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The Science of Healthy Skin

Edward M. Lieskovan Pharm.D., MBA
Doctor of Adjunct Assistant Professor of Clinical Pharmacy,
University of Southern California, School of Pharmacy
Vice President and Chief Scientist, Envie SkinCare
Tustin, California, USA

Many factors influence the health and appearance of skin tissue including genetics, diet, hormone levels, personal hygiene, and UV exposure from the sun. Experts have long recognized that diet and nutrients in the body play a key role in skin health. Even more important is the dietary content of specific skin nutrients, which may not be present in the typical diet in significant concentrations. These critical skin enhancing dietary elements include: specific mucopolysaccharides and glycoprotiens and the nutritional compounds responsible for their synthesis, a wide range of antioxidants, specific dietary fatty acids and other moisturizing agents, and various other vitamin and mineral co-factors and nutritional elements including herbs and plant materials.

The rapid turnover and replacement of skin cells requires a significant degree of nutritional support to remain healthy. While other organ systems may demonstrate a capacity to withstand nutritional negligence, the skin cannot, and usually manifests the negative effects of nutritional deficiencies within a relatively short period of time. The importance of proper nutritional support of the skin tissue is made even more important by the nature of the skins anatomical and physiological role. As the outermost covering of the body the skin comes into contact with the environment to a greater degree than any other tissue. Solar radiation and the atmosphere itself all affect the skin in a more dramatic manner than they affect any other tissues of the body. These elements, the rapid turnover of cells, and its role as a key biological barrier place demands upon the skin that can only be met when the nutritional status of the tissue is optimally supported.

Optimal support of the skin requires a wide range of nutritional materials that are not always readily available in the typical diet. The only way to guarantee optimal skin health is to supplement the diet with a scientifically formulated nutritional support formula designed to meet the skin’s unique needs. The process of creating this type of supplement had been in development for a long time due to the complexity of the physiological processes that take place in the skin. It has only been very recently and due to advances in science that we have been able to begin to understand how to properly support the skin with nutritional supplements designed to provide long-term health benefits.

The nutritional support of the skin involves four essential elements, which include: 1.) the support of the collagen, elastin, and connective tissues, 2.) the retention of moisture by the skin in order to keep all the elements of this delicate tissue well hydrated, 3.) the maintenance of a potent antioxidant system within the epidermis and dermis to counter the damaging effects of solar radiation, and exposure to chemical pollutants in the atmosphere, and 4.) the maintenance of vascular integrity within the dermal layer.

Review of Skin Anatomy
The skin is composed of two distinct layers, the epidermis and the dermis. The epidermis is the thin outer layer of the skin and is composed primarily of squamous epithelial cells that form within the inner basal or germinative zone and gradually move outward as they mature. These cells begin their life as undifferentiated polygonal cells and gradually flatten as they make their way to the surface layer of skin. The nuclei of these cells degenerates as they move toward the outer layer of the epidermis and the cells will eventually die and become keratinized (keratin is a special protein). Keratinization is typically heavy on the soles of the feet and other skin surfaces that are subject to heavy friction and wear. These keratinized cells continue to move outward and are eventually worn away or flaked off as a normal part of the life cycle of epidermal skin cells. The dead, keratinized cells make up the tough “horny zone” which serves as a barrier to the entry of water and other elements and protects the more delicate inner layers of skin from abrasion or contact with foreign matter.

The dermis is the inner layer of the skin and it contains the vast array of supporting structures that provide a living foundation for the epidermis and provides for the strength, elasticity, and form that allow the skin to fulfill its anatomical and physiological role. The supporting structures within the dermis include: blood and lymphatic vessels, nerves, sweat and sebaceous glands, hair follicles, collagen and elastin fibers (physical structure) and muscle tissue (deep within the dermis). The actual physical structure of the dermis (specifically the reticular layer) of the skin consists of a network of collagen and elastin fibers and an extracellular proteoglycan rich ground substance. Collagen and elastin fibers provide skin with strength and elasticity while the ground substance provides a base that supports other skin structures and provides the skin with its healthy moisture rich form. Proteoglycan (a family of protein rich mucopolysaccharides) are critical to skin health and appearance because they have a high affinity for water and help maintain a high moisture concentration within the jelly like ground substance. Proteoglycans contain important polysaccharide chains called Glucosaminoglycans (GAGs). Dermatin Sulfate and Keratin Sulfate are two of the most important GAGs found within the proteoglycans that make up the ground substance of skin tissues. Proteoglycans are complex macromolecules that provide a variety of roles within skin and connective tissues.

Skin pigmentation is caused by the deposit of melanin within the inner epidermis and outer dermis. The extent of pigmentation is controlled by the melanin-stimulating hormone, which is regulated by the anterior lob of the pituitary gland. Melanin itself is secreted by specialized Melanocyte cells and this process may be accelerated by inflammatory processes (oxidative damage) that occur secondary to excessive UV exposure (sunburns).

