Review Skin Pharmacol Physiol 2012;25:227–235 DOI: 10.1159/000338978 Received: July 18, 2011 Accepted after revision: April 20, 2012 Published online: June 20, 2012 Oily Skin: An Overview Thais H. Sakuma Howard I. Maibach University of California, San Francisco, Calif., USA Abstract Oily skin (seborrhea) is a common cosmetic problem that occurs when oversized sebaceous glands produce excessive amounts of sebum giving the appearance of shiny and greasy skin. This paper overviews the main concepts of sebaceous gland anatomy and physiology, including the biosynthesis, storage and release of sebum, as well as its relationship to skin hydration and water barrier function. We also address how skin oiliness may vary according to diet, age, gender, ethnicity and hot humid climates. The deeper understanding of this skin type provides the opportunity to better guide patients regarding skin care and also assist in the development of sebosuppressive agents. Copyright © 2012 S. Karger AG, Basel Introduction Oily skin (seborrhea) is common, affecting men as well as women and typically starting just before puberty. Oily skin looks shiny and greasy, and is frequently accompanied by large pores. It contributes to the development of acne and may be a cosmetic problem. It can negatively affect the patients’ self-image and have detrimental psychosocial effects. Many individuals feel em© 2012 S. Karger AG, Basel 1660–5527/12/0255–0227$38.00/0 Fax +41 61 306 12 34 E-Mail [email protected] www.karger.com Accessible online at: www.karger.com/spp barrassed and annoyed with the appearance of their oily skin, and the unpleasant feeling of uncleanness is also a source of complaint [1–3]. The relevance of a seemingly trivial matter becomes evident when we realize its constant frequency in women’s magazines or beauty websites and, most impressively, numerous products marketed by the cosmetics industry intended for this skin type. However, together with its popularity come speculation, controversy and myths. It is common to read inaccurate information conveyed by the media. In this manner, this overview attempts to fill the information gap of this common cosmetic problem, bridging scientific data to clinical practice. Skin Surface Oil Source The sebaceous gland, through its holocrine activity, excretes a complex mixture of lipids called sebum onto the skin surface. Other lipid sources are the epidermal keratinocytes, which, during their final stages of differentiation, extrude lamellar granules into intercellular spaces of the stratum corneum. They consist of lipid packages that fill these intercellular spaces like mortar or cement, ensuring the skin permeability barrier [4–6]. This paper is dedicated to the memory of Prof. Albert M. Kligman and Prof. Walter B. Shelley. Thais H. Sakuma 252 Swain Way Palo Alto, CA 94304 (USA) Tel. +1 650 919 4842 E-Mail thais.sakuma @ gmail.com Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/27/2018 5:39:24 PM Key Words Oily skin ⴢ Sebum ⴢ Sebaceous gland ⴢ Skin care Skin Surface Oil Composition The average composition of human sebum in adults consists of 57.5% triglycerides and their hydrolysis products, 26.0% wax esters, 12.0% squalene, 3.0% cholesterol esters and 1.5% cholesterol [9]. Among these, squalene and wax esters are unique to human sebum and not found anywhere else in the body nor among the epidermal surface lipids [5, 12–15]. By comparison, the human epidermal (stratum corneum) lipid is comprised of 50% ceramides, 25% cholesterol, 15% of free fatty acids [16] as well as smaller amounts of cholesterol esters and cholesterol sulfate [17]. In contrast to the free-flowing oils of the sebaceous gland, the epidermal lipids are in a solid state at room temperature. Sebaceous Gland Anatomy The sebaceous gland is located in the reticular dermis, where it is usually found in association with hair follicles, forming the pilosebaceous unit [8, 14]. The lanugo pilosebaceous units of the face can be of two types: the most common is superficial, tiny and its ostia and minute hairs 228 Skin Pharmacol Physiol 2012;25:227–235 are invisible to the naked eye. Its sebaceous glands are disproportionately large, as are all lanugo follicles. The less numerous type have multilobular sebaceous glands of extravagant size and depth, greater in volume than the much smaller glands of the superficial, tiny follicles. It empties to the skin surface through a wide duct, which is in fact the follicle, and is joined by a tiny hair of insignificant proportions. Their ostia are easily visible as the pores of adult facial skin and the gaping orifices are highly prominent in many oily patients, especially on the cheeks. This type of sebaceous follicles is practically limited to the face, scalp and upper trunk. The tiny superficial hair follicles outnumber these huger sebaceous follicles by a ratio of about 3:1, being evenly dispersed among them. The hairs associated with the huge sebaceous follicles are larger than those of the superficial hair follicles and are the ones generally seen with the