Vitamin D and prevention of breast cancer: pooled analysis

BACKGROUND: Inadequate photosynthesis or oral intake of Vitamin D are associated with high incidence and mortality rates of breast cancer in ecological and observational studies, but the dose-response relationship in individuals has not been adequately studied. METHODS: A literature search for all studies that reported risk by of breast cancer by quantiles of 25(OH)D identified two studies with 1760 individuals. Data were pooled to assess the dose-response association between serum 25(OH)D and risk of breast cancer. RESULTS: The medians of the pooled quintiles of serum 25(OH)D were 6, 18, 29, 37 and 48 ng/ml. Pooled odds ratios for breast cancer from lowest to highest quintile, were 1.00, 0.90, 0.70, 0.70 and 0.50 (p trend<0.001). According to the pooled analysis, individuals with serum 25(OH)D of approximately 52 ng/ml had 50% lower risk of breast cancer than those with serum <13 ng/ml. This serum level corresponds to intake of 4000 IU/day. This exceeds the National Academy of Sciences upper limit of 2000 IU/day. A 25(OH)D level of 52 ng/ml could be maintained by intake of 2000 IU/day and, when appropriate, about 12 min/day in the sun, equivalent to oral intake of 3000 IU of Vitamin D(3). CONCLUSIONS: Intake of 2000 IU/day of Vitamin D(3), and, when possible, very moderate exposure to sunlight, could raise serum 25(OH)D to 52 ng/ml, a level associated with reduction by 50% in incidence of breast cancer, according to observational studies.     

Epidemiology of disease risks in relation to vitamin D insufficiency

Vitamin D from ultraviolet-B (UVB) irradiance, food, and supplements is receiving increased attention lately for its role in maintaining optimal health. Although the calcemic effects of vitamin D have been known for about a century, the non-calcemic effects have been studied intently only during the past two-three decades. The strongest links to the beneficial roles of UVB and vitamin D to date are for bone and muscle conditions and diseases. There is also a preponderance of evidence from a variety of studies that vitamin D reduces the risk of colon cancer, with 1000 IU/day of vitamin D or serum 25-hydroxyvitamin D levels >33 ng/mL (82 nmol/L) associated with a 50% lower incidence of colorectal cancer. There is also reasonable evidence that vitamin D reduces the risk of breast, lung, ovarian, and prostate cancer and non-Hodgkin's lymphoma. There is weaker, primarily ecologic, evidence for the role of vitamin D in reducing the risk of an additional dozen types of cancer. There is reasonably strong ecologic and case-control evidence that vitamin D reduces the risk of autoimmune diseases including such as multiple sclerosis and type 1 diabetes mellitus, and weaker evidence for rheumatoid arthritis, osteoarthritis, type 2 diabetes mellitus, hypertension and stroke. It is noted that mechanisms whereby vitamin D exerts its effect are generally well understood for the various conditions and diseases discussed here.     

The Vitamin D requirement in health and disease

Advances in Vitamin D nutritional physiology since publication of the DRIs in 1997 are briefly summarized. Available data indicate that (1) Vitamin D's canonical function, optimizing intestinal calcium absorption, is fully expressed at serum 25-hydroxyvitamin D (25OHD) concentration of approximately 80nmol/L; (2) elevated parathyroid activity, typical of aging populations, is minimized at the same 25OHD value and (3) osteoporotic fractures are reduced when serum 25OHD is raised to near 80nmol/L. Depending upon starting value, achieving 25OHD concentrations of 80 or higher may require a daily oral intake of 2200IU (55microg) or more in addition to prevailing cutaneous inputs. The tolerable upper intake level (TUIL), currently set at 2000IU (50microg)/day, is too low to permit optimization of Vitamin D status in the general population. Actual toxicity is not seen below serum 25OHD values of 250nmol/L, a value that would be produced only at continuing oral intakes in excess of 10,000IU (250microg)/day.     

