Sebum Excretion Research Articles

Glary appearance of men's faces and an evaluation method

It is generally thought that the ‘glary’ appearance impression developed on men's faces is closely related to the amount of skin surface lipids. Although the amount of sebum excretion decreases gradually with aging, the glary appearance is noticeable in middle‐aged men. In order to elucidate the factors other than skin surface lipids affecting the glary appearance of the forehead, a correlation study between the visual evaluation score of glary appearance and morphological measurements of skin surface was conducted. As a result of multiple regression analysis, the standardized partial regression coefficients were 0.490 for the amount of skin surface lipids, –0.370 for skin micro texture and –0.314 for value of skin color. The data indicated that the amount of skin surface lipids was most important, but skin micro texture and value of skin color were also irreplaceable factors to comprehend the glary appearance. A multiple regression equation of glary appearance degree was determined with optical parameters of surface reflection and body reflection by image analysis at the forehead. The results suggested that the surface reflection parameter was influenced by the skin micro texture and actual amount of skin surface lipids. Since Japanese men still hesitate to use skin care products daily for UV protection, the continual exposure of their skin to UV rays gives rise to the flattened micro texture and darkened tone of the skin. These topographical and/or optical changes of skin surface enhance the generation of glary appearance on men's faces. It was concluded that the improvement of the skin micro texture and the tone with skin care products after the removal of excess surface lipids with face wash products was effective for the reduction of the glary appearance.

Die Talgdrüse

The development and function of the sebaceous gland in the fetal and neonatal periods appear to be regulated by maternal androgens and by endogenous steroid synthesis, as well as by other morphogens. The most apparent function of the glands is to excrete sebum. A strong increase in sebum excretion occurs a few hours after birth; this peaks during the first week and slowly subsides thereafter. A new rise takes place at about age 9 years with adrenarche and continues up to age 17 years, when the adult level is reached. The sebaceous gland is a target organ but also an important formation site of hormones, and especially of active androgens. Hormonal activity is based on an hormone (ligand)-receptor interaction, whereas sebocytes express a wide spectrum of hormone receptors. Androgens are well known for their effects on sebum excretion, whereas terminal sebocyte differentiation is assisted by peroxisome proliferator-activated receptor ligands. Estrogens, glucocorticoids, and prolactin also influence sebaceous gland function. In addition, stress-sensing cutaneous signals lead to the production and release of corticotrophin-releasing hormone from dermal nerves and sebocytes with subsequent dose-dependent regulation of sebaceous nonpolar lipids. Among other lipid fractions, sebaceous glands have been shown to synthesize considerable amounts of free fatty acids without exogenous influence. Atopic dermatitis, seborrheic dermatitis, psoriasis and acne vulgaris are some of the disease on which pathogenesis and severity sebaceous lipids may or are surely involved.

Can sebum reduction predict acne outcome?

Sebum excretion has generally been accepted as an important factor in the development of acne vulgaris. However, the relationship of sebum excretion and acne outcome has not yet been clearly demonstrated quantitatively. The objective of this analysis was to explore the correlation of sebum and acne by combining data from studies of various acne treatments that have demonstrated effects on both sebum excretion and acne outcome. Acne measures included total lesion count, inflammatory lesion count and acne severity grade. For each acne measure, data were pooled and analysed at the 3- and 4-month endpoints, when sebum reduction has generally equilibrated and efficacy in acne is approaching the maximum effect for most treatments. A linear model was used to describe the percentage reduction in each acne measure as a function of percentage reduction in sebum excretion. Slope values were similar for the three acne parameters and all were significantly different from zero (P < 0·025), suggesting a significant correlation of sebum and acne. The projected sebum reduction required to achieve 50% reduction in acne measures ranged from 30% to 50%. The results shown here suggest that the collective data across multiple studies may provide a useful generalization of the association of sebum reduction and acne outcome. As the relationship apparently remains consistent regardless of the treatment, it can be inferred that extrapolation to novel exploratory treatments may be valid.