naked eye [18]. This type of sebaceous follicles contributes by far to the greatest quantity of facial sebum. The oily appearance commonly found on the ‘T’ zone (forehead, nose and chin) reflects the dominance of these sebaceous follicles. Pagnoni et al. [19] found that sebum output and density of follicles followed a centrolateral decreasing gradient, and Lopez et al. [20] showed that such a ‘T’-like distribution could indeed be clearly observed even in the women presenting the lowest mean value of sebum casual level1. We conclude that all skins are of a ‘combination’ type, with increased sebum values on the ‘T’ zone compared to the rest of the face, regardless if the skin is oily or not. Biosynthesis, Storage and Release of Human Sebum The quantity of lipids delivered in a given time per unit area is proportionate to the total glandular volume (size and number of glands), a function of the total number of sebaceous cells generated. Miescher and Schonberg [22] performed planimetric measurements of glandular size (actually surface area) in biopsy specimens and showed that the ratio between lipid delivery and glandular size was constant; that is, the larger the glands, the more sebum produced in a given time [18]. The fully developed adult sebaceous gland contains sebocytes at different stages of differentiation. Its peripheral zone is composed of mitotically active sebocytes, which differentiate towards the center of the gland. During this 1 The sebum casual level (CL) is defined as the amount of lipids present at equilibrium when the skin surface remains untouched for several hours [21]. Sakuma/Maibach Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/27/2018 5:39:24 PM The relative contribution of lipid from each source depends upon the number of sebaceous glands present at the site sampled [7, 8], with as many as 900 glands/cm2 on the face to less than 50 on the forearm [7]. On sebaceous gland-rich areas, such as the face, lipids produced by the epidermal cells represent an insignificant fraction of the total extractable surface lipid. In adults, the amount of surface lipid on the forehead, for example, normally varies between 150 and 300 g of lipid/cm2, of which the epidermal contribution is only 5–10 g or 3–6% [9, 10]. However, when sebaceous gland development is minimal, as in the prepubertal child, or absent, as in the palms and soles, epidermal lipids constitute the major surface lipid [5]. Sebum forms an amorphous sheet of variable thickness on the skin. It can be !0.5 m or even negligible in sebum-poor areas, or 1 4 m in some areas of the sebumrich face [11]. With the knowledge that the face is rich in sebaceous glands and that the epidermal lipids are probably delivered to the surface at a constant rate as epidermal cells mature [5], we conclude that a global overvolume of sebaceous glands is the cause of oily skin. Areas commonly affected include those that have a higher sebaceous gland density, such as the face, ears, scalp and the upper trunk [8]. process, they lose their mitotic activity, increase their size and accumulate lipid droplets. Then, the terminally differentiated sebocytes disintegrate and release their content to the skin surface via holocrine secretion. This continuous differentiation activity is under the control of paracrine, endocrine and neural mediators acting on a wide array of receptors expressed by sebocytes [12, 14]. Until 1947, researchers stated that the sebum accumulated on the skin surface was the chief force regulating the gland’s excretory activity. Surface loss would accelerate sebum production, and skin surface saturation would lead the gland to shut down. However, Kligman and Shelley [18] performed experiments that dismissed this concept, termed by them as the ‘positive feedback theory’. Instead, they proposed that the sebaceous gland functions continuously, without regard to what is on the surface [18]. They demonstrated that the remarkable ability of sebum to spread over the skin surface could lead to the false impression that the sebaceous glands were in ‘sleep mode’. After preventing sebum from flowing away or being wiped off during the lipid’s collection, they obtained an average of 3.13 mg of sebum per 10 cm 2 on the volunteer’s forehead, compared to the amount of 1.4 mg per 10 cm2 when such precaution was not taken. Hence, the reason why the values of sebum collected from the skin are relatively constant is related to the fact that after a few hours, the skin surface of the studied site (e.g. the forehead) becomes saturated, and the excess spreads over to surrounding areas of the face. The ‘positive feedback’ theory was questioned after the explanation of a curious phenomenon that led many workers to support it. Literature data demonstrate that the more frequently sebum is collected from a given area, the larger the sum that will be obtained in equivalent time periods; for example, the sum of the quantities of lipids collected at several short intervals greatly exceeds the amount collected at a single removal at the end of