44 No wegian Jou nal o de elopmen o he In e na ional Science No 168/2025
MEDICAL SCIENCES
VITAMIN D AND MALE ERECTILE FUNCTION: AN UPDATED REVIEW
Shki yak A.
CEO and chie medical o ice “Shki yak Clinic”
Uk aine
Neu osu geon
MD, MsSc
ORCID: h ps://o cid.o g/0000-0002-2282-8285
Khanenko S.
“Shki yak Clinic”
Uk aine
Family doc o
MD, MBA
ORCID: h ps://o cid.o g/0009-0000-4237-1158
h ps://doi.o g/10.5281/zenodo.17608966
Abs ac
Li e a u e suppo ha i amin-D is impo an o di e en sys ems o he human body including, bu no
limi ed o endoc ine and immune sys ems, ascula u e and endo helial unc ion o he body. Male e ec ile unc ion
depends on many ac o s and can be pe cei ed as a heal h indica o o he body. Epidemiological da a ha e shown
ha i amin-D de iciency is also associa ed wi h e ec ile dys unc ion. In his e iew, ou aim is o in e p e he
mechanisms by which i amin-D migh egula e ana omy and physiology o penis. E idence showed ha i amin-
D is needed o an adequa e e ec ile unc ion. B ie ly, i amin-D is c ucial o a be e heal hy body and sexual
ac i i y.
Keywo ds: And ology, Endo helium, E ec ile dys unc ion, Ho mones, Male, Vascula endo helium
In oduc ion
Human sexual ac i i y is he manne in which hu-
mans expe ience and exp ess hei sexuali y. Male pe-
nile e ec ion is a physiological phenomenon in which
he penis becomes i m, engo ged, and enla ged in e-
sponse o sexual a ousal du ing sexual ac i i y (1). Pe-
nile e ec ion is he esul o a complex in e ac ion o
psychological, neu al, ascula , and endoc ine ac o s
in he p esence o a no mal penis ana omy (2). Penile
e ec ion is ini ia ed by ni ic oxide (NO), a po en as-
odila o , eleased om he ne e endings, u he p o-
duc ion o NO depends on inc eased blood low which
is also known as shea s ess (3). In mos ascula beds,
he NO is eleased by a s imulus ha inc eases he shea
s ess o e he endo helium. Endo helial dys unc ion is
a key a iable in he pa hogenesis o a he oscle osis
and i s complica ions, including e ec ile dys unc ion
(ED).
ED is de ined as he inabili y o a ain o main ain
e ec ion su icien o sa is ac o y sexual ac i i y (2).
O e he pas 20 yea s, he e ha e been nume ous e-
po s on he epidemiology o ED all o e he wo ld (4-
7). In all s udies, i was demons a ed ha he p e alence
o ED inc eases wi h age (4, 7). In o he wo ds, highe
age is s ongly associa ed wi h highe incidence o ED
(7, 8). In men unde he aged 40 o 49 yea s, he p e a-
lence o ED was ela i ely low (~40%) and in men aged
70 o 79 yea s, he p e alence o ED was signi ican ly
highe (~90%) (6, 7, 9). The e iology o ED has been
s udied comp ehensi ely and ound o be mul i ac o-
ial. ED is equen ly ound in ascula synd omes,
such as a he oscle o ic ca dio ascula (ASCV) dis-
eases, hype ension, ce eb o ascula disease, pe iph-
e al a e ial disease and diabe es melli us (DM) (8, 10,
11, 12). In ac , he penis is a highly ascula ized o gan
and e ec ions a e p ima ily ascula e en s. Bo h ED
and ASCV diseases ha e equen ly iden ical unc-
ional and mo phologic basis (3, 12). Because o i s as-
cula i y, ED is e en accep ed as a ma ke o co ona y
endo helial dys unc ion and a he oscle osis (10, 12).
In he las decades, se e al s udies ha e co ela ed
ED isk ac o s wi h i amin-D (VD) de iciency (VDD)
(5, 13, 14). Obse a ional and in e en ional s udies
published in li e a u e ha e es ablished a s ong ela-
ionship be ween VD le els and ED. This impo an
knowledge u ned scien is s o go in deep o he e ec
o VD on e ec ile unc ion. Sho ly, i is now well
known ha VD is a pa o well- unc ioning penis s a -
ing om he ea ly days o ou li es.