Skin – The Aging Process
Skin ages over time like all other tissues but because of its high visibility, age related changes in the skin are more easily recognized than similar changes in other tissues. The age related changes occur at different rates in different individuals depending upon their ethnic background, individual genetic makeup, hormonal factors, diet, UV exposure from the sun, and the degree of care they have given their skin. Thin skinned and fair (light) skinned individuals typically develop characteristics of aging more rapidly than do thicker, darker skinned individuals. Individuals who have greater exposure to the sun typically experience more rapid skin aging than those who have less solar exposure. Nutritional status also plays a vital role in the aging process. Individuals who maintain a better overall nutritional status (through better diet and the use of supplements) over their lifetimes typically show less skin aging than those with a nutritionally inferior diet and a lack of supplementation. Other factors like environmental pollution, smoking, drug and alcohol use, and stress can all affect the rate at which the skin ages. Recent studies show that the skin of smokers typically ages at an accelerated rate and that their skin may appear from 5 to 10 years older than that of a non-smoker. Other factors may further accelerate the aging process of the skin and it is quite possible to be 30 years old and have the skin of a 50 year old. Those who avoid these age accelerating factors and properly care for their skin with moisturizers, dietary supplements, and other protective measures may have the vibrant, healthy, and youthful skin of a 30-year old well into their 50’s or 60’s or even longer if they are fortunate enough to have good genes.

As the skin ages a variety of processes take place including: the appearance of dark age spots, discoloration and wrinkles, the loss of skin tone and elasticity (sagging and elastosis), the gradual appearance of a rougher skin texture and a thinning of the epidermis, and a general loss of skin moisture and fullness. All of these changes are part of the normal aging process but the rate and extent of change can be dramatically accelerated or retarded.

Age Related Dermal and Epidermal Changes

The normal aging process will eventually result in dermal and epidermal changes that will affect the structure and appearance of the skin. While many of the complex processes that affect the normal aging of the skin are still being researched, scientists now recognize oxidative damage as a major contributor to the aging process. And the single greatest cause of oxidative damage is UV radiation from exposure to sunlight. Scientists know that excessive exposure to sunlight can trigger inflammatory processes within the delicate skin tissues that result in an acceleration of the aging process. As the mechanism behind these oxidative processes has become better understood, we have now come to realize that the cumulative effects of even light to moderate exposure to UV radiation, over a lifetime, can cause significant pathological changes within the dermal and epidermal tissues. Since it is impossible to totally avoid exposure to solar radiation, it is important to get a greater understanding of these oxidative processes so that we can better protect our skin.

Skin tissues contain an amazing collection of enzymatic and non-enzymatic defense systems to help protect delicate dermal tissues from oxidative damage. These enzymatic systems include:

1. Superoxide Dismutase
2. Catalase
3. Peroxidases
4. The Glutathione System
5. Thioredoxin Reductase
6. The Lipoamide System
7. NADPH Ubiqinone Reductase

The mechanisms of action of these enzymatic systems are fairly well understood but are to complex to fully elaborate in this paper. For the purposes of this discussion it is sufficient to say that all of these systems are capable of protecting delicate tissues from the pathogenic effects of Reactive Oxygen Species and other Free Radicals associated with oxidative damage. These systems affect this mission by breaking down these free radicals before they have a chance to cause oxidative damage to the skin tissues.

In addition to the enzymatic systems, there are a number of non-enzymatic antioxidants, which also help to protect the skin. Well known non-enzymatic antioxidants include the following:

1. Vitamin C
2. Vitamin E
3. Caronenoids including Beta Carotene and Lycopene
4. Bioflavonoids
5. Oligomeric Proanthocyanidins (Grape Seed Extract)
6. Coenzyme Q10
7. Polyphenols (Green Tea)

These nutritional antioxidants work synergistically with the enzymatic antioxidants to provide maximum protection from free radicals and the oxidative damage that they cause. Because each type of enzymatic and non-enzymatic antioxidant systems has its own unique features and effects, it is important that all of the systems are well represented and fully functional within the skin tissues.

Age related changes that affect connective tissues within the dermal layer also play a profound role in the aging of skin. The reticular layer of the dermis contains a network of collagen and elastin fibers that give skin it strength and elasticity. The ongoing synthesis of stable collagen fibers requires the presence of the enzyme prolyl hydroxylase and Ascorbic (Vitamin C). Shortages of Vitamin C results in the production of defective and unstable collagen that has a tendency to breakdown within the normal body temperature range. The clinical manifestation of Vitamin C deficiency is known as Scurvy, a disease, which results in a loss of connective tissue integrity and eventually death if left untreated. Normal collagen synthesis also requires a readily available supply of amino acid. These critical collagen building blocks must be supplied by dietary proteins. Since the concentration of the amino acids Proline and Glycine are very high in collagen dietary protein sources must be of sufficient quality and quantity to provide for adequate amounts of these elements.

The proteoglycan macromolecules that comprise the moisture rich viscoelastic matrix that fills the space between collagen and elastin fibers are critical to skin health and appearance because they help keep the dermal tissues well hydrated. Due to the lack of capillaries (vascular tissues) in the epidermis these tissues receive vital nutrients via a passive diffusion process, from highly vascularized dermal tissue. This process is badly compromised if these tissues become dehydrated. Well-hydrated dermal tissues also give the skin a healthy and youthful appearance by helping to hide wrinkles and provide for an attractive fullness and resilience.

