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1.  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.
Adults
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
Adults
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.
Children
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.
Conclusions
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
2.  Inverse Association of Vitamin C with Cataract in Older People in India 
Ophthalmology  2011;118(10):1958-1965.e2.
Objective
To examine the association between vitamin C and cataract in the Indian setting.
Design
Population-based cross-sectional analytic study.
Participants
A total of 5638 people aged ≥60 years.
Methods
Enumeration of randomly sampled villages in 2 areas of north and south India to identify people aged ≥60 years. Participants were interviewed for socioeconomic and lifestyle factors (tobacco, alcohol, household cooking fuel, work, and diet); attended a clinical examination, including lens photography; and provided a blood sample for antioxidant analysis. Plasma vitamin C was measured using an enzyme-based assay in plasma stabilized with metaphosphoric acid, and other antioxidants were measured by reverse-phase high-pressure liquid chromatography.
Main Outcome Measures
Cataract and type of cataract were graded from digital lens images using the Lens Opacity Classification System III (LOCS III), and cataract was classified from the grade in the worse eye of ≥4 for nuclear cataract, ≥3 for cortical cataract, and ≥2 for posterior subcapsular cataract (PSC). Any cataract was defined as any unoperated or operated cataract.
Results
Of 7518 enumerated people, 5638 (75%) provided data on vitamin C, antioxidants, and potential confounders. Vitamin C was inversely associated with cataract (adjusted odds ratio [OR] for highest to lowest quartile = 0.61; 95% confidence interval (CI), 0.51–0.74; P=1.1×10−6). Inclusion of other antioxidants in the model (lutein, zeaxanthin, retinol, β-carotene, and α-tocopherol) made only a small attenuation to the result (OR 0.68; 95% CI, 0.57–0.82; P < 0.0001). Similar results were seen with vitamin C by type of cataract: nuclear cataract (adjusted OR 0.66; CI, 0.54–0.80; P < 0.0001), cortical cataract (adjusted OR 0.70; CI, 0.54–0.90; P < 0.002), and PSC (adjusted OR 0.58; CI, 0.45–0.74; P < 0.00003). Lutein, zeaxanthin, and retinol were significantly inversely associated with cataract, but the associations were weaker and not consistently observed by type of cataract. Inverse associations were also observed for dietary vitamin C and cataract.
Conclusions
We found a strong association with vitamin C and cataract in a vitamin C–depleted population.
Financial Disclosure(s)
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
doi:10.1016/j.ophtha.2011.03.016
PMCID: PMC3185206  PMID: 21705085
3.  A Prospective Study of Plasma Vitamin D Metabolites, Vitamin D Receptor Polymorphisms, and Prostate Cancer 
PLoS Medicine  2007;4(3):e103.
Background
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.
Conclusions
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
Background.
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 http://dx.doi.org/10.1371/journal.pmed.0040103.
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
doi:10.1371/journal.pmed.0040103
PMCID: PMC1831738  PMID: 17388667
4.  Causal Relationship between Obesity and Vitamin D Status: Bi-Directional Mendelian Randomization Analysis of Multiple Cohorts 
PLoS Medicine  2013;10(2):e1001383.
A mendelian randomization study based on data from multiple cohorts conducted by Karani Santhanakrishnan Vimaleswaran and colleagues re-examines the causal nature of the relationship between vitamin D levels and obesity.
Background
Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH)D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis.
Methods and Findings
We used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH)D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects.
Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n = 123,864). Each 1 kg/m2 higher BMI was associated with 1.15% lower 25(OH)D (p = 6.52×10−27). The BMI allele score was associated both with BMI (p = 6.30×10−62) and 25(OH)D (−0.06% [95% CI −0.10 to −0.02], p = 0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH)D (p≤8.07×10−57 for both scores) but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH)D concentrations (IV ratio: −4.2 [95% CI −7.1 to −1.3], p = 0.005). No association was seen for genetically instrumented 25(OH)D with BMI, a finding that was confirmed using data from the GIANT consortium (p≥0.57 for both vitamin D scores).
Conclusions
On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH)D, while any effects of lower 25(OH)D increasing BMI are likely to be small. Population level interventions to reduce BMI are expected to decrease the prevalence of vitamin D deficiency.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Obesity—having an unhealthy amount of body fat—is increasing worldwide. In the US, for example, a third of the adult population is now obese. Obesity is defined as having a body mass index (BMI, an indicator of body fat calculated by dividing a person's weight in kilograms by their height in meters squared) of more than 30.0 kg/m2. Although there is a genetic contribution to obesity, people generally become obese by consuming food and drink that contains more energy than they need for their daily activities. Thus, obesity can be prevented by having a healthy diet and exercising regularly. Compared to people with a healthy weight, obese individuals have an increased risk of developing diabetes, heart disease and stroke, and tend to die younger. They also have a higher risk of vitamin D deficiency, another increasingly common public health concern. Vitamin D, which is essential for healthy bones as well as other functions, is made in the skin after exposure to sunlight but can also be obtained through the diet and through supplements.
Why Was This Study Done?
Observational studies cannot prove that obesity causes vitamin D deficiency because obese individuals may share other characteristics that reduce their circulating 25-hydroxy vitamin D [25(OH)D] levels (referred to as confounding). Moreover, observational studies cannot indicate whether the larger vitamin D storage capacity of obese individuals (vitamin D is stored in fatty tissues) lowers their 25(OH)D levels or whether 25(OH)D levels influence fat accumulation (reverse causation). If obesity causes vitamin D deficiency, monitoring and treating vitamin D deficiency might alleviate some of the adverse health effects of obesity. Conversely, if low vitamin D levels cause obesity, encouraging people to take vitamin D supplements might help to control the obesity epidemic. Here, the researchers use bi-directional “Mendelian randomization” to examine the direction and causality of the relationship between BMI and 25(OH)D. In Mendelian randomization, causality is inferred from associations between genetic variants that mimic the influence of a modifiable environmental exposure and the outcome of interest. Because gene variants do not change over time and are inherited randomly, they are not prone to confounding and are free from reverse causation. Thus, if a lower vitamin D status leads to obesity, genetic variants associated with lower 25(OH)D concentrations should be associated with higher BMI, and if obesity leads to a lower vitamin D status, then genetic variants associated with higher BMI should be associated with lower 25(OH)D concentrations.
What Did the Researchers Do and Find?
