Get your penis to work with this big, bad steroid

If I had to pick one thing to optimize for erectile function before anything else…

It would be vitamin D.

Although the name implies that it’s a vitamin, it’s actually a steroid. It’s so strong, it potentiates the effects of steroids, such as progesterone, testosterone and DHT.

Not only that, but those steroids don’t actually work optimally without steroid D.

Vitamin D can have strong effects on sexual function without you even changing your diet. But naturally, if you want to maximize sexual function, then the diet should also be optimized.

Vitamin D, the penor and sexual function

It has been estimated that 20–100% of U.S., Canadian and European elderly men and women have low levels of 25OHD3 (the storage form of vitamin D). The Endocrine Society defines vitamin D deficiency when the blood levels of 25OHD3 are lower than 20ng/mL and vitamin D insufficiency for levels ranging from 21 to 29 ng/mL (R). Optimal levels are between 40-60 ng/mL.

“In men under the aged 40 to 49 years, the prevalence of ED was relatively low (~40%) and in men aged 70 to 79 years, the prevalence of ED was significantly higher (~90%) [6,7,9].” (R)

And…

“VDD (vitamin D deficiency) is about 50% at older ages and this result underlines the importance of VDD for public health [26,27].” (R)

So ED is much more prevalent in old age and so is vitamin D deficiency. Now I know that association is not always causation, but we’ll get into that in just a bit.

The vitamin D receptor (VDR) is expressed in all tissues of the human body including the penis (and nut sack), where it regulates cellular differentiation and function across many cell types.

Upon VD binding, VDR translocates from the plasma membrane to the nucleus where it transcriptionally activates genes via the VD response element, thereby affecting transcription of other genes. Human Genome Project study results showed that human DNA has between 20,000 and 25,000 genes, and more important to us, surprisingly, over 3,000 genes are responsive to VD (R).

Vitamin D activation in the nut sack

The testes express the enzyme CYP2R1, which converts cholecalciferol (vitamin D3) into calcidiol (25OHD3), the major circulatory form of the vitamin. Supplemental vitamin D is usually in the form of cholecalciferol. In particular, the testicular tissue of healthy men has a five-fold higher expression of CYP2R1 mRNA compared with the liver (R).

As a side note, CYP2R1 is found in the endoplasmic reticulum (ER) of the cell. ER damage (as induced by COVID), can reduce CYP2R1 and reduce vitamin D creation. TUDCA, a bile acid, is known to alleviate/attenuate ER damage, and should restore vitamin D synthesis in the testes.

Continuing with the side note: Toxins absorbed from the gut, such as endotoxin, can damage the testes in the same way. So using TUDCA to increase testicular vitamin D and improve testosterone and sexual function might be a good idea.

Back to CYP2R1. This enzyme is expressed in Leydig cells in a luteinizing hormone (LH)-dependent manner (R). “Indeed, human chorionic gonadotropin (hCG) administration to male patients with central hypogonadism is also able to restore blood 25(OH)D₃ levels, whereas testosterone replacement therapy is not. This confirms that the hydroxylation of vitamin D within the Leydig cells occurs with an LH-dependent mechanism. For these reasons, low blood concentrations of 25(OH)D₃ may be associated with male hypogonadism” (R, R).

Very interesting right?

Estrogen and prolactin reduce the sensitivity of the LH receptor. Endotoxin can also have a negative effect. On the other hand, thyroid hormone T3 enhances the LH receptor sensitivity.

The benefits of vitamin D on ED

Vitamin D increases other steroids

First on the list of the ED benefits of vitamin D is more commonly known steroids, such as testosterone.

Vitamin D has been shown to increase testosterone, free testosterone and the testosterone to estrogen ratio. High estrogen in relation to testosterone leads to ED.

Testosterone modulates nearly every component involved in erectile function and its deficiency is associated with ED. In an aging male population, hypogonadism is common (30% prevalence in men >60 years), and is associated with ASCV risks (e.g., atherogenic lipid profile, insulin resistance and obesity) (R).

Vitamin D is positively associated with testosterone, which interestingly, followed the seasons. Testosterone, free T and vitamin D were the lowest in winter and the highest in summer (R).

Recently, it was also demonstrated that vitamin D supplementation improves T levels, metabolic syndrome and erectile function in middle-aged vitamin D deficient men (R).

The most interesting thing to me is that, even if testosterone is good/high, someone can still have ED problems if their vitamin D is low.

