Zaira F. Kharaeva, Ismail A. Miziev, Diana H. Shorova, Michael Papacharalambous, Chiara De Luca and Liudmila Korkina
Objectives: Notwithstanding great progress in the management of erectile dysfunction (ED) by phosphodiesterase inhibitors, safety concerns hinder their routine use in men with mild-to-moderate forms. Several plant-derived supplements have been proven acceptable substituents of conventional anti-ED drugs. Most anti-ED drugs/supplements act through nitric oxide (NO)-dependent molecular pathways, due to NO-induced smooth muscle relaxation of the local Corpus cavernosum vessels. A randomised single-blind self-controlled clinical investigation recently showed that dietary supplementation with marine collagen peptides (MCP) in combination with selected antioxidants remarkably enhanced nitrite/nitrate plasma levels along with skin rejuvenation and general energising (hormesis-like) effects. This pilot study was designed to reveal possible clinical action of this supplement towards ED and its mechanisms.
Methods: Fifteen otherwise healthy men (age range 55-61 years), free of sex organ diseases/malformations, diabetes or pre-diabetes, atherosclerosis, metabolic syndrome, cardio-vascular diseases or testosterone deficiency suffering from the mild-to-moderate erectile dysfunction diagnosed by the International Index of Erectile Function (IIEF-5 ≤ 20) were recruited for a pilot, clinical trial. The participants were given 2 capsules containing MCP +antioxidants a day for 30 consecutive days. Several functions of circulating phagocytes (granulocytes and monocytes), plasma levels of macrophage-targeting cytokines and nitrites/nitrates, expression of genes encoding inducible and endothelial nitric oxide synthase (iNOS and eNOS, respectively) and ATP content in phagocytes, and activity of glutathione peroxidase (GPX) in erythrocytes were recorded twice, at enrolment and at the cessation of the oral supplementation. Eighteen age-matched men without ED and 41 healthy subjects of both sexes (age range 20-65 years) served as controls.
Results: The supplementation was proven safe, not causing any adverse reaction. The IIEF-5 score was increased in 100% of participants, of 3-4 points on average. The MCP+antioxidants supplementation lead to activation of phagocyte defence functions (phagocytosis, intracellular bacterial killing, and reactive oxygen species production), to increased plasma levels of nitrites/nitrates, TNF-alpha and INF-gamma, to increased phagocyte levels of ATP, and to up-regulation of iNOS RNA. Although statistically significantly increased, these parameters remained within the normal range of values. There were no changes in the eNOS expression, GPX activity, and IL-10 levels.
Discussion: We suggest a novel mechanism of possible regulation of penile erection through the initial selective stimulation of Toll-like receptors on circulating phagocytes, to convert them into defensive M1 cells producing enhanced quantities of TNF-alpha and INF-gamma, along with a hormesis-like moderate induction of iNOS. The measured increase of ATP levels might facilitate phagocyte NO release by the interaction with adenosine receptors.
Conclusions: For the first time, marine collagen peptides combined with selected antioxidants are shown to have pro-erectile effects, through different mechanisms than those described previously. This oral supplementation could be considered as a safe and effective alternative to anti-ED drugs in the case of mild-to-moderate ED. More mechanistic studies are needed, along with larger-scale multi-centre placebo-controlled clinical trials.