trial and obese women: A double blind randomized controlledclinical Effect of vitamin D supplementation on anthropometric indices amongoverweight Diabetes & Metabolic Syndrome: Clinical Research &Reviews

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Original Article

Effect of vitamin D supplementation on anthropometric indices among overweight and obese women: A double blind randomized controlled clinical trial

Sajjad Roosta

^a

, Mina Kharadmand

^b

, Farshad Teymoori

^c

, Mehdi Birjandi

^d

, Ahmad Adine

^e

, Ebrahim Falahi

^f,

*

aStudentResearchCommittee,SchoolofHealthandNutrition,LorestanUniversityofMedicalSciences,Khorramabad,IslamicRepublicofIran

bSchoolofMedicine,LorestanUniversityofMedicalSciences,Khorramabad,IslamicRepublicofIran

cNutritionandEndocrineResearchCenter,ResearchInstituteforEndocrineSciences,ShaheedBeheshtiUniversityofMedicalSciences,Tehran, IslamicRepublicofIran

dSchoolofHealthandNutrition,LorestanUniversityofMedicalSciences,Khorramabad,IslamicRepublicofIran

eDeputyofFoodandDrug,LorestanUniversityofMedicalSciences,Khorramabad,IslamicRepublicofIran

fNutritionalHealthResearchCenter,LorestanUniversityofMedicalSciences,Khorramabad,IslamicRepublicofIran

ARTICLE INFO

Keywords:

Obesity Overweight VitaminD

Anthropometricindices Weight

Waistcircumferences

ABSTRACT

Aims:TheaimofthisstudywastoinvestigateeffectofvitaminDsupplementationonanthropometric indicesamongwomenwithoverweightandobesity.

Methods:Thisdoubleblindrandomizeclinicaltrialwasconductedon66overweightandobesewomen.

ThoseininterventiongroupreceivedoralsupplementofvitaminD50,000IU(1250mcg)per25dayand incontrolgroupparticipantsreceivedplacebofor3months.Anthropometricindicesweremeasured beforeandafter3monthsintervention.Beforetheinterventiona24-hdietaryrecall(3days)wereusedto assessdietaryintakeofindividuals.Independentttestandmultivariaterepeatedmeasurewereusedto dataanalysis.

Results:Themeandifferenceofanthropometricindices,serumcalcium,25(OH)D3andserumPTH between the intervention and control groups were signiﬁcant (P<0/05). However, no signiﬁcant differencesinserumphosphorusbetweentheinterventionandcontrolgroupswereseen.

Conclusion:SupplementationwithvitaminD50m^g^forêach^day^for³^months^resultedⁱⁿâsignificant reductioninanthropometricindicesinwomenwithobesityandoverweightwithnormalprimary25(OH) D3serumlevels.

1.Introduction

Obesity,whichisdeﬁnedastheextraaccumulationoffatin body,canincreasetheriskofmanydiseasessuchascardiovas- culardisease,bloodlipiddisorders,typeIIdiabetesmellitus,and hypertension[1–3].In Iranbytheyear2013 theprevalenceof overweightandobesityhasbeenreportedas38.8%and10.2%for maleand34.5%and18.5%forfemalerespectively[4].Becauseof vitaminDstorage in deeppartsof fat massesin obesepeople which can make difﬁcult releasing this vitamin into blood circulation,obesitydecreasethevitaminDserumlevelinthose people[5].Theassociationbetweenincreasedbodymassindex

(BMI)andlowserum25-hydroxyvitaminDreportedinprevious studies [6–8]. Obesity leads to low serumvitamin D (OH) 25 followed by secondary hyperparathyroidism [9–11]. Increased intracellularcalciumbyPTHleadstoinhibitionoflipolysisand stimulating the fatty acid synthesis and consequently lipid accumulation in adipocyte will increase [12,13]. In the other hand, based on somestudies, treatment by vitaminD supple- mentationthrough thefacilitationofthecalciumentranceinto adipocytecanstimulatelipogenesisandaccumulationof fat in body [14,15].Therefore, the role of vitamin D in body weight regulationisunclear,asseveralstudieshavedemonstratedusing of vitamin D supplementation cause to weight loss in obese people,whereassomestudiesshownoeffect[16,17].Regarding this point both healthy and vitamin D deﬁcientsubjects have participated inpreviousstudiesit mightaffected theresultsof study,sinceitis possiblethatvitaminDsupplementationonly

* Correspondingauthor.

