A spermidine-based nutritional supplement prolongs the anagen phase of hair follicles in humans: a randomized, placebo-controlled, double-blind study
Keywords:
hair, polyamines, spermidine, anagen, randomized clinical trialAbstract
Background: Spermidine has been shown both in vitro and in mice models to have an anagen-prolonging effect on hair follicles (HFs).
Objectives: To evaluate the effects of a spermidine-based nutritional supplement on the anagen phase of HFs in healthy human subjects in a randomized, double-blind, placebo-controlled trial.
Methods: One hundred healthy males and females were randomized to receive a tablet containing a spermidine-based nutritional supplement or a placebo once daily for 90 days. At the beginning and the end of the treatment period, 100 HFs were plucked and subjected to microscopic evaluation to determine the number of anagen V-VI HFs, and immunohistochemical examination was performed to quantify the Ki-67 and c-KIT levels in the hair bulbs. Pull test was performed after three and six months.
Results: The spermidine-based nutritional supplement increased the number of anagen V-VI HFs after three months of treatment, accompanied by increased Ki-67, a marker for cellular proliferation, and decreased c-KIT, a marker for apoptosis, levels. All results were also significantly better when compared to the placebo group. The pull test remained negative after six months in all patients receiving the spermidine supplement, while 68% of the subjects in the placebo group had a positive pull test.
Conclusions: This preliminary study shows that a spermidine-based nutritional supplement can prolong the anagen phase in humans, and therefore might be beneficial for hair loss conditions. Further studies are needed to evaluate its effects in specific different clinical settings.
References
Alcazar R, Altabella T, Marco F, et al. Polyamines: molecules with regulatory functions in plant abiotic stress tolerance. Planta. 2010;231:1237-1249.
Nahar K, Hasanuzzaman M, Suzuki T, Fujita M. Polyamines-induced aluminum tolerance in mung bean: A study on antioxidant defense and methylglyoxal detoxification systems. Ecotoxicology. 2017;26:58-73.
Casero RA, Jr., Marton LJ. Targeting polyamine metabolism and function in cancer and other hyperproliferative diseases. Nat Rev Drug Discov. 2007;6:373-390.
Ou Y, Wang SJ, Li D, Chu B, Gu W. Activation of SAT1 engages polyamine metabolism with p53-mediated ferroptotic responses. Proc Natl Acad Sci U S A. 2016;113:E6806-E6812.
Gerner EW, Meyskens FL, Jr. Polyamines and cancer: old molecules, new understanding. Nat Rev Cancer. 2004;4:781-792.
Tabor CW, Tabor H. Polyamines in microorganisms. Microbiol Rev. 1985;49:81-99.
Yerra A, Mysarla DK, Siripurapu P, Jha A, Valluri SV, Mamillapalli A. Effect of polyamines on mechanical and structural properties of Bombyx mori silk. Biopolymers. 2017;107:20-27.
Coleman CS, Pegg AE, Megosh LC, Guo Y, Sawicki JA, O'Brien TG. Targeted expression of spermidine/spermine N1-acetyltransferase increases susceptibility to chemically induced skin carcinogenesis. Carcinogenesis. 2002;23:359-364.
Megosh L, Gilmour SK, Rosson D, et al. Increased frequency of spontaneous skin tumors in transgenic mice which overexpress ornithine decarboxylase. Cancer Res. 1995;55:4205-4209.
Panteleyev AA, Christiano AM, O'Brien TG, Sundberg JP. Ornithine decarboxylase transgenic mice as a model for human atrichia with papular lesions. Exp Dermatol. 2000;9:146-151.
Pietila M, Alhonen L, Halmekyto M, Kanter P, Janne J, Porter CW. Activation of polyamine catabolism profoundly alters tissue polyamine pools and affects hair growth and female fertility in transgenic mice overexpressing spermidine/spermine N1-acetyltransferase. J Biol Chem. 1997;272:18746-18751.
Pietila M, Parkkinen JJ, Alhonen L, Janne J. Relation of skin polyamines to the hairless phenotype in transgenic mice overexpressing spermidine/spermine N-acetyltransferase. J Invest Dermatol. 2001;116:801-805.
Pietila M, Pirinen E, Keskitalo S, et al. Disturbed keratinocyte differentiation in transgenic mice and organotypic keratinocyte cultures as a result of spermidine/spermine N-acetyltransferase overexpression. J Invest Dermatol. 2005;124:596-601.
