Caffeine is being increasingly used in cosmetics due to its high biological activity and ability to penetrate the skin barrier. This alkaloid is frequently used as a hydrophilic model substance in human and animal skin penetration as well as different synthetic membrane using Franz diffusion cell experiments. The commercially available topical formulations of caffeine normally contain 3% caffeine. As for a cosmetic purpose, caffeine is used as an active compound in anti-cellulite products because it prevents excessive accumulation of fat in cells. This alkaloid stimulates the degradation of fats during lipolysis through inhibition of the phosphodiesterase activity. Caffeine has potent antioxidant properties. It helps protect cells against the UV radiation and slows down the process of photoaging of the skin. Moreover, caffeine contained in cosmetics increases the microcirculation of blood in the skin and also stimulates the growth of hair through inhibition of the 5-α-reductase activity.

Kerrigan S, Lindsey T: Fatal caffeine overdose: two case reports. Forensic Sci Int 2005;153:67–69.
Burlando B, Verotta L, Cornara L, Bottini-Massa E: Herbal Principles in Cosmetics. Properties and Mechanism of Action. London, CRC Press, 2010, pp 178–179.
Fisone G, Borgkvist A, Usiello A: Caffeine as a psychomotor stimulant: mechanism of action. Cell Mol Life Sci 2004;61:857–872.
Huang ZL, Qu WM, Eguchi N, Chen JF, Schwarzschild MA, Fredholm BB, Urade Y, Hayaishi O: Adenosine A2A, but not A1, receptors mediate the arousal effect of caffeine. Nat Neurosci 2005;8:858–859.
Zhang WY: A benefit-risk assessment of caffeine as an analgesic adjuvant. Drug Saf 2001;24:1127–1142.
Smith A: Effects of caffeine on human behavior. Food Chem Toxicol 2002;40:1243–1255.
Kim C, Shim J, Han S, Chang I: The skin-permeation-enhancing effect of phosphatidylcholine: caffeine as a model active ingredient. J Cosmet Sci 2002;53:363–374.
Trauer S, Patzelt A, Otberg N, Knorr F, Rozycki C, Balizs G, Büttemeyer R, Linscheid M, Liebsch M, Lademann J: Permeation of topically applied caffeine through human skin – a comparison of in vivo and in vitro data. Br J Clin Pharmacol 2009;68:181–186.
Johnson S, Moss G, Thomas CP: In vitro transdermal delivery of caffeine, theobromine, theophylline and catechin from extract of Guarana, Paullinia Cupana. Int J Pharm 2006;317:26–31.
Shakeel F, Ramadan W: Transdermal delivery of anticancer drug caffeine from water-in-oil nanoemulsions. Colloids Surf B Biointerfaces 2010;75:356–362.
Trauer S, Lademann J, Knorr F, Richter H, Liebsch M, Rozycki C, Balizs G, Buttemeyer R, Linscheid M, Patzelt A: Development of an in vitro modified skin absorption test for the investigation of the follicular penetration pathway of caffeine. Skin Pharmacol Physiol 2010;23:320–327.
Treffel P, Muret P, Muret-D’Aniello P, Coumes-Marquet S, Agache P: Effect of occlusion on in vitro percutaneous absorption of two compounds with different physicochemical properties. Skin Pharmacol 1992;5:108–113.
van de Sandt JJ, van Burgsteden JA, Cage S, Carmichael PL, Dick I, Kenyon S, Korinth G, Larese F, Limasset JC, Maas WJ, Montomoli L, Nielsen JB, Payan JP, Robinson E, Sartorelli P, Schaller KH, Wilkinson SC, Williams FM: In vitro predictions of skin absorption of caffeine, testosterone, and benzoic acid: a multi-centre comparison study. Regul Toxicol Pharmacol 2002;39:271–281.
Wilkinson SC, Maas WJ, Nielsen JB, Greaves LC, van de Sandt JJ, Williams FM: Interactions of skin thickness and physicochemical properties of test compounds in percutaneous penetration studies. Int Arch Occup Environ Health 2006;79:405–413.
Brandner JM, Behne MJ, Huesing B, Moll I: Caffeine improves barrier function in male skin. Int J Cosmet Sci 2006;28:343–347.
