Topic of the Month

Micronutrients in human development – Part 3

September 1, 2013

Skin possesses the lifelong ability to renew itself, but as we age this process takes longer. Between the ages of 20 and 50 the rate of skin cell renewal gradually slows, and after the age of 50 it slows ever faster. The surface layer of the skin, the epidermis, becomes thinner and can store less water. In the dermis, or true skin, production of the collagen that supports and firms the skin declines. Menopause in women, during which the body reduces estrogen production, causes a further loss of firmness and elasticity. Environmental factors like UV radiation have a major impact, accelerating the decomposition of collagen and encouraging the formation of aggressive oxygen compounds that can damage skin cells from the membrane to the DNA. The subcutaneous layer of fat and loose connective tissue becomes thinner. At the same time, the supply of nutrients and energy to the skin deteriorates. It is therefore important to support the health of aging skin with a sufficient supply of micronutrients.

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Like the organism in general, the skin is dependent on an adequate intake of micronutrients to fulfill its physiological functions. Pathological changes in the skin can be early indicators of a nutritional deficit. Conversely, targeted consumption of certain nutrients can help combat the processes of skin aging. A balanced diet – containing vitamins, minerals and essential fatty acids that haveantioxidant properties, stimulate cell growth and division and ensure collagen synthesis – is just as important as avoiding harmful lifestyle factors. Wrinkles, saggy and dry skin or pigment abnormalities are clear signs of skin aging which are exacerbated by excessive exposure to UV radiation (sunbathing) and harmful substances in tobacco (smoking) and become visible at the latest from the age of 40 onwards. See also Micronutrients in human development – Part 1 and Part 2

Functions in the skin

Micronutrients can be found in almost all elements of the skin, according to their function. Vitamin A plays a central role in structuring the skin and in the maintenance of its health, because it controls skin cell division, differentiation and growth. Correspondingly, proteins that are directly or indirectly involved in the uptake, conversion and transport of vitamin A and its metabolites are found in all the layers of the skin. A deficiency of vitamin A can lead to excessive cornification (1), degeneration of sweat glands (2) or slower wound healing. Skin cells can also use the vitamin precursor beta-carotene as a source of vitamin A (3). This is stored mainly in the epidermis and the subcutaneous layers of the skin. There, like lycopene, it functions as an antioxidant and can help protect skin (4). The antioxidant activity of vitamin E, which is transported to the skin via the sebaceous glands, can contribute to skin protection (5). In addition to its antioxidant pro-perties, vitamin C is especially essential to healthy skin because of its key role in the synthesis of the collagen that lends tissues stability and tensile strength (6). Vitamin D can be formed in the epidermis through UVB radiation, where specialized cells synthesize the active form of vitamin D3 (1,25-dihydroxy vitamin D3) from a precursor (7). This then participates in the regulation of skin cell division and differen-tiation (8). The synthesis of vitamin D by the skin may be restricted by insufficiently long and intensive exposure to UVB radiation, covering the skin with clothing and the application of sun protection products, leading to vitamin D insufficiency. Vitamins B7 (biotin) and B5 (pantothenic acid) are essential components of the skin and its adnexa, hair and nails. Biotin and pantothenic acid are needed for the metabolism of certain essential amino acids that contribute to skin function and to the healthy growth of hair (9, 10). In humans a lack of biotin can lead to hair loss and increased skin flaking.

The functions of minerals and trace elements in the skin have been less intensively researched than those of vitamins. Attention has been focused on zinc, selenium and iron because of their antioxidant properties. Zinc, which is found mainly in the epidermis and dermis, supports cell differentiation and is involved in the division of the cell nucleus (mitosis) (11, 12). Symptoms of severe zinc deficiency include inflammatory reactions in the dermis (dermatitis), hair loss and nail growth disorders (13). Selenium is found in the skin as a component of several enzymes which could be involved in the protection of skin cell membranes (keratinocytes) against oxidative stress (14). In animal experiments an inadequate intake of selenium caused hair loss and disruption to keratinocyte growth (15). Iron plays a role in several enzymes that are involved in selective oxidation processes (oxygenases) and in the metabolism of certain amino acids that are of relevance to the skin (16). Magnesium appears to encourage regeneration of the skin by supporting cell division – and in particular DNA reproduction (17, 18).