The researchers created a “BMI allele score” based on 12 BMI-related gene variants and two “25(OH)D allele scores,” which are based on gene variants that affect either 25(OH)D synthesis or breakdown. Using information on up to 42,024 participants from 21 studies, the researchers showed that the BMI allele score was associated with both BMI and with 25(OH)D levels among the study participants. Based on this information, they calculated that each 10% increase in BMI will lead to a 4.2% decrease in 25(OH)D concentrations. By contrast, although both 25(OH)D allele scores were strongly associated with 25(OH)D levels, neither score was associated with BMI. This lack of an association between 25(OH)D allele scores and obesity was confirmed using data from more than 100,000 individuals involved in 46 studies that has been collected by the GIANT (Genetic Investigation of Anthropometric Traits) consortium.
What Do These Findings Mean?
These findings suggest that a higher BMI leads to a lower vitamin D status whereas any effects of low vitamin D status on BMI are likely to be small. That is, these findings provide evidence for obesity as a causal factor in the development of vitamin D deficiency but not for vitamin D deficiency as a causal factor in the development of obesity. These findings suggest that population-level interventions to reduce obesity should lead to a reduction in the prevalence of vitamin D deficiency and highlight the importance of monitoring and treating vitamin D deficiency as a means of alleviating the adverse influences of obesity on health.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001383.
The US Centers for Disease Control and Prevention provides information on all aspects of overweight and obesity (in English and Spanish); a data brief provides information about the vitamin D status of the US population
The World Health Organization provides information on obesity (in several languages)
The UK National Health Service Choices website provides detailed information about obesity and a link to a personal story about losing weight; it also provides information about vitamin D
The International Obesity Taskforce provides information about the global obesity epidemic
The US Department of Agriculture's ChooseMyPlate.gov website provides a personal healthy eating plan; the Weight-control Information Network is an information service provided for the general public and health professionals by the US National Institute of Diabetes and Digestive and Kidney Diseases (in English and Spanish)
The US Office of Dietary Supplements provides information about vitamin D (in English and Spanish)
MedlinePlus has links to further information about obesity and about vitamin D (in English and Spanish)
Wikipedia has a page on Mendelian randomization (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
Overview and details of the collaborative large-scale genetic association study (D-CarDia) provide information about vitamin D and the risk of cardiovascular disease, diabetes and related traits
doi:10.1371/journal.pmed.1001383
PMCID: PMC3564800  PMID: 23393431
5.  Association between vitamin D levels and central adiposity in an eastern Africa outpatient clinical population 
Dermato-endocrinology  2013;5(1):218-221.
Background
Eastern Africa is a vast area straddling the Equator at roughly between latitude 18° North and 25° South of the Equator. This region enjoys overhead or near overhead sunshine throughout the year receiving an estimated 200–275 W/M2 of UVB annually. It is a region undergoing rapid socio-economic changes and thus impacting change in work habits and environment from the outdoors to the indoors. There however exists a dearth of vitamin D3 data on people in this region despite the recognition of vitamin D3 deficiency being a global epidemic. The purpose of this study was to examine the status of vitamin D3 and central obesity in this clinical population and their relationship if any.
Methods
Serum 25(OH)D, Waist circumference (WC) and Waist to Hip ratio (WHR) data on 182 outpatients attending a Therapeutic Lifestyle Changes was retrospectively analyzed by gender, age category and ethnicity.
Results
Vitamin D deficiency and insufficiency in this clinical population in Eastern Africa, females had lower serum concentration, with the younger population having lower serum concentrations than the elderly. There was also a significant difference in serum levels when data was analyzed by ethnicity. Similarly central obesity was also highly prevalent in this population. The odds of being Vitamin D deficient was 3.3 times (p = 0.022) higher among individuals with elevated waist circumference than those with normal waist circumferences. Among the males, the odds of being Vitamin D deficient and having an elevated waist circumference was 6.8 times (p = 0.011) higher than for males with normal waist circumferences. This was however not observed among the females.
Conclusion
Living on or close to the equator and having overhead or near overhead sunshine throughout the year in and of itself is not a guarantee of adequate serum 25(OH)D concentrations. It may therefore be prudent for clinicians in this region to risk stratify their patients based on work location, age category and ethnicity.
doi:10.4161/derm.24654
PMCID: PMC3897594  PMID: 24494058
25 (OH)D3; eastern Africa; waist circumference; waist to hip ratio
6.  Plasma vitamin C and food choice in the third Glasgow MONICA population survey 
STUDY OBJECTIVE—To determine the contribution of different foods to the estimated intakes of vitamin C among those differing in plasma vitamin C levels, and thereby inform dietary strategies for correcting possible deficiency.
DESIGN—Cross sectional random population survey.
SETTING—North Glasgow, Scotland, 1992.
PARTICIPANTS—632 men and 635 women, aged 25 to 74 years, not taking vitamin supplements, who participated in the third MONICA study (population survey monitoring trends and determinants of cardiovascular disease).
MEASUREMENTS AND MAIN RESULTS—Dietary and sociodemographic information was collected using a food frequency and lifestyle questionnaire. Plasma vitamin C was measured in non-fasted venous blood samples and subjects categorised by cut points of 11.4 and 22.7 µmol/l as being of low, marginal or optimal vitamin C status. Food sources of dietary vitamin C were identified for subjects in these categories. Plasma vitamin C concentrations were compared among groups classified according to intake of key foods. More men (26%) than women (14%) were in the low category for vitamin C status; as were a higher percentage of smokers and of those in the older age groups. Intake of vitamin C from potatoes and chips (fried potatoes) was uniform across categories; while the determinants of optimal versus low status were the intakes of citrus fruit, non-citrus fruit and fruit juice. Optimal status was achieved by a combined frequency of fruit, vegetables and/or fruit juice of three times a day or more except in older male smokers where a frequency greater than this was required even to reach a marginal plasma vitamin C level.
CONCLUSION—Fruit, vegetables and/or fruit juice three or more times a day increases plasma vitamin C concentrations above the threshold for risk of deficiency.


Keywords: vitamin C; food frequency; fruit; vegetables
doi:10.1136/jech.54.5.355
PMCID: PMC1731679  PMID: 10814656
7.  Vitamin D: An overview of vitamin D status and intake in Europe 
Nutrition Bulletin / Bnf  2014;39(4):322-350.
In recent years, there have been reports suggesting a high prevalence of low vitamin D intakes and vitamin D deficiency or inadequate vitamin D status in Europe. Coupled with growing concern about the health risks associated with low vitamin D status, this has resulted in increased interest in the topic of vitamin D from healthcare professionals, the media and the public. Adequate vitamin D status has a key role in skeletal health. Prevention of the well-described vitamin D deficiency disorders of rickets and osteomalacia are clearly important, but there may also be an implication of low vitamin D status in bone loss, muscle weakness and falls and fragility fractures in older people, and these are highly significant public health issues in terms of morbidity, quality of life and costs to health services in Europe.
