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Summary table of Vitamin D Clinical Trials ( in English)
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Fallprevention with supplemental and active forms of vitamin D: ameta-analysis of randomised controlled trials.

Bischoff-FerrariHA, Dawson-HughesB, StaehelinHB, OravJE, StuckAE, TheilerR, WongJB, EgliA, KielDP, HenschkowskiJ.

Source

Centre on Aging andMobility, University of Zurich, Switzerland. [email protected]

Abstract

OBJECTIVE:

To test the efficacy ofsupplemental vitamin D and active forms of vitamin D with or withoutcalcium in preventing falls among older individuals.

DATASOURCES:

We searched Medline, theCochrane central register of controlled trials, BIOSIS, and Embase upto August 2008 for relevant articles. Further studies were identifiedby consulting clinical experts, bibliographies, and abstracts. Wecontacted authors for additional data when necessary. Review methodsOnly double blind randomised controlled trials of older individuals(mean age 65 years or older) receiving a defined oral dose ofsupplemental vitamin D (vitamin D(3) (cholecalciferol) or vitaminD(2) (ergocalciferol)) or an active form of vitamin D(1alpha-hydroxyvitamin D(3) (1alpha-hydroxycalciferol) or1,25-dihydroxyvitamin D(3) (1,25-dihydroxycholecalciferol)) and withsufficiently specified fall assessment were considered for inclusion.

RESULTS:

Eight randomisedcontrolled trials (n=2426) of supplemental vitamin D met ourinclusion criteria. Heterogeneity among trials was observed for doseof vitamin D (700-1000 IU/day v 200-600 IU/day; P=0.02) and achieved25-hydroxyvitamin D(3) concentration (25(OH)D concentration: <60nmol/l v >or=60 nmol/l; P=0.005). High dose supplemental vitamin Dreduced fall risk by 19% (pooled relative risk (RR) 0.81, 95% CI 0.71to 0.92; n=1921 from seven trials), whereas achieved serum 25(OH)Dconcentrations of 60 nmol/l or more resulted in a 23% fall reduction(pooled RR 0.77, 95% CI 0.65 to 0.90). Falls were not notably reducedby low dose supplemental vitamin D (pooled RR 1.10, 95% CI 0.89 to1.35; n=505 from two trials) or by achieved serum 25-hydroxyvitamin Dconcentrations of less than 60 nmol/l (pooled RR 1.35, 95% CI 0.98 to1.84). Two randomised controlled trials (n=624) of active forms ofvitamin D met our inclusion criteria. Active forms of vitamin Dreduced fall risk by 22% (pooled RR 0.78, 95% CI 0.64 to 0.94).

CONCLUSIONS:

Supplemental vitamin D ina dose of 700-1000 IU a day reduced the risk of falling among olderindividuals by 19% and to a similar degree as active forms of vitaminD. Doses of supplemental vitamin D of less than 700 IU or serum25-hydroxyvitamin D concentrations of less than 60 nmol/l may notreduce the risk of falling among older individuals.

JBone Miner Res. 2011Oct;26(10):2371-7. doi: 10.1002/jbmr.451.

Highserum 25-hydroxyvitamin D is associated with a low incidence ofstress fractures.

BurgiAA, GorhamED, GarlandCF, MohrSB, GarlandFC, ZengK, ThompsonK, LappeJM.

Source

Department of BehavioralSciences and Epidemiology, Naval Health Research Center, San Diego,CA, USA.

Abstract

Low serum25-hydroxyvitamin D [25(OH)D] concentrations are associated with hipfractures, but thedose-response relationship of serum 25(OH)D with risk of stressfractures in young women is unknown. This nestedcase-control study in a cohort of female Navy recruits was designedto determine whether those with low prediagnostic serum 25(OH)Dconcentrations had greater risk of stressfracture. Sera were drawn in 2002-2009 from 600 women who werediagnosed subsequently with stressfracture of the tibia or fibula and 600 matched controls who did notexperience a stress fracture.The 25(OH)D concentration was measured using the DiaSorinradioimmunoassay method. Controls were individually matched to caseson race (white, black, or other), length of service (±30days), and day blood was drawn (±2 days). There wasapproximately half the risk of stressfracture in the top compared with the bottom quintile of serum25(OH)D concentration (odds ratio [OR] = 0.51,95% CI 0.34-0.76, p ≤ 0.01).The range of serum 25(OH)D in the lowest quintile was 1.5 to 19.7(mean 13.9) ng/mL, whereas in the highest it was 39.9 to 112 (mean49.7) ng/mL. It is concluded that there was a monotonic inversedose-response gradient between serum 25(OH)D and risk of stressfracture. There was double the risk of stressfractures of the tibia and fibula in women withserum 25(OH)D concentrations of less than 20 ng/mLcompared to those with concentrations of 40 ng/mLor greater. A target for prevention of stressfractures would be a serum 25(OH)D concentrationof 40 ng/mLor greater, achievable with 4000 IU/dof vitamin D(3)supplementation.

ArchIntern Med. 2007Sep 10;167(16):1730-7.

VitaminD supplementation and total mortality: a meta-analysis of randomizedcontrolled trials.

AutierP, GandiniS.

Source

International Agency forResearch on Cancer, 150 cours Albert Thomas, F-69372 Lyon, [email protected]

Abstract

BACKGROUND:

Ecological andobservational studies suggest that low vitamin D status could beassociated with higher mortality from life-threatening conditionsincluding cancer, cardiovascular disease, and diabetes mellitus thataccount for 60% to 70% of total mortality in high-income countries.We examined the risk of dying from any cause in subjects whoparticipated in randomized trials testing the impact of vitamin Dsupplementation (ergocalciferol [vitamin D(2)] or cholecalciferol[vitamin D(3)]) on any health condition.

METHODS:

The literature up toNovember 2006 was searched without language restriction using thefollowing databases: PubMed, ISI Web of Science (Science CitationIndex Expanded), EMBASE, and the Cochrane Library.

RESULTS:

We identified 18independent randomized controlled trials, including 57 311participants. A total of 4777 deaths from any cause occurred during atrial size-adjusted mean of 5.7 years. Daily doses of vitamin Dsupplements varied from 300 to 2000 IU. The trial size-adjusted meandaily vitamin D dose was 528 IU. In 9 trials, there was a 1.4- to5.2-fold difference in serum 25-hydroxyvitamin D between theintervention and control groups. The summary relative risk formortality from any cause was 0.93 (95% confidence interval,0.87-0.99). There was neither indication for heterogeneity norindication for publication biases. The summary relative risk did notchange according to the addition of calcium supplements in theintervention.

CONCLUSIONS:

Intake of ordinary dosesof vitamin D supplements seems to be associated with decreases intotal mortality rates. The relationship between baseline vitamin Dstatus, dose of vitamin D supplements, and total mortality ratesremains to be investigated. Population-based, placebo-controlledrandomized trials with total mortality as the main end point shouldbe organized for confirming these findings.

AmJ Clin Nutr. 2009May;89(5):1321-7. Epub 2009 Mar 25.

VitaminD supplementation enhances the beneficial effects of weight loss oncardiovascular disease risk markers.

ZittermannA, FrischS, BertholdHK, GöttingC, KuhnJ, KleesiekK, StehleP, KoertkeH, KoerferR.

Source

Klinik fürThorax- und Kardiovaskularchirurgie and Institut fürLaboratoriums- und Transfusionsmedizin, Herzzentrum NRW, RuhrUniversität Bochum, Bad Oeynhausen, [email protected]

Abstract

BACKGROUND:

High blood concentrationsof parathyroid hormone and low concentrations of the vitamin Dmetabolites 25-hydroxyvitamin D [25(OH)D] and calcitriol areconsidered new cardiovascular disease risk markers. However, there isalso evidence that calcitriol increases lipogenesis and decreaseslipolysis.

OBJECTIVE:

We investigated the effectof vitamin D on weight loss and traditional and nontraditionalcardiovascular disease risk markers in overweight subjects.

DESIGN:

Healthy overweightsubjects (n = 200) with mean 25(OH)D concentrations of 30 nmol/L (12ng/mL) received vitamin D (83 microg/d) or placebo in a double-blindmanner for 12 mo while participating in a weight-reduction program.

RESULTS:

Weight loss was notaffected significantly by vitamin D supplementation (-5.7 +/- 5.8 kg)or placebo (-6.4 +/- 5.6 kg). However, mean 25(OH)D and calcitriolconcentrations increased by 55.5 nmol/L and 40.0 pmol/L,respectively, in the vitamin D group but by only 11.8 nmol/L and 9.3pmol/L, respectively, in the placebo group (P < 0.001), whereas amore pronounced decrease occurred in the vitamin D group than in theplacebo group in blood concentrations of parathyroid hormone (-26.5%compared with -18.7%; P = 0.014), triglycerides (-13.5% compared with+3.0%; P < 0.001), and the inflammation marker tumor necrosisfactor-alpha (-10.2% compared with -3.2%; P = 0.049). The beneficialbiochemical effects were independent of the loss in body weight, fatmass, and sex. However, compared with placebo, vitamin Dsupplementation also increased LDL-cholesterol concentrations (+5.4%compared with -2.5%; P < 0.001).

CONCLUSIONS:

The results indicate thata vitamin D supplement of 83 microg/d does not adversely affectweight loss and is able to significantly improve severalcardiovascular disease risk markers in overweight subjects withinadequate vitamin D status participating in a weight-reductionprogram. This trial was registered at clinicaltrials.gov asNCT00493012.

JBone Miner Res. 2008May;23(5):741-9.

Calciumand vitamin d supplementation decreases incidence of stress fracturesin female navy recruits.

LappeJ, CullenD, HaynatzkiG, ReckerR, AhlfR, ThompsonK.

Source

Creighton UniversityOsteoporosis Research Center, Omaha, Nebraska, USA.

Abstract

INTRODUCTION:

Stress fractures (SFx) areone of the most common and debilitating overuse injuries seen inmilitary recruits, and they are also problematic for nonmilitaryathletic populations. The goal of this randomized double-blind,placebo-controlled study was to determine whether a calcium andvitamin D intervention could reduce the incidence of SFx in femalerecruits during basic training.

MATERIALSAND METHODS:

We recruited 5201 femaleNavy recruit volunteers and randomized them to 2000 mg calcium and800 IU vitamin D/d or placebo. SFx were ascertained when recruitsreported to the Great Lakes clinic with symptoms. All SFx wereconfirmed with radiography or technetium scan according to the usualNavy protocol.

RESULTS:

A total of 309 subjectswere diagnosed with a SFx resulting in an incidence of 5.9% per 8 wk.Using intention-to-treat analysis by including all enrolled subjects,we found that the calcium and vitamin D group had a 20% lowerincidence of SFx than the control group (5.3% versus 6.6%,respectively, p = 0.0026 for Fisher's exact test). The per protocolanalysis, including only the 3700 recruits who completed the study,found a 21% lower incidence of fractures in the supplemented versusthe control group (6.8% versus 8.6%, respectively, p = 0.02 forFisher's exact test).

CONCLUSIONS:

Generalizing the findingsto the population of 14,416 women who entered basic training at theGreat Lakes during the 24 mo of recruitment, calcium and vitamin Dsupplementation for the entire cohort would have preventedapproximately 187 persons from fracturing. Such a decrease in SFxwould be associated with a significant decrease in morbidity andfinancial costs.

AmJ Clin Nutr. 2010May;91(5):1255-60. Epub 2010 Mar 10.

Randomizedtrial of vitamin Dsupplementation to prevent seasonal influenza A in schoolchildren.

UrashimaM, SegawaT, OkazakiM, KuriharaM, WadaY, IdaH.

Source

Division of MolecularEpidemiology, Jikei University School of Medicine, Nishi-shimbashi3-25-8, Minato-ku, Tokyo 105-8461, Japan. urashima@jikei.ac.jp

Abstract

BACKGROUND:

To our knowledge, norigorously designed clinical trials have evaluated the relationbetween vitamin D andphysician-diagnosed seasonal influenza.

OBJECTIVE:

We investigated the effectof vitamin D supplements onthe incidence of seasonal influenza A in schoolchildren.

DESIGN:

From December 2008 throughMarch 2009, we conducted a randomized, double-blind,placebo-controlled trial comparing vitamin D(3)supplements (1200 IU/d) with placebo in schoolchildren. The primaryoutcome was the incidence of influenza A, diagnosed with influenzaantigen testing with a nasopharyngeal swab specimen.

RESULTS:

Influenza A occurred in 18of 167 (10.8%) children in the vitamin D(3)group compared with 31 of 167 (18.6%) children in the placebo group[relative risk (RR), 0.58; 95% CI: 0.34, 0.99; P = 0.04]. Thereduction in influenza A was more prominent in children who had notbeen taking other vitamin Dsupplements (RR: 0.36; 95% CI: 0.17, 0.79; P = 0.006) and who startednursery school after age 3 y (RR: 0.36; 95% CI: 0.17, 0.78; P =0.005). In children with a previous diagnosis of asthma, asthmaattacks as a secondary outcome occurred in 2 children receivingvitamin D(3) compared with 12children receiving placebo (RR: 0.17; 95% CI: 0.04, 0.73; P = 0.006).

CONCLUSION:

This study suggests thatvitamin D(3) supplementationduring the winter may reduce the incidence of influenza A, especiallyin specific subgroups of schoolchildren. This trial was registered athttps://center.umin.ac.jp as UMIN000001373.

AnnIntern Med. 2011 Dec20;155(12):827-38.

VitaminD With or Without Calcium Supplementation for Prevention of Cancerand Fractures: An Updated Meta-analysis for the U.S. PreventiveServices Task Force.

ChungM, LeeJ,TerasawaT, LauJ,TrikalinosTA.

Source

Tufts Evidence-basedPractice Center, Institute for Clinical Research and Health PolicyStudies, Tufts Medical Center, Boston, Massachusetts, and Departmentof Medicine, Fujita Health University School of Medicine, Tsu, Japan.

Abstract

Background: Studiessuggest that vitamin D supplementation may reduce cancer and fracturerisks. Purpose: To examine the benefits and harms of vitamin D withor without calcium supplementation on clinical outcomes of cancer andfractures in adults. Data Sources: English-language studiesidentified from MEDLINE and the Cochrane Central Register ofControlled Trials through July 2011. Study Selection: Randomized,controlled trials (RCTs), prospective cohort studies, and nestedcase-control studies reporting incidence of or death from cancer andfracture outcomes. Data Extraction: Multiple reviewers extracteddetails about participant characteristics, including baseline vitaminD status and use of supplements; details of statistical analyses,including adjustments for confounding; and methodological quality.Differences were resolved by consensus. Data Synthesis: 19 RCTs (3for cancer and 16 for fracture outcomes) and 28 observational studies(for cancer outcomes) were analyzed. Limited data from RCTs suggestedthat high-dose (1000 IU/d) vitamin D supplementation can reduce therisk for total cancer, and data from observational studies suggestedthat higher blood 25-hydroxyvitamin D (25-[OH]D) concentrations mightbe associated with increased risk for cancer. Mixed-effectsdose-response meta-analyses showed that each 10-nmol/L increase inblood 25-(OH)D concentration was associated with a 6% (95% CI, 3% to9%) reduced risk for colorectal cancer but no statisticallysignificant dose-response relationships for prostate and breastcancer. Random-effects model meta-analysis showed that combinedvitamin D and calcium supplementation reduced fracture risk (pooledrelative risk, 0.88 [CI, 0.78 to 0.99]) in older adults, but theeffects differed according to study setting: institution (relativerisk, 0.71 [CI, 0.57 to 0.89]) versus community-dwelling (relativerisk, 0.89 [CI, 0.76 to 1.04]). One RCT showed adverse outcomesassociated with supplementation, including increased risk for renaland urinary tract stones. Limitations: Most trial participants wereolder (aged ≥65 years) postmenopausal women. Observational studieswere heterogeneous and were limited by potential confounders.Conclusion: Combined vitamin D and calcium supplementation can reducefracture risk, but the effects may be smaller amongcommunity-dwelling older adults than among institutionalized elderlypersons. Appropriate dose and dosing regimens, however, requirefurther study. Evidence is not sufficiently robust to drawconclusions regarding the benefits or harms of vitamin Dsupplementation for the prevention of cancer. Primary Funding Source:Agency for Healthcare Research and Quality.

TropMed Int Health. 2010Oct;15(10):1148-55. doi: 10.1111/j.1365-3156.2010.02578.x. Epub 2010Aug 17.

Effectsof vitamin D supplementationto children diagnosed with pneumonia in Kabul: a randomisedcontrolled trial.

Manaseki-HollandS, QaderG, IsaqMasher M, BruceJ, ZulfMughal M, ChandramohanD, WalravenG.

Source

Kabul Medical University,Kabul, Afghanistan. AgaKhan Health Services, Kabul, Afghanistan

Abstract

OBJECTIVES:

To determine whether (i)supplementation of oral 100,000 iu of vitaminD(3) (cholecalciferol) along with antibioticswill reduce the duration of illness in children with pneumonia; (ii)supplementation will reduce the risk of repeat episodes.

METHODS:

Double-blind individuallyrandomised placebo-controlled trial in an inner-city hospital inKabul, of 453 children aged 1-36 months, diagnosed with non-severe orsevere pneumonia at the outpatient clinic. Children with rickets,other concurrent severe diseases, very severe pneumonia or wheeze,were excluded. Children were given vitamin D(3)or placebo drops additional to routine pneumonia treatment.

RESULTS:

Two hundred andtwenty-four children received vitamin D(3;)and 229 received placebo. There was no significant difference in themean number of days to recovery between the vitaminD(3) (4.74 days; SD 2.22) and placebo arms (4.98days; SD 2.89; P = 0.17). The risk of a repeat episode of pneumoniawithin 90 days of supplementation was lower in the intervention(92/204; 45%) than the placebo group [122/211; (58%; relative risk0.78; 95% CI 0.64, 0.94; P = 0.01]. Children in the vitaminD(3) group survived longer without experiencing arepeat episode (72 days vs. 59 days; HR 0.71; 95% CI 0.53-0.95; P =0.02).

CONCLUSION:

A single high-dose oralvitamin D(3) supplementationto young children along with antibiotic treatment for pneumonia couldreduce the occurrence of repeat episodes of pneumonia.

AnnIntern Med. 2010 Mar2;152(5):307-14.

Systematicreview: Vitamin D and cardiometabolic outcomes.

PittasAG,ChungM,TrikalinosT, MitriJ,BrendelM, PatelK,LichtensteinAH, LauJ, BalkEM.

Source

Tufts Medical Center andFriedman School of Nutrition Science and Policy, and Jean Mayer USDAHuman Nutrition Research Center on Aging, Tufts University, Boston,Massachusetts 02111, USA.

Abstract

BACKGROUND:

Vitamin D may modify riskfor cardiometabolic outcomes (type 2 diabetes, hypertension, orcardiovascular disease).

PURPOSE:

To examine the associationbetween vitamin D status, including the effect of vitamin Dsupplementation, and cardiometabolic outcomes in generally healthyadults.

DATASOURCES:

English-language studiesin MEDLINE (inception to 4 November 2009) and the Cochrane CentralRegister of Controlled Trials (fourth quarter of 2009).

STUDYSELECTION:

11 reviewers screenedcitations to identify longitudinal cohort studies that reportedassociations between vitamin D status and cardiometabolic outcomes,including randomized trials of vitamin D supplementation.

DATAEXTRACTION:

5 independent reviewersextracted data about study conduct, participant characteristics,outcomes, and quality. Differences were resolved by consensus.

DATASYNTHESIS:

13 observational studies(14 cohorts) and 18 trials were eligible. Three of 6 analyses (from 4different cohorts) reported a lower incident diabetes risk in thehighest versus the lowest vitamin D status groups. Eight trials foundno effect of vitamin D supplementation on glycemia or incidentdiabetes. In meta-analysis of 3 cohorts, lower 25-hydroxyvitamin Dconcentration was associated with incident hypertension (relativerisk, 1.8 [95% CI, 1.3 to 2.4]). In meta-analyses of 10 trials,supplementation nonsignificantly reduced systolic blood pressure(weighted mean difference, -1.9 mm Hg [CI, -4.2 to 0.4 mm Hg]) anddid not affect diastolic blood pressure (weighted mean difference,-0.1 mm Hg [CI, -0.7 to 0.5 mm Hg]). Lower 25-hydroxyvitamin Dconcentration was associated with incident cardiovascular disease in5 of 7 analyses (6 cohorts). Four trials found no effect ofsupplementation on cardiovascular outcomes.

