Ac a De m Vene eol 96
INVESTIGATIVE REPORT
Ac a De m Vene eol 2016; 96: 490–493
© 2016 The Au ho s. doi: 10.2340/00015555-2269
Jou nal Compila ion © 2016 Ac a De ma o-Vene eologica. ISSN 0001-5555
Exposu e o sola ul a iole B adia ion du ing he sum-
me mon hs is he main sou ce o i amin D (VD) o
people li ing in no he n la i udes. The aim o his s udy
was o de e mine whe he a i icial na owband ul a-
iole B (NB-UVB) whole-body exposu es could main ain
VD le els in win e . The in e en ion g oup ecei ed 2
s anda d e y hema doses (SEDs) o NB-UVB exposu es
e e y second week om Oc obe 2013 o Ap il 2014. In
Oc obe 2013 se um 25-hyd oxy i amin D concen a-
ions we e 78.3 nmol/l in he in e en ion g oup (n = 16)
and 76.8 nmol/l in he con ol g oup (n = 18). By Ap il
2014 he concen a ions had inc eased by 11.7 nmol/l
(p = 0.029) in he in e en ion g oup and dec eased by
11.1 nmol/l (p = 0.022) in he con ol g oup. The base-
line VD concen a ion showed a nega i e co ela ion
(p = 0.012) wi h body mass index (BMI). In conclusion, a
sube y hemal NB-UVB dose o 2 SED e e y second week
main ains and e en inc eases se um VD concen a ions
du ing he win e . A high BMI seems o p edispose sub-
jec s o low le els o VD. Key wo ds: 25-hyd oxy i amin D;
ul a iole B; na ow-band ul a iole B; body mass index.
Accep ed Oc 29, 2015; Epub ahead o p in No 3, 2015
Ac a De m Vene eol 2016; 96: 490–493.
Toni Ka ppinen, Depa men o De ma ology, Tampe e
Uni e si y Hospi al, PO Box 2000, FIN-33521 Tampe e,
Finland. E-mail: [email p o ec ed]
Vi amin D (VD) insu iciency is a wo ldwide issue (1).
VD is syn hesized om 7-dehyd ocholes e ol in esponse
o ul a iole B (UVB) adia ion and i s key ole is in
adjus ing he se um calcium le el o enable me abolic
unc ions, signal ansduc ion and neu omuscula ac i-
i y (2). VD insu iciency has been linked o ch onic
skele al (3) and ex a-skele al diseases, such as obesi y
and ype 2 diabe es melli us (4, 5). The bes indica o
o VD s a us is i s ci cula ing o m, 25-hyd oxy i amin
D [25(OH)D] (2). Le els abo e 50 nmol/l a e hough
o be su icien o calcium and bone homeos asis, bu
he op imal le el o ex a-skele al e ec s is unclea
(6). The Ins i u e o Medicine (Washing on DC, USA)
ecommends a die a y in ake o VD supplemen s o 15
µg daily o people aged 1–70 yea s and 20 µg daily o
hose olde han 70 yea s (7). In addi ion o VD supp-
lemen s, a i icial ul a iole B (UVB) ligh ea men s
inc ease VD concen a ions (8). Na owband ul a iole
B (NB-UVB) exposu es gi en 3 imes a week inc ease
se um 25(OH)D concen a ions e en mo e han does 20
µg o 40 µg o al cholecalci e ol daily (9, 10). Bogh e
al. (11) showed ha 1 s anda d e y hema dose (SED) o
b oadband ul a iole B (BB-UVB) e e y second week
can be used o main ain se um 25(OH)D concen a ions
du ing he win e (11). On he o he hand, as NB-UVB
is be e ole a ed (12), widely used (13), and p o ides
a highe i amin D ac ion spec um-weigh ed i adiance
dose (14), we examined i s abili y o main ain summe
le els o i amin D h oughou he win e pe iod.
MATERIALS AND METHODS
Subjec s
Thi y-se en heal hy olun ee s we e andomized o an in e en-
ion g oup (n = 18) o a con ol g oup (n = 19). Inclusion c i e ia
we e: age 18 yea s o olde ; and a oidance o sola ium isi s,
pho o he apy, sunny holidays and i amin D supplemen a ion
du ing a 1-mon h washou pe iod p io o he ial and du ing i .
