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DR ANTONY RICHARD YOUNG (Orcid ID : 0000-0002-4163-6772)
Article type : Review Article
Sunscreen photoprotection and vitamin D status
Running head: Photoprotection and vitamin D status
Authors:
T. Passeron1, R. Bouillon2, V. Callender3, T. Cestari4, T. Diepgen5, A.C. Green6, J. van der
Pols7, B.A. Bernard8, F. Ly9, F. Bernerd10, L. Marrot10, M. Nielsen8, M. Verschoore8, N.G.
Jablonski11, A.R. Young12
1- Université Côte d’Azur. Department of Dermatology. CHU Nice & INSERM U1065 team
12, C3M. 150, route de St-Antoine de Ginestière, 06200 Nice, France
2- Schoonzichtlaan 22, Herent 3020, Belgium
3- 12200 Annapolis Rd #315, Glenn Dale, MD 20769, USA
4- Santo Inacio 500 AP 1002, Porto Alegre, 90570-150, Brazil
5- Universität Heidelberg, Klinische Sozialmedizin, Voßstr. 2, 69115, Heidelberg, Germany
6- Cancer and Population Studies Group, Locked Bag 2000, Royal Brisbane Hospital QLD
4029, Australia
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7- Level 4, 88 Musk Avenue, Kelvin Grove, Queensland 4059, Australia
8- L'Oréal R&I, Scientific Directorate, 9 rue Pierre Dreyfus, 92110 Clichy, France
9- University of Medicine and Pharmacy of Dakar and Cheikh Anta Diop University, Dakar,
Senegal
10- L’Oréal R&I, 1 Avenue Eugène Schueller, 93600 Aulnay-sous-bois, France
11- State college, 432 West Shadow Lane, PA 16803-1246, USA
12- King’s College London, St John’s Institute of Dermatology, London SE1 9RT, UK
Corresponding author: Antony Young, King’s College London, London, UK,
antony.young@kcl.ac.uk
Funding sources that supported the work:
This review was financed L’Oréal Company.
Conflict of interest disclosures
BAB, FB, LM, MN, MV are employees of L’Oréal Company. TP has received
grants/funding/speaking fee from Bioderma, Beiersdorf, Galderma, ISDIN, ISIS pharma,
L’Oréal, Pierre Fabre, SVR, Symrise. TC has received grants, funding or speaking fees from
Abbvie, Janssen Cilag, L’Oréal, Sanofi Genzyme and Vichy Laboratories. RB, VC, TD,
ACG, JVP, FL, NGJ and ARY received honoraria from L’Oréal for this project.
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Bulleted statements
What’s already known about this topic?
Knowledge of the relationship between solar exposure behaviour, sunscreen use,
and vitamin D is important for public health but there is confusion about optimal
vitamin D status and the safest way to achieve this. Practical recommendations on
the potential impact of daily and/or recreational sunscreens on vitamin D status
are lacking for healthy people.
What does this consensus add?
Judicious use of daily broad-spectrum sunscreens with high UVA protection will
not compromise vitamin D status in healthy people. However, photoprotection
strategies for patients with photosensitivity disorders that include high SPF
sunscreens with high UVA protection, along with protective clothing and shade
seeking are likely to compromise vitamin D status. Screening for vitamin D
status and supplementation are recommended in this group.
ABSTRACT
Background: Global concern about vitamin D deficiency has fueled debates on
photoprotection and the importance of solar exposure to meet vitamin D requirements.
Methods: An international panel of thirteen experts in endocrinology, dermatology,
photobiology, epidemiology and biological anthropology reviewed the literature prior to a
one-day meeting in June 2017, during which the evidence was discussed. Methods of
assessment and determining factors of vitamin D status, and public health perspectives were
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examined and consequences of sun exposure and the effects of photoprotection were
assessed.
Results: A serum level of ≥ 50 nmol/L 25(OH)D is a target for all individuals. Broad-
spectrum sunscreens, that prevent erythema, are unlikely to compromise vitamin D status in
healthy populations. Vitamin D screening should be restricted to those at risk of
hypovitaminosis, such as patients with photosensitivity disorders, who require rigorous
photoprotection. Screening and supplementation are advised for this group.
Conclusions: Sunscreen use for daily and recreational photoprotection does not compromise
vitamin D synthesis, even when applied under optimal conditions.
Keywords: UV radiation, solar exposure, vitamin D, photoprotection, sunscreen
1 INTRODUCTION
The prevention of rickets and osteoporosis by vitamin D has long been established. More
recently, vitamin D has been implicated in many metabolic and immunological disorders as
well as many cancers. Its pleiotropic activity may be mediated by modulation of ~1000 genes
via the vitamin D receptor (VDR)1,2, which is expressed by at least 60 human cell types3. The
VDR controls many cellular functions including growth, differentiation and apoptosis.
However, the role of vitamin D in the prevention of non-skeletal diseases remains highly
controversial 4-8.
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Terrestrial ultraviolet radiation (UVR) is the main determinant of vitamin D status.
Stratospheric ozone absorbs all solar UVC (100-280nm), attenuates UVB (280-315nm) but
not UVA (315-400nm). The sun’s height determines the UVR pathlength through the ozone
layer. Thus, UVB intensity (irradiance) depends mainly on latitude, season and time of day.
The ratio of UVA to UVB also varies with the sun’s height because of the differential effect
of the ozone layer. Thus, terrestrial UVR contains 5% UVB (~295-315nm) and 95 %UVA.