LIMITATIONS:

Studies included primarilywhite participants. Observational studies were heterogeneous. Severaltrials reported post hoc analyses.

CONCLUSION:

The association betweenvitamin D status and cardiometabolic outcomes is uncertain. Trialsshowed no clinically significant effect of vitamin D supplementationat the dosages given.

PRIMARYFUNDING SOURCE:

National Institute ofDiabetes and Digestive and Kidney Disease, the National Institutes ofHealth Office of Dietary Supplements, U.S. Food and DrugAdministration, Agency for Healthcare Research and Quality, andPublic Health Agency of Canada.

ArchIntern Med. 2009 Mar23;169(6):551-61.

Preventionof nonvertebral fractures with oral vitamin D and dose dependency: ameta-analysis of randomized controlled trials.

Bischoff-FerrariHA, WillettWC, WongJB, StuckAE, StaehelinHB, OravEJ, ThomaA, KielDP, HenschkowskiJ.

Source

Centre on Aging andMobility, University of Zurich, University Hospital, [email protected]

Abstract

BACKGROUND:

Antifracture efficacy withsupplemental vitamin D has been questioned by recent trials.

METHODS:

We performed ameta-analysis on the efficacy of oral supplemental vitamin D inpreventing nonvertebral and hip fractures among older individuals (>or =65 years). We included 12 double-blind randomized controlledtrials (RCTs) for nonvertebral fractures (n = 42 279) and 8 RCTs forhip fractures (n = 40 886) comparing oral vitamin D, with or withoutcalcium, with calcium or placebo. To incorporate adherence totreatment, we multiplied the dose by the percentage of adherence toestimate the mean received dose (dose x adherence) for each trial.

RESULTS:

The pooled relative risk(RR) was 0.86 (95% confidence interval [CI], 0.77-0.96) forprevention of nonvertebral fractures and 0.91 (95% CI, 0.78-1.05) forthe prevention of hip fractures, but with significant heterogeneityfor both end points. Including all trials, antifracture efficacyincreased significantly with a higher dose and higher achieved blood25-hydroxyvitamin D levels for both end points. Consistently, poolingtrials with a higher received dose of more than 400 IU/d resolvedheterogeneity. For the higher dose, the pooled RR was 0.80 (95% CI,0.72-0.89; n = 33 265 subjects from 9 trials) for nonvertebralfractures and 0.82 (95% CI, 0.69-0.97; n = 31 872 subjects from 5trials) for hip fractures. The higher dose reduced nonvertebralfractures in community-dwelling individuals (-29%) andinstitutionalized older individuals (-15%), and its effect wasindependent of additional calcium supplementation.

CONCLUSION:

Nonvertebral fractureprevention with vitamin D is dose dependent, and a higher dose shouldreduce fractures by at least 20% for individuals aged 65 years orolder.

JClin Endocrinol Metab.2011 Mar;96(3):E447-52. Epub 2010 Dec 22.

VitaminD(3) is more potent than vitaminD(2) in humans.

HeaneyRP, ReckerRR, GroteJ, HorstRL, ArmasLA.

Source

Creighton University, 601North 30th Street, Suite 4841, Omaha, Nebraska 68131, [email protected]

Abstract

BACKGROUND:

Current unitage for thecalciferols suggests that equimolar quantities of vitamins D(2) (D2)and D(3) (D3) are biologically equivalent. Published studies yieldmixed results.

OBJECTIVE:

The aim of the study wasto compare the potencies of D2and D3.

DESIGN:

The trial used asingle-blind, randomized design in 33 healthy adults. Calciferolswere dosed at 50,000 IU/wk for 12 wk. Principal outcome variableswere area under the curve for incremental total 25-hydroxyvitamin D[25(OH)D] and change in calciferol content of sc fat.

RESULTS:

Incremental mean (sd)25(OH)D area under the curve at 12 wk was 1366 ng · d/ml (516)for the D2-treated group and2136 (606) for the D3 (P < 0.001). Mean (sd) steady-state 25(OH)Dincrements showed similar differences: 24 ng/ml for D2(10.3) and 45 ng/ml (16.2) for D3 (P <0.001). Subcutaneous fatcontent of D2 rose by 50μg/kg in the D2-treatedgroup, and D3 content rose by 104 μg/kg in the D3-treated group.Total calciferol in fat rose by only 33 ng/kg in the D2-treated,whereas it rose by 104 μg/kg in the D3-treated group.Extrapolating to total body fat D3, storage amounted to just 17% ofthe administered dose.

CONCLUSION:

D3 is approximately 87%more potent in raising and maintaining serum 25(OH)D concentrationsand produces 2- to 3-fold greater storage of vitaminD than does equimolar D2. Forneither was there evidence of sequestration in fat, as had beenpostulated for doses in this range. Given its greater potency andlower cost, D3 should be the preferred treatment option whencorrecting vitamin Ddeficiency.

AmJ Clin Nutr. 2006Oct;84(4):694-7.

Thecase against ergocalciferol (vitamin D2)as a vitamin supplement.

HoughtonLA, ViethR.

Source

School of Nutrition andDietetics, Acadia University, Wolfville, Canada.lisa.houghton@acadiau.ca

Abstract

Supplemental vitaminD is available in 2 distinct forms: ergocalciferol (vitaminD2) and cholecalciferol (vitaminD3). Pharmacopoeias have officially regarded these 2 forms asequivalent and interchangeable, yet this presumption of equivalenceis based on studies of rickets prevention in infants conducted 70 yago. The emergence of 25-hydroxyvitamin D as a measure of vitaminD status provides an objective, quantitative measure of thebiological response to vitaminD administration. As a result, vitaminD3 has proven to be the more potent form of vitaminD in all primate species, including humans. Despite an emerging bodyof evidence suggesting several plausible explanations for the greaterbioefficacy of vitamin D3,the form of vitamin D used inmajor preparations of prescriptions in North America is vitaminD2. The case that vitamin D2should no longer be considered equivalent to vitaminD3 is based on differences in their efficacy at raising serum25-hydroxyvitamin D, diminished binding of vitaminD2 metabolites to vitaminD binding protein in plasma, and a nonphysiologic metabolism andshorter shelf life of vitamin D2.Vitamin D2, orergocalciferol, should not be regarded as a nutrient suitable forsupplementation or fortification.

AmJ Clin Nutr.2010 Apr;91(4):985-91. Epub 2010 Feb 3.

Once-weeklydose of 8400 IU vitamin D(3) compared with placebo: effects onneuromuscular function and tolerability in older adults with vitaminD insufficiency.

LipsP,BinkleyN,PfeiferM,ReckerR,SamantaS, CohnDA,ChandlerJ,RosenbergE,PapanicolaouDA.

Source

Department ofEndocrinology, Vrije Universiteit Medisch Centrum, Amsterdam, TheNetherlands. [email protected]

Abstract

BACKGROUND:

Vitamin D insufficiency,which is prevalent in older individuals, is associated with bone andmuscle weakness and falls.

OBJECTIVE:

We examined the effects ofa weekly dose of 8400 IU vitamin D(3) on postural stability, musclestrength, and safety.

DESIGN:

In this double-blindtrial, subjects aged > or =70 y with serum 25-hydroxyvitamin D[25(OH)D] concentrations < or =20 but > or =6 ng/mL wererandomly assigned to receive a weekly dose of 8400 IU vitamin D(3) (n= 114) or a placebo (n = 112). Mediolateral body sway with eyes open(assessed with the AccuSway(PLUS) platform; Advanced MedicalTechnology Inc, Watertown, MA) was the primary endpoint. Secondaryendpoints included the short physical performance battery (SPPB) andserum 25(OH)D concentrations. An analysis of covariance model wasused for treatment comparisons. Safety and tolerability weremonitored.

RESULTS:

Serum 25(OH)Dconcentrations rose significantly (from 13.9 to 26.2 ng/mL, P <0.001) in patients treated with 8400 IU vitamin D(3) but not inpatients treated with the placebo. After 16 wk, neither mediolateralsway nor SPPB differed significantly between treatment groups.However, in the post hoc analysis of patients subgrouped by baselinesway (> or = 0.46 compared with <0.46 cm), treatment with 8400IU vitamin D(3) significantly reduced sway compared with treatmentwith placebo (P = 0.047) in patients with elevated baseline sway butnot in patients with normal baseline sway. Adverse experiences andincidences of hypercalcemia, hypercalciuria, and elevated creatininewere similar with both treatments. In patients treated with 8400 IUvitamin D(3), but not in placebo-treated patients, parathyroidhormone decreased significantly.

CONCLUSIONS:

Weekly treatment with 8400IU vitamin D(3) raised 25(OH)D concentrations in elderly, vitaminD-insufficient individuals. Treatment with 8400 IU vitamin D(3) didnot reduce mediolateral sway significantly compared with treatmentwith placebo in this population, although in post hoc analysis,treatment with 8400 IU vitamin D(3) reduced sway in the subgroup ofpatients who had elevated sway at baseline. Weekly treatment with8400 IU vitamin D(3) was well tolerated. This trial was registered atclinicaltrials.gov as NCT00242476.

JBone Miner Res. 2011Jan;26(1):42-9.

Theeffects of whole-body vibration training and vitamin Dsupplementation on muscle strength, muscle mass, and bone density ininstitutionalized elderly women: a 6-month randomized, controlledtrial.

VerschuerenSM,BogaertsA,DelecluseC,ClaessensAL,HaentjensP,VanderschuerenD,BoonenS.

Source

Division ofMusculoskeletal Rehabilitation, Department of Rehabilitation Sciencesand, Faculty of Kinesiology and Rehabilitation Sciences, KatholiekeUniversiteit Leuven, Leuven, [email protected]

Abstract

Sarcopenia andosteoporosis represent a growing public health problem. We studiedthe potential benefit of whole-body vibration (WBV) training given aconventional or a high dose of daily vitamin D supplementation inimproving strength, muscle mass, and bone density in postmenopausalwomen. In a 2 × 2 factorial-design trial, 113 institutionalizedelderly females aged over 70 years (mean age 79.6 years) wererandomly assigned either to a WBV or a no-training group, receivingeither a conventional dose (880 IU/day) or a high dose (1600 IU/day)of vitamin D(3). The primary aim was to determine the effects of 6months of WBV and/or vitamin D supplementation on isometric anddynamic strength, leg muscle mass, and hip bone mineral density(BMD). Additionally, the increase in 25-hydroxyvitamin D [25(OH)D]levels between conventional and high-dose supplementation wascompared. After 6 months of treatment, dynamic muscle strength, hipBMD, and vitamin D serum levels improved significantly in all groups,whereas isometric strength and muscle mass did not change. Whencompared with no training, the WBV program did not result inadditional improvements. When compared with 880 IU, a high dose of1600 IU of vitamin D did result in higher serum vitamin D levels butdid not result in additional improvements. In institutionalized womenolder than 70 years, the WBV training protocol tested is not moreefficient in enhancing muscle mass, strength, and hip BMD comparedwith vitamin D supplementation. A higher dose of 1600 IU of vitamin Ddoes not provide additional musculoskeletal benefit in thispopulation compared with conventional doses.

AnnNutr Metab. 2009;54(4):291-300.Epub 2009 Aug 31.

Treatmentof vitamin D deficiency increases lower limb muscle strength ininstitutionalized older people independently of regular physicalactivity: a randomized double-blind controlled trial.

Moreira-PfrimerLD, PedrosaMA, TeixeiraL, Lazaretti-CastroM.

Source

Division of Endocrinology,School of Medicine, Federal University of São Paulo/UNIFESP,São Paulo, Brazil. [email protected]

Abstract

AIMS:

To investigate the effectsof a 6-month supplementation with calcium and cholecalciferol onbiochemical parameters and muscle strength of institutionalizedelderly.

METHODS:

This prospective,double-blind, placebo-controlled, randomized trial included Brazilianinstitutionalized people > or =60 years of age receiving a 6-monthsupplementation (December to May) of daily calcium plus monthlyplacebo (calcium/placebo group) or daily calcium plus oralcholecalciferol (150,000 IU once a month during the first 2 months,followed by 90,000 IU once a month for the last 4 months;calcium/vitamin D group). Fasting blood samples for 25(OH)D, PTH andcalcium determination were collected (n = 56) and muscle tests wereperformed (n = 46) to measure the strength of hip flexors (SHF) andknee extensors (SKE) before (baseline) and after the 6-monthintervention (6 months).

RESULTS:

Due to seasonalvariations, serum 25(OH)D significantly enhanced in both groups aftertreatment, but the calcium/vitamin D group had significantly higher25 (OH)D levels than the calcium/placebo group (84 vs. 33%,respectively; p < 0.0001). No cases of hypercalcemia wereobserved. While the calcium/placebo group showed no improvement inSHF and SKE at 6 months (p = 0.93 and p = 0.61, respectively), SHFwas increased in the calcium/vitamin D group by 16.4% (p = 0.0001)and SKE by 24.6% (p = 0.0007).

CONCLUSIONS:

The suggestedcholecalciferol supplementation was safe and efficient in enhancing25(OH)D levels and lower limb muscle strength in the elderly, in theabsence of any regular physical exercise practice.

ExpGerontol. 2006 Aug;41(8):746-52.Epub 2006 Jun 22.

Effectsof vitamin D supplementationand exercise training on physical performance in Chilean vitaminD deficient elderly subjects.

BunoutD, BarreraG, LeivaL, GattasV, dela Maza MP, AvendañoM, HirschS.

Source

INTA, University of Chile,Santiago, Chile. [email protected]

Abstract

The aim was to assess theeffects of resistance training and vitamin Dsupplementation on physical performance of healthy elderly subjects.Ninety-six subjects, aged 70 years or more with 25 OH vitaminD levels of 16 ng/ml or less, were randomized toa resistance training or control group. Trained and control groupswere further randomized to receive in a double blind fashion, vitaminD 400 IU plus 800 mg of calcium per day orcalcium alone. Subjects were followed for nine months. Serum 25 OHvitamin D increased from12.4+/-2.2 to 25.8+/-6.5 ng/ml among subjects supplemented withvitamin D. Trained subjectshad significant improvements in quadriceps muscle strength, the shortphysical performance test and timed up and go. The latter improvedmore in trained subjects supplemented with vitaminD. At the end of the follow up, gait speed washigher among subjects supplemented with vitamin (whether trained ornot) than in non-supplemented subjects (838+/-147 and 768+/-127 m/12min, respectively, p=0.02). Romberg ratio was lower amongsupplemented controls than non-supplemented trained subjects(128+/-40% and 144+/-37%, respectively, p=0.05). In conclusion,vitamin D supplementationimproved gait speed and body sway, and training improved musclestrength.

CancerPrev Res (Phila). 2009Mar;2(3):213-23. Epub 2009 Mar 3.

Effectsof vitamin D and calcium supplementation on markers of apoptosis innormal colon mucosa: a randomized, double-blind, placebo-controlledclinical trial.

FedirkoV, BostickRM, FlandersWD, LongQ, ShaukatA, RutherfordRE, DanielCR, CohenV, DashC.

Source

Department ofEpidemiology, Rollins School of Public Health, Emory University,Atlanta, Georgia 30322, USA.

Abstract

To further clarify and/ordevelop calcium and vitamin D as chemopreventive agents againstcolorectal cancer in humans, understand the mechanisms by which theseagents reduce risk for the disease, and develop "treatable"biomarkers of risk for colorectal cancer, we conducted a pilot,randomized, double-blind, placebo-controlled, 2 x 2 factorialclinical trial to test the effects of calcium and vitamin D3, aloneand in combination on markers of apoptosis, in the normal colorectalmucosa. Ninety-two men and women with at least onepathology-confirmed colorectal adenoma were treated with 2.0 g/dcalcium or 800 IU/d vitamin D3, alone or in combination, versusplacebo over 6 months. Overall expression and colorectal cryptdistributions of Bcl-2 (an apoptosis inhibitor) and Bax (an apoptosispromoter) in biopsies of normal-appearing rectal mucosa were detectedby automated immunohistochemistry and quantified by image analysis.After 6 months of treatment, Bax expression along the full lengths ofcrypts increased 56% (P = 0.02) in the vitamin D group and 33% inboth the calcium (P = 0.31) and calcium plus vitamin D (P = 0.36)groups relative to the placebo group. The vitamin D treatment effectwas more pronounced in the upper 40%, or differentiation zone, ofcrypts (80%; P = 0.01). There were no statistically significanttreatment effects on Bcl-2 expression. Overall, these preliminaryresults suggest that calcium and vitamin D, individually or together,may enhance apoptosis in the normal human colorectal epithelium, andthe strongest treatment effects may be vitamin D related and in theupper sections of the colorectal crypts.

CancerEpidemiol Biomarkers Prev. 2009Nov;18(11):2933-41. Epub 2009 Oct 27.

Effectsof vitamin d and calcium on proliferation and differentiation innormal colon mucosa: a randomized clinical trial.

FedirkoV, BostickRM, FlandersWD, LongQ, SidelnikovE, ShaukatA, DanielCR, RutherfordRE, WoodardJJ.

Source

Department ofEpidemiology, Rollins School of Public Health, Winship CancerInstitute, Emory University, Atlanta, Georgia, USA.

Abstract

To investigate thepotential efficacy of calcium and vitamin D in reducing risk forcolorectal neoplasms and to develop "treatable" phenotypicbiomarkers of risk for colorectal neoplasms, we conducted a pilot,randomized, double-blind, placebo-controlled, 2 x 2 factorialclinical trial to test the effects of these agents on cell cyclemarkers in the normal colorectal mucosa. Ninety-two men and womenwith at least one pathology-confirmed colorectal adenoma were treatedwith 2 g/day calcium and/or 800 IU/day vitamin D(3) versus placeboover 6 months. Overall expression and distributions of p21(waf1/cip1)(marker of differentiation), MIB-1 (marker of short-termproliferation), and hTERT (marker of long-term proliferation) incolorectal crypts in the normal-appearing rectal mucosa were detectedby automated immunohistochemistry and quantified by image analysis.In the calcium, vitamin D, and calcium plus vitamin D groups relativeto the placebo, p21 expression increased by 201% (P = 0.03), 242% (P= 0.005), and 25% (P = 0.47), respectively, along the full lengths ofcolorectal crypts after 6 months of treatment. There were nostatistically significant changes in the expression of either MIB-1or hTERT in the crypts overall; however, the proportion of hTERT, butnot MIB-1, expression that extended into the upper 40% of the cryptswas reduced by 15% (P = 0.02) in the vitamin D plus calcium grouprelative to the placebo. These results indicate that calcium andvitamin D promote colorectal epithelial cell differentiation and may"normalize" the colorectal crypt proliferative zone insporadic adenoma patients, and support further investigation ofcalcium and vitamin D as chemopreventive agents against colorectalneoplasms.

CancerEpidemiol Biomarkers Prev. 2010Jan;19(1):280-91.

Effectsof supplemental vitamin D and calcium on oxidative DNA damage markerin normal colorectal mucosa: a randomized clinical trial.

FedirkoV, BostickRM, LongQ, FlandersWD, McCulloughML, SidelnikovE, DanielCR, RutherfordRE, ShaukatA.

Source

Department ofEpidemiology, Rollins School of Public Health, Emory University,Atlanta, GA 30322, USA.

Abstract

The exact antineoplasticeffects of calcium and vitamin D(3) in the human colon are unclear.Animal and in vitro studies show that these two agents reduceoxidative stress; however, these findings have never beeninvestigated in humans. To address this, we conducted a pilot,randomized, double-blind, placebo-controlled, 2 x 2 factorialclinical trial to test the effects of calcium and vitamin D(3) on amarker of oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine(8-OH-dG), in the normal colorectal mucosa. Patients (N = 92) with atleast one pathology-confirmed colorectal adenoma were treated with 2g/d calcium and/or 800 IU/d vitamin D(3) versus placebo over 6months. Overall labeling and colorectal crypt distribution of 8-OH-dGin biopsies of normal-appearing rectal mucosa were detected bystandardized automated immunohistochemistry and quantified by imageanalysis. After 6 months of treatment, 8-OH-dG labeling along thefull lengths of colorectal crypts decreased by 22% (P = 0.15) and 25%(P = 0.10) in the calcium and vitamin D(3) groups, respectively, butnot in the calcium plus vitamin D(3) group. The estimated treatmenteffects were strongest among participants with higher baseline coloncrypt vitamin D receptor expression (P = 0.05). Overall, thesepreliminary results indicate that calcium and vitamin D(3) maydecrease oxidative DNA damage in the normal human colorectal mucosa,support the hypothesis that 8-OH-dG labeling in colorectal crypts isa treatable oxidative DNA damage biomarker of risk for colorectalneoplasms, and provide support for further investigation of calciumand vitamin D(3) as chemopreventive agents against colorectalneoplasms.