Vi amin D
VD, which is ac ually a s e oid ho mone, has
much mo e asso ed ole in human body o a i amin
han p e iously ecognized jus o calcium me abolism
(15). Since i was shown ha VD- ecep o (VDR) is ex-
p essed in all issues o human body including penis,
VD egula es cellula di e en ia ion and unc ion
ac oss many cell ypes (1, 16-23). VD e ec s a e acil-
i a ed h ough binding o he VDR and s imula ing no
only genomic bu also non-genomic e ec s (19^ 22).
Upon VD binding, VDR ansloca es om he plasma
memb ane o he nucleus whe e i ansc ip ionally ac-
i a es genes ia he VD esponse elemen , he eby a -
ec ing ansc ip ion o o he genes (19). Human Ge-
nome P ojec s udy esul s showed ha a human DNA
has be ween 20,000 and 25,000 genes (24), and mo e
impo an o us, su p isingly, o e 3,000 genes a e e-
sponsi e o VD (25).
No wegian Jou nal o de elopmen o he In e na ional Science No 168/2025 45
Un o una ely, he es ima ed wo ldwide p e a-
lence o VDD is eally high and common among he
elde ly. VDD is abou 50% a olde ages and his esul
unde lines he impo ance o VDD o public heal h
(26, 27). I we conside ha VD e ec many issues,
VDD becomes mo e and mo e impo an o a heal hy
sexual li e, in o he wo ds o e ec ile unc ion.
1. Essen ials o i amin-D
Vi amins D2 (e gocalci e ol) and D3 (cholecalci -
e ol) a e wo dominan o ms o VD. Vi amin D2 is
syn hesized by in e eb a es and plan s a e exposu e
o ul a iole adia ion (1). Vi amin D3 is na u ally p e-
sen in a small ange o oods (such as oily ish, egg and
o i ied dai y p oduc s) and is also made endogenously
in he skin. Die a y VD ypically comp ises only 10%
o 20% o ci cula ing le els o VD (28). I we look a
he VD physiology, one can see ha Vi amin D2 and
D3 a e biologically inac i e and subjec ed o double hy-
d oxyla ion, i s mainly in he li e and hen in he kid-
ney, o p oduce he biologically ac i e compound cal-
ci iol (1, 14, 21, 29, 30). Al hough 1,25(OH)2D is he
mos ac i e o m o VD and unde akes he majo bio-
logical unc ion, i has a sho e hal -li e (~0.3 and 25
days, espec i ely) and a 1,000- old lowe concen a-
ion han 25(OH)D (31). Mo e impo an ly, se um
25(OH)D is ela i ely s able and no di ec ly in luenced
by die (e.g., calcium in ake) and li e s yle (e.g., mobil-
i y) (31). Hence, o al-body VD s o es a e bes e lec ed
by 25(OH)D (31). Ea lie , i was p o ed ha a ailabil-
i y o ul a iole -B exposu e, and i 's esul an VD p o-
duc ion in skin, is highes in la e sp ing h ough ea ly
all and lowes om la e all h ough ea ly sp ing (26).
In addi ion o seasonal a ia ions, he e a e many o he
ac o s ha can a ec he p e alence o VDD. These
can be summa ized as egion and la i ude, die and sup-
plemen use, clo hing, obesi y, smoking, conce ns
abou sun damage, and he na u e o buil en i onmen
(32). Vi amin D and e ec ile dis unc ion
A gene al popula ion s udy showed ha low se um
VD was associa ed wi h highe p e alence o pe iph-
e al a e ial disease (33). Likewise, a e y ecen c oss-
sec ional analyses (3,390 men aged >20 yea s, ee o
ASCV disease) also epo ed ha VDD was associa ed
wi h an inc eased ED p e alence (14). In suppo , de i-
cien le els o VD <20 ng/mL we e associa ed wi h in-
c eased ED isk, whe e a dec eased p e alence o ED
was associa ed wi h VD le els >35 ng/mL (14). When
esea che s es ic ed hei analysis o he 562 men
(among 3,390 men) adjus ed o sex ho mone le els,
he associa ion o VD wi h ED became e en s onge
(14). The biological link be ween VDD and ED exhib-
i s se e al in e laced mechanisms ha could sugges
ha he link o VD wi h ED appea s o be independen
o sex ho mones (14).