The minor UVB component is responsible for vitamin D synthesis 9, the initiating event of
which is the isomerization of the epidermal chromophore (a UVR absorbing molecule) 7-
dehydrocholesterol (7DHC) into pre-vitamin D3, which is thermally converted into
cholecalciferol (vitamin D3) 10. Pre-vitamin D3 increases linearly as a function of time of
exposure to UVR (i.e. dose) over a period of 30 min 11. Vitamin D3 enters the circulation via
the vitamin D binding protein (DBP) and is hydroxylated into 25-hydroxyvitamin D3
(25(OH)D3) in the liver (by vitamin D3-25-hydroxylase (CYP2R1), and then in the kidney (by
25(OH)D3-1α-hydroxylase (CYP27B1)) to 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3), the
active form of vitamin D (calcitriol), which in fact is a hormone. However, many tissues
including the skin 12 also contain both hydroxylases for the synthesis of calcitriol.
Multiple intrinsic and extrinsic factors modulate vitamin D synthesis and overall status,
including genetic polymorphisms, age, geographical location, sun exposure behaviour, UVB
dose, clothing, body surface area exposed 13. These are summarized in figure 1 and Appendix
1 of the Supplementary Material. Vitamin D3 may also be obtained from supplementation
and/or animal-based foods (e.g. oily fish) and undergoes the same hydroxylations.
Alternatively, vitamin D2 from non-animal dietary uptake (e.g. mushrooms), is hydroxylated
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into 25(OH)D2 and then converted in 1,25(OH)2D2 (ergocalciferol). However, in general
intake from diet is low. For example, food intake in the US between 2005-2006 in 19-30 year
old males and females was 204 IU 12 (5.1 g) and 144 IU 12 (3.6 g) respectively that
represents 34% and 24% of recommended dietary allowance (RDA) 14.
Solar UVR has many adverse effects, the most obvious of which is sunburn (erythema). The
WHO has defined the global solar UV index (UVI)
(http://www.who.int/uv/publications/en/UVIGuide.pdf) to allow comparisons of erythemal
potential at various geographical locations (latitudes), seasons and times of day 15. This is a
numerical index of the erythemally weighted irradiance of terrestrial UVR. It is divided into
5 bands: “low” (1-2), “moderate” (3-5), “high’ (6-7), “very high” (8-10) and “extreme” (
11). The UVI is primarily an index of UVB irradiance because this spectral region is the main
cause of erythema (see section 3.3.2.1) and sun protection is advised when the UVI is 3 16.
Global concern about vitamin D deficiency has fueled debates on the importance of solar
exposure to meet vitamin D requirements 17-20. The acute and chronic health benefits of using
sunscreens are established 21 but there has been concern about their possible impact on
vitamin D status. An international panel was tasked to review the published evidence to
reach a consensus on the influence of photoprotection by sunscreens on vitamin D status,
considering other relevant factors.
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2 METHODS
The panel comprised experts from diverse disciplines including vitamin D, endocrinology,
dermatology, photoprotection, experimental photobiology, epidemiology and anthropology.
Panel members made a comprehensive search of literature published from January 1996 to
May 2017, using the Scopus database, with the following search term categories individually
and in combination: vitamin D, status, level, values, deficiency, measurement, assay, dosage,
evaluation, polymorphisms, genetics, diet, phototype, pigmentation, lifestyle, location,
latitude, sun, UV, UVR, ultraviolet, health, diseases, sunscreen, photoprotection or sun
protection. Members of the panel used their specific areas of expertise to identify relevant
papers and presented and discussed their results at a meeting in Paris in June 2017. The panel
discussion was recorded by a scientific writer and used as the basis of the manuscript.
Additional 2017-2019 references were included during the writing process. This paper
summarizes the consensus and provides clinical recommendations in terms of
photoprotection in order to ensure optimal vitamin D status.
3 CONCLUSIONS AND RECOMMENDATIONS FROM PANEL DISCUSSIONS
3.1 What is optimal vitamin D status and the best method to determine it?
Serum 25(OH)D is the best indicator of vitamin D status but there is no international
consensus on its optimal value, with recommendations varying from 25 nmol/L to
> 100 nmol/L22 . Figure 2 summarizes the definitions of vitamin D status by various
international bodies. The most widely held consensus for the boundary between insufficiency
and sufficiency is 50nmol/L. According to the Institute of Medicine (IOM)14, a serum
concentration of 50 nmol/L 25(OH)D meets or exceeds the requirement of 97.5% of the US
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population, but it is not possible to specify desired individual status 22. The determination of
vitamin D status is discussed in Appendix 2 of the Supplementary Material.
3.2 Public health perspectives
Hypovitaminosis D is globally prevalent 21,23,24. A systematic review covering 168 000
people from 44 countries reported serum 25(OH)D < 50 nmol/L in 37 % of studies 25. This
was mainly in the Middle East26 and Asia despite high insolation, emphasizing the
importance of human behaviour.
Medical conditions and treatments with high risk of vitamin D deficiency are summarized in
the Supplementary Material (Table 1S). Concern about vitamin D status has resulted in
increased screening with financial consequences 27. Guidelines from The American
Endocrine Society Clinical Practice advise screening only for those at risk of deficiency 28. In
France, the Research and Information Group on Osteoporosis (GRIO) recommends
systematic vitamin D supplementation without screening in everyone over 65 years 29.
