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Michels AJ, Micronutrients and Skin Health, Linus Pauling Institute, Oregon State University, Corvallis OR, http://lpi.oregonstate.edu/infocenter/skin.html , reviewed by Draelos ZD, Duke University School of Medicine, Durham NC, September 2011. [277]

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Micronutrients and Skin Health

Nutritional status plays an important role in the maintenance of healthy skin (1-4). Macronutrients(carbohydrates, proteins, and lipids) and micronutrients (vitamins and nutritionally essential minerals)work toether to maintain the barrier functions of skin in the face of everyday challenes. !hanes innutritional status that alter skin structure and function can also directly affect skin appearance. "nlikemany orans, skin nutrition may be enhanced directly throuh topical applications. #opical applicationof micronutrients can complement dietary consumption, leadin to a stroner, healthier protectivebarrier for the body. #his article discusses the roles of select micronutrients and other dietarycompounds in the maintenance of skin health. #opical use of these compounds is discussed, and theeffects of micronutrient deficiencies in the skin are also covered.

Skin Structure

$kin provides a physical and chemical barrier between the outside environment and the inside tissuesof the body (%, &). #his 'barrier function is critical to protect underlyin tissues from pathoens,chemicals, and environmental eposures (%, *). $tructurally, skin is comprised of two main layers, theepidermis and the dermis (&, *) (see figure). #he epidermis, the upper layer, is responsible for manyof the barrier functions of skin. #he dermis is the structural and nutritive support network underneaththe epidermis. $ince each layer has its own uni+ue structure and function, the nutritive re+uirementsof each must be considered separately.

Epidermis: The Outer Barrier

uman epidermis comprises the outermost layers of skin cells, ranin from .1 mm to .& mm thick,

dependin on the location on the body (*). eratinocytes compose the vast ma/ority (0-0%) of cellswithin the epidermis. #hese cells are found in layers of varyin si2e and thickness (&). #he bottom orbasal layer of the epidermis consists of a layer of round, undifferentiated keratinocytes that issupported by contact to the underlyin dermis. !ells in this layer are constantly dividin in order toproduce new cells that will make up the remainder of the epidermal layers (&, *). #hus, it is in thisfashion that skin is replenished, with new cells from the basal layer replacin the outer layer of skincells that is shed over time.

3nce a keratinocyte leaves the basal layer, it beins the process of cell differentiation known askeratinization (&). urin keratini2ation, keratinocytes undero several morpholoical chanes thatresult in the synthesis of uni+ue structural proteins (especially keratin) and the secretion of a variety of speciali2ed lipids that will comprise key components of the epidermal barrier. #hese cells also underoa process known as cornification, in which the synthesi2ed proteins are assembled in an envelope /ustinside the cell membrane (%-*). 5t the end of this process, the lare protein-laden cells, now known ascorneocytes, lose their nuclei and other cellular oranelles. #hus, there is little metabolic activitypresent in the outer layers of the skin (often referred to as 'dead cells).

#he outermost layer of skin, the stratum corneum, interacts with the outside environment. 6ipidssecreted by cells durin the keratini2ation process are now assembled with etracellular proteins into aprotective layer. #his barrier is often likened to a 'brick and mortar system7 lare, flattened,metabolically inactive corneocytes (the protein-rich 'bricks) are sealed toether with a variety of etracellular lipids and proteins (the 'mortar) (%, &). #he chemical properties and structural desin of this layer slow absorption and limit penetration of the skin, as well as limit the loss of vital nutrientsand water from the underlyin tissue. 5s new layers of cells are produced, the outer cells of thestratum corneum are en2ymatically detached from this layer and shed in a process called

desquamation (%).

8urther, other cells contribute to the function of the epidermis. Melanocytes are cells that producemelanin, a compound involved in skin pimentation produced in response to ultraviolet ("9) lihteposure (&). Melanin can absorb enery from "9 liht to shield underlyin tissues from damae.6anerhans cells are antien-presentin cells involved in epidermal immunity. Merkel cells havevarious neuronal and endocrine roles: these cells function as mechanical sensors and produce rowthfactors that reulate sweat lands, hair follicles, nail rowth, and nerve function in skin (&).

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  - .various neuronal and endocrine roles: these cells function as mechanical sensors and produce rowthfactors that reulate sweat lands, hair follicles, nail rowth, and nerve function in skin (&).

