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Influenza, solar radiation and vitamin D

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The annual death numbers of influenza and pneumonia in Norway were studied for the time period 1980-2000. No direct relationships were found with the variations of the annual UVB fluences, probably due to the fact that these variations did not exceed 30%. However, there was a very pronounced seasonal variation of both influenza deaths and pneumonia deaths, the vast majority occurring during the winter. Vitamin D levels were also estimated from several publications. The data support the hypothesis that a high vitamin D level, as that found in the summer, acts in a protective manner with respect to influenza as well as pneumonia. The findings are discussed and compared with data from tropical and subtropical areas.
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www.landesbioscience.com Dermato-Endocrinology 307
Dermato-Endocrinology 1:6, 307-309; November/December, 2009; © 2009 Landes Bioscience
BRIEF REPORT
BRIEF REPORT
Dermato-Endocrinology 1:6, 307-309; November/December, 2009; © 2009 Landes Bioscience
*Correspondence to: Asta Juzeniene; Email: asta.juzeniene@rr-research.no
Submitted: 01/21/10; Revised: 01/29/10; Accepted: 02/01/10
Previously published online: www.landesbioscience.com/journals/dermatoendocrinology/article/11357
Introduction
Nearly all human diseases related to respiratory pathogens
exhibit seasonal variations.1,2 The reasons for the seasonality,
however, are still not known. Among the poorly tested hypoth-
esis are: Seasonality of low temperatures, of dry air, of crowding
together indoor in the winter, travelling patterns, vacations, sea-
sonality of ultraviolet (UV) radiation from the sun that might
kill pathogens, circannual rhythms of hormones like the “dark
hormone” melatonin, etc.3 Additionally, the question of whether
it is the host or the vira/bacteria that exhibit seasonality arises.
In the present work we have compared the seasonality of deaths
of influenza and pneumonia in Norway with those of vitamin D
photosynthesis and vitamin D serum levels.
Results and Discussion
Figure 1 shows the seasonal variation of vitamin D formation
in human skin calculated from the known, 1990–2000 average
levels of UV as earlier described,8 using the action spectrum of
Galkin and Terenetskaya.9 The small dip in the curve in June is
related to the cloud cover, which is taken into account. In agree-
ment with earlier work, the vitamin D level is maximal about one
month after the time of maximal formation, which occurs close
to midsummer. This is due to the fact that the vitamin D level
is here determined as the concentration of 25-hydroxyvitamin
D [25(OH)D or calcidiol] in serum and that the formation of
this metabolite from previtamin D, via vitamin D (mainly in the
liver), takes some time. The fact that many have their vacation
in July may also play a role. The observed delay is in agreement
with earlier findings11-14 and has been discussed in these papers.
Inuenza, solar radiation and vitamin D
Johan Moan,1,2 Arne Dahlback,2 LiWei Ma1 and Asta Juzeniene1,*
1Departm ent of Radiation Biolo gy; Institute for Cancer R esearch; the Norweg ian Radium Hospital; Osl o University Hospit al; Montebello, Oslo No rway; 2Institute of Physic s;
Universit y of Oslo; Blindern, Osl o Norway
Key words: vitamin D, influenza, pneumonia, solar radiation, UVB radiation
Abbreviations: 25(OH)D, 25-hydroxyvitamin D; TOMS, total ozone mapping spectrometer; UV, ultraviolet
In fact, the lowest vitamin D level is found in February, and aver-
age levels as low as 25 nmol/l have been observed among women
avoiding direct sun exposure.
In both periods studied (1980–1989 and 1990–1999, Fig. 1),
the death rates are very small in the season when the vitamin D
status is best. The agreement between the death numbers in the
two periods is good. This argues, although only weakly, for the
common assumption that the seasonal variation of influenza is
host related rather than caused by differences in the viral strains
from year to year. This is also in agreement with recent observa-
tions that the same virus strain seems to be present in the hosts
over longer periods, two years or more, but leading to manifest
disease only under favourable conditions, mainly related to host
immune weakening.1,15,16 One might expect variations in the
immune system to play major roles. Vitamin D interacts with
the immune system, essentially strengthening it, in several ways
as reviewed elsewhere.17-19 Other pathways of interaction, like
via circannual rhythms, cannot yet be ruled out.20 The preven-
tive effect of vitamin D supplementation has been demonstrated
also in intervention studies.21 Furthermore, Ginde et al. found
that the serum levels of vitamin D were inversely associated with
upper respiratory tract infections,22 and it seems that exposure to
artificial UVB radiation has a protective effect.23 We, therefore,
propose that the seasonal variation of influenza death numbers is
related to the seasonal variation of vitamin D status.