Topical Boswellic acids for treatment of photoaged skin

Boswellic acids (BAs) are pentacyclic triterpenes extracted from the gum resins of the tropical tree Boswellia serrata. They are orally administered in traditional Indian medicine for the treatment of several inflammatory disease and cancer because of their anti-inflammatory and immunomodulatory activities as well as stimulatory effects on fibroblasts. The present authors have investigated efficacy, tolerability, and safety of a base cream containing 0.5% BAs in the treatment of clinical manifestations of photoaging of facial skin with a randomized, double-blind, placebo-controlled, split-face study. Fifteen female volunteers applied the creams with or without BAs on the half sides of the face once daily for 30 days. Significant improvements of the Dover's global score for photoaging, tactile roughness, and fine lines, as well as, with noninvasive diagnostic techniques, an increase of elasticity, a decrease of sebum excretion, and a change of echographic parameters were observed with topical BAs in comparison with placebo. The treatment was always well tolerated without adverse effects. The present findings seem to indicate that topical application of BAs may represent a suitable treatment option for selected features of skin photoaging.

Effect of dihydrotestosterone on the upregulation of inflammatory cytokines in cultured sebocytes

Acne is a complex, chronic and common skin disorder of pilosebaceous units. Hyperkeratinization of keratinocytes, increased sebum excretion from sebocytes via androgen stimulation and inflammatory cytokines are the major factors involved in the pathophysiology of acne. In addition, it is known that keratinocytes play an important role in acne synthesizing a number of inflammatory cytokines. However, the nature of the association between inflammatory cytokines and sebocytes in acne remains unclear. Culture of sebocytes provides a new insight into the participation of dihydrotestosterone (DHT) in the production of inflammatory cytokines in acne. To examine the possible involvement of DHT in the production of inflammatory cytokines in the cultured sebocytes, we used immunohistochemistry and RT-PCR to compare the expression of interleukin-1 (IL-1), IL-6, tumor necrosis factor-alpha (TNF-alpha). Upregulation of IL-6 and TNF-alpha in immunohistochemistry, and increase in RNA amplification for IL-6 and TNF-alpha were observed after addition of DHT compared with the control. This study suggests that DHT may not only be involved in sebum production but also in production of proinflammatory cytokines in acne.

Effects of Topical Boswellic Acid on Photo and Age-Damaged Skin: Clinical, Biophysical, and Echographic Evaluations in a Double-Blind, Randomized, Split-Face Study

Boswellic acids (BAs) are pentacyclic triterpenes with strong anti-inflammatory activity; their most important source is the extract of the gum resin of Boswellia serrata, a tropical tree that grows in India and Africa. In the present randomized, double-blind, split-face, comparative study we have assessed efficacy, tolerability, and safety of a base cream containing 0.5 % BAs as compared to the same cream without these active ingredients in the treatment of clinical manifestations of photoaging of facial skin. Fifteen female volunteers were enrolled; they applied creams once daily for 30 days. At baseline, at the end of the treatment, and after a 2-month follow-up, clinical findings were assessed according to the Dover classification scale for photoaging and by biophysical and ecographic measurements. We registered a significant improvement of tactile roughness and fine lines in the half side of the face treated with BAs; noninvasive instrumental diagnostic investigations showed an improvement of elasticity, a decrease of sebum excretion, and a change of echographic parameters suggesting a reshaping of dermal tissue. The treatment was always well tolerated without adverse effects. The present findings seem to indicate that the topical application of BAs may represent a suitable treatment option for selected features of skin photoaging.

Should dermatologists prescribe hormonal contraceptives for acne?

ABSTRACT One of the primary factors contributing to the development of acne vulgaris is excess sebum. Sebaceous glands and sebum excretion are regulated, at least in part, by androgen hormones. Acne treatments that block this androgen effect include spironolactone and combination oral contraceptives (COC). Three COC are now FDA approved to treat moderate acne. Dermatologists must become experts at prescribing these hormonal contraceptives. Likewise, it is vital to be aware of contraindications to hormonal contraceptive therapy. Proper patient selection relies on an appropriate medical history and an assessment of blood pressure. A pelvic exam and/or Papanicolaou smear are not required prior to initiating therapy with a COC. It is important to counsel patients about potential adverse effects of COC pills and to establish appropriate expectations concerning acne improvement.

