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European Journal of Clinical Nutrition (2009) 63, 1444–1447; doi:10.1038/ejcn.2009.96; published online 19 August 2009

Association between serum 25-hydroxyvitamin D and depressive symptoms in Japanese: analysis by survey season

A Nanri1, T Mizoue1, Y Matsushita1, K Poudel-Tandukar1, M Sato2, M Ohta3 and N Mishima4

  1. 1Department of Epidemiology and International Health, Research Institute, International Medical Center of Japan, Shinjuku-ku, Tokyo, Japan
  2. 2Department of Applied Biological Chemistry, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
  3. 3Department of Health Development, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Japan
  4. 4Ikemi Memorial Clinic of Mind-Body Medicine, chuo-ku, Fukuoka, Japan

Correspondence: Dr A Nanri, Department of Epidemiology and International Health, Research Institute, International Medical Center of Japan, Toyama 1-21-1, Shinjuku-ku, Tokyo 162-8655, Japan. E-mail:

Received 10 April 2009; Revised 4 June 2009; Accepted 7 July 2009; Published online 19 August 2009.



Both depressive symptoms and vitamin D insufficiency are common during winter. This study examined the association between serum 25-hydroxyvitamin D and depressive symptoms by survey season. Subjects were 527 municipal employees aged 21–67 years of two municipal offices in Japan. Overall, there was no measurable association. However, in the workplace surveyed in November, multivariate-adjusted odds ratios (95% confidence interval) of having depressive symptoms (Center for Epidemiologic Studies Depression score of greater than or equal to16) for the lowest through highest quartiles of serum 25-hydroxyvitamin D were 1.00 (reference), 0.84 (0.45–1.58), 0.83 (0.44–1.58) and 0.59 (0.30–1.15), respectively (trend P=0.14). The association with the severe depressive state was more pronounced. By contrast, there was no such association in the workplace surveyed in July. Overall, this study did not provide evidence linking higher blood vitamin D levels with decreased depressive symptoms. The suggestive inverse association in sun-deprived season warrants further investigation.


25-hydroxyvitamin D, cross-sectional studies, depression, Japanese



Depression is an important health issue worldwide (Doris et al., 1999). Persons with severe depression have limited social lives due to their symptoms and are at increased risk of suicide (Doris et al., 1999). Depressive symptoms are known to be more frequent in autumn and winter (Harmatz et al., 2000), when vitamin D concentrations are low due to the decreased production of vitamin D in the skin on sunlight exposure (Burnand et al., 1992). The vitamin D receptor and the vitamin D-activating enzyme 1-α-hydroxylase are widely distributed in the human brain (Berk et al., 2007). Despite such suggestive evidence for a role of vitamin D in depression, few population-based studies have explored depressive symptoms in relation to vitamin D status (Hoogendijk et al., 2008; Pan et al., 2009). We therefore investigated the association between serum 25-hydroxyvitamin D and depressive symptoms in Japanese employees. As the survey was conducted in summer and late autumn, we were able to analyze the data by season, a strong determinant of vitamin D status.


Subjects and methods

Details of the study procedure have been described elsewhere (Murakami et al., 2008). In short, the subjects were participants in a health survey conducted in July and November 2006 among employees of two municipal offices in Kyushu, Japan. Of 601 eligible workers, 547 subjects (91%) aged 21–67 years completed anthropometric measurements, venous blood drawing and lifestyle questionnaire. After exclusion of 20 subjects with missing information on covariates, 527 workers remained for analysis. The protocol of the study has been approved by the ethics committee of the International Medical Center of Japan, and written informed consent was obtained from each participant.

Serum 25-hydroxyvitamin D concentrations were measured at an external laboratory by using a competitive protein-binding assay (Mitsubishi Chemical Medience Corporation, Tokyo, Japan), a widely used, reliable analytic method. The intra-assay coefficient of variation was 7.3–10.3%. Depressive symptoms were assessed using a Japanese version of the Center for Epidemiologic Studies Depression (CES-D) scale (Radloff 1977). Depressive symptoms were defined as present when subjects had a CES-D score of greater than or equal to16. Those with a CES-D score of greater than or equal to23 were also defined as being in a severe depressive state. Difference of subject characteristics was assessed by using independent t-test or χ2-test. Multiple logistic regression analysis was done to calculate odds ratios of depressive symptoms for quartiles of serum 25-hydroxyvitamin D concentrations, taking the lowest quartile category as the reference. Variables adjusted in multivariate model were workplace, age, sex, body mass index, marital status, job position, occupation, non-job physical activity, smoking, alcohol consumption and folate intake. Analyses were done with SAS 9.1 (SAS Institute, Cary, NC, USA).