This study found that those with normal testosterone and low vitamin D have a higher risk of ED compared to those with normal testosterone and vitamin D. “Finally, we found that eugonadal patients with severe ED have lower 25(OH)D₃ levels than patients with mild ED. In conclusion, this meta-analysis suggests an association between vitamin D deficiency and the presence of severe forms of ED, independent of testicular function” (R).

Vitamin D and androgen receptors

Not only does vitamin D increase testosterone, but it also has to potential to bind to the androgen receptor itself.

“An extra mechanism of VD on erectile function seems to function via binding to T receptors. Computer (in silico) modeling shows that besides activating the VDR, 1,25-D displays high affinity for some of the body’s other nuclear receptors. This suggests that when 1,25-D increases above its normal range, it binds the α/β thyroid, the glucocorticoid, and the T receptors, displacing their native ligands [53]. Marshall [54] showed the symmetry with which endogenous ligands exhibited very similar affinities across some members of the type 1 nuclear receptor family [54]. For example, 1,25-D docked into the VDR with a (nanomolar) Kd of 8.48, but also exhibited a Kd of 8.05 into the T receptor.” (R)

Lastly, vitamin D increases the duration that the androgens bind to the androgen receptors, by inhibiting glucuronidase. Longer binding = stronger effect.

Vitamin D rocks because vitamin D:

• Increases total testosterone
• Increases free testosterone
• Increases DHT
• Improves the testosterne to estrogen ratio
• Binds to the androgen receptor
• Prolongs the duration that androgens bind to the androgen receptor

Vitamin D and penor anatomical structure

The human body requires vitamin D for the proper anatomical development of the penis during embryonal life (R). This study found that vitamin D deficient offspring had smaller penises, more collagen tissue and less elastic fibers (R). So not only is it smaller, but also has less potential for expansion during an erection.

Low testosterone and high estrogen also lead to more fat tissue and less muscle in the penis, which contributes to ED. Vitamin D should help against this as it shifts the testosterone to estrogen ratio in a positive direction.

Vascular complications and ED

ED is frequently found in vascular syndromes, such as atherosclerotic cardiovascular (ASCV) diseases, hypertension, cerebrovascular disease, peripheral arterial disease and diabetes mellitus.

Endothelial function

One of the most significant mechanisms of VD on erectile function seems to work via endothelial integrity (R).

Vitamin D has been shown to stabilize the quiescent endothelium, regulate certain stages of endothelial activation, and repair the damaged endothelium (R).

Vitamin D also seems to have antioxidant effects by reducing the expression of NADPH oxidase (NOX; which produces reactive oxygen species) and promoting the action of other antioxidant enzymes and molecules such as superoxide dismutase, glutathione peroxidase, catalase, ascorbic acid, α-tocopherol, and glutathione that act by counteracting free radicals (R).

Many ED patients are VD deficient, particularly patients with arteriogenic ED. A placebo-controlled randomized trial demonstrated that even a single large dose of VD improves endothelial function in patients with type 2 diabetes and VDD (R).

Nitric oxide and ED

Nitric oxide boosting drugs are the go-to for ED. Looks like, if vitamin D is optimized, your NO production should also be in a good place.

Sexual stimulation releases neurotransmitters from the corpus cavernosa as well as NO (a relaxing factor) from the endothelial cells of the penis.

Vitamin D itself stimulates the production of NO in endothelial cells, which helps was relaxation, which allows blood to enter the penis. This should help improve flaccid hand as well as erectile quality.

Vitamin D is also needed for proper dilation in response to NO. You can have all the NO you want, but without D, arteries can’t properly dilate. This study found that sildenafil non-responders had significantly lower levels of vitamin D than responders (R).

“Andrukhova et al [30] reported that VDR mutant mice are characterized by lower bioavailability of the vasodilator NO due to reduced expression of the key NO synthesizing enzyme i.e., eNOS. Reduction in eNOS ends with endothelial dysfunction, increased arterial stiffness, increased aortic impedance, structural remodeling of the aorta, and impaired systolic and diastolic heart function at later ages, independent of changes in the renin-angiotensin system [30]. This may also clarify why endothelium derived; NO-evoked dilation is halved in arteries from VD deficient male rats [35].” (R)

“In more detail, vitamin D seems to have an inhibitory effect on the nuclear factor kB (Nf-kB) pathway involved in the expression of several pro-inflammatory mediators such as TNFα, IL-1, and IL-6. In addition, vitamin D exerts a direct inhibitory effect on the expression of TNFα receptors 2 and 4, thus preventing the inhibitory action of this mediator on endothelial nitric oxide synthetase (eNOS) and its ability to promote inflammation through the further activation of the NF-kB.” (R)

Vitamin D, atherosclerotic cardiovascular diseases and ED

The 3rd point I’d like to make about vitamin D and proper blood flow is atherosclerotic ED. That’s when the arteries of the penis start getting plaque. Then blood flow is reduced and ED ensues.