the same length of time. Kligman and Shelley [18] ascribed this phenomenon to the follicular reservoir (the duct which connects the sebaceous gland located in the dermis to the skin surface), whose importance was later demonstrated by Downing et al. [23]. They measured sebum secretion in human skin over a period of 24 h and observed that it declines over a period of 12 h and then remains constant for the remaining 12 h. It was inferred that the final, sustainable rate represents the true rate at which sebum is secreted by the sebaceous glands, and that the additional sebum collected at earlier intervals was obtained from an accumulation in the stratum corneum or in the follicular canals. In this manner, Millns and Maibach [24] stated that the sebum measured on the skin surface should be seen as the end product of what they called a ‘multifunctional sebaceous apparatus’, which involves not only sebum production but also sebum storage (a volume function) and surface delivery (a rate function). With this three-component model in mind, it is easier to elucidate the ‘positive feedback’ misunderstanding. The lipid which rapidly reappears on the skin surface soon after defatting of a sebaceous-rich area, such as the face, is actually derived from preformed sebum stored in the follicular reservoir. This preformed sebum would flow out of the follicular reservoir into the meshy spaces of the stratum corneum, through a capillarity mechanism, refilling the space previously occupied by the removed sebum. The rate of replenishment is proportional to the size, number of glands and the amount of preformed sebum that can be stored in the follicular reservoir. On the forehead, total replacement of the removed sebum is expected after 3 h (if sebum run off is prevented), and sometimes even after 2 h in oily skin volunteers [18]. After defatting the skin by wiping the skin several times with an ethersoaked cloth, Butcher and Parnell [25] observed clear follicular droplets of sebum under the stereoscopic microscope (!12) within 15 min. These became visible to the naked eye in 40 min, giving the skin a star-spangled appearance under bright light. Kligman and Shelley [18] also demonstrated that it is probably impossible to exhaust the forehead follicular reservoirs completely. After applying absorbent cigarette papers to the forehead of 2 volunteers every 10 min for 6 h, large oil globules could still be expressed by hemostat compression. Also, neither ether nor absorptive papers significantly removed oil from the follicular reservoir. The authors stated that there is no physiological way to empty it [18]. Based on these data and contrary to what many think, overwashing the skin does not cause sebum overproduction, but just leads preformed sebum to flow up through a capillarity mechanism. Oily Skin Skin Pharmacol Physiol 2012;25:227–235 Skin Oiliness Assessment 229 Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/27/2018 5:39:24 PM Sebum present at the skin surface can be objectively measured non-invasively using one of several methods based on absorbent paper pads, photometric assessment (e.g. Sebumeter쏐 SM810; CK electronic), bentonite clay and lipid-sensitive tapes (e.g. Sebutape쏐; CuDerm Corp.). Sebaceous Gland Function Regulation The sebaceous gland is an androgen target organ, stimulated to produce sebum at puberty and beyond by androgens [27]. Akamatsu et al. [28] demonstrated that 230 Skin Pharmacol Physiol 2012;25:227–235 testosterone and 5-alpha-dihydrotestosterone (5␣-DHT) stimulated the proliferation of facial cultured human sebocytes in a significant dose-dependent manner. Also, according to their experiments, the effect of testosterone and 5␣-DHT on the proliferation of cultured human sebocytes may depend on the localization of the sebaceous glands at different skin regions. Androgens are more effective in increasing the proliferation of facial than nonfacial sebocytes [27, 28]. It has been proposed that, besides abnormal circulating androgen levels, sebum production can be increased by overproduction of androgens in the pilosebaceous units due to enhanced expression and activity of androgenic enzymes or/and by overexpression or hyperresponsiveness of androgen receptors [29]. Conversion of testosterone to 5␣-DHT (an intracellular metabolite of testosterone and the most active androgen in upregulating sebum production) is induced by the enzyme 5␣-reductase. 