Exclusion c i e ia we e: p egnancy, skin disease, p e ious skin
cance , in ake o pho osensi izing d ugs; and Fi zpa ick’s skin
eac i e ype 1 (15). Rec ui men began on 1 Sep embe 2013
and he ial was ca ied ou a he Depa men o De ma ology
o Tampe e Uni e si y Hospi al om 7 Oc obe 2013 o 5 May
2014. The p incipal in es iga o assessed he skin ypes o he
olun ee s. VD in ake a he onse was es ima ed by means o
a 3-day ood equency ques ionnai e. Al oge he 34 subjec s
comple ed he ial (Table I). Two in e en ion subjec s we e
disquali ied o ailing o ollow he i adia ion schedule and one
con ol subjec was disquali ied o aking VD supplemen s. All
3 we e excluded om he analyses. The p o ocol was app o ed
by he e hics commi ee o Tampe e Uni e si y Hospi al, and all
he olun ee s ga e hei in o med consen in ad ance.
Randomiza ion and sample size calcula ion
Volun ee s we e andomized o he in e en ion and con ol
g oups in blocks o 2 using a web-based alida ed p og am (Re-
sea ch Randomize (h p://www. andomize .o g)). The p ima y
in es iga o andomized and en olled all he pa icipan s. The
ial was designed o show an in e -g oup di e ence in 25(OH)
D o a leas 12 nmol/l, wi h an α- alue o 0.05 and a β- alue o
0.90. An assumed s anda d de ia ion (SD) o 9 nmol/l o he
Na owband Ul a iole B Exposu es Main ain Vi amin D Le els
Du ing Win e : A Randomized Con olled T ial
Toni KARPPINEN1,2, Me i ALA-HOUHALA1,2, Lasse YLIANTTILA3, Hannu KAUTIAINEN4, Heli VILJAKAINEN5,
Timo REUNALA1 and E na SNELLMAN1,2
1Medical School, Uni e si y o Tampe e, 2Depa men o De ma ology, Tampe e Uni e si y Hospi al, Tampe e, 3Radia ion and Nuclea Sa e y Au ho i y, Helsinki,
4Uni o P ima y Heal h Ca e, Helsinki Uni e si y Cen al Hospi al and Depa men o Gene al P ac ice, Uni e si y o Helsinki, and Uni o P ima y Heal h Ca e,
Kuopio Uni e si y Hospi al, Helsinki and Kuopio, and 5Child en’s Hospi al, Helsinki Uni e si y Cen al Hospi al and Uni e si y o Helsinki, Helsinki, Finland
491
Na owband ul a iole B exposu es main ain i amin D le els
25(OH)D analyses a 50 nmol/l was used. Thus, i was conside ed
necessa y ha 12 olun ee s pe g oup should comple e he ial.
Na owband ul a iole B ea men
The in e en ion g oup ecei ed a o al o 13 NB-UVB whole-
body exposu es, gi en e e y o he week o 24 weeks wi h
a Waldmann UV 7002 cabin equipped wi h 42 TL01 ubes
(Schulze & Böhm, B ühl, Ge many). The i s NB-UVB non-
weigh ed o al UV dose was 170 mJ/cm2 (1 SED), which was
subsequen ly inc eased o 340 mJ/cm2 (2 SED). One SED is
equi alen o an e y hemal e ec i e adian exposu e o 10 mJ/
cm2 CIE (16). The cabin was calib a ed by he Nuclea Sa e y
Au ho i y o Finland using an Ocean Op ics S2000 spec o a-
diome e . A e co ec ion o s ay ligh and o he sys ema ic
e o s, he es ima ed measu emen unce ain y (2σ) o he Ocean
Op ics S2000 is 14% (17) and he measu emen s a e aceable
o he Na ional Ins i u e o S anda ds and Technology, USA.
P e iously measu ed lamp spec a we e used o he NB-UVB
(TL01) and BB-UVB (Waldmann UV6) dose calcula ions (18).
Se um 25-hyd oxy i amin D and pa a hy oid ho mone measu emen s
Blood samples o 25(OH)D analyses we e d awn a he onse ,
and a weeks 6, 14, 20, 26 and 30. Du ing he in e en ion
pe iod he samples o he in e en ion g oup we e aken jus
be o e he scheduled exposu e o UVB. The samples we e
cen i uged and plasma was s o ed a –20°C and analysed o
25(OH)D by enzyme immunoassay (Roche Diagnos ics, Mann-
heim, Ge many). Plasma pa a hy oid ho mone (PTH) samples
we e aken a he onse o he ial and a 14 weeks. Blood was
collec ed in o e hylenediamine e aace ic acid (EDTA) ubes,
cen i uged and analysed by immunochemiluminome ic assay.
