Robert Scragg

Effect of Vitamin D3 Supplementation on Upper Respiratory Tract Infections in Healthy Adults: The VIDARIS Randomized Controlled Trial

CONTEXT Observational studies have reported an inverse association between serum 25-hydroxyvitamin D (25-OHD) levels and incidence of upper respiratory tract infections (URTIs). However, results of clinical trials of vitamin D supplementation have been inconclusive. OBJECTIVE To determine the effect of vitamin D supplementation on incidence and severity of URTIs in healthy adults. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, placebo-controlled trial conducted among 322 healthy adults between February 2010 and November 2011 in Christchurch, New Zealand. INTERVENTION Participants were randomly assigned to receive an initial dose of 200,000 IU oral vitamin D3, then 200,000 IU 1 month later, then 100,000 IU monthly (n = 161), or placebo administered in an identical dosing regimen (n = 161), for a total of 18 months. MAIN OUTCOME MEASURES The primary end point was number of URTI episodes. Secondary end points were duration of URTI episodes, severity of URTI episodes, and number of days of missed work due to URTI episodes. RESULTS The mean baseline 25-OHD level of participants was 29 (SD, 9) ng/mL. Vitamin D supplementation resulted in an increase in serum 25-OHD levels that was maintained at greater than 48 ng/mL throughout the study. There were 593 URTI episodes in the vitamin D group and 611 in the placebo group, with no statistically significant differences in the number of URTIs per participant (mean, 3.7 per person in the vitamin D group and 3.8 per person in the placebo group; risk ratio, 0.97; 95% CI, 0.85-1.11), number of days of missed work as a result of URTIs (mean, 0.76 days in each group; risk ratio, 1.03; 95% CI, 0.81-1.30), duration of symptoms per episode (mean, 12 days in each group; risk ratio, 0.96; 95% CI, 0.73-1.25), or severity of URTI episodes. These findings remained unchanged when the analysis was repeated by season and by baseline 25-OHD levels. CONCLUSION In this trial, monthly administration of 100,000 IU of vitamin D did not reduce the incidence or severity of URTIs in healthy adults. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12609000486224.

Effect of Vitamin D Supplementation on Blood Pressure: A Systematic Review and Meta-analysis Incorporating Individual Patient Data

IMPORTANCE Low levels of vitamin D are associated with elevated blood pressure (BP) and future cardiovascular events. Whether vitamin D supplementation reduces BP and which patient characteristics predict a response remain unclear. OBJECTIVE To systematically review whether supplementation with vitamin D or its analogues reduce BP. DATA SOURCES We searched MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and http://www.ClinicalTrials.com augmented by a hand search of references from the included articles and previous reviews. Google was searched for gray literature (ie, material not published in recognized scientific journals). No language restrictions were applied. The search period spanned January 1, 1966, through March 31, 2014. STUDY SELECTION We included randomized placebo-controlled clinical trials that used vitamin D supplementation for a minimum of 4 weeks for any indication and reported BP data. Studies were included if they used active or inactive forms of vitamin D or vitamin D analogues. Cointerventions were permitted if identical in all treatment arms. DATA EXTRACTION AND SYNTHESIS We extracted data on baseline demographics, 25-hydroxyvitamin D levels, systolic and diastolic BP (SBP and DBP), and change in BP from baseline to the final follow-up. Individual patient data on age, sex, medication use, diabetes mellitus, baseline and follow-up BP, and 25-hydroxyvitamin D levels were requested from the authors of the included studies. For trial-level data, between-group differences in BP change were combined in a random-effects model. For individual patient data, between-group differences in BP at the final follow up, adjusted for baseline BP, were calculated before combining in a random-effects model. MAIN OUTCOMES AND MEASURES Difference in SBP and DBP measured in an office setting. RESULTS We included 46 trials (4541 participants) in the trial-level meta-analysis. Individual patient data were obtained for 27 trials (3092 participants). At the trial level, no effect of vitamin D supplementation was seen on SBP (effect size, 0.0 [95% CI, -0.8 to 0.8] mm Hg; P=.97; I2=21%) or DBP (effect size, -0.1 [95% CI, -0.6 to 0.5] mm Hg; P=.84; I2=20%). Similar results were found analyzing individual patient data for SBP (effect size, -0.5 [95% CI, -1.3 to 0.4] mm Hg; P=.27; I2=0%) and DBP (effect size, 0.2 [95% CI, -0.3 to 0.7] mm Hg; P=.38; I2=0%). Subgroup analysis did not reveal any baseline factor predictive of a better response to therapy. CONCLUSIONS AND RELEVANCE Vitamin D supplementation is ineffective as an agent for lowering BP and thus should not be used as an antihypertensive agent.