5␣-reductase type 1 activity is significantly higher in sebaceous glands compared to other skin compartments. Furthermore, facial sebaceous glands exhibit higher 5␣-reductase type 1 activity than sebaceous glands from non-acne-prone areas. Using the human sebocyte culture model, thyroidstimulating hormone, hydrocortisone and, especially, insulin significantly stimulated proliferation of human sebocytes maintained in a serum-free medium in a dosedependent manner. These results indicate that not only androgens but also other hormones may modulate sebocyte activity, leading to a complex regulation of the sebaceous gland [27]. Sebum Secretion: Role of Diet Diet may be an important source of substrate for sebum synthesis. It is synthesized de novo in the gland from several sources (e.g. glucose, acetate and fatty acids); however, some dietary lipids (especially fatty acids) can also pass unchanged from the circulation to the sebaceous cells. It is presumed that undifferentiated cells of the sebaceous gland acquire the dietary lipids whilst in the basal layer exposed to the circulation [15]. Fulton et al. [30] measured the effect of excessive chocolate ingestion on 5 healthy adult male volunteers. All volunteers ingested two chocolate bars daily for 1 month. Although the authors concluded that chocolate and fat did not alter sebum composition and output, at the end of the study, an increase in collected sebum was observed in 3 of the 5 volunteers [30]. Pochi et al. [31] investigated Sakuma/Maibach Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/27/2018 5:39:24 PM Since many environmental and biological factors influence the data, rigorous methodological designs are mandatory. The Sebumeter SM810 and Sebutape are widely used. The Sebumeter affords direct photometric reading of the lipid collected on a probe of opaque plastic strip after a 30-second skin contact. Increases in transparency are directly proportional to the sebum present. The digital read-out displayed as micrograms per square centimeter provides estimated total amount of lipids present on the skin at one time point. The Sebutape is a white porous tape that traps oil and becomes translucent. After removal from the skin, it is laced in a black background. A pattern of dots of variable sizes and density develops, proportional to the amount of sebum delivered. This pattern is matched to a grading scale to generate a numerical report (details provided in [22, 26]). Arbuckle and colleagues [1, 2] developed and validated the content of two questionnaires focusing on the patients’ self-assessment of skin oiliness. The first one, the ‘Oily Skin Self-Assessment Scale’ (OSSAS), measures facial oily skin severity and consists of three questionnaires that assess subjects’ oily facial skin through visual perception of oily skin, tactile perception of oily skin and sensation of oily skin questions. The second one, the ‘Oily Skin Impact Scale’ (OSIS), assesses the emotional impact of oily skin using two questionnaires. One evaluates the subjects’ annoyance and the other their self-image/selfconcept. OSSAS scales have low correlations with the Sebumeter data [2]. As the validity of the Sebumeter has not been demonstrated, it is difficult to interpret this result. Note that the reliability of self-assessment questionnaires might be affected by numerous environmental (e.g. humidity, season of the year) and biological conditions (e.g. hormonal fluctuations), and, most importantly, it depends on the individuals’ subjective perception of skin oiliness. Self-perception of physical appearance may not always correspond with the biophysical measurements. Another validated questionnaire is the Oily Skin SelfImage Questionnaire (OSSIQ), developed with 18-item questions to assess perception as well as behavioral and emotional consequences associated with oily skin. In contrast to previous studies, OSSIQ scores accorded with objective sebum level measurements [3]. Oily Skin Genetic Influence A twin study investigating sebum secretion in 20 pairs of adolescent acne twins found that, differently from dizygotic twins, the sebum secretion rate was homogeneous between monozygotic twins [38]. Several genes regulate sebaceous gland function. Overexpression of the ageingassociated gene Smad7 in adult transgenic mice has been correlated with hyperplasia of the sebaceous gland, and c-myc overexpression has been shown to be associated with enhanced sebaceous lipid synthesis and to have a drastic decrease with age. Parathyroid hormone-related protein knock-out mice presented hypoplastic sebaceous glands, whereas parathyroid hormone-related protein overexpression led to sebaceous gland hyperplasia [39]. Age, Gender, Ethnic and Seasonal Variation Differences in sebum secretion at various times of life have been associated with concomitant changes in endogenous androgen production. Sebaceous glands are well developed in neonates, but their size decreases dramatically a few weeks after birth, starts to rise again with the adrenarche and reaches its maximum in young adults. While the number of sebaceous glands remains the same during life, sebum secretion rates are highest in the 15–35-year-olds and decline continuously throughout the adult age range [40]. At any age range, the mean sebum values in men exceed those of women. Although surface lipid levels fall with age, paradoxically, the sebaceous glands become larger, rather than smaller, as a result of decreased cellular turnover [5, 39, 41–43]. This could explain the larger pores observed on the elderly face. Black subjects have larger sebaceous glands which contribute to the increased sebum secretion. Hillebrand et al. [44] reported