Hypovitaminosis D in British adults at age 45 y: nationwide cohort study of dietary and lifestyle predictors
Elina Hyppönen and Chris Power
ABSTRACT
Background: Increased awareness of the importance of vitamin D to health has led to concerns about the prevalence of hypovitaminosis D in many parts of the world.
Objectives: We aimed to determine the prevalence of hypovitaminosis D in the white British population and to evaluate the influence of key dietary and lifestyle risk factors.
Design: We measured 25-hydroxyvitamin D [25(OH)D] in 7437 whites from the 1958 British birth cohort when they were 45 y old.
Results: The prevalence of hypovitaminosis D was highest during the winter and spring, when 25(OH)D concentrations_25,_40, and _75 nmol/L were found in 15.5%, 46.6%, and 87.1% of participants, respectively; the proportions were 3.2%, 15.4%, and 60.9%, respectively, during the summer and fall. Men had higher 25(OH)D concentrations, on average, than did women during the summer and fall but not during the winter and spring (P_0.006, likelihood ratio test for interaction). 25(OH)D concentrations were significantly higher in participants who used vitamin D supplements or oily fish than in those who did not (P _ 0.0001 for both) but were not significantly higher in participants who consumed vitamin D–fortified margarine than in those who did not (P_0.10). 25(OH)D concentrations_40 nmol/L were twice as likely in the obese as in the nonobese and in Scottish participants as in those from other parts of Great Britain (ie, England and Wales) (P _ 0.0001 for both).
Conclusion: Prevalence of hypovitaminosis D in the general population was alarmingly high during the winter and spring, which warrants action at a population level rather than at a risk group level. Am J Clin Nutr 2007;85:860–8.
KEY WORDS 25-Hydroxyvitamin D, vitamin D status, vitamin D supplements, vitamin D deficiency, seasonality, fortified food, population studies, Great Britain
INTRODUCTION
The thinking about the actions of vitamin D have made an important shift during the past 10 y. In addition to its well established role in the regulation of calcium metabolism, the active form of vitaminD has been shown to have antiproliferative and immunomodulatory effects that are thought to influence the development of several serious conditions, including diabetes,
cardiovascular disease, and cancer (1– 6). Vitamin D is a nutrient that functions as a hormone precursor, and wide-ranging health
effects are supported by the presence of vitamin D receptors in
several cell types and tissues of the body (eg, lymphocytes and
monocytes, brain, heart, pancreas, intestine, and placenta; 2).
With this increasing knowledge, a reconsideration of the cutoffs
for adequate vitamin D status has occurred. 25-Hydroxyvitamin
D [25(OH)D] is the best available indicator for vitamin D status
(7), and concentrations_25 nmol/L are sufficient to prevent the
severe hypovitaminosis D that leads to softening of bone tissue,
which manifests as rickets in children and as osteomalacia in
adults (1, 4, 8). Furthermore, it is now understood that even less
severe forms of hypovitaminosis D have short- and long-term
health implications, and accordingly, in a recent consensus statement,
concentrations of _75 nmol/L were identified as necessary
for optimum bone health (9). This cutoff was based on a
threshold required for a range of functional outcomes, including
maximal suppression of circulating parathyroid hormone, greatest
calcium absorption, and highest bone mineral density.
Concerns exist that hypovitaminosis D may be common in
many parts of the world; some discussion has been held of possible
epidemics in Western populations, and calls have been
heard for screening of vitamin D status in routine health care
surveillance (2). We aimed to evaluate the magnitude of hypovitaminosis
D as a public health problem in Great Britain (ie,
England, Scotland, and Wales), because several reasons exist for
suspicion that it is particularly prevalent there. Skin synthesis of
vitaminD(the major source of the vitamin) is likely to be affected
by Western lifestyles, which increasingly involve working indoors
during daylight hours, and this may be particularly important
when combined with residence in northern latitudes and a
cloudy climate (10). Moreover, dietary intake of vitamin D may
be low in Great Britain, where vitamin D fortification is mandatory
only for margarine. This situation contrasts with that in other
countries, such as the United States and Canada, where milk is
also fortified (11). With the exception of oily fish, most foods
naturally contain very little vitaminD(2, 3). Intake in the form of
supplements is limited to the availability of over-the-counter
products. Finally, the high prevalence of obesity in Great Britain
1 From the Centre for Paediatric Epidemiology and Biostatistics, Institute
of Child Health, London, United Kingdom.
