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1.  A Prospective Study of Plasma Vitamin D Metabolites, Vitamin D Receptor Polymorphisms, and Prostate Cancer 
PLoS Medicine  2007;4(3):e103.
Vitamin D insufficiency is a common public health problem nationwide. Circulating 25-hydroxyvitamin D3 (25[OH]D), the most commonly used index of vitamin D status, is converted to the active hormone 1,25 dihydroxyvitamin D3 (1,25[OH]2D), which, operating through the vitamin D receptor (VDR), inhibits in vitro cell proliferation, induces differentiation and apoptosis, and may protect against prostate cancer. Despite intriguing results from laboratory studies, previous epidemiological studies showed inconsistent associations of circulating levels of 25(OH)D, 1,25(OH)2D, and several VDR polymorphisms with prostate cancer risk. Few studies have explored the joint association of circulating vitamin D levels with VDR polymorphisms.
Methods and Findings
During 18 y of follow-up of 14,916 men initially free of diagnosed cancer, we identified 1,066 men with incident prostate cancer (including 496 with aggressive disease, defined as stage C or D, Gleason 7–10, metastatic, and fatal prostate cancer) and 1,618 cancer-free, age- and smoking-matched control participants in the Physicians' Health Study. We examined the associations of prediagnostic plasma levels of 25(OH)D and 1,25(OH)2D, individually and jointly, with total and aggressive disease, and explored whether relations between vitamin D metabolites and prostate cancer were modified by the functional VDR FokI polymorphism, using conditional logistic regression. Among these US physicians, the median plasma 25(OH)D levels were 25 ng/ml in the blood samples collected during the winter or spring and 32 ng/ml in samples collected during the summer or fall. Nearly 13% (summer/fall) to 36% (winter/spring) of the control participants were deficient in 25(OH)D (<20 ng/ml) and 51% (summer/fall) and 77% (winter/spring) had insufficient plasma 25(OH)D levels (<32 ng/ml). Plasma levels of 1,25(OH)2D did not vary by season. Men whose levels for both 25(OH)D and 1,25(OH)2D were below (versus above) the median had a significantly increased risk of aggressive prostate cancer (odds ratio [OR] = 2.1, 95% confidence interval [CI] 1.2–3.4), although the interaction between the two vitamin D metabolites was not statistically significant (pinteraction = 0.23). We observed a significant interaction between circulating 25(OH)D levels and the VDR FokI genotype (pinteraction < 0.05). Compared with those with plasma 25(OH)D levels above the median and with the FokI FF or Ff genotype, men who had low 25(OH)D levels and the less functional FokI ff genotype had increased risks of total (OR = 1.9, 95% CI 1.1–3.3) and aggressive prostate cancer (OR = 2.5, 95% CI 1.1–5.8). Among men with plasma 25(OH)D levels above the median, the ff genotype was no longer associated with risk. Conversely, among men with the ff genotype, high plasma 25(OH)D level (above versus below the median) was related to significant 60%∼70% lower risks of total and aggressive prostate cancer.
Our data suggest that a large proportion of the US men had suboptimal vitamin D status (especially during the winter/spring season), and both 25(OH)D and 1,25(OH)2D may play an important role in preventing prostate cancer progression. Moreover, vitamin D status, measured by 25(OH)D in plasma, interacts with the VDR FokI polymorphism and modifies prostate cancer risk. Men with the less functional FokI ff genotype (14% in the European-descent population of this cohort) are more susceptible to this cancer in the presence of low 25(OH)D status.
Results of this study by Haojie Li and colleagues suggest that vitamin D deficiency is common among men in the US, and that vitamin D status and genetic variation in theVDR gene affect prostate cancer risk.
Editors' Summary
Prostate cancer occurs when cells in the prostate gland (part of the male reproductive system) accumulate genetic changes that allow them to grow into a disorganized mass of cells. Patients whose disease is diagnosed when these cells are still relatively normal can survive for many years, but for patients with aggressive cancers—ones containing fast-growing cells that can migrate around the body—the outlook is poor. Factors that increase prostate cancer risk include increasing age, having a family history of prostate cancer, and being African American. Also, there are hints that some environmental or dietary factors affect prostate cancer risk. One of these factors is vitamin D, of which high levels are found in seafood and dairy products, but which can also be made naturally by the body—more specifically, by sunlight-exposed skin. One reason researchers think vitamin D might protect against prostate cancer is that this cancer is more common in sun-starved northern countries (where people often have a vitamin D deficiency) than in sunny regions. Prostate cancer is also more common in African American men than in those of European descent (when exposed to the same amount of sunlight, individuals with darker skin make less vitamin D than those with lighter skin). Once in the human body, vitamin D is converted into the vitamin D metabolite 25-hydroxyvitamin D3 (25[OH]D) and then into the active hormone 1,25 dihydroxyvitamin D3 (1,25[OH]2D). This binds to vitamin D receptors (VDRs) and inhibits cell proliferation and migration.
Why Was This Study Done?
The effect of 1,25(OH)2D on cells and the observation that related chemicals slow prostate cancer growth in rodents suggest that vitamin D protects against prostate cancer. But circulating levels of vitamin D metabolites in human male populations do not always reflect how many men develop prostate cancer. This lack of correlation may partly be because different forms of the VDR gene exist. One area of variation in the VDR gene is called the FokI polymorphism. Because everyone carries two copies of the VDR gene, individuals may have a FokI FF, FokI Ff, or FokI ff genotype. The f variant (or allele) codes for a receptor that is less responsive to 1,25(OH)2D than the receptor encoded by the FokI F allele. So levels of vitamin D sufficient to prevent cancer in one person may be insufficient in someone with a different FokI genotype. In this study, the researchers have investigated how levels of 25(OH)D and 1,25(OH)2D in combination with different VDR FokI alleles are influencing prostate cancer risk.
What Did the Researchers Do and Find?
The researchers identified 1,066 men who developed prostate cancer between enrollment into the US Physicians' Health Study in 1982 and 2000, and 1,618 cancer-free men of the same ages and smoking levels as “controls.” They measured vitamin D metabolite levels in many of the blood samples taken from these men in 1982 and determined their FokI genotype. Two-thirds of the men had insufficient blood levels of vitamin D metabolites in the winter/spring; almost one-third had a vitamin D deficiency. Men whose blood levels of both metabolites were below average were twice as likely to develop aggressive prostate cancer as those in whom both levels were above average. Compared with men with high blood levels of 25(OH)D and the FokI FF or Ff genotype, men with low 25(OH)D levels and the FokI ff genotype were 2.5 times as likely to develop aggressive prostate cancer. However, men with the ff genotype were not at higher risk if they had sufficient 25(OH)D levels. Among men with the ff genotype, sufficient 25(OH)D levels might therefore protect against prostate cancer, especially against the clinically aggressive form.
What Do These Findings Mean?
These findings confirm that many US men have suboptimal levels of circulating vitamin D. This vitamin is essential for healthy bones, so irrespective of its effects on prostate cancer, vitamin D supplements might improve overall health. In addition, this large and lengthy study reveals an association between low levels of the two vitamin D metabolites and aggressive prostate cancer that is consistent with vitamin D helping to prevent the progression of prostate cancer. It also indicates that the VDR FokI genotype modifies the prostate cancer risk associated with different blood levels of vitamin D. Together, these results suggest that improving vitamin D status through increased exposure to sun and vitamin D supplements might reduce prostate cancer risk, particularly in men with the FokI ff genotype. Because the study participants were mainly of European descent, the researchers caution that these results may not apply to other ethnic groups and note that further detailed studies are needed to understand fully how vitamin D affects prostate cancer risk across the population.
Additional Information.
Please access these Web sites via the online version of this summary at
MedlinePlus encyclopedia has pages on prostate cancer and on vitamin D
Information for patients and physicians is available from the US National Cancer Institute on prostate cancer and on cancer prevention
The Prostate Cancer Foundation's information on prostate cancer discusses the effects of nutrition on the disease
Patient information on prostate cancer is available from Cancer Research UK
Cancerbackup also has patient information on prostate cancer
PMCID: PMC1831738  PMID: 17388667
2.  Serum 25-Hydroxyvitamin D Concentrations and Season-Specific Correlates in Japanese Adults 
Journal of Epidemiology  2011;21(5):346-353.
Several lines of evidence indicate an important role for vitamin D in the prevention of a range of diseases. Blood vitamin D levels show clear seasonal variation; however, data on the determinants of vitamin D status for each season are limited. We investigated the association between lifestyle and serum vitamin D concentration by season in Japanese workers.
Subjects were 312 men and 217 women aged 21 to 67 years who worked in municipal offices in Northern Kyushu, Japan and participated in a periodic checkup in July or November. Multiple linear regression analysis was used to examine the association between serum 25-hydroxivitamin D concentrations and lifestyle factors for each season.
Mean serum 25-hydroxyvitamin D concentration was 27.4 ng/ml (68.4 nmol/L) and 21.4 ng/ml (53.4 nmol/L) for workers surveyed in July and November, respectively (P < 0.001); the prevalence of vitamin D deficiency (<20 ng/ml) was 9.3% and 46.7%, respectively (P < 0.001). In November, dietary vitamin D intake (in both sexes) and nonsmoking and physical activity (in men) were significantly associated with higher concentrations of serum 25-hydroxyvitamin D. In summer, fish/shellfish intake was associated with higher serum 25-hydroxyvitamin D concentrations in women.