1. Vi amin-D and a chi ec u e o he penis
The e a e many isk ac o s in he e iology o ED
which migh be di ec ly a ising om VDD. Since he
la es li e a u e showed he impo ance o VD on e ec-
ile unc ion, Fe nandes-Lima e al (34) in es iga ed he
e ec s o VD es ic ed die on Wis a a s o sp ing
penis mo phology. Fe nandes-Lima e al (34) demon-
s a ed ha VD es ic ion du ing pe ina al and pos na-
al pe iods induced me abolic and s uc u al changes
and ep esen ed impo an isk ac o s o ED in he pe-
nis o he adul o sp ing. The la e indings sugges
ha VD is an impo an mic onu ien in main aining
he cy oa chi ec u e o he penis (34). In o he wo ds,
human body equi es VD o he p ope ana omical de-
elopmen o he penis du ing emb yonal li e.
2. Vi amin-D and endo helial unc ion
The pa hophysiology o ED is mul i ac o ial, bu
common poin is a ascula diso de ela ed o de-
c eased endo helial unc ion. Indeed, one o he mos
signi ican mechanism o VD on e ec ile unc ion
seems o wo k ia endo helial in eg i y (30, 35). In mo-
lecula le els, VD s abilizes he quiescen endo helium,
egula es ce ain s ages o endo helial ac i a ion, and is
in ol ed in he epai o he damaged endo helium in
i o and in i o models. A ecen 12 c oss-sec ional
s udies, including 2,086 subjec s o a ying e hnic
g oups, showed an associa ion be ween endo helial
dys unc ion and VDD (36). Also, VD may di ec ly p o-
ec endo helial cells agains oxida i e s ess, and
hence, VDD may con ibu e o ED h ough in lamma-
ion (30).
Many ED pa ien s a e VD de icien , pa icula ly
pa ien s wi h a e iogenic ED (5). Epidemiological da a
in humans ha e shown ha VDD is associa ed wi h hy-
pe ension, le en icula hype ophy, inc eased a e-
ial s i ness, and endo helial dys unc ion in no mal
subjec s (30). Men wi h ED ha e an inc eased p e a-
lence o endo helial dys unc ion, and VD may imp o e
endo helial unc ion (14). A placebo-con olled an-
domized ial demons a ed ha e en a single la ge
dose o VD imp o es endo helial unc ion in pa ien s
wi h ype 2 diabe es and VDD (37). Since endo helial
unc ion imp o emen is he co ne s one o he ea -
men o ED, VD supplemen a ion may be bene icial in
he ea men o ED pa ien s.
3. Vi amin-D and ni ic oxide p oduc ion
Ano he impo an mechanism o ac ion o VD
seems o be ia NO media ed ascula dila ion. NO
syn hases (NOS) a e a amily o enzymes ha ca alyze
he p oduc ion o NO om L-a ginine. NO-pa hway is
a well-known physiologic signal essen ial o penile
e ec ion. Sho ly, sexual s imula ion eleases neu o-
ansmi e s om he co pus ca e nosa as well as NO
(a elaxing ac o ) om he endo helial cells o he pe-
nis (28). Any kind o diso de s ha educe NO syn he-
sis o elease in he e ec ile issue a e commonly asso-
cia ed wi h ED. Ac i a ed VD s imula es he p oduc-
ion o NO in endo helial cells and NOS (38), and is a
key o ascula dila ion and he eby c i ical o p e en -
ing ED. Molina i e al (38) demons a ed ha VD is
able o s imula e NO p oduc ion in human umbilical
ein endo helial cells h ough endo helial NOS (eNOS)
ac i a ion.