2 Supported by grant no. G0000934 from theUKMedical Research Council
(for data collection), by the BUPA Foundation (for the vitamin D substudy),
by a UK Department of Health Public Health Career Scientist Award
(to EH), and by the National Health Service (NHS) Executive (for research
at the Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust).
3 Reprints not available. Address correspondence to E Hyppönen, Centre
for Paediatric Epidemiology and Biostatistics, Institute of Child Health,
30 Guilford Street, WC1N 1EH London, United Kingdom. E-mail:
e.hypponen@ich.ucl.ac.uk.
Received July 19, 2006.
Accepted for publication October 10, 2006.
860 Am J Clin Nutr 2007;85:860–8. Printed in USA. © 2007 American Society for Nutrition
(12), a well-known risk factor for hypovitaminosis D (13, 14),
may adversely affect vitamin D status in the population.
Alarmingly high rates of hypovitaminosis D have been found
in ethnic minorities living in Great Britain (15–17). Case reports
document a reemergence of rickets in infants (18), children (19),
and adolescents (20); in addition, hypovitaminosis D is common
in the elderly, particularly those living in institutions (21, 22).We
measured serum 25(OH)D in 2002–2004 in a nationwide sample
of whites (aged 45 y)whoare participants in the 1958 birth cohort
study. Our aims here were to report current prevalence rates and
to examine seasonal, demographic, and lifestyle influences on
hypovitaminosis D.
SUBJECTS AND METHODS
Subjects
Participants are from the 1958 British birth cohort; all were
born in England, Scotland, or Wales during the same week of
March 1958 (n _ 16 751; 23, 24). Cohort members were most
recently contacted between September 2002 and April 2004 (24).
The target population for this survey consisted of 12 069 persons
currently living in Great Britain. Seventy-eight percent (n _
9349) of participants completed questionnaires, and 7591 (81%)
also provided a blood sample, which was used to determine their
vitamin D status. The cohort is mainly white (98%); immigrants
born during the target week were included in the birth cohort
study only up to 1974. The current study is restricted to whites
(including British, ethnically Irish living in Great Britain, and
other whites); persons of other ethnic origins (n _ 154) were
excluded.
Written informed consent for the use of information in medical
studies was obtained from the cohort members. The 2002–2004
survey was approved by the South-East Multi-Centre Research
Ethics Committee.
Methods
Weight and standing height at age 45 y were measured without
shoes and in light clothing by the nurse using scales and a stadiometer.
Body mass index (BMI; in kg/m2) was calculated, and
obesity was defined as BMI_30. The season in which the blood
sample was obtained was classified as winter (December through
February), spring (March through May), summer (June through
August), and fall (September through November). Geographic
location was based on current region of residence, which, for
presentation and analyses of north-south gradient, was grouped
as follows (denoted by using the standard British terminology for
regional boundaries in Great Britain): South (South East, South
West, and Greater London), Middle (East Anglia, Midlands, and
Wales), North (North, North West, and Yorkshire and the Humber),
and Scotland. Socioeconomic status (SES) was assessed by
using the Registrar General’s occupational classification based
on current or most recent occupation at age 42 y and categorized
as I and II (professional and managerial), III (skilled) nonmanual,
III (skilled) manual, and IV and V (partly skilled and unskilled).
Persons who were institutionalized, retired, or unemployed over
a long period were classified separately (n _ 319; 4.3%).
Information on selected dietary and lifestyle influences on
25(OH)D was collected by using a structured food-frequency
questionnaire (FFQ). Frequencies of dietary intake were reported
as never, occasionally, _1 d/wk, 1–2 d/wk, 3–6 d/wk, 1 time/d,
1–4 times/d, and _4 times/d. Consumption of oily fish (eg,
salmon, trout, and mackerel) was classified as weekly, less than
weekly, and never, and margarine use was classified as daily,
weekly, and less than weekly. Vitamin D fortification of margarine
(7.05– 8.82 _g/100 g) is mandatory in the United Kingdom
(25). Participants reported their use of cod liver or fish oil or other
supplements containing vitamin D [typical vitamin D concentration
in over-the-counter supplements sold in the United Kingdom
(D3 orD2) is 200 IU]. The usual time per day spent outdoors
in daylight hours during the previous month was reported as no
time,_15 min, 15–30 min, 30–60 min, 1–2 h, 3–4 h, and_4 h.
