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For Author's Personal Journal of Nutritional Therapeutics, 2013, 2, 59-73 59 Use of Vitamins and their Derivates in the Treatment of Cutaneous Disorders Andrea Chiricozzi1,2,*, Maria Sole Chimenti3, Mauro Bavetta1, Graziella Babino1, Sergio Chimenti1 and Rosita Saraceno1 1Department of Dermatology, University of Rome Tor Vergata. Viale Oxford 81, 00133, Rome, Italy 2Laboratory for Investigative Dermatology, The Rockefeller University, 1230 York Avenue, Box 178, New York, New York 10065-6399, USA 3Department of Rheumatology, University of Rome Tor Vergata. Viale Oxford 81, 00133, Rome, Italy Abstract: Vitamins represent fundamental substrates for various physiologic functions occurring in human body. This review seeks to highlight their relevance in skin biology and to describe the cutaneous manifestations correlated with their deficiency. Keywords: Vitamin deficiency, psoriasis, vitamin A, vitamin B, vitamin C, skin physiology. INTRODUCTION receptors that act as transcription factors, which promote the physiologicUse effects on DNA transcription. The intake and the metabolism of nutrients in These receptors fall into two classes, the retinoic acid appropriate proportion provide the substrates receptor (RARs) and the retinoid x receptor (RXRs). necessary for physiologic functions. Derangements of Human skin expresses predominantly RAR- and RXR- this normal proportion and balance lead to disease [3-5]. states that can produce cutaneous manifestations with an involvement of multiple organs [1]. Because of the Vitamin A deficiency is the most common cause of importance of nutrients for cellular metabolism in a preventable childhood blindness. Xerophthalmia is variety of tissues, this review provides an overview on initially characterized by defective dark adaptation and vitamins and their role in cutaneous disorders. Personalnight blindness. Perpetuating vitamin A deficiency determinates xerosis, ulceration and perforation of the VITAMIN A cornea, prolapse of the iris, and, ultimately, blindness [6,7]. The typical cutaneous hypovitaminosis A Vitamin A, retinol, is a fat-soluble vitamin that is manifestation is phrynoderma, characterized by xerosis required for retinal photoreceptor function, and keratotic follicular papules preferably located on hematopoiesis, embryonic development, skin cell the flexure and traction side of the upper arms, and on differentiation, immune system function and gene the trunk and nape (Table 1). Differential diagnoses transcription. Vitamin A cannot be synthesized; it must include pityriasis rubra pilaris and lichen spinulosus. be obtained through animal products,Author's such as cow's Phrynoderma is probably based on additional milk, liver, eggs, fish oils, as retinyl esters. Retinyl deficiencies of unsaturated fatty acids, vitamin C, and esters are converted to retinol and absorbed in the B-complex vitamins [8-13]. ileum. After absorption, a small percentage of retinol is converted to its Forbiologically active form, all-trans Vitamin A and its analogs in cosmetic applications retinoic acid (tretinoin), through an intermediary, are among the most important agents used for skin retinaldehyde. Most of retinol is converted to retinyl care. They have been used topically in treating acne ester, its storage form [1, 2]. Two vitamin A derivates, and photodamage skin and they have been tested for the topical treatment of striae, cellulitis, and wound namely retinal and retinoid acid, are used for healing [14-20]. In addition, they represent an approved therapeutic purposes. and well-established treatment for psoriasis, used both Retinoid signaling is mediated by various nuclear orally and topically as monotherapy or in therapeutic receptors, which belong to superfamily of nuclear combinations. Use of Retinoids in the Treatment of Acne *Address correspondence to this author at the Department of Dermatology, University of Rome Tor Vergata, Viale Oxford 81, 00133, Rome, Italy; Acne is a common skin disease showing a Tel: +39.06.20902742; Fax: +39.06.20902743; E-mail: [email protected] multifactorial pathogenesis, which includes increased E-ISSN: 1929-5634/13 © 2013 Lifescience Global 60 Journal of Nutritional Therapeutics, 2013 Vol. 2, No. 2 Chiricozzi et al. Table 1: Disorders and Clinical Manifestions Related to Vitamin Deficiency Vitamins Disorders associated with vitamin deficiency VITAMIN A Xerophthalmia, Phrynoderma BETA-CAROTENE Immunosuppression VITAMIN B1 "Beriberi" disease, Impaired wound heeling, Wernicke encephalopathy (acute) and Korsakoff syndrome (chronic) VITAMIN B2 Ariboflavinosis (angular cheilitis, pharyngitis, glossitis, seborrheic dermatitis, photosensitivity), Oro-oculo-genital syndrome VITAMIN B3 Pellagra (dermatitis, dementia, diarrhea, death) VITAMIN B6 Seborrheic eruption , Oral symptoms (glossitis, stomatitis, cheilitis, aphtha), Conjunctivitis, Intertrigo, Pellagra- like dermatitis (erythema, hyperpigmentation, scaling), Neurologic symptoms (somnolence, confusion, peripheral neuropathy), Hypochromic, microcytic anemia VITAMIN B12 Megaloblastic anemia, Hypersegmented neutrophils, Cutaneous hyperpigmentation, Mucocutaneous manifestations (angular cheilitis, Hunter glossitis , localized or diffuse hair depigmentation, mucocutaneous hyperpigmentation), Neurologic signs (paresthesias, ataxia, symmetric loss of vibration and proprioception, severe weakness, spasticity, paraplegia, apathy, somnolence, irritability, memory loss, dementia) VITAMIN C Scurvy, Collagen defects, Defective fibroblast responses, Defective white cell production, Abnormal scar tissue formation, Impaired use of oxygen free radicals for killing bacteria, ImpairedUse -globulin production VITAMIN D Osteomalacia, Rickets VITAMIN E Abetalipoproteinemia (poor transmission of nerve impulses, muscle weakness, retina degeneration), Neurolomuscolar signs (spinocerebellar ataxia, myopathies, dysarthria, absence of deep tendon reflexes, loss of vibratory sensation and proprioception), Anemia, Ocular diseases (retinopathy, cataracts), Immunosuppression, Male infertility, Dry hair or loss of hair VITAMIN K Multiorgan hemorrhage (cutaneous, gastrointestinal, genitourinary, and retroperitoneal bleeding), Purpura and ecchymosis, Impaired wound heeling, Immunosuppression, Neonatal vitamin K deficiency bleeding (VKDB) secretion of sebum, follicular hyperkeratinization, treatment of keratinizing disorders such as hidradenitis bacterial colonization by Propionibacterium acnes (P. Personalsuppurativa, Darier’s disease, granulomatous rosacea, acnes), and a potent inflammatory response. Retinoids lamellar ichthyosis, and non-bullous congenital might be considered as the ideal agents for treating ichthyosiform erythroderma [26,27]. Several studies acne because they are able to interfere with the reported that oral isotretinoin might induce extended majority of pathogenic aspects having (i) anti- remission or cure of pityriasis rubra pilaris [28-30]. Qui inflammatory effects, (ii) reducing seborrhea, (iii) vanno divise: nel punto [A] va messa la referenza 26 e regulating keratinocyte proliferation and differentiation. 28 mentre nel punto [B] vanno messe la referenza 27, 29, e 30. Retinoids, in particular trans-retinoic acid (tretinoin) as topical formulation, have beenAuthor's used to treat acne Retinoic acid and retinol are involved in the repair of since 1974 [21]. The principal Vitamin A metabolite photodamage by a restorative mechanism and by used for the treatment of acne is isotretinoin (13-Cis limiting the progression of existing damage. In retinoic acid). Isotretinoin regulates keratinocyte particular, they inhibit the UV-induced expression of the proliferation leadingFor to a reduction of comedone matrix metalloproteinases, which are responsible for formation (Table 2). It also suppresses sebaceous- the breakdown of collagen fibers in the dermis. Retinoic gland activity with a subsequent reduction of sebum acid regulates keratinocyte proliferation and production, which hampers P. acnes colonization. differentiation resulting in a physiological shedding of Because of this activity, isotretinoin is also successfully mature keratinocytes and in smoother skin-surface used in oral formulation for the management of severe texture. Moreover, it stimulates fibroblasts in producing nodulocystic acne [22-25]. abundant collagen, which reconstitutes regular dermal thickness and more resistance to trauma [14,15]. Use of Retinoids in the Treatment of other Cutaneous Disorders Regarding pigmentation, retinoids also inhibit UV- induced alterations constituted by brownish spots and Vitamin A and its derivatives, etretinate and overall uneven pigmentation. isotretinoin, have been proved effective in the Use of Vitamins and their Derivates in the Treatment Journal of Nutritional Therapeutics, 2013 Vol. 2, No. 2 61 Table 2: Functions and Effects of Vitamins on Skin Physiology Effects of vitamins on cutaneous physiologic processes VITAMIN A - anti-inflammatory effects - reduction of seborrhea - regulation of keratinocyte proliferation and differentiation - inhibition the UV-induced expression of the matrix metalloproteinases - promotion natural reparative processes in photodamaged skin BETA CAROTENE - protection cell membranes from lipid peroxidation process - inhibition of apoptosis VITAMINA B COMPLEX: VIT. B1 (THIAMIN), VIT. - metabolic and oxidation-reduction reactions B2 (RIBOFLAVIN), VIT. B3 (NIACIN), VIT. B6 - stabilization and protection of cell membrane VITAMIN C - protection against UV-induced DNA damage and lipid peroxidation - formation of stratum
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