Generic placeholder image

Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Role of Molecular Hydrogen in Skin Diseases and its Impact in Beauty

Author(s): Johny Bajgai, Kyu-Jae Lee*, Md. Habibur Rahman, Ailyn Fadriquela and Cheol-Su Kim

Volume 27, Issue 5, 2021

Published on: 25 September, 2020

Page: [737 - 746] Pages: 10

DOI: 10.2174/1381612826666200925124235

Price: $65


In today’s society, healthy skin and a beautiful appearance are considered the foundation of general well-being. The skin is the largest organ of the body and plays an important role in protecting it against various hazards such as environmental, physical, chemical, and biological hazards. These factors include mediators that lead to oxidation reactions that produce reactive oxygen/nitrogen species and additional oxidants in the skin cells. An increase in oxidants beyond the antioxidant capacity of its defense system causes oxidative stress and chronic inflammation in the body. This response can cause further disruption of collagen fibers and hinder the functioning of skin cells that may result in the development of various skin diseases including psoriasis, atopic dermatitis, and aging. In this review, we summarized the present information related to the role of oxidative stress in the pathogenesis of dermatological disorders, and its impact on physical beauty and the daily lives of patients. We also discussed how molecular hydrogen exhibits a therapeutic effect against skin diseases via its effects on oxidative stress. Furthermore, findings from this summary review indicate that molecular hydrogen might be an effective treatment modality for the prevention and treatment of skin-related illnesses.

Keywords: Skin, beauty, skin diseases, oxidants, dermatological disorder, molecular hydrogen, oxidative stress.