Protection of skin with the use of sunscreen or clothing during
sunny weather in the United Kingdom or abroad was reported as
“often,” “sometimes,” “rarely,” and “never.” Information on holidays
outside of Great Britain was not available. Skin color (inner
arm) was reported as light (white, fair, or ruddy), medium (olive
or light or medium brown), and dark (dark brown or black).
Participants reported the average time per day that they watched
television (TV) or used a personal computer (PC) as none,_1 h,
1–2 h, 2–3 h, 3–4 h, and_4 h; data from these separate questions
were combined for the current analyses.
Measurement of vitamin D status
25(OH)D was measured by using automated application of an
enzyme-linked immunosorbent assay (IDS OCTEIA Elisa; IDS,
Bolton, United Kingdom) and an analyzer (BEP 2000; Dade-
Behring, Milton Keynes, United Kingdom) with sensitivity of
5.0 nmol/L, linearity_155 nmol/L, and intraassayCV5.5–7.2%
(26, 27). The heterogeneity of 25(OH)D concentrations measured
by different assay methods is well known (7, 28). To apply
previously recommended cutoffs for hypovitaminosis D,
25(OH)D concentrations were standardized according to the
mean of the values found by the Vitamin D External Quality
Assurance Survey (DEQAS) of _100 laboratories around the
world (9, 28). Standardization was based on quality-control data
compared on 5 occasions during the study period; evaluations
were conducted at the start of the fieldwork and then at 3-mo
intervals. Hypovitaminosis D was defined by using 3 thresholds
for 25(OH)D concentrations: _25, _40, and _75nmol/L. Cutoffs
were selected on the basis of 1) concentrations sufficient to
prevent rickets and osteomalacia (ie,_25 nmol/L) (1, 4, 8); 2) a
lower reference concentration suggested to reflect the need for
vitamin D supplementation according to most laboratories carrying
out vitamin D assays (ie, _40 nmol/L) (3, 28); and 3)
current judgment as to the concentration required for optimal
bone health (ie, _75 nmol/L) (4, 9).
Statistical analysis
Natural log transformation was used to achieve normal distribution
for 25(OH)D. Log-transformed values were used in calculating
geometric means and for determining the outcome in
linear regression analyses. For descriptive purposes, mean
25(OH)D concentrations and the proportion of persons with hypovitaminosis
D are presented after standardization by sex and
season. Comparisons of seasonal and demographic factors with
dietary and lifestyle indicators of vitamin D status were analyzed
by chi-square test and by nonparametric test for trend in the case
of ordinal categorized variables. P _ 0.05 was considered significant.
Log likelihood ratio tests (LRT) and LRTs for trend
were used to determine associations with serum 25(OH)D.
All HYPOVITAMINOSIS D IN GREAT BRITAIN
861 analyses of serum 25(OH)D were done by using linear regression
after adjustment for sex and month of measurement.
Influences on hypovitaminosis D were evaluated by logistic
regression after adjustment of all models for sex and month of
measurement. Odds ratios and corresponding 95% CIs were used
to describe the influence of demographic, dietary, and lifestyle
indicators on the risk of hypovitaminosis D. LRTs and LRT trend
tests were used to test the significance of each factor in the
models. The first model included adjustment for sex and month
of measurement only. The fully adjusted model included, in
addition, all other indicators of hypovitaminosis D. Logistic regression
analyses were repeated by using the 3 thresholds for
hypovitaminosis D to evaluate whether influences on hypovitaminosis
D were similar regardless of the level of severity. Multiple
imputation (10 cycles) was used for missing information on
obesity, dietary, or lifestyle indicators in the final models of
hypovitaminosis D (29). Information on obesity was missing for
99 participants (1.3%), and 1117 cohort members (15.0%) were
missing data on skin color or_1 dietary or lifestyle indicator (eg,
vitamin D supplementation, intake of oily fish, margarine consumption,
use of sun protection, time spent outdoors, or watching
TV or using a PC). Analyses were repeated for the sample with
complete data, and results were unaffected by the treatment of
missing information unless otherwise indicated. Results are presented
with imputed data. Statistical analyses were carried out by
using STATA software (version 9.1; Stata Corp, College Station,
TX), and maps were constructed with the use of EPIMAP software
(version 3.3.2; Epi Info, Atlanta, GA).
RESULTS
Demographic characteristics and associations with supplement
use and time spent outdoors are presented in Table 1.