S a is ical analysis
Con idence in e als (95% CI) we e ob ained by bias-co ec ed
boo s apping (5,000 eplica ions). S a is ical compa isons we e
made using he analysis o - es co- a iance (ANCOVA). In
he case o iola ion o he assump ions (e.g. non-no mali y)
a boo s ap- ype es was used. Longi udinal measu es o
con inuous ou comes we e analysed using a boo s ap- ype
gene alized es ima ing equa ions (GEE) model, he GEE ha ing
been de eloped as an ex ension o he gene al linea model o
analysing longi udinal and o he co ela ed da a. GEE models
ake in o accoun he co ela ion be ween epea ed measu e-
men s in he same subjec , hey do no equi e comple e da a,
and a i can be achie ed e en when obse a ions o some
indi iduals a e lacking a ce ain ime-poin s. No adjus men
was made o mul iple es ing. When compa ing he inc eases
in VD concen a ions, he model was adjus ed o he baseline
alue, body mass index (BMI) and Fi zpa ick’s skin ype.
Pea son’s χ2- es was used when compa ing nominal da a.
The STATA 13.1, S a aCo p LP (College S a ion, TX, USA)
s a is ical package was used o he analyses.
RESULTS
Vi amin D in ake and NB-UVB exposu es
The mean ± SD daily VD in ake a onse was 7.0 ± 3.7
µg in he in e en ion g oup and 6.7
± 2.2 µg in he
con ol g oup (p = 0.78) (Table I). The in e en ion
g oup ecei ed 13 NB-UVB exposu es o e 24 weeks,
implying a cumula i e NB-UVB dose o 25 SED,
which co esponds o a physical dose o 4.25 J/cm
2
.
No ad e se e ec s we e de ec ed.
Se um 25-hyd oxy i amin D concen a ions
The mean baseline se um VD concen a ion in Oc obe
was 78.3 nmol/l in he in e en ion g oup and 76.8 nmol/l
in he con ol g oup (Table II, Fig. 1) showing a mode-
a e nega i e co ela ion wi h BMI ( = –0.43, p = 0.012).
The mean ± SD concen a ions in he in e en ion g oup
peaked a 104.5
± 40.2 nmol/l in Feb ua y, i.e. in week
20 (Fig. 1), and had a mean inc ease o 11.7 nmol/l
(p = 0.029) by he end o he in e en ion pe iod, in Ap il
(week 26), a which poin he mean o he con ol g oup
had dec eased by 11.1 nmol/l (p = 0.022, Fig. 1, Table
II). The di e ence be ween he g oups was s a is ically
highly signi ican (p < 0.001) when adjus ed o he ba-
seline alue, BMI and Fi zpa ick’s skin ype. Du ing
he 1-mon h ollow-up pe iod he mean concen a ion o
VD in he in e en ion g oup dec eased by 10.6 nmol/l
(p < 0.001) and ha in he con ol g oup by 2.7 nmol/l
(p = 0.18; Fig. 1, Table II).
Pa a hy oid ho mone
concen a ions
The mean
± SD ini ial PTH
le els we e 3.8 ± 1.1 pmol/l
in he in e en ion g oup and
4.2 ± 1.2 pmol/l in he con ol
g oup (p = 0.32), while hose a
week 14 we e 3.7 ± 1.4 pmol/l
and 4.7
± 1.8 pmol/l, espec i-
ely (p = 0.11) (Table I).
Table I. Demog aphics, i amin D in ake and plasma pa a hy oid
ho mone concen a ions a baseline in he na ow-band ul a iole
B (NB-UVB)- ea ed and con ol g oups
NB-UVB
n = 16
Con ol
n = 18 p- alue
Males/ emales, n3/13 1/17 0.32
Age, yea s, mean ( ange) 35 (21–61) 36 (20 –61) 0.76
BMI, kg/m2, mean ± SD 23.0 ± 1.9 25.2 ± 3.4 0.029
Fi zpa ick’s skin ype II/III/IV, n8/7/1 8/10/0 0.61
Vi amin D in ake, µg/day, mean ± SD 7.0 ± 3.7 6.7 ± 2.2 0.78
Pa a hy oid ho mone, pmol/l, mean ± SD 3.8 ± 1.1 4.2 ± 1.2 0.32
BMI: body mass index; SD: s anda d de ia ion.
