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Vitamin D Insufficiency in a Sunny Environment: a Demographic And IMAJ • VOL 12 • DECEMbEr 2010 ORIGINAL ARTICLES Vitamin D Insufficiency in aS unny Environment: A Demographic and Seasonal Analysis Yael Oren1*, Yinon Shapira MD1*, Nancy Agmon-Levin MD1,2, Shaye Kivity MD1,3,4, Yaron Zafrir MD1, Arie Altman MD1,2, Aaron Lerner MD5 and Yehuda Shoenfeld MD1,2 1Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel 2Department of Medicine B, Sheba Medical Center, Tel Hashomer, Israel 3Departments of Medicine A & C, Sheba Medical Center, Tel Hashomer, Israel 4Rheumatic Disease Unit, Sheba Medical Center, Tel Hashomer, Israel 5Pediatric Gastroenterology and Nutrition Unit, Carmel Medical Center, affiliated with Rappaport Faculty of Medicine, Technion-Israel Institute ofT echnology, Haifa, Israel n recent years, vitamin D has been attracting considerable ABSTRACT: Background: Hypovitaminosis D has been shown to be I attention. It is becoming increasingly clear that this vitamin extremely common in various regions around the world, has a wide range of biological activity in addition to the clas- mostly at high latitudes. Israel is characterized by certain sic endocrine pathway, emphasizing the importance of this features – cultural (e.g., ethnic isolates) and geographic hormone in many aspects of general health. Studies suggest (e.g., sunny climate) – that have been identified for their that vitamin D insufficiency plays a role in the development possible association with vitamin D status. of cancer, autoimmune diseases, hypertension, infectious dis- Objectives: To conduct an ecological study on a repre- eases, diabetes, cardiovascular disease, musculoskeletal disor- sentative sample of the population of Israel, testing vitamin ders, asthma, as well as several psychiatric conditions such as D status across age groups, genders, ethnic groups, and schizophrenia, depression and dementia [1-5]. Unfortunately, seasons. Methods: We obtained serum samples from 195 healthy it is estimated that as many as 1 billion people worldwide Israeli volunteers representing a broad demographic spec- suffer from vitamin D deficiency or insufficiency (commonly trum. Serum concentrations of 25(OH)D were measured with defined as levels below 20 ng/ml and 30 ng/ml respectively), the commercial kit Liaison 25(OH)D Assay (DiaSorin, Italy). and this was shown to be prevalent across all age groups, Results: The mean vitamin D level for the entire cohort genders, and geographic regions [1,6-13]. was surprisingly low (22.9 ± 10.1 ng/ml), with 149 subjects The aim of the present study was to assess vitamin D status (78%) suffering from vitamin D insufficiency (< 30 ng/ml). in Israel. For this purpose the study population encompassed Vitamin D status was better in infants than in older age a representative demographic spectrum, enabling a compara- groups. Differences by gender were significant only in the tive analysis of vitamin D levels across a range of age groups infant age group (i.e., vitamin D status was worse among and both genders. Furthermore, Israel has unique cultural and females) and were not prominent across older ages. Israelis geographic features, presenting the opportunity to investigate of Ashkenazi origin had higher vitamin D mean levels than the associations between such factors and vitamin D status. those of Sephardic origin, who, in turn, had higher vitamin D levels than Arab subjects (31.4 ± 12, 24.1 ± 10, and 17.6 ± ETHNICITY IN ISRAEL AND VITAMIN D 9 ng/ml respectively). With regard to season, there were no The diversity of ethnic groups in Israel is extremely rich and differences between the samples collected in winter and the thus ideal for investigating the effects of genetic and cultural samples collected in summer. factors on vitamin D levels. Israel's population comprises Conclusions: The results suggest that hypovitaminosis D is both Jewish and non-Jewish groups. The Jewish population common across all ages, genders and seasons in Israel, a of Israel is divided according to historical ethnic descent, country characterized by a sunny Mediterranean climate. namely Jews of European and American descent (known as Specific ethnic groups may be at especially high risk. Ashkenazi Jews), and Jews of North African (e.g., Morocco), IMAJ 2010; 12: 751–756 Asian and Middle East descent (known as Sephardic Jews). KEY WORDS: vitamin D insufficiency, ethnic differences, seasonality, The non-Jewish population living in Israel consists mostly of demographic analysis, autoimmunity Arabs and particularly Moslem Arabs. These three main ethnic groups potentially vary in several parameters, which may exert differential effects on vitamin D status, such as skin color (due to typical genetic differences), dress code and