Vitamin D deficiency (VDD) is associated with atherogenic dyslipidemia, diabetes, and reduced serum testosterone levels all of which are associated with endothelial dysfunction and are classic risk factors for the onset of ED.

Recently, Barassi et al demonstrated a higher presence of VDD in arterial ED patients compared with non-arterial-ED patients and a lower serum VD levels in more severe ED patients (R).

Low D not only leads to plaque buildup in the arteries but also larger platelets, which will show up as elevated mean platelet volume (MPV) in a blood test.

Larger platelets are metabolically and enzymatically more active with a greater prothrombotic potential leading to increased platelet aggregation, thromboxane synthesis, and increased expression of adhesion molecules.

All these factors increase the risk of vascular diseases including CVD and ED (R).

Immune activation and ED

ED is associated with incremental inflammatory activation and inflammation plays an important pathophysiological role in both ED and cardiovascular.

Inflammation can exert a detrimental effect on the cardiovascular system via two pathways: chronic, low-grade inflammation and an acute systemic inflammatory response. The former has been implicated in atherosclerotic processes (R), while the latter accounts for adverse atherosclerotic cardiovascular events following severe inflammatory stimulation. 

Point being, excess inflammation, in general, is bad. Or more specifically, inflammation your body can’t resolve quickly is bad. Exercise, which is hormetic stress, can also be detrimental if your body can’t recover quickly enough.

In more detail

“Vitamin D inhibits the pro-inflammatory activity of CD4+ Th1 cells resulting in a reduction of inflammatory cytokines such as IL-2, interferon (IFN)-γ, and tumor-necrosis factor-α. Moreover, vitamin D also promotes Th2 responses by enhancing IL-4, IL-5, and IL-10 production. Finally, it could increase regulatory T cell activity and suppress Th17 responses. On this basis, vitamin D promotes a transition from an inflammatory Th1 response to an anti-inflammatory Th2 response” (R).

Vitamin D, may protect the cells (Sertoli, Leydig, penile muscle tissue, vascular, etc.) through suppressing inflammation factors (e.g. interleukins-1, 6, 8, 12, and tumor necrosis factor-α), reducing ROS production, inactivating caspase cascade and alleviating cell apoptotic death (R, R, R). In summary, VD may directly defend endothelial cells against oxidative stress; and VDD may contribute to ED through inflammation.

Additionally, vitamin D has a suppressive effect on renin, angiotensin II, and aldosterone (R). Therefore, in vitamin D-deficient subjects, angiotensin increases and enhances nicotinamide adenine dinucleotide (phosphate) oxidase (NADPH oxide; NOX) activity, resulting in the production of superoxide ions (R). 

Finally, LH doesn’t only increase vitamin D, but vitamin D also increases LH-induced testosterone production (R). Interestingly, treatment with all doses of 1,25(OH)2 vitamin D in the absence of LH and 10 and 100 ng/mL LH in the absence of 1,25(OH)2 vitamin D increased mitochondrial dehydrogenase activity for cultured Leydig cells (R). Showing that vitamin D directly has a stimulatory effect on steroidogenesis.

Practical takeaway

Get more sunlight, simple as that.

If you struggle to up your vitamin D, check out my free guide on how to:

• Maximize vitamin D synthesis naturally
• Maximize vitamin D via alternative stragegies
• Never burn again!

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(Just out 0 in the price bracket)

If your vitamin D is already optimal, then you can look at different things to maximize your testosterone and other important hormones.

• Maximize testosterone: a 26 quick tip guide
• Erectile dysfunction Part 1: the solution for your neurotransmitters
• Erectile dysfunction Part 2 – which hormones to optimize and how
• Erectile dysfunction Part 3: nitric oxide, oxidative stress and insulin resistance
• Erectile dysfunction Part 4: effective supplements
• Erectile dysfunction Part 5: Porn and Masturbation