Table II. Se um 25-hyd oxy i amin D concen a ions in he na ow-band ul a iole B (NB-
UVB)- ea ed and con ol g oups a baseline and a he end o he in e en ion pe iod (week 26)
Se um 25-hyd oxy i amin D (nmol/l)
p- alue
NB-UVB g oup
n = 16
Con ol g oup
n = 18
Baseline (Oc obe 2013), mean ± SD 78.3 ± 36.1 76.8 ± 26.6 0.90a
Week 26 (Ap il 2014), mean ± SD 88.7 ± 29.2 65.8 ± 23.9 0.019a
Change om baseline o week 26, mean (95% CI) 11.7 (1.9 –20.0)b–11.1 (–19.4 o –2.7)c0.0017a
Change om week 26 o 30, mean (95% CI) –10.6 (–15.1 o –5.9)d–2.7 (–6.1–0.8)e0.015a
aNo adjus ed; bp = 0.029; cp = 0.022; dp < 0.001; ep = 0.18.
SD: s anda d de ia ion; 95% CI: 95% con idence in e al.
Ac a De m Vene eol 96
492 T. Ka ppinen e al.
DISCUSSION
The esul s o his s udy show ha an a i icial NB-UVB
exposu e o 2 SED e e y second week main ained VD
concen a ions h oughou he win e , whe eas le els in
he con ol g oup dec eased. No ad e se e ec s we e
obse ed. The NB-UVB dose was small, gi en ha an
a e age Dane ecei es 1.5 SED o sola UV adia ion
daily in July (19). Bogh e al.
(11)
ha e shown ha a
BB-UVB exposu e o 1 SED e e y second week will
main ain summe le els o VD. They ga e 9 BB-UVB
exposu es o e 16 weeks and obse ed a non-signi ican
dec ease o 4.7 nmol/l
om
he baseline concen a ion o
VD o 72.0 nmol/l. In he p esen ial we ga e 13 NB-
UVB exposu es o e 24 weeks and achie ed a signi ican
inc ease o 11.7 nmol/l o e a baseline concen a ion
o VD o 78.3 nmol/l. The dose (2 SED s. 1 SED)
and he leng h o exposu e (24 s. 16 weeks) seem o
be he majo easons o he be e VD esponse in ou
olun ee s, al hough he ac ha he i amin D ac ion
spec um-weigh ed i adiance dose
(14) o an exposu e
o 1 SED is highe wi h NB-UVB (23 mJ/cm
2
CIE) han
wi h BB-UVB (16 mJ/cm
2
CIE) may also ha e had an
e ec . I should be no ed ha he highes concen a ion
o VD was obse ed a week 20 (Fig. 1), be o e he las
3 NB-UVB exposu es we e gi en. The subsequen de-
c ease in concen a ion may ha e been due o nega i e
eedback in he 25(OH)D sys em
(20).
The adminis a ion o UVB i adia ion o e a long
pe iod o ime aises a ques ion ega ding he po en ial
isks ela ed o UV-induced immunosupp ession. The
human ac ion spec um o immunosupp ession peaks
a UVA and UVB wa eleng hs, as measu ed by UV-
induced supp es sion o elici a ion o delayed o con ac
ype hype sensi i i y (CHS) o nickel (21, 22). The mos
sensi i e UVA wa eleng h is 370 nm, whe e he minimum
immunosupp essi e physical dose is 409.4 mJ/cm
2
(21). In
he p esen ial a 1 SED dose was equal o an in eg a ed
non-weigh ed dose o 11 mJ/cm
2
be ween 360 and 390 nm
o bo h NB-UVB and BB-UVB lamps, which is below
he immunosupp essi e dose. In he UVB ange immuno-
supp ession peaks a 300 nm and no immunosupp ession
has been eco ded a 322 nm (22). Wi h a 1 SED dose o
NB-UVB o BB-UVB he minimum immunosupp essi e
dose is no exceeded, bu i could be exceeded wi h a 2
SED dose o ei he NB-UVB o BB-UVB. Howe e , sup-
p ession o he ecall ype (e e en ) immuni y, such as he
pa ch- es ing exis ing nickel alle gy, is jus one possible
end-poin o he immune esponse. O he po en ially mo e
ele an end-poin s a e he supp ession o he induc ion
o ei he local (CHS) o sys emic delayed ype hype sen-
si i i y ( he a e en immuni y) (23, 24). E en hough no
associa ion be ween NB-UVB ea men and skin cance
has been obse ed (25), he e a e no sa e limi s o pho o-
he apy. Wha is “sa e” o one indi idual is no sa e o
ano he (26, 27). Bo h UVB and UVA cause signa u e
mu a ions in DNA, and UVA wa eleng hs p omo e pho o-
aging. As ega ds he mu agenic po en ial o NB-UVB and
BB-UVB, hey appea o be equal (28).
