Can someone explain to me how PFS leads to low Vitamin D?

A few months ago I got my Vitamin D checked. It was as 12 nmol/l. Of course, I started supplementing.
In summer - although being in the sun every day for more than 1h - it was just 22 nmol/l.

Can someone explain to me the biochemical mechanism of how PFS leads to low Vitamin D levels?

Found an interesting article on Vitamin D and frailty in ageing men. Did someone also additionally check their PTH? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2691187/

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I’m not sure if it does I had crazy low levels way before finasteride

I have PSSD and crashed a couple of months ago after a few days of inositol.
I’ve got low vitamin D levels, which I’ve not had before, so I wondered if it was related or not…

Strange, there was a PAS guy claiming recovery with inositol recently…

Maybe the low vitamin D levels in PFS are a result of thinnend skin like it happens in old poeple?! @Redivivus

" Androgen levels and 25(OH)D levels are associated in men and reveal a concordant seasonal variation. Randomized controlled trials are warranted to evaluate the effect of vitamin D supplementation on androgen levels."
https://www.ncbi.nlm.nih.gov/pubmed/20050857

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Serum vitamin D levels and hypogonadism in men.

Hypogonadism was defined as TT <10.4 nmol/L…We found a significantly increased risk of hypogonadism in men within the highest 25(OH)D quintile (>102 nmol/L) compared to men in quintile 4 (reference) in crude (OR 5.10, 1.51-17.24, p = 0.009) as well as in multivariate adjusted analysis (OR 9.21, 2.27-37.35, p = 0.002). We found a trend towards increased risk of hypogonadism in men within the lowest 25(OH)D quintile (≤43.9 nmol/L). In conclusion, our data suggest that men with very high 25(OH)D levels (>102 nmol/L) might be at an increased risk of hypogonadism. Furthermore, we observed a trend towards increased risk of hypogonadism in men with very low vitamin D levels indicating a U-shaped association of vitamin D levels and hypogonadism. With respect to risk of male hypogonadism, our results suggest optimal serum 25(OH)D concentrations of 82-102 nmol/L.

https://www.ncbi.nlm.nih.gov/pubmed/25044703

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Interesting also the link to the seemingly higher prevalence of autoimmune diseases among PFS patients. There seems to be a link between low sex hormones, low vitamin D levels and higher likelihood of developing autoimmune diseases:

“This chapter describes our current understanding of the role of sex hormones, vitamin D, and the effect of menopause on the development of autoimmune skin diseases.”

Associations of vitamin D status and vitamin D-related polymorphisms with sex hormones in older men

Highlights

• Vitamin D might influence sex hormone and gonadotropin levels.

• Lower vitamin D status is associated with lower testosterone levels.

• There was no association between gene polymorphisms and sex hormone levels.

Highlights

• We examined the relationship between vitamin D and sex hormone levels among men and women.

• Low vitamin D was associated with lower sex hormone binding globulin and higher free testosterone levels in men and women.

• Low vitamin D levels was associated with lower estradiol and higher dehydroepiandrosterone levels in women.

• These associations between vitamin D and sex hormones were independent of adiposity and lifestyle.

• Future research is needed to determine whether vitamin D treatment influences sex hormone levels.

Vitamin D and sex steroid production in men with normal or impaired Leydig cell function

Highlights:

• Young men with vitamin D deficiency have lower testosterone/estradiol ratio
• Men with impaired Leydig cell function and vitamin D deficient are less sensitive to hCG stimulation
Testicular tissue culture exposed to calcitriol induces a significant increase in testosterone
Vitamin D may have a stimulatory role on androgen production in men

I find this one also interesting, as the outcome of HCG treatment in PFS patients varies a lot. I wonder if this has an association to impaired Leydig cells and low vitamin D levles.

@redivivus @Dubya_B

This may be a bit off but a little piece of the puzzle. Vitamin D seems to be able to increase the 3β-hydroxysteroid dehydrogenase activity https://www.sciencedirect.com/science/article/abs/pii/S0960076018306435

Also somewhat off: Vitamin D improves vaginal dryness in postmenopausal women. PFS seems to be some male pendant. So maybe this would would also improve the dryness of the glans penis:

We found a trend towards increased risk of hypogonadism in men within the lowest 25(OH)D quintile (≤43.9 nmol/L). In conclusion, our data suggest that men with very high 25(OH)D levels (>102 nmol/L) might be at an increased risk of hypogonadism. Furthermore, we observed a trend towards increased risk of hypogonadism in men with very low vitamin D levels indicating a U-shaped association of vitamin D levels and hypogonadism. With respect to risk of male hypogonadism, our results suggest optimal serum 25(OH)D concentrations of 82-102 nmol/L.

This, in my opinion my explain why some guys do well on vitamin D, but when they overdo it they may in up in a crash. Me myself I felt some overall improvements, but I also had terribly low vitamin D although I try to get as much sun as possible.