Although there is no agreement on optimal plasma levels of vitamin D, it is apparent that blood 25-hydroxyvitamin D [25(OH)D] levels are often below recommended ranges for the general population and are particularly low in some subgroups of the population, such as those in institutions or who are housebound and non-Western immigrants. Reported estimates of vitamin D status within different European countries show large variation. However, comparison of studies across Europe is limited by their use of different methodologies. The prevalence of vitamin D deficiency [often defined as plasma 25(OH)D <25 nmol/l] may be more common in populations with a higher proportion of at-risk groups, and/or that have low consumption of foods rich in vitamin D (naturally rich or fortified) and low use of vitamin D supplements.
The definition of an adequate or optimal vitamin D status is key in determining recommendations for a vitamin D intake that will enable satisfactory status to be maintained all year round, including the winter months. In most European countries, there seems to be a shortfall in achieving current vitamin D recommendations. An exception is Finland, where dietary survey data indicate that recent national policies that include fortification and supplementation, coupled with a high habitual intake of oil-rich fish, have resulted in an increase in vitamin D intakes, but this may not be a suitable strategy for all European populations. The ongoing standardisation of measurements in vitamin D research will facilitate a stronger evidence base on which policies can be determined. These policies may include promotion of dietary recommendations, food fortification, vitamin D supplementation and judicious sun exposure, but should take into account national, cultural and dietary habits. For European nations with supplementation policies, it is important that relevant parties ensure satisfactory uptake of these particularly in the most vulnerable groups of the population.
doi:10.1111/nbu.12108
PMCID: PMC4288313  PMID: 25635171
fortification; supplementation; vitamin D deficiency; vitamin D intake; vitamin D sources; vitamin D status
8.  Prevalence of vitamin D deficiency in north-west Punjab population: A cross-sectional study 
Background:
Many studies show a high prevalence of vitamin D deficiency across various populations the world over. There is relative lack of prevalence data in Punjab, India. This cross-sectional study was carried out to assess the prevalence of vitamin D deficiency in the north-west Punjab population.
Aim:
To study the prevalence of vitamin D deficiency in the north-west Punjab population across various population characteristics such as gender, education, locality, occupation, and dietary habits.
Materials and Methods:
Healthy volunteers (N = 150) of either sex were enrolled and their fasting plasma samples tested for 25-hydroxy vitamin D [25(OH) D] levels. Data were compiled as percentages and means across different population characteristics. Statistical analysis was done using Chi-square test and Fisher's exact test.
Results:
A high overall prevalence (90%) of vitamin D deficiency was observed in the study subjects. There was a significant difference in the prevalence of vitamin D insufficiency between rural and urban subjects (P < 0.05) and among the subjects pursuing different occupations (P < 0.001). A significant gender-specific difference was also recorded at the cut-off level of 25 (OH) D, with women showing higher prevalence of deficiency compared to men (P < 0.05).
Conclusions:
There is a high prevalence of vitamin D deficiency in the population of Punjab. Lower prevalence is displayed by those subjects who have greater opportunities for sunlight exposure, such as like rural individuals, farmers, and housewives.
doi:10.4103/2229-516X.149220
PMCID: PMC4318108  PMID: 25664260
Calcium; deficiency; parathormone; prevalence; vitamin D
9.  Seasonal variance of 25-(OH) vitamin D in the general population of Estonia, a Northern European country 
BMC Public Health  2009;9:22.
Background
Vitamin D has a wide variety of physiological functions in the human body. There is increasing evidence that low serum levels of this vitamin have an important role in the pathogenesis of different skeletal and extra-skeletal diseases. Vitamin D deficiency and insufficiency is common at northern latitudes. There are few population-based studies in the northern European region looking at the issue in a wider age group. We aimed to measure Vitamin D level in the general population of Estonia (latitude 59°N), a North-European country where dairy products are not fortified with vitamin D.
Methods
The study subjects were a population-based random selection of 367 individuals (200 women and 167 men, mean age 48.9 ± 12.2 years, range 25–70 years) from the registers of general health care providers. 25-(OH) vitamin D (25(OH)D) level and parathyroid hormone (PTH) were measured in summer and in winter. Additionally age, sex, body mass index (BMI) and self-reported sunbathing habits were recorded.
Results
The mean serum 25(OH)D concentration in winter was 43.7 ± 15 nmol/L and in summer 59.3 ± 18 nmol/L (p < 0.0001). In winter 73% of the subjects had 25(OH)D insufficiency (25(OH)D concentration below 50 nmol/L) and 8% had deficiency (25(OH)D below 25 nmol/L). The corresponding percentages in summer were 29% for insufficiency and less than 1% for deficiency. PTH reached a plateau at around 80 nmol/L. BMI and age were inversely associated with 25(OH)D, but lost significance when adjusted for sunbathing habits. A difference in the seasonal 25(OH)D amplitude between genders (p = 0.01) was revealed.
Conclusion
Vitamin D insufficiency is highly prevalent throughout the year in a population without vitamin D dairy fortification living at the latitude of 59°N.
doi:10.1186/1471-2458-9-22
PMCID: PMC2632995  PMID: 19152676
10.  Vitamin D Deficiency in India: Prevalence, Causalities and Interventions 
Nutrients  2014;6(2):729-775.
Vitamin D deficiency prevails in epidemic proportions all over the Indian subcontinent, with a prevalence of 70%–100% in the general population. In India, widely consumed food items such as dairy products are rarely fortified with vitamin D. Indian socioreligious and cultural practices do not facilitate adequate sun exposure, thereby negating potential benefits of plentiful sunshine. Consequently, subclinical vitamin D deficiency is highly prevalent in both urban and rural settings, and across all socioeconomic and geographic strata. Vitamin D deficiency is likely to play an important role in the very high prevalence of rickets, osteoporosis, cardiovascular diseases, diabetes, cancer and infections such as tuberculosis in India. Fortification of staple foods with vitamin D is the most viable population based strategy to achieve vitamin D sufficiency. Unfortunately, even in advanced countries like USA and Canada, food fortification strategies with vitamin D have been only partially effective and have largely failed to attain vitamin D sufficiency. This article reviews the status of vitamin D nutrition in the Indian subcontinent and also the underlying causes for this epidemic. Implementation of population based educational and interventional strategies to combat this scourge require recognition of vitamin D deficiency as a public health problem by the governing bodies so that healthcare funds can be allocated appropriately.
doi:10.3390/nu6020729
PMCID: PMC3942730  PMID: 24566435
vitamin D; vitamin D deficiency; 25-hydroxyvitamin D; India; Indian subcontinent; healthy individuals; fortification strategies; supplementation; sun exposure; osteoporosis; fractures
11.  Solar UV Doses of Young Americans and Vitamin D3 Production 
Environmental Health Perspectives  2011;120(1):139-143.