Vitamin D During Pregnancy and Infancy and Infant Serum 25-Hydroxyvitamin D Concentration

OBJECTIVE: To determine the vitamin D dose necessary to achieve serum 25-hydroxyvitamin D (25(OH)D) concentration ≥20 ng/mL during infancy. METHODS: A randomized, double-blind, placebo-controlled trial in New Zealand. Pregnant mothers, from 27 weeks’ gestation to birth, and then their infants, from birth to age 6 months, were randomly assigned to 1 of 3 mother/infant groups: placebo/placebo, vitamin D3 1000/400 IU, or vitamin D3 2000/800 IU. Serum 25(OH)D and calcium concentrations were measured at enrollment, 36 weeks’ gestation, in cord blood, and in infants at 2, 4, and 6 months of age. RESULTS: Two-hundred-and-sixty pregnant women were randomized. At enrollment, the proportions with serum 25(OH)D ≥20 ng/mL for placebo, lower-dose, and higher-dose groups were 54%, 64%, and 55%, respectively. The proportion with 25(OH)D ≥20 ng/mL was larger in both intervention groups at 36 weeks’ gestation (50%, 91%, 89%, P < .001). In comparison with placebo, the proportion of infants with 25(OH)D ≥20 ng/mL was larger in both intervention groups to age 4 months: cord blood (22%, 72%, 71%, P < .001), 2 months (50%, 82%, 92%, P < .001), and 4 months (66%, 87%, 87%, P = .004), but only in the higher-dose group at age 6 months (74%, 82%, 89%, P = .07; higher dose versus placebo P = .03, lower dose versus placebo P = .21). CONCLUSIONS: Daily vitamin D supplementation during pregnancy and then infancy with 1000/400 IU or 2000/800 IU increases the proportion of infants with 25(OH)D ≥20 ng/mL, with the higher dose sustaining this increase for longer.

Vitamin D and public health: an overview of recent research on common diseases and mortality in adulthood

OBJECTIVE There is increasing interest in vitamin D and its possible health effects. The aims of the present overview are to summarise the research on common diseases for which there is substantial evidence on vitamin D, identify diseases where vitamin D may be beneficial and discuss the public health implications of these findings. DESIGN Literature search of PubMed for the years 2000 to 2010 to identify cohort studies with baseline measures of 25-hydroxyvitamin D (25(OH)D) and randomised controlled trials (RCT) of vitamin D supplementation in relation to fractures, colorectal cancer, CVD and all-cause mortality. Risk ratios of disease from comparisons between 25(OH)D quantiles in these studies were summarised using RevMan software version 5·1 (The Nordic Cochrane Centre, Copenhagen). SETTING Community-based samples recruited into cohort studies from many countries. SUBJECTS Older men and women, mostly above 50 years of age. RESULTS When comparing the lowest 25(OH)D category with the highest (or reference), the pooled risk ratio (95 % CI) was: 1·34 (1·13, 1·59) for fractures from nine studies; 1·59 (1·30, 1·95) for colorectal cancer from nine studies; 1·35 (1·17, 1·56) for CVD from twelve studies; and 1·42 (1·23, 1·63) for all-cause mortality from twelve studies. CONCLUSIONS Cohort studies show that baseline 25(OH)D levels predict increased risk of fractures, colorectal cancer, CVD and all-cause mortality. These associations are weak and could be explained by confounding variables such as obesity and physical activity. Because of their potential public health significance, RCT using vitamin D doses ≥50 μg/d are required to determine whether vitamin D protects against these diseases.

Long-Term High-Dose Vitamin D3 Supplementation and Blood Pressure in Healthy Adults A Randomized Controlled Trial

Previous randomized controlled trials of vitamin D supplementation and blood pressure (BP) mainly have given vitamin D for short periods (<6 months) or at low doses (400 IU per day). This study aims to determine whether long-term high-dose vitamin D taken for 18 months lowers BP. Adults were recruited from a healthcare organization or university into a double-blind controlled trial and randomized to receive either vitamin D3 200 000 IU for 2 months followed by 100 000 IU monthly up to 18 months (n=161) or placebo (n=161). BP was measured at baseline, 5, and 18 months. Subjects had a mean (SD) age of 47.6 (9.7) years, 75% were women, and 94% were of European ancestry (white). Mean (SD) 25-hydroxyvitamin D3 changed from 73 (22) nmol/L at baseline to 124 (28) nmol/L at 18 months in the vitamin D group, and from 71 (22) nmol/L to 56 (22) nmol/L in the placebo group. Mean BP was similar for the vitamin D and placebo groups at baseline (123.4/76.3 versus 122.6/75.6 mm Hg; respectively). The mean change (95% confidence interval) in BP at 18 months minus baseline in the vitamin D group compared with placebo group was −0.6 (−2.8 to 1.6) mm Hg for systolic (P=0.61) and 0.5 (−1.1, 2.2) mm Hg for diastolic (P=0.53). Long-term vitamin D supplementation, which increased mean 25-hydroxyvitamin D3 concentration >100 nmol/L for 18 months, had no effect on systolic or diastolic BP in predominantly white, healthy adults without severe vitamin D deficiency. Beneficial effects on BP cannot be ruled out for other populations.