" Thus, it can be concluded that vitamin D3 delays testicular senescence by regulating proliferation and apoptosis."
https://www.nature.com/articles/s41598-019-50679-y

“The testes of vit. D-deficient rats showed incomplete spermatogenesis and degenerative changes. Although interpretation is complicated by the intricate communication among testis cell types, these data suggest that the Sertoli cell is a primary site of action of 1,25(OH)2D in the testis. Moreover, these data indicate that 1,25(OH)2D receptor function in the testis relates to germ cell division/maturation, although this may be an indirect effect via the Sertoli cells.”

“Vitamin D may have a stimulatory role on androgen production in men”

" Epidemiological data have shown that vitamin-D deficiency is also associated with erectile dysfunction. In this review, our aim is to interpret the mechanisms by which vitamin-D might regulate anatomy and physiology of penis. Evidence showed that vitamin-D is needed for an adequate erectile function"

  1. Vitamin-D and androgen receptors

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.

VD is positively associated with T, exhibits a concordant seasonal changeability [47], elevates when T was supplemented in hypogonadism [48]. Surprisingly, the reverse situation is also true, suggesting that VD supplementation might increase T levels [49]. In a clinical randomized controlled trial, which is the first on this topic in literature, Pilz et al [49] investigated the effect of VD supplementation on androgens in men. The results were significant and the researchers observed that overweight men with VDD had a clinically meaningful increase in serum T levels after VD supplementation for 1 year [49]. Recently, it was also demonstrated that VD supplementation improves T levels, metabolic syndrome and erectile function in middle-aged VD deficient men [8]. Canguven

Here’s a thread compiling various users’ Vitamin D levels:

I calculated these:

  • Average: 21.4 ng/mL
  • Median: 22.0 ng/mL

Here’s an article about what a normal Vitamin D level should be. Different experts have different recommendations:

Vitamin D: What’s the “right” level? from Harvard Health Blog
https://www.health.harvard.edu/blog/vitamin-d-whats-right-level-2016121910893

The majority of folks have a level between 20 and 40, in my experience, and this is corroborated by the IOM’s findings in that 2010 report.
Endocrine Society: "Based on all the evidence, at a minimum, we recommend vitamin D levels of 30 ng/mL, and because of the vagaries of some of the assays, to guarantee sufficiency, we recommend between 40 and 60 ng/mL for both children and adults.”
According to a NEJM article, “a more appropriate cutoff for vitamin D deficiency would be much lower, 12.5 ng/mL.”

Based on all the above, it’s not clear those levels reported from Forum users are in fact low.

The papers you posted point to a potential connection of Vitamin D and hypogonadism, but I’m not sure they establish whether Vitamin D is a real cause or risk factor for hypogonadism (I’ve only looked at abstracts).

In aging and hypogonadism (or any systemic disease) we can expect that many chemicals and systems are not at optimal levels/functioning. So when we see just one of them out of range, we don’t know if it has a causal role. Is it a symptom or a cause?

The more I look into the literature, the more it seems the post-finasteride condition could be a breakdown in the system’s ability to maintain equilibrium (‘androgenic system failure’ for short?). For example Vitamin D deficiency could be both a symptom and a cause. (Even the concepts of cause and effect are too simplistic.)

Why do you think the levels in the forum are normal? 40-60 is healthy, 82-102 is optimal for optimal testosterone levels.
The problem with the “normal range” is that it the normal range includes everyone who is 50, 60, 70, 80… as vitamin D levels go down with age they affect the statistics and what is “normal”. I didn’t find age-matched vitamin D levels but I am 99% sure that the mean 22 value of the forum is incredibly low.

And yes, vitamind D affects androgene levels. And yes, it seems that even the testes is involved in the vitamin D production. Vitamin D is important for the production of healthy sperm cells.
And yes, I believe both is affecting each other.

I think you are right, the whole feedback loop system in PFS is broken - there is no equilibrium, some metabolites are missing where they are needed for production of healthy sperm or protection of the brain. The closed comparison I think is the menopause in many ways. Although I think in menopause some tissues like the brain will still produce important neurosteroids and thus women won’t be affected as much as PFS patients.

Here’s another study that finds a Vitamin D <-> hypogonadism link:

Conclusions: Secondary and compensated hypogonadism were associated with vitamin D deficiency and the clinical significance of this relationship warrants further investigation.

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You’re making a few claims that I can’t evaluate:

Vitamin D level of 40-60 is healthy, 82-102 is optimal for optimal testosterone levels.

Most of the authorities quoted in the Harvard Health Blog article do not agree with this range.

Vitamin D levels go down with age.

Do you have a citation on the expected normal range for young men?

Vitamin D affects androgen levels.

Where is the evidence of a causal role? Most of the papers you’ve posted call it an association and don’t claim a causal role.

Vitamin D has been discussed at great length. See 175 posts in this thread starting in 2010:

Here’s a critical perspective from @ScaredMale30 that I think is worth keeping in mind:

I think this conclusively puts to an end the idea that there is a special relationship between PFS and low vitamin D. Most of you guys started with vit D levels between 20ng/ml and 30ng/ml: that is completely normal when set against most other healthy, non-PFS people. You don’t have low vitamin D.

I’m not saying there is no link; but there are a lot of variables and issues to rule out before it can be established. It might just be a correlation or noise.