Smith MK, Trempus CS, Gilmour SK. Co-operation between follicular ornithine decarboxylase and v-Ha-ras induces spontaneous papillomas and malignant conversion in transgenic skin. Carcinogenesis. 1998;19:1409-1415.
Soler AP, Gilliard G, Megosh LC, O'Brien TG. Modulation of murine hair follicle function by alterations in ornithine decarboxylase activity. J Invest Dermatol. 1996;106:1108-1113.
Suppola S, Pietila M, Parkkinen JJ, et al. Overexpression of spermidine/spermine N1-acetyltransferase under the control of mouse metallothionein I promoter in transgenic mice: evidence for a striking post-transcriptional regulation of transgene expression by a polyamine analogue. Biochem J. 1999;338 ( Pt 2):311-316.
Hamzavi I, Tan E, Shapiro J, Lui H. A randomized bilateral vehicle-controlled study of eflornithine cream combined with laser treatment versus laser treatment alone for facial hirsutism in women. J Am Acad Dermatol. 2007;57:54-59.
Wolf JE, Jr., Shander D, Huber F, et al. Randomized, double-blind clinical evaluation of the efficacy and safety of topical eflornithine HCl 13.9% cream in the treatment of women with facial hair. Int J Dermatol. 2007;46:94-98.
Kloepper JE, Sugawara K, Al-Nuaimi Y, Gaspar E, van Beek N, Paus R. Methods in hair research: how to objectively distinguish between anagen and catagen in human hair follicle organ culture. Exp Dermatol. 2010;19:305-312.
Ramot Y, Marzani B, Pinto D, Kloepper JE, Paus R. N(1)-methylspermidine, a stable spermidine analog, prolongs anagen and regulates epithelial stem cell functions in human hair follicles. Arch Dermatol Res. 2015;307:841-847.
Ramot Y, Tiede S, Biro T, et al. Spermidine promotes human hair growth and is a novel modulator of human epithelial stem cell functions. PLoS One. 2011;6:e22564.
Fashe TM, Keinanen TA, Grigorenko NA, et al. Cutaneous application of alpha-methylspermidine activates the growth of resting hair follicles in mice. Amino Acids. 2010;38:583-590.
Rinaldi F, Sorbellini E, Bezzola P, Marchioretto DI. Biogenina® based food supplement: hair growth enhancer. NutraFood. 2003;2:1-7.
Rinaldi F, Bezzola P, Sorbellini E, Giuliani G. The effect of polyamines on hair cycle clock. J Plast Dermatol. 2009;5:163-167.
Trink A, Sorbellini E, Bezzola P, et al. A randomized, double-blind, placebo and active-controlled, half-head study to evaluate the effects of platelet rich plasma on alopecia areata. Brit J Dermatol. 2013;169:690-694.
Grover C, Khurana A. Telogen effluvium. Indian J Dermatol Venereol Leprol. 2013;79:591-603.
Ramot Y, Pietila M, Giuliani G, Rinaldi F, Alhonen L, Paus R. Polyamines and hair: a couple in search of perfection. Exp Dermatol. 2010;19:784-790.
Luke CT, Casta A, Kim H, Christiano AM. Hairless and the polyamine putrescine form a negative regulatory loop in the epidermis. Exp Dermatol. 2013;22:644-649.
Ramot Y, Vardy LA. Commentary on: Hairless and the polyamine putrescine form a negative regulatory loop in the epidermis. Exp Dermatol. 2013;22:697-698.
Ramot Y, Horev L, Smolovich I, Molho-Pessach V, Zlotogorski A. Marie Unna hereditary hypotrichosis caused by a novel mutation in the human hairless transcript. Exp Dermatol. 2010;19:e320-322.
Ramot Y, Zlotogorski A. Molecular genetics of alopecias. Curr Probl Dermatol. 2015;47:87-96.
Eisenberg T, Abdellatif M, Schroeder S, et al. Cardioprotection and lifespan extension by the natural polyamine spermidine. Nat Med. 2016;22:1428-1438.
Kaeberlein M. Spermidine surprise for a long life. Nat Cell Biol. 2009;11:1277-1278.
Eisenberg T, Knauer H, Schauer A, et al. Induction of autophagy by spermidine promotes longevity. Nat Cell Biol. 2009;11:1305-1314.
Published
Issue
Section
License
Dermatology Practical & Conceptual applies a Creative Commons Attribution License (CCAL) to all works we publish (http://creativecommons.org/licenses/by-nc/4.0/). Authors retain the copyright for their published work.
How to Cite
Share