Vitamin D deficiency is common in Japanese workers during seasons with limited sunlight. The lifestyle correlates of favorable vitamin D status in November were physical activity, dietary vitamin D intake, and nonsmoking.
PMCID: PMC3899433  PMID: 21747209
25-hydroxyvitamin D; Japanese; lifestyle factors; vitamin D intakes
3.  Calcium Plus Vitamin D Supplementation and the Risk of Breast Cancer 
Although some observational studies have associated higher calcium intake and especially higher vitamin D intake and 25-hydroxyvitamin D levels with lower breast cancer risk, no randomized trial has evaluated these relationships.
Postmenopausal women (N = 36 282) who were enrolled in a Women's Health Initiative clinical trial were randomly assigned to 1000 mg of elemental calcium with 400 IU of vitamin D3 daily or placebo for a mean of 7.0 years to determine the effects of supplement use on incidence of hip fracture. Mammograms and breast exams were serially conducted. Invasive breast cancer was a secondary outcome. Baseline serum 25-hydroxyvitamin D levels were assessed in a nested case–control study of 1067 case patients and 1067 control subjects. A Cox proportional hazards model was used to estimate the risk of breast cancer associated with random assignment to calcium with vitamin D3. Associations between 25-hydroxyvitamin D serum levels and total vitamin D intake, body mass index (BMI), recreational physical activity, and breast cancer risks were evaluated using logistic regression models. Statistical tests were two-sided.
Invasive breast cancer incidence was similar in the two groups (528 supplement vs 546 placebo; hazard ratio = 0.96; 95% confidence interval = 0.85 to 1.09). In the nested case–control study, no effect of supplement group assignment on breast cancer risk was seen. Baseline 25-hydroxyvitamin D levels were modestly correlated with total vitamin D intake (diet and supplements) (r = 0.19, P < .001) and were higher among women with lower BMI and higher recreational physical activity (both P < .001). Baseline 25-hydroxyvitamin D levels were not associated with breast cancer risk in analyses that were adjusted for BMI and physical activity (Ptrend = .20).
Calcium and vitamin D supplementation did not reduce invasive breast cancer incidence in postmenopausal women. In addition, 25-hydroxyvitamin D levels were not associated with subsequent breast cancer risk. These findings do not support a relationship between total vitamin D intake and 25-hydroxyvitamin D levels with breast cancer risk.
PMCID: PMC2673920  PMID: 19001601
4.  Clinical Utility of Vitamin D Testing 
Executive Summary
This report from the Medical Advisory Secretariat (MAS) was intended to evaluate the clinical utility of vitamin D testing in average risk Canadians and in those with kidney disease. As a separate analysis, this report also includes a systematic literature review of the prevalence of vitamin D deficiency in these two subgroups.
This evaluation did not set out to determine the serum vitamin D thresholds that might apply to non-bone health outcomes. For bone health outcomes, no high or moderate quality evidence could be found to support a target serum level above 50 nmol/L. Similarly, no high or moderate quality evidence could be found to support vitamin D’s effects in non-bone health outcomes, other than falls.
Vitamin D
Vitamin D is a lipid soluble vitamin that acts as a hormone. It stimulates intestinal calcium absorption and is important in maintaining adequate phosphate levels for bone mineralization, bone growth, and remodelling. It’s also believed to be involved in the regulation of cell growth proliferation and apoptosis (programmed cell death), as well as modulation of the immune system and other functions. Alone or in combination with calcium, Vitamin D has also been shown to reduce the risk of fractures in elderly men (≥ 65 years), postmenopausal women, and the risk of falls in community-dwelling seniors. However, in a comprehensive systematic review, inconsistent results were found concerning the effects of vitamin D in conditions such as cancer, all-cause mortality, and cardiovascular disease. In fact, no high or moderate quality evidence could be found concerning the effects of vitamin D in such non-bone health outcomes. Given the uncertainties surrounding the effects of vitamin D in non-bone health related outcomes, it was decided that this evaluation should focus on falls and the effects of vitamin D in bone health and exclusively within average-risk individuals and patients with kidney disease.
Synthesis of vitamin D occurs naturally in the skin through exposure to ultraviolet B (UVB) radiation from sunlight, but it can also be obtained from dietary sources including fortified foods, and supplements. Foods rich in vitamin D include fatty fish, egg yolks, fish liver oil, and some types of mushrooms. Since it is usually difficult to obtain sufficient vitamin D from non-fortified foods, either due to low content or infrequent use, most vitamin D is obtained from fortified foods, exposure to sunlight, and supplements.
Clinical Need: Condition and Target Population
Vitamin D deficiency may lead to rickets in infants and osteomalacia in adults. Factors believed to be associated with vitamin D deficiency include:
darker skin pigmentation,
winter season,
living at higher latitudes,
skin coverage,
kidney disease,
malabsorption syndromes such as Crohn’s disease, cystic fibrosis, and
genetic factors.
Patients with chronic kidney disease (CKD) are at a higher risk of vitamin D deficiency due to either renal losses or decreased synthesis of 1,25-dihydroxyvitamin D.
Health Canada currently recommends that, until the daily recommended intakes (DRI) for vitamin D are updated, Canada’s Food Guide (Eating Well with Canada’s Food Guide) should be followed with respect to vitamin D intake. Issued in 2007, the Guide recommends that Canadians consume two cups (500 ml) of fortified milk or fortified soy beverages daily in order to obtain a daily intake of 200 IU. In addition, men and women over the age of 50 should take 400 IU of vitamin D supplements daily. Additional recommendations were made for breastfed infants.
A Canadian survey evaluated the median vitamin D intake derived from diet alone (excluding supplements) among 35,000 Canadians, 10,900 of which were from Ontario. Among Ontarian males ages 9 and up, the median daily dietary vitamin D intake ranged between 196 IU and 272 IU per day. Among females, it varied from 152 IU to 196 IU per day. In boys and girls ages 1 to 3, the median daily dietary vitamin D intake was 248 IU, while among those 4 to 8 years it was 224 IU.
Vitamin D Testing
Two laboratory tests for vitamin D are available, 25-hydroxy vitamin D, referred to as 25(OH)D, and 1,25-dihydroxyvitamin D. Vitamin D status is assessed by measuring the serum 25(OH)D levels, which can be assayed using radioimmunoassays, competitive protein-binding assays (CPBA), high pressure liquid chromatography (HPLC), and liquid chromatography-tandem mass spectrometry (LC-MS/MS). These may yield different results with inter-assay variation reaching up to 25% (at lower serum levels) and intra-assay variation reaching 10%.
The optimal serum concentration of vitamin D has not been established and it may change across different stages of life. Similarly, there is currently no consensus on target serum vitamin D levels. There does, however, appear to be a consensus on the definition of vitamin D deficiency at 25(OH)D < 25 nmol/l, which is based on the risk of diseases such as rickets and osteomalacia. Higher target serum levels have also been proposed based on subclinical endpoints such as parathyroid hormone (PTH). Therefore, in this report, two conservative target serum levels have been adopted, 25 nmol/L (based on the risk of rickets and osteomalacia), and 40 to 50 nmol/L (based on vitamin D’s interaction with PTH).
Ontario Context
Volume & Cost
The volume of vitamin D tests done in Ontario has been increasing over the past 5 years with a steep increase of 169,000 tests in 2007 to more than 393,400 tests in 2008. The number of tests continues to rise with the projected number of tests for 2009 exceeding 731,000. According to the Ontario Schedule of Benefits, the billing cost of each test is $51.7 for 25(OH)D (L606, 100 LMS units, $0.517/unit) and $77.6 for 1,25-dihydroxyvitamin D (L605, 150 LMS units, $0.517/unit). Province wide, the total annual cost of vitamin D testing has increased from approximately $1.7M in 2004 to over $21.0M in 2008. The projected annual cost for 2009 is approximately $38.8M.
Evidence-Based Analysis
The objective of this report is to evaluate the clinical utility of vitamin D testing in the average risk population and in those with kidney disease. As a separate analysis, the report also sought to evaluate the prevalence of vitamin D deficiency in Canada. The specific research questions addressed were thus:
What is the clinical utility of vitamin D testing in the average risk population and in subjects with kidney disease?
What is the prevalence of vitamin D deficiency in the average risk population in Canada?
What is the prevalence of vitamin D deficiency in patients with kidney disease in Canada?
Clinical utility was defined as the ability to improve bone health outcomes with the focus on the average risk population (excluding those with osteoporosis) and patients with kidney disease.
Literature Search
A literature search was performed on July 17th, 2009 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 1998 until July 17th, 2009. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. Articles with unknown eligibility were reviewed with a second clinical epidemiologist, then a group of epidemiologists until consensus was established. The quality of evidence was assessed as high, moderate, low or very low according to GRADE methodology.
Observational studies that evaluated the prevalence of vitamin D deficiency in Canada in the population of interest were included based on the inclusion and exclusion criteria listed below. The baseline values were used in this report in the case of interventional studies that evaluated the effect of vitamin D intake on serum levels. Studies published in grey literature were included if no studies published in the peer-reviewed literature were identified for specific outcomes or subgroups.
Considering that vitamin D status may be affected by factors such as latitude, sun exposure, food fortification, among others, the search focused on prevalence studies published in Canada. In cases where no Canadian prevalence studies were identified, the decision was made to include studies from the United States, given the similar policies in vitamin D food fortification and recommended daily intake.