that African-Americans showed significantly more sebum excretion than East Asians. African-Americans also had a greater pore count fraction, but the number of pores increased with age in all races [45]. Kligman and Shelley’s [18] comparative racial study also confirmed these observations. Blacks presented higher sebum casual levels compared to Whites [18]. However, the results of Pochi and Strauss [46] and Grimes et al. [47] showed no consistent difference in sebaceous gland activity between black and white skin. Experiments of Cunliffe et al. [48] demonstrated that the sebum excretion rate varies directly with temperature, so that an increase in temperature of 1 ° C produces Skin Pharmacol Physiol 2012;25:227–235 231 Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/27/2018 5:39:24 PM the response of the sebaceous gland to total caloric deprivation in 18 obese patients undergoing fasts for periods of 4–8 weeks. Sebum release reduced in an average of 40% [31]. These data may indicate that the composition and quantity of food could, when changed significantly, produce measurable variation in the sebaceous gland product [32]. Diets rich in carbohydrates with a high glycemic index are associated with hyperglycemia, reactive hyperinsulinemia and increased formation of insulin-like growth factor-1 (IGF-1). Except for cheese, milk and all dairy products also have potent insulinotropic properties, far exceeding those expected from their low glycemic indexes [33]. Insulin and IGF-1 levels also peak during late puberty and gradually decline until the third decade [34]. Insulin and IGF-1 stimulate sebaceous gland lipogenesis in vitro by increasing the expression of a transcription factor (SREBP-1) that regulates numerous genes involved in lipid biosynthesis [35]. IGF-1 also mediates the induction of androgen production and stimulation of peripheral androgen metabolism. Its signaling alleviates androgen receptor repression by the repressive protein Foxo1, resulting in androgen receptor gain-of-function. Thus, IGF-1 has direct influence on the intracrine androgen regulation of the skin and potentiates androgen signaling by the induction of 5␣-reductase activity and activation of the androgen receptor [34]. Vora et al. [36] compared facial sebum levels with serum IGF-1 levels in 16 patients (mean age 19.5 8 2 years) with acne. They found a positive correlation between the mean facial sebum excretion (g cm–2) and serum IGF-1 [36]. Smith et al. [34] compared the endocrine effects of an experimental low glycemic-load diet with a conventional high glycemic-load diet on 43 patients with acne. After 12 weeks, the low glycemic-load diet group showed a significant improvement in insulin sensitivity and a reduction in testosterone bioavailability and DHEAS concentrations [34]. Smith et al. [15] found that volunteers on a low glycemic-load diet demonstrated an increase in the saturated fatty acid/monounsaturated fatty acid ratio compared to a decrease in the control group. However, they did not detect an effect of the dietary intervention on sebum output [15]. Recent evidence suggests that only monounsaturated fatty acids induce hyperkeratinization and epidermal hyperplasia similar to that seen in comedo formation, whereas saturated fatty acids have little effect [37]. Further studies are required to better clarify the underlying role of diet in sebaceous gland physiology. Table 1. Correlations between sebum secretion and diet, genetic influence, age, gender as well as ethnic and seasonal variation Diet Genetic influence Age, gender, ethnic variation Seasonal variation – Composition and quantity of food, when changed significantly, may produce variation in sebum secretion [30, 31] – Insulin and IGF-1 stimulate sebaceous gland lipogenesis in vitro [35] – Vora et al. [36] found a positive correlation between mean facial sebum excretion and serum IGF-1 – Differently from dizygotic twins, sebum secretion is homogeneous between monozygotic twins [38] – Overexpression of the ageing-associated gene Smad7 in adult transgenic mice has been correlated with hyperplasia of the sebaceous gland [39] – Secretion rates are highest in 15–35-year-olds and decline continuously throughout the adult age range [40] – At any age, mean sebum values in men exceed those found in women – Some studies demonstrate no consistent difference in sebaceous gland activity between black and white skin, although others show that Blacks present higher sebum casual levels compared to whites [5, 18, 39, 41–43, 45] – An increase in temperature of 1° C produces an increase in the sebum excretion rate in the order of 10% (due to alterations in sebum viscosity, not in sebum production) [48] – Warming or cooling the skin changes the flow to the surface by making the preformed sebum either more or less viscous [49] 232 Skin Pharmacol Physiol 2012;25:227–235 sual levels. In general, the casual levels were not higher in those whom they estimated to be greasier. In fact, the two highest levels in the group were in subjects judged to be