E-mailaddress:[email protected](E.Falahi).

https://doi.org/10.1016/j.dsx.2018.03.022

ContentslistsavailableatScienceDirect

Diabetes & Metabolic Syndrome: Clinical Research &

Reviews

j o u r n a lh o m e p ag e : w w w . e l s e vi e r . c o m / l o c a t e / d s x

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cause to improve of vitamin deﬁciency and rebuilding of its supply,anddoesn’tshowtheexpectedeffectonanthropometric indices.Therefore,accordingtowhatwasmentioned,thepurpose ofthisstudyistodeterminetheeffectofvitaminDsupplemen- tationonbodyweight,BMI,serumlevelsofcalcium,phosphorus, vitaminD,andPTH hormonein overweightandobese women withnormallevelofserumvitaminD.

2.Subjects,materialsandmethods

This study was conducted as a controlled double blind randomizedclinicaltrial.ThesamplesizewascalculatedbyType Ierror(

a

⁾⁼^0.05,^Type^II^error⁽

b

⁾ând êffect^size⁼^0.6^for êach

groupequalto38individuals.Subjectswereselectedvoluntarily throughadvertisementonhospital,clinicandmedicalcollegesand among overweight and obese women visited the specialty nutritionclinicsofKhorramabadShahidRahimihospital.

TheeligiblecriteriawereBMIover25kg/m²andtheageranging from18to70yearsold.The exclusioncriteriawere:history of diseasessuchasbonediseases,diabetes,thyroiddiseases,kidney orliverdiseases,cardiovasculardisease,alsoconsumingvitamins andminerals,consuminganticonvulsantdrugs,drugscontaining estrogen and progesterone, corticosteroids, having special diet, hormonaltherapyandweightlossto10%withinthethreemonths beforestudy.Atthebeginningofthestudyanefﬁcient medical history including the history of heart diseases and consuming drugswas done.Thecriteria forinclusion andexclusiontothis studywereconsidered.Then,heightandweightweremeasured and body mass index was calculated. After conﬁrming the overweightandobesityinthesesubjects,otheranthropometric indicesincludingwaistandhipcircumferencealsoweremeasured.

Subject’sbloodsampleswerecollectedafter12hfastingand serum25-hydroxyvitamin D3levelsweredetermined for allof them.ThosewhohadvitaminDdeﬁciency(serumvitaminDlevels

<30ng/mL)wereexcludedandwereintroducedtoendocrinolo- gistfortreatment.InsubjectswithserumvitaminD30ng/mL, otherrequiredvariablesincludingserumcalcium,serumphosphor and PTH hormone were measured by using the same blood samples.

SubjectshavingvitaminDdeﬁciencywerecalledandconsulted about their treatment. Among 210 referred participants, 76 subjectswhomettheaboveinclusioncriteriawereselectedand randomlydivided intotwo groups;vitamin Dsupplementation groupandplacebogroup.TheinterventiongrouptookvitaminD supplementationin theformof pearls50,000UI colecalciferol, onceper25daysinfourdifferentdoses.Theplacebogrouptook placeboforthreemonth(fromthebeginningofSeptembertothe beginning of December 2013). To get assured from using the supplementationandplaceboinappointedtime,thesubjectswere called.