CancerRes. 2011 Jan 15;71(2):413-23.Epub 2010 Nov 17.

Arandomized clinical trial of the effects of supplemental calcium andvitamin D3 on markers of their metabolism in normal mucosa ofcolorectal adenoma patients.

AhearnTU, McCulloughML, FlandersWD, LongQ, SidelnikovE, FedirkoV, DanielCR, RutherfordRE, ShaukatA, BostickRM.

Source

Nutrition and HealthSciences Program, Graduate Division of Biological and BiomedicalSciences, Winship Cancer Institute, Emory University, Department ofEpidemiology, Rollins School of Public Health, Atlanta, Georgia30322, USA.

Abstract

In cancer cell lines androdent models, calcium and vitamin D favorably modulate cellproliferation, differentiation, and apoptosis in colonic epithelia.These effects may be modulated by local expression of the calciumreceptor (CaR), the vitamin D receptor (VDR), and the P450cytochromes, CYP27B1 and CYP24A1; however, they have yet to beinvestigated in humans. To address this gap, we conducted arandomized, double-blinded, placebo-controlled 2×2 factorialclinical trial. Patients with at least one pathology-confirmedcolorectal adenoma were treated with 2 g/d elemental calcium and/or800 IU/d vitamin D3 versus placebo over 6 months (n=92; 23 pergroup). CaR, VDR, CYP27B1, and CYP24A1 expression and distribution inbiopsies of normal appearing rectal mucosa were detected bystandardized, automated immunohistochemistry and quantified by imageanalysis. In the calcium-supplemented group, CaR expression increased27% (P=0.03) and CYP24A1 expression decreased 21% (P=0.79). In thevitamin D3-supplemented group, CaR expression increased 39% (P=0.01)and CYP27B1 expression increased 159% (P=0.06). In patientssupplemented with both calcium and vitamin D3, VDR expressionincreased 19% (P=0.13) and CaR expression increased 24% (P=0.05).These results provide mechanistic support for further investigationof calcium and vitamin D3 as chemopreventive agents againstcolorectal neoplasms, and CaR, VDR, CYP27B1, and CYP24A1 asmodifiable, preneoplastic risk biomarkers for colorectal neoplasms.

Neurology.2011 Oct 25;77(17):1611-8.

Arandomized trial of high-dose vitamin D2 in relapsing-remittingmultiple sclerosis.

SteinMS, LiuY, GrayOM, BakerJE, KolbeSC, DitchfieldMR, EganGF, MitchellPJ, HarrisonLC, ButzkuevenH, KilpatrickTJ.

Source

Department ofEndocrinology, Royal Melbourne Hospital, Parkville, Victoria,Australia. [email protected]

Abstract

OBJECTIVE:

Higher latitude, lowerultraviolet exposure, and lower serum 25-hydroxyvitamin D (25OHD)correlate with higher multiple sclerosis(MS) prevalence, relapse rate, and mortality. We therefore evaluatedthe effects of high-dose vitamin D2 (D2) in MS.

METHODS:

Adults with clinicallyactive relapsing-remitting MS (RRMS) were randomized to 6 months'double-blind placebo-controlled high-dose vitamin D2, 6,000 IUcapsules, dose adjusted empirically aiming for a serum 25OHD 130-175nM. All received daily low-dose (1,000 IU) D2 to prevent deficiency.Brain MRIs were performed at baseline, 4, 5, and 6 months. Primaryendpoints were the cumulative number of new gadolinium-enhancinglesions and change in the total volume of T2 lesions. Secondaryendpoints were Expanded Disability Status Scale (EDSS) score andrelapses.

RESULTS:

Twenty-three people wererandomized, of whom 19 were on established interferon or glatirameracetate (Copaxone) treatment. Median 25OHD rose from 54 to 69 nM(low-dose D2) vs 59 to 120 nM (high-dose D2) (p = 0.002). Nosignificant treatment differences were detected in the primary MRIendpoints. Exit EDSS, after adjustment for entry EDSS, was higherfollowing high-dose D2 than following low-dose D2 (p = 0.05). Therewere 4 relapses with high-dose D2 vs none with low-dose D2 (p =0.04).

CONCLUSION:

We did not find atherapeutic advantage in RRMS for high-dose D2 over low-dose D2supplementation.

CLASSIFICATIONOF EVIDENCE:

This study provides ClassI evidence that high-dose vitamin D2 (targeting 25OHD 130-175 nM),compared to low-dose supplementation(1,000 IU/d), was not effective in reducing MRI lesions in patientswith RRMS.

CancerPrev Res (Phila). 2011Oct;4(10):1645-54. Epub 2011 Jun 30.

Effectsof supplemental vitamin D and calcium on biomarkers of inflammationin colorectal adenoma patients: a randomized, controlled clinicaltrial.

HopkinsMH, OwenJ, AhearnT, FedirkoV, FlandersWD, JonesDP, BostickRM.

Source

Department ofEpidemiology, Rollins School of Public Health, Emory University,Atlanta, GA 30322, USA.

Abstract

Vitamin D and calciumaffect several pathways involved in inflammation, tumor growth, andimmune surveillance relevant to carcinogenesis. Also, epidemiologicevidence indicates that calcium and vitamin D may reduce risk fordeveloping colorectal adenomas and cancer. To investigate the effectsof calcium and vitamin D on biomarkers of inflammation in colorectaladenoma patients, we conducted a pilot, randomized, double-blind,placebo-controlled, 2 × 2 factorial clinical trial (n = 92) of2 g/d calcium and/or 800 IU/d vitamin D(3) supplementation versusplacebo over 6 months. Plasma concentrations of proinflammatorymarkers [C-reactive protein (CRP), TNF-α, interleukin (IL)-6,IL-1β, and IL-8] and an anti-inflammatory marker (IL-10) weremeasured using ELISAs. After 6 months of treatment, in the vitaminD(3) supplementation group, CRP decreased 32% overall (P = 0.11), 37%in men (P = 0.05), and 41% among non-nonsteroidal anti-inflammatorydrug (NSAID) users (P = 0.05) relative to placebo. In the vitaminD(3) supplementation group, TNF-α decreased 13%, IL-6 32%,IL-1β 50%, and IL-8 15%; in the calcium supplementation group,IL-6 decreased 37%, IL-8 11%, and IL-1β 27%. Although thesechanges were not statistically significant, a combined inflammatorymarkers z-score decreased 77% (P = 0.003) in the vitamin D(3)treatment group overall, 83% (P = 0.01) among men, and 48% amongnon-NSAID users (P = 0.01). There was no evidence of synergy betweenvitamin D(3) and calcium or effects on IL-10. These preliminaryresults are consistent with a pattern of reduction in tumor-promotinginflammation biomarkers with vitamin D(3) or calcium supplementationalone and support further investigation of vitamin D(3) as achemopreventive agent against inflammation and colorectal neoplasms.

DiabetMed. 2009 Jan;26(1):19-27.

Adouble-blind, randomized, placebo-controlled trial of the short-termeffect of vitamin D3 supplementation on insulin sensitivity inapparently healthy, middle-aged, centrally obese men.

NagpalJ, PandeJN, BhartiaA.

Source

Sitaram Bhartia Instituteof Science and Research, New Delhi, India.

Abstract

AIM:

To determine theshort-term effect of vitamin D(3)supplementation on insulin sensitivity in apparently healthy,middle-aged, centrally obese men.

SUBJECTSAND METHODS:

A double-blind randomizedcontrolled trial was conducted at a tertiary care facility in which100 male volunteers aged > or = 35 years received three doses ofvitamin D(3) (120,000 IUeach; supplemented group) fortnightly or placebo (control group).Hepatic fasting insulin sensitivity [homeostasis model assessment(HOMA), quantitative insulin-sensitivity check index, HOMA-2],postprandial insulin sensitivity [oral glucose insulin sensitivity(OGIS)], insulin secretion (HOMA%B, HOMA2-%B), lipid profile andblood pressure were measured at baseline and at 6 weeks' follow-up.

RESULTS:

Seventy-one of therecruited subjects completed the study (35 in supplemented group, 36in control group). There was an increase in OGIS with supplementationby per protocol analysis (P = 0.038; intention-to-treat analysis P =0.055). The age- and baseline 25-hydroxyvitamin D level-adjusteddifference in change in OGIS was highly significant (mean difference41.1 +/- 15.5; P = 0.01). No changes in secondary outcome measures(insulin secretion, basal indices of insulin sensitivity, bloodpressure or lipid profile) were found with supplementation.

CONCLUSION:

The trial indicates thatvitamin D(3) supplementationimproves postprandial insulin sensitivity (OGIS) in apparentlyhealthy men likely to have insulin resistance (centrally obese butnon-diabetic).

EndocrPract. 2009 Jul-Aug;15(5):438-49.

VitaminD for treatment and prevention of infectious diseases: a systematicreview of randomized controlled trials.

YamshchikovAV, DesaiNS, BlumbergHM, ZieglerTR, TangprichaV.

Source

Division of InfectiousDiseases, Department of Medicine, Emory University School ofMedicine, Atlanta, Georgia 30030, USA. [email protected]

Abstract

OBJECTIVE:

To review the existinghuman controlled intervention studies of vitamin D as adjunctivetherapy in settings of infection and provide recommendations fordesign and implementation of future studies in this field on thebasis of the evidence reviewed.

METHODS:

We conducted a systematicreview of randomized controlled clinical trials that studied vitaminD for treatment or prevention of infectious diseases in humans.Studies from 1948 through 2009 were identified through search termsin PubMed and Ovid MEDLINE.

RESULTS:

Thirteen publishedcontrolled trials were identified by our search criteria. Ten trialswere placebo controlled, and 9 of the 10 were conducted in a rigorousdouble-blind design. The selected clinical trials demonstratedsubstantial heterogeneity in baseline patient demographics, samplesize, and vitamin D intervention strategies. Serious adverse eventsattributable to vitamin D supplementation were rare across allstudies. On the basis of studies reviewed to date, the strongestevidence supports further research into adjunctive vitamin D therapyfor tuberculosis, influenza, and viral upper respiratory tractillnesses. In the selected studies, certain aspects of study designare highlighted to help guide future clinical research in the field.

CONCLUSION:

More rigorously designedclinical trials are needed for further evaluation of the relationshipbetween vitamin D status and the immune response to infection as wellas for delineation of necessary changes in clinical practice andmedical care of patients with vitamin D deficiency in infectiousdisease settings.

AmJ Respir Crit Care Med. 2007 Jul15;176(2):208-13. Epub 2007 Apr 26.

Asingle dose of vitamin D enhances immunity to mycobacteria.

MartineauAR, WilkinsonRJ, WilkinsonKA, NewtonSM, KampmannB, HallBM, PackeGE, DavidsonRN, EldridgeSM, MaunsellZJ, RainbowSJ, BerryJL, GriffithsCJ.

Source

Centre for HealthSciences, Queen Mary's School of Medicine and Dentistry, Barts andThe London, and Department of Clinical Biochemistry, North WestLondon Hospitals NHS Trust, Northwick Park Hospital, Harrow, E1 2AT,UK. a.martineau@qmul.ac.uk

Abstract

RATIONALE:

Vitamin D was used totreat tuberculosis (TB) in the preantibiotic era. Prospective studiesto evaluate the effect of vitamin D supplementation onantimycobacterial immunity have not previously been performed.

OBJECTIVES:

To determine the effect ofvitamin D supplementation on antimycobacterial immunity and vitamin Dstatus.

METHODS:

A double-blind randomizedcontrolled trial was conducted in 192 healthy adult TB contacts inLondon, United Kingdom. Participants were randomized to receive asingle oral dose of 2.5 mg vitamin D or placebo and followed up at 6weeks.

MEASUREMENTSAND MAIN RESULTS:

The primary outcomemeasure was assessed with a functional whole blood assay (BCG-luxassay), which measures the ability of whole blood to restrictluminescence, and thus growth, of recombinant reporter mycobacteriain vitro; the readout is expressed as a luminescence ratio(luminescence postinfection/baseline luminescence). IFN-gammaresponses to the Mycobacterium tuberculosis antigens early secretoryantigenic target-6 and culture filtrate protein 10 were determinedwith a second whole blood assay. Vitamin D supplementationsignificantly enhanced the ability of participants' whole blood torestrict BCG-lux luminescence in vitro compared with placebo (meanluminescence ratio at follow-up, 0.57, vs. 0.71, respectively; 95%confidence interval for difference, 0.01-0.25; p=0.03) but did notaffect antigen-stimulated IFN-gamma secretion.

CONCLUSIONS:

A single oral dose of 2.5mg vitamin D significantly enhanced the ability of participants'whole blood to restrict BCG-lux luminescence in vitro withoutaffecting antigen-stimulated IFN-gamma responses. Clinical trialsshould be performed to determine whether vitamin D supplementationprevents reactivation of latent TB infection. Clinical trialregistered with www.clinicaltrials.gov (NCT 00157066).

AmJ Kidney Dis. 2009Mar;53(3):408-16. Epub 2009 Jan 29.

Theeffect of combined calcium and vitamin D3 supplementation on serumintact parathyroid hormone in moderate CKD.

KooiengaL, FriedL, ScraggR, KendrickJ, SmitsG, ChoncholM.

Source

Division of Renal Diseasesand Hypertension, University of Colorado Health Sciences Center,Denver, CO 80262, USA.

Abstract

BACKGROUND:

Studies addressing theeffects of vitamin D(3) supplementation on secondaryhyperparathyroidism in patients with moderate chronic kidney diseaseare scarce.

STUDYDESIGN:

Post hoc analysis of therandomized clinical trial Vitamin D, Calcium, Lyon Study II (DECALYOSII) to assess effects according to baseline estimated glomerularfiltration rate (eGFR).

SETTING& PARTICIPANTS:

Multicenter, randomized,double-blinded, placebo-controlled study of 639 elderly womenrandomly assigned to calcium-vitamin D(3) fixed combination; calciumplus vitamin D(3) separate combination, or placebo.

INTERVENTIONS:

Placebo or calcium (1,200mg) and vitamin D(3) (800 IU) in fixed or separate combination.

OUTCOMES& MEASUREMENTS:

Proportion of participantswith a mean decrease in intact parathyroid hormone (iPTH) level of30% or greater. eGFR was calculated using the 4-variable Modificationof Diet in Renal Disease (MDRD) Study equation and categorized as 60or greater, 45 to 59, and less than 45 mL/min/1.73 m(2).

RESULTS:

610 participants had aneGFR at baseline: 288 (47.2%), 222 (36.4%), and 100 (16.4%) were ineach decreasing eGFR category. Across decreasing eGFR groups, 88%,86%, and 89% had 25-hydroxyvitamin D (25[OH]D) levels less than 15ng/mL at baseline. On treatment, similar improvements in theproportion of participants achieving 25(OH)D levels greater than 30ng/mL at 6 months were seen in all kidney function groups (43%, 49%,and 41%, respectively). Active regimens versus placebo increased mean25(OH)D levels from baseline in all eGFR groups at all times (P <0.001 for all). The proportion with a 30% or greater decrease in iPTHlevel at 6 months was 50% in all eGFR groups on treatment versus 6%to 9% for placebo (P < 0.001 for all). The effects of theintervention on iPTH levels did not differ according to baseline eGFR(interaction P > 0.1 for all times).

LIMITATIONS:

This study included onlyelderly white women.

CONCLUSION:

Vitamin D(3) was effectivein increasing 25(OH)D and decreasing iPTH levels in patients withmoderate chronic kidney disease.

JNephrol. 2009 Jan-Feb;22(1):75-82.

VitaminD insufficiency and treatment with oral vitamin D3 innorthern-dwelling patients with chronic kidney disease.

RuckerD, TonelliM, ColesMG, YooS, YoungK, McMahonAW.

Source

Department of Medicine,Division of General Internal Medicine, University of Alberta,University of Alberta Hospital, Edmonton, Alberta, Canada.

Abstract

BACKGROUND:

Vitamin D insufficiency iscommon in people living at northern latitudes and those with chronickidney disease (CKD). We studied persons with both of these riskfactors to determine the prevalence of vitamin D insufficiency andwhether serum 25-hydroxyvitamin D (25(OH)D) levels were affected byoral vitamin D3 supplementation.

METHODS:

This was a prospectivecontrolled trial of 128 patients with stage 3-5 non-dialysisdependent CKD. Patients were assigned to the intervention (oralvitamin D3 1,000 IU/day) in a 1:1 ratio at the discretion of theattending dietitian. Serum biochemical markers were measured atbaseline (May-July) and after 3 months of follow-up. There were 63control and 65 intervention subjects.

RESULTS:

Mean 25(OH)D levelsincreased significantly higher in the treatment group (mean increasefrom baseline: 10.3+/-10.4 ng/mL vs. 0.8+/-6.8 ng/mL, p<0.0001).This difference remained significant after adjustment for differingbaseline characteristics between groups (p<0.0001). Treatment withoral vitamin D3 reduced vitamin D insufficiency by 37%, as comparedwith a 2% increase in prevalence among the control group (p<0.0001).Considering the entire study population, 93% of patients had levelsless than <30 ng/mL at least once during the study.

CONCLUSION:

Vitamin D insufficiency ishighly prevalent in northern-dwelling patients with stage 3-5 CKD,and is moderated by oral supplementation with 1,000 IU of vitamin D3daily.

EurJ Clin Nutr.1995 Sep;49(9):640-6.

Effectof winter oral vitamin D3 supplementation on cardiovascular riskfactors in elderly adults.

ScraggR, KhawKT, MurphyS.

Source

Clinical Gerontology Unit,University of Cambridge School of Clinical Medicine, Addenbrooke'sHospital, UK.

Abstract

OBJECTIVE:

A possible role forvitamin D deficiency in contributing to the winter increase incardiovascular disease mortality was investigated by testing theeffect of vitamin D supplementation on blood pressure and othercardiovascular risk factors during winter.

DESIGN:

Randomised double-blindtrial of vitamin D supplementation in winter.

SUBJECTS:

Men and women, mean age 70years (range 63-76) recruited from general practitioner age-sexregisters in Cambridge (UK).

INTERVENTION:

95 people received asingle oral dose of 2.5 mg cholecalciferol and 94 received theplacebo at baseline interviews during December 1991. Follow-upassessment was 5 weeks later during January 1992.

RESULTS:

Comparing follow-up withbaseline assessment, serum 25-hydroxyvitamin D increased in thetreated group and decreased slightly in the placebo group [mean(s.d.) change: 7.2 (+/- 3.8) vs -1.4 (+/- 1.1) ng/ml, P = 0.0001];while parathyroid hormone decreased in the treated, and increased inthe placebo, group [-0.27 (+/- 0.78) vs 0.13 (+/- 0.75) pmol/l, P =0.0004]. However, the mean change in blood pressure was similar inboth groups: systolic -5 (+/- 13) vs -5 (+/- 16) mmHg, P = 0.81;diastolic -1 (+/- 9) vs -1 (+/- 9), P = 0.92; as was the mean changein serum cholesterol [-0.07 (+/- 0.52) vs -0.05 (+/- 0.60) mmol/l, P= 0.81]. In contrast, the mean change in radial pulse wassignificantly decreased in the treated group compared with placebo[-2 (+/- 9) vs 1 (+/- 7) beats per min, P = 0.030].

CONCLUSIONS:

The failure of vitamin Dsupplementation to change blood pressure or serum cholesterolsuggests that the winter increase in these factors is not caused bydecreased vitamin D levels.

ActaMed Indones. 2006Jan-Mar;38(1):3-5.