Women and nonobese participants (BMI _ 30) were significantly
more likely to use vitaminDsupplements and to spend less
time outdoors than were others. Variations in the frequency of
oily fish consumption were similar to those observed for supplement
use: compared with others, fish consumption was significantly
more frequent in females, the nonobese, participants living
in Southern England, and those in SES classification I and II
(P _ 0.001 for all comparisons, chi-square test). Women were
significantly more likely to use sun protection than were men:
70% and 49%, respectively, classified their use as “often” and
5% and 15%, respectively, classified their use as “rarely or
TABLE 1
Demographic characteristics and associations with the use of vitamin D supplements and time spent outdoors in the 1958 British birth cohort at age 45 y
Subjects
Vitamin D supplements1 Time spent outdoors/d2
No
(n 6080)
Yes
(n 1187) P3
30 min
(n 764)
30 min–3 h
(n 3133)
3 h
(n 2953) P3
n (%) n n
All 7437 (100) 83.7 16.3 11.2 45.7 43.1
Sex 0.0001 0.0001
Men 3725 (50.1) 87.1 12.9 9.2 42.0 48.9
Women 3712 (49.9) 80.2 19.8 13.1 49.4 37.5
Obese4 0.0001 0.02
No 5598 (76.3) 81.9 18.1 11.4 46.4 42.2
Yes 1740 (23.7) 89.3 10.7 10.4 43.6 46.1
Season5 0.17 0.0001
Winter 1290 (17.4) 81.5 18.5 21.1 49.9 29.0
Spring 1560 (21.0) 84.4 15.6 15.3 51.1 33.6
Summer 1748 (23.5) 84.0 16.0 5.5 42.1 52.4
Fall 2839 (38.2) 84.0 16.0 8.0 43.2 48.8
Region 0.0001 0.007
South 2853 (38.4) 80.1 19.9 11.0 48.3 40.7
Middle 1928 (26.0) 84.5 15.5 11.1 45.2 43.7
North 1937 (26.1) 85.9 14.1 12.2 43.3 44.5
Scotland 712 (9.6) 89.3 10.7 8.8 43.6 47.6
Socioeconomic status (British occupational
classifications) 0.0001 0.0001
I and II 3011 (40.5) 80.4 19.6 13.6 53.7 32.8
III Non-manual 1528 (20.6) 81.6 18.4 12.4 49.9 37.7
III Manual 1421 (19.1) 87.8 12.2 7.3 30.9 61.8
IV and V 1158 (15.6) 88.7 11.3 8.0 37.7 54.4
Unclassified 319 (4.30) 87.8 12.2 10.7 45.6 43.8
1 Use of cod liver or fish oil or other supplements containing vitamin D. n 170 with missing data. 2 During daylight hours in the previous month. n 587 with missing data. 3 Chi-square test: nonparametric trend test was used for ordinally grouped variables.
4 Defined as BMI (kg/m2) 30. n 99 with missing data.
5 Winter, December through February; spring, March through May; summer, June through August; fall, September through November.
6 n 7 with missing data. 7 I and II, professional or managerial; III, Non-manual or manual, skilled; IV and V, partly skilled and unskilled.
8 Includes cohort members who are institutionalized, retired, unemployed, and other.
HYPPO¨ NEN AND POWER
never” (P_0.0001, chi-square test). SES differences were seen
in the use of sun protection: the proportion of participants reporting
use “often” and “rarely or never,” respectively, was 63% and
8% in SES classification I and II, 67% and 7% in SES classification
III (skilled) nonmanual, 50% and 15% in SES classification
III (skilled) manual, 57% and 12% in SES classification IV
and V, and 57% and 14% in the unclassified group (P_0.0001,
chi-square test). Variation in sun protection by BMI was modest:
“often” and “rarely or never” in 58% and 12%, respectively, of
the obese compared with 61% and 9%, respectively, of the others
(P _ 0.03, chi-square test), whereas no significant variations
were seen by region (data not presented) (P _ 0.07, chi-square
test).
Serum 25(OH)D concentrations peaked in September and
were at their lowest from January through April (Figure 1).
Month of blood sampling was the strongest predictor; it explained
21.5% of the variation in 25(OH)D (P _ 0.0001, LRT).
The association between 25(OH)D and sex varied by month of
measurement; concentrations tended to be lower in women during
the summer and fall (June through November), whereas no
consistent monthly sex differences were apparent during the
winter and spring (December through May; Figure 1). The use of
vitamin D supplements and the consumption of oily fish but not
(fortified) margarine showed the expected associations with
25(OH)D (Figure 2). Time spent outdoors was strongly associated
with 25(OH)D during the summer and fall, but no association
was apparent during the winter months (P _ 0.0001, LRT
interaction).
