Actions of vitamins D2 and D3 and 25-OHD3 in anticonvulsant osteomalacia.

In 54 epileptic outpatients treated for at least one year with anticonvulsants the bone mineral content (B.M.C.), an estimate of total body calcium, and serum calcium were measured before and during treatment with three doses of cholecalciferol (vitamin D3; 200, 100, and 50 mu-g daily) and 25-hydroxycholecalciferol (25-OHD3; 40, 20, and 10 mu-g daily) for 12 weeks. The results, when compared with the effects of calciferol (vitamin D2; 200, 100, and 50 mu-g daily) in 40 epileptic outpatients, showed different actions in anticonvulsant osteomalacia of vitamin D2 on the one hand and vitamin D3 and 25-OHD3 on the other. In the patients who received vitamin D2 an increase in B.M.C. was found whereas serum calcium was unchanged. The patients who received vitamin D3 or 25-OHD3 showed an increase in serum calcium but unchanged values of B.M.C. The results suggest that liver enzyme induction cannot alone explain anticonvulsant osteomalacia.     

Vitamin D supplements and 25-hydroxy vitamin D concentrations in the elderly.

Serial 25-hydroxy vitamin D (25-OHD) concentrations were measured in long-stay geriatric patients treated with vitamin D. Comparison between a treatment and a control group showed that a daily dose of 500 IU vitamin D produced a significant increase in 25-OHD levels by two months. The supplement had a striking effect when the initial 25-OHD level was low and very little effect when it was high. 25-OHD levels in subjects on 2000 IU vitamin D daily were only marginally higher than those in subjects on 500 IU. A dose of 500 IU vitamin D daily should therefore produce adequate blood 25-OHD concentrations in most old people, and probably prevent most cases of osteomalacia in the elderly--though a large-scale study is needed to confirm this.     

Vitamin D Deficiency in Children with a Chronic Illness–Seasonal and Age-Related Variations in Serum 25-hydroxy Vitamin D Concentrations

Introduction

Children and adolescents with a chronic illness have potential risk factors for vitamin D deficiency. An optimal vitamin D status might have multiple health effects. This study evaluated vitamin D status and its association with age, gender, and season in a large cohort of chronically ill Finnish patients at a tertiary pediatric outpatient clinic. A cross-sectional register-based study was carried out, involving altogether 1351 children (51% boys, age range 0.2–18 years), who visited the outpatient clinic during 2007–2010 and had their vitamin D status (S-25-OHD) determined. A post-doc analysis was conducted to identify predisposing and preventing factors for vitamin D deficiency.

Results

Almost half (47%) of the S-25-OHD values were consistent with subnormal vitamin D status (S-25-OHD <50 nmol/L) while only 12% were >80 nmol/L. Age and season were the most important determinants for S-25-OHD concentration. Mean S-25-OHD concentration differed between age groups (Kruskal-Wallis; p<0.001), adolescents being at highest risk for vitamin D insufficiency. Young age and vitamin D supplementation were preventive factors for deficiency, while non-Finnish ethnic background was a predisposing factor. S-25-OHD showed significant seasonal variation in children older than 6 years. In the whole cohort, S-25-OHD was on average 13 nmol/L higher in summer than in winter, and the prevalence of vitamin D deficiency ( =  S-25-OHD <37.5 nmol/l) varied from 11% in summer to 29% in winter.

Conclusions

The finding that almost half of the studied Finnish children with a chronic illness had suboptimal vitamin D status is alarming. Inferior vitamin D status was noted in adolescents compared with younger children, suggesting that imbalance between intake and requirement evolves with age. Although less common during summer, subnormal vitamin D status was still observed in 28% of those evaluated in summer. Clinicians should identify individuals at risk and actively recommend vitamin D supplementation.     

Diet,sunlight, and 25-hydroxy vitamin D in healthy children and adults.

In 110 white West Midlands children serum 25-hydroxy vitamin D (25-OHD) concentrations showed a pronounced seasonal variation, the values being highest in August and lowest in February. The concentrations correlated significantly both with recorded sunlight and with seasonal ultraviolet energy of the sunlight. Children who had had a seaside holiday the previous summer had a higher mean 25-OHD concentration than those who had not had a summer holiday away from home. Correlation between vitamin D intake and serum 25-OHD concentration was not significant.     