Inclusion Criteria
Studies published in English
Publications that reported the prevalence of vitamin D deficiency in Canada
Studies that included subjects from the general population or with kidney disease
Studies in children or adults
Studies published between January 1998 and July 17th 2009
Exclusion Criteria
Studies that included subjects defined according to a specific disease other than kidney disease
Letters, comments, and editorials
Studies that measured the serum vitamin D levels but did not report the percentage of subjects with serum levels below a given threshold
Outcomes of Interest
Prevalence of serum vitamin D less than 25 nmol/L
Prevalence of serum vitamin D less than 40 to 50 nmol/L
Serum 25-hydroxyvitamin D was the metabolite used to assess vitamin D status. Results from adult and children studies were reported separately. Subgroup analyses according to factors that affect serum vitamin D levels (e.g., seasonal effects, skin pigmentation, and vitamin D intake) were reported if enough information was provided in the studies
Quality of Evidence
The quality of the prevalence studies was based on the method of subject recruitment and sampling, possibility of selection bias, and generalizability to the source population. The overall quality of the trials was examined according to the GRADE Working Group criteria.
Summary of Findings
Fourteen prevalence studies examining Canadian adults and children met the eligibility criteria. With the exception of one longitudinal study, the studies had a cross-sectional design. Two studies were conducted among Canadian adults with renal disease but none studied Canadian children with renal disease (though three such US studies were included). No systematic reviews or health technology assessments that evaluated the prevalence of vitamin D deficiency in Canada were identified. Two studies were published in grey literature, consisting of a Canadian survey designed to measure serum vitamin D levels and a study in infants presented as an abstract at a conference. Also included were the results of vitamin D tests performed in community laboratories in Ontario between October 2008 and September 2009 (provided by the Ontario Association of Medical Laboratories).
Different threshold levels were used in the studies, thus we reported the percentage of subjects with serum levels of between 25 and 30 nmol/L and between 37.5 and 50 nmol/L. Some studies stratified the results according to factors affecting vitamin D status and two used multivariate models to investigate the effects of these characteristics (including age, season, BMI, vitamin D intake, skin pigmentation, and season) on serum 25(OH)D levels. It’s unclear, however, if these studies were adequately powered for these subgroup analyses.
Study participants generally consisted of healthy, community-dwelling subjects and most excluded individuals with conditions or medications that alter vitamin D or bone metabolism, such as kidney or liver disease. Although the studies were conducted in different parts of Canada, fewer were performed in Northern latitudes, i.e. above 53°N, which is equivalent to the city of Edmonton.
Serum vitamin D levels of < 25 to 30 nmol/L were observed in 0% to 25.5% of the subjects included in five studies; the weighted average was 3.8% (95% CI: 3.0, 4.6). The preliminary results of the Canadian survey showed that approximately 5% of the subjects had serum levels below 29.5 nmol/L. The results of over 600,000 vitamin D tests performed in Ontarian community laboratories between October 2008 and September 2009 showed that 2.6% of adults (> 18 years) had serum levels < 25 nmol/L.
The prevalence of serum vitamin D levels below 37.5-50 nmol/L reported among studies varied widely, ranging from 8% to 73.6% with a weighted average of 22.5%. The preliminary results of the CHMS survey showed that between 10% and 25% of subjects had serum levels below 37 to 48 nmol/L. The results of the vitamin D tests performed in community laboratories showed that 10% to 25% of the individuals had serum levels between 39 and 50 nmol/L.
In an attempt to explain this inter-study variation, the study results were stratified according to factors affecting serum vitamin D levels, as summarized below. These results should be interpreted with caution as none were adjusted for other potential confounders. Adequately powered multivariate analyses would be necessary to determine the contribution of risk factors to lower serum 25(OH)D levels.
Seasonal variation
Three adult studies evaluating serum vitamin D levels in different seasons observed a trend towards a higher prevalence of serum levels < 37.5 to 50 nmol/L during the winter and spring months, specifically 21% to 39%, compared to 8% to 14% in the summer. The weighted average was 23.6% over the winter/spring months and 9.6% over summer. The difference between the seasons was not statistically significant in one study and not reported in the other two studies.
Skin Pigmentation
Four studies observed a trend toward a higher prevalence of serum vitamin D levels < 37.5 to 50 nmol/L in subjects with darker skin pigmentation compared to those with lighter skin pigmentation, with weighted averages of 46.8% among adults with darker skin colour and 15.9% among those with fairer skin.
Vitamin D intake and serum levels
Four adult studies evaluated serum vitamin D levels according to vitamin D intake and showed an overall trend toward a lower prevalence of serum levels < 37.5 to 50 nmol/L with higher levels of vitamin D intake. One study observed a dose-response relationship between higher vitamin D intake from supplements, diet (milk), and sun exposure (results not adjusted for other variables). It was observed that subjects taking 50 to 400 IU or > 400 IU of vitamin D per day had a 6% and 3% prevalence of serum vitamin D level < 40 nmol/L, respectively, versus 29% in subjects not on vitamin D supplementation. Similarly, among subjects drinking one or two glasses of milk per day, the prevalence of serum vitamin D levels < 40 nmol/L was found to be 15%, versus 6% in those who drink more than two glasses of milk per day and 21% among those who do not drink milk. On the other hand, one study observed little variation in serum vitamin D levels during winter according to milk intake, with the proportion of subjects exhibiting vitamin D levels of < 40 nmol/L being 21% among those drinking 0-2 glasses per day, 26% among those drinking > 2 glasses, and 20% among non-milk drinkers.
The overall quality of evidence for the studies conducted among adults was deemed to be low, although it was considered moderate for the subgroups of skin pigmentation and seasonal variation.
Newborn, Children and Adolescents
Five Canadian studies evaluated serum vitamin D levels in newborns, children, and adolescents. In four of these, it was found that between 0 and 36% of children exhibited deficiency across age groups with a weighted average of 6.4%. The results of over 28,000 vitamin D tests performed in children 0 to 18 years old in Ontario laboratories (Oct. 2008 to Sept. 2009) showed that 4.4% had serum levels of < 25 nmol/L.
According to two studies, 32% of infants 24 to 30 months old and 35.3% of newborns had serum vitamin D levels of < 50 nmol/L. Two studies of children 2 to 16 years old reported that 24.5% and 34% had serum vitamin D levels below 37.5 to 40 nmol/L. In both studies, older children exhibited a higher prevalence than younger children, with weighted averages 34.4% and 10.3%, respectively. The overall weighted average of the prevalence of serum vitamin D levels < 37.5 to 50 nmol/L among pediatric studies was 25.8%. The preliminary results of the Canadian survey showed that between 10% and 25% of subjects between 6 and 11 years (N= 435) had serum levels below 50 nmol/L, while for those 12 to 19 years, 25% to 50% exhibited serum vitamin D levels below 50 nmol/L.
The effects of season, skin pigmentation, and vitamin D intake were not explored in Canadian pediatric studies. A Canadian surveillance study did, however, report 104 confirmed cases1 (2.9 cases per 100,000 children) of vitamin D-deficient rickets among Canadian children age 1 to 18 between 2002 and 2004, 57 (55%) of which from Ontario. The highest incidence occurred among children living in the North, i.e., the Yukon, Northwest Territories, and Nunavut. In 92 (89%) cases, skin pigmentation was categorized as intermediate to dark, 98 (94%) had been breastfed, and 25 (24%) were offspring of immigrants to Canada. There were no cases of rickets in children receiving ≥ 400 IU VD supplementation/day.
Overall, the quality of evidence of the studies of children was considered very low.
Kidney Disease
Two studies evaluated serum vitamin D levels in Canadian adults with kidney disease. The first included 128 patients with chronic kidney disease stages 3 to 5, 38% of which had serum vitamin D levels of < 37.5 nmol/L (measured between April and July). This is higher than what was reported in Canadian studies of the general population during the summer months (i.e. between 8% and 14%). In the second, which examined 419 subjects who had received a renal transplantation (mean time since transplantation: 7.2 ± 6.4 years), the prevalence of serum vitamin D levels < 40 nmol/L was 27.3%. The authors concluded that the prevalence observed in the study population was similar to what is expected in the general population.
No studies evaluating serum vitamin D levels in Canadian pediatric patients with kidney disease could be identified, although three such US studies among children with chronic kidney disease stages 1 to 5 were. The mean age varied between 10.7 and 12.5 years in two studies but was not reported in the third. Across all three studies, the prevalence of serum vitamin D levels below the range of 37.5 to 50 nmol/L varied between 21% and 39%, which is not considerably different from what was observed in studies of healthy Canadian children (24% to 35%).
Overall, the quality of evidence in adults and children with kidney disease was considered very low.
Clinical Utility of Vitamin D Testing
A high quality comprehensive systematic review published in August 2007 evaluated the association between serum vitamin D levels and different bone health outcomes in different age groups. A total of 72 studies were included. The authors observed that there was a trend towards improvement in some bone health outcomes with higher serum vitamin D levels. Nevertheless, precise thresholds for improved bone health outcomes could not be defined across age groups. Further, no new studies on the association were identified during an updated systematic review on vitamin D published in July 2009.
With regards to non-bone health outcomes, there is no high or even moderate quality evidence that supports the effectiveness of vitamin D in outcomes such as cancer, cardiovascular outcomes, and all-cause mortality. Even if there is any residual uncertainty, there is no evidence that testing vitamin D levels encourages adherence to Health Canada’s guidelines for vitamin D intake. A normal serum vitamin D threshold required to prevent non-bone health related conditions cannot be resolved until a causal effect or correlation has been demonstrated between vitamin D levels and these conditions. This is as an ongoing research issue around which there is currently too much uncertainty to base any conclusions that would support routine vitamin D testing.
