The primary focus of this mini-review is on the vascular and hormonal factors influenced by vitamin D deficiency that may contribute to erectile dysfunction (ED). Psychogenic causes of ED are beyond the scope of this review. A systematic review is recommended for future research to comprehensively evaluate the association between vitamin D and ED. Vitamin D, often referred to as the ‘sunshine vitamin,’ plays a crucial role in maintaining overall health. Beyond its well-known effects on bone health, emerging research indicates that vitamin D may also influence other physiological systems, including sexual health [1]. ED, defined as the inability to achieve or maintain an erection sufficient for satisfactory sexual performance, is a significant global health issue affecting millions of men. Recent studies have suggested a possible link between vitamin D deficiency and ED, a condition typically associated with aging, cardiovascular disease, diabetes, and psychological factors [2]. The human body primarily synthesizes vitamin D through exposure to ultraviolet B radiation from sunlight, with smaller contributions from diet and supplements. Vitamin D is essential for regulating calcium absorption, immune function, and cell growth and differentiation. It also protects arterial health by influencing endothelial function, reducing inflammation, and controlling the proliferation of smooth muscle cells. Considering the close connection between vascular health and erectile function, the role of vitamin D in erectile physiology and its potential implications for ED prevention and treatment are currently being explored [3].

Recent evidence-based and clinical studies have highlighted the correlation between vitamin D and erectile function. Insufficiency of vitamin D, which can lead to endothelial dysfunction, oxidative stress, and decreased bioavailability of nitric oxide (NO), may increase the risk of ED. Conversely, vitamin D supplementation could improve endothelial function, vascular health, and erectile function in some individuals. Further research is needed to elucidate the molecular pathways involved and the clinical implications of vitamin D supplementation for ED [4].

This review synthesizes existing research on vitamin D and ED. We will explore the epidemiological evidence linking vitamin D deficiency to ED, the pathophysiological mechanisms involved, and the clinical implications of vitamin D supplementation for men with ED. By integrating existing knowledge and identifying gaps in our understanding, we aim to deepen our understanding of the complex relationship between vitamin D status and sexual health, thereby facilitating more targeted and effective prevention and management strategies for ED.

Optimal levels of vitamin D in the bloodstream are crucial for supporting male sexual health [5]. Vitamin D deficiency is associated with an increased prevalence of ED. After accounting for comorbidities, lifestyle factors, and medication use, researchers found that men with a vitamin D deficiency, specifically defined as a 25-hydroxyvitamin D (25(OH)D) level below 20 ng/mL, had a significantly higher occurrence of ED (30%) and severe ED (80%) than men with optimal levels (30 ng/mL or higher). Additionally, there was a notable 12% increase in the prevalence of ED for each 10 ng/mL decrease in 25(OH)D levels. Calcitriol, the biologically active form of vitamin D, promotes the synthesis of NO within the human body. NO, a potent vasodilator, plays a crucial role in the mechanism of penile erection [4]. A meta-analysis has shown that insufficient levels of 25(OH)D, specifically defined as serum concentrations below 20 ng/mL, are linked to male infertility and ED [6]. Men who have a deficiency in 25(OH)D (i.e., a serum concentration <20 ng/mL), as opposed to those who do not, experience a higher prevalence of ED [7]. Vitamin D deficiency can worsen ED by contributing to endothelial dysfunction [8].

Supplementation of vitamin D has been observed to enhance erectile function, a condition previously associated with increased testosterone levels in the blood of men in their 30s [9]. Optimal blood concentrations of vitamin D may improve cavernous blood supply by increasing arterial blood flow. This is achieved by modulating the bioavailability of NO, a potent vasodilator neurotransmitter in the endothelium, thereby enhancing endothelial vasodilation [10]. Additionally, vitamin D supplementation has been significantly linked to improved recovery rates in patients with cardiovascular disorders and diabetes, especially those who are deficient in vitamin D. These improvements in endothelial function have been connected to the observed enhancements among patients [11].

Normal serum levels of vitamin D, specifically 25(OH)D, should range from 20 to 50 ng/mL. Levels between 21 and 29 ng/mL are considered inadequate. Concentrations below 18 ng/mL are deemed insufficient and increase the risk of ED; severe vitamin D insufficiency is characterized by serum levels below 10 ng/mL [12]. Optimal concentrations of 25(OH)D are above 30–35 ng/mL. Low levels of 25(OH)D are linked to various diseases.

