madman
Super Moderator
Abstract
Background
Although nutraceutical-based treatments are often offered for erectile dysfunction (ED), their efficacy remains doubtful, and the choice of one substance over the other is challenged by the dearth of head-to-head comparative studies.
Aim
We aimed to compare the efficacy of available nutraceutical interventions, alone or in combination with phosphodiesterase type 5 inhibitors(PDE5i), in improving erectile function in men with ED through a network meta-analysis (NMA), which incorporates direct and indirect evidence into one model thus generating a hierarchy of effectiveness.
Methods
PubMed, Scopus, Web of Sciences, and Cochrane Library databases were searched for randomized placebo-controlled trials (RCTs) assessing the effect of any nutraceutical regimen in improving erectile function when compared to each other, placebo, and/or PDE5i in men with ED. Data were included in a random-effects NMA, where efficacy of treatments was ranked by surface under the cumulative ranking curve (SUCRA). Two NMAs were also conducted separately for organic and non-organic ED. Reciprocal comparisons between all treatments were analyzed by league tables.
Outcomes
The main outcome was the standardized mean difference in the score of the International Index of Erectile Function (IIEF)-5 or IIEF-6.
Results
Fifteen RCTs provided information on 1000 men with ED. In the overall NMA, compared to placebo, the combination propionyl L carnitine (PLC) + acetyl L-carnitine (ALC) + Sildenafil was associated with the highest SUCRA (97%) in improving erectile function score, followed by L-Arginine + Tadalafil (84%), Sildenafil (79%), Tadalafil (72%), and L-Arginine (52%). No other treatment regimen showed efficacy with statistical significance. In patients with organic ED, the efficacy of Sildenafil and Tadalafil was significantly improved by PLC + ALC and L-Arginine, respectively. On the contrary, in non-organic ED, nutraceuticals did not improve the therapeutic performance of daily Tadalafil.
Clinical Implications
This NMA contributes valuable insights into the potential of nutraceutical interventions for ED.
Strengths and Limitations
We employed strict inclusion criteria related to study design and diagnostic tool, ensuring the assumption of transitivity and the consistency of the analysis.
Conclusion
Against a background of general ineffectiveness of most nutraceutical interventions, L-Arginine and the mix PLC + ALC appeared to be of some usefulness in improving erectile function, especially in combination with PDE5i in organic ED.
*Indeed, nutraceuticals combine a good safety profile with mechanisms of action that directly or indirectly can theoretically improve erectile function.8 Some supplements, including L-Arginine, L-Citrulline, are involved in the molecular pathway of nitric oxide (NO) synthesis,9,10 some engage more downstream (eg, L-Cysteine), acting in synergy with cyclic guanosine 3’,5’-cyclic monophosphate (cGMP) or reducing its catabolism,11 while for others (eg, Tribulus terrestris), the ability to increase the levels of testosterone has been theorized.12 In addition, most nutraceuticals act as antioxidants counteracting the contribution of free radicals to endothelial dysfunction, which plays a key role in the pathogenesis of ED in many cases.4-6
In conclusion, our NMA contributes valuable insights into the potential of nutraceutical interventions for ED. L-Arginine and the mix PLC + ALC appeared to be of some usefulness in improving erectile function, especially in combination with PDE5i in organic ED. On the contrary, in nonorganic forms of ED, nutraceuticals did not improve the therapeutic performance of daily Tadalafil. Although doses and duration of treatments remain to be defined, considering the ineffectiveness of most nutraceutical preparations investigated in the available RCTs, these results may help select the few molecules worthy of further investigation in future prospective studies.
Background
Although nutraceutical-based treatments are often offered for erectile dysfunction (ED), their efficacy remains doubtful, and the choice of one substance over the other is challenged by the dearth of head-to-head comparative studies.
Aim
We aimed to compare the efficacy of available nutraceutical interventions, alone or in combination with phosphodiesterase type 5 inhibitors(PDE5i), in improving erectile function in men with ED through a network meta-analysis (NMA), which incorporates direct and indirect evidence into one model thus generating a hierarchy of effectiveness.
Methods
PubMed, Scopus, Web of Sciences, and Cochrane Library databases were searched for randomized placebo-controlled trials (RCTs) assessing the effect of any nutraceutical regimen in improving erectile function when compared to each other, placebo, and/or PDE5i in men with ED. Data were included in a random-effects NMA, where efficacy of treatments was ranked by surface under the cumulative ranking curve (SUCRA). Two NMAs were also conducted separately for organic and non-organic ED. Reciprocal comparisons between all treatments were analyzed by league tables.
Outcomes
The main outcome was the standardized mean difference in the score of the International Index of Erectile Function (IIEF)-5 or IIEF-6.
Results
Fifteen RCTs provided information on 1000 men with ED. In the overall NMA, compared to placebo, the combination propionyl L carnitine (PLC) + acetyl L-carnitine (ALC) + Sildenafil was associated with the highest SUCRA (97%) in improving erectile function score, followed by L-Arginine + Tadalafil (84%), Sildenafil (79%), Tadalafil (72%), and L-Arginine (52%). No other treatment regimen showed efficacy with statistical significance. In patients with organic ED, the efficacy of Sildenafil and Tadalafil was significantly improved by PLC + ALC and L-Arginine, respectively. On the contrary, in non-organic ED, nutraceuticals did not improve the therapeutic performance of daily Tadalafil.
Clinical Implications
This NMA contributes valuable insights into the potential of nutraceutical interventions for ED.
Strengths and Limitations
We employed strict inclusion criteria related to study design and diagnostic tool, ensuring the assumption of transitivity and the consistency of the analysis.
Conclusion
Against a background of general ineffectiveness of most nutraceutical interventions, L-Arginine and the mix PLC + ALC appeared to be of some usefulness in improving erectile function, especially in combination with PDE5i in organic ED.
*Indeed, nutraceuticals combine a good safety profile with mechanisms of action that directly or indirectly can theoretically improve erectile function.8 Some supplements, including L-Arginine, L-Citrulline, are involved in the molecular pathway of nitric oxide (NO) synthesis,9,10 some engage more downstream (eg, L-Cysteine), acting in synergy with cyclic guanosine 3’,5’-cyclic monophosphate (cGMP) or reducing its catabolism,11 while for others (eg, Tribulus terrestris), the ability to increase the levels of testosterone has been theorized.12 In addition, most nutraceuticals act as antioxidants counteracting the contribution of free radicals to endothelial dysfunction, which plays a key role in the pathogenesis of ED in many cases.4-6
In conclusion, our NMA contributes valuable insights into the potential of nutraceutical interventions for ED. L-Arginine and the mix PLC + ALC appeared to be of some usefulness in improving erectile function, especially in combination with PDE5i in organic ED. On the contrary, in nonorganic forms of ED, nutraceuticals did not improve the therapeutic performance of daily Tadalafil. Although doses and duration of treatments remain to be defined, considering the ineffectiveness of most nutraceutical preparations investigated in the available RCTs, these results may help select the few molecules worthy of further investigation in future prospective studies.