孕妇维生素D缺乏与妊娠期糖尿病的相关性分析

目的:调查孕妇妊娠早期维生素D水平及其影响因素,探讨维生素D缺乏与妊娠期糖尿病的相关性。方法:选取2012年7月至2013年4月在上海交通大学医学院附属新华医院产科正规产检并分娩的非孕前糖尿病孕妇,在其建卡初检时采用电化学发光免疫技术测定血清25(OH)D3水平;妊娠24-28周行糖筛查及糖耐量试验,诊断是否为妊娠期糖尿病GDM。收集并整理孕妇年龄,孕前体重指数BMI、维生素D测定孕周与测定季节、孕期维生素D补充情况等信息。结果:1000例孕妇中,GDM发病率为11.5%,维生素D缺乏比例占67.4%;其中,约有54%孕妇常规补充复合维生素,约含维生素400 IU/天,10%孕妇常规补充维生素D。GDM孕妇25(OH)D3水平显著低于正常对照组(P=0.007)。维生素D缺乏孕妇发生GDM的风险是维生素D水平较高组的1.944倍,且在秋冬季更易发生GDM。可以考虑在孕14-16周进行维生素D水平的早期测定。结论:孕妇维生素D缺乏十分普遍。妊娠早期孕妇低维生素D水平可能增加孕妇胰岛素抵抗及孕期发生GDM的发生风险。     

A prospective randomized controlled trial of the effects of vitamin D supplementation on cardiovascular disease risk

Vitamin D (VitD) supplementation has been advocated for cardiovascular risk reduction; however, supporting data are sparse. The objective of this study was to determine whether VitD supplementation reduces cardiovascular risk. Subjects in this prospective, randomized, double-blind, placebo-controlled trial of post-menopausal women with serum 25-hydroxyvitamin D concentrations >10 and <60 ng/mL were randomized to Vitamin D3 2500 IU or placebo, daily for 4 months. Primary endpoints were changes in brachial artery flow-mediated vasodilation (FMD), carotid-femoral pulse wave velocity (PWV), and aortic augmentation index (AIx). The 114 subjects were mean (standard deviation) 63.9 (3.0) years old with a 25-hydroxyvitamin D level of 31.3 (10.6) ng/mL. Low VitD (<30 ng/mL) was present in 47% and was associated with higher body-mass index, systolic blood pressure, glucose, CRP, and lower FMD (all p<0.05). After 4 months, 25-hydroxyvitamin D levels increased by 15.7 (9.3) ng/mL on vitamin D3 vs. -0.2 (6.1) ng/mL on placebo (p<0.001). There were no significant differences between groups in changes in FMD (0.3 [3.4] vs. 0.3 [2.6] %, p = 0.77), PWV (0.00 [1.06] vs. 0.05 [0.92] m/s, p = 0.65), AIx (2.7 [6.3] vs. 0.9 [5.6] %, p = 0.10), or CRP (0.3 [1.9] vs. 0.3 [4.2] mg/L, p = 0.97). Multivariable models showed no significant interactions between treatment group and low VitD status (<30 ng/mL) for changes in FMD (p = 0.65), PWV (p = 0.93), AIx (p = 0.97), or CRP (p = 0.26). In conclusion, VitD supplementation did not improve endothelial function, arterial stiffness, or inflammation. These observations do not support use of VitD supplementation to reduce cardiovascular disease risk.     

Which circulating level of 25-hydroxyvitamin D is appropriate?

Moderate Vitamin D deficiency causes secondary hyperparathyroidism and bone loss, leading to osteoporosis and fractures. Controversy exists which circulating level of 25-hydroxyvitamin D (25OH)D is appropriate. The high incidence of hip fractures at northern latitudes suggest a relationship with Vitamin D deficiency. However, international studies show lower serum 25(OH)D levels in southern than in northern Europe. Serum 25(OH)D was not a risk factor for hip fractures in several epidemiological studies. The required serum 25(OH)D is usually established by assessing the point where serum parathyroid hormone (PTH) starts to rise. This point varied in several studies between 30 and 78 nmol/l. However, interlaboratory variation may also influence the apparent required serum 25(OH)D level. Dietary calcium intake influences serum PTH and serum PTH may influence the turnover of Vitamin D metabolites. A low calcium intake causes an increase of serum PTH and serum 1,25(OH)2D thereby decreasing the half life of serum 25(OH)D. While a low calcium intake may aggravate Vitamin D deficiency, a high calcium intake may have a Vitamin D sparing effect. With current knowledge, a global estimate for the appropriate serum 25(OH)D is 50 nmol/l.     