The subjects in control group received placebo containing lactoseexactlythesameasthepearlsofvitaminDinsize,form, packingandname.Thenumberofconsumingand timespanof usingtheplaceboincontrolgroupwasexactlythesameaspearl vitaminin interventiongroup.At thebeginningof thestudy, a dietaryintakedatawascollectedwith3day24-hdietaryrecall (including 2 weekdays and 1 weekend).The dietarydata were convertedtoenergyandnutrientsusingthesoftwareNutritionist IV(version4.1,1997;FirstDataBank,TheHearstCorporation,San Bruno,CA).

2.1.Blindingmethod

Bothresearchersandparticipantsdidnotknowaboutalloca- tionintreatmentgroup.

After3monthsintervention,biochemicalandanthropometric indiceswererecalculated.

ThestudywasconﬁrmedintheCommitteeofEthicsofLorestan medicaluniversity.Alsowritteninformedconsentwasobtained fromparticipants.

2.2.Measuringthevariables

Aboutanthropometric data; weightwas calculated withthe leastclothingandwithoutshoesbySecascalewiththeprecisionof 0.1kg and height was measured by Seca stadiometer, without shoes and in standing positionwhile the shoulders were in a normalposition.BMIwascalculatedthroughdividingtheweight tothesquareofheight(kg/m²).Waistcircumference(WC)atthe levelofumbilicusandhipcircumferenceatthepointofmaximum circumferenceoverthebuttockweremeasuredincentimetersby usinganon-stretchtapemeter.Allmeasurementswererecorded withtheprecisionof0.1cm.

Formeasuringbiochemicaldata,after12hovernightfasting, 10ccveinbloodswastakenfromallparticipantsatbaselineand after intervention. The serum of received blood samples were segregatedaftercentrifugingfor10minat3000rpm.Theserum samples were kept at 70C for biochemical measurement of 25-hydroxyvitaminD,PTH, calcium,phosphorand lipidproﬁle.

Measuringserum25-hydroxyvitaminDlevelswasdoneviaELISA (Enzyme-LinkedImmunosorbentAssay)andbyIDSkit(25.OH.D.

EIA.KIT. IDS.UK). MeasurementofParathyroidhormoneserum levelswasdoneviaELISAandbyHOSOTkitmadefromNovin- AzmaCo.

Calciumand phosphorusserum levelwasmeasured through colorimetricmethodandbytheParsAzmoonCo.kits(Tehran,Iran) and via TB autoanalyser machine. Data analysis performed by Statistical Package for Social Sciences (SPSS version 19). To comparethe MeansofBMI in interventionand controlgroups, independentt-test,andtocomparetheseindicesbeforeandafter treatment in each group ANCOVA were used. P<0.05 was consideredstatisticallysigniﬁcance.

This clinical trial was recorded in IRCT (Iranian Registryof Clinical Trial). The registry code of this study is IRCT2013072814195N1.

3.Results

Duringthestudyfoursubjects,oneforpregnancy&threefor personalreasonswithdrewfromtheinterventiongroup.Alsosix subjectswithdrewforpersonalproblemsinplacebogroup.Finally, 34subjectsininterventiongroupand32subjectsincontrolgroup continuedtheircooperationforthreemonths.Nosideeffectsfor vitamin D supplementation or lactose-contained placebo were reportedinthisstudy.Table1showsthebaselinecharacteristicsof studyparticipants.Datahadshownnodifferenceintheaverage intakeofprotein,vitaminD,calciumandphosphorbetweentwo groups.However,theaverageintakeofenergyandfatinvitaminD groupweresigniﬁcantlyhigherthancontrolgroup(Table1).

MeansSDofanthropometricandbiochemicalindicesinboth groups before and after treatment, and anthropometric and biochemicalindiceschangesbetweenvitaminDgroupandplacebo group are presented in Table2. For assessing the interaction betweenweightandenergyintakeineachgroupaftertreatment the regression analyses was used. Since the interactionwasn’t signiﬁcant(P=0.17),analysisofcovariancewasusedforremove theeffectofenergyintakeintwogroups.Accordingtotheresults ofthisanalysisandafteradjustingofenergyintakeinbothgroups, themeanweightofthetwogroupsaftervitaminDandplacebo intakewasn’tstatisticallysigniﬁcant(P=0.72).