Because the 25(OH)D concentration was largely predicted by
the month of blood sampling, the prevalence of hypovitaminosis
D, as shown in Table 2, is stratified by season. Hypovitaminosis
D at all thresholds was more common in women than in men
during the summer and fall, whereas, during the winter and
spring, women were over represented among those with
25(OH)D 25nmol/L and _75nmol/L. The prevalence of hypovitaminosis D was markedly higher in the obese than in the others in all severity groups and regardless of season. There was a significant north-south gradient in the prevalence of hypovitaminosis D in all severity groups (Table 2). Regional variation in the prevalence of 25(OH)D concentrations _40 nmol/L during the 4 seasons is represented in Figure 3. As reported in Table 2, the association between sex and hypovitaminosis D was dependent on season. Women had a risk of having 25(OH)D 25nmol/L during the summer or fall
twice that of men, whereas women’s risk of concentrations
_ 40 nmol/L and _ 75 nmol/L were only 40% greater than that
of men after full adjustment for available background indicators
(LRT P _ 0.0001 for all comparisons adjusted for month of
measurement, skin color, obesity, region, SES, supplement use,
fish consumption, time spent outdoors, sun protection and time
spent watching TV or using a PC). During winter, the only
threshold at which the risk of hypovitaminosis D was increased
in women was the threshold of_25nmol/L (P_0.001; adjusted
OR: 1.50; LRT). Persons who were obese or who lived in Scotland
had a risk of 25(OH)D concentrations _40 nmol that was
twice that of non obese persons or those who did not live in 0 10 20 30 40 50 60 70 80 90 September October November December January February March April May June July August September October November December January February March 2002 2003 2004 Time of measurement (mo) Serum 25-hydroxyvitamin D (nmol/L)
FIGURE 1. Geometric mean (95% CI) monthly variation in serum 25-hydroxyvitamin D [25(OH)D] concentrations in men ( ; n_3725) and women (u; n _ 3712) in the 1958 British birth cohort at age 45 y. The interaction between sex and month was significant [P _ 0.02, linear regression analyses on log 25(OH)D]. n per sex and month ranged from 17 to 340: 98 in December 2003 for women and_100 for both sexes in December 2002 (n_40 M, 37 F), January 2004 (n _ 95 M, 75 F), February 2004 (n _ 58 M, 70 F), and March 2004 (n _ 22 M, 17 F).
HYPOVITAMINOSIS D IN GREAT BRITAIN
Scotland (Table 3). The strength of the association with vitamin
D supplementation and margarine consumption varied according
to the severity of hypovitaminosis D. Use of vitamin D
supplements was associated significantly more strongly with the
2 lowest thresholds (fully adjusted OR for 25 nmo/L: 0.33;
95% CI: 0.2, 0.5; OR for _40 nmol/L: 0.36; 95% CI: 0.3, 0.4)
than with a threshold of _75 nmol/L (OR: 0.52; 95% CI: 0.5,
0.6). Margarine consumption was not associated with 25(OH)D
concentrations _75 nmol/L and was not robustly associated
with those _40 nmo/L (Table 3), but the risk of a concentration
_25 nmol/L was less in cohort members who consumed margarine
daily (adjusted OR: 0.69; 95% CI: 0.6, 0.8) or weekly (adjusted
OR: 0.68; 95% CI: 0.5, 0.9) than in those with less frequent
consumption (adjusted LRT for trend, P 0.003). As
suggested by Figure 2, time spent outdoors during winter did
not affect the risk of hypovitaminosis D (P _ 0.18), however,
there was a strong linear association for all severity groups at
other times of the year (adjusted LRT for trend, P _ 0.0001
for all comparisons).
