Sexual function is an integral part of human health and is crucial for a good quality of life (1). Loss of sexual function is a major disorder, and it is mainly caused by erectile dysfunction (2). Although male sexual dysfunction can occur at any age, erectile function and libido decline with age (3). Erectile dysfunction is a disorder with an increasing rate of occurrence. As of 1995, about 150 million men were suffering from erectile dysfunction; meanwhile, about 322 million people were projected to likely have the disorder by 2025 (4). Erectile dysfunction is prevalent in the US, affecting 18–30 million men (5). Much of the reported upsurge could be attributed to a deteriorating diet and other unhealthy lifestyle choices (6). To support this, data from the National Health and Nutrition Examination Survey revealed that the population of US citizens with optimal serum vitamin D levels decreased by 49% between 1994 and 2004 (7), a period coinciding with an increase in the incidence of erectile dysfunction in the country.

Vitamin D is a micronutrient essential for optimal health throughout different stages of life. Vitamin D is a steroid hormone that can be obtained from the diet or synthesized in the human skin in the presence of sunlight, primarily the ultraviolet-B portion of sunlight, which accounts for approximately 80% of vitamin D (6). Recently, it has been established that vitamin D plays a more diverse role in humans than just maintaining calcium homeostasis (8, 13). The presence of vitamin D receptors (VDRs) in almost all human tissues, including those responsible for reproduction, indicates that vitamin D regulates numerous cellular differentiation and functions across different cell types (9–11). Vitamin D acts by binding to its receptor to stimulate genomic and non-genomic effects (12). After binding, the receptor translocates from the plasma membrane to the nucleus, bringing about gene activation via the hormone response element (13). According to the Human Genome Project, human DNA contains approximately 20,000–25,000 genes (14). Notably, approximately 3,000 out of these genes are responsive to vitamin D (13), further underscoring the numerous roles of vitamin D in human function. Therefore, if we consider that vitamin D has diverse functions in various tissues, vitamin D becomes more important for a healthy sexual life, especially for erectile function. Hence, this study reviewed existing literature to establish the sexual and erectile enhancing activities of vitamin D.

Vitamin D is a secosteroid because of the ruptured B ring of the canonical steroid structure. It is produced from 7-dehydrocholesterol, a metabolite obtained during cholesterol synthesis, and can also be obtained directly from the diet. Vitamin D can be classified into vitamin D3 (cholecalciferol) or vitamin D2 (ergocalciferol). Cholecalciferol is produced in the skin (especially during summer months) after ultraviolet light or sunlight exposure. Vitamin D3 can also be obtained from animal-sourced foods, while ergocalciferol is obtained from plant sources and fortified foods. The major difference between the two forms of vitamin D is found in their side chain since vitamin D2 has a double bond between C22 and C23 and a methyl group at C24 in the side chain (15). However, these differences do not affect metabolism (16, 17). In fact, both forms of vitamin D have been established to have similar responses in the body (18). However, Tripkovic et al. (19) identified vitamin D3 as more effective at increasing serum 25(OH)D than vitamin D2; thus, vitamin D3 could be a preferred choice for supplementation.

The two forms of vitamin D are considered biologically inactive until they undergo two enzymatic hydroxylation reactions. The first enzymatic reaction occurs in the liver in the presence of 25-hydroxylase, especially the cytochrome P450 2R1, which forms 25-hydroxyvitamin D. The second hydroxylation reaction occurs in the kidney, and it is mediated by 1α-hydroxylase, where 25-hydroxylase is converted to the biologically active form, calcitriol or 1,25-dihydroxyvitamin D (20). Notably, the expression of the 1α-hydroxylase gene has been identified in various extra-renal tissues, although their roles have not been fully elucidated (21). However, the likelihood of this enzyme acting on vitamin D metabolites in these extra-renal organs as something other than the calcium-regulating hormone is more likely a contribution to circulatory 1,25-dihydroxyvitamin D in these tissues. 25-hydroxyvitamin D is the main circulating form of vitamin D (22), and it is found bound to a particular carrier protein known as vitamin D binding protein (23). This binding protein also helps in the transportation of vitamin D (24).

As previously stated, the biological activities of vitamin D involve gene expression regulation at the transcriptional level, which is mediated by binding to VDRs. These receptors are widely distributed throughout the body, even in organs that are not directly involved in maintaining calcium and phosphate homeostasis. The presence of these receptors in various organs suggests that vitamin D can perform multiple functions beyond calcium homeostasis (25). Additionally, the specific vitamin D-responsive elements are widely present in human genes involved in different activities such as cell differentiation and apoptosis (26). In fact, vitamin D has been suggested to have the specific vitamin D-responsive element activities via autocrine and paracrine pathways (27). Furthermore, Masuda and Jones (93) further hypothesized that vitamin D may have anti-cancer properties and can serve as a therapeutic agent for managing other chronic conditions, such as metabolic disorders.