Background: Sunlight contains ultraviolet B (UVB) radiation (290–315 nm) that affects human health in both detrimental (skin cancers) and beneficial (vitamin D3) ways. Serum 25-hydroxyvitamin D concentrations from young Americans (≤ 19 years) show that many have deficient (< 50 nmol/L, 20 ng/mL) or insufficient (< 75 nmol/L, 30 ng/mL) vitamin D levels, indicating that they are not getting enough sun exposure. Those findings are in conflict with some calculated, published values that suggest people make “ample” vitamin D3 (~ 1,000 IU/day) from their “casual,” or everyday, outdoor exposures even if they diligently use sunscreens with sun protection factor (SPF) 15.
Objective: We estimated how much vitamin D3 young Americans (n = ~ 2,000) produce from their everyday outdoor ultraviolet doses in the North (45°N) and South (35°N) each season of the year with and without vacationing.
Methods: For these vitamin D3 calculations, we used geometric conversion factors that change planar to whole-body doses, which previous calculations did not incorporate.
Results: Our estimates suggest that American children may not be getting adequate outdoor UVB exposures to satisfy their vitamin D3 needs all year, except some Caucasians during the summer if they do not diligently wear sunscreens except during beach vacations.
Conclusion: These estimates suggest that most American children may not be going outside enough to meet their minimal (~ 600 IU/day) or optimal (≥ 1,200 IU/day) vitamin D requirements.
doi:10.1289/ehp.1003195
PMCID: PMC3261929  PMID: 21852226
cancer; environment; sunlight; sunscreen; vitamin D
12.  Prevalence of Cataract in an Older Population in India 
Ophthalmology  2011;118(2-19):272-278.e2.
Purpose
To describe the prevalence of cataract in older people in 2 areas of north and south India.
Design
Population-based, cross-sectional study.
Participants
Randomly sampled villages were enumerated to identify people aged ≥60 years. Of 7518 enumerated people, 78% participated in a hospital-based ophthalmic examination.
Methods
The examination included visual acuity measurement, dilatation, and anterior and posterior segment examination. Digital images of the lens were taken and graded by type and severity of opacity using the Lens Opacity Classification System III (LOCS III).
Main Outcome Measures
Age- and gender-standardized prevalence of cataract and 95% confidence intervals (CIs). We defined type of cataract based on the LOCS III grade in the worse eye of: ≥4 for nuclear cataract, ≥3 for cortical cataract, and ≥2 for posterior subcapsular cataract (PSC). Any unoperated cataract was based on these criteria or ungradable dense opacities. Any cataract was defined as any unoperated or operated cataract.
Results
The prevalence of unoperated cataract in people aged ≥60 was 58% in north India (95% CI, 56–60) and 53% (95% CI, 51–55) in south India (P = 0.01). Nuclear cataract was the most common type: 48% (95% CI, 46–50) in north India and 38% (95% CI, 37–40) in south India (P<0.0001); corresponding figures for PSC were 21% (95% CI, 20–23) and 17% (95% CI, 16–19; P = 0.003), respectively, and for cortical cataract 7.6% (95% CI, 7–9) and 10.2% (95% CI, 9–11; P<0.004). Bilateral aphakia/pseudophakia was slightly higher in the south (15.5%) than in the north (13.2%; P<0.03). The prevalence of any cataracts was similar in north (73.8%) and south India (71.8%). The prevalence of unoperated cataract increased with age and was higher in women than men (odds ratio [OR], 1.8). Aphakia/pseudophakia was also more common in women, either unilateral (OR, 1.2; P<0.02) or bilateral (OR, 1.3; P<0.002).
Conclusions
We found high rates of unoperated cataract in older people in north and south India. Posterior subcapsular cataract was more common than in western studies. Women had higher rates of cataract, which was not explained by differential access to surgery.
Financial Disclosure(s)
The authors have no proprietary or commercial interest in any of the materials discussed in this article.
doi:10.1016/j.ophtha.2010.05.020
PMCID: PMC3146699  PMID: 20801514
13.  Osteoporosis in Healthy South Indian Males and the Influence of Life Style Factors and Vitamin D Status on Bone Mineral Density 
Journal of Osteoporosis  2014;2014:723238.
Objective. To study the prevalence of osteoporosis and vitamin D deficiency in healthy men and to explore the influence of various life style factors on bone mineral density (BMD) and also to look at number of subjects warranting treatment. Methods. Ambulatory south Indian men aged above 50 were recruited by cluster random sampling. The physical activity, risk factors in the FRAX tool, BMD, vitamin D, and PTH were assessed. The number of people needing treatment was calculated, which included subjects with osteoporosis and osteopenia with 10-year probability of major osteoporotic fracture >20 percent and hip fracture >3 percent in FRAX India. Results. A total of 252 men with a mean age of 58 years were studied. The prevalence of osteoporosis and osteopenia at any one site was 20% (50/252) and 58%, respectively. Vitamin D deficiency (<20 ng/dL) was seen in 53%. On multiple logistic regression, BMI (OR 0.3; P value = 0.04) and physical activity (OR 0.4; P value < 0.001) had protective effect on BMD. Twenty-five percent warranted treatment. Conclusions. A significantly large proportion of south Indian men had osteoporosis and vitamin D deficiency. Further interventional studies are needed to look at reduction in end points like fractures in these subjects.
doi:10.1155/2014/723238
PMCID: PMC4244976  PMID: 25478284
14.  Sociodemographic patterning of non-communicable disease risk factors in rural India: a cross sectional study 
Objectives To investigate the sociodemographic patterning of non-communicable disease risk factors in rural India.
Design Cross sectional study.
Setting About 1600 villages from 18 states in India. Most were from four large states due to a convenience sampling strategy.
Participants 1983 (31% women) people aged 20–69 years (49% response rate).
Main outcome measures Prevalence of tobacco use, alcohol use, low fruit and vegetable intake, low physical activity, obesity, central adiposity, hypertension, dyslipidaemia, diabetes, and underweight.