customs (i.e., cul- *The first two authors contributed equally to this article tural variables) [1,6,13]. On the other hand, all ethnicities share 751 ORIGINAL ARTICLES IMAJ • VOL 12 • DECEMbEr 2010 Israel's small geographic size, and are thus subjected to similar D in sera. The method for quantitative determination of environmental exposures (such as ultraviolet radiation). We 25(OH)D is a direct, competitive chemiluminescence immu- thus sought to compare vitamin D levels among these three noassay. Specific antibody to vitamin D is used for coating main distinctive ethnic groups living in Israel. magnetic particles (solid phase) and vitamin D is linked to an isoluminol derivative. During the incubation, 25(OH)D SEASONS IN THE SUNNY REGION AND VITAMIN D is dissociated from its binding protein and competes with Israel is situated in a coastal area and is characterized by a labeled vitamin D for binding sites on the antibody. After warm Mediterranean climate that is mostly sunny year round. the incubation, the unbound material is removed with a The sunny weather notwithstanding, due to the country's wash cycle. Subsequently, the starter reagents are added and distance from the equator (latitude 30–33°N), radiation a flash chemiluminescent reaction is initiated. The light signal from the sun in the summer is approximately double that in is measured by a photomultiplier as relative light units (RLU) the winter. As sunlight exposure is the key factor in vitamin and is inversely proportional to the concentration of 25(OH) D synthesis, it is plausible that a winter trough in vitamin D present in calibrators, controls, or samples. D levels may manifest even in this sunny region [10,14]. As different investigators defined the normal lower limit Furthermore, while high-latitude regions are traditionally in the serum as 25(OH)D levels below 12 ng/ml (30 nmol/L) associated with inadequate levels of vitamin D, in recent or below 20 ng/ml (50 nmol/L) [1,10], in the present study we years accumulating reports from various sunny countries defined vitamin D deficiency as levels of 25(OH)D below 15 demonstrated that this hormone insufficiency is common in ng/ml. Vitamin D insufficiency was defined as levels below 30 tropical and subtropical regions as well. This suggests that ng/ml (75 nmol/L) [1]. vitamin D insufficiency is only partly explained by season and latitude [10-13]. In order to ascertain whether there are STATISTICAL ANALYSIS seasonal variations in vitamin D levels in Israel, we obtained Comparison of prevalence rates (i.e., vitamin D deficiency and serum samples in different seasons – summer and winter. insufficiency percentages) between groups was performed by the chi-square test or Fisher exact test (two-tailed), as appropriate. Continuous variables are expressed as mean ± standard devia- SUBJECTS AND METHODS tion. A two-tailed ANOVA was performed for comparison of We obtained serum samples from 195 healthy Israeli volun- vitamin D levels between groups. The Bonferroni correction was teers: 100 females, 95 males. Age was available for most of the applied in cases of multiple comparisons. For all tests P values subjects (N=191): 21 were under 5 years old (called Infants), < 0.05 were considered statistically significant and the StatSoft- 34 were between the age of 5 and 20 (Children), 121 were STATISTICA (v6.0) software was used for all analyses. 20–50 (Adults), and 15 subjects were over 50 (Older Adults). Ethnic origin was provided by 98 of the subjects, 8 of whom had mixed ethnic origin (i.e., offspring of Ashkenazi and RESULTS Sephardic admixture) and were not included in the final ethnic Serum vitamin D (25(OH)D) levels were normally distrib- analysis. Of the remaining 90 subjects, 26 were Ashkenazi Jews, uted around a mean value of 22.9 ± 10.1 ng/ml for the entire 38 were Sephardic Jews, and 26 were of Arab origin. cohort [Figure 1]. Of the 195 subjects who participated in this SEASONAL ANALYSIS Figure 1. Distribution of vitamin D levels among 195 healthy Israeli subjects Definition of ‘season’ in this region of the world may follow 55 a three-season model, with February-May as spring, June- 50 September as summer, and October-January as winter (i.e., 45 combining autumn and winter into a single “cold” season, 40 more accurately reflecting the actual changing of the temper- 35 atures in this region). The serum samples of 58 of the subjects 30 were collected during two distinct seasons for the purpose of 25 comparing vitamin D status, 35 of which were collected in 20 No. of subjects of No. the winter months (between November and January) and 23 15 in the summer months (between June and July). 10 5 VITAMIN D MEASUREMENT 0 We used the commercial kit LIAISON 25(OH)D Assay -5 0 5 10 15 20 25 30
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