non-greasy. They concluded that marked and persistent greasiness truly reflects increased quantities of surface lipids, but sudden or intermittent greasiness is more likely due to sweating. Warming or cooling the skin changes the flow to the surface by making the preformed sebum either more or less viscous. Therefore, after defatting the skin, the flow to the surface can be expected to be strongly temperature dependent. Furthermore, the wicking power of the emptied capillary reservoir will be greater when the liquid is less viscous. The increased greasiness of the face in the summer or in tropical climates may simply be an expression of increased eccrine sweating or a decreased sebum viscosity [18]. Correlations between sebum secretion and diet, genetic influence, age, gender as well as ethnic and seasonal variations are summarized in table 1. Sebum: Protective Effects The functions attributed to sebum in humans include the delivery of fat-soluble antioxidants to the skin surface and antimicrobial activity [12]. Sebum mantles the epidermis, representing the ultimate barrier of the body against exogenous oxidative insults. It is believed to deliver antioxidants to the surface in the form of vitamin E (␣-tocopherol) and CoQ10 [52]. Squalene is the first human skin surface lipid targeted by oxidative stresses such as sun light and, as a conseSakuma/Maibach Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/27/2018 5:39:24 PM an increase in the sebum excretion rate in the order of 10%. This result might reflect a change in the rate of delivery of sebum to the skin surface due to alterations in sebum viscosity, or an increase in the rate of absorption by the collecting papers. The possibility of sebum production increase was dismissed as the changes occurred within 90 min and the sebaceous gland turnover rate approximates 7 days [48–50]. Youn et al. [51] measured facial sebum secretion seasonally for 1 year and found summer to be the highest sebum-secreting season. Kligman and Shelley [18], while comparing lipoid deliveries in atropinized and non-atropinized sites of sweating subjects, made an observation of clinical significance. Although visible oil droplets formed in the dry atropinized sites, the skin showed no evidence of being greasy or oily. In the symmetrical sweating site, oiliness was prominent. According to them, the clinical impression of oiliness would not be a reliable index of surface lipids (this could explain the differences observed between the Sebumeter measurements and the subjective questionnaire results obtained by Arbuckle et al. [1]). The presence of sweat would impart the clinical appearance of oiliness. According to the authors, how oily a subject will appear at any one time will be influenced by the chance of his/ her having recently sweated or having been in an environment of high humidity. It is easy to understand why oiliness is less prominent in winter and, conversely, so marked in hot humid climates. Possibly, it is the emulsification of sweat with oil that is responsible for the oily appearance. Kligman and Shelley [18] also graded 12 white males in terms of clinical greasiness and determined their ca- Sebum: Undesirable Effects Besides surface oiliness, excess sebum blocks pores, provides nourishment to bacteria that live upon the skin (Propionibacterium acnes) and contributes to acne flareups. Along with increased sebum secretion rate, quantitative modifications of sebum are also likely to occur in acne [12]. Sebum participates in the induction of comedo formation, which represents the retention of hyperproliferating ductal corneocytes in the pilosebaceous duct [56]. Upon oxidative challenge (e.g. UV radiation), squalene is readily oxidized to squalene peroxide, which is comedogenic. Comedones have been triggered by exposing rabbit ears to irradiated squalene. A positive correlation exists between the degree of squalene peroxidation and the size of the comedones elicited. In addition, marked hyperplasia and hyperkeratosis of the epithelium in the follicular infundibulum and marked proliferation of sebaceous glands were observed. In vitro data showed that squalene peroxide beyond the induction of HaCaT keratinocytes proliferation led Oily Skin also to the upregulation and release of inflammatory mediators, which indicate a pro-inflammatory activity of by-products of squalene oxidation. The strategy that skin adopts to limit the potentially harmful effects of peroxidated squalene relies on the vitamin E supply to the skin surface, mentioned previously [12]. Sebum and Water Barrier Function The stratum corneum is an efficient biological barrier membrane, protecting the underlying living tissue from water loss, etc. Despite being on the skin surface, sebum does not seem to influence this function. Fluhr et al. [57] studied asebia J1 mice, which display profound sebaceous gland hypoplasia, and found transepidermal water loss levels comparable to those of control animals, and the ability to acutely restore permeability barrier function to normal after acute