Increase in Bone Mass After Correction of Vitamin D Insufficiency in Bisphosphonate-Treated Patients

ObjectiveTo assess the relative contribution of vitamin D insufficiency to loss of bone mineral density (BMD) in patients taking bisphosphonates.MethodsPatients were eligible for inclusion if they had osteoporosis or osteopenia and demonstrated a decline in BMD during the preceding year while taking stable doses of alendronate or risedronate, plus supplemental calcium and vitamin D. Patients with previously known secondary causes of osteoporosis were excluded from the study. Eligible patients underwent prospective measurement of bilateral hip and lumbar spine BMD by dual-energy x-ray absorptiometry, serum 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D, intact parathyroid hormone, osteocalcin, and thyroid-stimulating hormone (thyrotropin), and urinary calcium:creatinine ratio.ResultsAnnual BMD was assessed in 175 previously bisphosphonate-responsive patients with low BMD. Of the 175 patients, 136 (78%) had either a significant interval increase or no change in BMD, whereas 39 (22%) had a significant decrease. Of the 39 patients who lost BMD, 20 (51%) had vitamin D insufficiency (25-OHD < 30 ng/mL). After a single course of orally administered vitamin D₂ (500,000 IU during a 5-week period), the 25-OHD level returned to normal in 17 of the 20 vitamin D-insufficient patients and was associated with significant (P < .02) 3.0% and 2.7% increases in BMD at the lumbar spine and the femoral neck, respectively. Failure to normalize the serum 25-OHD level was associated with further loss of BMD.ConclusionVitamin D insufficiency was the most frequently identified cause of bone loss in patients with declining BMD during bisphosphonate therapy. Correction of vitamin D insufficiency in these patients led to a significant rebound in BMD. (Endocr Pract. 2008; 14:293-297)     

Vitamin D supplements in pregnant Asian women: effects on calcium status and fetal growth.

In a double-blind trial of vitamin D supplements in pregnant Asian women calciferol (ergocalciferol, 1000 IU/day) was administered to 59 women and placebo to 67 controls during the last trimester. The two groups had similar distributions of maternal age, height, parity, number of vegetarians, countries of origin, and sex and gestation of the infants. At entry to the trial maternal serum 25-hydroxy vitamin D (25-OHD) concentrations were low in both treatment and control groups and significantly lower in vegetarians than non-vegetarians. Mothers in the treatment group gained weight faster in the last trimester than those in the control group, and at term they and their infants all had adequate plasma 25-OHD concentrations, Mothers and infants in the control group, however, had low plasma concentrations of 25-OHD and calcium and raised plasma alkaline phosphatase (bone isoenzyme) activity. Five of these infants developed symptomatic hypocalcaemia. Almost twice as many infants in the control group were small for gestational age (29% v 15%), but there were no significant differences between the two groups of infants in antropometric measurements. Infants in the control group, however, had larger fontanelles, suggesting impaired ossification of the skull. Because of the benefits to mothers and infants in the treatment group and the absence of side effects, vitamin D supplements should be given to all pregnant Asian women in the United Kingdom.     

Serum concentrations of 25-hydroxy vitamin D in Europeans and Asians after oral vitamin D3.

Serum concentrations of 25-hydroxy vitamin D (25-OHD3) were measured in seven Asians of Indian extraction and eight Europeans before and at intervals after taking 1 mg vitamin D3 by mouth. In all subjects the concentrations rose in the 24 hours after ingestion. There was little change over the next nine days in the concentrations in the Europeans but those in the Asians continued to rise until about day 10. Subsequent rates of fall in 25-OHD3 were similar in the two groups. Our observations suggest that the low serum concentrations of 25-OHD3 found in Asians are not caused by either impaired intestinal absorption of vitamin D or rapid clearance of 25-ODH3 from the plasma.     