Disagreement on recommended doses for vitamin D supplementation arises, in part, from
discrepancies of opinion on optimal serum 25(OH)D levels. The doses recommended for
supplementation are discussed in the Supplementary Material (Appendix 2), but in case of
deficiency, vitamin D supplementation should be 600-800 IU (15-20g)/day (but 400 IU
(10g) in those less than 1 year old) to achieve at least a target serum level of 50 nmol/L.
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3.3 Sunscreens and sun protection indices
Sunscreens are topical formulations that contain chemicals that attenuate solar UVR30,31.
Global regulatory authorities have defined the sun protection factor (SPF) of a sunscreen as a
universal quantitative index of protection against erythema, assessed after a single exposure
of solar simulated radiation (SSR – figure 3a). In effect, the SPF is the ratio of SSR dose
necessary for a minimal erythema dose (MED) with and without sunscreen application. SPF
should be the primary driver of sunscreen choice. These authorities also require UVA
protection (see Section 3.3.2.2). A given sunscreen, applied according to prescribed SPF test
conditions at 2mg/cm2, transmits 1⁄SPF of the erythemally effective UVR. One MED is
equivalent to about 3 standard erythema doses (1 SED = 100J/m2 of erythemally weighted
UVR32) in a fair skinned-person33 . Thus, assuming a possible ambient exposure of 30 SED
during a sunbathing session, the correct use of SPF=20 will allow a sub-erythemal 1.5 SED
to reach the skin. However, people typically apply very much less with a commensurate
reduction of actual labelled SPF. For example, a study of Danes on holiday in Egypt reported
a mean application thickness of 0.79mg/cm2 34. This paradoxically means that sunscreen use
may be associated with sunburn as a result of more time in the sun35,36. Additional protection
factors have been proposed, such as immune protection factor (IPF), DNA protection factor 30
and a protection factor for visible light 37.
3.3.1 The benefits of sunscreens in photoprotection strategies
The acute and chronic adverse effects of solar UVR, especially to those with fair skins, are
well established and can be inhibited by effective sun protection21,24,38,39. This includes (i) sun
avoidance or seeking shade, (ii) clothing and (iii) sunscreen use. When used optimally
sunscreens can prevent erythema during a week-long holiday, even when the UVI is very
high 40. Laboratory studies have shown than sunscreens can prevent UVR-induced
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immunosuppression41 and the formation of DNA damage 42,43 (specifically cyclobutane
pyrimidine dimers (CPD), the action spectrum of which is very similar to erythema 44. CPD
are thought to be important in many skin cancers. Those with cancer prone fair skin are
especially sensitive to CPD formation, whereas the higher melanin content in dark skin
affords much better protection against CPD, especially in the basal layer 45-49. A recent study
with a high SPF sunscreen and high dose SSR for 5 consecutive days showed significant
protection against CPD, even when the sunscreen was applied at 0.75mg/cm2 to simulate
typical use 43. A large Norwegian cohort showed that sunscreen use reduced the risk of
melanoma 50. Extensive randomized controlled trials in Australia, with long-term follow-up,
have demonstrated the protective properties of a sunscreen against photoageing, melanoma,
squamous cell carcinoma (SSC) but not basal cell carcinoma (BCC) 51-55.
3.3.2 Spectral considerations
3.3.2.1 UVB
Action spectroscopy shows that UVB is orders of magnitude more effective than UVA for
erythema 44 (see figure 3b). This means that the SPF is primarily, but is not exclusively, a
measure of UVB protection 30. Such protection is essential when UVB doses are high with
recreational solar exposure, and in countries with high UVI.
3.3.2.2 UVA
There has been an increasing trend over recent years for better UVA protection, with the aim
of designing the ideal “neutral density” sunscreen with “spectral homeostasis” that mimics
shade, i.e. it does not distort the natural solar UVR spectrum56. There is no global standard
for UVA protection and requirements vary with regulatory domain30. The US FDA has
recently proposed greater UVA protection57. A UVA protection factor (UVA-PF) can be
obtained using a sunscreen’s ability to inhibit persistent pigment darkening (PPD) in vivo 58.
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Spectral approaches, based on UVB/UVA absorption ratios and bandwidth cover, give
qualitative but not quantitative information on UVA protection.
UVA irradiance is at least 20-fold greater than UVB in sunlight 59. Furthermore, because
UVA is not attenuated by the ozone layer, it is much less prone than UVB to daily, seasonal
and geographical variation. Efficient UVA protection is highly recommended in recreational
and daily photoprotection strategies, because good UVB protection, that inhibits sunburn,
enables prolonged solar exposure and the accumulation of unnaturally high UVA doses.
UVA1 (340-400nm) preferentially induces CPD in the basal layer that contains stem cells
and melanocytes 60, as well as damaging DNA repair enzymes61. Increasing UVA protection
for a given SPF results in a de facto reduction of UVB protection, which might be expected
to be beneficial for vitamin D synthesis.
Studies in vivo or in 3D skin models, have shown that for a given SPF with a high UVA-PF
sunscreen offers better protection against pigmentation, photoageing and DNA damage
compared to low UVA-PF, and that low SPF sunscreens with high UVA-PF offer such
protection (Table 1) 62-66. One study, on a reconstructed skin model exposed to daily SSR,
showed that a sunscreen with a lower SPF but strong UVA protection was more effective in
preventing photodamage compared to a sunscreen with a higher SPF but low UVA protection
65. Thus, overall there seems to be biological and clinical advantages from increasing UVA
protection for a given SPF.