An argument against this proposal from our data might be
that the influenza death rates start to increase almost two months
after the vitamin D levels have reached their minimum (Fig. 1).
However, one should remember that our register gives time-
points for death, not for disease initiation. A delay of weeks is
quite likely. Similarly, the death numbers start to decrease several
The annual death numbers of inuenza and pneumonia in Norway were studied for the time period 1980–2000. No direct
relationships were found with the variations of the annual UVB uences, probably due to the fact that these variations
did not exceed 30%. However, there was a very pronounced seasonal variation of both inuenza deaths and pneumonia
deaths, the vast majority occurring during the winter. Vitamin D levels were also estimated from several publications.
The data support the hypothesis that a high vitamin D level, as that found in the summer, acts in a protective manner
with respect to inuenza as well as pneumonia. The ndings are discussed and compared with data from tropical and
subtropical areas.
308 Dermato-Endocrinology Volume 1 Issue 6
synthesis in human skin is about five times larger in late June
than in late December. Sometimes secondary peaks are observed
in June–August.15,3 3 These peaks may be caused by other cli-
matic factors than those directly related solar elevation.34 Thus,
cloud cover is likely to be involved since it will influence both
humidity and UV penetration through the atmosphere. It seems
that that many respiratory syncytial virus epidemics begin in
coastal areas.35
Variations of the ambient UVB level have sometimes been
proposed as factors related to influenza periods.36 -38 However,
we have earlier shown that influence of variations of cloud cover
on the annual UVB fluence is more than three times as large
as that of variations of ozone levels.39,40 Furthermore, during a
sunspot cycle (about 11 years) the UVB fluence varies less than
1%.39,41,4 2
In conclusion, our data are in agreement with the assumption
that the high numbers of winter influenza and pneumonia deaths
in Norway are related to low vitamin D levels in this season.
Materials and Methods
Influenza and pneumonia deaths. The numbers of monthly
influenza and pneumonia deaths were calculated by Prof. ystein
Kravdal from individual data provided by Statistics Norway. The
numbers are averaged over the years 1980–1989 and 1990–1999.
months before the vitamin D level starts to increase significantly.
This is likely to be related to induction of better immunity. Thus,
influenza pandemies, starting outside the classical winter influ-
enza season, have a duration of not more than a few months, but
also in the case of classical pandemies, like the Spanish flu, 1918–
1919, there came a winter wave after the initial wave.24 The first
wave peaked in 1918, in October 19th in Baltimore, in October
26th in Augusta and in November 5th in San Francisco (an east–
west wave), while the secondary wave came January 1919.
In future work other factors than vitamin D, essentially those
mentioned in the introduction, should be taken into account.
Out of these temperature and humidity may be the most impor-
tant ones.25 -28
Variation of summer UVB levels over the two decades, from
1980 to 2000, as shown in Figure 2, upper panel, are signifi-
cant. For instance, from 1997 to 1998 there was a 20% decrease
in the level. Annual numbers of influenza deaths do not reflect
the variations of the UVB levels. This may be due to that the
UVB variations are too small, notably in view of the fact that
summer levels of vitamin D are not more than 30–50% higher
than winter levels. Thus, a 20% decrease in summer UVB
level would result in only a small overall decrease in vitamin D
level, probably too small to influence the immunity next winter
significantly.
Norway is localized from 58 to 70 degrees north, vitamin
D being synthesized in skin exclusively in the summer months.