For patients with chronic kidney disease (CKD), there is again no high or moderate quality evidence supporting improved outcomes through the use of calcitriol or vitamin D analogs. In the absence of such data, the authors of the guidelines for CKD patients consider it best practice to maintain serum calcium and phosphate at normal levels, while supplementation with active vitamin D should be considered if serum PTH levels are elevated. As previously stated, the authors of guidelines for CKD patients believe that there is not enough evidence to support routine vitamin D [25(OH)D] testing. According to what is stated in the guidelines, decisions regarding the commencement or discontinuation of treatment with calcitriol or vitamin D analogs should be based on serum PTH, calcium, and phosphate levels.
Limitations associated with the evidence of vitamin D testing include ambiguities in the definition of an ‘adequate threshold level’ and both inter- and intra- assay variability. The MAS considers both the lack of a consensus on the target serum vitamin D levels and assay limitations directly affect and undermine the clinical utility of testing. The evidence supporting the clinical utility of vitamin D testing is thus considered to be of very low quality.
Daily vitamin D intake, either through diet or supplementation, should follow Health Canada’s recommendations for healthy individuals of different age groups. For those with medical conditions such as renal disease, liver disease, and malabsorption syndromes, and for those taking medications that may affect vitamin D absorption/metabolism, physician guidance should be followed with respect to both vitamin D testing and supplementation.
Studies indicate that vitamin D, alone or in combination with calcium, may decrease the risk of fractures and falls among older adults.
There is no high or moderate quality evidence to support the effectiveness of vitamin D in other outcomes such as cancer, cardiovascular outcomes, and all-cause mortality.
Studies suggest that the prevalence of vitamin D deficiency in Canadian adults and children is relatively low (approximately 5%), and between 10% and 25% have serum levels below 40 to 50 nmol/L (based on very low to low grade evidence).
Given the limitations associated with serum vitamin D measurement, ambiguities in the definition of a ‘target serum level’, and the availability of clear guidelines on vitamin D supplementation from Health Canada, vitamin D testing is not warranted for the average risk population.
Health Canada has issued recommendations regarding the adequate daily intake of vitamin D, but current studies suggest that the mean dietary intake is below these recommendations. Accordingly, Health Canada’s guidelines and recommendations should be promoted.
Based on a moderate level of evidence, individuals with darker skin pigmentation appear to have a higher risk of low serum vitamin D levels than those with lighter skin pigmentation and therefore may need to be specially targeted with respect to optimum vitamin D intake. The cause-effect of this association is currently unclear.
Individuals with medical conditions such as renal and liver disease, osteoporosis, and malabsorption syndromes, as well as those taking medications that may affect vitamin D absorption/metabolism, should follow their physician’s guidance concerning both vitamin D testing and supplementation.
PMCID: PMC3377517  PMID: 23074397
5.  Test-Retest Reliability of the WHI Physical Activity Questionnaire 
Few physical activity (PA) questionnaires were designed to measure the lifestyles and activities of women. We sought to examine the test-retest reliability of a PA questionnaire used in the Women's Health Initiative (WHI) Study. Differences in reliability were also explored by important covariates.
Participants (n=1092) were post-menopausal women aged 50-79 years, randomly selected from the baseline sample of participants in the WHI Observational Study. The WHI physical activity questionnaire collects usual frequency, duration, and pace of recreational walking, frequency and duration of other recreational activities or exercises (mild, moderate and strenuous), household, and yard activities. Approximately half of the women (n=569) repeated questions on recreational PA, the other half (n=523) repeated questions related to household and yard activities (mean 3 months apart). Test-retest reliability was assessed with kappa and intraclass correlation coefficients (ICC1,1).
Overall, questions on recreational walking, moderate recreational PA, and strenuous recreational PA had higher test-retest reliability (weighted kappa range 0.50-0.60), than questions on mild recreational PA (weighted kappa range 0.35-0.50). The ICC1,1 for moderate to strenuous recreational PA was 0.77 (95% CI 0.73, 0.80) and total recreational PA was 0.76 (95% CI 0.71, 0.79). Substantial reliability was observed for the summary measures of yard activities (ICC1,1 0.71; 95% CI 0.66, 0.75) and household activities (ICC1,1 0.60, 95% CI 0.55, 0.66). No meaningful differences were observed by race/ethnicity, age, time between test and retest, and amount of reported PA.
The WHI PA questionnaire demonstrated moderate to substantial test-retest reliability in a diverse sample of post-menopausal women.
PMCID: PMC2692735  PMID: 19204598
Epidemiology; movement; reproducibility; women's health; exercise
6.  Serum 25 HydroxyVitamin D Concentrations and the Risk of Hip Fractures: The Women's Health Initiative 
Annals of internal medicine  2008;149(4):242-250.
The association between and vitamin D levels and fractures is uncertain.
To test the hypothesis that serum 25-hydroxyVitamin D (25(OH) vitamin D) levels are associated with the risk of hip fracture in community dwelling women.
Nested case-control study.
40 US clinical centers.
We studied 400 cases of incident hip fractures and 400 controls matched on age, race/ethnicity and date of blood draw (average follow-up time, 7.1 years). Subjects were selected from 39,795 postmenopausal women without previous hip fractures, not using estrogens or other bone-active therapies.
Serum 25(OH) vitamin D was measured on baseline serum using radioimmunoassay with DiaSorin reagents and divided into quartiles. Conditional logistic regression was used to estimate the odds ratio with 95% confidence intervals (CI). Multivariable models included age, body mass index, parental and personal history of fractures, smoking, alcohol and calcium intake, geographic location and corticosteroid use.
The mean (standard deviation, SD) 25(OH) vitamin D (nM) was lower in cases, 56.2(20.3) compared to controls, 59.7(18), p=0.007. A 25 nM (10ng/ml) decrease in 25(OH) vitamin D was associated with a 33% increased risk of hip fracture (odds ratio=1.33; 95%CI,1.06, 1.68) in multivariable models. Compared to women with 25(OH) vitamin D ≥70.7 nM (Quartile 4), the odds ratio of hip fracture was 1.71 (1.05, 2.79), 1.09 (0.70, 1.71) and 0.82 (0.51, 1.31) in women with 25(OH) vitamin D <47.5 nM, 47.5 to 60 nM, 60 to <70 nM, respectively, p trend =0.015. This association was in part mediated by a marker of bone resorption but remained statistically significant. Adjustment for falls, physical function, frailty, renal function, or sex steroid hormones had no effect on this association.
No measure of bone density.
Low serum 25(OH) vitamin D concentrations are associated with a higher risk of hip fracture. Measurement of 25(OH) vitamin D may be useful in identifying women at high risk of hip fracture.
PMCID: PMC2743412  PMID: 18711154
7.  Prevalence and correlates of vitamin D status in African American men 
BMC Public Health  2009;9:191.
Few studies have examined vitamin D insufficiency in African American men although they are at very high risk. We examined the prevalence and correlates of vitamin D insufficiency among African American men in Philadelphia.
Participants in this cross-sectional analysis were 194 African American men in the Philadelphia region who were enrolled in a risk assessment program for prostate cancer from 10/96–10/07. All participants completed diet and health history questionnaires and provided plasma samples, which were assessed for 25-hydroxyvitamin D (25(OH)D) concentrations. We used linear regression models to examine associations with 25(OH)D concentrations and logistic regression to estimate odds ratios (OR) for having 25(OH)D ≥ 15 ng/mL.
Mean 25(OH)D was 13.7 ng/mL, and 61% of men were classified as having vitamin D insufficiency (25(OH)D <15 ng/mL). Even among men with vitamin D intake ≥ 400 IU/day, 55% had 25(OH)D concentrations <15 ng/mL. In multivariate models, 25(OH)D concentrations were significantly associated with supplemental vitamin D intake (OR 4.3, 95% confidence interval (CI) 1.5, 12.4) for >400 vs. 0 IU/day), milk consumption (OR 5.9, 95% CI 2.2, 16.0 for ≥ 3.5 vs. <1 time per week), and blood collection in the summer. Additionally, 25(OH)D concentrations increased with more recreational physical activity (OR 1.3, 95% CI 1.1, 1.6 per hour). A significant inverse association of body mass index with 25(OH)D concentrations in bivariate analyses was attenuated with adjustment for season of blood collection.
The problem of low vitamin D status in African American men may be more severe than previously reported. Future efforts to increase vitamin D recommendations and intake, such as through supplementation, are warranted to improve vitamin D status in this particularly vulnerable population.
PMCID: PMC2708155  PMID: 19534831
8.  Mammographic density and serum 25-hydroxyvitamin D levels 
Vitamin D, which influences cellular proliferation and breast tissue characteristics, has been inversely correlated with breast cancer risk. Dietary vitamin D intake has been associated with lower mammographic density (MD), a strong intermediate marker of breast cancer risk.
We examined the relationship between MD and serum 25-hydroxyvitamin D [25(OH)D], an integrated measure of vitamin D status from dietary sources and sunlight exposure, in a multi-ethnic cohort of women undergoing screening mammography. We recruited women age 40–60 years without a history of breast cancer at the time of their routine screening mammogram, and conducted in-person interviews and collected blood specimens. We enrolled 195 women from 2007–2008, 120 gave blood, and 114 were evaluable, including 25% white, 41% African American, 18% African Caribbean, and 16% Hispanic. We digitized mammograms and calculated percent density, dense area, and non-dense area on cranial-caudal images. We measured serum 25(OH)D in batched, archived specimens. Median serum 25(OH)D was 22 ng/ml (range, 8–66 ng/ml). In univariable analysis, higher serum 25(OH)D was associated with white race, higher educational level, ever breast feeding, and blood draw during the summer. After adjusting for body mass index and other confounders, we found no association between serum 25(OH)D and different measures of MD. However, when stratified by season, 25(OH)D was inversely associated with dense area during July-December (p = 0.034).