Theeffect of vitamin D as supplementary treatment in patients withmoderately advanced pulmonary tuberculous lesion.

NursyamEW, AminZ,RumendeCM.

Source

Departement of InternalMedicine, Faculty of Medicine, University of Indonesia-dr.CiptoMangunkusumo Hospital, Jakarta.

Abstract

AIM:

to compare the vitamin Dgroup of pulmonary tuberculosis patients with a placebo group interms of clinical improvement, nutritional status, sputum conversion,and radiological improvement.

METHODS:

sixty seven tuberculosispatient visiting the Pulmonary Clinic, of Cipto MangunkusumoHospital, Jakarta, from January 1st to August 31st, 2001 wereincluded in this study. The subjects were randomised to receivevitamin D (0.25 mg/day) or placebo in a double blind method, duringthe 6th initial week of Tb treatment. The rate of sputum conversion,complete blood counts, blood chemistry as well as radiologicexamination were evaluated.

RESULTS:

there were more malepatients than females (39:28), 78.7% were in the productive agegroup, 71.6% had low nutritional status, 62.4% with low educationlevel, and 67.2% with low income. One hundred percent of the vitaminD group and only 76.7% of the placebo group had sputum conversion.This difference is statistically significant (p=0.002).

CONCLUSION:

the sputum conversion hadno correlation with the hemoglobin level, blood clotting time,calcium level, lymphocyte count, age, sex, and nutritional status.There were more subjects with radiological improvement in the vitaminD group.

EpidemiolInfect. 2009Oct;137(10):1396-404. Epub 2009Mar 19.

Arandomized controlled trial of vitamin D3 supplementation for theprevention of symptomatic upper respiratory tract infections.

Li-NgM, AloiaJF, PollackS, CunhaBA, MikhailM, YehJ, BerbariN.

Source

Bone Mineral ResearchCenter, Winthrop University Hospital, Mineola, NY, USA.

Abstract

Vitamin D has been shownto be an important immune system regulator. Vitamin D insufficiencyduring winter may cause increased susceptibility to upper respiratorytract infections (URIs). To determine whether vitamin Dsupplementation during the winter season prevents or decreases URIsymptoms, 162 adults were randomized to receive 50 microg vitamin D3(2000 IU) daily or matching placebo for 12 weeks. A bi-weeklyquestionnaire was used to record the incidence and severity of URIsymptoms. There was no difference in the incidence of URIs betweenthe vitamin D and placebo groups (48 URIs vs. 50 URIs, respectively,P=0.57). There was no difference in the duration or severity of URIsymptoms between the vitamin D and placebo groups [5.4+/-4.8 days vs.5.3+/-3.1 days, respectively, P=0.86 (95% CI for the difference induration -1.8 to 2.1)]. The mean 25-hydroxyvitamin D level atbaseline was similar in both groups (64.3+/-25.4 nmol/l in thevitamin D group; 63.0+/-25.8 nmol/l in the placebo group; n.s.).After 12 weeks, 25-hydroxyvitamin D levels increased significantly to88.5+/-23.2 nmol/l in the vitamin D group, whereas there was nochange in vitamin D levels in the placebo group. There was no benefitof vitamin D3 supplementation in decreasing the incidence or severityof symptomatic URIs during winter. Further studies are needed todetermine the role of vitamin D in infection.

Lancet.2011 Jan 15;377(9761):242-50. Epub 2011 Jan 5.

High-dosevitamin D(3) duringintensive-phase antimicrobial treatment of pulmonary tuberculosis: adouble-blind randomised controlled trial.

Source

Queen Mary University ofLondon, Barts and The London School of Medicine and Dentistry,London, UK. a.martineau@qmul.ac.uk

Abstract

BACKGROUND:

Vitamin Dwas used to treat tuberculosis in the pre-antibiotic era, and itsmetabolites induce antimycobacterial immunity in vitro. Clinicaltrials investigating the effect of adjunctive vitaminD on sputum culture conversion are absent.

METHODS:

We undertook a multicentrerandomised controlled trial of adjunctive vitaminD in adults with sputum smear-positive pulmonarytuberculosis in London, UK. 146 patients were allocated to receive2·5 mg vitamin D(3) orplacebo at baseline and 14, 28, and 42 days after starting standardtuberculosis treatment. The primary endpoint was time from initiationof antimicrobial treatment to sputum culture conversion. Patientswere genotyped for TaqI and FokI polymorphisms of the vitaminD receptor, and interaction analyses were done toassess the influence of the vitamin Dreceptor genotype on response to vitamin D(3).This trial is registered with ClinicalTrials.gov number NCT00419068.

FINDINGS:

126 patients were includedin the primary efficacy analysis (62 assigned to intervention, 64assigned to placebo). Median time to sputum culture conversion was36·0 days in the intervention group and 43·5 days inthe placebo group (adjusted hazard ratio 1·39, 95% CI0·90-2·16; p=0.14). TaqI genotype modified the effectof vitamin D supplementationon time to sputum culture conversion (p(interaction)=0·03),with enhanced response seen only in patients with the tt genotype(8·09, 95% CI 1·36-48·01; p=0·02). FokIgenotype did not modify the effect of vitamin Dsupplementation (p(interaction)=0·85). Mean serum25-hydroxyvitamin D concentration at 56 days was 101·4 nmol/Lin the intervention group and 22·8 nmol/L in the placebo group(95% CI for difference 68·6-88·2; p<0·0001).

INTERPRETATION:

Administration of fourdoses of 2·5 mg vitamin D(3)increased serum 25-hydroxyvitamin D concentrations in patientsreceiving intensive-phase treatment for pulmonary tuberculosis.Vitamin D did notsignificantly affect time to sputum culture conversion in the wholestudy population, but it did significantly hasten sputum cultureconversion in participants with the tt genotype of the TaqI vitaminD receptor polymorphism.

AmJ Med. 2001Oct 15;111(6):452-6.

Calciumand vitamin D supplements reduce tooth loss in the elderly.

KrallEA, WehlerC, GarciaRI, HarrisSS, Dawson-HughesB.

Source

Department of HealthPolicy and Health Services Research, Boston University Goldman Schoolof Dental Medicine, 715 Albany Street, Boston, MA O2118, USA.

Abstract

PURPOSE:

Oral bone and tooth lossare correlated with bone loss at nonoral sites. Calcium and vitamin Dsupplementation slow the rate of bone loss from various skeletalsites, but it is not known if intake of these nutrients affects oralbone and, in turn, tooth retention.

SUBJECTSAND METHODS:

Tooth loss was examined in145 healthy subjects aged 65 years and older who completed a 3-year,randomized, placebo-controlled trial of the effect of calcium andvitamin D supplementation on bone loss from the hip, as well as a2-year follow-up study after discontinuation of study supplements.Teeth were counted at 18 months and 5 years. A comprehensive oralexamination at 5 years included assessment of caries, oral hygiene,and periodontal disease. The odds ratio (OR) and 95% confidenceinterval (CI) of tooth loss were estimated by stepwise multivariatelogistic regression. Initial age (mean +/- SD) of subjects was 71 +/-5 years, and the number of teeth remaining was 22 +/- 7.

RESULTS:

During the randomizedtrial, 11 of the 82 subjects (13%) taking supplements and 17 of the63 subjects (27%) taking placebo lost one or more teeth (OR = 0.4;95% CI: 0.2 to 0.9). During the 2-year follow-up period, 31 of the 77subjects (40%) with total calcium intake of at least 1000 mg per daylost one or more teeth compared with 40 of the 68 subjects (59%) whoconsumed less (OR = 0.5; 95% CI: 0.2 to 0.9).

CONCLUSION:

These findings suggestthat intake levels of calcium and vitamin D aimed at preventingosteoporosis have a beneficial effect on tooth retention.

NephrolDial Transplant. 2008Nov;23(11):3670-6. Epub 2008 Jun 24.

Dailyoral 25-hydroxycholecalciferol supplementation for vitamin Ddeficiency in haemodialysis patients: effects on mineral metabolismand bone markers.

JeanG, TerratJC, VanelT, HurotJM, LorriauxC, MayorB, ChazotC.

Source

Centre de Rein Artificiel,42 avenue du 8 mai 1945, 69160, Tassin la Demi-lune, [email protected]

Abstract

BACKGROUND:

Vitamin D deficiency isfrequently observed in end-stage renal disease (ESRD) patients;however, the effects of vitamin D supplementation have rarely beenreported. We aimed to assess the effects of daily 25(OH)D(3)supplementation on mineral metabolism, bone markers and KidneyDisease Outcomes Quality Initiative (KDOQI) targets in haemodialysis(HD) patients for a period of 6 months.

METHODS:

HD patients were includedin this study if their serum 25(OH)D level was <75 mmol/L. Oral25(OH)D(3) was administered daily at 10-30 microg/day based on theseverity of the deficiency. Characteristics of the patients werecompared from the baseline to 6 months on the basis of their responseto 25(OH)D(3) administration and the patients were divided into threegroups. Patients who showed partial response [serum 25(OH)D <75nmol/L] were placed in group 1, those who showed normal response[serum 25(OH)D ranging from 75 to 150 nmol/L] were placed in group 2and those who showed excessive response [serum 25(OH)D >150nmol/L] were placed in group 3.

RESULTS:

Of the 253 HD patients,225 (89%) showed vitamin D insufficiency or deficiency, 172 wereincluded in the study and 149 patients completed the study. After 6months of treatment [mean daily 25(OH)D(3): 16 +/- 5 microg/day], theserum 25(OH)D level increased (30 +/- 19 to 126 +/- 46 nmol/ L, P <0.001), with 13% of patients in group 1, 57% in group 2 and 30% ingroup 3. The serum intact parathyroid hormone (iPTH) level decreased(235 +/- 186 to 189 +/- 137 pg/mL, P = 0.05), except in group 1. Bonealkaline phosphatase (BALP) showed a tendency to normalize (23 +/- 16to 18.3 +/- 11 microg/L, P < 0.05), leading to a decrease inalfacalcidol administration from 66% to 43% (P < 0.05), except ingroup 1. The KDOQI targets achieved increased significantly for serumcalcium (76% to 85%) and phosphate levels (66% to 77%) in allpatients. The serum albumin level increased in all groups (34.6 +/- 4to 36.8 +/- 4 g/L, P < 0.05), without any significant improvementin normalized protein catabolic rate (nPCR) or C-reactive proteins(CRP).

CONCLUSION:

With a daily dose rangingfrom 10 to 30 microg, daily oral 25(OH)D(3) supplementation correctsmost vitamin D deficiencies or insufficiencies in HD patients,without any evident toxicity. The main effects observed includedcorrection of excessive bone turnover, despite less alfacalcidoladministration, increase in serum albumin level and increase in thepercentage of patients with serum calcium and phosphorus levelswithin the recommendation of the KDOQI guidelines.

JIntern Med. 2008Dec;264(6):599-609. Epub 2008 Sep 10.

Effectsof vitamin D supplementation on symptoms of depression in overweightand obese subjects: randomized double blind trial.

JordeR, SneveM, FigenschauY, SvartbergJ, WaterlooK.

Source

Institute of ClinicalMedicine, University of Tromsø, Tromsø, [email protected]

Abstract

OBJECTIVES:

The objective of thepresent study was to examine the cross-sectional relation betweenserum 25-hydroxyvitamin D [25-(OH) D] levels and depression inoverweight and obese subjects and to assess the effect of vitamin Dsupplementation on depressive symptoms.

DESIGN:

Cross-sectional study andrandomized double blind controlled trial of 20,000 or 40,000 IUvitamin D per week versus placebo for 1 year.

SETTING:

A total of 441 subjects(body mass index 28-47 kg m(-2), 159 men and 282 women, aged 21-70years) recruited by advertisements or from the out-patient clinic atthe University Hospital of North Norway.

MAINOUTCOME MEASURES:

Beck Depression Inventory(BDI) score with subscales 1-13 and 14-21.

RESULTS:

Subjects with serum25(OH)D levels < 40 nmol L(-1) scored significantly higher (moredepressive traits) than those with serum 25(OH)D levels > or = 40nmol L(-1) on the BDI total [6.0 (0-23) versus 4.5 (0-28) (median andrange)] and the BDI subscale 1-13 [2.0 (0-15) versus 1.0 (0-29.5)] (P< 0.05). In the two groups given vitamin D, but not in the placebogroup, there was a significant improvement in BDI scores after 1year. There was a significant decrease in serum parathyroid hormonein the two vitamin D groups without a concomitant increase in serumcalcium.

CONCLUSIONS:

It appears to be arelation between serum levels of 25(OH)D and symptoms of depression.Supplementation with high doses of vitamin D seems to amelioratethese symptoms indicating a possible causal relationship.

ObesSurg. 2009 Feb;19(2):173-9. Epub2008 Sep 16.

Findingthe optimal dose of vitamin D following Roux-en-Y gastric bypass: aprospective, randomized pilot clinical trial.

GoldnerWS, StonerJA, LydenE, ThompsonJ, TaylorK, LarsonL, EricksonJ, McBrideC.

Source

Section of Diabetes,Endocrinology, and Metabolism, Department of Internal Medicine,University of Nebraska Medical Center, Omaha, NE 68198-3020, [email protected]

Abstract

BACKGROUND:

Vitamin D deficiency iscommon following bariatric surgery and is due to a combination ofbaseline deficiency and postoperative malabsorption. There are fewprospective studies evaluating the appropriate dose of vitamin D toprevent and treat vitamin D deficiency following bariatric surgery.

METHODS:

We evaluated three dosesof vitamin D3 (800, 2,000, and 5,000 IU/day) in a prospective,randomized pilot trial of 45 patients undergoing Roux-en-Y gastricbypass. Serum 25 hydroxy Vitamin D (25OHD), intact PTH (iPTH),calcium, and urine calcium/creatinine ratios were measured at 6, 12,and 24 months postoperatively. Due to a high dropout rate at 24months, we focus on the 12-month data.

RESULTS:

At 12 months, the 800-,2,000-, and 5,000-IU groups had a mean +/- SD increase in 25OHD of27.5 +/- 40.0, 60.2 +/- 37.4, and 66.1 +/- 42.2 nmol/L, respectively(p = 0.09) with a maximum increase in each group of 87.4, 114.8, and129.8 nmol/L. Forty-four percent, 78%, and 70% achieved 25OHD levels>or=75 nmol/L (p = 0.38). Results for the 6- and 24-month timepoints were similar to the 12-month results. Mean weight loss at 24months of the study was not different among groups (p = 0.52). Serumcalcium did not change significantly, and there were no cases ofhypercalcemia or sustained hypercalciuria.

CONCLUSIONS:

Higher doses of vitamin Dsupplementation trend towards higher levels of 25OHD. Vitamin Dreplacement as high as 5,000 IU /day is safe and necessary in manypatients to treat vitamin D deficiency following Roux-en-Y gastricbypass yet is still suboptimal in others.

OsteoporosInt. 2009 Feb;20(2):315-22. Epub2008 Jul 16.

Effectsof a long-term vitamin D and calcium supplementation on falls andparameters of muscle function in community-dwelling olderindividuals.

PfeiferM, BegerowB, MinneHW, SuppanK, Fahrleitner-PammerA, DobnigH.

Source

Institute of ClinicalOsteology Gustav Pommer and Clinic Der Fürstenhof, Bad Pyrmont,Germany. [email protected]

Abstract

In 242 community-dwellingseniors, supplementation with either 1000 mg of calcium or 1000 mg ofcalcium plus vitamin D resulted in a decrease in the number ofsubjects with first falls of 27% at month 12 and 39% at month 20.Additionally, parameters of muscle function improved significantly.

INTRODUCTION:

The efficacy of vitamin Dand calcium supplementation on risk of falling in the elderly isdiscussed controversially. Randomized controlled trials using fallsas primary outcome are needed. We investigated long-term effects ofcalcium and vitamin D on falls and parameters of muscle function incommunity-dwelling elderly women and men.

METHODS:

Our study populationconsisted of 242 individuals recruited by advertisements and mailinglists (mean [ +/- SD] age, 77 +/- 4 years). All serum25-hydroxyvitamin D (25[OH]D) levels were below 78 nmol/l.Individuals received in a double blinded fashion either 1000 mg ofcalcium or 1000 mg of calcium plus 800 IU of vitamin D per day over atreatment period of 12 months, which was followed by a treatment-freebut still blinded observation period of 8 months. Falls weredocumented using diaries. The study took place in Bad Pyrmont,Germany (latitude 52 degrees ) and Graz, Austria (latitude 46 degrees).

RESULTS:

Compared to calcium mono,supplementation with calcium plus vitamin D resulted in a significantdecrease in the number of subjects with first falls of 27% at month12 (RR = 0.73; CI = 0.54-0.96) and 39% at month 20 (RR = 0.61; CI =0.34-0.76). Concerning secondary endpoints, we observed significantimprovements in quadriceps strength of 8%, a decrease in body sway of28%, and a decrease in time needed to perform the TUG test of 11%.

DISCUSSION:

Combined calcium andvitamin D supplementation proved superior to calcium alone inreducing the number of falls and improving muscle function incommunity-dwelling older individuals.

AgeAgeing. 2007 Sep;36(5):507-13.Epub 2007 Jul 26.

Doesvitamin D stop inpatients falling? A randomised controlled trial.

BurleighE, McCollJ, PotterJ.

Source

Department of Medicine forthe Elderly, Mansionhouse Unit, Victoria Infirmary, 21 MansionhouseRoad, Glasgow, G41 3DX, UK. [email protected]

Abstract

BACKGROUND:

Vitamin D deficiency iscommon in older people and may increase risk of falls and fracture.Hospital inpatients are at particular risk of falling. Previousstudies suggest that vitamin D improves neuromuscular function andreduces falls.

OBJECTIVE:

To determine whetherroutine supplementation with vitamin D plus calcium reduces numbersof fallers and falls in a cohort of hospital admissions while theyare inpatients.

DESIGN:

Randomised, double-blind,controlled study. Participants: two hundred and five acute admissions>65 years to a geriatric medical unit.

METHODS:

Patients were randomisedto intervention of daily vitamin D 800 iu plus calcium 1,200 mg orcontrol group of daily calcium 1,200 mg, until discharge or death.

RESULTS:

Baseline characteristicswere similar in both groups with a median age 84 years and a medianlength of stay = 30 days (IQR 14.75-71.00). In a pre-selectedsub-group (54/205 participants), median admission vitamin D level =22.00 nmol/l (IQR 15.00-30.50). This did not significantly increasein the treatment versus control group. Median study drug adherence =88%, with no significant difference between study groups(Mann-Whitney: P = 0.711). Although there were fewer fallers in thevitamin D cohort, this did not reach statistical significance(vitamin D: calcium = 36:45 fallers; RR 0.82 (CI 0.59-1.16). Neitherthe mean number of falls (vitamin D: calcium = 1.040:1.155;Mann-Whitney P = 0.435) or time to first fall (Log-rank test P =0.377) differed between groups.

CONCLUSIONS:

In a population ofgeriatric hospital inpatients, vitamin D did not reduce the number offallers. Routine supplementation cannot be recommended to reducefalls in this group.

AgeAgeing. 2004Nov;33(6):589-95.

VitaminD supplementation improves neuromuscular functionin older people who fall.

DhesiJK, JacksonSH, BearneLM, MonizC, HurleyMV, SwiftCG, AllainTJ.

Source

Elderly Day Hospital,Thomas Guy House, Guys Hospital, St Thomas Street, London, UK.jugdeep.dhesi@gsst.nhs.uk

Abstract

BACKGROUND:

vitamin Dsupplementation reduces the incidence of fractures in older adults.This may be partly mediated by effects of vitaminD on neuromuscular function.

OBJECTIVE:

to determine the effectsof vitamin D supplementationon aspects of neuromuscular function known to be risk factors forfalls and fractures.

DESIGN:

randomised, double-blind,placebo-controlled study.

SETTING:

falls clinic takingreferrals from general practitioners and accident and emergencydepartment.

SUBJECTS:

139 ambulatory subjects(>/=65 years) with a history of falls and 25-hydroxyvitamin D(25OHD)

OUTCOMEMEASURES:

assessments includingbiochemistry, postural sway, choice reaction time (CRT), aggregatefunctional performance time (AFPT), and quadriceps strength werecarried out at baseline and 6 months post-intervention.