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3.4 Does photoprotection by sunscreens have an influence on vitamin D status?
3.4.1 Sunscreen use and vitamin D status
Given that solar UVB is the main source of vitamin D67,68, a possible adverse effect of
sunscreen use on vitamin D synthesis has important public health implications. This has been
studied using different approaches described below. Reviews on sunscreen use and vitamin D
synthesis have concluded that sunscreen use is likely to have minimal impact on vitamin D
status9,69,70 even though the action spectra (Fig. 3b) for erythema and pre-vitamin D show
considerable UVB overlap. One reason suggested for this is sub-optimal sunscreen
application that reduces its efficacy. However, little is known about the minimal UVB dose
and exposed BSA requirements to maintain optimal vitamin D status.
Action spectroscopy shows that UVA protection will have no effect on vitamin D synthesis
(figure 3a), although one in vitro study has suggested that UVA2 (315-340 nm) may cause
vitamin D degradation 71, in which case UVA protection may be beneficial for vitamin D
production.
Laboratory and modelling studies have shown that serum 25(OH)D can be increased with
repeated sub-erythemal UVR exposure72-74 ; such doses can be as low as 4 exposures of 0.375
SED over 24% BSA75. A study of Polish children, who did apply sunscreen, on holiday by
the Baltic Sea showed that daily borderline erythemal exposure results in a highly significant
increase of serum 25(OH)D3 76. These studies suggest that vitamin D synthesis occurs with
low UVR doses and therefore sufficient UVR may be transmitted through a sunscreen for
vitamin D synthesis.
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3.4.2 Sunscreen use and vitamin D status in photosensitive patients with strict
photoprotection
Patients with genetic and acquired photosensitivity disorders, and those at risk/with history of
skin cancer are advised to practice strict photoprotection, including sunscreen use. This
population is an ideal group to assess the effects of rigorous photoprotection. Table 2 shows
some of these conditions, in which patients present with low levels of 25(OH)D3 except in
the study of Ulrich et al. 77, in which 25(OH)D3 was > 132.5 nmol/L in 120 organ transplant
patients. However, it is impossible to attribute low serum 25(OH)D3 to a given
photoprotection strategy because more than one was used. Furthermore, for this most part
there were no controls, and supplementation was given in many of the studies. Overall, it is
not possible to use these studies for sunscreen guidance for the general population.
3.4.3 Sunscreen use and vitamin D3 synthesis in studies using non-solar UVR from artificial
sources
Laboratory studies offer an obvious way to study the effects of sunscreens under controlled
conditions. Five studies have shown that sunscreen application (0.5 to 2 mg/cm2) inhibited
the synthesis of vitamin D (Table 3). However, the sources used were mainly UVB-rich
(figure 3a), including non-solar UVB (<295nm) that is very effective at pre-vitamin D
production (Fig. 3b). Figure 3c shows that such non-solar wavelengths have a
disproportionally large effect, and thus do not reflect environmental reality. Of note, one
study showed that 25(OH)D synthesis is dependent on the BSA exposed and application
thickness 78. It was recently shown that sunscreens block cutaneous vitamin D3
(cholecalciferol) production with only a minimal effect on circulating 25(OH)D after a single
narrow-band UVB (~313nm) exposure 79. In general, the UVR dose of these studies is low,
e.g. this was 0.8 MED (estimated to be ~3 SED in skin type III volunteers) with SPF =50 at
2mg/cm2 in the study of Libon et al79 . Taking the SPF at face value means the dose through
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the sunscreen is 3/50 = 0.06 SED. However, it should be noted that labelled SPF value is
specific to SSR sources used for SPF testing that meet certain spectral specifications. The
“actual SPF” with non-solar UVB rich sources may be considerably higher80 than labelled
SPF in sunlight. This means that the labelled SPFs are in fact meaningless. Overall, when
taking photobiological considerations into account, the use of sunscreens with non-SSR
sources cannot provide reliable data on their effect on vitamin D synthesis for public health
purposes. The only way to do such studies reliably would be to use an SSR as used in SPF
testing, or a fluorescent SSR source81. It should be noted that the higher UVB content of SSR
than “typical” terrestrial UVR may also influence results 82. Furthermore, the SSR doses
given should be environmentally realistic and represent a serious challenge to the sunscreen
under test.
3.4.4 Sunscreen use for daily and recreational photoprotection and vitamin D status
3.4.4.1 Questionnaire-based studies
Table 2S (Supplementary material) shows that most questionnaire-based studies report no
correlation between sunscreen use and serum 25(OH)D3 levels. However, two studies showed
a negative correlation and a positive correlation was observed in three studies. The negative
correlation in a Brazilian study, reported that 25(OH)D3 was sufficient (73 nmol/L) in the
sunscreen group 83. Godar et al. reported, from a modelling study, that young Americans
(≤ 19 years) using sunscreen with SPF > 15 had insufficient vitamin D3 status, and concluded
that most American children may not get sufficient solar exposure to meet their minimal
vitamin D requirements 84. One explanation for the positive correlations, including one large
Danish study in 2625 adults and 569 children 85, is increased solar exposure without
erythema.
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Questionnaire based studies have obvious limitations including compliance, unknown
confounding factors, the use of non-sunscreen photoprotection and recall bias. UVR exposure
was based on proxies such as time outdoors.