Fardouly J, Vartanian LR. Social media and body image concerns: Current research and future directions. Curr Opin Psychol 2016; 9: 1-5.
Halliwell E, Diedrichs PC. The Oxford handbook of the psychology of appearance. 2012; 217-38.
Hay RJ, Johns NE, Williams HC, et al. The global burden of skin disease in 2010: an analysis of the prevalence and impact of skin conditions. J Invest Dermatol 2014; 134(6): 1527-34.
[] [PMID: 24166134]
Fritsch P, Burgdorf W. The skin and its diseases: an overview. Eur J Dermatol 2006; 16(2): 209-12.
[PMID: 16606586]
GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017; 390(10100): 1211-59.
[] [PMID: 28919117]
Korman NJ, Zhao Y, Pike J, Roberts J, Sullivan E. Increased severity of itching, pain, and scaling in psoriasis patients is associated with increased disease severity, reduced quality of life, and reduced work productivity. Dermatol Online J 2015; 21(10) .
Korman NJ, Zhao Y, Pike J, Roberts J. Relationship between psoriasis severity, clinical symptoms, quality of life and work productivity among patients in the USA. Clin Exp Dermatol 2016; 41(5): 514-21.
[] [PMID: 27061102]
Bidaki R, Majidi N, Moghadam Ahmadi A, et al. Vitiligo and social acceptance. Clin Cosmet Investig Dermatol 2018; 11: 383-6.
[] [PMID: 30046249]
Molina-Leyva A, Almodovar-Real A, Ruiz-Carrascosa JC, Naranjo-Sintes R, Serrano-Ortega S, Jimenez-Moleon JJ. Distribution pattern of psoriasis affects sexual function in moderate to severe psoriasis: a prospective case series study. J Sex Med 2014; 11(12): 2882-9.
[] [PMID: 25266400]
Łakuta P, Marcinkiewicz K, Bergler-Czop B, Brzezińska-Wcisło L. How does stigma affect people with psoriasis? Postepy Dermatol Alergol 2017; 34(1): 36-41.
[] [PMID: 28261029]
Zhang XJ, Wang AP, Shi TY, et al. The psychosocial adaptation of patients with skin disease: a scoping review. BMC Public Health 2019; 19(1): 1404.
[] [PMID: 31664970]
Alpsoy E, Polat M, FettahlıoGlu-Karaman B, et al. Internalized stigma in psoriasis: A multicenter study. J Dermatol 2017; 44(8): 885-91.
[] [PMID: 28407292]
Lewis-Beck C, Abouzaid S, Xie L, Baser O, Kim E. Analysis of the relationship between psoriasis symptom severity and quality of life, work productivity, and activity impairment among patients with moderate-to-severe psoriasis using structural equation modeling. Patient Prefer Adherence 2013; 7: 199-205.
[PMID: 23508007]
Ahmed AE, Al-Dahmash AM, Al-Boqami QT, Al-Tebainawi YF. Depression, anxiety and stress among Saudi Arabian dermatology patients: Cross-sectional study. Sultan Qaboos Univ Med J 2016; 16(2): e217-23.
[] [PMID: 27226914]
Levy AR, Davie AM, Brazier NC, et al. Economic burden of moderate to severe plaque psoriasis in Canada. Int J Dermatol 2012; 51(12): 1432-40.
[] [PMID: 23171010]
Ohsawa I, Ishikawa M, Takahashi K, et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med 2007; 13(6): 688-94.
[] [PMID: 17486089]
Sato Y, Kajiyama S, Amano A, et al. Hydrogen-rich pure water prevents superoxide formation in brain slices of vitamin C-depleted SMP30/GNL knockout mice. Biochem Biophys Res Commun 2008; 375(3): 346-50.
[] [PMID: 18706888]
Ichihara M, Sobue S, Ito M, Ito M, Hirayama M, Ohno K. Beneficial biological effects and the underlying mechanisms of molecular hydrogen - comprehensive review of 321 original articles. Med Gas Res 2015; 5: 12.
[] [PMID: 26483953]
Ohta S. Recent progress toward hydrogen medicine: potential of molecular hydrogen for preventive and therapeutic applications. Curr Pharm Des 2011; 17(22): 2241-52.
[] [PMID: 21736547]
Kura B, Bagchi AK, Singal PK, et al. Molecular hydrogen: potential in mitigating oxidative-stress-induced radiation injury. Can J Physiol Pharmacol 2019; 97(4): 287-92.
[] [PMID: 30543459]