Results Prevalence of most risk factors increased with age. Tobacco and alcohol use, low intake of fruit and vegetables, and underweight were more common in lower socioeconomic positions; whereas obesity, dyslipidaemia, and diabetes (men only) and hypertension (women only) were more prevalent in higher socioeconomic positions. For example, 37% (95% CI 30% to 44%) of men smoked tobacco in the lowest socioeconomic group compared with 15% (12% to 17%) in the highest, while 35% (30% to 40%) of women in the highest socioeconomic group were obese compared with 13% (7% to 19%) in the lowest. The age standardised prevalence of some risk factors was: tobacco use (40% (37% to 42%) men, 4% (3% to 6%) women); low fruit and vegetable intake (69% (66% to 71%) men, 75% (71% to 78%) women); obesity (19% (17% to 21%) men, 28% (24% to 31%) women); dyslipidaemia (33% (31% to 36%) men, 35% (31% to 38%) women); hypertension (20% (18% to 22%) men, 22% (19% to 25%) women); diabetes (6% (5% to 7%) men, 5% (4% to 7%) women); and underweight (21% (19% to 23%) men, 18% (15% to 21%) women). Risk factors were generally more prevalent in south Indians compared with north Indians. For example, the prevalence of dyslipidaemia was 21% (17% to 33%) in north Indian men compared with 33% (29% to 38%) in south Indian men, while the prevalence of obesity was 13% (9% to 17%) in north Indian women compared with 24% (19% to 30%) in south Indian women.
Conclusions The prevalence of most risk factors was generally high across a range of sociodemographic groups in this sample of rural villagers in India; in particular, the prevalence of tobacco use in men and obesity in women was striking. However, given the limitations of the study (convenience sampling design and low response rate), cautious interpretation of the results is warranted. These data highlight the need for careful monitoring and control of non-communicable disease risk factors in rural areas of India.
doi:10.1136/bmj.c4974
PMCID: PMC2946988  PMID: 20876148
15.  Vitamin C Supplementation Slightly Improves Physical Activity Levels and Reduces Cold Incidence in Men with Marginal Vitamin C Status: A Randomized Controlled Trial 
Nutrients  2014;6(7):2572-2583.
The early indications of vitamin C deficiency are unremarkable (fatigue, malaise, depression) and may manifest as a reduced desire to be physically active; moreover, hypovitaminosis C may be associated with increased cold duration and severity. This study examined the impact of vitamin C on physical activity and respiratory tract infections during the peak of the cold season. Healthy non-smoking adult men (18–35 years; BMI < 34 kg/m2; plasma vitamin C < 45 µmol/L) received either 1000 mg of vitamin C daily (n = 15) or placebo (n = 13) in a randomized, double-blind, eight-week trial. All participants completed the Wisconsin Upper Respiratory Symptom Survey-21 daily and the Godin Leisure-Time Exercise Questionnaire weekly. In the final two weeks of the trial, the physical activity score rose modestly for the vitamin C group vs. placebo after adjusting for baseline values: +39.6% (95% CI [−4.5,83.7]; p = 0.10). The number of participants reporting cold episodes was 7 and 11 for the vitamin C and placebo groups respectively during the eight-week trial (RR = 0.55; 95% CI [0.33,0.94]; p = 0.04) and cold duration was reduced 59% in the vitamin C versus placebo groups (−3.2 days; 95% CI [−7.0,0.6]; p = 0.06). These data suggest measurable health advantages associated with vitamin C supplementation in a population with adequate-to-low vitamin C status.
doi:10.3390/nu6072572
PMCID: PMC4113757  PMID: 25010554
vitamin C; physical activity; cold symptoms
16.  The Status of Vitamin B12 and Folate among Chinese Women: A Population-Based Cross-Sectional Study in Northwest China 
PLoS ONE  2014;9(11):e112586.
Objective
To assess the status of the vitamin B12 and folate of Chinese women living in northwest China.
Methods
A population-based cross-sectional study was conducted in 2008 among Chinese women aged 10–49 years living in Shaanxi province of northwest China. A stratified multistage random sampling method was adopted to obtain a sample of 1170 women. The women were interviewed for collection of their background information and their plasma vitamin B12 and folate were measured with the immunoassay method. The status of both vitamins was evaluated and the prevalence of deficiency was estimated.
Results
The median value of the women was 214.5 pg/mL for vitamin B12 and 4.6 ng/mL for folate. The urban women had a significantly higher vitamin B12 (254.1 vs. 195.9 pg/mL) but lower folate (4.4 vs. 4.7 ng/mL) than rural women. Total prevalence of deficiency was 45.5% (95% CI: 42.6%∼48.4%) for vitamin B12 and 14.7% (95% CI: 12.6%∼16.8%) for folate. About 36% of women presented vitamin B12 deficiency alone, 5.2% belonged to folate deficiency alone and 9.5% was combined deficiency in both vitamins. More than 25% of the women were in marginal vitamin B12 status (200–299 pg/mL) and 60% in marginal status of folate (3–6 ng/mL). About 75.2% of rural women with folate deficiency were deficient in vitamin B12 and 46% for urban women. Quantile regression model found decreasing coefficient of folate status across 73 different quantiles of vitamin B12, which indicated that the women with folate deficiency had lower vitamin B12 significantly compared with those with no deficiency.
Conclusions
The deficiency of vitamin B12 and folate is still prevalent among the Chinese women in northwest China. Vitamin B12 deficiency could be more serious and the improvement of poor vitamin B12 status should be invoked when practicing the supplementation of folate against the neural tube defects in northwest China.
doi:10.1371/journal.pone.0112586
PMCID: PMC4229226  PMID: 25390898
17.  Vitamin D status and sun exposure in India 
Dermato-endocrinology  2013;5(1):130-141.
Background: Little if any cutaneous production of vitamin D3 occurs at latitudes above and below 35° N and 35° S during the winter months. It was postulated that those residing in tropics synthesize enough vitamin D3 year round. Several studies have documented the effect of latitude, season and time of the day on the cutaneous production of vitamin D3 in an ampoule model. Studies from India have shown high prevalence of vitamin D deficiency despite abundant sunshine.
Methods: We studied the influence of season and time of the day on synthesis of previtamin D3 in an ampoule model in Tirupati, (latitude 13.40° N and longitude 77.2° E) south India, between May 2007 to August 2008. Sealed borosilicate glass ampoules containing 50 μg of 7-DHC in 1 ml of methanol were exposed to sunlight hourly from 8 a.m. until 4 p.m. The percent conversion of 7-DHC to previtamin D3 and its photoproducts and the percent of previtamin D3 and vitamin D3 formed was estimated and related to solar zenith angle.