Sexual dysfunction is a distortion in sexual behaviour and stimulation that can occur at any of the different stages of the normal sexual cycle, such as desire, arousal, or erection, and orgasm (71). Low sexual desire or libido is a lack of sexual drive or motivation, either alone or with a partner. Libido is regulated primarily by the mesolimbic dopamine signaling (ventral tegmental area and nucleus accumbens) (72). Therefore, dopamine and other related trace amines that regulate dopamine neurotransmission are mainly responsible for regulating libido.

Erectile dysfunction (ED) is the inability to attain or maintain optimal penile erection required for sexual satisfaction. ED is a prevalent condition that affects a significant portion of the male population. Studies estimate that approximately 10%–30% of men develop some degree of erectile problem in the course of their lifetime (73). This is not just a physical illness, as it usually results in psychological disturbance, anxiety, and a decrease in the quality of life. Often, these feelings of guilt, shame, and reduced self-esteem are associated with ED in men, aggravating the condition and affecting relationships (57, 74). Thus, awareness about the causes of ED and consideration of various treatment modalities will be essential to address the sexual life and overall health of men.

Orgasm is the peak of sexual pleasure and is characterized by intense pleasurable feelings in the genitals, and it is an accompaniment to ejaculation. Orgasm is a complex physiological process that involves a cascade of physical and psychological changes, including muscle contractions, hormonal releases, and altered brain activity, leading to a peak sensation of pleasure and a release of sexual tension. However, these aforementioned sexual cycles have been shown to be influenced by vitamin D status.

Recent evidence has sought to elucidate the relationship between the level of 25-hydroxy vitamin D and erectile function, with a view to the biological plausibility of an association and the potential role of vitamin D supplementation in ED treatment (30, 75). Vitamin D is primarily obtained through sun exposure and dietary intake, playing a crucial role in various physiological processes, including maintaining bone health, immune function, and cellular growth (33). Its implications for sexual health, especially erectile function, have been increasingly realized.

Crafa et al., in their meta-analysis involving cross-sectional studies, investigated the relationship between vitamin D deficiency and ED. Indeed, from the meta-analysis, their findings indicated that a lower level of 25-hydroxyvitamin D is significantly associated with the more serious forms of ED. Interestingly, this study underlined that, even though the mean level of 25(OH)D was not significantly different between the two groups of men with and without ED, patients with vitamin D deficiency had remarkably worse erectile function scores. This finding was, moreover, pronounced in eugonadal patients and therefore likely indicates vitamin D deficiency as an additional factor worsening the severity of ED, independent of testicular function. This again focuses more on Vitamin D as a modifiable risk factor in the management of erectile dysfunction.

Similarly, Demirci et al. (64) investigated how vitamin D supplementation, when added to tadalafil, one of the most commonly prescribed medications for ED, would impact treatment outcomes. The participants consisted of “vitamin D-deficient male patients” and received 4,000 IU of vitamin D3 along with tadalafil. Although the study period was not specified, the results showed that men who received vitamin D supplementation experienced a greater improvement in their erectile function compared to those who took tadalafil only. This finding suggests that vitamin D may enhance conventional ED treatment responses, leading to improved overall outcomes in patients with concomitant vitamin D deficiency. These results point out the importance of considering vitamin D levels in the comprehensive management of erectile dysfunction.

The study of Farag et al. (65) involving 3,390 US men aged ≥20 years, revealed low levels of vitamin D in men with erectile dysfunction compared to normal subjects. Furthermore, the study of Tirabassi et al. (66) concluded that ED is associated with vitamin D and is independent of testosterone level. In the same vein, a study involving fifty patients revealed that severe ED is common in patients with low vitamin D levels (67). Additionally, a study involving a large cohort of diabetic patients found that vitamin D is inversely related to intima-media thickness and directly proportional to the IIEF-5 score and cavernous peak systolic velocity (68). This same study also identified vitamin D as a major diagnostic marker for sexual dysfunction. Another study, carried out on thirty-seven dialysis patients, revealed a negative relationship between the ASEX total score and serum vitamin D (76), indicating the importance of vitamin D in sexual function. In support of these clinical studies, findings from animal models also reported a positive correlation between vitamin D levels and sexual function. For example, the study of Zhu et al. (69) established that vitamin D improved erectile function in cavernous nerve-injured rats. Also, Fernandes-Lima et al. (70) concluded that vitamin D is an important micronutrient required for penile cytoarchitecture maintenance.