3.4.4.2 Controlled studies
Controlled field studies with real sun exposure are the best way to determine the effect of
sunscreen use on vitamin D synthesis. Such studies present ethical considerations when
considering control groups because lack of sunscreen use could result in sunburn and
increased skin cancer risk. Results of such studies are shown in Table 4 that reports that most
studies showed no change in serum 25(OH)D3 with sunscreen use 86-88 but two showed
reduction 89,90. These studies mostly ignore the most important factors that influence
outcome, namely personal UVR exposure, sunscreen application thickness and BSA exposed.
Marks et al90, who found no difference between sunscreen and control groups, measured
UVR exposure in the last week of a 7-week study in Australia using polysulphone badge
personal dosimeters. The UVR exposures in the sunscreen and control groups were not
different, but the last week’s exposure is unlikely to have been critical for the outcome
because serum 25(OH)D3 was best predicted in Australian adults by solar exposure 6 weeks
prior to measurement 91.
One factor that has been ignored in all types of study described above, except for the study of
Faurschou et al78, is the effect of baseline 25(OH)D3 on the response to UVR. The lower the
baseline, the greater the response to UVR 92 and this must be considered in the statistical
analyses. A similar observation has been made in vitamin D supplementation studies93.
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A holiday study in Tenerife (Canary Islands) during a week of very high UVI was designed
to take the above factors into account, including a discretionary sunscreen use control group.
This showed that intervention with optimal SPF=15 sunscreen use (2mg/cm2), that inhibited
erythema40 still enabled very considerable vitamin D production94 compared with the
discretionary sunscreen use group that had sunburn. A comparison of high vs. low UVA-PF
showed greater vitamin D synthesis with the former. Thus, optimal UVA+B protection does
not compromise vitamin D increase during recreational exposure. It was estimated that the
daily UVR dose through the sunscreen was 0.4 SED, which is equivalent to 0.1 MED in a
fair-skinned person40. Thus, the UVB doses needed for the biosynthesis of vitamin D3 are
indeed very low. Overall, this study shows that it is possible to have the benefits or solar
exposure while minimizing the risks.
In conclusion, effective sunscreens must attenuate UVB to prevent erythema. In theory, this
should inhibit vitamin D3 biosynthesis. However, the doses of UVB necessary are low (i.e.
substantially sub-erythemal) so that typical sunscreen use does not lead to vitamin D
insufficiency in practice in healthy people. Indeed, even optimal sunscreen use allows good
vitamin D synthesis under high UVI conditions. Better UVA protection for a given SPF
results in a de facto reduction of UVB protection. UVA protection will have no impact on
vitamin D synthesis (see 3b), and indeed may prevent photodegradation. Increased UVB for a
given SPF should in theory and in practice result in better vitamin D synthesis. Studies done
to date have been with lighter skinned individuals, and conclusions may not apply to those
with darker skin types IV-VI who use sunscreens. In such cases, oral supplementation may be
advisable.
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4 SUMMARY
Cutaneous vitamin D3 synthesis is initiated by terrestrial-range UVB and can be achieved
with sub-erythemal exposures to a relatively small BSA. Daily sunscreen use, for non-
intentional solar exposure, is mainly based on products with low SPF and high UVA-PF. This
is unlikely to impact on vitamin D production. In fact, most published studies to date have
shown no association between sunscreen use and vitamin D deficiency, even with regular use
of SPF > 15. Some studies have even reported a positive association between sunscreen use
and 25(OH)D3, suggesting that their use may have increased sun exposure. Indeed, time spent
outdoors and BSA exposed to sun have been positively correlated with vitamin D status.
Overall, other photoprotection behaviour (such as seeking shade, wearing protective clothing
and long sleeves) may have more impact on vitamin D status than sunscreen use. The
recommendations of the panel for daily and recreational photoprotection, as well as the need
for vitamin D screening and supplementation are summarized in table 5.
Acknowledgments: We wish to thank Marielle Romet, PhD and Françoise Nourrit-Poirette,
PhD, from Santé Active Edition, France, who provided medical writing assistance on behalf
of L’Oréal France. We also thank Karl Lawrence PhD for preparing the figures.
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Table 1: Daily photoprotection studies with solar type sources and emphasis on impact
of UVA protection
Summary of main conclusions from laboratory photoprotection studies. DUVR = Daylight UV
radiation with ratio UVA/UVB ~ 27 (96.5 % UVA, 3.5 % UVB) that is more typical of temperate
sunlight compared with solar simulating radiation (SSR) used for SPF testing. FST = Fitzpatrick
skin type. GAG = glycosaminoglycans. SS = sunscreen. Ratio SPF/UVA-PF ≤ 3: well-balanced
UVB-UVA protection (according to EC requirements). Ratio SPF/UVAPF > 3: unbalanced SS with
low UVA protection. The UVA star (*) rating refers to a sunscreen’s UVA:UVB absorbance ratio
(Boots star rating method). The higher the rating, the better the UVA protection with a maximal value
of 5 (that represents a more or less a neutral density sunscreen).