DISCUSSION
Previous studies have highlighted the emerging problems of
hypovitaminosis D in the elderly in Great Britain (21, 22) and
ethnic minority groups (15–17). Our results suggest that the
problem is widespread also in middle-aged British whites. It is
striking that nearly half of the population had 25(OH)D concentrations
40 nmol/L during the winter and spring (3, 28); this showed that, for part of the year at least, the problem is not restricted to high-risk groups. With the use of the higher cutoff from a recent consensus on optimal status (ie, _75 nmol/L) (9), it is disturbing from the viewpoint of future bone health that nearly 90% of the current study population was affected by hypovitaminosis D during the winter and spring, and 60% had suboptimal concentrations year-round. Old age is a well-established risk factor for hypovitaminosisD (2) and as expected our middle-aged population compares favorably to Britons aged _65 y (21, 22). It is reassuring that our results are confirmed by statistics for 35–49-y-olds in the National Diet and Nutrition survey (mean concentration for both men and women: 48 nmol/L) (30). Nonetheless, the mean 25(OH)D concentration was lower and the prevalence of hypovitaminosis D higher in our study than in the general adult population in Canada or the United States. For example, in a study from Calgary, Canada (latitude 51°N) 20% of participants had 25(OH)D concentrations _40 nmol/L during the winter (31), whereas, in the current study, that proportion was 46%. In the 2 FIGURE 2. Geometric mean (95% CI) 25-hydroxyvitamin D [25(OH)D] concentrations by dietary and lifestyle indicators, standardized by sex and season. ; winter and spring (December through May); u, summer and fall (June through November) in Great Britain. *December through May: log likelihood ratio test,P_0.0001 for supplementation; log likelihood ratio trend test,P_0.0001 for fish consumption and time spent watching television (TV) or using a personal computer (PC), P 0.002 for sun protection. **June through November: log likelihood ratio test, P _ 0.0001 for supplementation; log likelihood ratio trend test, P _ 0.0001 for fish consumption, time spent outdoors, and time spent watching TV or using a PC, P _ 0.007 for sun protection. All tests were adjusted for sex and month of measurement. 25(OH)D concentrations for time spent outdoors are presented for December through February, and those for all other indicators are presented for December through May. ***Number of unknown observations for December through May (first column) and for June through November (second column), respectively: supplementation, 95 and 75; fish consumption, 99 and 70; margarine use, 144 and 105; time spent outdoors, 336 and 251; sun protection, 319 and 244; and time spent using a PC or watching TV, 201 and 141.
HYPPO¨ NEN AND POWER
TABLE 2
Average 25-hydroxyvitamin D [25(OH)D] and the prevalence of hypovitaminosis D at 3 thresholds (25, _40, and _75 nmol/L) stratified by season and demographic characteristics1 Characteristics and season Subjects 25(OH)D Average _25 nmol/L (n 148/439)
40 nmol/L (n 705/1327)
75 nmol/L (n 2794/2481)
n nmol/L %
All2
Winter and spring 2850 41.1 (40.4, 41.8)3 15.5 46.6 87.1
Summer and fall 4587 60.3 (59.5, 61.0) 3.2 15.4 60.9
Sex
Winter and spring
Men 1413 41.1 (40.2, 42.1) 13.9 47.0 88.7
Women 1437 41.2 (40.2, 42.3) 17.1 46.3 85.4
P 0.91 0.009 0.72 0.005
Summer and fall
Men 2312 61.9 (60.9, 62.9) 2.2 13.4 58.1
Women 2275 58.6 (57.6, 59.6) 4.3 17.4 63.7
P 0.0001 _0.0001 0.0001 _0.0001 Obesity4 Winter and spring No 2129 42.8 (41.9, 43.6) 13.5 43.3 84.9 Yes 674 36.7 (35.5, 38.0) 21.4 56.4 93.2 Summer and fall No 3469 62.8 (62.0, 63.7) 2.8 12.3 57.3 Yes 1066 52.7 (51.4, 54.0) 4.5 25.3 72.7 P _0.0001 _0.0001 _0.0001 _0.0001 Region of residence5 Winter and spring South 1226 42.6 (41.5, 43.7) 12.5 43.8 86.2 Midlands and Wales 690 40.6 (39.3, 42.0) 16.1 46.9 87.9 North 676 41.2 (39.7, 42.7) 17.5 46.6 85.9 Scotland 256 35.4 (33.4, 37.5) 23.5 60.0 92.2 Summer and fall South 1627 62.4 (61.2, 63.6) 2.7 12.3 56.7 Midlands and Wales 1238 60.4 (59.1, 61.8) 2.1 14.8 62.4 North 1261 60.9 (59.5, 62.3) 3.3 15.7 60.0 Scotland 456 50.9 (48.9, 53.0) 8.3 27.5 74.9 P for trend _0.0001 _0.0001 _0.0001 _0.0001 Socioeconomic status (British occupational classifications)6 Winter and spring I and II 1165 41.8 (40.7, 42.9) 14.2 45.6 86.3 III Nonmanual 596 42.0 (40.1, 43.9) 15.7 44.9 86.3 III Manual 521 39.9 (37.9, 42.0) 17.8 46.4 88.0 IV and V 453 40.2 (38.5, 42.0) 16.1 48.9 88.4 Unemployed/other5 115 36.0 (33.1, 39.1) 26.8 59.1 89.0 P for trend 0.004 0.01 0.04 0.09 Summer and fall I and II 1846 60.9 (59.8, 62.0) 3.2 14.0 60.0 III Nonmanual 932 59.9 (58.0, 