Associations of serum 25-hydroxyvitamin D concentrations with quality of life and self-rated health in an older population.

ORIGINAL E n d o c r i n e

ARTICLE C a r e

Associations of Serum 25-Hydroxyvitamin D Concentrations With Quality of Life and Self-Rated Health in an Older Population R. Rafiq, K. M. A. Swart, N. M. van Schoor, D. J. Deeg, P. Lips, and R. T. de Jongh Department of Internal Medicine and Endocrinology (R.R., P.L., R.T.d.J.), VU University Medical Center, and Department of Epidemiology and Biostatistics (K.M.A.S., N.M.v.S., D.J.D., P.L.), EMGO Institute for Health and Care Research, VU University Medical Center, VU University Medical Center, 1081 BT Amsterdam, The Netherlands

Context: Vitamin D deficiency has been associated with impaired physical functioning, depression, and several chronic diseases and might thereby affect quality of life and self-rated health. Objective: The aim of this study was to assess relationships of serum 25-hydroxyvitamin D [25(OH)D] with quality of life and self-rated health and to examine whether physical performance, depressive symptoms, and number of chronic diseases mediate these relationships. Design: We analyzed data from the Longitudinal Aging Study Amsterdam, an ongoing populationbased cohort study of older Dutch individuals. Main Outcome Measures: Serum 25(OH)D was classified into the following categories: less than 25, 25–50, and 50 nmol/L or greater. We assessed quality of life (QOL) using the Short Form-12 Health Survey (SF-12; n ⫽ 862) and self-rated health (SRH) with a single question, dichotomized into good vs poor SRH (n ⫽ 1248). Results: Individuals with serum 25(OH)D less than 25 nmol/L scored lower on the physical component score of the SF-12 and had a lower odds on good SRH score compared with individuals with serum 25(OH)D greater than 50 nmol/L (␤ (95% confidence interval) ⫺3.9 (⫺6.5 to ⫺1.3) for SF-12, and odds ratio [95% confidence interval) 0.50 (0.33– 0.76) for SRH]. Physical performance, depressive symptoms, and the number of chronic diseases were associated with vitamin D status, QOL, and SRH. Adding all these potential mediators to regression models attenuated associations of 25(OH)D less than 25 nmol/L with QOL with 78% and SRH with 32%. Conclusion: Lower 25(OH)D status is related to lower scores on QOL and SRH. A large part of the association with QOL can statistically be explained by physical performance, depressive symptoms, and the number of chronic diseases. (J Clin Endocrinol Metab 99: 3136 –3143, 2014)

itamin D has a broad effect on health. Vitamin D deficiency may cause bone mineralization defects, which may lead to osteoporosis and fractures (1). Also, it has been shown to be associated with multiple chronic diseases such as cardiovascular diseases, diabetes, cancer, and autoimmune diseases (2). Vitamin D contributes to optimal physical functioning and muscle strength (3, 4). In addition, low

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vitamin D status has been related to depressive disorders (5). Epidemiologic studies showed that vitamin D deficiency is highly prevalent, especially in older individuals and patients with chronic diseases, with a prevalence ranging from 40% to 100% (2, 6). Vitamin D status might also be associated with quality of life (QOL) and self-rated health, although studies on these latter relationships are scarce.

ISSN Print 0021-972X ISSN Online 1945-7197 Printed in U.S.A. Copyright © 2014 by the Endocrine Society Received December 16, 2013. Accepted May 19, 2014. First Published Online June 2, 2014

Abbreviations: BMI, body mass index; CES-D, Center for Epidemiological Studies Depression; CI, confidence interval; 25(OH)D, 25-hydroxyvitamin D; QOL, quality of life; RCT, randomized controlled trial; SF-12, Short Form-12 Health Survey; SRH, self-rated health.