Author,
date
Study
Model
Exposure
Sunscreen
Conclusion
Young et
al., 2007 62
Healthy
volunteers
FST I/II
Daily sub-
erythemal
SSR
exposure (11
days)
Broad spectrum SS
SPF 7.5 UVA 4*
Prevention of DNA
damage, P53
accumulation and
Langerhans cell depletion
Seité et al.,
2010 63
Healthy
volunteers
FST II/III
Daily sub-
erythemal
DUVR
exposure (19
days)
Broad SS SPF 8 UVA-
PF 7 UVA 3*
Prevention of P53 positive
cells, melanin increase,
loss of HLA-DR positive
cells and induction of
dermal modifications
(GAG)
Fourtanier
et al.,
201295
SE Asian
(FST III-V)
and
Indian
volunteers
(FST IV-V)
DUVR
SS with SPF 19, 30
and 50, each with high
and low, each with
high and low UVA-PF
Better inhibition of
pigmentation (at 7 days)
with high UVA-PF (Ratio
SPF/UVAPF ≤3)
Lejeune et
al., 2008, 65
3D human
skin models
DUVR Dose
response (0-
90 J/cm²)
SS with SPF 15 but
high and low UVA-PF
with ratio
SPF/UVAPF ≤3 or >3
High UVA-PF (ratio
SPF/UVAPF ≤3) showed
better prevention of
dermal alterations.
Marionnet
et al., 2012
66
3D human
skin models
DUVR
exposure.
12 J/cm²
SS with SPF 13 and
high UVA-PF (ratio
SPF/UVAPF ≤ 3)
Inhibition of gene
expression for adverse
effects of DUVR
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Table 2: Vitamin D status in photosensitive patients under strict photoprotection
Authors
Pathology
Nb patients
Follow up
Zone/
latitude
Vit D intake
SS use
Vit D status/conclusions
Bogaczewicz et al. 2016
96
SLE n = 104
Controls n = 34
16 weeks
Poland
Lodz
52 °N
After study
Yes + clothing and hats
Summer 25(OH)D 73.2 nmol/L in controls and 56.8
nmol/L in SLE patients
Cusack et al. 2008 97
Cutaneous lupus erythematous
n = 52
FST I-IV
3 months in
summer
Ireland
Dublin
53°N
40.4% took minimum 10
μg/day
4 groups:
SS user
Shade seeker
Non-SS user
Non-shade seeker
25(OH)D 57.9 nmol/L
25(OH)D 58.8 nmol/L
25(OH)D 73.5 nmol/L
25(OH)D 81.8 nmol/L
deLong et al. 2010 98
Skin cancer patients (incl. XP)
n = 144
2 years (Sept-
December period)
USA
Atlanta, Georgia
34oN
94% < 10 µg/day from
diet
60% taking supplements
Adherent or not sun
protection
Mean 25(OH)D of 70 nmol/L in adherent (15% <
50 nmol/L)
Mean 25(OH)D of 73 nmol/L in non-adherent (16% <
50nmol/L)
Gentzsch et al. 2014 99
Gorlin (incl. multiple BCC) n = 1
case report
NA
Germany
Freiburg
48oN
Supplementation initiated
Yes + clothing and shade
seeking
25(OHD) < 10 nmol/L
Hoesl et al. 2010 100
XP n = 15
NA
Germany
Tubignen
49oN
NA
Sun protection
Mean 25(OH)D of 27 nmol/L
Holme et al. 2008 101
Erythropoietic protoporphyria
n = 201
7 months
January/July
UK
51°N-57.5°N
3 took fish liver oil daily
80% shade seeking
68% used SS when
sunny
63% had 25(OH)D < 50 nmol/L.
Kuwabara et al. 2015 102
XP-A n = 21
2 days for vit D
intake
Japan
Kobe
35oN
Mean dietary intake of
4.1 µg/day
SPF > 30
76% had 25(OH)D < 25 nmol/L
Querings et al. 2004 103
XP n = 3
Basal cell Nevus syndrome n = 1
End of winter
Germany
Homburg
49oN
NA
Not specified
Mean 25(OH)D of 23.8 nmol/L
Querings et al. 2006 104
Kidney transplant patients n = 31
Controls n = 31
End of winter
Germany
Homburg
NA
SS + clothing
Mean 25(0H) of 27.3 nmol/L vs. 50.0 nmol/L in controls
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25(OH)D: 25-hydroxyvitamin D; App: application; BCNS: basal cell nevus syndrome; NA: data not available or not applicable; SLE: Systemic Lupus Erythematosus; SS: Sunscreen; XP: Xeroderma Pigmentosum
49oN
Reid et al. 2012 105
Photosensitive patients
n = 165
(of which n = 35 with strict
photoprotection)
1 year
Scotland
Dundee
56oN
Supplements used by
14 patients
Not specified
Mean 25(OH)D of 41.9 nmol/L. 40% with < 50 nmol/L
and 25% with < 25 nmol/L.
Supplementation associated with significantly higher
25(OH)D (57.5 vs. 39.5 nmol/L) and strict vs. sensible
photoprotection associated with lower 25(OH)D (33.4
vs. 42.1 nmol/L)
Sollitto et al. 1997 106
XP n = 8
6 years
USA
7.7 µg/day
SPF > 1 daily
clothing
Mean 25(OH)D of 44.5 nmol/L
Tang et al. 2010 107
BCNS n = 41
FST I-III
NHANES controls n = 360
2 years
USA
All parts
34% daily multivitamin
80% used daily SPF > 15
daily
56% patients with 25(OH)D <50 nmol/L compared with
18% controls
Ulrich et al. 2009 77
Organ transplant patients Applied
SS n = 60
No SS n = 60
2 years
Germany
Berlin
53oN
NA
SPF 50+
2 mg/cm²
Lower 25(OH)D in SS users (132.5 vs. 150.0 nmol/L).