Overall, our findings suggest that circulating vitamin D, a potentially modifiable breast cancer risk factor, is not associated with MD; the seasonal effects we observed need to be replicated in larger cohorts.
PMCID: PMC3996501  PMID: 24742098
Vitamin D; 25-hydroxyvitamin D; Breast cancer; Mammographic density
9.  Housework Reduces All-Cause and Cancer Mortality in Chinese Men 
PLoS ONE  2013;8(5):e61529.
Leisure time physical activity has been extensively studied. However, the health benefits of non-leisure time physical activity, particular those undertaken at home on all-cause and cancer mortality are limited, particularly among the elderly.
We studied physical activity in relation to all-cause and cancer mortality in a cohort of 4,000 community-dwelling elderly aged 65 and older. Leisure time physical activity (sport/recreational activity and lawn work/yard care/gardening) and non-leisure time physical activity (housework, home repairs and caring for another person) were self-reported on the Physical Activity Scale for the Elderly. Subjects with heart diseases, stroke, cancer or diabetes at baseline were excluded (n = 1,133).
Among the 2,867 subjects with a mean age of 72 years at baseline, 452 died from all-cause and 185 died from cancer during the follow-up period (2001–2012). With the adjustment for age, education level and lifestyle factors, we found an inverse association between risk of all-cause mortality and heavy housework among men, with the adjusted hazard ratio (HR) of 0.72 (95%CI = 0.57–0.92). Further adjustment for BMI, frailty index, living arrangement, and leisure time activity did not change the result (HR = 0.71, 95%CI = 0.56–0.91). Among women, however, heavy housework was not associated with all-cause mortality. The risk of cancer mortality was significantly lower among men who participated in heavy housework (HR = 0.52, 95%CI = 0.35–0.78), whereas among women the risk was not significant. Men participated in light housework also were at lower risk of cancer mortality than were their counterparts, however, the association was not significant. Leisure time physical activity was not related to all-cause or cancer mortality in either men or women.
Heavy housework is associated with reduced mortality and cancer deaths over a 9-year period. The underlying mechanism needs further study.
PMCID: PMC3647044  PMID: 23667441
10.  Simplified Categorization of Outdoor Activities for Male and Female U.S. Indoor Workers—A Feasibility Study to Improve Assessment of Ultraviolet Radiation Exposures in Epidemiologic Study Questionnaires 
Skin cancer studies depend on questionnaires to estimate exposure to ultraviolet light and subsequent risk but are limited by recall bias. We investigate the feasibility of developing a short checklist of categories comprising outdoor activities that can improve sun exposure questionnaires for use in epidemiologic studies. We recruited 124 working and retired U.S. radiologic technologists (52% women). Each subject was instructed to complete a daily activity diary, listing main indoor and outdoor activities between 9:00 A.M. and 5:00 P.M. during a 7 day period. A total of 4697 entries were associated with 1408 h (21.1%) of the total 6944 h spent outdoors. We were able to classify the activities into seven main activity categories: driving, yard work, home-maintenance, walking or performing errands, water activities, other recreational or sports activities and leisure activities or relaxing outside. These activities accounted for more than 94% of time spent outdoors both for working and retired men and women. Our data document the feasibility and guidance for developing a short checklist of outdoor activities for use in epidemiologic questionnaires for estimating sunlight exposures of working and retired indoor workers.
PMCID: PMC3956440  PMID: 18643910
11.  Vitamin D Status and Early Age-Related Macular Degeneration in Postmenopausal Women 
Archives of ophthalmology  2011;129(4):481-489.
The relationship between serum 25-hydroxyvitamin D (25(OH)D) concentrations (nmol/L) and the prevalence of early age-related macular degeneration (AMD) was investigated among participants of the Carotenoids in Age-Related Eye Disease Study.
Stereoscopic fundus photographs, taken from 2001–2004, assessed AMD status. Baseline (1994–1998) serum samples were available for 25(OH)D assays in 1,313 women with complete ocular and risk factor data. Odds ratios (ORs) and 95% confidence intervals (CIs) for early AMD (n=241), among 1,287 without advanced disease, were estimated with logistic regression and adjusted for age, smoking, iris pigmentation, family history of AMD, cardiovascular disease, diabetes, and hormone therapy use.
In multivariate models, no significant relationship was observed between early AMD and 25(OH)D (OR for quintile 5 vs. 1=0.79, 95% CI=0.50–1.24; p for trend=0.47). A significant age interaction (p=0.0025) suggested selective mortality bias in women ≥75 years: serum 25(OH)D was associated with decreased odds of early AMD in women <75 years (n=968) and increased odds in women ≥75 years (n=319) (OR for quintile 5 vs. 1=0.52, 95% CI=0.29–0.91; p for trend=0.02 and 1.76, 95% CI=0.77–4.13; p for trend=0.05, respectively). Further adjustment for body mass index and recreational physical activity, predictors of 25(OH)D, attenuated the observed association in women <75 years. Additionally, among women <75 years, intake of vitamin D from foods and supplements was related to decreased odds of early AMD in multivariate models; no relationship was observed with self-reported time spent in direct sunlight.
High serum 25(OH)D concentrations may protect against early AMD in women <75 years.
PMCID: PMC3075411  PMID: 21482873
vitamin D; 25-hydroxyvitamin D; sunlight; diet; macular degeneration; cohort studies; epidemiology
12.  Intensity and Timing in Life of Recreational Physical Activity in Relation to Breast Cancer Risk Among Pre- and Postmenopausal Women 
Regular recreational physical activity has been found to be associated with a decrease in breast cancer risk in women in the majority of epidemiologic studies, but research findings are inconsistent regarding the intensity of activity and timing in life. To address these issues the relations of moderate and vigorous intensity recreational physical activity during ages 14-20, 21-34, 35-50, and over age 50 years to pre- and postmenopausal breast cancer risk were examined. A case-control study of 858 women, with histological confirmation of invasive breast cancer, and 1085 controls, free of any cancer diagnosis, all subjects aged 28-79 years was conducted in the Region of Western Pomerania (Poland). Physical activity was assessed using a self-administered questionnaire with questions on type of activity, duration, frequency, and intensity for each type of activity. Odds ratios (OR) and 95% confidence intervals (CI) of breast cancer associated with physical activity were calculated using unconditional logistic regression. Vigorous physical activity at ages 14-20 and 21-34 years lowered breast cancer risk by at least 35% in premenopausal women and by at least 51% in postmenopausal women for the highest versus lowest quartiles of the activity. The risk was also reduced in postmenopausal women who reported on average more than 1.74 hours per week of vigorous intensity recreational activity in ages >50 years (OR = 0.58; 95%CI = 0.27-0.97; P for trend = 0.013). For moderate activity the relationships remained statistically significant only in postmenopausal women active during ages 14- 20 years. The results indicate also a plausible risk reduction among premeno-pausal women. These results support the hypothesis that recrea-tional activity, particularly done early in life, is associated with a decrease in the invasive breast cancer risk in postmenopausal women. Among premenopausal women, only vigorous forms of activity may significantly decrease the risk.
Key pointsRecreational physical activity of vigorous intensity during ages 14-20 and 21-34 years protect against breast cancer regardless of menopausal status.Vigorous recreational physical activity at ages >50 years was also associated with reduced postmeno-pausal breast cancer risk.The risk reduction was also observed among post-menopausal women engaged in recreational physical activity of moderate intensity at ages 14-20 years.
PMCID: PMC3761722  PMID: 24149701
Exercise; breast cancer; case-control study; prevention
13.  Physical Activity During Pregnancy and Risk of Hyperglycemia 
Journal of Women's Health  2012;21(7):769-775.
To determine the association between moderate and vigorous physical activities (MVPA) during midpregnancy and the risk of hyperglycemia.
Data were from 1437 pregnant women. Frequency, duration, and intensity of MVPA during the previous 7 days were collected via questionnaire at 17–22 weeks' gestation. Modes of MVPA included work, recreation, transportation, caregiving, and indoor and outdoor household activities. Hyperglycemia was defined as a glucose concentration ≥130 mg/dL on a 1-hour, 50-g glucose challenge test or gestational diabetes mellitus (GDM) assessed at ∼27 weeks' gestation. Multivariable Poisson regression estimated risks of hyperglycemia associated with total and mode-specific MVPA.
There were 269 women (18.7%) with hyperglycemia. Any metabolic equivalent (MET) hours/week of recreational MVPA was associated with a 27% lower risk of hyperglycemia (adjusted relative risk, [aRR] 0.73, 95% confidence interval [95%CI] 0.54-0.99). Multiplicative interaction terms were significant for prepregnancy body mass index (BMI) and recreational MVPA (p=0.01). Among women with prepregnancy BMI <25 kg/m2, recreational MVPA was associated with a 48% lower risk of hyperglycemia (aRR 0.52, 95%CI 0.33-0.83) compared to women who reported none. There was no association of hyperglycemia and recreational MVPA among women with prepregnancy BMI <25 kg/m2.
