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Causality in acne vulgaris

Treating acne breakouts require thorough understanding of its pathogenesis [1], etiological factors [2] and manifestations and types of acne. Acne is common among teenagers (prevalence of 80% in the majority of countries worldwide) [3], yet it could affect people over 20. Acne causes has been researched extensively and multitude of factors have been identifies in etiology. Although acne is most prevalent among teen-aged males, most can expect spontaneous treatment by age 25. Adult females may continue to experience acne into the adult years, sometimes beyond the age of 40. It is more common in males, 29.9% in men versus 23.7 in females [4]. Problem skin ( skin implicated with acne ) characterizes by clogged enlarged pores, excess production of sebum and fatty inclusions , abnormal bacterial function and production of inflammation in acne lesions.
mtorc1 signals upregulation of lipogenesis and implicates in acne causes

mTORC1 signals upregulation of lipogenesis

Fibroblast growth factor receptor signaling

Fibroblasts growth factor receptor (FGFR), a family of tyrosine kinase receptros, signaling appear to be another mechanism in orchestrating follicular hyperkeratinization and sebocytes proliferation and contribute to developement of acne vulgaris. This concept envision the idea that FGFR signaling may manipulate known mechanisms by which anti acne treatments operate. In line with these studies, it has been proposed that free radicals generated by benzoyl peroxide, a key molecule in fighting the bacteria that causes acne, downregulates signal transduction by fibroblast growth factor receptors and leads to dwindled sebocyte proliferation and sebum production.
Fibroblast growth factor receptor signaling in pathogenesis of acne vulgaris

Fibroblast growth factor receptor signaling in pathogenesis of acne vulgaris, decreased sebocytes proliferation and sebum production

Role of different factors in development of acne

Acne is a multi factorial disease. Genetic [5], racial [6], hormonal, dietary and environmental factors have been implicated and broadly recognized as acne causes, while it is clear that its psychological implications may be severe. Although the role of heredity in acne has not been clearly denied, there is a great tendency toward more serious involvement if one or both parents had severe acne during their youth .

Hormonal factors, what causes adult acne

Hormones, androgens [7], are well known amid adult acne causes and pathogenesis. Sebaceous glands ( part of sebaceous follicles ) are extremely sensitive to androgenic stimulation, and their enlargement usually precedes other obvious signs of puberty even before any sign of acne [8]. Terminal sebaceous differentiation is assisted by peroxisome proliferator-activated receptor ligands [9]. Relationship between sebum out put and testosterone as a representative plasma androgen.[9].

Sebocytes are under endocrine control and so it is not surprising that sebum production varies with age and sex [10]. Increase in sebum production is associated with increase in free fatty acids rather than an increase in essential fatty acids. Males have a significantly greater sebum production than females. The sebum production continues to increase after puberty, reaching a peak in both sexes between 30 and 40 years, and thereafter there is a gradual decline. Sebum appears to be central amid factors contended with by acne causes.

Androgens affect differentiation of pilosebaceous unit

Solid lines indicate the effects of androgen, dashed lines indicate the effects of anti-androgens. In balding scalp (bracketed area) terminal hairs not previously dependent of androgen regress to vellus hairs under the influence of androgen [11].

It is evident that the sebaceous gland is an androgen target organ and any measure pharmacologically to control androgens is a logical approach to treatment of acne. Hormonal therapy remains an important part of the arsenal of acne treatments available to the clinician [12].

Emotional factors and acne

As with any disease whose course is prolonged and capricious, the importance of psychological factors in treatment of breakouts has been repeatedly stressed and should be seriously taken into account when using treatments or in developing protocols how to prevent acne[13]. Patients with cysts frequently report being self conscious, anxious and socially isolated. Not only the psychological status is influenced in subjects with stress but also their sympathoadrenal system [14]. There seems to be no doubt that stressful situations such as final examinations regularly explained as what causes acne exacerbations in patients. This is probably the result of increased glucocorticoid secretion by the adrenal glands that seem to potentiate the effect of androgens.

One more evidence suggesting role of stress in acne pathogenesis is studies on substance P. Substance P, which can be elicited by stress and expressed in the nerve endings at the vicinity of healthy-looking glands, promoted the development of cytoplasmic organells in sebaceous cells, induce significant inncreases in the area of sebaceous gland and increased the size of individual sebaceous cells, all of which suggests that substance P promotes both the proliferation a and the differentiation of sebaceouls glands [15]. Attention should be paid to psychosomatic aspects especially if depressive-anxious disorders are suspected, particularly with evidence of suicidal tendencies, body dysmorphic disorders or also in disrupted compliance [16].

Environmental factors and acne causes

Role of various lights on acne vulgaris

Environmental factors also play a major role in determining types, severity and extent of acne and affect topical treatments. In most cases the manifestations are worse in winter and improves during the summer, suggesting a salutary effect of sunlight [17]. Sun-bathing may be beneficial for psychological reason and may produce euphoric effects. Nonetheless, some studies recognize sun exposure and air pollution as aggravating by oxidative stress causing dysseborrhea and comedone formation illuminating role of proper suncare in acne patients. Some forms of light therapy were of short-term benefit. However, very few trials have been conducted to examine long-term benefit of this treatment [18]. Photodynamic therapy (PDT) appears to be a useful therapeutic option for acne patients who are recalcitrant to standard treatments and poor candidates for systemic retinoids [19].