Characteristics of study subjects did not significantly differ between the two workplaces except marital status and job position (Table 1). Dietary vitamin D intake was similar in the two workplaces, but serum 25-hyroxyvitamin D concentrations were much lower in workplace B (surveyed in November) than those in workplace A (surveyed in July). CES-D score and the prevalence of depressive symptoms were higher in workplace B than those in workplace A.

Overall, there was no measurable association between serum vitamin D concentrations and depressive symptoms (data not shown). However, differential association emerged when analysis was done by workplace (Table 2). In workplace B surveyed in November, the prevalence of depressive symptoms tended to decrease with serum vitamin D levels; the multivariate-adjusted odds ratios (95% confidence interval) of depressive symptoms for the lowest through highest quartiles of serum 25-hydroxyvitamin D were 1.00 (reference), 0.84 (0.45–1.58), 0.83 (0.44–1.58) and 0.59 (0.30–1.15), respectively (trend P=0.14). A more pronounced association was observed for severe depressive symptoms (CES-D score of greater than or equal to23); odds ratio (95% confidence interval) for the highest versus lowest quartile was 0.40 (0.16–1.03). By contrast, there was no such association in workplace A (surveyed in July). We also analyzed data for sufficient (greater than or equal to30ng/ml) versus insufficient levels (<30ng/ml) of blood vitamin D, a cutoff value proposed for the prevention of chronic diseases (Bischoff-Ferrari et al., 2006).The multivariate-adjusted odds ratios (95% confidence interval) for persons with sufficient vitamin D were 0.96 (0.41–2.23) in workplace A and 1.29 (0.63–2.65) in workplace B.



Overall, depressive symptoms were not appreciably associated with serum 25-hydroxyvitamin D concentrations. However, we found a suggestion of a lower prevalence of depressive symptoms among persons with high serum 25-hydroxyvitamin D concentrations in the workplace surveyed in late autumn.

A higher prevalence of depressive symptoms during winter, when vitamin D insufficiency is common, has led to the hypothesis that vitamin D is involved in the seasonality of mood (Berk et al., 2007). Our finding suggesting a protective effect of vitamin D on depressive symptoms in late autumn is compatible with this hypothesis. Vitamin D supplementation has been shown to improve depressive symptoms during the winter period, known as seasonal affective disorders (Berk et al., 2007). Although we had no information about the seasonality of symptoms, it may be reasonable to assume that depressive symptoms in persons who received survey in late autumn were more likely to be associated with vitamin D insufficiency than those in persons surveyed in summer.

To our knowledge, only two population-based studies have explored the association between blood vitamin D levels and depressive symptoms. In the Longitudinal Aging Study Amsterdam (Hoogendijk et al., 2008), lower serum 25-hydroxyvitamin D concentrations were observed among elderly subjects with depressive symptoms than those without. In another study of Chinese populations, depressive symptoms were not associated with serum 25-hydroxyvitamin D concentrations (Pan et al., 2009). However, the study was conducted in April and June, and thus cannot assess the association during a winter period, when more persons are at risk of both vitamin D deficiency and depressive mood. In our study, subjects who donated blood in July had much higher 25-hydoxyvitamin D concentrations than those who donated blood in November (mean: 27 versus 21ng/ml). In previous studies, means of blood vitamin D levels were 21ng/ml (Hoogendijk et al., 2008) and 16ng/ml (mean of the middle tertile; Pan et al., 2009). As regards depressive symptoms (CES-D greater than or equal to16), this study showed a much higher prevalence (36.6%) than did previous studies, but the value is similar to the prevalence reported from a large-scale study among Japanese workers (38.3% of men and 39.8% of women; Nakata et al., 2008).

Major strengths of this study include high study participation rate, adjustment of potential confounding variables and stratified analysis by season. Our study also had some limitations. First, an association derived from cross-sectional study does not necessarily indicate causality. Second, we measured serum vitamin D concentrations only at one point in time, which may not reflect long-term status. Third, our sample size was not sufficiently large to detect a modest association with statistical significance. Finally, because study subjects were employees of municipal offices in Japan, the findings may not be generalized to other populations.

In conclusion, overall result of this study did not support a protective role of vitamin D in the pathogenesis of depression. The inverse, albeit statistically non-significant, association observed in sun-deprived season warrants further investigation.


Conflict of interest

The authors declare no conflict of interest.



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This study was supported by a Grants-in-Aid for Scientific Research (C)(18590601) from Japan Society for the Promotion of Science.



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