Recreational MVPA during pregnancy is associated with a lower risk of hyperglycemia, specifically among women with prepregnancy BMI <25 kg/m2. Further research is warranted to determine recommended amounts and intensities of physical activity and to discern whether there are differences in the effects of physical activity between specific modes of physical activity or among subgroups of women in relation to hyperglycemia.
PMCID: PMC3387759  PMID: 22537020
14.  Recreational Physical Activity and Steroid Hormone Levels in Postmenopausal Women 
American Journal of Epidemiology  2009;170(9):1095-1104.
Recreational physical activity has been both positively and inversely associated with cancer risk for postmenopausal women, acting presumably through hormonal mechanisms. Relatively little is known about the effects of exercise on postmenopausal steroid hormone levels. The authors evaluated the association between recreational activity and plasma steroid hormones among 623 US healthy, postmenopausal women in the Nurses’ Health Study not using exogenous hormones at the time of blood draw (1989–1990). Participants self-reported recreational physical activity by questionnaire in 1986, 1988, and 1992. Plasma samples were assayed for estrogens, androgens, and sex hormone-binding globulin. Geometric mean hormone levels adjusted and not adjusted for body mass index were calculated. In general, estrogen and androgen levels were lower in the most- and the least-active women compared with those reporting moderate activity, suggesting a U-shaped relation. For example, estrone sulfate levels in quintiles 1–5 of metabolic equivalent task-hours were 197, 209, 222, 214, and 195 pg/mL, respectively. Tests for nonlinearity using polynomial regression were significant for several estrogens, androgens, and sex hormone-binding globulin (2-sided P ≤ 0.01). These results suggest the possibility of a nonlinear relation between recreational physical activity and hormone levels in postmenopausal women.
PMCID: PMC2781741  PMID: 19783585
androgens; biological markers; cohort studies; estrogens; exercise; hormones
15.  Relationship between intensity of night shift work and antioxidant status in blood of nurses 
Light-at-night exposure can disrupt the human circadian rhythm via clock gene expressions. The circadian rhythm influences antioxidant enzymes’ activity and cellular mRNA levels of these enzymes. The employees working based on a shift system adjust to the changes occurring both on the cell level and on the level of the whole organism. Therefore, a question should be answered whether shift work disturbs oxidant–antioxidant balance and/or generates oxidative stress.
A cross-sectional study was conducted among nurses selected from the Local Registry of the Chamber of Nurses and Midwives in Lodz: 359 nurses worked daily only and 349 working rotating night shifts. These two groups differed significantly in respect of age (p < 0.0001), menopausal status (p < 0.0001), and current smoking habit (p = 0.02). The average total work duration was significantly shorter (12.4 years) in nurses working currently rotating night shifts who worked significantly longer on night shifts than day-workers (26.6 years).
We found statistically significant higher red blood cell glutathione peroxidase in nurses working on night shifts (21.0 ± 4.6 vs. 20.0 ± 5.0 U/g Hb, p < 0.009) after adjusting for age, oral contraceptive hormone use, smoking, and drinking alcohol during last 24 h. Statistically significant lower vitamin A and E levels were found in the premenopausal women working in rotating system (0.690 ± 0.238 vs. 0.786 ± 0.262 μg/ml, p < 0.0001 for vitamin A and 10.93 ± 4.15 vs. 12.78 ± 4.75 μg/ml, p < 0.0001 for vitamin E). The marker of lipid peroxidation (TBARS concentration) was significantly lower in the premenopausal nurses than postmenopausal ones working day shifts only (2.06 ± 0.76 vs. 2.21 ± 0.80 nmol/ml, p < 0.038). We observed that erythrocyte GSH-Px activity rose statistically significant in nurses working more night shifts per month (p < 0.01).
The results quoted above seem to support the existence of an association between light-at-night exposure and blood glutathione peroxidase activity in female shift workers. Nevertheless, in order to explain the mechanisms of this association, we need more studies.
PMCID: PMC3825624  PMID: 23179107
Antioxidants; TBARS; Night shift work; Selenium; Light-at-night exposure
16.  Walking behaviour and glycemic control in type 2 diabetes: seasonal and gender differences-Study design and methods 
The high glucose levels typically occurring among adults with type 2 diabetes contribute to blood vessel injury and complications such as blindness, kidney failure, heart disease, and stroke. Higher physical activity levels are associated with improved glycemic control, as measured by hemoglobin A1C. A 1% absolute increase in A1C is associated with an 18% increased risk for heart disease or stroke. Among Canadians with type 2 diabetes, we postulate that declines in walking associated with colder temperatures and inclement weather may contribute to annual post-winter increases in A1C levels.
During this prospective cohort study being conducted in Montreal, Quebec, Canada, 100 men and 100 women with type 2 diabetes will undergo four assessments (once per season) over a one-year period of observation. These assessments include (1) use of a pedometer with a concealed viewing window for a two-week period to measure walking (2) a study centre visit during which venous blood is sampled for A1C, anthropometrics are assessed, and questionnaires are completed for measurement of other factors that may influence walking and/or A1C (e.g. food frequency, depressive symptomology, medications). The relationship between spring-fall A1C difference and winter-summer difference in steps/day will be examined through multivariate linear regression models adjusted for possible confounding. Interpretation of findings by researchers in conjunction with potential knowledge "users" (e.g. health professionals, patient groups) will guide knowledge translation efforts.
Although we cannot alter weather patterns to favour active lifestyles, we can design treatment strategies that take seasonal and weather-related variations into account. For example, demonstration of seasonal variation of A1C levels among Canadian men and women with T2D and greater understanding of its determinants could lead to (1) targeting physical activity levels to remain at or exceed peak values achieved during more favourable weather conditions. Strategies may include shifting to indoor activities or adapting to less favourable conditions (e.g. appropriate outdoor garments, more frequent but shorter duration periods of activity) (2) increasing dose/number of glucose-lowering medications during the winter and reducing these during the summer, in anticipation of seasonal variations (3) examining the impact of bright light therapy on activity and A1C among T2D patients with an increase in depressive symptomology when sunlight hours decline.
PMCID: PMC1783642  PMID: 17224062
17.  Correlates of Circulating 25-Hydroxyvitamin D 
American Journal of Epidemiology  2010;172(1):21-35.
Low vitamin D status is common globally and is associated with multiple disease outcomes. Understanding the correlates of vitamin D status will help guide clinical practice, research, and interpretation of studies. Correlates of circulating 25-hydroxyvitamin D (25(OH)D) concentrations measured in a single laboratory were examined in 4,723 cancer-free men and women from 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers, which covers a worldwide geographic area. Demographic and lifestyle characteristics were examined in relation to 25(OH)D using stepwise linear regression and polytomous logistic regression. The prevalence of 25(OH)D concentrations less than 25 nmol/L ranged from 3% to 36% across cohorts, and the prevalence of 25(OH)D concentrations less than 50 nmol/L ranged from 29% to 82%. Seasonal differences in circulating 25(OH)D were most marked among whites from northern latitudes. Statistically significant positive correlates of 25(OH)D included male sex, summer blood draw, vigorous physical activity, vitamin D intake, fish intake, multivitamin use, and calcium supplement use. Significant inverse correlates were body mass index, winter and spring blood draw, history of diabetes, sedentary behavior, smoking, and black race/ethnicity. Correlates varied somewhat within season, race/ethnicity, and sex. These findings help identify persons at risk for low vitamin D status for both clinical and research purposes.
PMCID: PMC2892536  PMID: 20562191
body mass index; cohort studies; diet; dietary supplements; ethnic groups; exercise; seasons; vitamin D
18.  Vitamin K Supplementation in Postmenopausal Women with Osteopenia (ECKO Trial): A Randomized Controlled Trial 
PLoS Medicine  2008;5(10):1-12.
Vitamin K has been widely promoted as a supplement for decreasing bone loss in postmenopausal women, but the long-term benefits and potential harms are unknown. This study was conducted to determine whether daily high-dose vitamin K1 supplementation safely reduces bone loss, bone turnover, and fractures.
Methods and Findings
This single-center study was designed as a 2-y randomized, placebo-controlled, double-blind trial, extended for earlier participants for up to an additional 2 y because of interest in long-term safety and fractures. A total of 440 postmenopausal women with osteopenia were randomized to either 5 mg of vitamin K1 or placebo daily. Primary outcomes were changes in BMD at the lumbar spine and total hip at 2 y. Secondary outcomes included changes in BMD at other sites and other time points, bone turnover markers, height, fractures, adverse effects, and health-related quality of life. This study has a power of 90% to detect 3% differences in BMD between the two groups. The women in this study were vitamin D replete, with a mean serum 25-hydroxyvitamin D level of 77 nmol/l at baseline. Over 2 y, BMD decreased by −1.28% and −1.22% (p = 0.84) (difference of −0.06%; 95% confidence interval [CI] −0.67% to 0.54%) at the lumbar spine and −0.69% and −0.88% (p = 0.51) (difference of 0.19%; 95% CI −0.37% to 0.75%) at the total hip in the vitamin K and placebo groups, respectively. There were no significant differences in changes in BMD at any site between the two groups over the 2- to 4-y period. Daily vitamin K1 supplementation increased serum vitamin K1 levels by 10-fold, and decreased the percentage of undercarboxylated osteocalcin and total osteocalcin levels (bone formation marker). However, C-telopeptide levels (bone resorption marker) were not significantly different between the two groups. Fewer women in the vitamin K group had clinical fractures (nine versus 20, p = 0.04) and fewer had cancers (three versus 12, p = 0.02). Vitamin K supplements were well-tolerated over the 4-y period. There were no significant differences in adverse effects or health-related quality of life between the two groups. The study was not powered to examine fractures or cancers, and their numbers were small.