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AlsoaftershowingnosignificanceinteractionbetweenBMIand energy intake (P=0.55), analysis of covariance was done for adjustingtheeffectofenergyintakeintwogroups,resultsshowno significantdifferenceformeanBMIaftertreatmentinvitaminD andplacebogroups(P=0.74).Toevaluateofinteractionbetween weight and fat intake after intervention in each group, the regressionanalysesforbeinghomogenizedwasconducted,Since interactionwasn’tsignificant(P=0.17),analysisofcovariancewas usedforadjustingtheeffectoffatintakefortwogroups,results demonstratethattherewasnostatisticallysignificantdifference (P=0.56)forthemeanweightoftwogroupsaftervitaminDand placebointake.AsinteractionbetweenBMIandfatintakewasn’t significant(P=0.59),foradjustingtheeffectoffatintakeintwo groups,analysisofcovariance wasusedand results indicateno significantdifference(P=0.49)forthemeanofBMIaftervitaminD andplacebointake.

4.Discussion

Inthisstudy,anthropometricindicessuchasweight,waistand hip circumference and BMI were signiﬁcantly reduced in interventiongroupcomparedwiththeplacebo group.Theoreti- cally, vitamin D affects weight through different mechanisms.

Variousclinicalstudiesindicatethereductionriskofoverweight byincreasingthecalciumintakes[18],whilstvitaminDincreases theabsorptionofcalciumfromintestine.Incontrast,theprevious studieshaveprovedthatPTHhormoneleadstotheaccumulation of adipose tissue in body through increasing the intercellular absorption of calcium, whilst supplementation withvitamin D leads to reduction of serum PTH [12]. Alsoit was shown that Supplementation with vitamin D via increasing the 1,25- dihydroxyvitaminDcausestheelevatingofintercellularabsorp- tionofcalciumandthereforecanculminatetooverweight[19].

Zittermanetal.assessedtheeffectofvitaminD(83

m

^g^per^day)

comparingtoaplaceboonweightlossandriskofcardiovascular diseasesinoverweightsubjects.Thedurationofthisclinicaltrial was12months.Attheend,theresultsdemonstratedthatalthough weightlosswasn’tclearlyinfluencedbyvitaminDsupplementa- tion,butwaistcircumferencewasovertlydecreased(from101to 96.2cm) in intervention group [20]. Also in our study, waist circumferencewasovertlyreduced after3monthstreatmentin interventiongroupthatthisfindingisinagreementwithZitter- mans etal.Zitterman'sstudywas doneonoverweightsubjects with the serum 25-hydroxyvitamin D levels 12ng/ml, whilst the participantsin our studyhad novitamin D deficiency and the average amount of their serum 25-hydroxyvitamin D was Table2

ComparisonofmeananthropometricindicesandbiochemicalchangesinvitaminDgroupandplacebogroupbeforeandafterintervention.^a Beforeintervention

(MeanSD)

Afterintervention (MeanSD)

Change Pwithinthe groups

Pbetweenthegroups

Weight(kg) VitaminD

group

81.149.14 78.319.16 3.131.62 <0.001 <0.001

Placebogroup 78.0510.35 77.9110.36 0.141.06 0.46

Waistcircumference (cm)