It is, therefore, of interest to compare our data with data from
tropical and subtropical regions. Generally, there is no distinct
seasonal pattern in the tropics.30 -32 In Singapore small peaks
were found in June–July and in November–January, coincid-
ing with the winter in the Southern and northern hemisphere,
respectively.30 At latitudes between 20 and 30 degrees north,
clear winter seasons of influenza are found.15,3 3 This is at first
sight surprising. However, we have calculated by the methods
described above, that at 25 degrees north the rate of vitamin D
Figure 1. Seasonal variations of serum levels of vitamin D () in the
Nordic countries, given as averages from three reports in ref. 9. Photo-
synthesis of vitamin D for Southern Norway () is calculated by use of
the action spectrum in ref. 7, UV measurements in Oslo and radiative
transfer calculations using a cylinder model as described in the text.
The results are presented in relative units (rel. u.). Inuenza deaths in
two periods (, ) in Norway are also given.
Figure 2. Upper: The UVB levels in Norway in the period 1980–2000.29
In this case the UVB uences were determined for a horizontal plane
with the CIE erythema spectrum, which is UVB weighted and very close
to the vitamin D spectrum used in the rest of this work. Lower: The av-
erage number of inuenza and pneumonia deaths per year in Norway
in the same period.
www.landesbioscience.com Dermato-Endocrinology 309
in converting 7-dehydrocholesterol to previtamin D.9 Br iey,
an efficiency spectrum is calculated by multiplying the inten-
sity of the solar radiation (wavelength by wavelength) with
the action spectrum for the vitamin D production for the cor-
responding wavelength. The vitamin D action spectrum was
taken from the publication of Galkin and Terenetskaya9 which
is similar to that measured by MacLaughlin et al. in ex vivo
skin specimens.10
The vitamin D levels in different seasons are taken from an
earlier publication11 and are averages from three different experi-
mental Nordic series described there.
Acknowledgements
We want to thank ystein Kravdal from the Institute of
Economy (Oslo University, Norway) for calculating the number
of deaths of influenza and pneumonia. Direct overpass TOMS
data were provided by NASA/GSFC.
It may be difficult know if the influenza deaths are caused directly
by influenza or by secondary diseases.
Solar exposure and seasonal vitamin D formation. The main
factors influencing the UV irradiances at ground level are solar
zenith angle (variable with season, latitude and time of day),
cloud and snow cover and the thickness of the ozone layer.4
In this study, the solar UV exposures were calculated using
a radiative transfer model.5,6 Total ozone amounts used in this
model were measured by the Total Ozone Mapping Spectrometer
(TOMS) satellite instruments. The daily cloud cover was derived
from measured reflectivities by TOMS instruments and ground-
based UV measurements in Oslo. A cylinder geometry of the
human body was used. The arguments for this choice have been
presented earlier.7, 8
The results are presented as vitamin D forming U V doses.
The efficiency spectrum for vitamin D production gives the
relative effectiveness of solar radiation at different wavelengths
References
1. Dowell SF, Ho MS. Seasonality of infectious diseases
and severe acute respiratory syndrome-what we don’t
know can hurt us. Lancet Infect Dis 2004; 4:704-8.
2. Eccles R. An explanation for the seasonality of acute
upper respiratory tract viral infections. Acta Otolaryngol
2002; 122:183-91.
3. Monto AS. Global burden of influenza: what we know
and what we need to know. Int Congr Ser 2004;
1263:3-11.
4. Madronich S, McKenzie RL, Bjorn LO, Caldwell MM.
Changes in biologically active ultraviolet radiation
reaching the Earth’s surface. J Photochem Photobiol B
1998; 46:5-19.
5. Stamnes K, Tsay SC, Wiscombe WJ, Jayaweera K.
Numerically stable algorithm for discrete-ordinate-
method radiative transfer in multiple scattering and
emitting layered media. Appl Opt 1988; 2509-27.
6. Dahlback A, Stamnes K. A new spherical model for
computing the radiation field available for photolysis
and heating rate at twilight. Planet Space Sci 1991;
39:671-83.
7. Moan J, Dahlback A, Porojnicu AC. At what time
should one go out in the sun? Adv Exp Med Biol 2008;
624:86-8.
8. Moan J, Dahlback A, Lagunova Z, Cicarma E,
Porojnicu AC. Solar radiation, vitamin D and cancer
incidence and mortality in Norway. Anticancer Res
2009; 29:3501-9.