Polyunsaturated fatty acids (omega-3 and omega-6 fatty acids) are important components of cell mem-branes and are important for skin cell growth and regeneration. They play a decisive role in maintaining stable skin structure and protecting against UV damage. As precursors of certain messenger substances (eicosanoids) they play a significant part in regulating the immune system and inflammatory reactions in the skin (19).

Damage from UV light and other environmental factors

While the genetically controlled (intrinsic) process of skin aging cannot be influenced, it is possible to prevent accelerated (extrinsic) aging or damage to the skin from environmental factors (like UV light and chemical reagents). Excessive exposure of the skin to UVA radiation is primarily responsible for extrinsic skin aging. In contrast to UVB radiation, UVA radiation penetrates deep into the skin. UVA rays can trigger the activation of enzymes (metalloproteinases) which destroy tissue-stabilizing collagen in the dermis and contribute to the formation of wrinkles and other structural changes. Metalloproteinases are also activated by cigarette smoke, which is one reason why skin aging is accelerated in smokers. Increased production of reactive oxygen species (oxidative stress) is also regarded as responsible for an increase in losses of structure and function in the skin. Reactive oxygen species can damage or even destroy components of epidermal and dermal cells (membrane, proteins and DNA).
Micronutrients with antioxidant properties have been extensively examined for their potential to combat oxidative stress and hence prevent premature skin aging. Beta-carotene and lycopene, which after consumption travel through the blood stream to reach the vascular system of the skin and finally their site of action, have been particularly thoroughly investigated. To achieve antioxidant, protective effects the micro-nutrients must accumulate in sufficient quantities at the site of action in the skin (4). There they support neutralization of the oxygen radicals formed during UV-induced oxidative processes (20). Carotenoids also appear to contribute to skin protection on the cellular level through their influence on gene expression (21). According to one meta-analysis, dietary supplementation with beta-carotene can clearly reduce a sunburn reaction (22). Oral consumption of lycopene over a relatively long period of time has also been observed to provide extra protection against sunlight (23). Lycopene possesses the highest oxygen-radical-neutralizing potential of all the carotenoids investigated (24).

Vitamins with antioxidant properties, too, can stop skin cell damage from excessive free-radical formation. Studies were able to demonstrate that vitamin E (alpha-tocopherol) protects in particular against the oxidation of lipids (as components of membranes) (25). Moreover, vitamin E seems to be able to absorb the energy of UV light (26). Vitamin C not only acts directly as a radical scavenger but can regenerate vitamin E after a radical transfer (27). Both vitamins protect against UVB-triggered damage to DNA and can reduce a sunburn reaction (28). For optimal protection against UV-related skin aging a sufficient intake of all anti-oxidant micronutrients is recommended, since they act synergistically. There is also evidence for a protective local (topical) effect when they are applied to the skin in sun protection products (29-31).

There are indications that vitamin-A-related substances (retinoids, especially tretinoin) applied topically can reduce visible signs of UV-light-triggered skin aging such as wrinkles and pigmentation disorders (32). It seems possible that pre-treatment with tretinoin can also prevent UV damage by stopping the collagen-damaging processes induced by UV radiation (33, 34). Other study results indicate antioxidant and (in some cases) topical protective effects for zincseleniumiron and magnesium (35). Further, omega-3 fatty acids are considered to be promising micronutrients which could help neutralize oxygen radicals and hence protect the skin against UV radiation (36). Specifically, a protective effect against the formation of UV-radiation-induced skin reddening (erythema) could be demonstrated for eicosapentaenoic acid (37).

Declining cell renewal

One characteristic of aging skin is its declining ability to renew cells. Slowed skin renewal contributes to weakening of the skin barrier that protects the skin against moisture loss and penetration by foreign substances and microorganisms. Micronutrients stimulate and aid the process of regeneration and self-healing in the skin, which takes place mainly at night when the person is sleeping.

Vitamin A and its derivatives (e.g. retinol) encourage skin cell growth and differentiation. Local (topical) application of low-dose (0.1%) retinol has been shown to encourage proliferation of the skin cells (keratino-cytes) in the epidermis and to strengthen the uppermost layer of the skin (38). There are indications that vitamin D promotes cell differentiation at the gene-regulation level and simultaneously counteracts excessive proliferation of skin cells (7). Skin regeneration also seems to benefit from zinc and magnesium – especially when applied topically. Zinc oxides are probably involved in cell growth (39). Magnesium not only promotes growth and proliferation of keratinocytes, and thus regeneration of the uppermost layer of the skin (18), but also stimulates DNA reproduction and RNA synthesis (40).