Dermis: The Inner Support

#he dermis is the inner layer of skin situated between the epidermis and other tissues of the body,such as connective tissue, subcutaneous fat, muscle, and bone. #he dermis can vary in depth from .;mm to 4 mm dependin on body location and is enerally at least ten times thicker than the epidermis

(*, <). owever, nearly *% of the weiht of the dermis is a matri of collaen, an etracellularprotein that allows for both structural support and elasticity of the skin. #hus, the primary role of thedermis is a mechanical support network for the epidermis, providin interity and fleibility to skin.=lood vessels that supply nutrients for all skin layers are found in the dermis (&).

#he dermis, which is less cell dense than the epidermis, is primarily comprised of a matri of etracellular proteins. 5 ma/ority of cells found in the dermis are fibroblasts that synthesi2e structuralproteins like collaen. >mmune cells, such as monocytes, macrophaes, and dermal dendrocytes, alsoreside in the dermis, where they contribute to the defense of skin and modulate the response to in/ury(&). $ubcutaneous fat cells provide structural support and enery reserves, as well assistance inthermoreulation. air follicles, sensory nerve endins, and sweat and sebaceous lands are alsofound in the dermis: each is made of speciali2ed cells that support the various functions of the skin.

Challenges Faced ! Health! Skin

5lthouh difficult to define, healthy skin has the ability to respond to challenes that would otherwiseundermine its structure and function. =alanced nutrition complements the host of endoenous factorsthat preserve skin health. Moreover, skin that functions properly has aesthetically pleasin properties,ivin skin a healthful appearance and feel. #herefore, conditions that adversely affect the bioloicalfunctions of skin often correspond to a less attractive appearance of skin.

#his section focuses on the 'everyday challenes to skin health and the prevention of chronicconditions (where applicable) rather than treatment of skin diseases.

"hotodamage: ?rimary eposures to ultraviolet ("9) liht are throuh sunliht and tannin beds.5lthouh "9 penetration of skin aids in vitamin synthesis (see the separate article on 9itamin ), ithas the potential to damae the cells and etracellular components of the skin (0-11). 8ree radicals areproduced when liht enery is absorbed by cellular components (1, 11). @hile the skin hasendoenous antioidant systems to combat free radicals and repair proteins, ecessive eposures mayoverwhelm these defenses and lead to permanent damae (11, 1A). #his is often referred to asphotodamae (11-1;).

$unburn is the most common form of acute photodamae, where the damae caused by ecessiveeposure of "9 liht leads to a lare inflammatory response (erythema) (1;). ?roloned or repeatedeposures to "9 liht may cause permanent damae. #his is often referred to as 'photoain due tothe amount of time needed for these chanes to appear and their similarities to intrinsic ain effects(see below) (1A, 1;). @hile skin laity, wrinklin, and thickenin are the most apparent sins of 

photodamae, chanes in skin teture, abnormal skin rowths, and impaired wound healin are alsopossible (1;-1%). $kin discoloration may also occur with chronic "9 eposure, especially in the form of solar lentiines, also known as liver spots.

?revention of photodamae beins with limitin eposure to "9 liht. =ecause avoidance of sunliht isnot always practical, photoprotective aents are often used to limit eposure (0, 1A). $unscreens arethe most commonly used photoprotective aents. owever, use of sunscreens may only providelimited sun protection, epose the skin to chemicals that miht otherwise damae or disrupt barrierfunction, or induce inflammatory reactions in the skin. #herefore, care must be taken in their use (1A).

$ince "9 liht eposure depletes antioidant levels in the skin, includin ascorbic acid (vitamin !) andalpha-tocopherol (vitamin B) (1&-10), increasin antioidant defenses in skin cells andCor nutritional

support of cellular repair en2ymes are also important routes to limit photodamae.