Numerous mechanisms have been hypothesized to explain the relationship between sexual dysfunction and vitamin D. One of those is the inhibitory effect of vitamin D on prolactin. Prolactin is an important hormone that increases during orgasm, and it's responsible for creating the post-orgasmic refractory period by inhibiting sexual motivation and arousal (71). Additionally, an increase in prolactin disrupts the hypothalamic-pituitary-testicular axis, which is responsible for maintaining male sexual function by inhibiting testosterone and luteinizing hormone synthesis (77, 78). Hence, the inhibitory effect of vitamin D on prolactin (79) suggests that vitamin D increases sexual motivation and arousal via a hormone-dependent mechanism.

Another important mechanism that could account for the role of vitamin D in male sexual function is its role in the monoamine neurotransmitters, since the nervous system is involved in male sexual activities. One major monoamine neurotransmitter required for male sexual function is dopamine, also known as “the addiction hormone” (80). Optimal circulatory dopamine is required for the motor activities required for sexual activities (81). Additionally, in the mesolimbic tract, dopamine stimulates various motivated behaviors, such as copulation. In the medial preoptic area, it regulates genital reflexes, copulatory patterns, and specifically, sexual motivation (82). Furthermore, dopamine stimulates penile erection by acting on the oxytocinergic neurons located in the hypothalamic paraventricular nucleus and the pro-erectile sacral parasympathetic nucleus of the spinal cord (72). Vitamin D, on the other hand, has been shown to maintain optimal levels of circulating dopamine. Pertile et al. (83) established that chronic vitamin D exposure enhanced the developing neurons' capacity to release dopamine, while Lima et al. (84) revealed the protective role of vitamin D on the dopaminergic neurons and associated it with their anti-inflammatory properties (85, 86). Additionally, a clinical study (87) revealed that vitamin D enhanced amphetamine-induced dopamine release in healthy subjects. Hence, the stimulatory effect of vitamin D on dopamine could account for its sexual performance-enhancing abilities.

Another key mechanism of action of vitamin D appears to be via Nitric oxide-mediated vascular dilation, as it stimulates NO production and release (13, 88, 89). Penis is a highly vascularized organ responsible for erection, and nitric oxide is a major mediator of penile erection via its vasodilatory effects. NO is a main secretion from the endothelial cells lining the blood vessels, and it is a neurotransmitter with vasodilatory function and therefore important for erectile function. Once released from the penile smooth muscles, NO becomes activated in the presence of sexual stimulus via the dopamine-oxytocin-NO pathway (71). Once activated, NO will act on the guanosine cyclase in the corpus cavernosum smooth muscles to produce cGMP to promote a cascade of events that will eventually lead to corpora cavernosa smooth muscle relaxation and penile erection (90, 91). Okechukwu (75) supported the fact that vitamin D is associated with erectile function mostly through its effect on endothelial health. The study stated that vitamin D increases the generation of NO, an effective vasodilator, and it is also necessary for the initiation and maintenance of an erection. A proper balance and adequate availability of NO are crucial to ensure normal blood flow to the penile tissue, a key physiological mechanism underlying erectile function. Thus, from the point of view of the relationship that vitamin D shares with the production of NO, optimization of levels may improve endothelial function and enhance erectile responses. Therefore, due to the presence of vitamin D and its receptors in the endothelial cells (92) and its stimulatory effect on NO release, it is conceivable that the interaction between vitamin D and NO plays a vital role in sexual function.

Given the growing awareness of the relationship between vitamin D and erectile health, it would seem reasonable to have healthcare providers evaluate men presenting with ED for levels of vitamin D and possibly use supplementation as part of an overall treatment plan.

However, based on promising findings, further research is needed to establish definitive cause-and-effect relationships between vitamin D levels and erectile function. Questions that remain unanswered include dosage, the duration of treatment required for significant positive effects to occur, and which populations may benefit most from supplementation. Further investigation is also needed to describe in detail the biological pathways through which vitamin D impacts erectile function and to develop an understanding of potential interactions between other factors, including lifestyle, comorbid conditions, and age.

Also, the daily supplementation threshold for maximum sexual function should be determined. It should be noted that while the tolerable upper intake level of vitamin D is 4,000 IU per day, some individuals, especially those with vitamin D deficiency or certain health conditions, may require higher doses under medical supervision.