responsible for the skin’s ability to retain moisture."

Research suggests a lack of filaggrin can result in conditions such as dry skin (ichthyosis vulgaris) and atopic eczema, a chronic inflammatory skin disease characterized by a defective skin barrier function that affects 10 to 20 percent of children and 1 to 3 percent of adults in industrialized countries.¹ University of Dundee, Scotland researchers, led by Irwin Mclean, found a defect in the filaggrin gene can cause dry skin, eczema, eczema-associated asthma and other allergies.² Additionally, researchers from the National Jewish Medical and Research Center, Denver, investigated whether reduced filaggrin expression already existed in patients with atopic dermatitis (AD), or if the filaggrin was modulated as a response to atopic inflammation. They concluded after evaluating 69 subjects that patients with AD have an acquired defect in filaggrin expression that can be modulated by the atopic inflammatory response.³

Current topical solutions for these conditions consist of emollients and ointments used to keep the skin moist, as well as anti-inflammatories to treat inflammation. New cosmeceutical ingredients also hold promise in helping ease the symptoms or lower the risk of eczema. For example, a study published in the Journal of Allergy and Clinical Immunology found mothers taking probiotic supplementation during pregnancy and providing young infants with Lactobacillus reuteri after birth could reduce the incidence of eczema.⁴ Another study suggested supplementation with the omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) may offer bioactive benefits for atopic eczema sufferers.⁵

THE NATURAL MOISTURIZING FACTOR

In the course of the last few decades, a group of compounds, consisting of free amino acids (some of which are broken down filaggrins), lactic acid, urea and salts, have been identified as key nutrients in attracting and retaining water, which are responsible for maintaining a healthy balance for moist and pliable skin. These components, as well as ingredients that mimic their actions, are often referred to as the natural moisturizing factor (NMF). "The natural moisturizing factor is an integral component of the horny layer of the skin," said Bruce Gesslein, technical manager, Ajinomoto USA Inc., Specialty Chemicals Division. "The horny layer is comprised of about 30 percent NMF, 10 percent lipids and 60 percent PCA [pyrrolidone carboxylic acid, an amino acid-derived component]. The NMF is responsible for maintaining moisture and suppleness of the skin. It has been shown that in unhealthy and damaged skin, the NMF is depleted to an extent."

NMF components absorb water from outside elements and combine the liquid with its own water content, keeping the outer layer of the stratum corneum hydrated. Interestingly, because these compounds are water soluble, overhydration can make the skin drier. In a study published in the Journal of Investigative Dermatology, researchers investigated the specific influences of NMF components other than amino acids and found seasonal changes in the physical properties of the stratum corneum from summer to winter were accompanied by significant decreases in the levels of lactate, potassium, sodium and chloride.⁶ Lactate and potassium were the two components found to correlate significantly with the state of hydration, stiffness and pH level. Moreover, potassium lactate restored the stratum corneum hydration state decreased by extraction of NMF, suggesting lactate and potassium may play roles in maintaining the physical properties of the stratum corneum.

When the NMF content is reduced, a variety of complications can occur, ranging from tough skin and flaking to wrinkles. A prolonged stratum corneum malfunction can weaken the skin’s intercellular matrix.^7,8 A variety of constituents such as amino acids, proteins, ceramides, hyaluronic acid, fatty acids, linoleic acid are just a few elements that work in keeping the skin moisturized.

WATER RETENTION

Amino acids are fundamental constituents of the 100,000 different proteins found in the human body. The sequence of amino acids determines the unique properties of each protein. If one essential amino acid is missing, the protein cannot be formed. Each protein is composed of different quantities of amino acids, which include alanine, arginine, asparagine, aspartic acid, cysteine, cystine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine and valine. Some of these amino acids, called non-essential, can be synthesized by the body; essential amino acids must be obtained from the diet. According to Ajinomoto, about half of the NMF in the skin is made up of amino acids and PCA derived from glutamate, another amino acid. "Skeletal muscles, organs, skin and hair are comprised of these proteins," Gesslein added. "They also occur in the free state in the skin where they act as moisturizers, enter into metabolic cycles and are essential for health and life."

Yoichiro Sugimura, director of business development, Kyowa Hakko Kogyo, added: "Amino acids are the building blocks of protein. Skin is made up mostly of collagen, and collagen of protein. Hence, amino acids work as basic structure components of the skin."

According to in vitro and in vivo clinical research, Kyowa found a certain amino acid, L-hydroxproline (as Lumistor®, from Kyowa Hakko), stimulates collagen synthesis, increases skin moisture and has an anti-wrinkling affect. "In other words, it is not just a ‘passive’ building block, but a ‘proactive’ cosmeceutical, too," Sugimura said, adding L-hydroxproline works topically and internally to achieve an anti-wrinkling result.