The inding o an in ol emen o VD in NO p o-
duc ion by endo helial cells is qui e ele an . Recen ly,
And ukho a e al (30) epo ed ha VDR mu an mice
a e cha ac e ized by lowe bioa ailabili y o he aso-
dila o NO due o educed exp ession o he key NO
syn hesizing enzyme i.e., eNOS. Reduc ion in eNOS
ends wi h endo helial dys unc ion, inc eased a e ial
46 No wegian Jou nal o de elopmen o he In e na ional Science No 168/2025
s i ness, inc eased ao ic impedance, s uc u al emod-
eling o he ao a, and impai ed sys olic and dias olic
hea unc ion a la e ages, independen o changes in
he enin-angio ensin sys em (30). This may also cla i y
why endo helium de i ed; NO-e oked dila ion is
hal ed in a e ies om VD de icien male a s (35). Un-
de he ligh o ecen scien i ic esea ches, unsu p is-
ingly, he e exis s a highe p e alence o ED among VD
de icien pa ien s compa ed o hose wi h op imal le els
(14). 4. Vi amin-D and a he oscle o ic ca dio ascu-
la diseases
Penile e ec ion p edominan ly depends on ascu-
la e en and acco ding o se e al s udies he e is a
s ong associa ion be ween ED and ASCV diseases
(39). Un o una ely, VDD is associa ed wi h a he o-
genic dyslipidemia, DM, and educed se um es os-
e one (T) le els all o which a e associa ed wi h endo-
helial dys unc ion and a e classic isk ac o s o he
onse o ED (13, 14, 18).
Recen ly, Ba assi e al (5) demons a ed a highe
p esence o VDD in a e ial ED pa ien s compa ed wi h
non-a e ial-ED pa ien s and a lowe se um VD le els
in mo e se e e ED pa ien s. Melamed e al (33) has
shown ha low se um VD le els a e associa ed wi h a
highe p e alence o pe iphe al a e ial disease in he
gene al popula ion. Addi ionally, an ea lie s udy done
wi h mo e han 7,000 VD de icien pa ien s showed an
associa ion be ween VDD and se e al ca dio ascula
disease (CVD) s a es such as hype ension, co ona y a -
e y disease as well as ASCV isk ac o s (DM,
dyslipidemia e c.) (18). Howe e , a ecen c oss-sec-
ional analysis o 3,390 men aged >20 yea s, ound ha
VDD in indi iduals ee o ASCV diseases was associ-
a ed wi h an inc eased p e alence o ED (14).
The a ailable li e a u e e alua ing VD supple-
men a ion and i s ela ionship o ASCV diseases a e
limi ed in numbe . Howe e , in an obse a ional e o-
spec i e s udy in ol ing mo e han 10,000 pa ien s
Vacek e al (18) showed ha VD supplemen use im-
p o ed su i al in de icien subjec s, suppo ing he po-
en ial bene i o his in e en ion. La e , in a andom-
ized placebo-con olled p elimina y s udy, Al-Dujaili
e al (40) sugges ed ha daily VD supplemen a ion may
amelio a e CVD isk ac o s.
5. Vi amin-D and endoc ine sys em
T modula es nea ly e e y componen in ol ed in
e ec ile unc ion and i s de iciency associa ed wi h ED
(41). In an ageing male popula ion, hypogonadism is
common (30% p e alence in men >60 yea s), and is as-
socia ed wi h ASCV isks (e.g., a he ogenic lipid p o-
ile, insulin esis ance and obesi y) (42) . The Longi u-
dinal Aging S udy Ams e dam, showed se um VD was
posi i ely associa ed wi h o al and bioa ailable T le -
els (43). In ano he s udy, wi h la ge popula ion g oup
(2,854 men), in es iga o s e ealed ha a lowe VD
le el is associa ed wi h a highe p e alence o hy-
pogonadism (44). The la e esul was suppo ed by an-
o he s udy o 652 men o e 40 yea s o age (45). VD
was signi ican ly and posi i ely associa ed wi h T le -
els be o e and a e adjus men o age and e hnici y
(46).
VD is posi i ely associa ed wi h T, exhibi s a con-
co dan seasonal changeabili y (47), ele a es when T
was supplemen ed in hypogonadism (48). Su p isingly,
he e e se si ua ion is also ue, sugges ing ha VD
supplemen a ion migh inc ease T le els (49). In a clin-
ical andomized con olled ial, which is he i s on
his opic in li e a u e, Pilz e al (49) in es iga ed he
e ec o VD supplemen a ion on and ogens in men.