Envie Provides Targeted Nutritional Support for the Skin

Envie is a powerful all natural formula that provides targeted nutritional support for the skin through the following mechanisms:

Envie Prevents the Excessive Crossbinding of Collagen Fibers
UV radiation from the sun is responsible for an inflammatory reaction that causes oxidative damage to collagen and elastin fibers. The process results in excessive and abnormal crossbinding of collagen and elastin fibers within the dermal layer of the skin. This process disrupts the normal structural role that collagen plays and results in an abnormal contraction of the dermal tissue and in a marked decrease in the dermal moisture content due to a reduction in the proteoglycan content of affected tissue. A reduction in the moisture content of the skin also disrupts the normal passive diffusion process that supplies critical nutrients to the epidermis. This results in a reduced turnover of epidermal tissues and anatomical changes that are associated with the aging process. This type of damage is cumulative and even moderate exposure to solar radiation can eventually lead to a significant acceleration of the aging process within these tissues. Skin that is damaged by this type of process lacks the normal moisture content of healthy skin and appears thinner, rougher, and more wrinkled. Oligomeric Proanthocyanidins (OPC’s from Grape Seed Extract) in Envie bind directly to collagen and elastin fibers within the dermal tissues and prevent the oxidative reactions that lead to excessive and abnormal crossbinding. OPC’s are also believed to help realign damaged collagen fibers and help to restore normal collagen activity within the dermal tissues.

Though OPC’s have the most potent results against this type of oxidative damage, other enzymatic and non-enzymatic antioxidants play a role in this protective process. Envie supplies skin tissues with Vitamin A (beta carotene), C, and E which all provide potent nutritional antioxidant activity to further protect the integrity of the collagen and elastin connective tissue network. Green Tea (a source of antioxidant polyphenols) and Citrus Bioflavonoids provide additional antioxidant protection. Envie also contains the trace minerals Selenium and Zinc, which are both mineral cofactors that are required for the production of the powerful endogenous Glutathione Antioxidant Systems (one of the powerful enzymatic systems present in skin tissue). The Glutathione Antioxidant Systems plays a major role in destroying reactive oxygen species that are responsible for oxidative damage to collagen, elastin, and other dermal tissue.

Envie Protects Collagen and Elastin from Destructive Enzymes
OPC’s contained within the Envie formula also bind to collagen and elastin fibers and protect them from abnormal and accelerated breakdown by powerful and overactive collagenase and elastase enzymes. It is not known why these destructive enzymes become overactive during the aging process of the skin, but it is believed that this process may also be caused by inflammatory reactions linked to UV radiation exposure and related causes. OPC’s seem to reverse this process regardless of its cause.

Envie Protects the Delicate Dermal Vascular System
OPC’s, Citrus Bioflavonoids (Rutin, Hesperidan, and Quercetin), as well as Vitamins A (retinly palmitate and beta carotene), Vitamin C and E work synergistically to help prevent oxidative damage to the critical vascular tissues (capillaries) that support dermal tissues (and epidermal tissues via passive diffusion). Because of their location, these capillaries are easily damaged by solar radiation. Damaged and broken capillaries within the dermal tissue cause a great deal of damage to the surrounding tissues (edema) and can result in a loss of vascular integrity within effected areas of the tissue.

Envie Helps Prevent the Oxidation of Dermal Fats
Lipid Soluble antioxidants including Vitamin E and Ascorbyl Palmitate help prevent the oxidation of Fats within the Tela Subcutanea and also help prevent oxidative damage to lipid rich cellular membranes. Oxidized Lipids can be highly pathogenic to surrounding tissues and their formation must be blocked by antioxidants that are capable of concentrating in these tissues. Envie contains a balanced blend of water and fat soluble antioxidants to provide complete coverage in a wide range of tissues.

Envie Helps Promote Healthy Collagen and Elastin Fibers
Envie helps promote healthy collagen by serving as both a concentrated source of critical amino acids containing protein substrates and by stimulating the cellular production of new collagen fibers. Two proprietary natural protein containing substances, Numarine™ and Cymogen™, have been included in the Envie formula to help upregulate the synthesis of healthy collagen and connective tissues and to provide critical amino acid substrates for this process.

Envie Helps Stimulate Proteoglyan Synthesis and Promotes Improved Moisture Retention within Dermal Tissues
Numarine™ also helps to stimulate the synthesis of vital proteoglycans by upregulating natural biological pathways. Proteoglycans are critical to skin health because they form the viscoelasatic matrix that forms the moisture rich ground substance within the dermal tissue. Proteoglycan synthesis slows with age and must be reactivated in order to maintain optimal skin hydration and appearance.

Envie Helps to Reduce the Occurrence of Age Spots
Age spots are deposits of Melanin that are released by the body as a means of protecting itself from solar radiation. This process is mediated by an inflammatory response within the dermal tissues that creates oxidative damage. Envie helps prevent this type reaction by providing a concentrated source of antioxidants that can destroy free radical species before they can damage delicate tissues.


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