Zesch A, Schaefer H, Stuttgen G: The quantitative distribution of percutaneously applied caffeine in the human skin. Arch Dermatol Res 1979;266:277–283.
Touitou E, Levi-Schaffer F, Dayan N, Alhaique F, Riccieri F: Modulation of caffeine skin delivery by carrier design: liposomes versus permeation enhancers. Int J Pharm 1994;103:131–136.
Amnuaikit T, Maneenuan D, Boonme P: Evaluation of caffeine gels on physicochemical characteristics and in vivo efficacy in reducing puffy eyes. J Appl Pharmac Sci 2011;1:56–59.
Mustapha RB, Lafforgue C, Fenina N: Effect of concentration on skin permeation of caffeine from gel formulations. Journal of Pharmacy & Bioresources 2010;7:43–54.
Dias M, Farinha A, Faustino E, Hadgraft J, Pais J, Toscano C: Topical delivery of caffeine from some commercial formulations. Int J Pharm 1999;182:41–47.
Mustapha RB, Lafforgue C, Fenina N, Marty J: Influence of drug concentration on the diffusion parameters of caffeine. Indian J Pharmacol 2011;43:157–162.
Bourgeois S, Bolzinger MA, Pelletier J, Valour JP, Briançon S: Caffeine microspheres – an attractive carrier for optimum skin penetration. Int J Cosmet Sci 2010;32:318–321.
Rawlings AV: Cellulite and its treatment. Int J Cosmet Sci 2006;28:175–190.
Cawthorn WP, Sethi JK: TNF-α and adipocyte biology. FEBS Lett 2008;582:117–131.
Conti M: Phosphodiesterases and cyclic nucleotide signaling in endocrine cells. Mol Endocrinol 2000;14:1317–1327.
Diepvens K, Westerterp KR, Westerterp-Plantenga MS: Obesity and thermogenesis related to the consumption of caffeine, ephedrine, capsaicin, and green tea. Am J Physiol Regul Integr Comp Physiol 2007;292:77–85.
Dodd SL, Herb RA, Powers SK: Caffeine and exercise performance. An update. Sports Med 1993;15:14–23.
Panchal SK, Poudyal H, Waanders J, Brown L: Coffee extract attenuates changes in cardiovascular and hepatic structure and function without decreasing obesity in high-carbohydrate, high-fat diet-fed male rats. J Nutr 2012;142:690–697.
Vogelgesang B, Bonnet I, Godard N, Sohm B, Perrier E: In vitro and in vivo efficacy of sulfo-carrabiose, a sugar-based cosmetic ingredient with anti-cellulite properties. Int J Cosmet Sci 2011;33:120–125.
Pires-de-Campos MS, Leonardi GR, Chorilli M, Spadari-Bratfisch RC, Polacow ML, Grassi-Kassisse DM: The effect of topical caffeine on the morphology of swine hypodermis as measured by ultrasound. J Cosmet Dermatol 2008;7:232–237.
Velasco MV, Tano CT, Machado-Santelli GM, Consiglieri VO, Kaneko TM, Baby AR: Effects of caffeine and siloxanetriol alginate caffeine, as anticellulite agents, on fatty tissue: histological evaluation. J Cosmet Dermatol 2008;7:23–29.
Bertin C, Zunino H, Pittet JC, Beau P, Pineau P, Massonneau M, Robert C, Hopkins J: A double-blind evaluation of the activity of an anti-cellulite product containing retinol, caffeine, and ruscogenine by a combination of several non-invasive methods. J Cosmet Sci 2001;52:199–210.
Cameron OG, Modell JG, Hariharan M: Caffeine and human cerebral blood flow: a positron emission tomography study. Life Sci 1990;47:1141–1146.
Okuno T, Sugiyama T, Tominaga M, Kojima S, Ikeda T: Effects of caffeine on microcirculation of the human ocular fundus. Jpn J Ophthalmol 2002;46:170–176.
Lupi O, Semenovitch IJ, Treu C, Bottino D, Bouskela E: Evaluation of the effects of caffeine in the microcirculation and edema on thighs and buttocks using the orthogonal polarization spectral imaging and clinical parameters. J Cosmet Dermatol 2007;6:102–107.