Physical and mechanical contact

The constant friction caused by protective devices such as a helmet, shoulder pads or pillows will make acne management futile and may be counted as one of acne causes. Cosmetic face friction as a cosmetic care becomes more and more fashionable, which may lead to exogenous acne in those without any history of acne [20]. Athletes may be more prone to acne due to combating pressure and friction, which is more known as acne mechanica [21].

High glycemic diet and foods, what food causes acne?

Compelling evidence exists that high glycemic load diets may be viewed as what causes acne [22]. Foods with significant sugar content and other carbohydrates yielding high glycemic loads affect serum insulin and insulin-like-growth-factor-1 (IGF-1) levels, both of which promote increase production of available androgens and the subsequent development of acne [23]. In addition, dairy products can change the hormonal levels. The natural function of mild being to stimulate growth, it contains anabolic steroids as well as true growth hormones and other growth factors [23]. Insulin sensitivity and sex-hormone-binding globulin (SHBG) are directly correlated, such that falls in insulin sensitivity increase the free androgen index (FAI) [preziosi].
Acne etiology and interplay of dietary factors

Acne etiology and interplay of dietary factors

The intake of abundant hypoglycemic carbohydrate-rich foods and high consumption of mild and dairy protein such as whey protein [*] predominantly during puberty, a period of high insulin/IGF1 signaling, may over-activate mTORC1, which enhances sebocyte growth and proliferation and SREBP-1 (Sterol regulatory element binding protein-1), the key transcription factor of lipid biosynthesis, mediated sebaceoous lipogenesis [24]. Individuals with higher serum level of linoleic acid, ω-6, and alpha linolenic acid, ω-3, have been found less prone to keratinocyte tumors such as squamous cell carcinoma and basal cell carcinoma, a fact which may shed light on contribution of diet, omega-3 and omega-6 poly unsaturated fatty acids to comedogenesis and acne causes in less differentiated overly proliferated cells.

Enhancement of insulin/IGF1 signaling by diary products

There is substantial epidemiological and biochemical evidence supporting the effects of milk and dairy foods and products as enhancers of insulin-IGF1 signaling, counted as one of likely acne causes, leading to its aggravation. Moreover, milk signaling potentiates the signaling effects of hyperglycemic carbohydrates. By the same token, the branched chain essential amino acid, BCAA, leucine, abundant in whey protein, commonly consumed by athletes,  and enhanced IGF-1 by diary products sensed and integrated by mTORC1 and cause its activation, which, in turn, activates the transcription factor, SREBP, and thereby by merit of sebaceous lipogenesis may be counted toward acne causes.On the other hand, leucine can be directly converted to free fatty acids and sterols within sebocytes for lipid synthesis. Wheat protein (7%) contains half as much leucine as whey protein (14%). Signaling pathways in acne mediated by high glycemic load and diary products. Note how high insulin/IGF1 activates mTORC1 [24].

Acne causes, role of high glycemic food

Acne causes, how high glycemic nutrition increases mTORC1

These findings shed new light on the role of milk signaling during adolescence and may explain the observed association of severe acne and increased risk of prostate cancer later in life by a common mode of signal transmission [25].

Role of inheritance and genetics

Acne is rather universal in adolescent population within western societies while its frequency in certain remote islands appear to be nearly rare. Role of hereditary can not be disregarded in acne vulgaris as differences in prevalence across various geographical areas has been observed. This in part can be attributed to the distinct dietary choices, environmental variations as well as heterogeneity in genetic makeup [26]. Examination of dietary habits and patterns in multifarious societies is a valuable means to elucidate diet-acne link [27].


A significant linear relationship between acne prevalence and number of cigarettes smoked daily was obtained (P<0.001) in a study done by Ring J et al to evaluate contribution of smoking to acne causes[4]. In addition, a significant dose-dependent relationship between acne severity and daily cigarette consumption was shown by linear regression analysis [4] . Comedonal postaldolescent acne appears as the most frequent clinical form of postadolescent acne and seems to be strictly correlated with cigarette smoking [28].


Within the dermatology community, a general consensus has emerged that a poor or ambiguous association exists between diet and the etiology of acne vulgaris for more than twenty years [29] [30]. Role of hereditary has been reported by several studies [31]. However, genetic factors may not fully account for this influence and environmental contributions especially through dietary regimens may be considered. Today several studies indicate role of diet induced through modification of genetic expression [32]. Surge of insulin and IGF1 following consumption of certain diets leads to depletion of transcription factor FoxO1, which is activatory for acne target genes and one of mechanism by which acne causes exert, at molecular level, their leverage.

High glycemic diet, dairy products and animal protein has been recognized as affecting this expression through activation of IGF-1/insulin, which, in turn, influence mTORC1 [33]. Transcriptor factor sterol regulatory element binding protein-1 (SREBP-1) is influenced by mTORC1. This pathway leads to pathogenesis in sebaceous glands and more synthesis of free fatty acids, with well known role in acne vulgaris pathogenesis.

In comparison diets high in saturated fat have been associated with increase in IGF-1 and androgens [34]. Moreover, composition of fatty diet is of significance. Omega-3 fatty acids show decrease in pro-inflammatory pathways and IGF-1 [35]. IGF-1 is comedogenic by activation of nuclear transcription factors such as FoxO1 and mTORC1 which directly affect genes influencing acne through androgen receptor trans activation, increase in sebaceous gland secretions and follicular inflammation.

Influence of dietary changes in activation of mTORC1. Reduction in high glycemic food diet, dairy preparations and foods rich in animal protein (leucine) changes this pathway. Effect of isotretinoin, benzoyl peroxide on attenuation of mTORC1 is demonstrated [36].


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