Severe Vitamin D Deficiency in Arab-American Women Living in Dearborn,Michigan

ObjectiveTo determine the prevalence and degree of 25-hydroxyvitamin D deficiency in a group of Arab- American women in the largest, most-concentrated Arab- American settlement in the United States and to search for correlations with dress, diet, and use of vitamin D–fortified foods and vitamin supplements.MethodsIn this cross-sectional study, Arab-American women, 18 years and older, who attended an ethnic market on April 7 or 14, 2007, were recruited. Participants were interviewed by bilingual English- and Arabic-speaking investigators using a semi-structured interview to assess dress; demographic variables; medical history; medication use; clinical symptoms associated with vitamin D deficiency (eg, joint or bone pain, muscle weakness); and dietary intake of vitamin D from fortified orange juice, milk, and vitamin supplementation. Blood samples were drawn to measure concentrations of serum calcium, creatinine, phosphorus, alkaline phosphatase, parathyroid hormone, and 25-hydroxyvitamin D. Participants were initially divided into 2 groups based on whether the woman was veiled and further subdivided into 3 groups on the basis of vitamin D intake from supplemented food sources (milk or vitamin D–fortified orange juice) and vitamin pills: unveiled, veiled and taking supplements, and veiled and taking no supplements.ResultsEighty-seven women participated. Serum 25-hydroxyvitamin D levels were uniformly low, with the highest levels in the unveiled group (median [interquartile range]) (8.5 ng/mL [5.75-13.5 ng/mL]) followed by the veiled, supplemented group (7 ng/mL [4-11.5 ng/mL]) and the veiled, unsupplemented group (4 ng/mL [2-6.8 ng/ mL]). 25-Hydroxyvitamin D levels were lower in women with less experience in the United States and in those with less education. Vitamin D–fortified orange juice consumption had a greater positive predictive effect on serum 25- hydroxyvitamin D levels than either milk or vitamin pills and may possibly serve as a surrogate marker for vitamin D awareness.ConclusionsVitamin D deficiency, as assessed by 25-hydroxyvitamin D concentrations, is endemic in a sample of Arab-American women living in Dearborn, Michigan. These findings potentially identify an important health problem in the largest, most-concentrated Arab- American population in the United States. (Endocr Pract. 2009;15:35-40)     

Vitamin D,Calcium, and Cardiovascular Mortality: A Perspective from A Plenary Lecture Given at the Annual Meeting of the American Association of Clinical Endocrinologists

ObjectiveTo examine data showing associations between serum 25-hydroxyvitamin D levels and calcium intake and cardiovascular mortality.MethodsThe articles reviewed include those published from 1992-2011 derived from search engines (PubMed, Scopus, Medscape) using the following search terms: vitamin D, calcium, cardiovascular events, cardiovascular mortality, all-cause mortality, vascular calcification, chronic kidney disease, renal stones, and hypercalci- uria. Because these articles were not weighted (graded) on the level of evidence, this review reflects my own perspective on the data and how they should be applied to clinical management.ResultsFor skeletal health, vitamin D and calcium are both needed to ensure proper skeletal growth (modeling) and repair (remodeling). Nutritional deficiencies of either vitamin D or calcium may lead to a spectrum of metabolic bone disorders. Excessive consumption of either nutrient has been linked to a variety of medical disorders, such as hypercalcemia or renal stones. There have also been associations between vitamin D or calcium intake and cardiovascular disease. However, neither of these associations have established evidence nor known causality for increasing cardiovascular risk or all-cause mortality in patients with creatinine clearances greater than 60 mL/ min. In patients with more severe chronic kidney disease, stronger data link excess calcium (or phosphorus) intake and increase in vascular calcification, but not mortality. The safe upper limit for vitamin D intake is at least 4000 IU daily and probably 10 000 IU daily; for calcium, the safe upper limit is between 2000 and 3000 mg daily.ConclusionsWhile no solid scientific evidence validates that serum vitamin D levels between 15 and 70 ng/ mL are associated with increased cardiovascular disease risk, stronger but inconsistent evidence shows an association between calcium supplementation greater than 500 mg daily and an increase in cardiovascular disease risk. Most professional societies suggest that replacement levels of these nutrients be personalized with the goal of reaching a 25-hydroxyvitamin D concentration between 30 and 50 ng/ mL and a calcium intake of 1200 mg daily. (Endocr Pract. 2011;17:798-806)     