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J Clin Endocrinol Metab, September 2014, 99(9):3136 –3143

doi: 10.1210/jc.2013-4431

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doi: 10.1210/jc.2013-4431

Quality of life is the subjective evaluation of one’s own physical, mental, and social functioning. It is determined by many factors and can be arranged according to several dimensions. QOL is an important outcome in epidemiological studies, randomized controlled trials (RCTs), and cost-utility studies. A related parameter to QOL is selfrated health. Self-rated health is the perception of one’s own health and a summary measure of health status. Self-rated health gives a good indication of one’s health and has proven to be a predictor of mortality (7, 8). Relationships between vitamin D status and QOL and self-rated health may be mediated by several factors. Patients with chronic diseases and persons with mobility limitations score lower in questionnaires on QOL (9, 10). Self-rated health is correlated with number of chronic diseases and might therefore be associated with vitamin D status (11). Depression is an important predictor of QOL and self-rated health and might also mediate the relationship with vitamin D status (12). In this study we aimed to assess the relationships between serum 25-hydroxyvitamin D [25(OH)D] concentrations and QOL and self-rated health in a populationbased cohort of older Dutch individuals. In addition, we examined the role of physical performance, number of chronic diseases, and depressive symptoms as potential mediators.

Materials and Methods Study participants The Longitudinal Ageing Study Amsterdam is a populationbased cohort study on predictors and consequences of healthy aging in an older Dutch population. The outline of the study has been described elsewhere (13, 14). For the current study, data from the second (1995–1996) and third cycle (1998 –1999) were used. In 1995–1996 the medical data were obtained from 1509 participants who were aged 65 years and older as of January 1, 1996. Participants underwent a medical interview including the question on self-rated health. Participants without a blood sample, with incomplete or no performance tests, or with missing values for potential confounders were excluded. This resulted in the data of 1248 participants in the statistical analysis. Data on QOL were collected in 1998 –1999, during the third cycle. QOL questionnaires were completed by 862 of 1248 participants. The study was approved by the Medical Ethics Committee of the VU University Medical Center, and informed consent was obtained from all participants.


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Short Form-12 Health Survey (SF-12) The SF-12 is a multidimensional short-form generic measure of health status. It is a valid subset of the larger Short Form-36 and monitors health in general and specific populations. Two subscales are derived from the SF-12: the physical component summary and the mental component summary. These summary scales based on the SF-12 correlate very highly with the Short Form-36 version (15). Each of the subscales is scored within the 0 to 100 range, with a higher score indicating better healthrelated quality of life (HRQOL). Data are obtained by a selfadministered questionnaire during the third measurement cycle in 1998 –1999.

Self-rated health Self-rated health is evaluated by asking the participants how they perceive their health in general. There are five response categories: 1) poor, 2) sometimes good/bad, 3) fair, 4) good, and (5) excellent (16). Data were obtained during the second cycle in 1995–1996.

Mediators: number of chronic diseases, physical performance, and depressive symptoms The selection of seven major chronic diseases was based on their prevalence (⬎5%) in the 55⫹ year age group in The Netherlands (17). These were the following: chronic obstructive pulmonary disease (asthma, chronic bronchitis, and pulmonary emphysema); cardiac disease; peripheral arterial disease; stroke; diabetes mellitus; rheumatoid arthritis/osteoarthritis; and cancer. Information about the diseases was based on self-report (18). Physical performance was assessed by means of three performance tests. The scores were summed to obtain a total performance score (4, 19). The tests included the time taken to walk 3 m, turn 180°, and walk back as fast as possible (walking test); time needed to rise five times from a chair with arms folded in front of the chest (chair stands test); and the ability to stand with the heel of one foot directly in front of, and touching the toes of the other foot for at least 10 seconds (tandem stand). For the walking test and the chair stands test, one to four points could be scored corresponding to the quartile of the distribution of time needed. Score 0 was given to those respondents who could not complete a test. The score of the tandem test was categorized into three groups: unable (0 points), able to hold position for 3–9 seconds (2 points), and able to hold position for 10 seconds (4 points). The total score ranged from 0 to 12, with 12 points representing an excellent performance (20). Depressive symptoms were measured using a self-report rating scale [Center for Epidemiological Studies Depression (CESD)] (21, 22). The total score on the CES-D ranges between 0 and 60. To identify those with clinically relevant levels of symptoms, a cutoff score of 16 or more is generally used (23). Data were gathered in face-to-face interviews. The data of the second measurement cycle in 1995–1996 were used for all potential mediators.