RESULTS:

baseline characteristicswere comparable between both groups. 25OHD in the treatment groupincreased significantly at 6 months. AFPT deteriorated in the controlgroup and improved in the intervention group, representing asignificant difference between groups (+6.6 s versus -2.0 s, t =2.80, P < 0.05). Similar changes were observed for CRT (-0.06 sversus +0.41 s, t = -2.52, P < 0.01) and postural sway (+0.0025versus -0.0138, t = 2.35, P < 0.02). There was no significantdifference in muscle strength change between groups (-10 N versus -2N, t = -1.26, ns). A significant correlation between change in AFPTand change in 25OHD levels was observed (r = 0.19, P = 0.03). Therewas no significant difference in the number of falls (0.39 versus0.24, t = 1.08, P = 0.28) or fallers (14 versus 11, P = 0.52) betweentwo groups.

CONCLUSIONS:

vitamin Dsupplementation, in fallers with vitamin Dinsufficiency, has a significant beneficial effect on functionalperformance, reaction time and balance, but not muscle strength. Thissuggests that vitamin Dsupplementation improves neuromuscular or neuroprotective function,which may in part explain the mechanism whereby vitaminD reduces falls and fractures.

AmJ Respir Crit Care Med. 2009 May1;179(9):843-50. Epub 2009 Jan 29.

VitaminD as supplementary treatment for tuberculosis: adouble-blind, randomized, placebo-controlled trial.

WejseC, GomesVF, RabnaP, GustafsonP, AabyP, LisseIM, AndersenPL, GlerupH, SodemannM.

Source

Infectious DiseaseResearch Unit, Aarhus University Hospital, Skejby,Brendstrupgaardsvej, 8200 Aarhus N, Denmark. wejse@dadlnet.dk

Abstract

RATIONALE:

Vitamin Dhas been shown to be involved in the host immune response towardMycobacterium tuberculosis.

OBJECTIVES:

To test whether vitaminD supplementation of patients with tuberculosis(TB) improved clinical outcome and reduced mortality.

METHODS:

We conducted a randomized,double-blind, placebo-controlled trial in TB clinics at a demographicsurveillance site in Guinea-Bissau. We included 365 adult patientswith TB starting antituberculosis treatment; 281 completed the12-month follow-up. The intervention was 100,000 IU ofcholecalciferol or placebo at inclusion and again 5 and 8 monthsafter the start of treatment.

MEASUREMENTSAND MAIN RESULTS:

The primary outcome wasreduction in a clinical severity score (TBscore) for all patientswith pulmonary TB. The secondary outcome was 12-month mortality. Noserious adverse effects were reported; mild hypercalcemia was rareand present in both arms. Reduction in TBscore and sputum smearconversion rates did not differ among patients treated with vitaminD or placebo. Overall mortality was 15% (54 of365) at 1 year of follow-up and similar in both arms (30 of 187 forvitamin D treated and 24 of178 for placebo; relative risk, 1.19 [0.58-1.95]). HIV infection wasseen in 36% (131 of 359): 21% (76 of 359) HIV-1, 10% (36 of 359)HIV-2, and 5% (19 of 357) HIV-1+2.

CONCLUSIONS:

Vitamin Ddoes not improve clinical outcome among patients with TB and thetrial showed no overall effect on mortality in patients with TB; itis possible that the dose used was insufficient. Clinical trialregistered with www.controlled-trials.com/isrctn (ISRCTN35212132).

DiabetesCare. 2007Apr;30(4):980-6. Epub 2007Feb 2.

Theeffects of calcium and vitamin Dsupplementation on blood glucose and markers of inflammation innondiabetic adults.

PittasAG, HarrisSS, StarkPC, Dawson-HughesB.

Source

Department ofEndocrinology, Diabetes, and Metabolism, Tufts-New England MedicalCenter, Boston, MA 02111, USA. [email protected]

Abstract

OBJECTIVE:

We sought to compare theeffects of combined calcium and vitamin Dsupplementation versus placebo on blood glucose and markers ofinflammation in nondiabetic adults aged > or =65 years.

RESEARCHDESIGN AND METHODS:

A total of 314 Caucasianadults without diabetes received either 500 mg calcium citrate and700 IU vitamin D(3) orplacebos daily for 3 years in a double-blind, randomized, controlledtrial designed for bone-related outcomes. In a post hoc analysis,fasting plasma glucose (FPG), insulin sensitivity (estimated byhomeostasis model assessment of insulin resistance [HOMA-IR]), plasmaC-reactive protein, and interleukin-6, were measured at baseline and3 years.

RESULTS:

The effects of combinedcalcium-vitamin Dsupplementation on 3-year change in FPG depended on baseline FPG (P =0.02 for interaction). Therefore, we conducted analyses separately inparticipants with normal fasting glucose (NFG) (FPG <5.6 mmol/l, n= 222) and impaired fasting glucose (IFG) (FPG 5.6-6.9 mmol/l, n =92) at baseline. Among participants with IFG at baseline, those whotook combined calcium-vitamin Dsupplements had a lower rise in FPG at 3 years compared with those onplacebo (0.02 mmol/l [0.4 mg/dl] vs. 0.34 mmol/l [6.1 mg/dl],respectively, P = 0.042) and a lower increase in HOMA-IR (0.05 vs.0.91, P = 0.031). In the NFG subgroup, there was no difference in thechange in FPG or HOMA-IR between the two treatment arms. There wereno differences in C-reactive protein or interleukin-6 between the twotreatment arms in either subgroup.

CONCLUSIONS:

In healthy, older adultswith IFG, supplementation with calcium and vitaminD may attenuate increases in glycemia and insulinresistance that occur over time. However, our findings should beconsidered hypothesis generating and need to be confirmed inrandomized trials specifically designed for the outcomes of interest.

AnnIntern Med. 2010Mar 2;152(5):315-23.

Systematicreview: Vitamin D and calciumsupplementation in prevention of cardiovascular events.

WangL,MansonJE, SongY, SessoHD.

Source

Brigham and Women'sHospital and Harvard School of Public Health, Boston, Massachusetts02215, USA. [email protected]

Abstract

BACKGROUND:

Vitamin Dand calcium may affect the cardiovascular system independently andinteractively.

PURPOSE:

To assess whether vitaminD and calcium supplements reduce the risk forcardiovascular events in adults.

DATASOURCES:

Studies published inEnglish from 1966 to July 2009 in MEDLINE, EMBASE, and the CochraneCentral Register of Controlled Trials.

STUDYSELECTION:

Two investigatorsindependently selected 17 prospective studies and randomized trialsthat examined vitamin Dsupplementation, calcium supplementation, or both and subsequentcardiovascular events.

DATAEXTRACTION:

Three investigatorsextracted and checked data about study designs, participants,exposures or interventions, outcomes, and data quality.

DATASYNTHESIS:

Five prospective studiesof patients receiving dialysis and 1 study involving a generalpopulation showed consistent reductions in cardiovascular disease(CVD) mortality among adults who received vitaminD supplements. Four prospective studies ofinitially healthy persons found no differences in incidence of CVDbetween calcium supplement recipients and nonrecipients. Results ofsecondary analyses in 8 randomized trials showed a slight butstatistically nonsignificant reduction in CVD risk (pooled relativerisk, 0.90 [95% CI, 0.77 to 1.05]) with vitamin Dsupplementation at moderate to high doses (approximately 1000 IU/d)but not with calcium supplementation (pooled relative risk, 1.14 [CI,0.92 to 1.41]), or a combination of vitamin Dand calcium supplementation (pooled relative risk, 1.04 [CI, 0.92 to1.18]) compared with placebo.

LIMITATIONS:

Only articles published inEnglish that reported cardiovascular event outcomes were included.The small number of studies, the lack of trials designed specificallyto assess primary effects on cardiovascular outcomes, and importantbetween-study heterogeneity preclude definitive conclusions.

CONCLUSION:

Evidence from limited datasuggests that vitamin Dsupplements at moderate to high doses may reduce CVD risk, whereascalcium supplements seem to have minimal cardiovascular effects.Further research is needed to elucidate the role of these supplementsin CVD prevention.

ArchIntern Med. 2005 Jul25;165(14):1618-23.

Arandomized controlled trial of vitamin D3 supplementation in AfricanAmerican women.

AloiaJF, TalwarSA, PollackS, YehJ.

Source

Department of Medicine,Bone Mineral Research Center, Winthrop University Hospital, Mineola,NY 11501, USA. [email protected]

Abstract

BACKGROUND:

We conducted a randomized,placebo-controlled, double-blind trial to test the hypothesis thatvitamin D(3) supplementation would prevent bone loss incalcium-replete, African American postmenopausal women.

METHODS:

Two hundred eight healthyblack postmenopausal women, 50 to 75 years of age, were assigned toreceive either placebo or 20 microg/d (800 IU) of vitamin D(3).Calcium supplements were provided to ensure a total calcium intake of1200 to 1500 mg/d. After 2 years, the vitamin D(3) dose was increasedto 50 microg/d (2000 IU) in the active group, and the study continuedfor an additional year. Bone mineral density (BMD) was measured every6 months. Markers of bone turnover, vitamin D metabolites, andparathyroid hormone (PTH) levels were measured in serum.

RESULTS:

There were no significantdifferences in BMD between the active and control groups throughoutthe study. There was also no relationship between serum25-hydroxyvitamin D levels attained and rates of bone loss. There wasan increase in BMD of the total body, hip, and radius at 1 year inboth groups. Over the 3 years, BMD declined at these sites by 0.26%to 0.55% per year. The BMD of the lumbar spine increased slightly inthe placebo and active groups. There were no persistent changes inserum PTH levels or the markers of bone turnover, although there wasa transient decline in PTH in both groups at 3 months. No significantadverse events were attributed to vitamin D supplementation.

CONCLUSIONS:

There was no observedeffect of vitamin D(3) supplementation on bone loss or bone turnovermarkers in calcium-replete, postmenopausal African American women.Further studies are needed to determine if these findings areapplicable to women of other ethnic groups.

JBone Miner Res. 2004Aug;19(8):1221-30. Epub 2004 May 24.

Supplementationwith oral vitamin D3 and calcium during winter prevents seasonal boneloss: a randomized controlled open-label prospective trial.

MeierC, WoitgeHW, WitteK, LemmerB, SeibelMJ.

Source

Bone Research Program,ANZAC Research Institute, University Sydney, Concord, New SouthWales, Australia.

Abstract

Bone metabolism follows aseasonal pattern with high bone turnover and bone loss during thewinter. In a randomized, open-label 2-year sequential follow-up studyof 55 healthy adults, we found that supplementation with oral vitaminD3 and calcium during winter abolished seasonal changes incalciotropic hormones and markers of bone turnover and led to anincrease in BMD. Supplementation with oral vitamin D3 and calciumduring the winter months seems to counteract the effects of seasonalchanges in vitamin D and thusmay be beneficial as a primary prevention strategy for age-relatedbone loss.

INTRODUCTION:

Bone metabolism follows aseasonal pattern characterized by high bone turnover and bone lossduring winter. We investigated whether wintertime supplementationwith oral vitamin D3 and calcium had beneficial effects on thecircannual changes in bone turnover and bone mass.

MATERIALSAND METHODS:

This prospective studycomprised an initial observation period of 12 months ("year 1"),followed by an intervention during parts of year 2. Fifty-fivehealthy subjects living in southwestern Germany (latitude, 49.5degrees N) were randomized into two groups: 30 subjects were assignedto the treatment group and received oral cholecalciferol (500 IU/day)and calcium (500 mg/day) during the winter months of year 2(October-April), while 25 subjects assigned to the control groupobtained no supplements. Primary endpoints were changes incalciotropic hormones [serum 25(OH)D, 1,25(OH)2D, and parathyroidhormone], markers of bone formation (serum bone-specific alkalinephosphatase) and of bone resorption (urinary pyridinoline anddeoxypyridinoline), and changes in lumbar spine and femoral neck BMD.

RESULTS:

Forty-three subjectscompleted the study. During year 1, calciotropic hormones, markers ofbone turnover, and BMD varied by season in both groups. During thewinter months of year 1, bone turnover was significantly accelerated,and lumbar spine and femoral BMD declined by 0.3-0.9%. In year 2,seasonal changes in calciotropic hormones and markers of boneturnover were either reversed or abolished in the intervention groupwhile unchanged in the control cohort. In the subjects receiving oralvitamin D3 and calcium, lumbar and femoral BMD increasedsignificantly (lumbar spine: +0.8%, p = 0.04 versus year 1; femoralneck: +0.1%, p = 0.05 versus year 1), whereas controls continued tolose bone (intervention group versus control group: lumbar spine, p =0.03; femoral neck, p = 0.05).

CONCLUSIONS:

Supplementation with oralvitamin D3 and calcium during winter prevents seasonal changes inbone turnover and bone loss in healthy adults. It seems conceivablethat annually recurring cycles of low vitamin Dand mild secondary hyperparathyroidism during the winter monthscontributes, at least in part and over many years, to age-relatedbone loss. Supplementation with low-dose oral vitamin D3 and calciumduring winter may be an efficient and inexpensive strategy for theprimary prevention of bone loss in northern latitudes.

AmJ Clin Nutr.2006Apr;83(4):754-9.

VitaminD supplementation improves cytokine profiles inpatients with congestive heart failure: a double-blind, randomized,placebo-controlled trial.

SchleithoffSS,ZittermannA,TenderichG,BertholdHK,StehleP,KoerferR.

Source

Institute of Nutrition andFood Science, University of Bonn, Bonn, Germany.

Abstract

BACKGROUND:

Elevated circulatingconcentrations of proinflammatory cytokines may contribute to thepathogenesis of congestive heart failure (CHF). In vitro studiessuggest that vitamin Dsuppresses proinflammatory cytokines and increases antiinflammatorycytokines.

OBJECTIVE:

We evaluated the effect ofvitamin D supplementation onthe survival rate and different biochemical variables in patientswith CHF.

DESIGN:

One hundred twenty-threepatients randomly received either 50 mug vitaminD(3)/d plus 500 mg Ca/d [D(+) group] or placeboplus 500 mg Ca/d [D(-) group] for 9 mo. Biochemical variables wereassessed at baseline and after 9 mo. The survival rate was calculatedfor a follow-up period of 15 mo.

RESULTS:

Ninety-three patientscompleted the study. Significant treatment effects were observed onlogarithmic-transformed serum concentrations of 25-hydroxyvitamin D(P = 0.001), parathyroid hormone (P = 0.007), tumor necrosis factoralpha (P = 0.006), and interleukin 10 (P = 0.042). 25-HydroxyvitaminD increased by 26.8 ng/mL in the D(+) group but increased only by 3.6ng/mL in the D(-) group. Compared with baseline, parathyroid hormonewas significantly lower and the antiinflammatory cytokine interleukin10 was significantly higher in the D(+) group after 9 mo. Theproinflammatory cytokine tumor necrosis factor alpha increased in theD(-) group but remained constant in the D(+) group. The survival ratedid not differ significantly between the study groups during thefollow-up period.

CONCLUSIONS:

Vitamin D(3)reduces the inflammatory milieu in CHF patients and might serve as anew antiinflammatory agent for the future treatment of the disease.Our data provide evidence for the involvement of an impaired vitaminD-parathyroid hormone axis in the progression ofCHF.

JClin Endocrinol Metab. 2006Feb;91(2):405-12. Epub 2005 Nov 8.

Effectof vitamin D replacement onmusculoskeletal parameters in school children: a randomizedcontrolled trial.

El-HajjFuleihan G, NabulsiM, TamimH, MaaloufJ, SalamounM, KhalifeH, ChoucairM, ArabiA, ViethR.

Source

Calcium Metabolism andOsteoporosis Program, American University of Beirut-Medical Center,Bliss Street, 113-6044 Beirut, Lebanon. [email protected]

Abstract

BACKGROUND:

Despite the highprevalence of hypovitaminosis D in children and adolescentsworldwide, the impact of vitamin Ddeficiency on skeletal health is unclear.

METHODS:

One hundred seventy-ninegirls, ages 10-17 yr, were randomly assigned to receive weekly oralvitamin D doses of 1,400 IU(equivalent to 200 IU/d) or 14,000 IU (equivalent to 2,000 IU/d) in adouble-blind, placebo-controlled, 1-yr protocol. Areal bone mineraldensity (BMD) and bone mineral content (BMC) at the lumbar spine,hip, forearm, total body, and body composition were measured atbaseline and 1 yr. Serum calcium, phosphorus, alkaline phosphatase,and vitamin D metaboliteswere measured during the study.

RESULTS:

In the overall group ofgirls, lean mass increased significantly in both treatment groups (P< or = 0.05); bone area and total hip BMC increased in thehigh-dose group (P < 0.02). In premenarcheal girls, lean massincreased significantly in both treatment groups, and there wereconsistent trends for increments in BMD and/or BMC at severalskeletal sites, reaching significance at lumbar spine BMD in thelow-dose group and at the trochanter BMC in both treatment groups.There was no significant change in lean mass, BMD, or BMC inpostmenarcheal girls.

CONCLUSIONS:

Vitamin Dreplacement had a positive impact on musculoskeletal parameters ingirls, especially during the premenarcheal period.

BMJ.2011 May 31;342:d2975. doi: 10.1136/bmj.d2975.

Effectof weekly vitamin Dsupplements on mortality, morbidity, and growth of low birthweightterm infants in India up to age 6 months: randomisedcontrolled trial.

KumarGT,SachdevHS,ChellaniH,RehmanAM,SinghV, AroraH,FilteauS.

Source

Institute of HomeEconomics, Delhi University, F-4 Haus Khas Enclave, New Delhi 110016,India. [email protected]

Abstract

OBJECTIVE:

To investigate whethervitamin D supplementation candecrease the mortality and morbidity of low birthweight infants inlow income countries.

DESIGN:

Randomised controlledtrial.

SETTING:

Large government hospitalin New Delhi, India.

PARTICIPANTS:

2079 low birthweightinfants born at term (>37 weeks' gestation).

MAINOUTCOME MEASURES:

Primary outcome wasadmission to hospital or death during the first six months of life.Main secondary outcome was growth.

INTERVENTIONS:

Weekly vitaminD supplements for six months at a dose of onerecommended nutrient intake per day (35 µg/week). Infants werevisited weekly at home for observed supplementation and were broughtto the clinic monthly for clinical examination and anthropometricmeasurements.

RESULTS:

Between group differenceswere not significant for death or hospital admissions (92 among 1039infants in the vitamin Dgroup v 99 among 1040 infants in the placebo group; adjusted rateratio 0.93, 95% confidence interval 0.68 to 1.29; P = 0.68), orreferral to the outpatient clinic for moderate morbidity. VitaminD supplementation resulted in better vitaminD status as assessed by plasma calcidiol levelsat six months. In adjusted analyses, vitamin Dtreatment significantly increased standard deviation (z) scores atsix months for weight, length, and arm circumference and decreasedthe proportion of children with stunted growth (length for age zscore ≤ 2) or with arm circumference z scores of 2 or less.

CONCLUSION:

A weekly dose of vitaminD resulted in better vitaminD status and benefited the classic vitaminD function of bone growth but did not decreasethe incidence of severe morbidity or death among young lowbirthweight infants. Trial registration ClinicalTrials.govNCT00415402.

BMCMusculoskelet Disord. 2011 Jun20;12:135.

Arandomized controlled trialof vitamin D dosingstrategies after acute hip fracture: no advantage of loading dosesover daily supplementation.

PapaioannouA, KennedyCC, GiangregorioL, IoannidisG, PritchardJ, HanleyDA, FarrautoL, DeBeerJ, AdachiJD.

Source

McMaster University, HHSC,St. Peter's Hospital Juravinski Research Centre, 88 Maplewood AvenueHamilton, ON L8M 1W9, Canada. [email protected]

Abstract

BACKGROUND:

There remains uncertaintyregarding the appropriate therapeutic management of hip fracturepatients. The primary aim of our study was to examine whether largeloading doses in addition to daily vitamin Doffered any advantage over a simple daily low-dose vitaminD regimen for increasing vitaminD levels.