Abnormalities of Vitamin D and Calcium Metabolism after Surgical Treatment of Morbid Obesity: A Study of 136 Patients

ObjectiveTo assess the effect of bariatric surgical treatment of morbid obesity on bone mineral metabolism.MethodsWe analyzed pertinent vitamin D and calcium metabolic variables in 136 patients who had undergone a malabsorptive bariatric operation. Measurements of bone mineral density (BMD), serum 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D [1,25-(OH)₂D], parathyroid hormone (PTH), calcium, phosphorus, and alkaline phosphatase were performed. Statistical analyses assessed correlations among various factors.ResultsThe mean age (± SD) of the study group was 48.34 ± 10.28 years. Their mean weight loss was 114.55 ± 45.66 lb, and the mean duration since the bariatric surgical procedure was 54.02 ± 51.88 months. Seventeen patients (12.5%) had a T-score of -2.5 or less, and 54 patients (39.7%) had a T-score between –1.0 and –2.5. Of 119 patients in whom serum 25-OHD was measured, 40 (34%) had severe hypovitaminosis D (25-OHD < 8 ng/mL), and 50 patients (42%) had low hypovitaminosis D (serum 25-OHD 8 to 20 ng/mL). The magnitude of weight loss correlated negatively with serum 25-OHD, calcium, phosphorus, and calcium × phosphorus product values and positively with serum alkaline phosphatase level. Serum 25-OHD and calcium concentrations correlated positively with the BMD. PTH, serum 1,25-(OH)₂D, and alkaline phosphatase concentrations correlated negatively with the BMD, a reflection of the presence of secondary hyperparathyroidism, an accelerated conversion of 25-OHD to 1,25-(OH)₂D by the elevated PTH levels, and increased osteoblastic activity. The mean daily vitamin D supplementation was 6,472 ± 9,736 IU.ConclusionHypovitaminosis D and subsequent bone loss are common in patients who have undergone a bariatric surgical procedure for morbid obesity. These patients require rigorous vitamin D supplementation. (Endocr Pract. 2007;13:131-136)     

Vitamin D is a major determinant of bone mineral density at school age

Background

Vitamin D insufficiency in children may have long-term skeletal consequences as vitamin D affects calcium absorption, bone mineralization and bone mass attainment.

Methodology/Principal Findings

This school-based study investigated vitamin D status and its association with vitamin D intake and bone health in 195 Finnish children and adolescents (age range 7–19 years). Clinical characteristics, physical activity and dietary vitamin D intake were evaluated. Blood and urine samples were collected for serum 25-hydroxyvitamin D (25-OHD) and other parameters of calcium homeostasis. Bone mineral density (BMD) and body composition were measured with dual-energy X-ray absorptiometry (DXA). Altogether 71% of the subjects were vitamin D insufficient (25-OHD <50 nmol/L). The median 25-OHD was 41 nmol/L for girls and 45 nmol/L for boys, and the respective median vitamin D intakes 9.1 µg/day and 10 µg/day. In regression analysis, after adjusting for relevant factors, 25-OHD concentration explained 5.6% of the variance in lumbar BMD; 25-OHD and exercise together explained 7.6% of the variance in total hip BMD and 17% of the variance in whole body BMD. S-25-OHD was an independent determinant of lumbar spine and whole body BMD and in magnitude surpassed the effects of physical activity.

Conclusions/Significance

Vitamin D insufficiency was common even when vitamin D intake exceeded the recommended daily intake. Vitamin D status was a key determinant of BMD. The findings suggest urgent need to increase vitamin D intake to optimize bone health in children.     

Vitamin D status in different subgroups of British Asians.

To assess the effect of religious dietary practices and social customs on the vitamin D status of Asian immigrants, we kept records of the dietary intake and time spent out of doors of 81 Ugandan Asian men, women, and girls (9-19 years old). Sera were analysed for 25-hydroxycholecalciferol (25-OHD3), and 28% of the subjects were found to have levels below the lower limit of normal. The (vegetarian) Hindus had the lowest dietary intakes, least time out of doors, and lowest serum 25-OHD3. The Goan (Roman Catholic) Asians, despite more pigmentation, had 25-OHD3 levels similar to those found among indigenous British people and had the most satisfactory vitamin D intakes. Among Asians, whose exposure to sunlight may be limited, dietary vitamin D becomes the major determinant of serum 25-OHD3.     