Fluhr JW, Sassning S, Lademann O, et al. in vivoskin treatment with tissue-tolerable plasma influences skin physiology and antioxidant profile in human stratum corneum. Exp Dermatol 2012; 21(2): 130-4.
[] [PMID: 22142271]
Cravello B, Ferri A. Relationships between skin properties and environmental parameters. Skin Res Technol 2008; 14(2): 180-6.
[] [PMID: 18412560]
Cheng Y, Dong YY, Dong MX, et al. Protection effect of cosmetics on human skin under simulated rigorous environment. Skin Res Technol 2008; 14(1): 45-52.
[PMID: 18211601]
Egawa M, Oguri M, Kuwahara T, Takahashi M. Effect of exposure of human skin to a dry environment. Skin Res Technol 2002; 8(4): 212-8.
[] [PMID: 12423539]
Jennemann R, Rabionet M, Gorgas K, et al. Loss of ceramide synthase 3 causes lethal skin barrier disruption. Hum Mol Genet 2012; 21(3): 586-608.
[] [PMID: 22038835]
Kadam DP, Suryakar AN, Ankush RD, Kadam CY, Deshpande KH. Role of oxidative stress in various stages of psoriasis. Indian J Clin Biochem 2010; 25(4): 388-92.
[] [PMID: 21966111]
Chen L, Hu JY, Wang SQ. The role of antioxidants in photoprotection: a critical review. J Am Acad Dermatol 2012; 67(5): 1013-24.
[] [PMID: 22406231]
Bogdan Allemann I, Baumann L. Antioxidants used in skin care formulations. Skin Therapy Lett 2008; 13(7): 5-9.
[PMID: 18839043]
McDaniel D, Farris P, Valacchi G. Atmospheric skin aging-Contributors and inhibitors. J Cosmet Dermatol 2018; 17(2): 124-37.
[] [PMID: 29575554]
Kruk J, Duchnik E. Oxidative stress and skin diseases: possible role of physical activity. Asian Pac J Cancer Prev 2014; 15(2): 561-8.
[] [PMID: 24568458]
Halliwell B, Gutteridge JMC. Free radicals in biology and medicine (3rd ed) Oxford, UK: Oxford University Press 1999.
Bachelor MA, Bowden GT. UVA-mediated activation of signaling pathways involved in skin tumor promotion and progression. Semin Cancer Biol 2004; 14(2): 131-8.
[] [PMID: 15018897]
Bickers DR, Athar M. Oxidative stress in the pathogenesis of skin disease. J Invest Dermatol 2006; 126(12): 2565-75.
[] [PMID: 17108903]
Verheij M, Bose R, Lin XH, et al. Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis. Nature 1996; 380(6569): 75-9.
[] [PMID: 8598911]
Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME. Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 1995; 270(5240): 1326-31.
[] [PMID: 7481820]
Chung JH, Kang S, Varani J, Lin J, Fisher GJ, Voorhees JJ. Decreased extracellular-signal-regulated kinase and increased stress-activated MAP kinase activities in aged human skin in vivo. J Invest Dermatol 2000; 115(2): 177-82.
[] [PMID: 10951233]
Matos TJ, Duarte CB, Gonçalo M, Lopes MC. Role of oxidative stress in ERK and p38 MAPK activation induced by the chemical sensitizer DNFB in a fetal skin dendritic cell line. Immunol Cell Biol 2005; 83(6): 607-14.
[] [PMID: 16266312]
Biedermann T, Röcken M, Carballido JM. TH1 and TH2 lymphocyte development and regulation of TH cell-mediated immune responses of the skin. J Investig Dermatol Symp Proc 2004; 9(1): 5-14.
[] [PMID: 14870978]
Kawakubo Y, Nakamori M, Schöpf E, Ohkido M. Acetylator phenotype in patients with p-phenylenediamine allergy. Dermatology (Basel) 1997; 195(1): 43-5.
[] [PMID: 9267736]
Black HS. ROS: A step closer to elucidating their role in the etiology of light-induced skin disorders. J Invest Dermatol 2004; 122(6): 13-4.
Nichols JA, Katiyar SK. Skin photoprotection by natural polyphenols: anti-inflammatory, antioxidant and DNA repair mechanisms. Arch Dermatol Res 2010; 302(2): 71-83.
[] [PMID: 19898857]
Leiter U, Garbe C. Sunlight, vitamin D and skin cancer. Advances in experimental medicine and biology J R, Ed 2008; 89-103.