Estimated benefit of increased vitamin D status in reducing the economic burden of disease in western Europe

Vitamin D has important benefits in reducing the risk of many conditions and diseases. Those diseases for which the benefits are well supported and that have large economic effects include many types of cancer, cardiovascular diseases, diabetes mellitus, several bacterial and viral infections, and autoimmune diseases such as multiple sclerosis. Europeans generally have low serum 25-hydroxyvitamin D [25(OH)D] levels owing to the high latitudes, largely indoor living, low natural dietary sources of vitamin D such as cold-water ocean fish, and lack of effective vitamin D fortification of food in most countries. Vitamin D dose–disease response relations were estimated from observational studies and randomized controlled trials. The reduction in direct plus indirect economic burden of disease was based on increasing the mean serum 25(OH)D level to 40 ng/mL, which could be achieved by a daily intake of 2000–3000 IU of vitamin D. For 2007, the reduction is estimated at €187,000 million/year. The estimated cost of 2000–3000 IU of vitamin D3/day along with ancillary costs such as education and testing might be about €10,000 million/year. Sources of vitamin D could include a combination of food fortification, supplements, and natural and artificial UVB irradiation, if properly acquired. Additional randomized controlled trials are warranted to evaluate the benefits and risks of vitamin D supplementation. However, steps to increase serum 25(OH)D levels can be implemented now based on what is already known.     

Vitamin D status and response to Vitamin D(3) in obese vs. non-obese African American children

Background: Serum 25‐hydroxyvitamin D (25(OH)D) is low in obese adults. Objective: To examine serum 25(OH)D in obese (BMI >95th percentile for age) vs. non‐obese (BMI = 5th–75th percentile for age) 6–10‐year‐old African American children and compare their differences in therapeutic response to vitamin D supplementation. Methods and Procedures: In an open label non‐randomized pre‐post comparison 21 obese (OB) and 20 non‐obese (non‐OB) subjects matched for age, sex, skin color, and pubertal maturation were treated with 400 IU of vitamin D₃ daily for 1 month. Serum 25(OH)D, 1,25‐dihydroxyvitamin D (1,25(OH)₂D), parathyroid hormone (PTH), leptin, and markers of bone turnover (serum bone‐specific alkaline phosphatase (BSAP), osteocalcin (OC), and urine n ‐telopeptide cross‐links of type 1 collagen (urine NTX)) were measured. Vitamin D deficiency was defined as serum 25(OH)D ≤20 ng/ml and insufficiency as 21–29 ng/ml respectively. Results: Vitamin D deficiency occurred in 12/21 (57%) OB vs. 8/20 (40%) non‐OB at baseline (P = 0.35) and persisted in 5/21 (24%) OB vs. 2/18 (11%) non‐OB (P = 0.42) after treatment. When the cohort was stratified by the baseline levels of 25(OH)D, there were differences in the response to treatment in the obese and non‐obese cohorts. Discussion: Vitamin D deficiency was common among OB and non‐OB preadolescent African American children, and 400 IU of vitamin D₃ (2× the recommended adequate intake) daily for 1 month was inadequate to raise their blood levels of 25(OH)D to ≥30 ng/ml.     

Automated method for the determination of fat-soluble vitamins in serum

A new fully automated high-performance liquid chromatography (HPLC) method using 1 ml of serum has been developed for the determination of retinol (Vitamin A), alpha-tocopherol (Vitamin E), 25-hydroxyvitamin D(3) and 24 R,25-hydroxyvitamin D(3). The eluate was monitored with a photodiode-array detector at three wavelengths-namely: 265 nm for Vitamin D(3), 291 nm for Vitamin E and 325 nm for Vitamin A. The detection limits were equal to or lower than 1 ng ml(-1) for all vitamins. The linearity obtained with serum samples (standard addition method) gives correlation coefficients (r(2)) ranging between 0.999 and 0.996 in all cases, with standard deviation of the slope between 3.2 and 1.6%. The repeatability was between 4.0 and 6.0% and the within-laboratory reproducibility was lower than 10% in all cases. The most outstanding features of the present method are its ease of use, its rapidity and fully automation, which enables its use for routine analysis. The time required per sample was 30 min, because the overlapped development of the steps. This method was used for the determination of normality range of these vitamins in healthy people in the 18-80-year-old interval.     