Serum 25(OH)D In 1995–1996, fasting morning blood samples were collected and centrifuged. Serum samples were stored at ⫺20°C, and serum 25(OH)D was measured by a competitive protein-binding assay (Nichols Diagnostics) in 1997–1998 at the Endocrine Laboratory of the VU University Medical Center. The interassay coefficient of variation was 10%.

Confounders The following potential confounders, measured in 1995– 1996, were included in the statistical analysis: gender, age, body mass index (BMI), alcohol consumption, smoking status, season of blood collection, and serum creatinine. Body weight was measured without clothes and shoes, using a calibrated balance beam


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Vitamin D, QoL, and Self-Rated Health


using spline plots and likelihood ratio tests. All spline regression analyses were performed using R version 2.15.0. To assess whether physical performance, number of chronic diseases, and depressive symptoms acted as mediators, a statistical mediator analysis was performed according to Baron and Kenney (described in Ref. 26) (Figure 1). A mediator is a variable that Figure 1. Mediation model of the association between vitamin D status and QOL and selfspecifies how a given effect occurs. Accordrated health. ing to the model of Baron and Kenney, a variable can be considered a mediator if four conditions are met: 1) the predictor (A) scale. Body height was measured with a stadiometer. The alcohol must be significantly associated with the hypothesized mediator consumption index was used to classify alcohol drinkers into (B), 2) the predictor (A) must me be significantly associated with four categories [nondrinker, light drinker, moderate drinker, the dependent variable (C), 3) the mediator (B) must be signifiand (very) excessive drinker] based on the number of days on cantly associated with the dependent variable (C), and 4) the which alcohol was consumed and the number of alcoholic drinks impact of the predictor (A) on the dependent variable (C) is less consumed each time (24). Information on smoking status was after controlling for the mediator (B). In our models we first based on self-report and was classified as never smoker, former analyzed associations of vitamin D status (predictor) with QOL smoker, or current smoker. Season for blood collection was diand self-rated health (dependent variables). Then we studied aschotomized in winter (October through March) and summer sociations of vitamin D status (predictor) with physical perfor(April through September). Vitamin D synthesis depends on sun mance, number of chronic diseases, and depressive symptoms exposure and season, and in The Netherlands it is not synthesized (mediators). Subsequently, relationships between physical perbetween October and March (25). Serum creatinine was used as formance, the number of chronic diseases, and depressive sympa marker of renal function and was analyzed according to stantoms (mediators) with SF-12 scores and self-rated health (dedard laboratory methods. pendent variables) were analyzed. Finally, physical performance, the number of chronic diseases, and depressive symptoms (meStatistical analysis diators) were added separately and together to the regression To assess the differences in the baseline characteristics bemodels to examine the contribution of these potential mediators 2 tween 25(OH)D categories, Pearson ␹ tests were used for the to the association between vitamin D category (predictor) and categorical variables, ANOVA for the normally distributed conboth QOL and self-rated health (dependent variables). tinuous variables, and the Kruskall-Wallis H test for the skewed continuous variables. Multiple linear regression analysis was used to investigate the association between serum 25(OH)D and SF-12 scores. Because Results the relationship between serum 25(OH)D and SF-12 scores was not linear, vitamin D was categorized into three categories using Participants included in the analyses (n ⫽ 1248) were traditional cutoff points (1): less than 25 nmol/L, 25–50 nmol/L, younger than the total study population [n ⫽ 1509, mean and 50 nmol/L or greater. The vitamin D category of 50 nmol/L age (SD): 75.6 (6.6) vs 78.5 (6.6), P ⬍ .001] and had an or greater served as the reference category. SF-12 scores were identical gender distribution. Participants who completed used as a continuous variable. the QOL questionnaire were younger [74.1(6.0) vs For the association of serum 25(OH)D and self-rated health, a logistic regression analysis was used. Self-rated health (SRH) 78.5(6.6), P ⬍ .001] than the total study population in scores were dichotomized into good self-rated health and poor 1998 –1999 (n ⫽ 1509). self-rated health. The first category (good SRH) included the Characteristics of participants are shown in Table 1 scores of excellent and good and the second category (poor SRH) stratified to the serum 25(OH)D category. Participants in contained the scores of fair, sometimes good/bad, and poor (16). the lower categories, as compared with the highest cateIn the analyses we compared the odds for each vitamin D category to respond with good SRH vs poor SRH. Again, the vitamin gory of 25(OH)D concentrations, were older and more D category of 50 nmol/L or greater served as a reference category. often female. They had lower scores on physical perforWe used restricted cubic spline plots to estimate an optimal mance tests, more chronic diseases, and more depressive cutoff level for serum 25(OH)D in the relationship with the symptoms. Participants from the lowest vitamin D cateSF-12 scores. This is a nonparametric model. Cubic splines are gory scored lower on the physical component of the SF-12 piecewise polynomial functions that are constrained to join smoothly at points called knots. These spline functions provide and on self-rated health as compared with the highest catbetter insight into dose-response relationships compared with egory. The mental component score of the SF-12 did not analyses using categorized variables. Restricted cubic spline vary between the categories of serum 25(OH)D. functions use all data points to estimate the risk at each level of The findings of the regression models are shown in exposure, as opposed to step functions using categorical variTable 2. The first model (model A) showed an association ables, which assume a constant risk within categories. Cubic of serum 25(OH)D with the physical component score of spline functions were tested in regression models at three knots