The esul s we e signi ican and he esea che s ob-
se ed ha o e weigh men wi h VDD had a clinically
meaning ul inc ease in se um T le els a e VD supple-
men a ion o 1 yea (49). Recen ly, i was also demon-
s a ed ha VD supplemen a ion imp o es T le els,
me abolic synd ome and e ec ile unc ion in middle-
aged VD de icien men (8). Cangu en e al (8) sup-
po ed ea lie esea ch whe e se um o al-T e ec i ely
inc eased a e VD ea men (49б 50). Likewise, Weh
e al (47) demons a ed ha and ogen le els we e asso-
cia ed wi h VD le els in 2,299 olde men; and also a
c oss-sec ional analysis o men in a na ional su ey
ound ha inc easing VD ends wi h highe o al-T le -
els (51). Ce ainly, i has been ad oca ed ha he mos
ad an ageous se um VD concen a ions begin a 30
ng/mL, and he bes a e be ween 36 o 40 ng/mL (52).
6. Vi amin-D and and ogen ecep o s
An ex a mechanism o VD on e ec ile unc ion
seems o unc ion ia binding o T ecep o s. Compu e
(in silico) modeling shows ha besides ac i a ing he
VDR, 1,25-D displays high a ini y o some o he
body's o he nuclea ecep o s. This sugges s ha when
1,25-D inc eases abo e i s no mal ange, i binds he
α/β hy oid, he glucoco icoid, and he T ecep o s, dis-
placing hei na i e ligands (53). Ma shall (54) showed
he symme y wi h which endogenous ligands exhibi ed
e y simila a ini ies ac oss some membe s o he ype
1 nuclea ecep o amily (54). Fo example, 1,25-D
docked in o he VDR wi h a (nanomola ) Kd o 8.48,
bu also exhibi ed a Kd o 8.05 in o he T ecep o .
7. Vi amin-D and immune sys em
ED is associa ed wi h an inc emen al in lamma-
o y ac i a ion and in lamma ion plays an impo an
pa hophysiological ole in bo h ED and ASCV diseases
(12, 39, 55). I has been ex ensi ely deba ed ha in-
lamma ion can exe a de imen al e ec on he ASCV
sys em ia wo pa hways: ch onic, low-g ade in lam-
ma ion and an acu e sys emic in lamma o y esponse.
The o me has been implica ed in a he oscle o ic p o-
cesses (56), while he la e accoun s o ad e se ASCV
e en s ollowing se e e in lamma o y s imula ion.
Sildena il, one o he phosphodies e ase inhibi o s used
as i s line ea men in ED, induces a signi ican acu e
dec ease in le els o p o-in lamma o y ma ke s/media-
o s (55). The an i-in lamma o y ac ion migh play an
impo an ole in addi ion o elaxa ion o penile
smoo h muscles.
Ding e al (50) e ealed ha VD supplemen may
p o ec he cells h ough supp essing in lamma ion ac-
o s and alle ia ing cell apop o ic dea h, as well o e-
p oduc ion and T syn hesis. Ding e al' s udy (50) indi-
ca ed ha VD played a p o ec i e ole o es es and es-
icula damage induced by diabe es, and he possible
mechanism migh be egula ing a enua ing in lamma-
ion and inac i a ing caspase cascade. Eme ging da a
No wegian Jou nal o de elopmen o he In e na ional Science No 168/2025 47
sugges s ha VD has a po en ial ole in egula ing in-
lamma ion. In esea ch, i was shown ha VD inhibi s
he exp ession o in lamma o y cy okines in mono-
cy es, including in e leukins-1, 6, 8, 12, and umo ne-
c osis ac o -α (57, 58). In summa y, VD may di ec ly
de end endo helial cells agains oxida i e s ess; and
VDD may con ibu e o ED h ough in lamma ion.
Conclusions
Based on he e idence om bench and bed, i was
shown ha VD is impo an o e ec ile unc ion. Meas-
u emen o VD in ED pa ien s is e y c ucial wi h sup-
plemen a ion as equi ed. VD supplemen a ion po en-
ially ep esen s a low-cos , low- isk me hod o ea
and p e en ED. In summa y, we need VD s a ing om
he ea ly emb yonal days o he end o ou li es o a
be e , heal hy and sexually ac i e li e.
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