Dr! Skin: 5lthouh the lower layers of the epidermis are moist, there is a sharp decline inetracellular water content as the cells mirate outward toward the skin surface (A, A1). #his ispartially by desin7 the hydrophobic environment found in the stratum corneum slows the passae of water from the body out into the atmosphere, a phenomenon known as Transepidermal Water Loss(TEWL). $ince water loss is directly related to the skins ability to maintain its barrier functions,measurements of #B@6 are often used to determine skin dysfunction. owever, small amounts of 

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  ,(TEWL). $ince water loss is directly related to the skins ability to maintain its barrier functions,measurements of #B@6 are often used to determine skin dysfunction. owever, small amounts of water are needed for the stratum corneum to maintain its structure. 5 miture of stratum corneumcomponents form a water-bindin barrier, toether known as natural moisturi2in factor (NM8), toretain moisture content even in dry environments (A).

ry skin can be caused by many factors, but it is usually accompanied by chanes in the epidermalbarrier and increased #B@6 (more water lost to the environment). >ntrinsic chanes in the lipid barrier

or NM8 of the stratum corneum can disrupt the barrier and cause water loss. #his can stem fromsimple chemical eposures, such as washin with deterents (A) or from more comple nutritionaldeficiencies, such as a lack of essential fatty acids (AA). owever, dry skin can also be an effect of atmospheric conditions or eposures. !hanes in temperature, air flow, and humidity can pull wateraway from the skin and reduce barrier interity. >f left untreated, dry skin is often predisposed toinsults from other sources, leadin to cycles of cell damae and inflammation that perpetuate thecondition.

5n important stratey to treat dry skin is to maintain the lipid barrier and NM8 components of thestratum corneum (A). #his can be achieved either throuh nutritional support of the underlyinepidermis or by the use of a variety of topical applications (A;).

Skin #a$it! and %rinkles: 6ittle is known about the oriin of wrinkles (A4). owever, skin laity isassociated with poor support of the epidermis by the underlyin dermis. 6oss of collaen, damae tocollaen and elastin fibers in the dermis, or structural chanes in the /unction between the dermis andepidermis are thouht to contribute to wrinkle formation (A%-A*).

$kin laity may be accentuated by loss of blood vessels in the dermis (A<). 5dditionally, smokin andphotodamae increase skin wrinklin (A*, A0). #hus, avoidin these sources of damae would benefitskin tone. Nutritional factors are thouht to influence wrinklin (1), but their roles are not clear.

%ound Healing: #he process of wound healin involves a coordinated effort by a number of differentcell types. #he priorities of the skin durin wound healin are to clear the damaed area of infection,re-establish the epidermal barrier, and reconstruct the damaed underlyin dermis. 3verall, healin of an in/ury to the skin re+uires interplay of the epidermis, dermis, and inflammatory mediators (;, ;1).

5fter skin has been wounded, inflammatory cells are recruited to the area. #he first responders areneutrophils, which clear the wounded area of damaed tissue and infectious particles and sinal for therecruitment of macrophaes to the wound (;). Macrophaes, stimulated by rowth factors at thewound site, take on a variety of roles in the wound healin process. $ome macrophaes assist in theremoval of debris and damaed tissue, while others coordinate the remodelin of tissue at the woundsite (;1). Macrophaes are essential to produce the sinals for reepitheliali2ation and dermal repair.

Deepitheliali2ation is the process of restorin the skins barrier, thereby providin a safe environmentfor tissue remodelin underneath. "pon stimulation by the inflammatory response and loss of neihborin cells at wound edes, epidermal keratinocytes flow into a damaed area in an attempt tocontact other keratinocytes and connect with the matri of the dermis. #his miration is coordinated

with a rapid proliferation of the epidermis, which provides additional cells to fill in the wound site (;1).

8ibroblasts of the surroundin dermis move into the wound durin various staes of healin. 8ollowina wound, a fibrin clot is often established if blood vessels were ruptured. 8ibroblasts stimulate theorderly removal of fibrin, replacin the clot with a more stable collaen matri (;1). 8ibroblasts alsoparticipate in wound contraction, which involves drawin toether edes of the wound and undamaedtissue in order to restore skin interity (;). urin later staes of wound healin, fibroblasts areinvolved in reorderin these collaen fibers into a more stable structure, interated with elastin.Erowth factors produced by macrophaes, keratinocytes, and fibroblasts stimulate proliferation of blood vessels into the newly remodeled dermis to restore nutrient and oyen flow (;1).

@ound repair is never perfect. $kin tensile strenth at a site of a healed in/ury is always lower than

unin/ured skin (;, ;1). $carrin of the skin is a conse+uence of the repair process resultin fromdisorani2ed collaen deposits by fibroblasts and cytokine sinals from inflammatory cells. !urrently,no intervention has proven effective at preventin scar tissue formation.