61.8) 2.5 15.8 62.9 III Manual 900 62.4 (60.2, 64.6) 2.7 13.2 56.9 IV and V 705 58.2 (56.3, 60.1) 4.2 16.7 65.1 Unemployed or other7 204 55.1 (51.6, 58.9) 7.3 26.5 62.4 P for trend 0.006 0.04 0.008 0.17 1 All means and proportions are standardized by sex and season (winter and spring_December through May; summer and fall_June through November). P values for differences in 25(OH)D or prevalence of hypovitaminosis D from log likelihood ratio tests or log likelihood ratio trend tests as indicated. Sex, obesity, and socioeconomic status were distributed equally across seasons (P_0.41 for all comparisons, chi-square test).Asmall difference was found between regions of interviews carried out in the summer and fall: 54% in southern England compared with 64% in the Midlands and 65% in northern England compared with 64% in Scotland (P 0.0001, chi-square test). Season modified the association between sex and 25(OH)D (P _ 0.0006) and socioeconomic status and
25(OH)D (P _ 0.01); no interaction was observed for other factors.
2 The number of subjects with hypovitaminosis D in December through May and June through November.
3 Geometric x_ standardized by sex and season; 95% CI in parentheses (all such values).
4 Defined as BMI (in kg/m2)30. Unknown: December through May, n_47; June through November, n_52. P value from test including data for full year. 5 Unknown: December through May, n 2; June through November, n _ 5. P value from test including data for full year.
6 I and II, professional or managerial; III, nonmanual or manual, skilled; IV and V, partly skilled and unskilled.
7 Includes cohort members who were institutionalized, retired, unemployed, and other.
HYPOVITAMINOSIS D IN GREAT BRITAIN
seasonal subpopulations participating in the third National
Health and Nutrition Examination Survey (NHANES III), the
average 25(OH)D concentration was 66 nmol/L during winter in
the southern group (median latitude 32°N) and 73 nmol/L during
the summer in the northern group (median 39°N) (32). The prevalence
of 25(OH)D concentrations _25nmol/L was low (_3%)
in NHANES III (32). The vitamin D status of the general US
population is increasingly acknowledged to be unsatisfactory
(2, 32, 33), and thus the even higher prevalence of hypovitaminosis
D in the British population in the current study than in
the US population highlights the urgency of the situation in
Great Britain.
The high prevalence of hypovitaminosisDobserved in British
45 y-olds is not surprising. First, Great Britain is located between
50°N and 60°N, which corresponds to the latitude of Canada up
to the southern tip of Alaska. North of London, no cutaneous
vitamin D synthesis occurs in December and January, and, even
during the remainder of the year, cloud cover can block up to99%
of vitaminDproduction (10). The effect of latitude on production
was apparent within the current study; the highest rates of hypovitaminosis
D were observed in Scottish participants. Second,
vitamin D supplements appear to be taken less frequently in
Great Britain than in other countries. We found that 13% of men
and 20% of women used supplements, whereas the corresponding
proportions reported for the United States were30%and40%
(11). Estimates of supplement use from the current study agree
well with those reported from the National Diet and Nutrition
Survey (12% and 24%, respectively) (34). Limited availability of
supplements (eg, lack of over-the-counter single vitaminDproducts)
is likely to contribute to these differences. In addition, the
average dietary intake of vitamin D in the British National Diet
and Nutrition Survey was only half of that reported for the United
States, which may at least partly reflect differences in food fortification
policy (11, 34). Unlike the situation in the United
States, milk is not fortified with vitamin D in the United Kingdom,
and only fortification of margarine is mandatory. The
amount of added vitaminDis relatively low, because the purpose
of the fortification is only to increase the vitaminDconcentration
of margarine to concentrations that occur naturally in butter (25).
In the current study, the frequency of margarine consumption
was not associated with the average 25(OH)D concentration, but
the risk of 25(OH)D concentrations _25nmol/L was slightly
reduced. This suggests that, whereas fortification of margarine is
largely ineffective in improving vitamin D status at population
level, it may be sufficient to raise 25(OH)D concentrations in the
extreme state of deficiency. However, we acknowledge that only
relatively crude information on margarine use was available;
hence, we cannot exclude the possibility that underlying measurement
error contributed to these observations.