Bose B, Choudhury H, Tandon P, Kumaria S. Studies on secondary metabolite profiling, anti-inflammatory potential, in vitrophotoprotective and skin-aging related enzyme inhibitory activities of Malaxis acuminata, a threatened orchid of nutraceutical importance. J Photochem Photobiol B 2017; 173: 686-95.
[] [PMID: 28743100]
Cuelho CHF, Alves GAD, Lovatto MO, et al. Topical formulation containing Ilex Paraguariensis extract increases metalloproteinases and myeloperoxidase activities in mice exposed to UVB radiation. J Photochem Photobiol B 2018; 189: 95-103.
[] [PMID: 30317053]
Ratz-Lyko A, Arct J, Pytkowska K. Methods for evaluation of cosmetic antioxidant capacity. Skin Res Technol 2012; 18(4): 421-30.
[] [PMID: 22093040]
Baek J, Lee MG. Oxidative stress and antioxidant strategies in dermatology. Redox Rep 2016; 21(4): 164-9.
[] [PMID: 26020527]
Röck K, Fischer JW. Role of the extracellular matrix in extrinsic skin aging. Hautarzt 2011; 62(8): 591-7.
[PMID: 21681543]
Guan P, Sun ZM, Luo LF, et al. Hydrogen gas alleviates chronic intermittent hypoxia-induced renal injury through reducing iron overload. Molecules 2019; 24(6): E1184.
[] [PMID: 30917568]
Itoh T, Fujita Y, Ito M, et al. Molecular hydrogen suppresses FcepsilonRI-mediated signal transduction and prevents degranulation of mast cells. Biochem Biophys Res Commun 2009; 389(4): 651-6.
[] [PMID: 19766097]
Sobue S, Yamai K, Ito M, et al. Simultaneous oral and inhalational intake of molecular hydrogen additively suppresses signaling pathways in rodents. Mol Cell Biochem 2015; 403(1-2): 231-41.
[] [PMID: 25707580]
Ostojic SM. Molecular hydrogen: An inert gas turns clinically effective. Ann Med 2015; 47(4): 301-4.
[] [PMID: 25936365]
Chen Y, Jiang J, Miao H, Chen X, Sun X, Li Y. Hydrogen-rich saline attenuates vascular smooth muscle cell proliferation and neointimal hyperplasia by inhibiting reactive oxygen species production and inactivating the Ras-ERK1/2-MEK1/2 and Akt pathways. Int J Mol Med 2013; 31(3): 597-606.
[] [PMID: 23340693]
Li DZ, Zhang QX, Dong XX, Li HD, Ma X. Treatment with hydrogen molecules prevents RANKL-induced osteoclast differentiation associated with inhibition of ROS formation and inactivation of MAPK, AKT and NF-kappa B pathways in murine RAW264.7 cells. J Bone Miner Metab 2014; 32(5): 494-504.
[] [PMID: 24196871]
Wang C, Li J, Liu Q, et al. Hydrogen-rich saline reduces oxidative stress and inflammation by inhibit of JNK and NF-κB activation in a rat model of amyloid-beta-induced Alzheimer’s disease. Neurosci Lett 2011; 491(2): 127-32.
[] [PMID: 21238541]
Wei L, Ge L, Qin S, et al. Hydrogen-rich saline protects retina against glutamate-induced excitotoxic injury in guinea pig. Exp Eye Res 2012; 94(1): 117-27.
[] [PMID: 22154552]
Liu FT, Xu SM, Xiang ZH, et al. Molecular hydrogen suppresses reactive astrogliosis related to oxidative injury during spinal cord injury in rats. CNS Neurosci Ther 2014; 20(8): 778-86.
[] [PMID: 24685114]
Guo SX, Jin YY, Fang Q, et al. Beneficial effects of hydrogen-rich saline on early burn-wound progression in rats. PLoS One 2015; 10(4): e0124897.
[] [PMID: 25874619]
Shin MH, Park R, Nojima H, Kim HC, Kim YK, Chung JH. Atomic hydrogen surrounded by water molecules, H(H2O)m, modulates basal and UV-induced gene expressions in human skin in vivo. PLoS One 2013; 8(4): e61696.
[] [PMID: 23637886]
Liu YQ, Liu YF, Ma XM, et al. Hydrogen-rich saline attenuates skin ischemia/reperfusion induced apoptosis via regulating Bax/Bcl-2 ratio and ASK-1/JNK pathway. J Plast Reconstr Aesthet Surg 2015; 68(7): e147-56.
[] [PMID: 26003800]
Ono H, Nishijima Y, Adachi N, et al. Hydrogen(H2) treatment for acute erythymatous skin diseases. A report of 4 patients with safety data and a non-controlled feasibility study with H2 concentration measurement on two volunteers. Med Gas Res 2012; 2(1): 14.
[] [PMID: 22607973]