Chloracne in seven organic chemists exposed to novel polycyclic halogenated chemical compounds (triazoloquinoxalines)

Chloracne is an acneiform eruption caused though poisoning by aromatic compounds (usually halogenated) showing a specific molecular configuration. We describe an outbreak of chloracne among seven discovery chemists who synthesized novel polycyclic halogenated chemical compounds which were classified as triazoloquinoxalines, not known to be chloracnegenic. The diagnosis of chloracne, made clinically, elicited a thorough risk assessment and monitoring programme by the occupational health department. The chemists were investigated by serum excretion rates, skin sampling for Propionibacterium acnes, skin biopsy and laboratory blood investigations. Sebum excretion was normal in five cases, raised in one case and severely reduced in another. Skin levels of P. acnes were normal in all patients except for the one subject who had low sebum excretion, in whom they were undetectable. One subject had a slightly raised serum level of alanine aminotransferase. There were no other signs of systemic toxicity. Two subjects were treated with an oral antibiotic, two received topical therapy only and three required no treatment at all. The patients have had thorough health surveillance at 6-monthly and yearly intervals. In each case the chloracne mostly resolved within 18-24 months although on examination about 3 years later, five of the seven still showed minor changes of chloracne. This outbreak emphasizes the need for vigilance in discovery science. The triazoloquinoxalines were not previously recognized as being chloracnegens although their chemical characteristics were subsequently identified as being in keeping with other chemicals that can cause chloracne. Chloracne can be a difficult diagnosis to make when it occurs in a novel setting: occupational physicians and dermatologists need to be vigilant when dealing with unusual eruptions in discovery chemists.

Increased interferon-γ, interleukin-12p40 and IL-8 production in Propionibacterium acnes-treated peripheral blood mononuclear cells from patient with acne vulgaris

Acne vulgaris is a multifactorial inflammatory disease of the sebaceous follicles of the face and torso that frequently occurs in adolescence. Initially, acne starts as a non-inflammatory comedo. Subsequently, inflammatory reactions evolve to pustules, granulomas and cystic lesions. Many pathogenic mechanisms have been proposed including sebum excretion, obstruction of hair follicles, impaired keratinization of hair epithelium, bacterial overgrowth and immunological mechanisms; the role of Propionibacterium acnes (P. acnes) is particularly important. Facultative anaerobic gram-positive rods have been implicated in acne pathogenesis. However, the host immune response to P. acnes has not been as yet elucidated. The aim of the present study is to evaluate the importance of the immune response to P. acnes and the bacteriological factor in the pathogenesis of acne. P. acnes isolated from acne lesions and healthy volunteers skin were cultured. The peripheral blood mononuclear cells (PBMC) from acne patients or healthy volunteers were stimulated with viable P. acnes, and cytokine production was evaluated using RT-PCR and ELISA. IFN-gamma, IL-12p40, and IL-8 mRNA and protein production were significantly increased in PBMC from acne patients compared to that from normal donors. However, different P. acnes species isolated from acne lesions or normal subjects showed no difference in cytokines production from acne patients and normal subjects PBMC. The inflammatory response of acne appears to be attributable to P. acnes-induced host immune response rather than P. acnes strains from normal skin or acne lesions.

Diet and acne: a review of the evidence

Pharmaceutical acne treatments are costly and have potentially severe side-effects. Adolescent acne is typically the result of clogged, infected, pilosebaceous follicles. Adults may experience fewer comedones and more inflammatory lesions. 1 Normally, sebum travels up the follicle to the skin surface. Hormones may increase sebum production and cause follicular cells to hyperproliferate and block the follicular opening, forming a comedo. 4 Complete follicle blockage results in closed comedones (i.e. “whiteheads”), whereas incomplete blockage results in open comedones (“blackheads”). Comedo formation typically occurs over the course of 2–3 weeks. Acne may manifest in the form of noninflammatory comedones, superficial inflammatory lesions (papules, pustules), and/or deeper inflammatory lesions (nodules, cysts). Inflammatory lesion formation occurs most commonly when Propionibacterium acnes colonizes the pilosebaceous unit, triggering follicular rupture and a neutrophil cascade. 5

