Spermidine

Spermidine is an endogenous polyamine.¹ It is formed from putrescine by spermidine synthase. Spermidine (25 µM) inhibits the activity of the human inward-rectifying potassium channel K_ir2.3 in a patch-clamp assay.² It induces autophagy in HeLa cells when used at a concentration of 100 µM and increases the lifespan of D. melanogaster, yeast, and C. elegans.³ Spermidine (30 mM in the drinking water) reduces demyelination of the optic nerve and disease severity in a mouse model of experimental autoimmune encephalomyelitis (EAE).⁴ It reduces increases in blood pressure, left ventricular posterior wall thickness, and heart weight in salt-sensitive Dahl rats fed a high-salt diet, a model of hypertension-induced congestive heart failure.⁵ Formulations containing spermidine have been used as dietary supplements.

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1. Madeo, F., Eisenberg, T., Pietrocola, F., et al. Spermidine in health and disease. Science 359(6374), eaan2788 (2018).

2. Lopatin, A.N., Makhina, E.N., and Nichols, C.G. Potassium channel block by cytoplasmic polyamines as the mechanism of intrinsic rectification. Nature 372(6504), 366-369 (1994).

3. Eisenberg, T., Knauer, H., Schauer, A., et al. Induction of autophagy by spermidine promotes longevity. Nat. Cell Biol. 11(11), 1305-1314 (2009).

4. Guo, X., Harada, C., Namekata, K., et al. Spermidine alleviates severity of murine experimental autoimmune encephalomyelitis. Invest. Ophthalmol. Vis. Sci. 52(5), 2696-2703 (2011).

5. Eisenberg, T., Abdellatif, M., Schroeder, S., et al. Cardioprotection and lifespan extension by the natural polyamine spermidine. Nat. Med. 22(12), 1428-1438 (2016).