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Table 1.


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Baseline Characteristics of the Study Population According to 25(OH)D Categories 25(OH), nmol/L

Age, y Gender Women BMI, kg/m2 Creatinine, ␮mol/L Smoking Never smoker Former smoker Current smoker Alcohol use None Light Moderate (Very) excessive Season of blood collection Winter Physical performance score Number of chronic diseases CES-D score SF-12 score Self-rated health score Poor Sometimes good/bad Fair Good Excellent

50 (n ⴝ 653)

Overall P Value

79.9 (5.9)

77.0 (6.6)

73.4 (5.8)

⬍.001

63.0 27.4 (5.3) 91.8 (35.8)

59.8 27.3 (4.4) 97.2 (50.1)

42.6 26.5 (3.7) 94.7 (20.5)

⬍.001 .003 ⬍.001

48.9 28.1 23.0

38.9 42.0 19.1

30.3 52.8 16.8

⬍.001

31.1 53.3 14.8 0.7

30.4 48.7 15.0 5.9

17.6 51.0 24.0 7.4

⬍.001

68.1 5.0 (3.1) 1.0 (1.0 –2.0) 9.9 (9.2) 38.4 (11.9)

57.2 6.8 (3.2) 1.0 (0.0 –2) 8.8 (7.8) 43.2 (11.2)

49.2 8.3 (2.7) 1.0 (0.0 –2.0) 6.6 (7.0) 46.0 (9.7)

⬍.001 ⬍.001 ⬍.001 ⬍.001 ⬍.001

6.0 13.4 34.2 39.6 6.7

2.4 11.8 25.9 49.6 10.2

2.6 7.9 21.9 54.9 12.6

⬍.001

Data are presented as mean (SD), percentages, or median (interquartile range).

the SF-12 after adjustment for confounders. The score in the lowest category of serum 25(OH)D was 3.9 points lower [95% confidence interval (CI) ⫺6.5 to ⫺1.3)] than in the reference category. Figure 2 shows the multivariable spline function of serum 25(OH)D and the physical component score of the SF-12. Up to serum 25(OH)D levels of approximately 70 nmol/L, the SF-12 score increased with increasing serum 25(OH)D. Serum 25(OH)D was not associated with the scores of the mental component of the SF-12 (data not shown). Serum 25(OH)D was significantly associated with scores on self-rated health. The participants from the lowest category of 25(OH)D had lower odds to score higher on self-rated health compared with the participants from the highest category of serum 25(OH)D (Table 2, model A). To investigate whether physical performance and number of chronic diseases acted as mediators, a mediator analysis according to Baron and Kenney was performed (Figure 1, Table 3). Participants from the lowest category of serum 25(OH)D scored lower on physical performance, had more chronic diseases, and more depressive symptoms compared with participants from the highest category (condition 1). As described earlier, a significant association of vitamin D status and SF-12 and SRH scores was shown in Table 2 (condition 2). Physical performance,