Results: The percent conversion of 7-DHC to previtamin D3 and its photoproducts and formation of previtamin D3 and vitamin D3 was maximal between 11 a.m. to 2 p.m. of the day during the entire year (median 11.5% and 10.2% respectively at 12.30 p.m.).
Conclusions: Therefore at this latitude exposure to sunlight between the hours of 11 a.m. and 2 p.m. will promote vitamin D production in the skin year round.
doi:10.4161/derm.23873
PMCID: PMC3897581  PMID: 24494046
7-dehydrocholesterol (7-DHC); India; previtamin D3; sun exposure; vitamin D3; zenith angle
18.  Prevalence of vitamin D deficiency among Turkish, Moroccan, Indian and sub-Sahara African populations in Europe and their countries of origin: an overview 
Osteoporosis International  2010;22(4):1009-1021.
Summary
Vitamin D status of nonwestern immigrants in Europe was poor. Vitamin D status of nonwestern populations in their countries of origin varied, being either similar to the immigrant populations in Europe or higher than in European indigenous populations. Vitamin D concentrations in nonwestern immigrant populations should be improved.
Purpose
The higher the latitude, the less vitamin D is produced in the skin. Most European countries are located at higher latitudes than the countries of origin of their nonwestern immigrants. Our aim was to compare the serum 25-hydroxyvitamin D (25(OH)D) concentration of nonwestern immigrant populations with those of the population in their country of origin, and the indigenous population of the country they migrated to.
Methods
We performed literature searches in the “PubMed” and “Embase” databases, restricted to 1990 and later. The search profile consisted of terms referring to vitamin D or vitamin D deficiency, prevalence or cross-sectional studies, and countries or ethnicity. Titles and abstracts were reviewed to identify studies on population-based mean serum 25(OH)D concentrations among Turkish, Moroccan, Indian, and sub-Sahara African populations in Europe, Turkey, Morocco, India, and sub-Sahara Africa.
Results
The vitamin D status of immigrant populations in Europe was poor compared to the indigenous European populations. The vitamin D status of studied populations in Turkey and India varied and was either similar to the immigrant populations in Europe (low) or similar to or even higher than the indigenous European populations (high).
Conclusions
In addition to observed negative consequences of low serum 25(OH)D concentrations among nonwestern populations, this overview indicates that vitamin D status in nonwestern immigrant populations should be improved. The most efficacious strategy should be the subject of further study.
doi:10.1007/s00198-010-1279-1
PMCID: PMC3046351  PMID: 20461360
Indian; Moroccan; Prevalence; Serum 25-hydroxyvitamin D; Sub-Sahara African; Turkish
19.  VITAMIN B12 DEFICIENCY IN AFRICAN AMERICAN AND WHITE OCTOGENARIANS AND CENTENARIANS IN GEORGIA 
Objective
Test the hypotheses that vitamin B12 deficiency would be prevalent in octogenarians and centenarians and associated with age, gender, race/ethnicity, living arrangements (community or skilled nursing facility), animal food intake, B-vitamin supplement use, atrophic gastritis, folate status, and hematological indicators.
Design
Population-based multi-ethnic sample of adults aged 80 to 89 and 98 and above.
Setting
Northern Georgia in the United States.
Participants
Men and women aged 80 to 89 (octogenarians, n = 80) and 98 and older (centenarians, n = 231).
Measurements
Wilcoxon signed-rank tests, Fisher’s exact tests, and logistic regression analysis was used to examine the associations of vitamin B12 status with the variables of interest.
Results
After excluding participants receiving vitamin B12 injections (n = 17), the prevalence of vitamin B12 deficiency was higher in centenarians than in octogenarians (35.3% vs. 22.8%, p < 0.05, defined as plasma vitamin B12 < 258 pmol/L and serum methylmalonic acid > 271 nmol/L and methylmalonic acid > serum 2-methylcitrate) and in both age groups was correlated with significantly higher homocysteine (p < 0.05) and lower plasma and red cell folate (p < 0.01), but was not related to hemoglobin, anemia, mean cell volume, or macrocytosis. In logistic regression analysis, the probability of being vitamin B12-deficient was significantly increased by being a centenarian vs. octogenarian (p < 0.03), by being white vs. African American (p < 0.02), by increasing severity of atrophic gastritis (p < 0.001), and by not taking oral B-vitamin supplements (p < 0.01), but was not related to gender, living arrangements, or animal food intake.
Conclusions
Centenarians and octogenarians are at high risk for vitamin B12 deficiency for many of the same reasons identified in other older adult populations. Given the numerous potential adverse consequences of poor vitamin B12 status, efforts are needed to ensure vitamin B12 adequacy in these older adults.
PMCID: PMC2978918  PMID: 20424799
20.  Vitamin K Supplementation in Postmenopausal Women with Osteopenia (ECKO Trial): A Randomized Controlled Trial 
PLoS Medicine  2008;5(10):1-12.
Background
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.
Conclusions
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: ClinicalTrials.gov (#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
Background.
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 http://dx.doi.org/10.1371/journal.pmed.0050196.
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 ClinicalTrials.gov 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
doi:10.1371/journal.pmed.0050196
PMCID: PMC2566998  PMID: 18922041
21.  Dietary intake of vitamin D in a northern Canadian Dené First Nation community 
International Journal of Circumpolar Health  2013;72:10.3402/ijch.v72i0.20723.
Background
Increased awareness of the wide spectrum of activity of vitamin D has focused interest on its role in the health of Canada's Aboriginal peoples, who bear a high burden of both infectious and chronic disease. Cutaneous vitamin D synthesis is limited at northern latitudes, and the transition from nutrient-dense traditional to nutrient-poor market foods has left many Canadian Aboriginal populations food insecure and nutritionally vulnerable.
Objective
The study was undertaken to determine the level of dietary vitamin D in a northern Canadian Aboriginal (Dené) community and to determine the primary food sources of vitamin D.
Design
Cross-sectional study.
Methods
Dietary vitamin D intakes of 46 adult Dené men and women were assessed using a food frequency questionnaire and compared across age, gender, season and body mass index. The adequacy of dietary vitamin D intake was assessed using the 2007 Adequate Intake (AI) and the 2011 Recommended Dietary Allowance (RDA) values for Dietary Reference Intake (DRI).