Serum 25-hydroxyvitamin-D responses to multiple UV exposures from solaria: inferences for exposure to sunlight

We investigate the relationship between blood serum 25-hydroxyvitamin D (25(OH)D) and UV exposure from two artificial sources. We then use the results to test the validity of the action spectrum for vitamin D production, and to infer the production from summer and winter sunlight. The results are based on a two-arm randomised clinical trial of biweekly UV exposure for 12 weeks using two different types of dermatological booths: one emitting primarily UV-A radiation, and the other emitting primarily UV-B radiation (booth A and booth B respectively). In terms of the vitamin D production per unit erythema, one of the booths mimics summer noon sunlight, while the other mimics winter noon sunlight. Blood samples were taken before and after the exposures. For all participants, the phototherapy booth treatments arrested the usual wintertime decline in 25(OH)D, and for most the treatments from either booth resulted in significant increases. The increases were highly non-linear and there was a high degree of variability in 25(OH)D and its response to UV from person to person. By the end of the 12 week period, the mean increase was >30 nmol l(-1) from a cumulative exposure of 17 SED from the UV-A booth, and twice that for the UV-B booth for which the cumulative exposure was 268 SED. Assuming a logarithmic relationship between UV and vitamin D, the results for the two booths show no obvious inconsistency in the action spectrum for pre-vitamin D production. However, further measurements with similar exposures from each booth are required to confirm its validity. A model was developed to describe the increases in serum 25(OH)D resulting from the UV exposures, which differed markedly between the two booths. The deduced initial rate of increase of 25(OH)D was approximately 5 nmol l(-1) per SED. From the large increases in 25(OH)D from each booth, along with knowledge of the spectral distribution of sunlight and assuming the currently-accepted action spectrum for photo-conversion to pre-vitamin D, we infer that the production of 25(OH)D from sunlight should be possible throughout the year, although in winter the exposures necessary to maintain optimal levels of 25(OH)D would be impractically long. This finding is at variance with the commonly-held view that no vitamin D is produced at mid-latitudes in the winter. Further work is needed to resolve that inconsistency.     

25-Hydroxycholecalciferol absorption in steatorrhoea and postgastrectomy osteomalacia.

Post-absorption levels of 25-hydroxy vitamin D (25-OHD) after oral administration of 25-hydroxycholecalciferol (25-OHD3) were measured in 11 subjects. Five had presented with steatorrhoea of various causes while six had post-gastrectomy osteomalacia. Post-absorption levels of 25-OHD were low in four of the patients with steatorrhoea but normal in five of those with post-gastrectomy osteomalacia. There was a significant inverse correlation between peak post-absorption 25-OHD levels and faecal fat excretion. All patients with active post-gastrectomy osteomalacia had subnormal baseline plasma 25-OHD levels, which indicates that the condition is due to a deficiency of vitamin D. Only two of the patients with osteomalacia had estimated dietary vitamin D intakes ofer 1-75 microng/day. These findings suggest that an oral 25-OHD absorption test may be a valuable measure of small intestinal function and that poor dietary vitamin D intake rather than impaired absorption of the vitamin may be the major cause of post-gastrectomy osteomalacia.     

UVB radiation and its role in the treatment of postmenopausal women with osteoporosis

 In humans, the serum concentration of parathyroid hormone (PTH) is higher in winter than in summer. The increase of PTH can be suppressed by oral vitamin D supplements, which is considered beneficial to those with osteoporosis. The present study investigates whether this effect can also be achieved by serial ultraviolet (UV) irradiation of the skin. In total, 34 women suffering from postmenopausal osteoporosis were included in the open trial. In late winter, 20 patients were irradiated with a spectrum containing UVB, eight times over a period of 4 weeks. The serum concentrations of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)₂D], PTH, osteocalcin, alkaline phosphatase (AP), calcium and phosphorus were measured before the first, and 2 days after the last, dose of radiation. The data were compared to the controls (n=14, no UV exposure), who were evaluated once at the start of the study and then again 4 weeks later. After UV irradiation the level of 25(OH)D was increased, whilst that of PTH remained unchanged. The serum level of osteocalcin decreased in the control group, but did not change in the group of women who had been exposed to UV radiation. The present study of osteoporotic women does not confirm previous findings in studies of healthy volunteers i.e. that PTH can be suppressed by exposure to UVB radiation in winter. Further studies are required to specify whether there are subgroups of osteoporotic people who may benefit from exposure to UVB radiation during winter. Received: 31 October 1996 / Accepted: 21 October 1997     