Epidermal surface lipids

A layer of lipids, which are of both sebaceous and keratinocyte origin, covers the surface of the skin. The apparent composition of surface lipids varies depending on the selected method of sampling. Lipids produced by the epidermal cells are an insignificant fraction of the total extractable surface lipid on areas rich in sebaceous glands. Due to the holocrine activity of the sebaceous gland, its product of secretion (sebum) is eventually released to the surface of the skin and coats the fur as well. Lipids of epidermal origin fill the spaces between the cells, like mortar or cement. The sebaceous lipids are primarily non polar lipids as triglycerides, wax esters and squalene, while epidermal lipids are a mixture of ceramides, free fatty acids and cholesterol. The composition of the sebaceous lipids is unique and intriguing and elevated sebum excretion is a major factor involved in the pathophysiology of acne. Recent studies have elucidated the roles that epidermal surface lipids have on normal skin functions and acne.

Effects of a 1,450 nm diode laser on facial sebum excretion

Laser therapy with a 1,450 nm diode laser is a clinically effective treatment for acne vulgaris, although the mechanism of action is unknown. To investigate this, we conducted a small, prospective, controlled clinical trial to assess this laser's effects on the facial sebum excretion rate (SER). Fourteen healthy volunteers without active acne were enrolled in this study and received three laser treatments on test areas of the nose and forehead. Nine subjects completed the treatment regimen and were available for follow-up. SER was measured with Sebumeter prior to the first treatment, and at 1 week and 1 month after the third treatment. Photographs were taken and subjective assessment of skin oiliness and pore size determined by questionnaires at 1 month follow-up. No significant reduction in SER was observed comparing treated with control on all treatment sites (P>0.05) on the nose. Reduction in the absolute SER was observed for both test and control sites on the forehead, reaching significance on the treatment site (P = 0.04) and marginal significance on the control site (P = 0.08). While our study was designed to detect only large changes in SER, we conclude that three 1,450 nm laser treatment sessions did not cause marked changes in SER compared to the control (i.e., >44%). Thus, major destruction of sebaceous glands as a result of this treatment is unlikely. However, reduced sebum production was observed on both treatment and control sides at 1 month. Therefore alternative mechanisms should also be considered to explain the clinical efficacy of this treatment for acne vulgaris.

Single Low-dose Red Light is as Efficacious as Methyl-aminolevulinate-photodynamic Therapy for Treatment of Acne: Clinical Assessment and Fluorescence Monitoring

This controlled study investigated single low-dose red light photodynamic therapy and methyl-aminolevulinate (MAL) for treatment of moderate to severe facial acne in 19 patients. The right cheek was treated with MAL (160 mg/g) for 3 h prior to illumination. The left cheek received red light only. Both cheeks were illuminated with narrow-band red light (635 nm) at a light dose of 15 J/cm2. The global severity of acne was assessed at baseline and at follow-up, 10 and 20 weeks after treatment. Fluorescence images, clinical photographs and skin surface biopsies were obtained. Both MAL-photodynamic therapy and control areas showed a significant decrease in acne score at follow-up; no significant difference was found compared with control. MAL-photodynamic therapy was associated with adverse effects such as erythema and stinging. Fluorescence images revealed poor selectivity of MAL-induced fluorescence to the acne lesions, suggesting a general photoablating mechanism rather than selective destruction of sebaceous glands. No significant reduction in Propionibacterium acnes or sebum excretion was found.

Non‐invasive diagnostic evaluation of phototherapeutic effects of red light phototherapy of acne vulgaris

During the past few years, various phototherapeutic protocols with full-spectrum visible light or selected wavebands have been investigated in the treatment of acne vulgaris with variable results. Fifteen women suffering from moderate acne vulgaris of the face were exposed to 20 J/cm(2) of broad-band red (lambda: 600-750 nm) light twice weekly for 4 weeks. In addition, with the aim to improve the present knowledge of the mechanisms of action of phototherapy, we measured skin sebum, pH, hydration and trans-epidermal water loss (TEWL). Lesions of the trunk were not irradiated and served as controls. A significant improvement of acne lesions and a significant decrease of skin sebum excretion and TEWL of the face were registered at the end of the therapy and at the 3-month follow-up visit. The results could be related to a reduced follicular colonization of Propionibacterium acnes, in that it was lethally damaged by photoactivated endogenous porphyrins. The present findings seem to indicate that red light phototherapy may represent an effective, well-tolerated, safe, simple and inexpensive treatment option for moderate acne vulgaris.