@hile treatment of a wound involves preventin infection, support of the wound healin process canoccur at different staes of repair. Bfficient immune responses and support of reepitheliali2ation arekey factors in initial healin (;1), removin damaed tissue, re-establishin the barrier from theenvironment, and remodelin the surroundin tissue. Nutritional support of the reeneratin epidermis

-

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  .key factors in initial healin (;1), removin damaed tissue, re-establishin the barrier from theenvironment, and remodelin the surroundin tissue. Nutritional support of the reeneratin epidermisand dermis durin the latter staes of wound healin is not only important in lon-term woundresolution but is thouht to promote the restoration of stron, healthy skin (;A).

Skin &ging: $kin is often the first visible manifestation of the ain process. owever, the effects of ae on skin appearance are often similar to the effects associated with photodamae andenvironmental eposures. #his makes the chanes induced by chronoloical ae on skinFoften

referred to as intrinsic agingFdifficult to distinuish from other effects (A*).

>nstrinsic skin ain is characteri2ed by decreasin support from the dermis to the epidermis. Dideson the interface between the two layers are diminished, preventin the dermis from providinade+uate mechanical support to the epidermis (A*, ;;). !ollaen levels are lower and etracellularproteins in the dermis are more disorani2ed in skin of older individuals compared to youner adults(A*, ;;, ;4). #hese chanes result in increased skin fraility and laity, as well as decreased si2e of the dermis and reduced vasculari2ation, which reduces nutrient availability to the skin (A*, A0). 5edskin keratinocytes are relatively slow to differentiate and shed, which alters their ability to maintain thestratum corneum. #hese chanes may lead to an overall dull skin appearance and loss of protectiveability of skin (A*).

5ntioidant protection is often thouht to diminish in the skin of older individuals, but the etent of these chanes is unclear. #he results of one human study suest that catalase (an antioidanten2yme) levels in the epidermis of elderly sub/ects were increased compared to youn sub/ectsindependent of sun eposure (1&). #he capacity of ain skin to maintain levels of other antioidanten2ymes was unchaned. owever, elderly sub/ects had lower levels of alpha-tocopherol in theepidermis and lower levels of ascorbic acid in both skin layers (1&).

Most of intrinsic skin ain cannot be avoided. #he cumulative effects of decades of skin wear cannotbe reversed, althouh the effects on skin appearance may be temporarily masked. 5in skin has adiminished ability to respond to stress: therefore, skin damae from other sources can enhance thesins of skin ain. #his is particularly true for ultraviolet ("9) eposures, because antioidantcapacity, immune function, and melanin production may all be impaired in aed skin (A*). #herefore,treatments desined to attenuate damae from other sources are also important factors in limitin

ae-associated skin damae.

Skin and 'utrition

(eneral 'utrition )e*uirements

#he primary fuel for skin cells is lucose: lucose oidation rates in skin are similar to those observedin restin skeletal muscle. Elucose also provides carbohydrate backbones for modification of proteins(lycoproteins) and lipids (lycoplipids) that comprise the etracellular environment of the epidermis(;%). 5berrant lucose handlin drastically affects skin structure and appearance (;&).

$peciali2ed lipids re+uired for the development of the stratum corneum, such as sterols and ceramides,

are synthesi2ed in the epidermis from amino acids, carbohydrates, and phospholipids. owever,differentiatin keratinocytes also utili2e fatty acids from circulatin stores or dermal fat layers forenery. #he etruded fatty acids that make up the mortar of the stratum corneum (described above)can absorb lipid-soluble materials placed on the eternal surface of this outermost skin layer. #his isespecially the case for sebum, a way substance secreted from the sebaceous lands that are attachedto hair follicles, but it is also true for topically applied materials (;%).

5mino acids are essential for the production of both dermal and epidermal structures, producin theetracellular matri proteins and en2ymes needed for the synthesis of the epidermal barrier. #heamino acid re+uirements of skin are poorly understood (;*).