METHODS:

In this randomizedcontrolled study, patients over age 50 with an acute fragility hipfracture were enrolled from two hospital sites in Ontario, Canada.Participants were randomized to one of three loading dose groups:placebo; 50,000 IU vitamin D2; or 100,000 IU D2. Following aplacebo/loading dose, all patients received a daily tablet of 1,000IU vitamin D3 for 90 days. Serum 25-hydroxy vitaminD (25-OHD) was measured at baseline, dischargefrom acute care (approximately 4-weeks), and 3-months.

RESULTS:

Sixty-five patients wereenrolled in the study (44% male). An immediate rise in 25-OHDoccurred in the 100,000 group, however there were no significantdifferences in 25-OHD between the placebo, 50,000 and 100,000 loadingdose groups after 4-weeks (69.3, 84.5, 75.6 nmol/L, p = 0.15) and3-months (86.7, 84.2, 73.3 nmol/L, p = 0.09), respectively. At theend of the study, approximately 75% of the placebo and 50,000 groupshad reached the target therapeutic range (75 nmol/L), and 44% of the100,000 group.

CONCLUSIONS:

In correcting vitaminD insufficiency/deficiency in elderly patientswith hip fracture, our findings suggest that starting with a lowerdaily dose of Vitamin D3 achieved similar results as providing anadditional large loading dose of Vitamin D2. At the end of the study,all three groups were equally effective in attaining improvement in25-OHD levels. Given that a daily dose of 1,000 IU vitamin D3 (withor without a loading dose) resulted in at least 25% of patientshaving suboptimal vitamin Dstatus, patients with acute hip fracture may benefit from a higherdaily dose of vitamin D.

AmJ Clin Nutr.2011 Aug;94(2):486-94. Epub 2011 Jun 29.

Effectsof vitamin D and calciumsupplementation on pancreatic β cell function, insulinsensitivity, and glycemia in adults at high risk of diabetes: theCalcium and Vitamin D forDiabetes Mellitus (CaDDM) randomized controlledtrial.

MitriJ, Dawson-HughesB, HuFB, PittasAG.

Source

Division of Endocrinology,Diabetes, and Metabolism, Tufts Medical Center, Boston, MA 02111,USA.

Abstract

BACKGROUND:

A suboptimal vitaminD and calcium status has been associated withhigher risk of type 2 diabetes in observational studies, but evidencefrom trials is lacking.

OBJECTIVE:

We determined whethervitamin D supplementation,with or without calcium, improved glucose homeostasis in adults athigh risk of diabetes.

DESIGN:

Ninety-two adults wererandomly assigned in a 2-by-2 factorial-design, double-masked,placebo-controlled trial to receive either cholecalciferol (2000 IUonce daily) or calcium carbonate (400 mg twice daily) for 16 wk. Theprimary outcome was the change in pancreatic β cell function asmeasured by the disposition index after anintravenous-glucose-tolerance test. Other outcomes were acute insulinresponse, insulin sensitivity, and measures of glycemia.

RESULTS:

Participants had a meanage of 57 y, a body mass index (BMI; in kg/m(2)) of 32, and glycatedhemoglobin (Hb A(1c)) of 5.9%. There was no significant vitaminD × calcium interaction on any outcomes.The disposition index increased in the vitamin Dgroup and decreased in the no-vitamin Dgroup (adjusted mean change ± SE: 300 ± 130 comparedwith -126 ± 127, respectively; P = 0.011), which was explainedby an improvement in insulin secretion (62 ± 39 compared with-36 ± 37 mU · L(-1) · min, respectively; P =0.046). Hb A(1c) increased less, but nonsignificantly, in the vitaminD group than in the no-vitaminD group (0.06 ± 0.03% compared with 0.14 ±0.03%, respectively; P = 0.081). There was no significant differencein any outcomes with calcium compared with no calcium.

CONCLUSION:

In adults at risk of type2 diabetes, short-term supplementation with cholecalciferol improvedβ cell function and had a marginal effect on attenuating therise in Hb A(1c). This trial was registered at clinicaltrials.gov asNCT00436475.

JClin Oncol. 2011 Aug1;29(22):3078-84. Epub 2011 Jun 27.

Calciumplus vitamin Dsupplementation and the risk of nonmelanoma and melanoma skin cancer:post hoc analyses of the women's health initiative randomizedcontrolled trial.

TangJY, FuT,LeblancE,MansonJE,FeldmanD, LinosE,VitolinsMZ,ZeitouniNC,LarsonJ,StefanickML.

Source

Department of Dermatology,Stanford University School of Medicine, 450 Broadway, Pavilion C, MC5334, Redwood City, CA, USA. [email protected]

Abstract

PURPOSE:

In light of inverserelationships reported in observational studies of vitaminD intake and serum 25-hydroxyvitamin D levelswith risk of nonmelanoma skin cancer (NMSC) and melanoma, weevaluated the effects of vitamin Dcombined with calcium supplementation on skin cancer in a randomizedplacebo-controlled trial.

METHODS:

Postmenopausal women age50 to 79 years (N = 36,282) enrolled onto the Women's HealthInitiative (WHI) calcium/vitamin Dclinical trial were randomly assigned to receive 1,000 mg ofelemental calcium plus 400 IU of vitamin D3 (CaD) daily or placebofor a mean follow-up period of 7.0 years. NMSC and melanoma skincancers were ascertained by annual self-report; melanoma skin cancersunderwent physician adjudication.

RESULTS:

Neither incident NMSC normelanoma rates differed between treatment (hazard ratio [HR], 1.02;95% CI, 0.95 to 1.07) and placebo groups (HR, 0.86; 95% CI, 0.64 to1.16). In subgroup analyses, women with history of NMSC assigned toCaD had a reduced risk of melanoma versus those receiving placebo(HR, 0.43; 95% CI, 0.21 to 0.90; P(interaction) = .038), which wasnot observed in women without history of NMSC.

CONCLUSION:

Vitamin Dsupplementation at a relatively low dose plus calcium did not reducethe overall incidence of NMSC or melanoma. However, in women withhistory of NMSC, CaD supplementation reduced melanoma risk,suggesting a potential role for calcium and vitaminD supplements in this high-risk group. Resultsfrom this post hoc subgroup analysis should be interpreted withcaution but warrant additional investigation.

CochraneDatabase Syst Rev.2011 Jul 6;(7):CD007470.

VitaminD supplementation for prevention of mortality inadults.

BjelakovicG, GluudLL, NikolovaD, WhitfieldK, WetterslevJ, SimonettiRG, BjelakovicM, GluudC.

Source

Department of InternalMedicine - Gastroenterology and Hepatology, Medical Faculty,University of Nis, Zorana Djindjica 81, Nis, Serbia, 18000.

Abstract

BACKGROUND:

The available evidence onvitamin D and mortality isinconclusive.

OBJECTIVES:

To assess the beneficialand harmful effects of vitamin Dfor prevention of mortality in adults.

SEARCHSTRATEGY:

We searched The CochraneLibrary, MEDLINE, EMBASE, LILACS, the Science Citation IndexExpanded, and Conference Proceedings Citation Index-Science (toJanuary 2011). We scanned bibliographies of relevant publications andasked experts and pharmaceutical companies for additional trials.

SELECTIONCRITERIA:

We included randomisedtrials that compared vitamin Dat any dose, duration, and route of administration versus placebo orno intervention. Vitamin Dcould have been administered as supplemental vitaminD (vitamin D(3)(cholecalciferol) or vitamin D(2)(ergocalciferol)) or an active form of vitamin D(1α-hydroxyvitamin D (alfacalcidol) or 1,25-dihydroxyvitamin D(calcitriol)).

DATACOLLECTION AND ANALYSIS:

Six authors extracted dataindependently. Random-effects and fixed-effect model meta-analyseswere conducted. For dichotomous outcomes, we calculated the riskratios (RR). To account for trials with zero events, meta-analyses ofdichotomous data were repeated using risk differences (RD) andempirical continuity corrections. Risk of bias was considered inorder to minimise risk of systematic errors. Trial sequentialanalyses were conducted to minimise the risk of random errors.

MAINRESULTS:

Fifty randomised trialswith 94,148 participants provided data for the mortality analyses.Most trials included elderly women (older than 70 years). VitaminD was administered for a median of two years.More than one half of the trials had a low risk of bias. Overall,vitamin D decreased mortality(RR 0.97, 95% confidence interval (CI) 0.94 to 1.00, I(2) = 0%). Whenthe different forms of vitamin Dwere assessed separately, only vitamin D(3)decreased mortality significantly (RR 0.94, 95% CI 0.91 to 0.98, I(2)= 0%; 74,789 participants, 32 trials) whereas vitaminD(2), alfacalcidol, or calcitriol did not. Trialsequential analysis supported our finding regarding vitaminD(3), corresponding to 161 individuals treated toprevent one additional death. Vitamin D(3)combined with calcium increased the risk of nephrolithiasis (RR 1.17,95% CI 1.02 to 1.34, I(2) = 0%). Alfacalcidol and calcitriolincreased the risk of hypercalcaemia (RR 3.18, 95% CI 1.17 to 8.68,I(2) = 17%). Data on health-related quality of life and healtheconomics were inconclusive.

AUTHORS'CONCLUSIONS:

Vitamin Din the form of vitamin D(3)seems to decrease mortality in predominantly elderly women who aremainly in institutions and dependent care. VitaminD(2), alfacalcidol, and calcitriol had nostatistically significant effect on mortality. VitaminD(3) combined with calcium significantlyincreased nephrolithiasis. Both alfacalcidol and calcitriolsignificantly increased hypercalcaemia.

Diabetes.2011 Nov;60(11):2748-57. Epub 2011 Sep 12.

VitaminD, insulin secretion, sensitivity, and lipids:results from a case-control study and a randomizedcontrolled trial using hyperglycemic clamptechnique.

GrimnesG,FigenschauY, AlmåsB, JordeR.

Source

Tromsø EndocrineResearch Group, Department of Clinical Medicine, University ofTromsø, Tromsø, Norway. [email protected]

Abstract

OBJECTIVE:

Vitamin Ddeficiency is associated with an unfavorable metabolic profile inobservational studies. The intention was to compare insulinsensitivity (the primary end point) and secretion and lipids insubjects with low and high serum 25(OH)D (25-hydroxyvitamin D) levelsand to assess the effect of vitamin Dsupplementation on the same outcomes among the participants with lowserum 25(OH)D levels.

RESEARCHDESIGN AND METHODS:

Participants wererecruited from a population-based study (the Tromsø Study)based on their serum 25(OH)D measurements. A 3-h hyperglycemic clampwas performed, and the participants with low serum 25(OH)D levelswere thereafter randomized to receive capsules of 20,000 IU vitaminD(3) or identical-looking placebo twice weeklyfor 6 months. A final hyperglycemic clamp was then performed.

RESULTS:

The 52 participants withhigh serum 25(OH)D levels (85.6 ± 13.5 nmol/L [mean ±SD]) had significantly higher insulin sensitivity index (ISI) andlower HbA(1c) and triglycerides (TGs) than the 108 participants withlow serum 25(OH)D (40.3 ± 12.8 nmol/L), but the differences inISI and TGs were not significant after adjustments. Aftersupplementation, serum 25(OH)D was 142.7 ± 25.7 and 42.9 ±17.3 nmol/L in 49 of 51 completing participants randomized to vitaminD and 45 of 53 randomized to placebo,respectively. At the end of the study, there were no statisticallysignificant differences in the outcome variables between the twogroups.

CONCLUSIONS:

Vitamin Dsupplementation to apparently healthy subjects with insufficientserum 25(OH)D levels does not improve insulin sensitivity orsecretion or serum lipid profile.

JBone Miner Res. 2011 Sep 28. doi:10.1002/jbmr.524. [Epub ahead of print]

Effectsof three monthly oral 150,000 IU cholecalciferol supplementation onfalls, mobility and muscle strength in older postmenopausal women: arandomised controlled trial.

GlendenningP, ZhuK, InderjeethC, HowatP, LewisJR, PrinceRL.

Source

School of Medicine andPharmacology, University of Western Australia, Perth, Australia;School of Pathology and Laboratory Medicine, University of WesternAustralia, Perth, Australia; Department of Core Clinical Pathologyand Biochemistry, Royal Perth Hospital, Perth, Australia.

Abstract

Daily vitaminD in addition to calcium supplementation reducesfalls and fractures in older women. However, poor adherence totherapy is a common clinical problem. To examine the effects ofsupervised oral 3 monthly vitamin Dtherapy on falls, muscle strength and mobility, we conducted anine-month randomised, double-blind, placebo-controlled trial in 686community-dwelling ambulant women aged over 70 years. Participantsreceived either oral cholecalciferol 150,000 IU every 3 months(n = 353)or an identical placebo (n = 333).All participants were advised to increase dietary calcium intake.Falls data were collected three monthly. At baseline, 3, 6 and 9months, muscle strength was measured by a handheld dynamometer andmobility by the Timed Up and Go (TUG) test. Serum 25 hydroxyvitamin D(25OHD) was measured in a subgroup of 40 subjects. Mean age atbaseline was 76.7 ± 4.1years. The average serum 25OHD value at baseline was 65.8 ± 22.7nmol/L. By three, six and nine months after supplementation, 25OHDlevels of the vitamin D groupwere approximately 15 nmol/L higher than the placebo group. Calciumintake did not change significantly between baseline(864 ± 412 mg/day)and 9 months (855 ± 357 mg/day).Faller rates in the two groups did not differ: vitaminD group 102/353(29%); placebo group 89/333(27%).At 9 months, compared to placebo or baseline, muscle strength and TUGwere not altered by vitamin D.In conclusion, oral cholecalciferol 150,000 IU therapy administeredthree monthly had neither beneficial nor adverse effects on falls orphysical function. These data together with previous findings confirmthat intermittent large doses of vitamin Dare ineffective or have a deleterious effect on falls. Thus despiteadherence issues with daily vitamin Dreplacement, an intermittent, high dose vitamin Dregimen cannot be supported as a strategy to reduce falls andfractures. © 2011 American Society for Bone and MineralResearch.

PLoSOne. 2011;6(11):e25966. Epub 2011Nov 4.

Effectsof vitamin d supplementationon cognitive and emotional functioning in young adults - a randomisedcontrolled trial.

DeanAJ, BellgroveMA, HallT, PhanWM, EylesDW, KvaskoffD, McGrathJJ.

Source

Queensland BrainInstitute, The University of Queensland, St Lucia, Australia.

Abstract

BACKGROUND:

Epidemiological researchlinks vitamin D status tovarious brain-related outcomes. However, few trials examine whethersupplementation can improve such outcomes and none have examinedeffects on cognition. This study examined whether VitaminD supplementation led to improvements in diversemeasures of cognitive and emotional functioning, and hypothesisedthat supplementation would lead to improvements in these outcomescompared to placebo.

METHODS/PRINCIPALFINDINGS:

Healthy young adults wererecruited to a parallel-arm, double-blind trial conducted at TheUniversity of Queensland. Participants were randomly allocated toreceive Vitamin D (onecapsule daily, containing 5000 IU cholecalciferol) or identicalplacebo capsule for six weeks. All participants and outcome assessorswere blinded to group assignment. Primary outcome measures assessedat baseline and 6 weeks were working memory, response inhibition andcognitive flexibility. Secondary outcomes were:hallucination-proneness, psychotic-like experiences, and ratings ofdepression, anxiety and anger. 128 participants were recruited,randomised and included in primary analyses (vitaminD n=63;placebo n=65).Despite significant increases in vitamin Dstatus in the active group, no significant changes were observed inworking memory (F=1.09;p=0.30),response inhibition (F=0.82;p=0.37),cognitive flexibility (F=1.37;p=0.24)or secondary outcomes. No serious adverse effects were reported.

CONCLUSIONS:

Our findings indicate thatvitamin D supplementationdoes not influence cognitive or emotional functioning in healthyyoung adults. Future controlled trials in targeted populations ofinterest are required to determine whether supplementation canimprove functioning in these domains. Australian and New ZealandClinical Trials Registry; ACTRN12610000318088.

IndianPediatr. 2011 Aug 15. pii:S097475591100214-1. [Epub ahead of print]

VitaminD Supplementation for Severe Pneumonia ARandomized Controlled Trial.

ChoudharyN, GuptaP.

Source

Department of Pediatrics,University College of Medical Sciences and Guru Teg Bahadur Hospital,Dilshad Garden, Delhi, India. Correspondence to: Dr Nidhi Choudhary,Block ED, 72A, Pitampura, Delhi 110 034, India,[email protected].

Abstract

OBJECTIVE:

To determine the role oforal vitamin Dsupplementation for resolution of severe pneumonia in under-fivechildren.

DESIGN:

Randomized double blindplacebo-controlled trial.

SETTING:

Inpatients from a tertiarycare hospital.

PARTICIPANTS:

Two hundred children [mean(SD) age: 13.9 (11.7) months; boys: 120] between 2 months to 5 yearswith severe pneumonia. Pneumonia was diagnosed in the presence offever, cough, tachypnea (as per WHO cutoffs) and crepitations.Children with pneumonia and chest indrawing or at least one of thedanger sign (inability to feed, lethargy, cyanosis) were diagnosed ashaving severe pneumonia. The two groups were comparable for baselinecharacteristics including age, anthropometry, socio-demographicprofile and clinical and laboratory parameters.

INTERVENTION:

Oral vitaminD (1000 IU for <1 year and 2000 IU for >1year) (n=100) or placebo (lactose) (n=100) once a day for 5 days,from enrolment. Both the groups received antibiotics as per theIndian Academy of Pediatrics guidelines, and supportive care (oxygen,intravenous fluids and monitoring).

OUTCOMEVARIABLES:

Primary: time toresolution of severe pneumonia. SECONDARY: duration ofhospitalization and time to resolution of tachypnea, chestretractions and inability to feed.

RESULTS:

Median duration (SE, 95%CI) of resolution of severe pneumonia was similar in the two groups[vitamin D: 72 (3.7,64.7-79.3) hours; placebo: 64 (4.5, 55.2-72.8)hours]. Duration ofhospitalization and time to resolution of tachypnea, chestretractions, and inability to feed were also comparable between thetwo groups.

CONCLUSION:

Short-term supplementationwith oral vitamin D(1000-2000 IU per day for 5 days) has no beneficial effect onresolution of severe pneumonia in under-five children. Furtherstudies needs to be conducted with higher dose of VitaminD or longer duration of supplementation tocorroborate these findings.

EurJ Nutr. 2011 Nov 16. [Epub aheadof print]

Isa daily supplementation with 40 microgram vitaminD(3) sufficient? A randomisedcontrolled trial.

TossG, MagnussonP.

Source

Department ofEndocrinology and Gastroenterology, County Council of Östergötland,SE-581 85, Linköping, Sweden.

Abstract

PURPOSE:

The effect of 40 μg(1,600 IU) per day of vitamin D(3)on serum 25-hydroxyvitamin D (25(OH)D) and markers of bone andmineral metabolism was evaluated.

METHODS:

This intervention studywas designed as a double-blind randomisedcontrolled trial. Forty-five community-dwellingsubjects (32 females), age 55-84 years, at 58° Northlatitude were supplemented for 1 year with 40 μg vitaminD(3) plus 1,000 mg calcium per day, or with1,000 mg calcium per day for controls. Safety parameters and25(OH)D, intact parathyroid hormone (PTH), ionized calcium,bone-specific alkaline phosphatase (BALP), and tartrate-resistantacid phosphatase isoform 5b (TRACP5b) were measured over the studyperiod.

RESULTS:

All subjects supplementedwith vitamin D(3) reached a25(OH)D level above 50 nmol/L. Mean (SD) serum 25(OH)D increasedfrom 50.4 (13.5) nmol/L to 84.2 (17.5) nmol/L, range55.0-125.0 nmol/L in the vitamin D(3)supplemented group and the corresponding levels for the control groupwere 47.3 (14.1) nmol/L and 45.7 (13.4) nmol/L, range26.0-73.0 nmol/L. No serious adverse event was recorded and thehighest 25(OH)D level reached, 125.0 nmol/L, is well below toxiclevels. BALP and TRACP5b did not change significantly over the studyperiod.

CONCLUSIONS:

This trial suggests that adaily supplementation with 40 μg vitaminD(3) is sufficient to secure a 25(OH)D level of50 nmol/L. No side effects were observed in the study group.

JClin Endocrinol Metab. 2011 Nov23. [Epub ahead of print]

Long-TermFollow-Up for Mortality and Cancer in a Randomized Placebo-ControlledTrial of Vitamin D3 and/or Calcium (RECORD Trial).