Ignacio RM, Kwak HS, Yun YU, et al. The drinking effect of hydrogen water on atopic dermatitis induced by Dermatophagoides farinae allergen in NC/Nga mice. Evid Based Complement Alternat Med 2013; 2013: 538673.
[] [PMID: 24348704]
Yoon YS, Sajo ME, Ignacio RM, Kim SK, Kim CS, Lee KJ. Positive Effects of hydrogen water on 2,4-dinitrochlorobenzene-induced atopic dermatitis in NC/Nga mice. Biol Pharm Bull 2014; 37(9): 1480-5.
[] [PMID: 25177031]
Ishibashi T, Ichikawa M, Sato B, et al. Improvement of psoriasis-associated arthritis and skin lesions by treatment with molecular hydrogen: A report of three cases. Mol Med Rep 2015; 12(2): 2757-64.
[] [PMID: 25936373]
Li Q, Kato S, Matsuoka D, Tanaka H, Miwa N. Hydrogen water intake via tube-feeding for patients with pressure ulcer and its reconstructive effects on normal human skin cells in vitro. Med Gas Res 2013; 3(1): 20.
[] [PMID: 24020833]
Yu WT, Chiu YC, Lee CH, Yoshioka T, Yu HS. Hydrogen-enriched water restoration of impaired calcium propagation by arsenic in primary keratinocytes. J Asian Earth Sci 2013; 77: 342-8.
Zhu Q, Wu Y, Li Y, et al. Positive effects of hydrogen-water bathing in patients of psoriasis and parapsoriasis en plaques. Sci Rep 2018; 8(1): 8051.
[] [PMID: 29795283]
Niki E. Lipid peroxidation: physiological levels and dual biological effects. Free Radic Biol Med 2009; 47(5): 469-84.
[] [PMID: 19500666]
Briganti S, Picardo M. Antioxidant activity, lipid peroxidation and skin diseases. What’s new. J Eur Acad Dermatol Venereol 2003; 17(6): 663-9.
[] [PMID: 14761133]
Huang CS, Kawamura T, Toyoda Y, Nakao A. Recent advances in hydrogen research as a therapeutic medical gas. Free Radic Res 2010; 44(9): 971-82.
[] [PMID: 20815764]
Yu XJ, Li CY, Dai HY, et al. Expression and localization of the activated mitogen-activated protein kinase in lesional psoriatic skin. Exp Mol Pathol 2007; 83(3): 413-8.
[] [PMID: 17599830]
Itoh T, Hamada N, Terazawa R, et al. Molecular hydrogen inhibits lipopolysaccharide/interferon γ-induced nitric oxide production through modulation of signal transduction in macrophages. Biochem Biophys Res Commun 2011; 411(1): 143-9.
[] [PMID: 21723254]
Ohno K, Ito M, Ichihara M, Ito M. Molecular hydrogen as an emerging therapeutic medical gas for neurodegenerative and other diseases. Oxid Med Cell Longev 2012; 2012: 353152.
[] [PMID: 22720117]
Lifschitz C. The impact of atopic dermatitis on quality of life. Ann Nutr Metab 2015; 66(Suppl. 1): 34-40.
[] [PMID: 25925339]
Barton M, Sidbury R. Advances in understanding and managing atopic dermatitis. F1000 Res 2015; 4: 1296.
[] [PMID: 26918129]
Dembic Z. The role and regulation of the immune responses The Cytokines of the Immune System Cambridge, MA: Academic Press 2015.
Kajisa T, Yamaguchi T, Hu A, Suetake N, Kobayashi H. Hydrogen water ameliorates the severity of atopic dermatitis-like lesions and decreases interleukin-1β, interleukin-33, and mast cell infiltration in NC/Nga mice. Saudi Med J 2017; 38(9): 928-33.
[] [PMID: 28889151]
Xie K, Yu Y, Huang Y, et al. Molecular hydrogen ameliorates lipopolysaccharide-induced acute lung injury in mice through reducing inflammation and apoptosis. Shock 2012; 37(5): 548-55.
[] [PMID: 22508291]
Farage MA, Miller KW, Elsner P, Maibach HI. Intrinsic and extrinsic factors in skin ageing: a review. Int J Cosmet Sci 2008; 30(2): 87-95.
[] [PMID: 18377617]
Puri P, Nandar SK, Kathuria S, Ramesh V. Effects of air pollution on the skin: A review. Indian J Dermatol Venereol Leprol 2017; 83(4): 415-23.
[] [PMID: 28195077]
Lorencini M, Brohem CA, Dieamant GC, Zanchin NI, Maibach HI. Active ingredients against human epidermal aging. Ageing Res Rev 2014; 15: 100-15.
[] [PMID: 24675046]
Poljšak B, Dahmane RG, Godić A. Intrinsic skin aging: the role of oxidative stress. Acta Dermatovenerol Alp Panonica Adriat 2012; 21(2): 33-6.