9. Galkin ON, Terenetskaya IP. ‘Vitamin D’ biodosim-
eter: basic characteristics and potential applications. J
Photochem Photobiol B 1999; 53:12-9.
10. MacLaughlin JA, Anderson RR, Holick MF. Spectral
character of sunlight modulates photosynthesis of
previtamin D3 and its photoisomers in human skin.
Science 1982; 216:1001-3.
11. Moan J, Porojnicu AC, Robsahm TE, Dahlback A,
Juzeniene A, Tretli S, Grant W. Solar radiation, vita-
min D and survival rate of colon cancer in Norway. J
Photochem Photobiol B 2005; 78:189-93.
12. Beadle PC, Burton JL, Leach JF. Correlation of seasonal
variation of 25-hydroxycalciferol with UV radiation
dose. Br J Dermatol 1980; 103:289-93.
13. Brot C, Vestergaard P, Kolthoff N, Gram J, Hermann
AP, Sorensen OH. Vitamin D status and its adequacy in
healthy Danish perimenopausal women: relationships
to dietary intake, sun exposure and serum parathyroid
hormone. Br J Nutr 2001; 86:97-103.
14. Moan J, Porojnicu A, Lagunova Z, Berg JP, Dahlback
A. Colon cancer: prognosis for different latitudes, age
groups and seasons in Norway. J Photochem Photobiol
B 2007; 89:148-55.
15. Shih SR, Chen GW, Yang CC, Yang WZ, Liu DP, Lin
JH, et al. Laboratory-based surveillance and molecular
epidemiology of influenza virus in Taiwan. J Clin
Microbiol 2005; 43:1651-61.
16. Tang JW, Ngai KL, Lam WY, Chan PK. Seasonality
of influenza A(H3N2) virus: a Hong Kong perspective
(1997–2006). PLoS One 2008; 3:2768.
17. Cannell JJ, Vieth R, Umhau JC, Holick MF, Grant
WB, Madronich S, et al. Epidemic influenza and vita-
min D. Epidemiol Infect 2006; 134:1129-40.
18. Cannell JJ, Zasloff M, Garland CF, Scragg R,
Giovannucci E. On the epidemiology of influenza.
Virol J 2008; 5:29.
19. Grant WB, Giovannucci E. The possible roles of solar
ultraviolet-B radiation and vitamin D in reducing case-
fatality rates from the 1918–1919 influenza pandemic
in the United States. Dermato-Endocrinology 2009;
1:215-9.
20. Dowell SF. Seasonal variation in host susceptibility and
cycles of certain infectious diseases. Emerg Infect Dis
2001; 7:369-74.
21. Aloia JF, Li-Ng M. Re: epidemic influenza and vitamin
D. Epidemiol Infect 2007; 135:1095-6.
22. Ginde AA, Mansbach JM, Camargo CA Jr. Association
between serum 25-hydroxyvitamin D level and upper
respiratory tract infection in the Third National Health
and Nutrition Examination Survey. Arch Intern Med
2009; 169:384-90.
23. Fleming DM, Elliot AJ. Epidemic influenza and vita-
min D. Epidemiol Infect 2007; 135:1091-2.
24. Britten RH. The incidence of epidemic influenza,
1918–1919. Pub Healht Rep 1932; 47:303-39.
25. Liao CM, Chang SY, Chen SC, Chio CP. Influenza-
associated morbidity in subtropical Taiwan. Int J Infect
Dis 2009; 13:589-99.
26. Nafstad P, Skrondal A, Bjertness E. Mortality and
temperature in Oslo, Norway, 1990–1995. Eur J
Epidemiol 2001; 17:621-7.
27. Lowen AC, Mubareka S, Steel J, Palese P. Influenza
virus transmission is dependent on relative humidity
and temperature. PLoS Pathog 2007; 3:1470-6.
28. Lowen A, Palese P. Transmission of influenza virus in
temperate zones is predominantly by aerosol, in the
tropics by contact: A hypothesis. PLoS Curr Influenza
2009; Aug 17:RRN1002.
29. Moan J, Porojnicu AC, Dahlback A. Epidemiology
of cutaneous malignant melanoma. In: Ringborg U,
Brandberg Y, Breitbart EW, Greinert R, ed. Skin cancer
prevention. New York: Informa Healthcare 2007; 179-
201.