VitaminD group

102.069.81 100.1510.30 1.911.70 <0.001 <0.001

Placebogroup 100.269.83 100.3110.06 0.051.04 0.80

BMI(kg/m²) VitaminD group

31.833.61 30.613.60 1.230.65 <0.001 <0.001

Placebogroup 30.593.36 30.543.40 0.050.41 0.49

25(OH)D3(ng/ml) VitaminD group

73.635.6 92.834.9 19.210.5 0.0001 <0.001

Placebogroup 69.845.9 53.545.8 16.218 0.0001

PTH(pmol/L) VitaminD

group

41.216.8 39.922.2 1.2711.4 0.52 P<0.001

Placebogroup 38.213.8 47.512.4 12.4414.45 0.001

SerumCa(mg/dl) VitaminD group

9.250.41 9.320.39 0.070.27 0.15 0.02

Placebogroup 9.260.30 9.150.29 0.110.28 0.03

SerumP(mg/dl) VitaminD group

3.790.35 4.010.27 0.220.26 <0.001 0.94

Placebogroup 3.750.33 3.980.67 0.2350 0.01

aMultivariaterepeatedmeasurewasused.

Table1

PrimaryinformationofVitaminDgroupandplacebogroup.

Indices VitaminDreceiverSDMeanN=34 PlaceboreceiverSDMeanN=32 P

Age(year) 4112 389 0.12

Weight(kg) 81.49.1 78.010.4 0.16

Waistcircumference(cm) 1029.8 100.39.8 0.46

Hipcircumference(cm) 111.98.1 110.57.5 0.45

BMI(kg/m²) 31.83.6 30.583.4 0.15

25(OH)D3(ng/ml) 73.635.6 69.845.9 0.71

SerumParathormone(pmol/L) 41.216.8 38.213.8 0.44

SerumCalcium(ml/dl) 9.30.4 9.20.3 0.97

SerumPhosphor(ml/dl) 3.80.4 3.70.3 0.7

Receivedenergy(kcal) 2324.8395.9 2053.3386.9 0.006

Receivedprotein(gr) 85.615.4 80.223.6 0.27

ReceivedFat(gr) 98.732.7 77.820.2 0.003

Receivedcalcium(mg) 1306.1242.9 1270.6365.7 0.64

ReceivedvitaminD(m^g) ^1.41 1.82.5 0.14

Receivedphosphor(mg) 853330.4 986.2391.3 0.13

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73.56ng/mlbeforethestudy.Itcanbethereasonforthelackof weightloss in Zitterman's study in response tothe vitamin D supplementationisagainstthecurrentstudy.

Inanotherstudy,Mahdavietal.assessedtheeffectofvitaminD supplementation on serum leptin levels and the amount and compositionofbodyfaton53diabeticpatientsduring12weeks.

They used of 400 IU vitamin D with 1000mg calcium for supplementation.Attheendofstudy,BMIininterventiongroup reducedfrom27.28.5to26.28.3,and incontrolgroupBMI increasedjust a bit, but there wasn’tany signiﬁcant difference beforeand after treatmentneitherwithin nor betweengroups [21].Inourstudy,BMIandweightdecreasedsigniﬁcantlyafter3 monthsin interventiongroup.The difference in theamountof receivedvitaminDsupplementationcanjustifytheoutcomesin bothstudies.It’salsomerittomentionthatourstudywasdoneon more subjects and without any background diseases that can justifywhytheresultsofthesetwostudiesaredifferent.

The effect of vitamin D supplementation on weight and adiposetissue investigated bySalehpoor et al., and77 partic- ipantswererandomlydividedintovitaminD(25

m

^g^per^day)^and

controlgroup(placebo)for12weeks.Attheendofintervention, weight loss in vitamin D group and control group were ( 0.31.5) and (– 0.11.7) respectively. But, there wasn’t statisticallysigniﬁcantdifferencebetweenthetwogroups.They alsofoundthat waistcircumference wasreducedin vitaminD group but increased in control group, for Hip circumference;

although decreased in vitamin D group, but there was not signiﬁcantdifferencebeforeandafterintervention.Theirresults indicatedthat vitaminD supplementation (daily intake for 12 weeks)doesn’taffectwaist andhipcircumference[22].Inour study,therewasa statisticallyobvious difference betweenthe two groups in weight and waist and hip circumference. One reasonforthedifferencebetweenthesetwostudiescanbethe lowerdoseofvitaminDassupplementationinSalehpoor'sstudy, whereasthevitaminDdoseistwotimesmoreinourstudy.Also theparticipantsinSalehpoor'sstudyhadtheaverageserum25- hydroxyvitamin D levels=16.72

m

^g/ml ^and ^were ^vitamin ^D

deﬁcient.Buttheparticipantsinourstudyhad normalvitamin Dlevel(73.56

m

^g/ml).^It^seems^that^vitamin^Dsupplementation hasmoreeffectsonweightlossinparticipantswithnormalserum levelsof25-hydroxyvitaminD.