Daily 5 mg of vitamin K1 supplementation for 2 to 4 y does not protect against age-related decline in BMD, but may protect against fractures and cancers in postmenopausal women with osteopenia. More studies are needed to further examine the effect of vitamin K on fractures and cancers.
Trial registration: (#NCT00150969) and Current Controlled Trials (#ISRCTN61708241)
Angela Cheung and colleagues investigate whether vitamin K1 can prevent bone loss among postmenopausal women with osteopenia.
Editors' Summary
Osteoporosis is a bone disease in which the bones gradually become less dense and more likely to break. In the US, 10 million people have osteoporosis and 18 million have osteopenia, a milder condition that precedes osteoporosis. In both conditions, insufficient new bone is made and/or too much old bone is absorbed. Although bone appears solid and unchanging, very little bone in the human body is more than 10 y old. Old bone is continually absorbed and new bone built using calcium, phosphorous, and proteins. Because the sex hormones control calcium and phosphorous deposition in the bones and thus bone strength, the leading cause of osteoporosis in women is reduced estrogen levels after menopause. In men, an age-related decline in testosterone levels can cause osteoporosis. Most people discover they have osteoporosis only when they break a bone, but the condition can be diagnosed and monitored using bone mineral density (BMD) scans. Treatments can slow down or reverse bone loss (antiresorptive therapies) and some (bone formation therapies) can even make bone and build bone tissue.
Why Was This Study Done?
Although regular exercise and a healthy diet can help to keep bones strong, other ways of preventing osteoporosis are badly needed. Recently, the lay media has promoted vitamin K supplements as a way to reduce bone loss in postmenopausal women. Vitamin K (which is found mainly in leafy green vegetables) is required for a chemical modification of proteins called carboxylation. This modification is essential for the activity of three bone-building proteins. In addition, there is some evidence that low bone density and fractures are associated with a low vitamin K intake. However, little is known about the long-term benefits or harms of vitamin K supplements. In this study, the researchers investigate whether a high-dose daily vitamin K supplement can safely reduce bone loss, bone turnover, and fractures in postmenopausal women with osteopenia in a randomized controlled trial called the “Evaluation of the Clinical Use of Vitamin K Supplementation in Post-Menopausal Women With Osteopenia” (ECKO) trial.
What Did the Researchers Do and Find?
In the study, 440 postmenopausal women with osteopenia were randomized to receive 5mg of vitamin K1 (the type of vitamin K in North American food; the recommended daily adult intake of vitamin K1 is about 0.1 mg) or an inactive tablet (placebo) daily for 2 y; 261 of the women continued their treatment for 2 y to gather information about the long-term effects of vitamin K1 supplementation. All the women had regular bone density scans of their lower back and hips and were examined for fractures and for changes in bone turnover. After 2 y and after 4 y, lower back and hip bone density measurements had decreased by similar amounts in both treatment groups. The women who took vitamin K1 had 10-fold higher amounts of vitamin K1 in their blood than the women who took placebo and lower amounts of a bone formation marker; the levels of a bone resorption marker were similar in both groups. Over the 4-y period, fewer women in the vitamin K group had fractures (nine versus 20 women in the placebo group), and fewer had cancer (three versus 12). Finally, vitamin K supplementation was well tolerated over the 4-y period and adverse health effects were similar in the two treatment groups.
What Do These Findings Mean?
These findings indicate that a high daily dose of vitamin K1 provides no protection against the age-related decline in bone density in postmenopausal women with osteopenia, but that vitamin K1 supplementation may protect against fractures and cancers in these women. The apparent contradiction between the effects of vitamin K1 on bone density and on fractures could mean that vitamin K1 supplements strengthen bone by changing factors other than bone density, e.g., by changing its fine structure rather than making it denser. However, because so few study participants had fractures, the difference in the fracture rate between the two treatment groups might have occurred by chance. Larger studies are therefore needed to examine the effect of vitamin K1 on fractures (and on cancer) and, until these are done, high-dose vitamin K1 supplementation should not be recommended for the prevention of osteoporosis.
Additional Information.
Please access these Web sites via the online version of this summary at
The US National Institute of Arthritis and Musculoskeletal and Skin Diseases provides detailed information about osteoporosis (in English and Spanish) and links to other resources, including an interactive web tool called Check Up On Your Bones
MedlinePlus provides links to additional information about osteoporosis (in English and Spanish)
The MedlinePlus Encyclopedia has a page about vitamin K
The UK Food Standards Agency provides information about vitamin K
Full details about the ECKO trial are available on the Web site
The Canadian Task Force for Preventive Health Care provides recommendations on the prevention of osteoporosis and osteoporotic fractures in postmenopausal women
Osteoporosis Canada provides information on current topics related to osteoporosis
PMCID: PMC2566998  PMID: 18922041
19.  Vitamin D inadequacy in Belgian postmenopausal osteoporotic women 
BMC Public Health  2007;7:64.
Inadequate serum vitamin D [25(OH)D] concentrations are associated with secondary hyperparathyroidism, increased bone turnover and bone loss, which increase fracture risk. The objective of this study is to assess the prevalence of inadequate serum 25(OH)D concentrations in postmenopausal Belgian women. Opinions with regard to the definition of vitamin D deficiency and adequate vitamin D status vary widely and there are no clear international agreements on what constitute adequate concentrations of vitamin D.
Assessment of 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone was performed in 1195 Belgian postmenopausal women aged over 50 years. Main analysis has been performed in the whole study population and according to the previous use of vitamin D and calcium supplements. Four cut-offs of 25(OH)D inadequacy were fixed : < 80 nmol/L, <75 nmol/L, < 50 nmol/L and < 30 nmol/L.
Mean (SD) age of the patients was 76.9 (7.5) years, body mass index was 25.7 (4.5) kg/m2. Concentrations of 25(OH)D were 52.5 (21.4) nmol/L. In the whole study population, the prevalence of 25(OH)D inadequacy was 91.3 %, 87.5 %, 43.1 % and 15.9% when considering cut-offs of 80, 75, 50 and 30 nmol/L, respectively. Women who used vitamin D supplements, alone or combined with calcium supplements, had higher concentrations of 25(OH)D than non-users. Significant inverse correlations were found between age/serum PTH and serum 25(OH)D (r = -0.23/r = -0.31) and also between age/serum PTH and femoral neck BMD (r = -0.29/r = -0.15). There is a significant positive relation between age and PTH (r = 0.16), serum 25(OH)D and femoral neck BMD (r = 0.07). (P < 0.05)
Vitamin D concentrations varied with the season of sampling but did not reach statistical significance (P = 0.09).
This study points out a high prevalence of vitamin D inadequacy in Belgian postmenopausal osteoporotic women, even among subjects receiving vitamin D supplements.
PMCID: PMC1866237  PMID: 17462085
20.  Pre-diagnosis physical activity and mammographic density in breast cancer survivors 
To investigate the association between physical activity (PA) and mammographic density in the year before diagnosis in a population-based sample of 474 women diagnosed with stage 0–IIIA breast cancer and enrolled in the Health, Eating, Activity, and Lifestyle Study.
We collected information on PA during an interview administered at a baseline visit scheduled within the first year after diagnosis. Participants recalled the type, duration, and frequency of different PAs for the year prior to their diagnosis. Dense area and percent density were estimated, from mammograms imaged approximately one year before diagnosis, as a continuous measure using a computer-assisted software program. Analysis of covariance methods were used to obtain mean density across PA tertiles adjusted for confounders. We stratified analyses by menopausal status and body mass index (BMI) because these factors strongly influence density.
We observed a statistically significant decline in mammographic dense area (p for trend = 0.046) and percent density (p for trend = 0.026) with increasing level of sports/recreational PA in postmenopausal women with a BMI ≥ 30 kg/m2. Conversely, in premenopausal women with a BMI < 30 kg/m2, we observed a statistically significant increase in percent density with increasing level of sports/recreational PA (p for trend = 0.037).
Both mammographic dense area and percent density are inversely related to level of sports/recreational PA in obese postmenopausal women. Increasing PA among obese postmenopausal women may be a reasonable intervention approach to reduce mammographic density.
PMCID: PMC3034407  PMID: 16319988
breast cancer; body fat; exercise; obesity; weight
21.  Physical Activity, Body Mass Index and Mammographic Density in Postmenopausal Breast Cancer Survivors 
To investigate the association between physical activity, body mass index (BMI) and mammographic density in an ethnically-diverse population-based sample of 522 postmenopausal women diagnosed with stage 0–IIIA breast cancer and enrolled in the Health, Eating, Activity, and Lifestyle Study.
We collected information on BMI and physical activity during a clinic visit two to three years after diagnosis. Weight and height were measured in a standard manner. Using an interview-administered questionnaire, participants recalled the type, duration, and frequency of physical activities in the past year. We estimated dense area and percent density as a continuous measure using a computer-assisted software program from mammograms imaged approximately one to two years after diagnosis. Analysis of covariance methods were used to obtain mean density across World Health Organization BMI categories and physical activity tertiles adjusted for confounders.
We observed a statistically significant decline in percent density (p for trend = .0001), and mammographic dense area (p for trend = 0.0052), with increasing level of BMI adjusted for potential covariates. We observed a statistically significant decline in mammographic dense area (p for trend = .036) with increasing level of sports/recreational physical activity in women with a BMI ≥ 30 kg/m2. Conversely, in women with a BMI < 25 kg/m2, we observed a nonstatistically significant increase in mammographic dense area and percent density with increasing level of sports/recreational physical activity.