We ound a mode a e nega i e co ela ion be ween
BMI and baseline VD s a us in ou olun ee s. A me a-
analysis has con i med he occu ence o low VD con-
cen a ions among obese subjec s, sugges ing ha he
eason o his may be olume ic dilu ion o 25(OH)
D in he a issue
(29). A high BMI he e o e seems o
p edispose subjec s o VD insu iciency, which in u n
inc eases he isk o con ac ing VD- ela ed diseases
(3–5). The die a y VD in ake was 7.0 µg in he in e -
en ion g oup and 6.7 µg in he con ol g oup. These
in akes we e app oxima ely he same as in ou p e ious
s udy wi h heal hy subjec s
(8), bu emained lowe han
in he ecen na ional su ey ca ied ou in Finland
(30).
Only a ew o he p esen olun ee s we e ecei ing he
es ima ed a e age equi emen o 10 µg die a y VD
daily, and none had eached he ecommended die a y
allowance o 15 µg
(7). I seems ha an addi ional 10
µg VD supplemen is needed o ensu e adequa e VD
s a us in he adul popula ion (7, 31).
We ha e shown p e iously ha egula NB-UVB
exposu es inc ease se um VD concen a ions mo e han
20 µg o o al cholecalci e ol daily (9). In addi ion, NB-
UVB exposu es inc eased he mean VD concen a ion
by as much as 58% in pa ien s wi h pso iasis who we e
ecei ing a 20 µg o al cholecalci e ol supplemen daily
(32). Laguno a e al. (33) compa ed he e ec o VD
supplemen a ion (50 µg o al cholecalci e ol daily) and
10 UVB exposu es o a o al dose o 23.8 SED on VD
concen a ion in a 1-mon h s udy. Bo h in e en ions
inc eased se um 25(OH)D concen a ions simila ly, by
Time, weeks
0 6 14 20 26 30
Se um 25-hyd oxy i amin D, nmoll
-1
0
20
40
60
80
100
120
140
160
180
200
NB-UVB g oup
Con ol g oup
Fig. 1. 25-Hyd oxy i amin D concen a ions in he na ow-band ul a iole
B (NB-UVB)- ea ed and con ol g oups du ing he in e en ion (weeks
0–26) and ollow-up pe iods (weeks 26–30).
Ac a De m Vene eol 96
493
Na owband ul a iole B exposu es main ain i amin D le els
20–25 nmol/l. The o al UVB dose was compa able o
he 25 SEDs gi en in ou s udy, bu he in e en ion
pe iod was only 5 weeks compa ed wi h ou 24 weeks.
In he ollowing commen a y, UV dose- esponse s udies
wi h mo e ca e ul and possibly sa e exposu e p o ocol
we e wa an ed (34). The s eng hs o ou s udy a e he
andomized and con olled design, he long ime- ame
co e ing all win e , and he simila i y o he g oups. A
limi a ion o ou s udy is he need o s anda dize u he
he analy ical me hods o 25(OH)D, as sugges ed by
Volme e al. (35).
Ou goal was o examine he capaci y o low-dose NB-
UVB exposu es o main ain VD concen a ions du ing
he win e . The esul s con i med ha he 2 SED dose
gi en e e y second week om Oc obe o Ap il was
enough o main ain he baseline concen a ions o VD
and e en o inc ease hem, sugges ing ha a NB-UVB
dose o 1 SED migh be app op ia e o his pu pose. A
pa allel compa ison o con inuous NB-UVB exposu es
and he ecommended o al VD supplemen a ion o 10
µg daily du ing he win e should be ca ied ou (7, 31).
In conclusion, a sube y hemal dose o NB-UVB o
2 SED gi en o heal hy subjec s e e y second week
o e he win e mon hs can main ain and e en inc ease
pos -summe VD concen a ions.
ACKNOWLEDGEMENTS
The au ho s would like o hank he pe sonnel o he Depa -
men o De ma ology and Alle gology a Tampe e Uni e si y
Hospi al o hei help in ec ui men and o o ganizing and
pa icipa ing in he ial.
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