Serum Vitamin D in Patients with Chronic Obstructive Lung Disease Does Not Correlate with Mortality – Results from a 10-Year Prospective Cohort Study

Background

Recent studies have found vitamin D (25-OHD) deficiency and insufficiency to be common among patients with COPD. Serum level of 25-OHD seems to correlate to pulmonary function, COPD disease staging, and increased susceptibility to respiratory infections. We wanted to investigate whether vitamin D deficiency or insufficiency was associated with mortality rate in patients suffering from advanced COPD.

Methods

25-OHD serum levels were measured in 462 patients suffering from moderate to very severe COPD. Patients were stratified into three groups according to serum levels of 25-OHD. Outcome measure was mortality in a 10 year follow-up period. Kaplan-Meier curves (KM) were plotted and mortality hazard ratios (HR) were calculated using Cox Proportional Hazard regression (Cox PH).

Results

Serum 25-OHD deficiency and insufficiency were prevalent. We were unable to demonstrate any association between baseline serum levels of 25-OHD and mortality rate. We found an association between mortality and age [HR 1.05 (CI 95%: 1.03–1.06)], Charlson score [HR 1.49 (CI 95%: 1.06–2.09)], increasing neutrophil count [HR 1.05 (CI 95%: 1.02–1.09)], severe [HR 1.41 (CI 95%: 1.06–1.86)]/very severe COPD [HR 2.19 (CI 95%: 1.58–3.02)] and a smoking history of more than 40 pack years [HR 1.27 (CI 95%: 1.02–1.70)].

Conclusions

Serum level of 25-OHD does not seem to be associated with mortality rate, suggesting no or only a minor role of 25-OHD in disease progression in patients with moderate to very severe COPD.     

Vitamin D metabolism in polar vertebrates

1. Studies of serum 25-hydroxy-vitamin D (25-OHD) in the Antarctic have been undertaken in husky dog, seal and penguin and compared to man. 2. Husky dogs showed a reversal of the expected seasonal variation of serum 25-OHD with maxima in June when the hours of bright sunshine and amount of u.v. -B radiation were lowest. 3. Values for random serum 25-OHD values in seals showed large interspecies differences, the values for Weddell seals being significantly greater than for Crabeater seals (P less than 0.01). 4. Penguin sera showed low concentrations of serum 25-OHD with no evidence of a response to prolonged exposure to sunlight.     

Metabolism of vitamin D2 in pig liver homogenates: evidence for a free radical reaction

In vitro hydroxylation of vitamin D2 at carbon-24 (C-24) was demonstrated with pig liver homogenate. The putative 24-hydroxyvitamin D2 (24-OHD2) comigrated with standard 24-OHD2 on a Zorbax Sil column developed in hexane/isopropanol (98/2). Rechromatography in methylene chloride/methanol (99.8/0.2) resolved the putative 24-OHD2 into two components. The identity of these compounds was determined to be 24(R)-OHD2 and 24(S)-OHD2 (epimers) by low resolution mass spectroscopy and proton NMR spectroscopy. The fact that epimers of 24-OHD2 were produced from vitamin D2 in the absence of pig liver homogenate in vitro was strong evidence for the participation of free radicals in the reaction. Further support for free radical involvement was provided by the following observations: (a) hydroxyl free radical scavengers such as alpha-tocopherol, catalase, and ethanol reduced the amount of 24-OHD2 produced by 18-64%; (b) use of autoclaved homogenate in the incubation mixture had little or no effect on the amount of 24-OHD2 produced; and (c) the failure of the enzyme-substrate saturation curve to level off as expected with high levels of vitamin D2 (100-2000 micrograms = 50-1009 microM). Maximum production of 24-OHD2 was obtained at pH 4.75 and represented a sevenfold increase relative to the amount produced at pH 7.4. The omission of citrate or the addition of electron transport inhibitors, cyanide or antimycin, had little or no effect on the reaction. These data suggested that C-24 hydroxylation of vitamin D2 in vitro was a free radical-mediated process not involving the electron transport system. In vitro hydroxylation at C-24 appeared to be driven by free radicals, and the dominance of this reaction made it difficult to determine whether there was an enzyme involved in the reaction.     