AvenellA, MaclennanGS, JenkinsonDJ, McPhersonGC, McDonaldAM, PantPR, GrantAM, CampbellMK, AndersonFH, CooperC, FrancisRM, GillespieWJ, RobinsonCM, TorgersonDJ, WallaceWA; theRECORD Trial Group.

Source

Health Services ResearchUnit (A.A., G.S.M., D.J.J., G.C.M., A.M.M., P.R.P., A.M.G., M.K.C.),University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UnitedKingdom; Geriatric Medicine (F.H.A.), Developmental Origins of Healthand Disease, Research Division, and Medical Research CouncilLifecourse Epidemiology Unit (C.C.), University of Southampton,Southampton SO16 6YD, and Institute of Musculoskeletal Sciences,University of Oxford, Oxford OX3 7LD, United Kingdom; Institute forAgeing and Health (R.M.F.), Newcastle University, Newcastle upon TyneNE4 5PL, United Kingdom; Hull York Medical School (W.J.G.),University of Hull, Hull HU6 7RX, United Kingdom; Royal Infirmary ofEdinburgh (C.M.R.), Edinburgh EH3 9HB, United Kingdom; York TrialsUnit (D.J.T.), University of York, York YO10 5DD, United Kingdom; andMedical and Surgical Sciences (W.A.W.), University of Nottingham,Nottingham NG7 2UH, United Kingdom.

Abstract

Context:VitaminD or calcium supplementation may have effects onvascular disease and cancer.Objective:Our objective was toinvestigate whether vitamin Dor calcium supplementation affects mortality, vascular disease, andcancer in older people.Design and Setting:The study includedlong-term follow-up of participants in a two by two factorial,randomized controlled trialfrom 21 orthopedic centers in the UnitedKingdom.Participants:Participants were 5292 people (85% women) agedat least 70 yr with previous low-trauma fracture.

Interventions:Participantswere randomly allocated to daily vitamin D(3)(800 IU), calcium (1000 mg), both, or placebo for 24-62 months, witha follow-up of 3 yr after intervention.Main OutcomeMeasures:All-cause mortality, vascular disease mortality, cancermortality, and cancer incidence were evaluated.

Results:Inintention-to-treat analyses, mortality [hazard ratio (HR) = 0.93; 95%confidence interval (CI) = 0.85-1.02], vascular disease mortality (HR= 0.91; 95% CI = 0.79-1.05), cancer mortality (HR = 0.85; 95% CI =0.68-1.06), and cancer incidence (HR = 1.07; 95% CI = 0.92-1.25) didnot differ significantly between participants allocated vitaminD and those not. All-cause mortality (HR = 1.03;95% CI = 0.94-1.13), vascular disease mortality (HR = 1.07; 95% CI =0.92-1.24), cancer mortality (HR = 1.13; 95% CI = 0.91-1.40), andcancer incidence (HR = 1.06; 95% CI = 0.91-1.23) also did not differsignificantly between participants allocated calcium and those not.In a post hoc statistical analysis adjusting for compliance, thuswith fewer participants, trends for reduced mortality with vitaminD and increased mortality with calcium wereaccentuated, although all results remain nonsignificant.

Conclusions:Daily vitaminD or calcium supplementation did not affectmortality, vascular disease, cancer mortality, or cancer incidence.

AmJ Cardiol. 2011 Nov 7. [Epub aheadof print]

VitaminD Deficiency and Supplementationand Relation to CardiovascularHealth.

VacekJL, VangaSR, GoodM, LaiSM, LakkireddyD, HowardPA.

Source

Mid America Cardiology,Division of CardiovascularMedicine, University of Kansas Medical Center and Hospital, KansasCity, Kansas.

Abstract

Recent evidence supportsan association between vitamin Ddeficiency and hypertension, peripheral vascular disease, diabetesmellitus, metabolic syndrome, coronary artery disease, and heartfailure. The effect of vitamin Dsupplementation, however, hasnot been well studied. We examined the associations between vitaminD deficiency, vitamin Dsupplementation, and patientoutcomes in a large cohort. Serum vitamin Dmeasurements for 5 years and 8 months from a large academicinstitution were matched to patient demographic, physiologic, anddisease variables. The vitamin Dlevels were analyzed as a continuous variable and as normal (≥30ng/ml) or deficient (<30 ng/ml). Descriptive statistics,univariate analysis, multivariate analysis, survival analysis, andCox proportional hazard modeling were performed. Of 10,899 patients,the mean age was 58 ± 15 years, 71% were women (n = 7,758),and the average body mass index was 30 ± 8 kg/m(2). The meanserum vitamin D level was24.1 ± 13.6 ng/ml. Of the 10,899 patients, 3,294 (29.7%) werein the normal vitamin D rangeand 7,665 (70.3%) were deficient. Vitamin Ddeficiency was associated with several cardiovascular-relateddiseases, including hypertension, coronary artery disease,cardiomyopathy, and diabetes (all p <0.05). VitaminD deficiency was a strong independent predictorof all-cause death (odds ratios 2.64, 95% confidence interval 1.901to 3.662, p <0.0001) after adjusting for multiple clinicalvariables. Vitamin Dsupplementation conferredsubstantial survival benefit (odds ratio for death 0.39, 95%confidence interval 0.277 to 0.534, p <0.0001). In conclusion,vitamin D deficiency wasassociated with a significant risk of cardiovasculardisease and reduced survival. Vitamin Dsupplementation wassignificantly associated with better survival, specifically inpatients with documented deficiency.

AmJ Clin Nutr. 2011Oct;94(4):1144-9. Epub 2011 Aug 31.

Calciumand vitamin D supplements andhealth outcomes: a reanalysis of the Women's Health Initiative (WHI)limited-access data set.

BollandMJ, GreyA, GambleGD, ReidIR.

Source

Department of Medicine,University of Auckland, New Zealand. m.bolland@auckland.ac.nz

Abstract

BACKGROUND:

Frequent use of personal,nonprotocol calcium supplements obscured an adverse effect ofcoadministered calcium and vitamin D(CaD) on cardiovascular risk in the Women's Health Initiative (WHI).

OBJECTIVE:

We investigated theeffects of the use of personal calcium or vitaminD supplements on other outcomes in the WHI CaDStudy (WHI CaD) by using the WHI limited-access clinical trials dataset.

DESIGN:

The WHI CaD was a 7-y,randomized, placebo-controlled trial of CaD (1 g Ca/400 IU vitaminD daily) in 36,282 community-dwelling,postmenopausal women. The incidence of total cancer (excludingnonmelanoma skin cancers), breast and colorectal cancers, hip andtotal fracture, and mortality was assessed by using Cox proportionalhazards models.

RESULTS:

In the WHI CaD,interactions between the use of either personal calcium or vitaminD supplements and CaD were found for total,breast, and colorectal cancers but not for fracture or mortality. In15,646 women (43%) who were not taking personal calcium or vitaminD supplements at randomization, CaD significantlydecreased the risk of total, breast, and invasive breast cancers by14-20% and nonsignificantly reduced the risk of colorectal cancer by17%. In women taking personal calcium or vitaminD supplements, CaD did not alter cancer risk (HR:1.06-1.26).

CONCLUSIONS:

For women in the WHI CaDwho were not taking personal calcium or vitamin Dsupplements at randomization, CaD decreased the risk of total,breast, and colorectal cancers and did not change the risk offractures or total mortality. The nonskeletal effects of CaD may bemore important than the skeletal effects and should be consideredwhen evaluating these supplements. The WHI CaD trial is registered atclinicaltrials.gov as NCT00000611.

AmJ Clin Nutr.2007 Jun;85(6):1586-91.

VitaminD and calcium supplementation reduces cancerrisk: results of a randomized trial.

LappeJM, Travers-GustafsonD, DaviesKM, ReckerRR, HeaneyRP.

Source

Osteoporosis ResearchCenter, Creighton University, Omaha, NE 68131, [email protected]

Erratumin

Am J Clin Nutr. 2008 Mar;87(3):794.

Abstract

BACKGROUND:

Numerous observationalstudies have found supplemental calcium and vitaminD to be associated with reduced risk of commoncancers. However, interventional studies to test this effect arelacking.

OBJECTIVE:

The purpose of thisanalysis was to determine the efficacy of calcium alone and calciumplus vitamin D in reducingincident cancer risk of all types.

DESIGN:

This was a 4-y,population-based, double-blind, randomized placebo-controlled trial.The primary outcome was fracture incidence, and the principalsecondary outcome was cancer incidence. The subjects were 1179community-dwelling women randomly selected from the population ofhealthy postmenopausal women aged >55 y in a 9-county rural areaof Nebraska centered at latitude 41.4 degrees N. Subjects wererandomly assigned to receive 1400-1500 mg supplemental calcium/dalone (Ca-only), supplemental calcium plus 1100 IU vitamin D3/d (Ca +D), or placebo.

RESULTS:

When analyzed by intentionto treat, cancer incidence was lower in the Ca + D women than in theplacebo control subjects (P < 0.03). With the use of logisticregression, the unadjusted relative risks (RR) of incident cancer inthe Ca + D and Ca-only groups were 0.402 (P = 0.01) and 0.532 (P =0.06), respectively. When analysis was confined to cancers diagnosedafter the first 12 mo, RR for the Ca + D group fell to 0.232 (CI:0.09, 0.60; P < 0.005) but did not change significantly for theCa-only group. In multiple logistic regression models, both treatmentand serum 25-hydroxyvitamin D concentrations were significant,independent predictors of cancer risk.

CONCLUSIONS:

Improving calcium andvitamin D nutritional statussubstantially reduces all-cancer risk in postmenopausal women. Thistrial was registered at clinicaltrials.gov as NCT00352170.

TropMed Int Health. 2010Oct;15(10):1148-55. doi: 10.1111/j.1365-3156.2010.02578.x. Epub 2010Aug 17.

Effectsof vitamin D supplementationto children diagnosed with pneumonia in Kabul:a randomised controlled trial.

Manaseki-HollandS, QaderG, IsaqMasher M, BruceJ, ZulfMughal M, ChandramohanD, WalravenG.

Source

Aga Khan Health Services,Kabul ,Afghanistan Kabul MedicalUniversity, Kabul,Afghanistan.

Abstract

OBJECTIVES:

METHODS:

Double-blind individuallyrandomised placebo-controlled trial in an inner-city hospital inKabul, of 453 children aged1-36 months, diagnosed with non-severe or severe pneumonia at theoutpatient clinic. Children with rickets, other concurrent severediseases, very severe pneumonia or wheeze, were excluded. Childrenwere given vitamin D(3) orplacebo drops additional to routine pneumonia treatment.

RESULTS:

CONCLUSION:

A single high-dose oralvitamin D(3) supplementationto young children along with antibiotic treatment for pneumonia couldreduce the occurrence of repeat episodes of pneumonia.

JAMA.2005 May 11;293(18):2257-64.

Fractureprevention with vitamin D supplementation: a meta-analysis ofrandomized controlled trials.

Bischoff-FerrariHA, WillettWC, WongJB, GiovannucciE, DietrichT, Dawson-HughesB.

Source

Department of Nutrition,Harvard School of Public Health, Boston, Mass 02115, [email protected]

Abstract

CONTEXT:

The role and dose of oralvitamin D supplementation in nonvertebral fracture prevention havenot been well established.

OBJECTIVE:

To estimate theeffectiveness of vitamin D supplementation in preventing hip andnonvertebral fractures in older persons.

DATASOURCES:

A systematic review ofEnglish and non-English articles using MEDLINE and the CochraneControlled Trials Register (1960-2005), and EMBASE (1991-2005).Additional studies were identified by contacting clinical experts andsearching bibliographies and abstracts presented at the AmericanSociety for Bone and Mineral Research (1995-2004). Search termsincluded randomized controlled trial (RCT), controlled clinicaltrial, random allocation, double-blind method, cholecalciferol,ergocalciferol, 25-hydroxyvitamin D, fractures, humans, elderly,falls, and bone density.

STUDYSELECTION:

Only double-blind RCTs oforal vitamin D supplementation (cholecalciferol, ergocalciferol) withor without calcium supplementation vs calcium supplementation orplacebo in older persons (> or =60 years) that examined hip ornonvertebral fractures were included.

DATAEXTRACTION:

Independent extraction ofarticles by 2 authors using predefined data fields, including studyquality indicators.

DATASYNTHESIS:

All pooled analyses werebased on random-effects models. Five RCTs for hip fracture (n = 9294)and 7 RCTs for nonvertebral fracture risk (n = 9820) met ourinclusion criteria. All trials used cholecalciferol. Heterogeneityamong studies for both hip and nonvertebral fracture prevention wasobserved, which disappeared after pooling RCTs with low-dose (400IU/d) and higher-dose vitamin D (700-800 IU/d), separately. A vitaminD dose of 700 to 800 IU/d reduced the relative risk (RR) of hipfracture by 26% (3 RCTs with 5572 persons; pooled RR, 0.74; 95%confidence interval [CI], 0.61-0.88) and any nonvertebral fracture by23% (5 RCTs with 6098 persons; pooled RR, 0.77; 95% CI, 0.68-0.87) vscalcium or placebo. No significant benefit was observed for RCTs with400 IU/d vitamin D (2 RCTs with 3722 persons; pooled RR for hipfracture, 1.15; 95% CI, 0.88-1.50; and pooled RR for any nonvertebralfracture, 1.03; 95% CI, 0.86-1.24).

CONCLUSIONS:

Oral vitamin Dsupplementation between 700 to 800 IU/d appears to reduce the risk ofhip and any nonvertebral fractures in ambulatory or institutionalizedelderly persons. An oral vitamin D dose of 400 IU/d is not sufficientfor fracture prevention.

HormMetab Res. 2011 Mar;43(3):223-5.Epub 2010 Dec 10.

Effectof vitamin D supplementation on testosterone levels in men.

PilzS,FrischS,KoertkeH, KuhnJ,DreierJ,Obermayer-PietschB, WehrE,ZittermannA.

Source

Department of InternalMedicine, Division of Endocrinology and Metabolism, MedicalUniversity of Graz, Austria.

Abstract

The male reproductivetract has been identified as a target tissue for vitamin D, andprevious data suggest an association of 25-hydroxyvitamin D [25(OH)D]with testosterone levels in men. We therefore aimed to evaluatewhether vitamin D supplementation influences testosterone levels inmen. Healthy overweight men undergoing a weight reduction program whoparticipated in a randomized controlled trial were analyzed fortestosterone levels. The entire study included 200 nondiabeticsubjects, of whom 165 participants (54 men) completed the trial.Participants received either 83 μg (3,332 IU) vitamin D daily for1 year (n = 31) or placebo (n =2 3). Initial 25(OH)D concentrationswere in the deficiency range (< 50 nmol/l) and testosterone valueswere at the lower end of the reference range (9.09-55.28 nmol/l formales aged 20-49 years) in both groups. Mean circulating 25(OH)Dconcentrations increased significantly by 53.5 nmol/l in the vitaminD group, but remained almost constant in the placebo group. Comparedto baseline values, a significant increase in total testosteronelevels (from 10.7 ± 3.9 nmol/l to 13.4 ± 4.7 nmol/l; p< 0.001), bioactive testosterone (from 5.21 ± 1.87 nmol/lto 6.25 ± 2.01 nmol/l; p = 0.001), and free testosteronelevels (from 0.222 ± 0.080 nmol/l to 0.267 ± 0.087nmol/l; p = 0.001) were observed in the vitamin D supplemented group.By contrast, there was no significant change in any testosteronemeasure in the placebo group. Our results suggest that vitamin Dsupplementation might increase testosterone levels. Furtherrandomized controlled trials are warranted to confirm thishypothesis.

BrJ Nutr.2010 Feb;103(4):549-55. Epub 2009 Sep 28.

VitaminD supplementation reduces insulin resistance in South Asian womenliving in New Zealand who are insulin resistant and vitamin Ddeficient - a randomised, placebo-controlled trial.

vonHurst PR, StonehouseW, CoadJ.

Source

Institute of Food,Nutrition and Human Health, Massey University, Private Bag 102 904,North Shore Mail Centre, Auckland, New [email protected]

Abstract

Low serum25-hydroxyvitamin D (25(OH)D) has been shown to correlate withincreased risk of type 2 diabetes. Small, observational studiessuggest an action for vitamin D in improving insulin sensitivityand/or insulin secretion. The objective of the present study was toinvestigate the effect of improved vitamin D status on insulinresistance (IR), utilising randomised, controlled, double-blindintervention administering 100 microg (4000 IU) vitamin D(3) (n 42)or placebo (n 39) daily for 6 months to South Asian women, aged 23-68years, living in Auckland, New Zealand. Subjects were insulinresistant - homeostasis model assessment 1 (HOMA1)>1.93 and hadserum 25(OH)D concentration < 50 nmol/l. Exclusion criteriaincluded diabetes medication and vitamin D supplementation >25microg (1000 IU)/d. The HOMA2 computer model was used to calculateoutcomes. Median (25th, 75th percentiles) serum 25(OH)D(3) increasedsignificantly from 21 (11, 40) to 75 (55, 84) nmol/l withsupplementation. Significant improvements were seen in insulinsensitivity and IR (P = 0.003 and 0.02, respectively), and fastinginsulin decreased (P = 0.02) with supplementation compared withplacebo. There was no change in C-peptide with supplementation. IRwas most improved when endpoint serum 25(OH)D reached > or = 80nmol/l. Secondary outcome variables (lipid profile and highsensitivity C-reactive protein) were not affected by supplementation.In conclusion, improving vitamin D status in insulin resistant womenresulted in improved IR and sensitivity, but no change in insulinsecretion. Optimal vitamin D concentrations for reducing IR wereshown to be 80-119 nmol/l, providing further evidence for an increasein the recommended adequate levels. Registered Trial No.ACTRN12607000642482.

OsteoporosInt. 2010 Jul;21(7):1121-32. Epub2009 Dec 3.

Benefit-riskassessment of vitamin D supplementation.

Bischoff-FerrariHA, ShaoA, Dawson-HughesB, HathcockJ, GiovannucciE, WillettWC.

Source

Centre on Aging andMobility, Department of Rheumatology and Institute of PhysicalMedicine, University Hospital Zurich, Gloriastrasse 25, 8091, Zurich,Switzerland. [email protected]

Abstract

Current intakerecommendations of 200 to 600 IU vitamin D per day may beinsufficient for important disease outcomes reduced by vitamin D.

INTRODUCTION:

This study assessed thebenefit of higher-dose and higher achieved 25-hydroxyvitamin D levels[25(OH)D] versus any associated risk.

METHODSAND RESULTS:

Based on double-blindrandomized control trials (RCTs), eight for falls (n = 2426) and 12for non-vertebral fractures (n = 42,279), there was a significantdose-response relationship between higher-dose and higher achieved25(OH)D and greater fall and fracture prevention. Optimal benefitswere observed at the highest dose tested to date for 700 to 1000 IUvitamin D per day or mean 25(OH)D between 75 and 110 nmol/l (30-44ng/ml). Prospective cohort data on cardiovascular health andcolorectal cancer prevention suggested increased benefits with thehighest categories of 25(OH)D evaluated (median between 75 and 110nmol/l). In 25 RCTs, mean serum calcium levels were not related tooral vitamin D up to 100,000 IU per day or achieved 25(OH)D up to 643nmol/l. Mean levels of 75 to 110 nmol/l were reached in most RCTswith 1,800 to 4,000 IU vitamin D per day without risk.

CONCLUSION:

Our analysis suggests thatmean serum 25(OH)D levels of about 75 to 110 nmol/l provide optimalbenefits for all investigated endpoints without increasing healthrisks. These levels can be best obtained with oral doses in the rangeof 1,800 to 4,000 IU vitamin D per day; further work is needed,including subject and environment factors, to better define the dosesthat will achieve optimal blood levels in the large majority of thepopulation.

JBone Miner Res. 2011Oct;26(10):2341-57. doi: 10.1002/jbmr.463.

VitaminD supplementation during pregnancy: double-blind,randomized clinical trial of safety and effectiveness.

HollisBW, JohnsonD, HulseyTC, EbelingM, WagnerCL.