No effect of ultraviolet radiation on blood pressure and other cardiovascular risk factors.

Objectives Recent epidemiological studies have reported inverse associations between vitamin D status and blood pressure. The study aim is to determine if exposure to ultraviolet B radiation, which synthesizes vitamin D, lowers blood pressure, compared with ultraviolet A radiation. Methods Men and women (n = 119) with low vitamin D levels [serum 25-hydroxyvitamin D [25(OH)D] <50 nmol/l], completed a randomized clinical trial carried out during winter. Blood pressure was measured for 12–14 h with an ambulatory monitor at baseline and 12 weeks. In between, participants received 24 whole body exposures of either ultraviolet B (n = 58) or ultraviolet A (n = 61) over 12 weeks. Results Mean (SD) 25(OH)D increased from 43.7 (9.7) to 92.6 (16.9) nmol/l in the ultraviolet B arm after 12 weeks, and from 45.4 (9.2) to 64.9 (11.3) nmol/l in the ultraviolet A arm. However, mean blood pressure, which was similar for the ultraviolet B and ultraviolet A at baseline (134.9/79.2 vs. 132.9/77.8 mmHg; P = 0.59 and 0.56, respectively), did not change from baseline to 12 weeks in either group. The mean change [95% confidence interval (CI)] in blood pressure over this period in the ultraviolet B group compared with the ultraviolet A group was −2.2 (−7.8, 3.3) mmHg for systolic (P = 0.42) and −2.7 (−6.5, 1.0) mmHg for diastolic (P = 0.15). Conclusion Exposure to ultraviolet B did not lower blood pressure. Our results suggest that if vitamin D protects against cardiovascular disease, it involves some mechanism other than blood pressure.

Dietary intakes of European, Māori, Pacific and Asian adults living in Auckland: the Diabetes, Heart and Health Study.

Objective: To compare dietary intakes of European, Māori, Pacific, and Asian men and women living in Auckland.

Reduced primary care respiratory infection visits following pregnancy and infancy vitamin D supplementation: a randomised controlled trial.

To determine whether vitamin D supplementation reduces primary care visits for acute respiratory infection (ARI).

Do we need to take calcium with vitamin D supplements to prevent falls, fractures, and death?

Purpose of reviewThe 2011 report by the US Institute of Medicine (IOM) on dietary reference intakes for calcium and vitamin D is based on meta-analyses of randomized controlled trials (RCTs), which concluded that vitamin D supplements need to be taken with calcium supplements to prevent falls, fractures, and all-cause mortality. This study reviews recent meta-analyses of RCTs of vitamin D supplementation to determine whether their conclusions are consistent with the meta-analyses underpinning the IOM report. Recent findingsSince 2007 when the first IOM meta-analysis was published, up to May 2012, there have been nine meta-analyses of RCTs of vitamin D supplements on risk of falls, 10 on fractures, and five on all-cause mortality. About half of these reported summary effects for both vitamin D combined with calcium supplements and also vitamin D alone. However, statistical testing of results from recent meta-analyses does not support the conclusions of the IOM meta-analyses. SummaryThe inconsistency in the conclusions from meta-analyses is due to limitations in the design of previous RCTs of vitamin D supplementation. Large RCTs, giving higher doses of vitamin D (without calcium), should provide a clear answer within several years as to whether vitamin D supplements are beneficial by themselves.

Waist circumference modifies the association between serum 25(OH)D and systolic blood pressure: results from NHANES 2001-2006.

Objective: Results on the association between vitamin D and blood pressure are conflicting and little is known about how their relationship may be affected by obesity. Thus, we explored whether waist circumference modified the association between serum 25-hydroxyvitamin D (25(OH)D) and blood pressure in participants of the U.S. National Health and Nutrition Examination Surveys 2001–2006. Methods: We included 10 331 nonpregnant participants aged 20 years or older. The association of serum 25(OH)D with systolic and diastolic blood pressure, in the total sample and stratified by waist circumference category (abdominal overweight: 80 to <88 cm in females / 94 to <102 cm in males; abdominal obesity: ≥88 cm in females/ ≥102 cm in males), was examined using multiple linear regression. Effect modification by waist circumference was assessed through a cross-product interaction term between 25(OH)D category and waist circumference category. Results: Waist circumference significantly modified the inverse association between 25(OH)D and systolic blood pressure (SBP) (P value for interaction: 0.09). A stronger association of 25(OH)D levels below 15 ng/ml (reference: ≥30 ng/ml) with SBP was found in abdominally obese (&bgr; = 3.5 mmHg) than in abdominally overweight (&bgr; = 2.0 mmHg) and normal waist participants (&bgr; = 1.2 mmHg), but this interaction was only significant in participants without antihypertensive treatment. No significant effect modification was found for diastolic blood pressure. Conclusion: Results from this large, cross-sectional sample suggest that the association between 25(OH)D and SBP is stronger in individuals with abdominal obesity than in those with a normal waist or with abdominal overweight.