High dietary cholecalciferol increases plasma 25-hydroxycholecalciferol concentration, but does not attenuate the hypertension of Dahl salt-sensitive rats fed a high salt diet

The Dahl salt-sensitive rat, a model for salt-induced hypertension, develops hypovitaminosis D during high salt intake, which is caused by loss of protein-bound vitamin D metabolites into urine. We tested the hypothesis that high dietary cholecalciferol (5- and 10-fold standard) would increase plasma 25-hydroxycholecalciferol (25-OHD(3)) concentration (indicator of vitamin D status) of salt-sensitive rats during high salt intake. Salt-sensitive rats were fed 0.3% salt (low salt, LS), 3% salt (HS), 3% salt and 7.5 microg cholecalciferol/d (HS-D5), or 3% salt and 15 microg cholecalciferol/d (HS-D10) and sacrificed at week 4. Plasma 25-OHD(3) concentrations of the two groups of HS-D rats were similar to that of LS rats and more than twice that of HS rats. Urinary cholecalciferol metabolite content of HS-D rats was more than seven times that of HS rats. Systolic blood pressures of the hypertensive HS and HS-D rats did not significantly differ, whereas LS rats were not hypertensive. We conclude that high dietary cholecalciferol increases plasma 25-OHD(3) concentration, but does not attenuate the hypertension of salt-sensitive rats during high salt intake. Low salt intake may be necessary to both maintain optimal vitamin D status and prevent hypertension in salt-sensitive individuals.     

Comparison of Vitamin D Replacement Strategies with High-Dose Intramuscular or Oral Cholecalciferol: A Prospective Intervention Study

Objective: To ascertain the frequency of correction of vitamin D deficiency (VDD) with single or multiple doses of oral (PO) and intramuscular (IM) administration of 2 high-dose preparations of vitamin D₃ (VD₃).Methods: This was a prospective intervention study conducted in an ambulatory care setting. One hundred participants with VDD (25-hydroxy vitamin D &lsqb;25-OHD] <20 ng/mL) were randomized to receive a dose of 600,000 or 200,000 IU of VD₃ via a PO or IM route. The main outcome measure was serum 25-OHD levels at 2, 4, and 6 months after the intervention.The same dose was repeated in participants if 25-OHD remained <30 ng/mL at 2 and 4 months.Results: At 2 months, VDD was corrected in 93.8% of participants in Group 1 (600,000 IU IM); 83.3% in Group 2 (600,000 IU PO), 87.5% in Group 3 (200,000 IU IM), and 70.6% in Group 4 (200,000 IU PO). The mean changes from baseline in vitamin D levels at 2 months were 29.6 ± 13.7, 19.8 ± 12.3, 18.3 ± 10.6, and 13.7 ± 7.8 ng/mL in Groups 1, 2, 3, and 4, respectively. The mean levels remained significantly higher from baseline in all groups at all time points during the 6 months of observation. The mean 25-OHD level achieved in Group 1 was significantly higher than all other groups at 6 months.Conclusion: Two months after the intervention, VDD was corrected in more than 70% of participants with a single dose of either 600,000 or 200,000 IU given PO or IM.Abbreviations: ALT = alanine transaminase IM = intramuscular iPTH = intact parathyroid hormone IQR = interquartile range 25-OHD = 25 hydroxyvitamin D PO = oral VD₃ = vitamin D3 (cholecalciferol) VDD = vitamin D deficiency VDI = vitamin D insufficiency     