Results
Mean daily vitamin D intake was 271.4 IU in winter and 298.3 IU in summer. Forty percent and 47.8% of participants met the vitamin D 1997 AI values in winter and summer, respectively; this dropped to 11.1 and 13.0% in winter and summer using 2011 RDA values. Supplements, milk, and local fish were positively associated with adequate vitamin D intake. Milk and local fish were the major dietary sources of vitamin D.
Conclusions
Dietary intake of vitamin D in the study population was low. Only 2 food sources, fluid milk and fish, provided the majority of dietary vitamin D. Addressing low vitamin D intake in this population requires action aimed at food insecurity present in northern Aboriginal populations.
doi:10.3402/ijch.v72i0.20723
PMCID: PMC3752286  PMID: 23984265
vitamin D; First Nations; indigenous; Aboriginal; diet; nutrition; food security
22.  Solar UV doses of adult Americans and vitamin D3 production 
Dermato-endocrinology  2011;3(4):243-250.
Background
Sunlight contains UV radiation that affects human health in both detrimental (skin cancers) and beneficial (vitamin D3) ways. An evaluation of the vitamin D status of adult Americans (22–40, 41–59, 60+ yr) show many have deficient or insufficient serum levels of 25-hydroxyvitamin D, indicating they are not getting enough from dietary sources or sunlight. Those findings are in conflict with calculated values from the American Academy of Dermatology who insist people make “ample” vitamin D3 (≥1,000 IU/day) from their “casual,” or everyday, outdoor UV exposures even if they use sunscreens with sun protection factor 15.
Objective
We investigated this situation using the everyday outdoor UV doses of indoor-working adult Americans (∼7,000) in the north (45°N) and south (35°N) to calculate how much vitamin D3 they produce each season with and without vacationing.
Results
Only during the summer can skin type II Caucasian adults (21–59 yr) meet their minimum (600 IU/day) vitamin D3 needs from everyday exposures, but only if they do not wear professional clothes or sunscreens (except beach vacations).
Method
To do vitamin D3 calculations properly, we used action spectrum and geometric conversion factors, not previously incorporated into other calculations.
Conclusions
Most adult Americans do not go outside enough to meet their minimum or optimum (≥1,200 IU/day) vitamin D3 needs all year. The darker skin types (III–VI) and the oldest people (>59 yr) are at the highest risk for not making enough vitamin D3 during the year from everyday outdoor exposures even with a 2–3 week summer vacation.
doi:10.4161/derm.3.4.15292
PMCID: PMC3256341  PMID: 22259652
age; benefit; environment; health; race; risk; sunlight; sunscreen; vitamin D
23.  Association Between Vitamin D Status and Physical Performance: The InCHIANTI Study 
Background
Vitamin D status has been hypothesized to play a role in musculoskeletal function. Using data from the InCHIANTI study, we examined the association between vitamin D status and physical performance.
Methods
A representative sample of 976 persons aged 65 years or older at study baseline were included. Physical performance was assessed using a short physical performance battery (SPPB) and handgrip strength. Multiple linear regression was used to examine the association between vitamin D (serum 25OHD), parathyroid hormone (PTH), and physical performance adjusting for sociodemographic variables, behavioral characteristics, body mass index, season, cognition, health conditions, creatinine, hemoglobin, and albumin.
Results
Approximately 28.8% of women and 13.6% of men had vitamin D levels indicative of deficiency (serum 25OHD < 25.0 nmol/L) and 74.9% of women and 51.0% of men had vitamin D levels indicative of vitamin D insufficiency (serum 25OHD < 50.0 nmol/L). Vitamin D levels were significantly associated with SPPB score in men (β coefficient [standard error (SE)]: 0.38 [0.18], p = .04) and handgrip strength in men (2.44 [0.84], p = .004) and women (1.33 [0.53], p =.01). Men and women with serum 25OHD < 25.0 nmol/L had significantly lower SPPB scores whereas those with serum 25OHD < 50 nmol/L had significantly lower handgrip strength than those with serum 25OHD ≥25 and ≥50 nmol/L, respectively (p < .05). PTH was significantly associated with handgrip strength only (p = .01).
Conclusions
Vitamin D status was inversely associated with poor physical performance. Given the high prevalence of vitamin D deficiency in older populations, additional studies examining the association between vitamin D status and physical function are needed.
PMCID: PMC2645652  PMID: 17452740
24.  Polymorphisms in MTHFR, MS and CBS Genes and Homocysteine Levels in a Pakistani Population 
PLoS ONE  2012;7(3):e33222.
Background
Hyperhomocysteinemia (>15 µmol/L) is highly prevalent in South Asian populations including Pakistan. In order to investigate the genetic determinants of this condition, we studied 6 polymorphisms in genes of 3 enzymes - methylenetetrahydrofolate reductase (MTHFR; C677T; A1298C), methionine synthase (MS; A2756G), cystathionine-β-synthase (CBS; T833C/844ins68, G919A) involved in homocysteine metabolism and investigated their interactions with nutritional and environmental factors in a Pakistani population.
Methodology/Principal Findings
In a cross-sectional survey, 872 healthy adults (355 males and 517 females; age 18–60 years) were recruited from a low-income urban population in Karachi. Fasting venous blood was obtained and assessed for plasma/serum homocysteine; folate, vitamin B12, pyridoxal phosphate and blood lead. DNA was isolated and genotyping was performed by PCR-RFLP (restriction-fragment-length- polymorphism) based assays. The average changes in homocysteine levels for MTHFR 677CT and TT genotypes were positive [β(SE β), 2.01(0.63) and 16.19(1.8) µmol/L, respectively]. Contrary to MTHFR C677T polymorphism, the average changes in plasma homocysteine levels for MS 2756AG and GG variants were negative [β(SE β), −0.56(0.58) and −0.83(0.99) µmol/L, respectively]. The average change occurring for CBS 844ins68 heterozygous genotype (ancestral/insertion) was −1.88(0.81) µmol/L. The combined effect of MTHFR C677T, MS A2756G and CBS 844ins68 genotypes for plasma homocysteine levels was additive (p value <0.001). Odds of having hyperhomocysteinemia with MTHFR 677TT genotype was 10-fold compared to MTHFR 677CC genotype [OR (95%CI); 10.17(3.6–28.67)]. Protective effect towards hyperhomocysteinemia was observed with heterozygous (ancestral/insertion) genotype of CBS 844ins68 compared to homozygous ancestral type [OR (95% CI); 0.58 (0.34–0.99)]. Individuals with MTHFR 677CT or TT genotypes were at a greater risk of hyperhomocysteinemia in folate and vitamin B12 deficiencies and high blood lead (p value <0.05) level.
