Novel predictive risk factor for Erectile Dysfunction: Serum folic acid

Abstract

Erectile dysfunction (ED) is defined as the persistent inability to attain or maintain an erection sufficient to permit satisfactory sexual activity (Hatzimouratidis et al., 2016). Penile erection is a complex neurovascular phenomenon, and ED may result from various abnormalities arising from vasculogenic, neurogenic, hormonal, anatomical, drug-induced and psychogenic causes (Zhengyan et al., 2014). Endothelial dysfunction (EDys) has been found to be central to atherosclerosis which is one of the most common causes of ED (Gandaglia et al., 2014; Shah et al., 2016). EDys has also been linked to various risk factors like hypertension, diabetes, smoking and other oxidative stressors (Vlachopoulos et al., 2007). Thus, ED has been suggested to be an early marker of cardiovascular disease (CVD) (Shah et al., 2016). Endothelial cells have nitric oxide synthase (eNOS) which is responsible for the formation of nitric oxide (NO) which acts as a relaxing factor and plays a major role in activation and maintenance of the erection process (Aversa et al., 2010). Hyperhomocysteinaemia (HHcy) has a marked inhibitory effect on eNOS and promotes NOS uncoupling (Zhang et al., 2016). Folic acid (FA) has been demonstrated to play an important role in the metabolism of NO by potentially inverting NOS uncoupling (Stoll et al., 2010; Yang et al., 2014). FA supplementation has been found to improve endothelial dysfunction in patients with DM or hypertension (Cui et al., 2017; Hamidi Madani et al., 2013). Compared to the western countries, Asian population differ in genetic makeup, dietary and lifestyle profiles. It has also been found that nutritional deficiencies in FA account for increased

Serum folic acid levels and erectile dysfunction: A meta‐analysis and systematic review

“…(2014) reported for the first time that serum FA levels in the ED group were significantly lower than those in the non‐ED group and suggested that FA deficiency might be one of the risk factors for ED. Several subsequent studies reported similar results and further suggested that the degree of FA deficiency was related to the severity of ED (Attia et al., 2019; Gupta et al., 2020; Karabakan et al., 2016). But recent cross‐sectional study of 1,381 participants found no significant difference in FA levels between ED patients and controls (Chen et al., 2019).…”

“…In four studies (Gupta et al., 2020; Karabakan et al., 2016; Sansone et al., 2018; Yan et al., 2014), there was no significant difference in age between the ED group and the non‐ED group. Meta‐analysis results showed that the FA level of the non‐ED group was significantly higher than that of the ED group, with low heterogeneity (MD = 3.24, 95% CI 2.15–4.34, p < 0.001, I 2 = 20%).…”

“…According to the established retrieval formula, we searched a total of 1,341 related studies, deleted duplicates and made preliminary screening according to titles and abstracts, and the remaining 21 literatures entered the full‐text reading stage. After reading through the full text of 21 articles, a total of six studies (Attia et al., 2019; Chen et al., 2019; Gupta et al., 2020; Karabakan et al., 2016; Sansone et al., 2018; Yan et al., 2014) including 1,842 participants were finally included in our meta‐analysis. Among the six studies, five are case–control studies and one is cross‐sectional.…”

“…We conducted a methodological quality assessment of case–control studies using NOS and found that four articles (Gupta et al., 2020; Karabakan et al., 2016; Sansone et al., 2018; Yan et al., 2014) were of high quality and the remaining one (Attia et al., 2019) was of moderate quality (Table 2). The cross‐sectional study was assessed by AHRQ scale, and its quality was moderate.…”

“…Six studies reporting the FA levels in the ED group and non‐ED group were included in the meta‐analysis(Attia et al., 2019; Chen et al., 2019; Gupta et al., 2020; Karabakan et al., 2016; Sansone et al., 2018; Yan et al., 2014). The pooled MD revealed that individuals without ED had about 3.37 ng/ml higher of FA levels than those with ED (MD = 3.37, 95% CI 1.49–5.52, p = 0.004), with severe heterogeneity existed ( I 2 = 86%) (Figure 2).…”