30. Shek LP, Lee BW. Epidemiology and seasonality of
respiratory tract virus infections in the tropics. Paediatr
Respir Rev 2003; 4:105-11.
31. Chew FT, Doraisingham S, Ling AE, Kumarasinghe G,
Lee BW. Seasonal trends of viral respiratory tract infec-
tions in the tropics. Epidemiol Infect 1998; 121:121-
8.
32. Doraisingham S, Goh KT, Ling AE, Yu M. Influenza
surveillance in Singapore: 1972–86. Bull World Health
Organ 1988; 66:57-63.
33. Suzuki Y, Taira K, Saito R, Nidaira M, Okano S, Zaraket
H, et al. Epidemiologic study of influenza infection in
Okinawa, Japan, from 2001 to 2007: changing patterns
of seasonality and prevalence of amantadine-resistant
influenza A virus. J Clin Microbiol 2009; 47:623-9.
34. Viboud C, Pakdaman K, Boelle PY, Wilson ML, Myers
MF, Valleron AJ, et al. Association of influenza epi-
demics with global climate variability. Eur J Epidemiol
2004; 19:1055-9.
35. Stensballe LG, Devasundaram JK, Simoes EA.
Respiratory syncytial virus epidemics: the ups and
downs of a seasonal virus. Pediatr Infect Dis J 2003;
22:21-32.
36. Ertel S. Influenza pandemics and sunspots—easing the
controversy. Naturwissenschaften 1994; 81:308-11.
37. Vaquero JM, Gallego MC. Sunspot numbers can detect
pandemic influenza A: the use of different sunspot
numbers. Med Hypotheses 2007; 68:1189-90.
38. Hayes DP. Influenza pandemics, solar activity cycles
and vitamin D. Med Hypotheses 2009.
39. Moan J. Visible Light and UV radiation. In: Brune D,
Hellborg R, Persson BRR, Paakkonen R, ed. Radiation
at Home, Outdoors and in the Workplace. Oslo:
Scandinavian Publisher 2001; 69-85.
40. Moan J, Dahlback A. Ultraviolet Radiation and Skin
Cancer: Epidemiological Data from Scandinavia. In:
Young AR, Bjorn LO, Moan J, Nultsch W, ed.
Enviromental UV Photobiology. New York and
London: Plenum Press 1993; 255-93.
41. Lean J. Solar ultraviolet irradiance variations. J Geophys
1987; 92:839-68.
42. Rottman G, Woods T, Snow M, DeToma G. The solar
cycle variation in ultraviolet irradiance. Adv Space Res
2001; 27:1927-32.
... In detail, solar UV dampens the production and development of T-cells (CD4+ CD25+ foxp3+ cells) as well as activating regulatory B-cells which further suppress activation of T-cells [90][91][92]. High human sensitivity to UV is evidenced by deaths from pneumonia fluctuating with sunspots [93]. Our findings are supported by the fact that influenza pandemics caused by novel viruses occurred during the summer when the NH would be receiving above average solar radiation. ...
... This can be explained by a lack of vitamin D hindering activation of the immune system. Indeed, there is a growing body of evidence that vitamin D can be immunosuppressive if its quantity is either too low or too high [93,94]. The traditional Chinese diet lacking dairy is likely low in vitamin D and may have promoted winter emergence in Wuhan. ...
... However, vitamin D was no longer recommended by summertime [98]. These results are consistent with certain ranges of UV and vitamin D each being beneficial to immune response, whereas shortages and excesses have converse effects [93,94]. ...
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... Previous work on adults who are affected by influenza viruses has shown that they also exhibit a higher incidence of hypovitaminosis due to factors that affect vitamin D metabolism such as the efficiency of skin at synthesizing vitamin D or reduced renal production of the active form of vitamin D, 1,25(OH)2D [50]. An observational study done between 1980 and 2000 in Norway found that influenza-related mortality during the colder season was linked to the low level of vitamin D among people [51]. An observational study conducted on school children investigated the effects of vitamin D supplementation in the prevention of influenza A infection during the winter season when the incidence of flu is much higher. ...
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