Increasing physical activity among obese postmenopausal breast cancer survivors may be a reasonable intervention approach to reduce mammographic density.
PMCID: PMC3839099  PMID: 17261853
breast cancer; body fat; exercise; obesity; weight; breast tissue; breast density
22.  25-Hydroxyvitamin-D3 levels are positively related to subsequent cortical bone development in childhood: findings from a large prospective cohort study 
Osteoporosis International  2011;23(8):2117-2128.
In exploring relationships between vitamin D status in childhood and cortical bone, little relationship was observed with plasma concentrations of 25-hydroxyvitamin-D2 [25(OH)D2], whereas 25-hydroxyvitamin-D3 [25(OH)D3] was positively related to cortical bone mineral content (BMCC) and cortical thickness, suggesting D3 exerts a beneficial effect on cortical bone development in contrast to D2.
The study is aimed to determine whether vitamin D status in childhood is related to cortical bone development by examining prospective relationships between plasma concentrations of 25(OH)D2 and 25(OH)D3 at 7.6, 9.9 or 11.8 years and peripheral quantitative computed tomography (pQCT) measurements of the mid-tibia at age 15.5 years, in children from the Avon Longitudinal Study of Parents and Children.
Relationships between vitamin D status and pQCT outcomes were analysed by bootstrap linear regression, adjusted for age, sex, body composition, socioeconomic position and physical activity, in 2,247 subjects in whom all covariates were available. 25(OH)D3 was also adjusted for season and 25(OH)D2, and 25(OH)D2 for 25(OH)D3.
25(OH)D3 was positively related to BMCC [0.066(0.009,0.122), P = 0.02], whereas no association was seen with 25(OH)D2 [−0.008(−0.044,0.027), P = 0.7] [beta (with 95% CI) represents SD changes per doubling of vitamin D], P = 0.03 for difference in associations of 25(OH)D2 and 25(OH)D3 with BMCC. There were also differences in associations with cortical geometry, since 25(OH)D3 was positively related to cortical thickness [0.11(0.04, 0.19), P = 0.002], whereas no association was seen with 25(OH)D2 [−0.04(−0.08,0.009), P = 0.1], P = 0.0005 for difference. These relationships translated into differences in biomechanical strength as reflected by buckling ratio, which was positively related to 25(OH)D2 [0.06(0.01,0.11), P = 0.02] indicating less resistance to buckling, but inversely related to 25(OH)D3 [−0.1(−0.19,-0.02), P = 0.03], P = 0.001 for difference.
In contrast to 25(OH)D2, 25(OH)D3 was positively related to subsequent cortical bone mass and predicted strength. In vitamin D-deficient children in whom supplementation is being considered, our results suggest that D3 should be used in preference to D2.
Electronic supplementary material
The online version of this article (doi:10.1007/s00198-011-1813-9) contains supplementary material, which is available to authorized users.
PMCID: PMC3406315  PMID: 22080378
Adolescence; ALSPAC; Cortical bone; pQCT; Vitamin D
23.  Seasonal variations in serum vitamin D according to age and sex 
Background: Exposure to sunlight is the main source of vitamin D production. This study was performed to assess the status of serum vitamin D across the different seasons in geographic region of Babol, with latitude of 36 in northern Iran.
Methods: The study – female participants were 15 years old and above selected prospectively according to the inclusion criteria who attended an Outpatient clinic. The serum 25-hydroxyvitamin D 25-OHD was measured with enzyme-linked immunosorbent assay (ELISA). Serum OHD <20 ng/ml was considered as vitamin D deficiency. Serum 25-OHD levels were compared across various seasons according to sex and age. Proportions of serum 25-OHD deficiency were also compared between the various seasons according to sex and age.
Results: A total of 576 females and 120 males with respective mean age of 44.8±14.1 and 47.8±29 years entered into the study. The mean serum 25-OHD was 20.8±27 ng/ ml, the prevalence of serum 25-OHD deficiency was 70.1%. In women compared with men, the mean serum 25-OHD was significantly lower but the proportion of deficiency was not significant (20.6±24.9 ng/ml vs 23.2±31.4 ng/ l. p=0.021 and 70.8% vs 67.5% p=0.60 respectively). The mean 25-OHD nd proportion of deficiency did not vary across the different seasons with regard to age. However, in the summer and in the autumn, the women had significantly lower serum 25-OHD concentrations than the men (p= 0.021and 0.016 respectively).
Conclusion: The findings of this study indicated no significant seasonal variations of vitamin D in geographic regions of Babol. However, during the autumn and the winter months, the women are at high risk of vitamin D deficiency which corresponds to nadir of serum 25-OHD levels.
PMCID: PMC3755860  PMID: 24009930
Vitamin D; Seasonal change; Sex; Age; Deficiency
24.  Reactivation of tuberculosis and vitamin D deficiency: the contribution of diet and exposure to sunlight 
Thorax  2007;62(11):1003-1007.
As well as its role in the regulation of calcium metabolism, vitamin D is an immunoregulatory hormone. Epidemiological evidence also suggests a link between vitamin D deficiency and tuberculosis (TB). A study was undertaken to examine serum vitamin D concentrations before treatment in patients with active TB and their contacts from the same ethnic and social background and to investigate the relative contributions of diet and sunlight exposure.
Serum vitamin D concentrations were measured before treatment in 178 patients with active TB and 130 healthy contacts. The prevalence of vitamin D deficiency and its relation to skin colour, month of estimation and TB diagnosis were determined. 35 patients and 35 frequency‐matched contacts completed dietary and sun exposure questionnaires to determine the relative contribution of these to serum vitamin D concentrations.
There was a statistically significant difference in serum vitamin D concentrations between patients and contacts (20.1 vs 30.8 nmol/l, 95% CI 7.1 to 14.3; p<0.001) and significantly more patients had severely deficient concentrations (<21 nmol/l) than controls (114/178 (64%) vs 40/130 (31%), p<0.001). There was no association between serum concentrations of vitamin D and skin pigmentation. The healthy contacts showed a predictable seasonal pattern, rising to peak concentrations in the summer months, but this response was absent in patients with TB. Dietary intake was the same in both patients with TB and contacts matched for age, sex and skin colour, but patients with TB displayed a stronger correlation between serum vitamin D concentrations and dietary intake (r = 0.42, p = 0.016) than controls (r = 0.13, p>0.1). There was no difference in sunlight exposure between the groups.
Patients with active TB have lower serum vitamin D concentrations than contacts from similar ethnic and social backgrounds and with comparable dietary intake and sun exposure, and do not show the expected seasonal variation. These observations indicate that other factors are contributing to vitamin D deficiency in patients with TB and suggest abnormal handling of this vitamin.
PMCID: PMC2117124  PMID: 17526677
25.  Prevalence of hypovitaminosis D and predictors of vitamin D status in Italian healthy adolescents 
Vitamin D plays an important role in health promotion during adolescence. Vitamin D deficiency and insufficiency are common in adolescents worldwide. Few data on vitamin D status and risk factors for hypovitaminosis D in Italian adolescents are currently available.
25-hydroxyvitamin D (25-OH-D) and parathyroid hormone (PTH) levels were evaluated in 427 Italian healthy adolescents (10.0-21.0 years). We used the following cut-off of 25-OH-D to define vitamin D status: deficiency < 50 nmol/L; insufficiency 50-75 nmol/L; sufficiency ≥ 75 nmol/L. Hypovitaminosis D was defined as 25-OH-D levels < 75.0 nmol/L and severe vitamin D deficiency as 25-OH-D levels < 25.0 nmol/L. We evaluated gender, residence, season of blood withdrawal, ethnicity, weight status, sun exposure, use of sunscreens, outdoor physical activity, and history of fractures as predictors of vitamin D status.
Enrolled adolescents had a median serum 25-OH-D level of 50.0 nmol/L, range 8.1-174.7, with 82.2% having hypovitaminosis D. Vitamin D deficiency and insufficiency were detected in 49.9% and 32.3% of adolescents, respectively. Among those with deficiency, 38 subjects were severely deficient (38/427, 8.9% of the entire sample). Non-white adolescents had a higher prevalence of severe vitamin D deficiency than white subjects (6/17-35.3% vs 32/410-7.8% respectively, p = 0.002). Logistic regression showed increased risk of hypovitaminosis D as follows: blood withdrawal taken in winter-spring (Odds ratio (OR) 5.64) compared to summer-fall period; overweight-obese adolescents (OR 3.89) compared to subjects with normal body mass index (BMI); low sun exposure (OR 5.94) compared to moderate-good exposure and regular use of sunscreens (OR 5.89) compared to non regular use. Adolescents who performed < 3 hours/week of outdoor exercise had higher prevalence of hypovitaminosis D. Gender, residence, and history of fractures were not associated with vitamin D status. Serum 25-OH-D levels were inversely related to PTH (r = -0.387, p < 0.0001) and BMI-SDS (r = -0.141, p = 0.007). 44/427 (10.3%) adolescents showed secondary hyperparathyroidism.
Italian adolescents have high prevalence of vitamin D deficiency and insufficiency. Pediatricians should tackle predictors of vitamin D status, favoring a healthier lifestyle and promoting supplementation in the groups at higher risk of hypovitaminosis D.
PMCID: PMC4064504  PMID: 24902694
Adolescents; Hypovitaminosis D; Vitamin D deficiency; Vitamin D insufficiency; Parathyroid hormone

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