number of chronic diseases and depressive symptoms were related to SF-12 scores and self-rated health (Table 3). Participants with a better score on physical performance, fewer chronic diseases, and fewer depressive symptoms scored higher on the SF-12 and had higher odds on good self-rated health (condition 3). The last step in the analysis is the adjustment for the potential mediators. In Table 2, the regression models are shown after adjusting for number of chronic diseases (model B), depressive symptoms (model C), and physical performance (model D) (condition 4). Adjustment for number of chronic diseases decreased the strength of the association of 25(OH)D with the physical component of SF-12 and self-rated health with 33% and 8%, respectively. Adjustment for depressive symptoms decreased the strength of the associations with 26% and 20%, respectively. Adjustment for physical performance decreased the strength of the associations with 54% and 24%, respectively. Adding the three mediators together to the models decreased the strength of the association with QOL with 78% and the strength of the association with self-rated health with 32% (model E).

Discussion This is the first population-based study that shows an association between serum 25(OH)D concentrations and


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Table 2. 25(OH)D, nmol/L



Results of Regression Analyses of Serum 25(OH)D With SF-12 Scores and Self-Rated Health Scores Aa

SF-12 physical component (n ⫽ 862) ⬍25 B (95% CI) ⫺3.9 (⫺6.5 to ⫺1.3) P .004 25–50 B (95% CI) ⫺0.8 (⫺2.3 to 0.6) P .264 ⬎50 Reference category

Bb

Cc

Dd

⫺2.6 (⫺5.1 to ⫺0.2) ⫺2.9 (⫺5.4 to ⫺0.3) ⫺1.8 (⫺4.3 to 0.6) .035 .029 .147 ⫺0.6 (⫺2.0 to 0.8) .389 Reference category

Self-rated health cross-sectional (n ⫽ 1248)f ⬍25 OR (95% CI) 0.50 (0.33 to 0.76) 0.55 (0.35 to 0.85) P .001 .008 25–50 OR (95% CI) 0.88 (0.67 to 1.15) 0.91 (0.68 to 1.22) P .355 .538 ⬎50 Reference category Reference category

Ee

⫺0.9 (⫺3.2 to 1.5) .466

⫺0.5 (⫺2.0 to 0.9) .468 Reference category

0.0 (⫺1.4 to 1.4) 0.1 (⫺1.2 to 1.4) .968 .857 Reference category Reference category

0.62 (0.40 to 0.94) .025

0.66 (0.42 to 1.02) .060

0.97 (0.73 to 1.29) .879 Reference category

0.96 (0.72 to 1.27) 1.03 (0.76 to 1.41) .796 .842 Reference category Reference category

0.73 (0.45 to 1.18) .192

Abbreviations: B, regression coefficient B derived from linear regression analyses; OR, odds ratio derived from logistic regression analyses. a

Model A: adjustments were made for gender, age, BMI, alcohol consumption, smoking status, season of blood collection, and serum creatinine.

b

Model B: as model A with adjustment for number of chronic diseases.

c

Model C: as model A with adjustment for depressive symptoms (CES-D score).

d

Model D: as model A with adjustment for physical performance.

e

Model D: as model A with adjustment for number of chronic diseases, depressive symptoms, and physical performance.

f

Good vs poor SRH: odds for good SRH.