Dryness and loss of elasticity

With increasing age the proportion of strong, stabilizing collagen fibers and elastic fibers in the skin de-creases rapidly. As a consequence, the skin is no longer able to store so much moisture. It becomes chapped and rough, and loses elasticity. Vitamin C plays a key part as a co-factor in the synthesis of collagen (41). Since it can improve the structure of collagen fibers; it is not only useful for maintaining skin health but can also aid wound healing when applied locally (topically) (42).

The vitamin B5 precursor panthenol contributes significantly to the supply of moisture (water) to the skin. The active substance may be applied directly to the skin, is readily absorbed and then converted to vitamin B5. The vitamin then penetrates the deeper layers of the skin and binds moisture there (43). Essential fatty acids, too, can combat the loss of moisture from the skin and hence favorably influence its elasticity. In one clinical study, for example, three-month administration of a dietary supplement containing omega-3 fatty acids from fish oil increased skin elasticity by 10 percent (44).

Inflammatory processes

The skin is designed to protect the organism against harmful external influences, such as penetration by viruses, bacteria and harmful substances, by erecting a mechanical barrier. At the same time it functions as an organ of immunological defense which includes a number of cells and structures. Hence keratinocytes – a type of cell occurring primarily in the epidermis – are actively involved in the immune response, in inflam-matory processes and in wound healing. Even minor injuries can make the skin vulnerable to pathogens. If the latter manage to penetrate the skin, they will ideally trigger a defense reaction or an inflammatory process. Dry skin is particularly prone to inflammation. A sufficient supply of micronutrients can help main-tain the integrity of the skin barrier and strengthen the skin’s own immune system.

Vitamin E has an anti-inflammatory action that inhibits the production of pro-inflammatory factors in the skin (45). It influences the synthesis of prostaglandins, which play a part in the local regulation of inflam-matory reactions, and of interleukins, which are produced as pro-inflammatory signal substances by immune cells (macrophages). Vitamin D aids skin immune defenses (46) by helping regulate the activity of the keratinocytes involved in the inflammatory reactions (47). Vitamin D applied to the skin seems to increase the number and activity of T helper cells (48). Vitamin C also has an anti-inflammatory effect: it has antimicrobial properties, activates natural killer cells (a subgroup of the white blood cells), triggers the proliferation of lymphocytes and can reduce oversensitivity in the skin (45). Locally (topically) applied panthenol (a precursor of vitamin B5) has been shown to have a specific anti-inflammatory effect on skin reddened and inflamed due to UV radiation (49).

Zinc plays an equally decisive role in the regulation of the immune system. Various studies have shown that zinc can not only stimulate a specific immune reaction in the skin, but also the prior unspecific reaction. This latter is especially important for the skin, since inflammatory processes at the start of the wound-healing process have a significant influence on its course (50). Studies have described a positive effect on wound healing of zinc applied directly to the skin (51).

After initiation of inflammatory reactions in the skin, specific regulatory proteins (cytokines) coordinate the molecular and cellular processes in the subsequent stages of inflammation. Polyunsaturated fatty acids increase pro-inflammatory cytokine production and thus assist the healing process (52).

Damage to hair and nails

The hair and nails are adnexa of the skin, and consist mainly of the protein keratin.  While the inside of the hair is constructed of protein fibers, the external layer is composed of flat, overlapping cells. Its root is surrounded by a gland that secretes protective fat which protects the hair against dryness and breaking. Dryness can be caused by the use of chemicals (e.g. bleach or hair color), too much sun or constant wash-ing. But nutrient deficiency, as well as environmental pollution, can lead to structural damage to the hair and nails. Hair health depends mainly on supplying the hair follicle with enough nutrients. Inadequate supply has a negative effect on the production of new healthy hair material: growth slows, the structure is weakened, the hair becomes fragile and can start to fall out. Nails, too, react sensitively to an inadequate supply of nutrients: they can become soft or brittle, and split or break.

Biotin (vitamin B7) consumed in the diet plays a key role in the metabolism of fats, carbohydrates and proteins as well as in the processes of cell division and is crucial for the formation and renewal of skin, hair and nails (53). An inadequate supply of biotin can lead to impaired growth and poor quality hair and nails (54).

Hair loss has been associated in some studies with an insufficient supply of vitamin A and trace elements like iron and zinc (55). In one clinical study evidence was found that dietary supplementation with iron can combat hair loss (56).

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