LXRα Enhances Lipid Synthesis in SZ95 Sebocytes

Differentiation of sebocytes is strongly associated with enhanced lipid synthesis and accumulation in the cells. Liver X receptors (LXRs) are members of the nuclear receptor superfamily, which play a critical role in cholesterol homeostasis and lipid metabolism. We examined whether LXRalpha regulated lipid synthesis in the immortalized human sebaceous gland cell line SZ95. When the SZ95 sebocytes were treated with the ligand of LXR such as TO901317 or 22(R)-hydroxycholesterol, lipid droplets were accumulated in the majority of cells when examined by Oil Red O staining. The expression of the known LXR targets, such as fatty acid synthase and sterol regulatory-binding protein-1, was induced by TO901317. TO901317 treatment increased expression of LXRalpha but not that of LXRbeta. Transfection of antisense LXRalpha significantly decreased TO901317-induced target gene expression and lipid droplet accumulation, suggesting a major role of LXRalpha in differentiation of sebocytes. Further, TO901317 decreased the expression of cyclooxygenase-2 and inducible nitric oxide synthase that was induced by lipopolysaccharide treatment. Together, these results indicate that important roles of LXRalpha in differentiation and inflammatory signaling in sebaceous glands. Thus, we suggest that LXR ligands could provide a new class of therapeutic agents for sebaceous gland-associated disorders such as seborrhea and acne.

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Quantitative evaluation of sebum lipid components with nuclear magnetic resonance

A NMR spectroscopic method is described that enables the quantitation of specific lipid classes and components, independent of fatty acid composition. We demonstrate this method for measuring cholesterol, squalene, and pools of sterol esters, wax esters (WEs), and triglyceride (TG) components in sebum and meibum. When 600 MHz NMR equipment is used in conjunction with highly sensitive cryogenically cooled probes, this method has adequate sensitivity, and for some applications, advantages over commonly used HPLC-evaporative light-scattering detection and mass spectrometry-based approaches. This method is shown to be useful for preclinical and clinical monitoring of the efficacy of sebum-reducing agents in animals and humans. In Syrian hamsters, 3% topical flutamide and 20 mg/kg oral isotretinoin reduced sterol esters by 18.7% and 30.0%, respectively, and reduced WEs by 32.9% and 31.8%, respectively, as measured in a punch biopsy of the ear. In a 72 patient clinical methodology study, the assay delivered reproducible and noninvasive measurements of WEs, cholesteryl esters, TGs, and squalene from Sebutape skin blots. The quantitative results of sebum analysis obtained by the NMR method correlate well with those obtained with HPLC-based approaches. This approach may be broadly applicable to cases in which fatty acid-independent quantification of lipid classes is desired.

A Citrus Polymethoxy Flavonoid, Nobiletin Inhibits Sebum Production and Sebocyte Proliferation, and Augments Sebum Excretion in Hamsters

Acne vulgaris is characterized by excess sebum production, and apart from all-trans retinoic acid (atRA) or 13-cis retinoic acid (13-cisRA), there are few effective agents for acne therapy that directly suppresses sebaceous lipogenesis. In this study, we demonstrated that topical application of a citrus polymethoxy flavonoid, nobiletin, to hamster auricles decreased skin surface triacylglycerols (TG) level and the size of sebaceous glands along with inhibition of diacylglycerol acyltransferase (DGAT)-dependent TG synthesis and sebocyte proliferation. The inhibitory actions were similar to that observed with atRA and 13-cisRA in hamster sebocytes. The antilipogenic and antiproliferative actions of nobiletin were also reproduced in UVB (5.4 kJ/m2)-irradiated hamsters, which showed aberrant enhancement of sebum accumulation and sebaceous enlargement. Furthermore, nobiletin, but not 13-cisRA, augmented sebum excretion along with increases in intracellular cAMP level, protein kinase A (PKA) activation, and apoptosis-independent phosphatidylserine (PS) externalization in cell membrane. These phenomena were reproduced by forskolin and inhibited by a PKA inhibitor, H-89. These results provide early evidence that nobiletin is an effective candidate for acne therapy through mechanisms that include the inhibition of DGAT-dependent TG synthesis and sebocyte proliferation, and the progression of apoptosis-independent and PS-externalization-dependent sebum excretion by PKA activation.