QOL and self-rated health in an older population. Participants with lower cross-sectional serum concentrations scored lower on the physical component of the SF-12 and self-rated health. Physical performance, number of chronic diseases and depressive symptoms acted as mediators and largely explained the relationship between vitamin D and QOL. This outcome is in line with other observational studies that have been performed in other populations. These studies showed that low serum 25(OH)D was associated with impaired QOL. In patients with Crohn’s disease, vitamin D deficiency was independently associated with lower scores on questionnaires on QOL (27). In a study in dialysis patients, vitamin D deficiency was also associated with poorer QOL (28). In that study, vitamin D status was associated with the mental component of the SF-12 and not with the physical component. The difference between the latter and our study might be explained by the difference in study populations, dialysis patients vs a population-based cohort of older individuals. The prevalence of vitamin D deficiency in the study with dialysis patients (65%) was higher than in our study (48%). Dialysis therapy has a great impact on social functioning and dependency and might therefore influence the mental aspect of QOL more than the physical aspect. In a study among Turkish women with osteoporosis, lower serum 25(OH)D was associated with impaired QOL, both for patients with and without fractures (29). In this study no correlation

was found between vitamin D status and number of concomitant diseases. In our study we found a significant association between vitamin D categories and number of chronic diseases. Participants in the lowest 25(OH)D category had 0.2 chronic diseases more compared with participants in the highest category. This difference might be explained by the exclusion criteria used in the study with women with osteoporosis. In that study persons with diseases affecting QOL (eg, cancer, chronic renal insufficiencies, chronic respiratory diseases, decompensate cardiovascular diseases, and fracture within the 6 months of the study) were excluded. This influences the number of concomitant diseases and might therefore alter associations with serum 25(OH)D. To assess whether vitamin D is a cause or a consequence of low QOL, the effect of vitamin D supplementation on QOL should be investigated. In a RCT among community-dwelling older women at increased risk of a hip fracture, vitamin D supplementation did not improve QOL after 6 and 12 months of follow-up (30). In another RCT, vitamin D supplementation during 20 weeks in vitamin D-deficient (⬍50 nmol/L) older patients with heart failure did not improve QOL (31). In a RCT among elderly people with a low-trauma fracture in the past years, vitamin D supplementation during 2 years did not improve QOL (32). The lack of an effect of vitamin D supplementation in these studies suggests that vitamin D is an indicator rather than a cause of impaired QOL. However, in two of


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self-rated health as a part of the QOL scores but did not analyze the association between vitamin D status and self-rated health as such. This study also showed that a large part of the association of vitamin D status with the physical component of QOL and self-rated health can be statistically explained by physical performance. These findings are in line with several studies, which have shown a positive association of vitamin D with physical performance and muscle strength (3, 4). Several RCTs also showed a positive effect of vitamin D supplementation on muscular function (33, 34). An impaired physical function may lead to a lower QOL because of the loss of autonomy and impaired social functioning. The number of chronic diseases Figure 2. Relationship between serum 25(OH)D and the physical component score of the SF-12 was also a statistical mediator of the after adjustment for gender, age, BMI, alcohol consumption, smoking status, season of blood relationship between vitamin D and collection, and serum creatinine. the physical component of QOL and for a smaller part of the association the above three studies vitamin D status was not assessed and participants might not have been deficient enough to with self-rated health. A possible explanation for the small show a beneficial effect of vitamin D supplementation. mediating effect on the relationship between vitamin D This suggestion is in line with our findings. Vitamin D and self-rated health might be the frame of reference of deficiency [25(OH)D ⬍ 25 nmol/L] but not vitamin D persons with several chronic diseases. Persons with insufficiency [25(OH)D 25–50 nmol/L] was associated chronic diseases may adapt their health perceptions to the presence of their diseases (response shift). An epidemiowith a decrease in QOL. Our study showed that vitamin D status was associated logical study investigating the 17-year time trend of selfwith self-rated health. To the best of our knowledge, this rated health showed a stable trend in self-rated health, is the first study that investigated the association between whereas the mean number of chronic diseases and the serum 25(OH)D and self-rated health. Other studies used prevalence of mild disability increased (35). The results of Table 3. Results of the Mediation Analysis of Physical Performance, Number of Chronic Diseases, and Depressive Symptoms With Serum 25(OH)D Categories, SF-12, and Self-Rated Health Scores Number of Chronic Diseases