Kerzendorfer C, O’Driscoll M: UVB and caffeine: inhibiting the DNA damage response to protect against the adverse effects of UVB. J Invest Dermatol 2009;129:1611–1613.
Koo SW, Hirakawa S, Fujii S, Kawasumi M, Nghiem P: Protection from photodamage by topical application of caffeine after ultraviolet irradiation. Br J Dermatol 2007;156:957–964.
Kawasumi M, Lemos B, Bradner JE, Thibodeau R, Kim Y, Schmidt M, Higgins E, Koo SW, Angle-Zahn A, Chen A, Levine D, Nguyen L, Heffernan TP, Longo I, Mandinova A, Lud YP, Conney AH, Nghiem P: Protection from UV-induced skin carcinogenesis by genetic inhibition of the ataxia telangiectasia and Rad3-related (ATR) kinase. Proc Nat Acad Sci USA 2011, DOI: 10.1073/pnas.1111378108.
Leon-Carmona JR, Galano A: Is caffeine a good scavenger of oxygenated free radicals? J Phys Chem B 2011;115:4538–4454.
Abel EL, Hendrix SO, McNeeley SG, Johnson KC, Rosenberg CA, Mossavar-Rahmani Y, Vitolins M, Kruger M: Daily coffee consumption and prevalence of nonmelanoma skin cancer in Caucasian women. Eur J Cancer Prev 2007;16:446–452.
Jonason AS, Kunala S, Price GJ, Restifo RJ, Spinelli HM, Persing JA, Leffell DJ, Tarone RE, Brash DE: Frequent clones of p53-mutated keratinocytes in normal human skin. Proc Natl Acad Sci USA 1996;93:14025–14029.
Lu YP, Lou YR, Xie JG, Peng QY, Liao J, Yang CS, Huang MT, Conney AH: Topical applications of caffeine or (α)-epigallocatechin gallate (EGCG) inhibit carcinogenesis and selectively increase apoptosis in UVB-induced skin tumors in mice. Proc Natl Acad Sci USA 2002;99:12455–12460.
Kramata P, Lu YP, Lou YR, Cohen JL, Olcha M, Liu S, Conney AH: Effect of administration of caffeine or green tea on the mutation profile in the p53 gene in early mutant p53-positive patches of epidermal cells induced by chronic UVB-irradiation of hairless SKH-1 mice. Carcinogenesis 2005;26:1965–1974.
Heffernan TP, Kawasumi M, Blasina A, Anderes K, Conney AH, Nghiem P: ATR–Chk1 pathway inhibition promotes apoptosis after UV treatment in primary human keratinocytes: potential basis for the UV protective effects of caffeine. J Invest Dermatol 2009;129:1805–1815.
Conney AH, Lu YP, Lou YR, Huang MT: Inhibitory effects of tea and caffeine on UV-induced carcinogenesis: relationship to enhanced apoptosis and decreased tissue fat. Eur J Cancer Prev 2002;11:28–36.
Conney AH, Kramata P, Lou YR, Lu YP: Effect of caffeine on UVB-induced carcinogenesis, apoptosis, and the elimination of UVB-induced patches of p53 mutant epidermal cells in SKH-1 mice. Photochem Photobiol 2008;84:330–338.
Fischer TW, Hipler UC, Elsner P: Effect of caffeine and testosterone on the proliferation of human hair follicles in vitro. Int J Dermatol 2007;46:27–35.
Teichmann A, Richter H, Knorr F, Antoniou C, Sterry W, Lademann J: Investigation of the penetration and storage of a shampoo formulation containing caffeine into the hair follicles by in vivo laser scanning microscopy. Laser Phys Lett 2007;4:464–468.
Lademann J, Richter H, Schanzer S, Klenk A, Sterry W, Patzelt A: Analysis of the penetration of a caffeine containing shampoo into the hair follicles by in vivo laser scanning microscopy. Laser Phys 2010;20:551–556.
Otberg N, Patzelt A, Rasulev U, Hagemeister T, Linscheid M, Sinkgraven R, Sterry W, Lademann J: The role of hair follicles in the percutaneous absorption of caffeine. Br J Clin Pharmacol 2008;65:488–492.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.