Much of the role of nutrition in skin health focuses on the effects of deficiency, since the structural

components of the skin are supported by a variety of nutritive factors, such as small peptides,minerals, and vitamins, which serve as en2yme cofactors, activators, or inhibitors (4). #he skin is alsoconstantly eposed to hih concentrations of oyen, "9 liht, and oidi2in chemicals, hihlihtin arole for antioidant vitamins in skin function (;<, ;0). 8urther, nutritional support of the skin isimportant for inflammatory response durin wound healin (;A).

Oral 'utrition +s, Topical Supplementation

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Oral 'utrition +s, Topical Supplementation

#he architecture of skin deserves special consideration in reard to nutrition. #he epidermal layers of the skin do not contain blood vessels that supply the cells with nutrients: blood vessels are found onlyin the dermis. 5dditionally, as the epidermis develops, its uni+ue protein and lipid structure (theaforementioned Gbricks and mortarH model) prevents the circulation of etracellular fluids (*).#herefore, the outer layers of the epidermis are provided with less nutritional support than theunderlyin cells. ietary interventions to affect skin health may be limited in effect and slow to occur.

"ni+ue amon orans, the skin may be directly affected by the use of topical applications. #he stratumcorneum prevents the passae of many different types of molecules, but some compounds passthrouh to the underlyin layers. >n eneral, unchared or lipid-soluble molecules pass throuh theepidermis and may also penetrate the dermis. !oncentrations of nutrients in the skin may becomparable to that achieved throuh oral inestion. Iet, topical application may be a more efficient,tareted method for supplyin nutrients to the skin, especially to the epidermis (1A, ;0).

Micronutrients Important for Skin Health

!hanes in the appearance of skin were associated with poor nutrition lon before any biochemicalrelationships were discovered. 5mon the first to make these associations was the $cottish physician

James 6ind, who described the bleedin ums, skin discoloration, abnormal hair rowth, and poorwound healin associated with the vitamin ! deficiency disease known as scurvy (see the article on9itamin ! and the $kin). 3ther investiators would soon find skin abnormalities in vitamin deficiencydiseases (?ellara, 5riboflavinosis, etc.) that could be corrected with an appropriate diet. #hus, manymicronutrients were initially identified for their impact on skin health.

#he effect of micronutrient supplementation on skin health is a relatively new field of study, asassociations between diet and skin conditions are only now startin to emere (1-;, 4). >n addition,topical applications of micronutrients have only recently been considered to be reasonable alternativesto oral supplementation (0, 1A, ;0).

#he remainder of this article focuses on select micronutrients and other natural factors that areimportant for skin health. ?lease note that this site is under development, and new articles will beadded once they are completed and reviewed. !ommercially available products occasionally refer tothese compounds as GbionutrientsH due to their abundance in natural sources. #he role of these factorsin the uni+ue environment of the skin will be eplained, and the effects of micronutrient deficiencies onthe skin will be discussed. 8urther, the effects of dietary intake and topical application of these naturalproducts on skin health will be eplored.

-itamin & and Skin Health

-itamin C and Skin Health

-itamin D and Skin Health

-itamin E and Skin Health

Minerals and Skin Health

Essential Fatt! &cids and Skin Health

Fla+onoids and Skin Health

"eptides and Skin Health

)eferences

@ritten in $eptember A11 by75leander J. Michels, ?h..

6inus ?aulin >nstitute3reon $tate "niversity

Deviewed in $eptember A11 by7Koe iana raelos, M..

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Deviewed in $eptember A11 by7Koe iana raelos, M..

!onsultin ?rofessorepartment of ermatoloy

uke "niversity $chool of Medicineurham, N!

#his article was underwritten, in part, by a rant from

Neutroena !orporation, 6os 5neles, !alifornia.

  !opyriht A11-A14 6inus ?aulin >nstitute

Disclaimer

#he 6inus ?aulin >nstitute Micronutrient >nformation !enter provides scientific information on thehealth aspects of dietary factors and supplements, foods, and beveraes for the eneral public. #heinformation is made available with the understandin that the author and publisher are not providinmedical, psycholoical, or nutritional counselin services on this site. #he information should not beused in place of a consultation with a competent health care or nutrition professional.

#he information on dietary factors and supplements, foods, and beveraes contained on this @eb sitedoes not cover all possible uses, actions, precautions, side effects, and interactions. >t is not intendedas nutritional or medical advice for individual problems. 6iability for individual actions or omissionsbased upon the contents of this site is epressly disclaimed.

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  . .

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