disruption was unchanged [58]. Sebum and Hydration Note that skin oiliness is a property of the sebaceous glands and that skin moisture is largely a property of the stratum corneum. Low sebum secretion and high water content are considered main features of fair skin. The latter is dependent upon the rates of water movement into and out of this tissue (barrier function), as well as upon the ability of the stratum corneum to retain water [59, 60]. Hydrated skin is soft and smooth, and reflects the optimum water content in the superficial stratum corneum. It results from the complex and perfect interaction of water-holding substances, (i.e. amino acids produced by proteolysis of filaggrin that occurs during their slow upward movement in the stratum corneum), lactate and potassium derived from sweat as well as intercellular lipids, specially their major component ceramides that play a crucial role in providing barrier function to the stratum corneum [59]. In conjunction with cholesterol, free fatty acids and cholesterol sulfate, they form arrays of hydrophobic chains, constructing lipid bilayers with closely packed interiors which dramatically reduce their permeability to water and solutes. Commonly used tools to assess skin hydration are the Corneometer쏐 (CK electronic), the Skin Surface Hygrometer (Skicon-200) and the DermaPhase meter (Nova DPM 9003), which measure capacitance, conductance and impedance-based capacitance, respectively [61]. Skin Pharmacol Physiol 2012;25:227–235 233 Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/27/2018 5:39:24 PM quence, is depleted where a toxic photo-oxidation product (squalene monohydroperoxide isomers) is produced [53]. Passi et al. [54] demonstrated that exposure of sebum to UV irradiation (4 MED) depleted 84.2% of vitamin E, 70% of CoQ10 and only 13% of squalene, while 10-MED UV exposure produced a 26% loss of squalene. The same UV dose when applied in the absence of vitamin E and CoQ10 produced a 90% decrease in squalene [54]. This antioxidant function of sebum is important as the buildup of reactive oxygen species on the skin surface can cause a breakdown of the skin barrier and signs of aging [8]. Sebocytes are part of the innate immune system. By sonicating total sebum into bacterial culture medium, Wille and Kydonieus [55] observed that the Gram-positive bacteria tested (Staphylococcus aureus, Streptococcus salivarius) were exceedingly susceptible to sebum, with a significant (1 4 orders of magnitude) decrease in the number of viable cells. However, most Gram-negative bacteria tested (Escherichia coli, Pseudomonas aeruginosa and Echinococcus faecalis) were unaffected. Fractionation of the human sebum lipids showed that the C16:1⌬6 isomer of palmitoleic acid (cPA) was the most active antibactericidal fatty acid component and the most active fraction in blocking the adherence of a pathogenic strain of Candida albicans to the porcine stratum corneum [55]. Harsh cleaners or overwashing the skin to remove excess sebum might remove these lipids from the stratum corneum surface, resulting in excessive skin drying. Another essential factor to guarantee minimally permeable water barrier is the physical state of the lipid chains in the non-polar regions of the bilayers. Due to their high melting point, at physiological temperature they are mainly in a solid crystalline or gel state, enabling low lateral diffusional properties. Contrary to the permeability barrier results, Fluhr et al. [57] found that the water-holding capacity of the stratum corneum was reduced in asebia J1 mice. This appeared to be due to a decrease in glycerol, a well-known humectant and a potential catabolic product of sebaceous gland-derived triglycerides. We conclude that the intuitive belief that a low sebum secretion rate is the main cause of dry skin is not accurate, although sebum seems to play a minor role in skin hydration. It is also inappropriate to use the term dry skin as the opposite of oily skin. If dry skin represented the opposite of greasy skin, one should expect little sebum in xerotic conditions. In many types of xerosis, however, sebum excretion remains in the physiological range [8]. The skin should be better referred as oily or non-oily when referring to the sebum content or, when regarding water content, dry or non-dry. Conclusions Oily skin is a common cosmetic problem that occurs when oversized sebaceous glands produce excessive amounts of sebum, giving the appearance of shiny and greasy skin. These glands are under androgen control of and appear influenced by increased IGF-1 generation by high glycemic-index diets. Age, gender, ethnicity and hot humid climates may also play a role in skin oiliness variations. With this overview, we shed some scientific light to some common daily questions and misconceptions, such as why overwashing the skin does not cause sebum overproduction but may cause dryness, why all skin are of a ‘combination’ type and why dry skin is not the opposite of oily skin. 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