Note these values are very high
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Table 3: Sunscreen use and vitamin D status in studies using normal human volunteers exposed to UVR from artificial sources
In vivo/ ex vivo
Age
UVR source
Dose
Exposed area
SPF
Amount of
sunscreen
Time of assessment
Conclusions/ Points to be
discussed
Faurschou et al, 2012
78
In vivo
n = 37
(18-49 y)
UVB phototherapy
tubes (290-360nm with
peak at 320nm)
4 x 3 SED
2-3 days
interval
25% BSA
(upper front and
back)
SPF 8
0, 0.5, 1.0, 1.5,
2.0 mg/cm²
3 days after final irradiation
Increase of 25(OH)D is dependent on
SS application thickness. All
increases significantly greater than
baseline apart from SS at 2.0 mg/cm2
Matsuoka et al, 1987
108
Ex vivo
(skin from 1 donor)
n = 3 (SS+UVR)
n = 3 (vehicle + UVR)
n= 3 (control)
SSR
1 MED
6.2cm2
NA
5% (w/v) PABA
Pre and post UVR
SS blocked photoisomerization of
stratum corneum 7-DHC
In vivo
n = 8
(n = 4 SS, n = 4
placebo)
(21-45 y)
UVB phototherapy tubes
(260-360nm with peak at
313 nm)
1 MED
Whole body
SPF 8
Cannot say with
confidence
24h, 2h prior UVR, 1,2,3,7,14
days post exposure
Without SS there was a 17-fold
increase in serum vit D peaking at 1
day post-UVR. SS totally blocked
serum vit D increase.
Matsuoka et al, 1990
109
In vivo
n = 27
(23-32 y)
UVB phototherapy tubes
(260-360nm with peak at
313 nm)
Slightly < 1
MED
Six groups with
different SS
application zones:
G1: whole body, G2:
except head & neck
G3: except arms
G4: except trunk
G5: except buttock &
legs, G6: control no
SS
SPF 15
No data
Before and 24h after exposure
In absence of SS there was a ~5-fold
significant increase of serum vit D.
Whole body SS totally blocked vit D
formation. Lack of SS on legs and
trunk allowed significant synthesis.
But synthesis not significant when
arms and head & neck were spared.
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Libon et al, 201779
In vivo
N = 72
(19- 25 y)
Narrow band UVB
phototherapy tubes (311-
313nm)
0.8 MED
Different body areas
with and without SS
SPF 50+
2mg/cm2
Pre and post-UVR up to 5 days
SS use decreased serum 25(OH)D by
8-13% and
Decreased cutaneous vit D by
76-93%
25(OH)D: 25-hydroxyvitamin D; 7-DHC: 7-dehydrocholesterol; MED: Minimal Erythema Dose; NA; not applicable; SED: Standard Erythema Dose; SS: Sunscreen; SSR: Solar-simulated Radiation; vit D: vitamin D
(not 25(OH)D)
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Table 4: Sunscreen use and vitamin D status/outcomes in real sun exposure
(Controlled studies)
Author
Date
n=
(Age)
Location
Latitude
SPF
Assessment
period
Baseli
ne
values
UVR
monitored
Conclusions
Farrerons et al.,
1998 86
n = 24
(71 ± 8 y)
Control n=19
(59 ± 7 y)
Spain
Barcelona,
41oN
SPF 15
2 years, 4 time
points
1,25(OH)2D,
PTH, bone
markers also
measured
yes
no
outdoors
once
daily
25(OH)D significantly
lower in SS users at 3 time
points. Overall, no other
differences*.
Young et al,
201994
Narbutt et al,
201940
n = 79 (34 ± 8
y)
Spain
Tenerife
28°N
Controls
in
Poland
Łódź 52oN
SPF 15
(2mg/cm2)
intervention
i) High
UVA-PF
ii) Low
UVA-PF
Discretionar
y SS use
1-week holiday
in March
yes
yes
personal
electronic
dosimeter
s
measuring
SED
SS SPF 15 (no sunburn)
reduced 25(OH)D
compared to discretionary
use (sunburn) but all
increases highly significant.
Significantly more
25(OH)D with high UVA-
PF SS. No difference in
UVR exposure between
holiday groups
No change in control group
in Poland
Matsuoka et al.,
1988 89
n = 20 (65 ±3 y)
Control n=20
(58 ±3 y)
USA
Springfiel
d 40oN,
Illinois,
Philadelph
ia 40oN
Pennsylva
nia
Not given
Summer after
SS use > 1 year
no
no
25(OH) significantly lower
(44%) than SS group
Azizi et al.,
2012 88
Outdoor male
workers (~40 y)
3 sun protection
intervention
groups
i) Complete
given SS
ii) Partial
iii) Minimal
Israel, 30-
33oN
3 locations
SPF 42
Two successive
winters (8 and 20
months)
no
(samp
les
lost)
yes
Ambient
SED/day
40 ± 10
spring
15 ± 4
winter
25(OH)D not significantly
different at any time or
between any intervention
group
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Farrerons et al.,
2001 87
n = 10
(71 ± 8 y)
Control n = 18
(59 ± 7 y)
Spain
Barcelona
41oN
SPF 15
Two years
Bone mass
yes
no
outdoors
once
daily
No significant differences
between the two groups
Marks et al.,
1995 90
n = 113
(aged ≥ 40 y)
Australia
Maryboro
ugh
37°3 S
SPF 17
Controls
given base
cream
7 months
(after summer)
1,25(OH)2D also
assessed
yes
yes
dosimeter
badges
(last
week)
25(OH)D not significantly
different between groups.