ED is more prevalent among males with low levels of 25(OH)D in their blood. This condition is particularly common in those with an arteriogenic thrombosis etiology, indicating that vitamin D deficiency may play a role in exacerbating endothelial dysfunction and consequently impairing erectile function [13]. The daily recommended intake of vitamin D is 600 IU for individuals aged 18 to 70 years. For those over 70, the recommended intake increases to 800 IU [14]. The preservation or enhancement of endothelial and erectile function is crucial. Male adults with a triglyceride level of more than 150 mg/dL should take at least 1.5 to 2.0 g of zinc and additional vitamin D at a concentration of 2,000 IU per day [9].

A nuclear receptor that interacts with vitamin D, known as the vitamin D receptor (VDR), is widely distributed across various tissues and is crucial for cellular growth and proliferation in different cell types. Vitamin D influences a vast array of genes, with estimates suggesting it affects over 3,000. Its pharmacological actions are facilitated through its binding to the VDR. This binding triggers a series of responses that are categorized into either genomic or non-genomic downstream effects [15].

Genomic effects involve the direct regulation of gene expression. When vitamin D binds to its receptor, the resulting VDR complex interacts with specific DNA sequences in the nucleus, initiating changes in gene transcription. This process ultimately affects the synthesis of proteins encoded by the regulated genes. In contrast, non-genomic effects occur more rapidly and do not involve changes in gene expression. Instead, they include rapid signaling pathways or alterations in cellular processes that happen independently of gene transcription changes. These non-genomic effects of vitamin D may involve interactions with various signaling molecules or cell membrane receptors, leading to immediate cellular responses [16].

Upon the binding of vitamin D to its receptor, it translocates to the chromosomes. There, it initiates a genetic pathway through the vitamin D signaling process, which alters the transcription of genes that were previously transcribed [17]. When a male is physically stimulated, it leads to the activation of neuronal NO synthase. This activation prompts the dilation of smooth muscle due to the presence of NO. Subsequently, endothelial nitric oxide synthase (eNOS) breaks down NO and released following endothelium stimulation. Ultimately, NO increases the levels of the second messenger cyclic guanosine monophosphate (cGMP), which further enhances the vasodilation of the smooth muscle [16].

Penile dysfunction is defined as the inability to achieve and/or maintain an adequate erection for sexual intercourse, a condition that results when the NOS-NO-cGMP chain reaction is disrupted. Various factors including the neurological system, testosterone levels, nerves, muscles, psychological influences, environmental conditions, and blood vessels all play roles in male libido. Penile erection is primarily a vascular event, and studies have shown a strong link between ED and atherosclerotic cardiovascular disease (ASCVD). Additionally, ED can act as an early warning sign of atherosclerosis and obstructive coronary artery disease. Risk factors such as diabetes, hypertension, smoking, elevated triglycerides, and a sedentary lifestyle significantly contribute to both ED and ASCVD [18].

Severe ED, characterized by the inability to achieve an erection, affects 2% of men aged 20 to 39 and increases to 47% in men aged 75 and older. The incidence of ED rises with age [19]. The penis, which is highly vascularized, depends primarily on vascular mechanisms to achieve erections. NO is produced by the endothelial cells in the penis, and neurotransmitters are released from the corpus cavernosum, the two cylindrical structures that run the length of the penis, in response to sexual stimulation [20].

NO plays a crucial role in vasodilation by inducing relaxation in the vascular endothelium, which is essential for achieving an erection. When neurotransmitters and NO work together, they promote relaxation in the corpus cavernosum, allowing blood to flow into the penis. This leads to an erection that expands and is maintained until the process reverses [21].

Endothelial dysfunction refers to the impaired regulation of the endothelium, which lines the interior surface of blood vessels. The endothelium plays a crucial role in regulating vascular tone and blood flow. In cases of ED, endothelial dysfunction plays a significant part in the inability to achieve or maintain an erection by interfering with several mechanisms. Primarily, it hinders the production and release of vasodilators such as NO, which are vital for the relaxation of smooth muscle cells in the penile arteries and cavernous bodies [22]. This relaxation is essential for increasing blood flow during sexual stimulation.

Endothelial dysfunction leads to a reduction in available NO as it is more rapidly degraded by reactive oxygen species, as shown in Table 1 [4,6-9,12,13,23-37]. This process results in oxidative stress and subsequent damage to the endothelial cells. Additionally, the dysregulation of eNOS, which is responsible for NO synthesis, further diminishes NO production. Furthermore, endothelial dysfunction prompts the excessive production of vasoconstrictors such as endothelin-1 and thromboxane A2. This exacerbates the contraction of smooth muscles in the blood vessels of the penis, thereby reducing blood flow to the penile region [38].

