Abstract

A multivitamin and mineral supplementation study of 6 weeks was conducted with male and female mice. The control group received a standard dose of vitamins and minerals of 1× the Recommended Daily Intake (RDI), whereas a second group received 3× RDI. A third group received a high dose of vitamin E (25× RDI), close to the upper limit of toxicity (UL), but still recommended and considered to be harmless and beneficial. The high dose of vitamin E caused a number of beneficial, but also adverse effects. Different biomarkers of tissue toxicity, oxidative stress related processes and inflammation were determined. These biomarkers did not change in plasma and erythrocytes to a large extent. In the liver of male mice, some beneficial effects were observed by a lower concentration of several biomarkers of inflammation. However, in the kidney of male mice, a number of biomarkers increased substantially with the higher dose of vitamin E, indicating tissue toxicity and an increased level of inflammation. Since this dose of vitamin E, which is lower than the UL, cause some adverse effects, even after a short exposure period, further studies are required to reconsider the UL for vitamin E.

Highlights

  • Vitamins are generally considered beneficial for a number of physiological processes, such as anti-oxidant status [1]

  • We have examined the effects of three-fold Recommended Daily Intake (RDI) of multi-vitamins and minerals in mice

  • The current study examined possible effects of increased intake of vitamins and minerals

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Summary

Introduction

Vitamins are generally considered beneficial for a number of physiological processes, such as anti-oxidant status [1]. A high dose of 25-fold RDI of vitamin E was used, which is still below the established level of toxicity In both exposure studies, possible adverse effects of vitamin E on biomarkers of oxidative stress, redox status and liver and kidney were monitored in the circulation (plasma and erythrocytes) and in liver and kidney tissue. LLiivveerr IInn tthhee lliivveerr ooff mmaallee mmiiccee,, tthhee iinnttaakkee ooff ffeeeedd BB ccoommppaarreedd wwiitthh ffeeeedd AA ccaauusseedd aa ssttaattiissttiiccaallllyy ssiiggnniifffiiiccaannttllyyy lllooowwweeerrrcccooonnnccceeennntttrrraaatttiiiooonnnoooffftththhrrreeeeeeiinninffllflaaammmmmmaaattiitooionnnbbbiiooiommmaarrakkrekerressr,,sbb, eebiienniggngMMMCCPCP--P11-1((pp(==p 00=..00011.00)1),,0II)LL, --I66L(-(p6p (==p00=..00000.110550))15aa)nnaddnTTdNNTFFN--aaF-((app (==p 00=..00011.0771)) 7((F)Fii(ggFuuigrrueer33e))..3)TT.hhTeehlleoolwwoweerrellreelvveeevllesslisinninAAALLTTLT,, ,LLLDDDHHH,, ,BBBAAAPPP,,,PPPAAAIII---111 aanndd rreessiissttiinn wweerree nnnooottt ssstttaaatttiiissstttiiicccaaalllllyyysssiiggignnniiffiiificccaaannntt..t.IInnInffeemmfemaalleealmme iimcceei,,cssett,aasttitissatttiiiccsaatillcllyyalssliyiggnnsiigffiinccaiafinncttallyyntlloloywwleeorrwaaeccrttiivvaicitttiiieevssitooieff sAAoLLfTTA((ppLT== (00p..00=11440)).0aa1nn4dd) aLLnDDdHHLD((ppH==(p00.=.0011066.0))1ww6)eewrreeerffoeouufonnuddn((dFFii(ggFuuigrreue r44e)).. TThhee eeffffeeccttss ooff ffeeeedd CC ccoommppaarreedd wwiitthh ffeeeedd BB wweerree oobbsseerrvveedd bbyy aa ssttaattiissttiiccaallllyy ssiiggnniifffiiiccaanntt ddeeccrreeaassee iinn tthhheee aaaccctttiiivvviiitttyyyooofffLLLDDDHHH((pp(p===00..00.110331))3,,)BB, AABPAP P((pp(==p00=..00022.220))2,,2aa)nn, ddanrredessirissettsiiinnst((ippn==(p00..0=011055.))0ff1oo5rr)mmfoaarlleemmmaliiecceem((FFiciiggeuu(rFreeig33u))..rTeThh3ee). ((AA(A)))AAAcccttiitvviviittiiiteeiesssooofff AAALLLTTT,,, AAASSSTTT aaannnddd LLLDDDHHH,,, aaannnddd cccooonnnccceeennntttrrraaatttiiiooonnnsss ooofff BBBAAAPPP aanndd TTTTPP iinn tthhee ppoosstt--mmiittoocchhoonnddrriiaalll ssuuppeerrnnnaaatttaaannnttt ooofff lliivveerr ttiissssuuee ooff mmaallee mmiiccee. In order to test whether there were interactions between the two sex groups, a Bonferroni post-Itnesotorwrddeaersrtpoteotreftsoetrswmt hewedht.heTethrheethrreetrwheeewrreeerwsetaientritesetriiacncattelirodanicfstfieborenetnwscebeeesntiwntheaeenntwutmohesbeetxrwgoorfobsueipoxsm,gaarroBkuoepnrsfse,brareotwnBioepneonfesrmt-rtoaenlseti awpnoadsst-pfteemrsftaowlremaasendpi.emTrfaholesrr.meTewhdie.srTewhsaetarsetieswstpieceraceliadstlilafyfteisortebincscaeelrsvdeiinfdfeairnneunamcenbsueimrnobafenbruioomfmbbaeirorkmoerfasrbbkioeemtrwsaeirneknegrmrsoabuleptsawnreedecnfeeimvianlge faenedidmfAael:msi.naTltehhieasnewirmyatsahlersso. pcTyehctiesaslwflyoarosGbesPseXprev, cienidatlhilnyeaolibvnseuermrfvoberedrMionCf Pba-i1on,muImLa-rb6ke,erTrsNoifFnb-agio,rromeusapirssktierner,scAeiinSvTign,rgBoAufepPesdarnAedc:eiiinnvtitnhhgee kfeerideydntheAryo: cfinoyrttehMsefCeorPry-Gt1h,PrIXoLc,-y6int,eTtshNfeoFrl-iGav,ePrrXefs,oiirsntMitnh.CeTPlih-v1ee,sreILfod-r6if,MfTeCrNePnF-c-1ae,,sIrLwe-s6ei,rseTtiNnn,oFAt-aSo,Tbr,esesBirAsvtePinda, AbnedStTwin,eBtehAnePtkhaienddngreionyutfphoser wkMihdCinPceh-y1r,efIocLer-i6vM,eTCdNPfFe-1e-a,d,IrBLe-sa6in,sdtTinNf.eFeT-dhae,Csr.eesdiisftfienr.enTcheessewderieffenroetnocbesewrveerdebneotwt oebensetrhveedgrobuetpwsewenhictheregcreoiuvepds wfeehdichB raencdeifveeedd fCee. d B and feed C

Discussion
Experimental Animals and Exposure Protocol
Preparation of Blood Samples
Biochemical Analysis in Blood Samples
Preparation of Tissue Samples
Biochemical Analysis in Tissue Samples
Findings
Statistical Analysis

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