Intake of vitamin D and risk of breast cancer--a meta-analysis

Vitamin D insufficiency has been shown to be associated with a number of conditions including diabetes, multiple sclerosis and the overall risk of cancer. We aimed at studying the association between vitamin D intake and risk of breast cancer in a meta-analysis. We searched Pubmed, Embase, and Web of Science using the MESH terms "vitamin D" and "breast cancer". A total of 1731 studies were identified, but only 6 studies contained original data on the association between intake of vitamin D and risk of breast cancer. Overall there was no association between amount of vitamin D and risk of breast cancer (RR=0.98, 95% CI: 0.93-1.03, test for heterogeneity p<0.01). However, most studies reported on very low intakes of vitamin D (typically in the range 100-400IU/day). Restricting the analyses to intakes >/=400IU/day yielded a more homogenous result with a trend towards less breast cancer with >/=400IU/day vs. the lowest intake (typically <50-150IU/day), RR=0.92, 95% CI: 0.87-0.97, p for heterogeneity 0.14. In conclusion there may be a trend towards fewer cases of breast cancer with higher intakes of vitamin D (>/=400IU/day). However, more research is needed, preferably in the form of randomized-controlled trials.     

Why the optimal requirement for Vitamin D3 is probably much higher than what is officially recommended for adults

The physiologic range for circulating 25-hydroxyvitamin D3 [25(OH)D; the measure of Vitamin D nutrient status] concentration in humans and other primates extends to beyond 200 nmol/L (>80 ng/mL). This biologic "normal" value is greater than current population norms for 25(OH)D. Concentrations of 25(OH)D that correlate with desirable effects extend to at least 70 nmol/L, with no obvious threshold. Randomized clinical trials using 20 mcg (800 IU) per day of Vitamin D show that this suppresses parathyroid hormone, preserves bone mineral density, prevents fractures, lowers blood pressure and improves balance. Calcium absorption from diet correlates with 25(OH)D in the normal range. Health effects of Vitamin D beyond osteoporosis are mostly supported by the circumstantial evidence of epidemiologic studies and laboratory research. These include prevention of cancer and the autoimmune diseases, insulin-dependent diabetes and multiple sclerosis. One mcg per day of Vitamin D(3) (cholecalciferol) increases circulating 25(OH)D by about 1 nmol/L (0.4 ng/mL). A recommended dietary allowance (RDA) is the long-term daily intake level that meets the total requirements for the nutrient by nearly all healthy individuals (it would presume no sunshine). If 70 nmol/L is regarded as a minimum desirable target 25(OH)D concentration, then current recommendations of 15 mcg per day do not meet the criterion of an RDA.     

Investigation of the VDR gene polymorphisms association with susceptibility to colorectal cancer

The effects of 1,25-dihydroxyvitamin D3 are mediated by binding to a specific intracellular vitamin D receptor (VDR), which has been identified in a variety of tissues. Certain polymorphisms in the VDR gene have been associated with various neoplasms. For this purpose, we studied whether VDR TaqI or FokI genotype are associated with serum 25-hydroxyvitamin D3 in 52 controls and 26 patients with colorectal cancer. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP), and agarose gel electrophoresis tecniques were used to detect these polymorphisms. We measured 25-hydroxyvitamin D3 serum levels by ELISA. The frequencies of the FF, Ff and ff genotypes were 73.1%, 11.5%, 15.4% in colorectal cancer patients and 38.5%, 59.6%, 1.9% in healthy controls, respectively. We observed the T allele in 50% and 58.7%, and the t allele in 50% and 41.3% of colorectal cancer patients and the control group, respectively. In patients with colorectal cancer who have TT genotype, serum 25-hydroxyvitamin D3 level was lower than those with Tt/tt genotype (p:0.016). The frequency of subjects with TTFf or TtFf genotype in colorectal cancer patients was very low compared with all other genotypes (OR = 0.112; 95%CI 0.030-0.419). These data suggest that VDR TtFf or TTFf genotypes may protect against colorectal carcinogenesis. However, further studies are necessary to confirm these findings.     