SS group had significantly
lower 1,25(OH)2D but still
in the reference range. No
difference in UVR exposure
between groups
Jayaratne et al,
2012110
N=556 (daily
sunscreen) vs.
n=557
(discretionary
use)
(19-70+ y)
Australia
Nambour
26° S
SPF 15
End of a 4.5-year
RCT
no
no
25(OH)D not significantly
different in daily vs.
discretionary SS use
25(OH)D 25-hydroxyvitamin D, RCT randomized control trial, SS sunscreen, * Significant reduction of bone turnover
marker (osteocalcin) in one autumn measurement
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Table 5: General recommendations
Key Messages
The concentration of serum 25(OH)D is a good indicator of vitamin D status.
Target serum 25(OH)D should be at least 50 nmol/L (20 ng/mL).
Vitamin D status is modulated by many intrinsic and extrinsic factors including
genetic polymorphisms, age, health, sun exposure behaviour, season, latitude,
clothing, and nutrition.
Routine 25(OH)D screening is not recommended for healthy children and adults,
nor systematic oral vitamin D supplementation. However, it should be considered
for people with deeply pigmented skins, those wearing clothing that covers most
of the body, especially during pregnancy, and the elderly, or persons in
institutions.
Daily photoprotection is recommended for all skin phototypes, subject to local
weather conditions and activities. This includes seeking shade, wearing hats and
clothing, using sunglasses and broad-spectrum sunscreen use on exposed skin.
These strategies will help prevent sunburn, skin cancer, and photoageing.
SPF should also be adapted to lifestyle (clothing, outdoor activity, diet). High
UVA-PF is advised in all cases. The panel recommends:
- A daily use of low SPF protection (i.e. SPF 15) with UVA-PF protection in
temperate climates with low UVB in wintertime to inhibit photoageing.
- SPF30 in countries/locations with intense UVB radiation (lower latitudes,
high altitudes) irrespective of season.
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- High SPF and UVA-PF for recreational activities under intense solar
exposure along with, clothing and the use of shade.
Sunscreen use for daily and recreational photoprotection need not compromise
skin vitamin D synthesis, even when applied under optimal conditions. Increasing
the UVA-PF for a given SPF improves vitamin D3 production.
Patients with genetic or acquired photosensitivity disorders require strict
photoprotection. Also, at risk are patients with a history of skin cancer and organ
transplant recipients and those with malabsorption syndromes. Daily SPF50+ with
high UVA protection is strongly recommended for all these patients along with
wearing protective clothing and shade seeking. This makes them prone to vitamin
D deficiency and supplementation and screening is therefore advised for this
population.
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Legends to figures
Figure 1: Factors that affect the synthesis of vitamin D3. Many factors determine
vitamin D3 production. The most important external factor is UVB dose that is the
product UVB intensity (irradiance) and exposure time. Cutaneous pre-vitamin D3 is
synthesized from 7-dehydrocholesterol after UVB exposure. Thermally converted into
vitamin D3, it then binds to vitamin D-binding protein (DBP) in the blood to be activated
sequentially by liver and kidney. Cytochrome P450 (CYP) enzymes are crucial for the
synthesis of biologically active vitamin D3 (calcitriol) that binds to intracellular vitamin D
receptor (VDR) in most cells in the body. Adapted from 111. More details of these factors are
given in the Supplementary Material.
Figure 2: Thresholds of serum 25(OH)D concentration recommended by different
bodies for definitions of vitamin D status (adapted from Bouillon, 201722)
Red = deficiency, orange = insufficiency, green = sufficiency. AAP: American Academy
of Paediatrics, AGS: American Geriatrics Society; DACH: Deutschland, Austria and
Confederation Helvetica; GRIO: French Research and Information Group
on Osteoporosis; IOF: International Osteoporosis Foundation; IOP: Institute of Medicine;
SACN: Scientific Advisory Committee on Nutrition (UK).
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Figure 3: UVR spectra and their interactions with action spectra
a) UVR emission spectra of natural temperate noon summer sunlight (London (51.5oN),
UK), solar simulated radiation (SSR) from a Solar® Light 16S-001 v4.0 (Solar®
Light, Glenside, Pennsylvania) with an emission spectrum compliant for SPF testing
with the International Organization for Standardisation (ISO) Standard 24444 and
Cosmetics Europe 2006) and a UVB phototherapy source (Philips TL20W/12
fluorescent tubes in combination with and without a UVC blocking filter (Kodacel)
that has been widely used in vitamin D studies. Spectra are normalized at 315nm (CIE
boundary between UVB and UVA).
b) CIE action spectra for erythema112 and formation of pre-vitamin D3113.
c) UVR emission spectra weighed for erythema and pre-vitamin D3 using the emission
spectra in Figure 3a and action spectra in Figure 3b. These products give biologically
effective energy and are normalized at 315nm (CIE boundary between UVB and
UVA). Comparisons of the UVB source, with and without Kodacel, weighted with the
pre-vitamin D action spectrum show the large influence of non-solar UVR in many
laboratory studies. Comparisons of the London solar spectrum weighted with the
erythema and pre-vitamin D action spectra show that UVA filters have no influence
on vitamin D production.
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