[PMID: 23000938]
Ignacio RM, Yoon YS, Sajo MEJ, et al. The balneotherapy effect of hydrogen reduced water on UVB-mediated skin injury in hairless mice. Mol Cell Toxicol 2013; 9(1): 15-21.
Yoon KS, Huang XZ, Yoon YS, et al. Histological study on the effect of electrolyzed reduced water-bathing on UVB radiation-induced skin injury in hairless mice. Biol Pharm Bull 2011; 34(11): 1671-7.
[] [PMID: 22040878]
Han AL, Park SH, Park MS. Hydrogen treatment protects against cell death and senescence induced by oxidative damage. J Microbiol Biotechnol 2017; 27(2): 365-71.
[] [PMID: 27780950]
Johnson RM, Richard R. Partial-thickness burns: identification and management. Adv Skin Wound Care 2003; 16(4): 178-87.
[] [PMID: 12897674]
Singer AJ, McClain SA, Taira BR, Guerriero JL, Zong W. Apoptosis and necrosis in the ischemic zone adjacent to third degree burns. Acad Emerg Med 2008; 15(6): 549-54.
[] [PMID: 18616442]
Yu P, Wang Z, Sun X, et al. Hydrogen-rich medium protects human skin fibroblasts from high glucose or mannitol induced oxidative damage. Biochem Biophys Res Commun 2011; 409(2): 350-5.
[] [PMID: 21596020]
Zhao L, Wang YB, Qin SR, et al. Protective effect of hydrogen-rich saline on ischemia/reperfusion injury in rat skin flap. J Zhejiang Univ Sci B 2013; 14(5): 382-91.
[] [PMID: 23645175]
Imai S, Kozai H, Matsuda M, et al. Intervention with delivery of diabetic meals improves glycemic control in patients with type 2 diabetes mellitus. J Clin Biochem Nutr 2008; 42: 59-63.
[] [PMID: 18231632]
Bergfeld WF. The pathophysiology of acne vulgaris in children and adolescents, Part 1. Cutis 2004; 74(2): 92-7.
[PMID: 15379361]
Gollnick H. Current concepts of the pathogenesis of acne: implications for drug treatment. Drugs 2003; 63(15): 1579-96.
[] [PMID: 12887264]
Dell’anna ML, Picardo M. A review and a new hypothesis for non-immunological pathogenetic mechanisms in vitiligo. Pigment Cell Res 2006; 19(5): 406-11.
[] [PMID: 16965269]
Colucci R, Dragoni F, Moretti S. Oxidative stress and immune system in vitiligo and thyroid diseases. Oxid Med Cell Longev 2015; 2015: 631927.
[] [PMID: 25838868]
Kajiya M, Sato K, Silva MJB, et al. Hydrogen from intestinal bacteria is protective for Concanavalin A-induced hepatitis. Biochem Biophys Res Commun 2009; 386(2): 316-21.
[] [PMID: 19523450]
Raj D, Brash DE, Grossman D. Keratinocyte apoptosis in epidermal development and disease. J Invest Dermatol 2006; 126(2): 243-57.
[] [PMID: 16418733]
Du H, Sheng M, Wu L, et al. Hydrogen-rich saline attenuates acute kidney injury after liver transplantation via activating p53-mediated autophagy. Transplantation 2016; 100(3): 563-70.
[] [PMID: 26714124]
Kawamura T, Huang CS, Tochigi N, et al. Inhaled hydrogen gas therapy for prevention of lung transplant-induced ischemia/reperfusion injury in rats. Transplantation 2010; 90(12): 1344-51.
[] [PMID: 21048533]
Zákostelská Z, Málková J, Klimešová K, et al. Intestinal microbiota promotes psoriasis-like skin inflammation by enhancing Th17 response. PLoS One 2016; 11(7): e0159539.
[] [PMID: 27434104]
Jahng J, Jung IS, Choi EJ, Conklin JL, Park H. The effects of methane and hydrogen gases produced by enteric bacteria on ileal motility and colonic transit time. Neurogastroenterol Motil 2012; 24(2): 185-90.
Carbonero F, Benefiel AC, Gaskins HR. Contributions of the microbial hydrogen economy to colonic homeostasis. Nat Rev Gastroenterol Hepatol 2012; 9(9): 504-18.
[] [PMID: 22585131]
Thauer RK, Jungermann K, Decker K. Energy conservation in chemotrophic anaerobic bacteria. Bacteriol Rev 1977; 41(1): 100-80.
[] [PMID: 860983]

Rights & Permissions Print Export Cite as
© 2023 Bentham Science Publishers | Privacy Policy