Functional characteristics of the stratum corneum in photoaged skin in comparison with those found in intrinsic aging

Among various functions of the skin, the most vital one is carried out by the stratum corneum (SC), because the SC effectively protects our body from desiccation even in a dry environment as well as from external invasion of injurious agents. Despite the general decline of various bodily functions in advanced age, the barrier function of the SC does not deteriorate but rather improves with aging, reflecting the reduced epidermal proliferation associated with slower desquamation of the SC. Although the intercellular lipid production that is crucial for the SC barrier is reduced in aged epidermis, it is compensated by the thicker SC, consisting of larger corneocytes covering the aged skin surface due to the retardation of the desquamating process. However, such SC is deficient in water-binding capacity, another important function of the SC that keeps the skin surface soft and smooth, due to decreased amounts of water-binding substances in the SC. Thus, large portions of the covered skin begin to develop xerotic changes in a dry environment of winter, being frequently accompanied by pruritus. In contrast, most elderly individuals display the unique features of photoaging on their exposed skin such as the face and hands due to chronic exposure to the ultraviolet light (UV) of sunlight. However, functional derangements of the SC are rather mild in the photoaged skin. Our functional analyses of the SC of the chronically sun-exposed skin found in the symmetrical located areas, i.e., the dorsa of the hands in middle-aged Japanese golf players who always wore a glove only on the one of the hands demonstrated significant impairment in SC water-binding capacity in the sun-exposed side, while its barrier function was well retained. Despite the decreased water content of the SC, elderly people can live without any inconvenience even when they expose the facial skin to the dry environment of winter, because there take place sebum excretion and non-apparent sweating by comparison with the skin of the sun-protected areas such as the trunk and limbs that easily develop xerotic changes in cold seasons.

Efficacy of ALA‐PDT vs blue light in the treatment of acne

Photodynamic therapy (PDT) is based on the principle of using light excitation of a wavelength-specific endogenous or exogenous photosensitizer to destroy the target tissue, and has shown efficacy in the treatment of certain non-melanoma skin cancers. PDT using aminolevulinic acid (5-ALA) has attracted attention in the treatment of acne vulgaris. Twenty patients with moderate to severe acne vulgaris on the face were treated with four sessions of topical ALA-PDT with blue light (415 nm) on the right side of the face compared with blue light alone on the left side of the face, each treatment being 1 week apart. Ten percent of topical ALA was applied to acne spots on the right side of the face with a 1-h incubation period and the entire face was treated with 48 J/cm(2) of 415 +/- 5 nm light from an articulated LED planar array. Evaluation was performed by counting acne lesions at baseline, 4, 8, 12 and 16 weeks after the beginning of the treatment. Biophysical measurements included sebum levels and the erythema, and melanin indices. At the given assessment times 4, 8, 12 and 16 weeks after the beginning of the treatment, the mean percent reduction in inflamed lesions counts tended to be higher in the ALA-PDT areas; it was 32%, 50.9%, 65.9% and 71.1%, respectively, compared with the blue-light-alone treatment, which was 20.7%, 27%, 57.7% and 56.7%, respectively, but without any statistical significance (P=0.092). There was no demonstrable significant change in sebum excretion, erythema or the melanin index after treatment. The side effects were pain, stinging, peeling, erythema, pruritus, oozing and pustules. These side effects were stronger on the ALA-PDT-treated side. From this study, the trend for ALA-PDT with blue light to be superior to blue light alone was observed, but it did not reach statistical significance. ALA-PDT had more side effects.