Physical Performance 95% CI

P Value

25(OH) vitamin D ⬍25 B (⫺1.7 [⫺2.2 to ⫺1.2]) ⬍.001 25–50 B (⫺0.5 [⫺0.8 to ⫺0.2]) .003 ⬎50 Reference category Reference category SF-12 physical B (1.5 [1.2 to 1.7]) ⬍.001 component Self-rated health OR (1.09 [1.07 to 1.11]) ⬍.001 LASA-C

95% CI

Depressive Symptoms (CES-D Score) P Value

B (0.2 [0.0 – 0.4]) B (0.0 [⫺0.1 to 0.2]) Reference category

.047 .562 Reference category B (⫺3.8 [⫺4.4 to ⫺3.2]) ⬍.001 OR (0.47 [0.40 – 0.53])

⬍.001

95% CI

P Value

B (2.5 [1.1– 4.0]) .001 B (0.9 [0.0 –1.9]) .045 Reference category Reference category B (⫺0.4 [⫺0.5 to ⬍.001 ⫺0.3]) OR (0.89 [0.87– ⬍.001 0.91])

Abbreviation: LASA, Longitudinal Ageing Study Amsterdam; OR, odds ratio. Adjustments were made for gender, age, BMI, alcohol consumption, smoking status, season of blood collection, and serum creatinine.


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this study indicated that a shift took place in which factors were deemed important for self-rated health. People focused more on poor functioning but less on their diseases. In addition, when rating their health, people often implicitly applied social comparison. Depressive symptoms also mediated the relationship between vitamin D status and the physical component of QOL and self-rated health. Several studies have investigated the relationship between vitamin D status and depression, and the results are conflicting (5, 36, 37). On the one hand, vitamin D deficiency might be a consequence of depression because the underlying causes of vitamin D deficiency such as decreased outdoor activity are secondary to depression. On the other hand, vitamin D has been proved to influence several mediators, which are believed to play a role in the pathogenesis of depression (38, 39). Vitamin D deficiency can also cause hyperparathyroidism, which is often associated with mood disorders, which disappear after normalizing PTH levels (40). The three mediators together explain 78% of the association between vitamin D status and QOL and 32% of the association between vitamin D status and self-rated health. Physical performance explains the largest part of these associations. A part of the associations remains unexplained. This might be due to the inaccuracy of the measurement instruments. The remaining part of the associations might also be mediated by other unknown variables. Associations with self-rated health remain largely unexplained, which implies other contributing variables to play a role, which remains to be examined in further studies. The strengths of the present study are its large study population and population-based nature. The outcomes of this study can be applied to the general older population. A limitation is the fact that the SF-12 was not measured at baseline but after 3 years. Despite this, we did find an association between vitamin D status and SF-12-scores. Another limitation is the potential selection bias that occurred in the population that filled in the SF-12-questionnaire. These participants were younger than the total study population. This may have led to an underestimation of the association. In addition, the number of chronic diseases was not objectively assessed but by the self-report of respondents. In conclusion, results of this population-based study show that lower serum 25(OH)D is associated with lower scores on QOL and self-rated health. A large part of this association can statistically be explained by physical performance, the number of chronic diseases, and depressive symptoms. A part of the association of vitamin D status and self-rated health remains unexplained by these mediators. It is important to further investigate these associa-


tions because of the high prevalence of vitamin D deficiency and the great impact of impaired QOL. In addition, treatment of vitamin D deficiency is easy and safe. To investigate whether vitamin D deficiency is a cause or just an indicator of low QOL, additional RCTs in vitamin D-deficient individuals are essential.

Acknowledgments Address all correspondence and requests for reprints to: Renate T. de Jongh, MD, PhD, Department of Internal Medicine and Endocrinology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. E-mail: [email protected]. The Longitudinal Aging Study Amsterdam is largely supported by a grant from The Netherlands Ministry of Health Welfare and Sports, Directorate of Long-term Care and Older Persons. The vitamin D status was assessed with a grant from ZonMw. Disclosure Summary: The authors have nothing to disclose.

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