InstudythatconductedbySneveetal.theeffectofvitaminD andcalciumsupplementationonweightlossin334overweight andobesesubjectsassessed.Inthisstudy20,000IUvitaminDwith 500mgcalciumwasusedtwiceaweekandfor12months.Atthe end,therewasn’tanysignificantdifferenceinweight,waistandhip circumference before and after treatment in both groups. The serum levels of 25-hydroxyvitamin D increased and PTH level decreasedininterventiongroup,butserumcalciumdidnotchange [14].ParticipantsinSneve'setal.studyhadtheaverageofserum 25-hydroxyvitaminDlevelsequalto53.116.9beforetreatment that wasn’t in normal range (less than normal) whereas participantsin ourstudyhad normalserum25-hydroxyvitamin Dlevels.Duetothisfindingitseemsthatweightgainoccurredin vitaminDdeficiencystatus.

Caan et al.in a controlleddouble blindrandomizedclinical trial,evaluatetheeffectofcalciumandvitaminDsupplementa- tionanthropometric indicesof50–79yearsold women.Inthis study400IUvitaminDwasusedwith1000mgcalciumperday.

After three years treatment, women in intervention group showed a little but desirable and stable change in weight compared with the control group (average change = 0.13;

P=0.001).Thenparticipantswerefollowedfor 7years; women withlowerage(50–54)hadthemost weightgain(2.1kg) and were the only group which permanently had weight gain. In contrast older women (70–79) were the only group who had

weight loss permanently and had the most changes in their weight( 2.5kg).Generally,women’sweightincreaseduntilthe ageof60a littlebutpermanently,then itwould beﬁxedfora periodoftimeandthenagaindecreasedfromthemiddletothe end of 60sand will becontinued tothe 70s. As a result the interventiongrouphadlessweighingthanthecontrolgroupand weren’tattheriskofbeingoverweight[23].Regardingtotime periodofourstudywhichlastedafterthreemonths,ifourstudy continuedthe same results could be achieved similar toCaan studybetweeninterventionandcontrolgroups.

Tocontrolthedietaryintakeduringthecurrentstudy,foreach personprescribedowndietandforassessingthedietadherence, theywereaskedand theiranswerbasicallywaspositive.Itwas askedfrom participantstohavethe samephysical activitiesas beforetreatment.Insubsequentvisiting,participantswereasked about increasingor decreasing theirphysical activities, sothat thosewithchangewerebeenomittedfromthestudy.

Somelimitationofthisstudyinclude:thelackofanypractical supervisiononparticipantsaboutalterationsintheirlifestylesand adherencetotheirprescribeddiet,andanotherlimitationisthat our population study weren’t checked about their sunlight exposure.

Ourdataindicatethatdailysupplementationof50

m

^g^Vitamin

Dfor3monthsleadstoasignificantreductioninweight,BMI,waist and hip circumference and weight-hip ratio in obese and overweightwomenwithnormalserumlevelsof25-hydroxyvita- minD.wealsofoundasignificantincreasingofserumcalciumand serum25-hydroxyvitaminD,anda significantreductioninPTH hormonelevelattheendofstudy.

Conﬂictsofinterest None.

Acknowledgments

The authors express appreciation to Lorestan University of Medical Sciences Deputy of Research and Technology for fund supportofthisstudy;alsowethankthealloftheparticipantsfor theirparticipationinthisresearch.

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