Twice single doses of 100,000 IU of vitamin D in winter is adequate and safe for prevention of vitamin D deficiency in healthy children from Ushuaia, Tierra Del Fuego, Argentina

In order to improve vitamin D status of children from Ushuaia (55°S), at the South of Argentina, double supplementation with 100.000 IU of vitamin D was administered at the beginning of winter (March 2004), and 3 months later during winter (June 2004). In 2004, serum 25-hydroxyvitamin D (25OHD) was measured before the first supplementation, a month after, and 3 months after receiving the second supplementation (March, April and September). We studied 18 healthy children from Ushuaia, age (mean ± S.D.) 7.3 ± 4.4 years old (range 1.2–14.6), seven girls and 11 boys. Before treatment, serum 25OHD was 29.3 ± 5.9 ng/ml. It increased significantly 1 month after the first supplementation (April): 35.3 ± 4.4 ng/ml (p < 0.001), and decreased significantly 3 months after the second supplementation: 22.4 ± 4.6 ng/ml (September (p < 0.001). No child was neither deficient (<10 ng/ml) nor insufficient (10–15 ng/ml) of vitamin D. On April, a month after the first supplementation, no children had vitamin D intoxication levels (>50 ng/ml). These results disclosed that to prevent vitamin D deficiency for children at zones of risk at the south of our country, double supplementation of 100,000 IU of vitamin D during autumn and winter, would be adequate and safe.     

Vitamin D Metabolism and Guidelines for Vitamin D Supplementation

Vitamin D is essential for bone health and is known to be involved in immunomodulation and cell proliferation. Vitamin D status remains a significant health issue worldwide. However, there has been no clear consensus on vitamin D deficiency and its measurement in serum, and clinical practice of vitamin D deficiency treatment remains inconsistent. The major circulating metabolite of vitamin D, 25-hydroxyvitamin D (25(OH)D), is widely used as a biomarker of vitamin D status. Other metabolic pathways are recognised as important to vitamin D function and measurement of other metabolites may become important in the future. The utility of free 25(OH)D rather than total 25(OH)D needs further assessment. Data used to estimate the vitamin D intake required to achieve a serum 25(OH)D concentration were drawn from individual studies which reported dose-response data. The studies differ in their choice of subjects, dose of vitamin D, frequency of dosing regimen and methods used for the measurement of 25(OH)D concentration. Baseline 25(OH)D, body mass index, ethnicity, type of vitamin D (D₂ or D₃) and genetics affect the response of serum 25(OH)D to vitamin D supplementation. The diversity of opinions that exist on this topic are reflected in the guidelines. Government and scientific societies have published their recommendations for vitamin D intake which vary from 400–1000 IU/d (10–25 μg/d) for an average adult. It was not possible to establish a range of serum 25(OH)D concentrations associated with selected non-musculoskeletal health outcomes. To recommend treatment targets, future studies need to be on infants, children, pregnant and lactating women.     

Vitamin D deficiency as a risk factor for urinary tract infection in women at reproductive age

Vitamin D deficiency is a pandemic problem and an ever-increasing issue in human nutrition and health. Vitamin D (serum 25-hydroxyvitamin D) deficiency causes many health problems such as autoimmune diseases, Crohn’s disease, diabetes, inflammation, asthma, hypertension, and cancer. Vitamin D3 (cholecalciferol) deficiency has been documented as a persistent problem among adults, children, and elderly persons in most of the countries. Our main objective of this study was to determine the hypothesis that the vitamin D deficiency among women can lead to them developing frequent urinary tract infections. Vitamin D has a potential role in immune regulation and it prevents infections especially urinary tract infections (UTI). Therefore it has positive regulatory role in both acute and recurrent infections especially in women of reproductive ages. As women at this age group have specific differences in their urinary tract and the reproductive organ anatomy, make them more prone for micro-organisms' invasion, The present study was carried out to ascertain certain relation between serum 25-hydroxyvitamin D levels and UTI in women while contemplating the significance of knowing the risk factors associated with UTI and also finding ways to avoid serious complications. 75 women with (case group) UTI were differentiated with 35 healthy with no UTI (control group) and 40 women with UTI and their serum 25-hydroxyvitamin D levels were checked in a case control study. The women were between at 17–52 years of age. Using ELISA, Serum 25-hydroxyvitamin D levels were measured. Analysis and comparison of the results were done among the two groups. Vitamin D mean levels in the case group was considerably lower when in comparison with the control group (11.09 ± 7.571 ng/mL vs. 24.08 ± 11.95 ng/mL, P < 0.001).     