Source

Division of Neonatologyand Department of Obstetrics and Gynecology, Medical University ofSouth Carolina, Charleston, SC 29425, USA. [email protected]

Abstract

The need, safety, andeffectiveness of vitamin Dsupplementation during pregnancy remain controversial. In thisrandomized, controlled trial, women with a singleton pregnancy at 12to 16 weeks' gestation received 400, 2000, or 4000 IUof vitamin D(3) per day untildelivery. The primary outcome was maternal/neonatal circulating25-hydroxyvitamin D [25(OH)D] concentration at delivery, withsecondary outcomes of a 25(OH)D concentration of 80 nmol/Lor greater achieved and the 25(OH)D concentration required to achievemaximal 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] production. Ofthe 494 women enrolled, 350 women continued until delivery: Mean25(OH)D concentrations by group at delivery and 1 month beforedelivery were significantly different (p < 0.0001),and the percent who achieved sufficiency was significantly differentby group, greatest in 4000-IU group (p < 0.0001).The relative risk (RR) for achieving a concentration of 80 nmol/Lor greater within 1 month of delivery was significantly differentbetween the 2000- and the 400-IU groups (RR = 1.52,95% CI 1.24-1.86), the 4000- and the 400-IU groups (RR = 1.60,95% CI 1.32-1.95) but not between the 4000- and. 2000-IU groups(RR = 1.06,95% CI 0.93-1.19). Circulating 25(OH)D had a direct influence oncirculating 1,25(OH)(2)D(3) concentrations throughout pregnancy(p < 0.0001),with maximal production of 1,25(OH)(2)D(3) in all strata in the4000-IU group. There were no differences between groups on any safetymeasure. Not a single adverse event was attributed to vitaminD supplementation or circulating 25(OH)D levels.It is concluded that vitamin Dsupplementation of 4000 IU/dfor pregnant women is safe and most effective in achievingsufficiency in all women and their neonates regardless of race,whereas the current estimated average requirement is comparativelyineffective at achieving adequate circulating 25(OH)D concentrations,especially in African Americans.

Outcome	Conditions	Finding	Reference
All cause mortality	Mean oral in take 528 IU/d	RR = 0.93 (95% CI, 0.87-0.99)	Autier and Gandini, 2007
	daily vitamin D(3) (800 IU), calcium (1000 mg), both, or placebo for 24-62 months, with a follow-up of 3 yr after intervention	(HR) = 0.93; 95% confidence interval (CI) = 0.85-1.02]	Avenell, epub
Atopic dermatitis			Sidbury, 2008
Bone loss in winter	oral cholecalciferol (500 IU/day) and calcium (500 mg/day) during the winter months	In the subjects receiving oral vitamin D3 and calcium, lumbar and femoral BMD increased significantly (lumbar spine: +0.8%, p = 0.04 versus year 1; femoral neck: +0.1%, p = 0.05 versus year 1), whereas controls continued to lose bone (intervention group versus control group: lumbar spine, p = 0.03; femoral neck, p = 0.05).	Meier, 2004
Cancer, All	1100 IU/d, 1450 mg/d calcium	When analysis was confined to cancers diagnosed after the first 12 mo, RR for the Ca + D group fell to 0.232 (CI: 0.09, 0.60; P < 0.005) but did not change significantly for the Ca-only group.	Lappe, 2007
	daily vitamin D(3) (800 IU), calcium (1000 mg), both, or placebo for 24-62 months, with a follow-up of 3 yr after intervention	cancer mortality (HR = 0.85; 95% CI = 0.68-1.06), and cancer incidence (HR = 1.07; 95% CI = 0.92-1.25)	Avenell, epub
Breast, colorectal cancer	400 IU/d vitamin D3, 1500 mg/d or placebo	In 15,646 women (43%) who were not taking personal calcium or vitamin D supplements at randomization, CaD significantly decreased the risk of total, breast, and invasive breast cancers by 14-20% and nonsignificantly reduced the risk of colorectal cancer by 17%. In women taking personal calcium or vitamin D supplements, CaD did not alter cancer risk (HR: 1.06-1.26).	Bolland, 2011
Cardiometric	In meta-analyses of 10 trials	supplementation nonsignificantly reduced systolic blood pressure (weighted mean difference, -1.9 mm Hg [CI, -4.2 to 0.4 mm Hg]) and did not affect diastolic blood pressure (weighted mean difference, -0.1 mm Hg [CI, -0.7 to 0.5 mm Hg]).	Pittas, 2010
Cardiovascular	Vitamin D supplementation during weight loss	more pronounced decrease occurred in the vitamin D group than in the placebo group in blood concentrations of parathyroid hormone (-26.5% compared with -18.7%; P = 0.014), triglycerides (-13.5% compared with +3.0%; P < 0.001), and the inflammation marker tumor necrosis factor-alpha (-10.2% compared with -3.2%; P = 0.049).	Zittermann, 2009
Cardiovascular disease event	Pooled study	.Results of secondary analyses in 8 randomized trials showed a slight but statistically nonsignificant reduction in CVD risk (pooled relative risk, 0.90 [95% CI, 0.77 to 1.05]) with vitamin D supplementation at moderate to high doses (approximately 1000 IU/d) but not with calcium supplementation (pooled relative risk, 1.14 [CI, 0.92 to 1.41]), or a combination of vitamin D and calcium supplementation (pooled relative risk, 1.04 [CI, 0.92 to 1.18]) compared with placebo.	Wang, 2010
CVD survival		Vitamin D supplementation conferred substantial survival benefit (odds ratio for death 0.39, 95% confidence interval 0.277 to 0.534, p <0.0001).	Vacek, epub
Chronic kidney disease	Placebo or calcium (1,200 mg) and vitamin D(3) (800 IU) in fixed or separate combination. Effect on parathyroid hormone	The proportion with a 30% or greater decrease in iPTH level at 6 months was 50% in all eGFR groups on treatment versus 6% to 9% for placebo (P < 0.001 for all). The effects of the intervention on iPTH levels did not differ according to baseline eGFR (interaction P > 0.1 for all times).	Kooienga, 2009
	1000 IU/d vs. placebo	Mean 25(OH)D levels increased significantly higher in the treatment group (mean increase from baseline: 10.3+/-10.4 ng/mL vs. 0.8+/-6.8 ng/mL, p<0.0001).	Rucker, 2009
Depression	Cross-sectional study and randomized double blind controlled trial of 20,000 or 40,000 IU vitamin D per week versus placebo for 1 year.	In the two groups given vitamin D, but not in the placebo group, there was a significant improvement in BDI scores after 1 year. There was a significant decrease in serum parathyroid hormone in the two vitamin D groups without a concomitant increase in serum calcium.	Jorde, 2008
Falls, fractures	700-1000 IU/d	Pooled RR = 0.81 (95% CI 0.71 to 0.92) No effect for 400 IU/d	Bischoff-Ferrari, 2009b
Falls	Our study population consisted of 242 individuals recruited by advertisements and mailing lists (mean [ +/- SD] age, 77 +/- 4 years). All serum 25-hydroxyvitamin D (25[OH]D) levels were below 78 nmol/l. Individuals received in a double blinded fashion either 1000 mg of calcium or 1000 mg of calcium plus 800 IU of vitamin D per day over a treatment period of 12 months, which was followed by a treatment-free but still blinded observation period of 8 months.	Compared to calcium mono, supplementation with calcium plus vitamin D resulted in a significant decrease in the number of subjects with first falls of 27% at month 12 (RR = 0.73; CI = 0.54-0.96) and 39% at month 20 (RR = 0.61; CI = 0.34-0.76). Concerning secondary endpoints, we observed significant improvements in quadriceps strength of 8%, a decrease in body sway of 28%, and a decrease in time needed to perform the TUG test of 11%.	Pfeifer, 2009
Non-vertebrate fractures	700-1000 IU/d	pooled RR was 0.80 (95% CI, 0.72-0.89;	Bischoff-Ferrari, 2009a
Gastric bypass	We evaluated three doses of vitamin D3 (800, 2,000, and 5,000 IU/day) in a prospective, randomized pilot trial of 45 patients undergoing Roux-en-Y gastric bypass.	At 12 months, the 800-, 2,000-, and 5,000-IU groups had a mean +/- SD increase in 25OHD of 27.5 +/- 40.0, 60.2 +/- 37.4, and 66.1 +/- 42.2 nmol/L, respectively (p = 0.09) with a maximum increase in each group of 87.4, 114.8, and 129.8 nmol/L. Forty-four percent, 78%, and 70% achieved 25OHD levels >or=75 nmol/L (p = 0.38).	Goldner, 2009
Glucose (fasting plasma) (FPG)	A total of 314 Caucasian adults without diabetes received either 500 mg calcium citrate and 700 IU vitamin D(3) or placebos daily for 3 years in a double-blind, randomized, controlled trial designed for bone-related outcomes.	Among participants with IFG at baseline, those who took combined calcium-vitamin D supplements had a lower rise in FPG at 3 years compared with those on placebo (0.02 mmol/l [0.4 mg/dl] vs. 0.34 mmol/l [6.1 mg/dl], respectively, P = 0.042) and a lower increase in HOMA-IR (0.05 vs. 0.91, P = 0.031).	Pitas, 2007
Haemodialysis	HD patients were included in this study if their serum 25(OH)D level was <75 mmol/L. Oral 25(OH)D(3) was administered daily at 10-30 microg/day based on the severity of the deficiency.	After 6 months of treatment [mean daily 25(OH)D(3): 16 +/- 5 microg/day], the serum 25(OH)D level increased (30 +/- 19 to 126 +/- 46 nmol/ L, P < 0.001), with 13% of patients in group 1, 57% in group 2 and 30% in group 3. The serum intact parathyroid hormone (iPTH) level decreased (235 +/- 186 to 189 +/- 137 pg/mL, P = 0.05), except in group 1. Bone alkaline phosphatase (BALP) showed a tendency to normalize (23 +/- 16 to 18.3 +/- 11 microg/L, P < 0.05), leading to a decrease in alfacalcidol administration from 66% to 43% (P < 0.05), except in group 1. The KDOQI targets achieved increased significantly for serum calcium (76% to 85%) and phosphate levels (66% to 77%) in all patients. The serum albumin level increased in all groups (34.6 +/- 4 to 36.8 +/- 4 g/L, P < 0.05), without any significant improvement in normalized protein catabolic rate (nPCR) or C-reactive proteins (CRP).	Jean, 2008
Heart failure, congestive	either 50 mug vitamin D(3)/d plus 500 mg Ca/d [D(+) group] or placebo plus 500 mg Ca/d [D(-) group] for 9 mo	Compared with baseline, parathyroid hormone was significantly lower and the antiinflammatory cytokine interleukin 10 was significantly higher in the D(+) group after 9 mo. The proinflammatory cytokine tumor necrosis factor alpha increased in the D(-) group but remained constant in the D(+) group. The survival rate did not differ significantly between the study groups during the follow-up period.	Schleithoff, 2006
Infectious diseases			Yamshchikov, 2009
Infections, symptomatic upper respiratory tract	50 microg vitamin D3 (2000 IU) daily or matching placebo for 12 weeks.	The mean 25-hydroxyvitamin D level at baseline was similar in both groups (64.3+/-25.4 nmol/l in the vitamin D group; 63.0+/-25.8 nmol/l in the placebo group; n.s.). After 12 weeks, 25-hydroxyvitamin D levels increased significantly to 88.5+/-23.2 nmol/l in the vitamin D group, whereas there was no change in vitamin D levels in the placebo group. There was no benefit of vitamin D3 supplementation in decreasing the incidence or severity of symptomatic URIs during winter.	Li-Ng, 2009
Influenza	800 or 2000 IU/d	40 or 90% reduction	Aloia & Li-Ng, 2007
Influenza type A	1100 IU/d, no other oral intake	RR: 0.36; 95% CI: 0.17, 0.79; P = 0.006 No effect for type B	Urashima, 2010
Insulin sensitivity	120,000 IU/fortnight	Seventy-one of the recruited subjects completed the study (35 in supplemented group, 36 in control group). There was an increase in oral glucose insulin sensitivity (OGIS) with supplementation by per protocol analysis (P = 0.038; intention-to-treat analysis P = 0.055). The age- and baseline 25-hydroxyvitamin D level-adjusted difference in change in OGIS was highly significant (mean difference 41.1 +/- 15.5; P = 0.01). No changes in secondary outcome measures (insulin secretion, basal indices of insulin sensitivity, blood pressure or lipid profile) were found with supplementation.	Nagpal, 2009
	double-blind intervention administering 100 microg (4000 IU) vitamin D(3) (n 42) or placebo (n 39) daily for 6 months to South Asian women, aged 23-68 years, living in Auckland, New Zealand	Significant improvements were seen in insulin sensitivity and IR (P = 0.003 and 0.02, respectively), and fasting insulin decreased (P = 0.02) with supplementation compared with placebo.	Von hurst, 2010
	participants with low serum 25(OH)D levels were thereafter randomized to receive capsules of 20,000 IU vitamin D(3) or identical-looking placebo twice weekly for 6 months.	The 52 participants with high serum 25(OH)D levels (85.6 ± 13.5 nmol/L [mean ± SD]) had significantly higher insulin sensitivity index (ISI) and lower HbA(1c) and triglycerides (TGs) than the 108 participants with low serum 25(OH)D (40.3 ± 12.8 nmol/L), but the differences in ISI and TGs were not significant after adjustments. After supplementation, serum 25(OH)D was 142.7 ± 25.7 and 42.9 ± 17.3 nmol/L in 49 of 51 completing participants randomized to vitamin D and 45 of 53 randomized to placebo, respectively. At the end of the study, there were no statistically significant differences in the outcome variables between the two groups.	Grimnes, 2011
	cholecalciferol (2000 IU once daily) or calcium carbonate (400 mg twice daily) for 16 wk.	The disposition index increased in the vitamin D group and decreased in the no-vitamin D group (adjusted mean change ± SE: 300 ± 130 compared with -126 ± 127, respectively; P = 0.011), which was explained by an improvement in insulin secretion (62 ± 39 compared with -36 ± 37 mU · L(-1) · min, respectively; P = 0.046). Hb A(1c) increased less, but nonsignificantly, in the vitamin D group than in the no-vitamin D group (0.06 ± 0.03% compared with 0.14 ± 0.03%, respectively; P = 0.081).	Mitri, 2011
Muscle strength	6-month supplementation (December to May) of daily calcium plus monthly placebo (calcium/placebo group) or daily calcium plus oral cholecalciferol (150,000 IU once a month during the first 2 months, followed by 90,000 IU once a month for the last 4 months; calcium/vitamin D group)	SHF was increased in the calcium/vitamin D group by 16.4% (p = 0.0001) and SKE by 24.6% (p = 0.0007). [strength of hip flexors (SHF) and knee extensors (SKE)]	Moreira-Pfrimer, 2009
	800 or 1600 IU/d plus vibration	Same improvements with both doses	Verschueren, 2011
Musculoskeletal parameters	One hundred seventy-nine girls, ages 10-17 yr, were randomly assigned to receive weekly oral vitamin D doses of 1,400 IU (equivalent to 200 IU/d) or 14,000 IU (equivalent to 2,000 IU/d) in a double-blind, placebo-controlled, 1-yr protocol.	In the overall group of girls, lean mass increased significantly in both treatment groups (P < or = 0.05); bone area and total hip BMC increased in the high-dose group (P < 0.02). In premenarcheal girls, lean mass increased significantly in both treatment groups, and there were consistent trends for increments in BMD and/or BMC at several skeletal sites, reaching significance at lumbar spine BMD in the low-dose group and at the trochanter BMC in both treatment groups. There was no significant change in lean mass, BMD, or BMC in postmenarcheal girls.	El-Hajj, 2006
Multiple sclerosis	6000 IU/d vitamin D2 vs. 1000 IU/d vitamin D2	There were 4 relapses with high-dose D2 vs none with low-dose D2 (p = 0.04).	Stein, 2011
Neuromuscular	8400 IU/week	significantly reduced sway compared with treatment with placebo (P = 0.047) in patients with elevated baseline sway but not in patients with normal baseline sway.	Lips, 2010
Physical performance		gait speed was higher among subjects supplemented with vitamin (whether trained or not) than in non-supplemented subjects (838+/-147 and 768+/-127 m/12 min, respectively, p=0.02).	Bunout, 2006
Pneumonia	Children, 100,000 IU once	Children in the vitamin D(3) group survived longer without experiencing a repeat episode (72 days vs. 59 days; HR 0.71; 95% CI 0.53-0.95; P = 0.02).	Manaseki-Holland, 2010
	Oral vitamin D (1000 IU for <1 year and 2000 IU for >1 year) (n=100) or placebo (lactose) (n=100) once a day for 5 days, from enrolment.	Median duration (SE, 95% CI) of resolution of severe pneumonia was similar in the two groups [vitamin D: 72 (3.7, 64.7-79.3) hours; placebo: 64 (4.5, 55.2-72.8)hours]. Duration of hospitalization and time to resolution of tachypnea, chest retractions, and inability to feed were also comparable between the two groups.	Choudhary & Gupta, 2011
Pregnancy	4000 IU/d	No adverse effects on serum or urine calcium	Hollis, 2011
Stress fractures	Navy females, 800 IU/d, 2000 mg/d calcium	21% lower incidence	Lappe, 2008
Testosterone	Participants received either 83 μg (3,332 IU) vitamin D daily for 1 year (n = 31) or placebo (n =2 3).	Compared to baseline values, a significant increase in total testosterone levels (from 10.7 ± 3.9 nmol/l to 13.4 ± 4.7 nmol/l; p < 0.001), bioactive testosterone (from 5.21 ± 1.87 nmol/l to 6.25 ± 2.01 nmol/l; p = 0.001), and free testosterone levels (from 0.222 ± 0.080 nmol/l to 0.267 ± 0.087 nmol/l; p = 0.001) were observed in the vitamin D supplemented group. By contrast, there was no significant change in any testosterone measure in the placebo group	Pilz, 2011
Tooth loss	Elderly, taking supplements or not	During the randomized trial, 11 of the 82 subjects (13%) taking supplements and 17 of the 63 subjects (27%) taking placebo lost one or more teeth (OR = 0.4; 95% CI: 0.2 to 0.9).	Krall, 2001
Tuberculosis	The subjects were randomised to receive vitamin D (0.25 mg/day) or placebo in a double blind method, during the 6th initial week of Tb treatment.	One hundred percent of the vitamin D group and only 76.7% of the placebo group had sputum conversion. This difference is statistically significant (p=0.002).	Nursyam, 2006
	The intervention was 100,000 IU of cholecalciferol or placebo at inclusion and again 5 and 8 months after the start of treatment.	Overall mortality was 15% (54 of 365) at 1 year of follow-up and similar in both arms (30 of 187 for vitamin D treated and 24 of 178 for placebo; relative risk, 1.19 [0.58-1.95]).	Wejse, 2009
	A single oral dose of 2.5 mg (100,000 IU) vitamin D	significantly enhanced the ability of participants' whole blood to restrict BCG-lux luminescence in vitro without affecting antigen-stimulated IFN-gamma responses.	Martineau, 2011

Review of Vitamin D trials - Grant Jan 2012

This web page consists of 3 sections

CLICK HERE for Nov 2012 update

See also by Dr. Grant

Fallprevention with supplemental and active forms of vitamin D: ameta-analysis of randomised controlled trials.

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Highserum 25-hydroxyvitamin D is associated with a low incidence ofstress fractures.

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VitaminD supplementation and total mortality: a meta-analysis of randomizedcontrolled trials.

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VitaminD supplementation enhances the beneficial effects of weight loss oncardiovascular disease risk markers.

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Calciumand vitamin d supplementation decreases incidence of stress fracturesin female navy recruits.

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Randomizedtrial of vitamin Dsupplementation to prevent seasonal influenza A in schoolchildren.

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VitaminD With or Without Calcium Supplementation for Prevention of Cancerand Fractures: An Updated Meta-analysis for the U.S. PreventiveServices Task Force.

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Effectsof vitamin D supplementationto children diagnosed with pneumonia in Kabul: a randomisedcontrolled trial.

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Systematicreview: Vitamin D and cardiometabolic outcomes.

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Preventionof nonvertebral fractures with oral vitamin D and dose dependency: ameta-analysis of randomized controlled trials.

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VitaminD(3) is more potent than vitaminD(2) in humans.

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