Instrumental variable estimation of the causal effect of plasma 25-hydroxy-vitamin D on colorectal cancer risk: a mendelian randomization analysis

Vitamin D deficiency has been associated with several common diseases, including cancer and is being investigated as a possible risk factor for these conditions. We reported the striking prevalence of vitamin D deficiency in Scotland. Previous epidemiological studies have reported an association between low dietary vitamin D and colorectal cancer (CRC). Using a case-control study design, we tested the association between plasma 25-hydroxy-vitamin D (25-OHD) and CRC (2,001 cases, 2,237 controls). To determine whether plasma 25-OHD levels are causally linked to CRC risk, we applied the control function instrumental variable (IV) method of the mendelian randomization (MR) approach using four single nucleotide polymorphisms (rs2282679, rs12785878, rs10741657, rs6013897) previously shown to be associated with plasma 25-OHD. Low plasma 25-OHD levels were associated with CRC risk in the crude model (odds ratio (OR): 0.76, 95% Confidence Interval (CI): 0.71, 0.81, p: 1.4×10(-14)) and after adjusting for age, sex and other confounding factors. Using an allele score that combined all four SNPs as the IV, the estimated causal effect was OR 1.16 (95% CI 0.60, 2.23), whilst it was 0.94 (95% CI 0.46, 1.91) and 0.93 (0.53, 1.63) when using an upstream (rs12785878, rs10741657) and a downstream allele score (rs2282679, rs6013897), respectively. 25-OHD levels were inversely associated with CRC risk, in agreement with recent meta-analyses. The fact that this finding was not replicated when the MR approach was employed might be due to weak instruments, giving low power to demonstrate an effect (<0.35). The prevalence and degree of vitamin D deficiency amongst individuals living in northerly latitudes is of considerable importance because of its relationship to disease. To elucidate the effect of vitamin D on CRC cancer risk, additional large studies of vitamin D and CRC risk are required and/or the application of alternative methods that are less sensitive to weak instrument restrictions.     

Diabetes: cost of illness in Norway

Background

Hypovitaminosis D is a common condition among elderly individuals in temperate-climate countries, with a clear seasonal variation on 25 hydroxyvitamin D levels, increasing after summer and decreasing after winter, but there are few data from sunny countries such as Brazil. Many factors can interfere on vitamin D cutaneous synthesis. We aimed at studying the 25OHD variations during winter and summer in an outdoor physically active elderly population living in São Paulo city, and analysed their determining factors.

Methods

Ninety-nine individuals (52 women and 47 men, from 55 to 83 years old) from different ethnic groups were selected from an outdoor physical activity group. Data are reported as Mean ± SD, and we used Pearson Linear Correlation, Student's t-test for non-related samples, Chi-square (χ²) test and One-way ANOVA for analysis.

Results

Mean 25OHD value for the whole group was 78.9 ± 30.9 nmol/L in the winter and 91.6 ± 31.7 nmol/L in the summer (p = 0.005). Mean winter serum 25OHD concentrations were not different between men and women (81.2 ± 30.1 nmol/L vs. 76.7 ± 31.8 nmol/L, respectively), and 19.2% of the individuals showed values < 50 nmol/L. In the summer, we noticed an increase only for men (107.6 ± 31.4 nmol/L) compared to women (76.7 ± 24.0 nmol/L), and 6.5% showed values < 50 nmol/L. A decrease in the mean PTH in the summer compared to the winter was noticed, with PTH levels showing a relationship with 25OHD concentrations only in the winter (r = -0.208, p = 0.041). White individuals showed an increase in mean serum 25OHD in the summer (p = 0.016) which was not noticed for other ethnic groups (Asians, native Brazilians and blacks). An increase in 25OHD values in the summer was observed in the age groups ranging from 51-60 and 61-70 years old (p < 0.05), but not in the age group from 71 years old on.

Conclusions

25OHD values increased during the summer in elderly residents of São Paulo, but to different extents depending on ethnicity, gender and age. This season-dependent increase was noticed only among men, white and who were in the youngest group of individuals.