Vitamin D Status: A Different Story in the Very Young versus the Very Old Romanian Patients

BackgroundIn Romania (latitude 48°15’N to 43°40’N), vitamin D supplementation is common practice mostly in infants 0-1 year old. No published information is available regarding epidemiological data on vitamin D status in the Romanian population for a wide age range and geographical territory. In this context, we aimed to evaluate the seasonal and age variation of vitamin D status in a large Romanian population.Methods6631 individuals from across Romania had performed 7544 vitamin D assessments (2012-2014) in a chain of private laboratories. Vitamin D (25-hydroxyvitamin D2 and 25-hydroxyvitamin D3) was measured using High Performance Liquid Chromatography. Vitamin D levels were classified as severe deficiency<10ng/mL, deficiency 10-20ng/mL, insufficiency 21-29ng/mL, sufficiency≥30ng/mL and potentially harmful>100ng/ml.ResultsMale to female ratio was 1:2.9. Age ranged from 0 to 85 years. Mean vitamin D levels increased from April (26.3ng/ml) to September (35.6ng/ml) and decreased from October (33.5ng/ml) to March (24.4 ng/ml). Overall 40% had sufficient vitamin D, while the rest were insufficient 33%, deficient 22%, severely deficient 4% and 1% potentially harmful (of them 81% under 1 year old). Males compared to females showed higher percentages of sufficiency (47% vs. 38%). Children 0- 2 years presented the highest percentage of vitamin D sufficiency (77%). Lowest percentages (21%) of sufficiency were in people 80-84 years.ConclusionIn Romania, suboptimal vitamin D levels are common (59%), especially in older age, wintertime and in women. Vitamin D supplementation would be most warranted from January to April in the Romanian population. 25-hydroxyvitamin D levels>100ng/ml were relatively prevalent in children 0-1 year old (17.3%). This was attributed to supplementation errors and the fact that high-risk individuals were more likely to visit for medical check-up. Nonetheless, it stresses the need to increase awareness of the importance of preventing Vitamin D supplementation administration errors in the young.     

Serum 25-Hydroxyvitamin D Concentrations ≥40 ng/ml Are Associated with >65% Lower Cancer Risk: Pooled Analysis of Randomized Trial and Prospective Cohort Study

BackgroundHigher serum 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with a lower risk of multiple cancer types across a range of 25(OH)D concentrations.ObjectivesTo investigate whether the previously reported inverse association between 25(OH)D and cancer risk could be replicated, and if a 25(OH)D response region could be identified among women aged 55 years and older across a broad range of 25(OH)D concentrations.MethodsData from two cohorts representing different median 25(OH)D concentrations were pooled to afford a broader range of 25(OH)D concentrations than either cohort alone: the Lappe cohort (N = 1,169), a randomized clinical trial cohort (median 25(OH)D = 30 ng/ml) and the GrassrootsHealth cohort (N = 1,135), a prospective cohort (median 25(OH)D = 48 ng/ml). Cancer incidence over a multi-year period (median: 3.9 years) was compared according to 25(OH)D concentration. Kaplan-Meier plots were developed and the association between 25(OH)D and cancer risk was examined with multivariate Cox regression using multiple 25(OH)D measurements and spline functions. The study included all invasive cancers excluding skin cancer.ResultsAge-adjusted cancer incidence across the combined cohort (N = 2,304) was 840 cases per 100,000 person-years (1,020 per 100,000 person-years in the Lappe cohort and 722 per 100,000 person-years in the GrassrootsHealth cohort). Incidence was lower at higher concentrations of 25(OH)D. Women with 25(OH)D concentrations ≥40 ng/ml had a 67% lower risk of cancer than women with concentrations <20 ng/ml (HR = 0.33, 95% CI = 0.12–0.90).Conclusions25(OH)D concentrations ≥40 ng/ml were associated with substantial reduction in risk of all invasive cancers combined.