Conclusions
Gene polymorphism (especially MTHFR C677T transition), folate and vitamin B12 deficiencies, male gender and high blood lead level appear to be contributing towards the development of hyperhomocysteinemia in a Pakistani population.
doi:10.1371/journal.pone.0033222
PMCID: PMC3310006  PMID: 22470444
25.  The Effect of Rural-to-Urban Migration on Obesity and Diabetes in India: A Cross-Sectional Study 
PLoS Medicine  2010;7(4):e1000268.
Shah Ebrahim and colleagues examine the distribution of obesity, diabetes, and other cardiovascular risk factors among urban migrant factory workers in India, together with their rural siblings. The investigators identify patterns of change of cardiovascular risk factors associated with urban migration.
Background
Migration from rural areas of India contributes to urbanisation and may increase the risk of obesity and diabetes. We tested the hypotheses that rural-to-urban migrants have a higher prevalence of obesity and diabetes than rural nonmigrants, that migrants would have an intermediate prevalence of obesity and diabetes compared with life-long urban and rural dwellers, and that longer time since migration would be associated with a higher prevalence of obesity and of diabetes.
Methods and Findings
The place of origin of people working in factories in north, central, and south India was identified. Migrants of rural origin, their rural dwelling sibs, and those of urban origin together with their urban dwelling sibs were assessed by interview, examination, and fasting blood samples. Obesity, diabetes, and other cardiovascular risk factors were compared. A total of 6,510 participants (42% women) were recruited. Among urban, migrant, and rural men the age- and factory-adjusted percentages classified as obese (body mass index [BMI] >25 kg/m2) were 41.9% (95% confidence interval [CI] 39.1–44.7), 37.8% (95% CI 35.0–40.6), and 19.0% (95% CI 17.0–21.0), respectively, and as diabetic were 13.5% (95% CI 11.6–15.4), 14.3% (95% CI 12.2–16.4), and 6.2% (95% CI 5.0–7.4), respectively. Findings for women showed similar patterns. Rural men had lower blood pressure, lipids, and fasting blood glucose than urban and migrant men, whereas no differences were seen in women. Among migrant men, but not women, there was weak evidence for a lower prevalence of both diabetes and obesity among more recent (≤10 y) migrants.
Conclusions
Migration into urban areas is associated with increases in obesity, which drive other risk factor changes. Migrants have adopted modes of life that put them at similar risk to the urban population. Gender differences in some risk factors by place of origin are unexpected and require further exploration.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
India, like the rest of the world, is experiencing an epidemic of diabetes, a chronic disease characterized by dangerous levels of sugar in the blood that cause cardiovascular and kidney disease, which lower life expectancy. The prevalence of diabetes (the proportion of the population with diabetes) has been increasing steadily in India over recent decades, particularly in urban areas. In 1984, only 5% of adults living in the towns and cities of India had diabetes, but by 2004, 15% of adults in urban areas were affected by diabetes. In rural areas of India, diabetes is less common than in urban areas but even here, the prevalence of diabetes is now 6%. Obesity—too much body fat—is a major risk factor for diabetes and, in parallel with the greater increase in diabetes in urban India compared to rural India, there has been a greater increase in obesity in urban areas than in rural areas.
Why Was This Study Done?
Experts think that the increasing prevalence of obesity and diabetes in India (and in other developing countries) is caused in part by increased consumption of saturated fats and sugars and by reduced physical activity, and that these changes are related to urbanization—urban expansion into the countryside and migration from rural to urban areas. If living in an urban setting is a major determinant of obesity and diabetes risk, then people migrating into urban areas should acquire the high risk of the urban population for these two conditions. In this cross-sectional study (a study in which participants are studied at a single time point), the researchers investigate whether rural to urban migrants in India have a higher prevalence of obesity and diabetes than rural nonmigrants. They also ask whether migrants have a prevalence of obesity and diabetes intermediate between that of life-long urban and rural dwellers and whether a longer time since migration is associated with a higher prevalence of obesity and diabetes.
What Did the Researchers Do and Find?
The researchers recruited rural-urban migrants working in four Indian factories in north, central, and south regions and their spouses (if they were living in the same town) into their study. Each migrant worker and spouse asked one nonmigrant brother or sister (sibling) still living in their place of origin to join the study. The researchers also enrolled nonmigrant factory workers and their urban siblings into the study. All the participants (more than 6,500 in total) answered questions about their diet and physical activity and had their fasting blood sugar and their body mass index (BMI; weight in kg divided by height in meters squared) measured; participants with a fasting blood sugar of more than 7.0 nmol/l or a BMI of more than 25 kg/m2 were classified as diabetic or obese, respectively. 41.9% and 37.8% of the urban and migrant men, respectively, but only 19.0% of the rural men were obese. Similarly, 13.5% and 14.3% of the urban and migrant men, respectively, but only 6.2% of the rural men had diabetes. Patterns of obesity and diabetes among the women participants were similar. Finally, although the prevalence of diabetes and obesity was lower in the most recent male migrants than in those who had moved more than 10 years previously, this difference was small and not seen in women migrants.
What Do These Findings Mean?
These findings show that rural-urban migration in India is associated with rapid increases in obesity and in diabetes. They also show that the migrants have adopted modes of life (for example, reduced physical activity) that put them at a similar risk for obesity and diabetes as the urban population. The findings do not show, however, that migrants have an intermediate prevalence of obesity and diabetes compared to urban and rural dwellers and provide only weak support for the idea that a longer time since migration is associated with a higher risk of obesity and diabetes. Although the study's cross-sectional design means that the researchers could not investigate how risk factors for diabetes evolve over time, these findings suggest that urbanization is helping to drive the diabetes epidemic in India. Thus, targeting migrants and their families for health promotion activities and for treatment of risk factors for obesity and diabetes might help to slow the progress of the epidemic.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000268.
The International Diabetes Federation provides information about all aspects of diabetes, including information on diabetes in Southeast Asia (in English, French, and Spanish)
DiabetesIndia.com provides information on the Indian Task Forces on diabetes care in India
Diabetes Foundation (India) has an international collaborative research focus and provides information about health promotion for diabetes; it has also produced consensus guidelines on dietary change for prevention of diabetes in India
The US National Diabetes Information Clearinghouse provides detailed information about diabetes for patients, health care professionals, and the general public (in English and Spanish)
MedlinePlus provides links to further resources and advice about diabetes (in English and Spanish)
doi:10.1371/journal.pmed.1000268
PMCID: PMC2860494  PMID: 20436961

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