Amino acids function on several levels. "Amino acids are important components of the skin and the NMF," Gesslein said. "They have various functions including the promotion of collagen production, modulating micro-circulation, and keeping the skin moisturized and supple. By working both on and in the skin, the effects can be maximized."

When used as ingredients within cosmetics, amino acids most often serve as humectants or water-binding agents. They’ve also been suggested to enhance the bioavailability of minerals, according to Albion Advanced Nutrition. However, recent discoveries have suggested amino acids may possess both antioxidant and wound-healing properties. AGI Dermatics, for example, released comparative data that claimed its L-ergothioneine, an exclusive natural amino acid used in topical applications, is a powerful antioxidant that protects against oxidative damage and reduces ultraviolet (UV)-induced hydrogen peroxide generation.⁹

Collagen, a key protein found in connective tissues, provides structure and strength to these tissues. Ajinimoto noted collagen actually consists of various amino acids and, when used as a cosmetic ingredient, keeps the skin supple. According to Ajinomoto, the administration of the amino acid arginine promotes the regeneration of skin due to its enhanced collagen synthesis in the dermis, and the involvement of glutamine and arginine may participate in the synthesis of collagen and elastin¹⁰—the bundles of protein that allow the skin to stretch and snap back to its original state.

The NMF factor continues to serve as inspiration for new research and ingredient innovations. While amino acids in general have been used in moisturizing creams and anti-aging properties for quite some time, combination amino acids hold promise as potential cosmeceutical ingredients. Kyowa, for example, is focusing on di-peptides, molecules comprised of two amino acids joined by a peptide bond. According to Sugimura, di-peptides yield a completely different physiological effect from that of the two component amino acids. Kyowa’s Alanyl-Glutamine acts as an energy source for cells, vitalizing the skin and offering collagen synthesis ability.

Gesslein noted more personal care products will feature amino acids in their ingredient profile: "Individual amino acids, especially optimized combinations of amino acids, to deliver specific functions will continue to grow. Since these materials can be easily formulated in personal care products and produce real consumer perceptible effects, amino acids will play a key ingredient now and in the future."

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The NMF Glossary

Amino acids, lipids, ceramides, hyaluronic acid are similar in the way they serve as building blocks for the skin.

Lipids cannot penetrate the skin, so they provide a cover layer and protect skin from external environmental pollutants.

Ceramides are intercellular lipids composed of sphignolipids and fatty acids. They form bilayers that help the skin maintain moisture and recover from damage—especially good for the skin membrane.

Hyaluronic acid is a non-sulfated glycosaminoglycan found in connective tissue and epithelial cells. It is used mainly as a topical moisturizer since its molecular weight is too large to penetrate the skin surface. It has an extremely high water retention capacity and can capture moisture internally and from the outside environment.

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References

1. Schultz-Larson FV, et al. “Epidemiology of atopic dermatitis” (Immunol Allergy Clin North Am. 2002; 22:1-24).

2. Mclean, Irwin, et al. “Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema” (Nature Genetics. 2007; 39” 650-54).

3. Howell MD, et al. “Cytokine modulation of atopic dermatitis filaggrin skin expression” (J Allergy Clin Immunol. 2007; 120: 150-5).

4. Abrahamsson TR, et al. “Probiotics in prevention of IgE-associated eczema: a double-blind, randomized, placebo-controlled trial” (J Allergy Clin Immunol. 2007;119(5):1174-80).

5. Koch C, et al. “Docosahexaenoic acid (DHA) supplementation in atopic eczema: a randomized, double-blind, controlled trial” (Br J Dermatol. 2007; OnlineEarly: doi:10.1111/j.1365-2133.2007.08430.x).

6. Nakagawa N, et al. “Relationship between NMF (lactate and potassium) content and the physical properties of the stratum corneum in healthy subjects” (J Inv Dermat.2004; 122: 755-63).

7. Sakai S, et al. “Characterization of the physical properties of the stratum corneum by a new tactile sensor” (Skin Res Technol. 2000; 6(3): 128-134).

8. Rawlings AV, et al. “Moisturization and skin barrier function” (Dermat Ther. 2004; 17(1): 43-48).

9. Ballon G, et al. “Glutamine increases collagen gene transcription in cultured human fibroblasts” (Biochim Biophys Acta. 1995; 1268(21): 311).

10. Dong KK, et al. “L-ergothioneine reduces UVA340-induced hydrogen peroxide in fibroblasts more efficiently than idebenone” (AGI Dermatics, 2007; presented at the 65^{th Annual Meeting of American Academy of Dermatology)}