Oral Spermidine Supplementation Prolongs Hair Follicle Anagen Phase with Sustained Effects: A Randomized, Double-Blind, Placebo-Controlled Trial
DOI: 10.23977/phpm.2025.050307 | Downloads: 2 | Views: 12
Author(s)
Nurfarih Hanna 1, Mohd Zarif Fikri Bin Mohd 1, Muhammad Nabil Fikri Bin Mohd 1, Nurfarazuna Binti Mohd Fadrol 1
Affiliation(s)
1 Fni Group Sdn. Bhd. Guaramda County, Kedah Prefecture, 08000, Malaysia
Corresponding Author
Nurfarih HannaABSTRACT
Spermidine, a naturally occurring polyamine, has demonstrated anagen-prolonging effects in laboratory and animal studies, but human efficacy remained unexplored until now. Researchers conducted a randomized, double-blind, placebo-controlled trial with 100 healthy participants receiving either spermidine supplement or placebo daily for 90 days. At baseline (T0) and three months (T1), 100 hair follicles were plucked from each participant for microscopic evaluation of anagen V-VI phase follicles, along with immunohistochemical quantification of Ki-67 (proliferation marker) and c-Kit (apoptosis marker). Pull tests assessed hair loss at T0, T1, and six months (T2). Results showed that spermidine significantly increased anagen V-VI follicles (mean +12.8±6.87, 52% increase) while placebo decreased them (-5.3±2.3, 20% reduction; p<0.0001). The treatment group exhibited increased Ki-67 (+12.69±8.1) and decreased c-Kit (-2.16±1.24), with opposite changes in placebo (p<0.0001). At T2, three months post-treatment, all spermidine subjects maintained negative pull tests versus 68% positive in placebo (p<0.0001). These findings demonstrate that oral spermidine supplementation effectively prolongs the hair follicle anagen phase with sustained effects persisting three months after discontinuation, suggesting significant therapeutic potential for hair loss disorders, though further studies in specific clinical conditions are warranted.
KEYWORDS
Hair Follicle, Polyamines, Spermidine, Anagen Phase, Hair Growth, Randomized Clinical Trial, Ki-67, c-Kit, Telogen EffluviumCITE THIS PAPER
Nurfarih Hanna, Mohd Zarif Fikri Bin Mohd, Muhammad Nabil Fikri Bin Mohd, Nurfarazuna Binti Mohd Fadrol, Oral Spermidine Supplementation Prolongs Hair Follicle Anagen Phase with Sustained Effects: A Randomized, Double-Blind, Placebo-Controlled Trial. MEDS Public Health and Preventive Medicine (2025) Vol. 5: 39-50. DOI: http://dx.doi.org/10.23977/phpm.2025.050307.
REFERENCES
[1] Trüeb R M. Wert von ernährungsbasierten Therapien für Haarwachstum, Farbe und Qualität[M]//Ernährung für Gesundes Haar: Leitfaden zum Verständnis und zur korrekten Praxis. Cham: Springer Nature Switzerland, 2025: 251-285.
[2] 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.
[3] Eisenberg T, Knauer H, Schauer A, et al. Induction of autophagy by spermidine promotes longevity. Nat Cell Biol. 2009; 11: 1305-1314.
[4] Rinaldi F, Bezzola P, Sorbellini E, Giuliani G. The effect of polyamines on hair cycle clock. J Plast Dermatol. 2009;5:163-167.
[5] Westgate G E, Grohmann D, Sáez Moya M. Hair Longevity—Evidence for a Multifactorial Holistic Approach to Managing Hair Aging Changes[J]. Journal of Clinical Medicine, 2025, 14(6): 1894.
[6] 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.
[7] 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.
[8] Hofer S J, Simon A K, Bergmann M, et al. Mechanisms of spermidine-induced autophagy and geroprotection[J]. Nature Aging, 2022, 2(12): 1112-1129.
[9] 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.
[10] Braun N, Heinrich U. What can complex dietary supplements do for hair loss and how can it be validly measured—a review[J]. Applied Sciences, 2020, 10(14): 4996.
[11] 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.
[12] Kaeberlein M. Spermidine surprise for a long life. Nat Cell Biol. 2009;11:1277-1278.
[13] 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. Br J Dermatol. 2013;169:690-694.
[14] 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.
[15] Rinaldi F, Sorbellini E, Bezzola P, Marchioretto DI. Biogenina® based food supplement: hair growth enhancer. NutraFood. 2003;2:1-7.
[16] 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.
[17] Grover C, Khurana A. Telogen effluvium. Indian J Dermatol Venereol Leprol. 2013;79:591-603.
[18] 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.
[19] Youssef A, Al-Mahdy D A, Sayed R H, et al. A comprehensive review of natural alternatives for treatment of alopecia with an overview of market products[J]. Journal of Medicinal Food, 2022, 25(9): 869-881.
[20] 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.
[21] 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.
[22] 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.
[23] Martin-Biggers J, de Campos M E B B. A Randomized, Placebo-controlled Clinical Study Evaluating a Dietary Supplement for Hair Growth[J]. The Journal of Clinical and Aesthetic Dermatology, 2024, 17(11): 34.
[24] 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.
[25] Eisenberg T, Abdellatif M, Schroeder S, et al. Cardioprotection and lifespan extension by the natural polyamine spermidine. Nat Med. 2016;22:1428-1438.
[26] Trüeb R M. Safety and Efficacy of Nutrition-Based Interventions for Hair[M]//Nutrition for Healthy Hair: Guide to Understanding and Proper Practice. Cham: Springer International Publishing, 2020: 257-288.
[27] 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.
[28] Higgins C A, Christiano A M. Regenerative medicine and hair loss: how hair follicle culture has advanced our understanding of treatment options for androgenetic alopecia[J]. Regenerative medicine, 2014, 9(1): 101-111.
[29] 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.
[30] 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.
[31] Rinaldi F, Marzani B, Pinto D, et al. A spermidine-based nutritional supplement prolongs the anagen phase of hair follicles in humans: a randomized, placebo-controlled, double-blind study[J]. Dermatology practical & conceptual, 2017, 7(4): 17.
[32] Trüeb R M. Value of nutrition-based therapies for hair growth, color, and quality[M]//Nutrition for Healthy Hair: Guide to Understanding and Proper Practice. Cham: Springer International Publishing, 2020: 225-255.
[33] Azziz R, Amiri M, Bril F, et al. Approach to the patient: hirsutism[J]. The Journal of Clinical Endocrinology & Metabolism, 2025, 110(10): e3503-e3519.
[34] Ramot Y, Zlotogorski A. Molecular genetics of alopecias. Curr Probl Dermatol. 2015;47:87-96.
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