The imbalance between vasodilators and vasoconstrictors hinders the process of vasodilation, which in turn impairs erectile function. By adopting lifestyle changes and utilizing therapies aimed at restoring endothelial function, there is potential to improve erectile health and reduce the negative impact of endothelial dysfunction on sexual performance (Figure 1).

The role of vascular disorders in ED has been integrated into the introduction, providing a foundation for understanding the impact of vitamin D on these conditions. ED is more common among men with reduced levels of 25(OH)D in their blood. It is particularly prevalent in those with an arteriogenic etiology, indicating that hypovitaminosis D may contribute to increased endothelial dysfunction and consequently impair erectile function.

The link between vitamin D deficiency and ED should be interpreted with caution due to several limitations in the research. Firstly, vitamin D deficiency is prevalent in numerous diseases, both cardiovascular and non-cardiovascular (such as cardiovascular disease, metabolic syndrome, and inflammatory disorders), which independently affect ED risk factors, particularly cardiovascular and endothelial dysfunction [39,40]. These comorbid conditions introduce confounding variables that complicate a direct attribution of ED improvement to vitamin D.

While vitamin D is believed to play a protective role in endothelial function and NO synthesis, as suggested by in vitro and animal studies, clinical research in this area remains insufficient [41,42]. There are proposed physiological mechanisms through which vitamin D may influence endothelial cells, such as increasing eNOS activity and reducing oxidative stress. These mechanisms are plausible but require further investigation in human subjects [10]. Additionally, variations in study designs, population demographics, methods of assessing vitamin D levels, and differences in the doses and durations of vitamin D supplementation complicate the comparison of studies and the generalization of results [43]. Interestingly, recent randomized controlled trials examining the effects of vitamin D on ED symptoms have yielded mixed results, with some trials reporting no effects [44].

Ultimately, understanding the impact of vitamin D on ED will necessitate well-designed, long-term trials that control for potential confounders, utilize standardized supplementation protocols, and account for dosing effects. Further research is needed to comprehensively understand the molecular pathways through which vitamin D may influence endothelial health and NO bioavailability, thereby improving predictions of the relationship between vitamin D levels and ED.

Maintaining appropriate levels of vitamin D is crucial for a healthy sexual life in men. Insufficient levels of vitamin D have been directly linked to a higher incidence of ED. Research shows that men who are vitamin D deficient, defined as having 25(OH)D levels below 20 ng/mL, experience a significantly higher incidence of ED and severe ED compared to men with optimal levels (30 ng/mL or higher). Additionally, a 12% increase in the prevalence of ED has been associated with a decrease in 25(OH)D levels. Vitamin D, particularly calcitriol, the active form of the vitamin, stimulates the production of NO, a potent vasodilator necessary for penile erection. Some studies are currently exploring a connection between vitamin D and ED, likely through vitamin D’s ability to modulate endothelial function and NO production. However, clinical evidence remains inconclusive. One of the most recent large randomized controlled trials, the D-Health Trial, assessed the effects of three years of vitamin D supplementation on ED in men aged 60 to 84. The trial found no significant differences in ED prevalence between the vitamin D and placebo groups, suggesting that vitamin D supplementation alone may not mitigate or prevent ED symptoms in this age group [44]. These findings underscore the need for more controlled trials to distinguish the direct effects of vitamin D on ED from other potential causes, including loss of muscle integrity and disorders such as diabetes, cardiovascular disease, cognitive decline, and prostate issues. These conditions, particularly in older individuals, could undoubtedly contribute to ED symptoms and highlight the necessity of an integrated ED management strategy for older adults. Furthermore, studies on vitamin D supplementation have shown improvements in erectile function, often associated with increased endothelial vasodilation and arterial blood flow. Vascular diseases and ED are strongly linked, and addressing vitamin D deficiency can help improve both endothelial and erectile function. To reduce the risk of ED, it is essential to maintain optimal levels of vitamin D, typically ranging from 20 to 50 ng/mL. A balanced diet, regular exercise, abstaining from smoking and excessive alcohol consumption, and other lifestyle modifications are also vital in preventing ED. It’s important to remember that there are multiple potential causes of ED; vitamin D deficiency is just one of them. A comprehensive approach that considers lifestyle choices, overall health, and targeted treatment of underlying causes is necessary to effectively treat and prevent ED. Individuals with persistent or recurrent symptoms of ED should consult healthcare professionals for a comprehensive assessment and appropriate guidance.