Methodologic considerations
Cutoffs for adequate vitamin D status are a key influence on
our perception of the extent hypovitaminosis D. For this reason,
we presented data for 3 thresholds that are in part defined by
known health outcomes [ie,_25 nmol/L to reflect calcium malabsorbtion
and rickets (1, 4, 8) and_75 nmol/L from a consensus
statement on requirements for bone health (4, 9)]. For an intermediate
cutoff (_40 nmol/L), we relied on the view of most
laboratories carrying out vitamin D assays that_40 nmol/L was
the concentration reflecting the need for vitamin D supplementation,
and it is commonly used as the lower reference level by the
laboratories (3, 28). An alternative strategy would have been to
use a higher threshold of 50 nmol/L (4). Furthermore, 25(OH)D
concentrations can vary with assay method (7, 28). We used an
automated application that is particularly suitable for large population
surveys because of its excellent repeatability and the lack
of variation by the operator carrying out the assay (26). Standardization
of values to data from DEQAS facilitated the use of
previously determined cutoffs for hypovitaminosis D.
The main strength of the study lies in the large sample of
whites for whom information on 25(OH)D concentrations was
available. With nationwide coverage and measures spanning the
year, the current study provides valuable information on the
FIGURE 3. Seasonal and geographical variation in the prevalence of hypovitaminosis D (25-hydroxyvitamin D _40 nmol/L) in Great Britain.
HYPPO¨ NEN AND POWER
current prevalence of hypovitaminosis D in British adults. Although
the 1958 cohort provides a representative sample of the
current adult white population, it is not representative of immigrant
ethnic minorities (24). Nevertheless, in agreement with
previous reports for ethnic minority groups living in Great Britain
(15–17), the prevalence of hypovitaminosis D in 154 nonwhites
in the cohort was markedly high: 50% had concentrations
_25 nmol/L, 80% had concentrations _40 nmol/L, and 100%
had concentrations _75 nmol/L during the winter and spring. A
further limitation is the self-reported information on dietary vitamin
D intake, supplementation, and sun exposure. However,
the strong associations observed between the available indicators
and serum 25(OH)D concentrations add face validity to our findings,
as do the clear seasonal trends.
Use of sun protection is known to reduce vitamin D production
in the skin (2). However, in the current study, the use of sun
protection was associated with slightly higher (rather than lower)
25(OH)D concentrations. This suggests that the use of sun protection
partly reflects levels of sun exposure. The lack of any
apparent adverse effects of sun protection on vitamin D status in
the current study could indicate that, at the population level, sun
screen and protective clothing are used by those who need them,
rather than being seen as an excessively cautious measure
strongly interfering with vitamin D synthesis.
Public health implications and conclusions
Data from the 1958 birth cohort suggest that, at different cutoffs
for hypovitaminosis D, a substantial public health problem
exists in British whites. Obese participants and those living in
Scotland were at the highest risk of hypovitaminosis D. However,
the prevalence in the general population was very high
during the winter and spring, which suggests that, to improve the
situation, action is required at a population level rather than at a
risk-group level. In the United States, calls have gone out for an
increase in vitamin D fortification of foods (11), and the data
from the current study suggest that such action is also warranted
in the United Kingdom. Vitamin D is currently available without
prescription as a dietary supplement only as part of cod liver oil
or multivitamin products; hence, a need clearly exists to consider
increased availability of over-the-counter supplements. Hypovitaminosis
D has been implicated in the development of serious
conditions, including diabetes, various types of cancer, and cardiovascular
diseases, in addition to its essential role in maintaining
bone health (1, 2). The high rates of hypovitaminosis D
reported in this study suggest that immediate action is needed to
improve the vitamin D status of the British population.
We thank Ian Gibb, Steve Turner, and Marie-Claude Fawcett (Royal
Victoria Infirmary, Newcastle-on-Tyne, United Kingdom) for carrying out
the 25-hydroxyvitamin D assays, and the Centre for Longitudinal Studies,
Institute of Education (original data producers) for providing the data.
EH initiated the substudy of 25-hydoxyvitamin D, carried out statistical
analyses, and wrote the manuscript. EH and CP jointly obtained funding for
the study, participated in critical evaluation of the findings and in revision of
the manuscript, and approved the final version of the manuscript. Neither
author had a personal or financial conflict of interest
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