Hydroxy Minerls - The Newest Development in Minerl Nutrition By Jeff Cohen nd F. A. Stewrd For t lest 3 yers nutritionl sources of essentil trce minerls such s iron, zinc, copper nd mngnese hve een commonly descried s eing either orgnic or inorgnic products. However, recent nd more intensive reserch studies hve shown tht this distinction is of little vlue in reveling how given metl source will perform in iologicl system. Similrly, for most of the lst 6 yers, comprisons of reltive iovilility hve een the primry focus when evluting lterntive sources of minerls. By comprison, newer pulished studies mke it cler tht the picture is more complex thn previously elieved. In ddition to differences in efficiency of sorption of the trget metl into the loodstrem, different sources cn ffect nutrition nd niml performnce in t lest four other importnt wys: (1) destruction of nutrients, including vitmins, in feed mixture, (2) interctions with other nutrients in the digestive trct, (3) direct influence of gut microil ecology; nd (4) effects on the niml s nturl immune functions. The common thred which links the mechnisms in ll of these performnce criteri is the speed with which the trget metl is relesed in the feed mixture or in the gut. There re mny possile chemicl nd iochemicl rections which re constntly competing for the supplemented metl. The min thing tht differentites how different minerl products perform is the strength of the onds holding them in the source compound. Erly History After copper nd zinc were found to e essentil nutrients in the 192 s nd 193 s, vrious lowcost sources of these metls, such s industril y-products nd wstes were dded to niml diets to provide the metls. However, prolifertion of university studies fter World Wr II led to the generlly ccepted view tht only wter-solule metl slts could e esily sored from the gut. This led to progressive shift in the niml feed industry wy from metl oxides nd towrd the use of highly-solule metl sulftes, which were ritrrily ssigned vlue of 1% reltive iovilility (RBV). Orgnics Strting in the 198 s, there ws new trend towrd the use orgno-metllic complexes of essentil trce minerls in niml nutrition. Initilly this trend ws sed on the notion tht such complexes would e more efficiently sored since they were felt to pproximte nturl iologicl complexes of metls. Lter, numer of studies reveled tht n niml deploys specific lignds to escort essentil metls through epithelil tissues, so it then ppered tht the
min vlue of the mnufctured orgno-metllics ws to protect the ingested metl from ecoming entngled in prsitic rections which compete with sorption. In fct, under certin conditions, the est of the orgno-metllic products cn hve somewht etter iovilility thn metl sulftes (>1% RBV). This occurs ecuse the higher strength of the onds holding the metl impedes side, or prsitic, rections. This cn e thought of s form of controlled relese over time, thus incresing the proility tht the metl will e successfully presented to the nturl sorption mechnism t the epithelium. Hydroxy Minerls The most recent trend in minerl nutrition hs een towrd metl slts tht hve een prtilly rected with n lkli to produce hydrolyzed inorgnic metl complexes. The first such commercil product, dicopper chloride trihydroxide (sic copper chloride or IntelliBond C), ws introduced in 1995. This compound ws chosen ecuse it nturlly forms well-defined threedimensionl crystl lttice structure with unusul stility. Tht structure is desirle ecuse growth of crystl lttice is nturl purifiction step tht excludes impurities nd ecuse it utilizes the sme type of chemicl onds (covlent) tht llow the good orgno-metllic products to outperform metl sulftes, which hve wek ionic onds to the metl. These covlent onds with the metl re strong enough to limit prsitic rections, ut wek enough to redily hnd off the metl to the escort lignds deployed y n orgnism to fcilitte sorption. Thus, these hydroxy compounds result in RBV vlues greter thn 1%, while voiding the higher mnufcturing cost nd environmentl impct involved in mnufcturing orgno-metllic compounds. They lso improve the stility of feed mixtures, thus reducing losses of other vlule nutrients, such s vitmins, nd enzymes. Finlly, due to the stility of the crystl structure, these products hold the trget metl tight enough tht it is still eing slowly relesed in the lter sections of the intestine where the mjority of pthogen chllenges occur nd where the immune tissues re concentrted. Stges in the Evolution of Minerl Nutrition For Animls Stge Approx.Dtes Description 1 st Genertion 193 s thru 195 s Metl oxides & industril y-products 2 nd Genertion 195 s thru 198 s Shift to metl slts of sulfuric cid for higher RBV 3 rd Genertion 198 s thru current Metl slts of orgnic cids 4 th Genertion 199 s thru current Bsic metl slts of low-cost minerl cids An illustrtion of Comprtive Bond Strengths Smples of vrious copper sources were stirred in modertely ggressive solvent to illustrte the comprtive rte t which they would relese the metl. This test does not mke ny ttempt to simulte conditions in n niml s gut which re very complex nd vrile over time nd loction. It simply shows the vriility of ond strengths in different source compounds.
Rectivity of Copper Sources in.1 M Sodium Acette Buffer Solution (ph 4.72) Amount of Cu Dissolved (g/l) 4. 3.5 3. 2.5 2. 1.5 1..5..5 1. 1.5 2. 2.5 3. 3.5 4. Time (Hours) Copper Oxide Copper Sulfte (TBCC) Orgnic Prod.1-15% Cu Orgnic Prod 2-1% Cu Orgnic Prod 3-1% Cu Minerls In The Gstrointestinl Trct Recent studies in Dr. Kirk Klsing s l t the University of Cliforni Dvis hve provided clerer picture of the reltionship etween ond strength nd minerl function in the gstrointestinl trct. In work from 21, luminl contents from roiler chicks fed either sic copper chloride () or copper sulfte were nlyzed to determine the form of the copper in vrious portions of the intestinl trct. The results indicted tht s the digest moved further long the smll intestines, more copper ws ound nd unextrctle (or unville) when copper sulfte ws the source. This is likely due to more prticiption in ntgonistic side rections. This work confirmed the chemicl mechnism y which sic copper chloride demonstrtes higher reltive iovilility s well s its incresed opportunity to interct with the micro flor in n niml s gut. 5 Amount of Cu (mg/kg DM) 45 4 35 3 25 2 15 1 5 Duodenum Jejunum Ileum 1 Ileum 2 Ileum 3 Cecum Wter solule Cu EHPG extrctle Cu Unremovle Cu Within tissue nd Cu type, mens re different (p<.5).
In follow up study using similr protocol, the two copper sources were gin fed to chicks for seven dys. Luminl content ws collected nd 5 colony forming units of E. coli were introduced to determine the effects of the copper on cteriosttic ctivity. Results indicted significntly greter reduction in E. coli growth with the luminl contents from chicks fed sic copper chloride. E. coli growth (% of originl inocultion) 12 Control (no dded Cu) 1 Cu sulfte (15 ppm) (15 ppm) 8 6 4 2 3 minute incution -c Mens with different superscripts re significntly different (p<.5). c A third tril consisted of two prts. The initil experiment demonstrted tht sic copper chloride hs lower miniml inhiitory concentrtion (MIC) thn copper sulfte. Surprisingly, copper sulfte s higher soluility nd rectivity did not result in greter ctericidl effects. The second prt gin looked t the effects of the luminl contents, ut this time included E. coli, Clostridi perfringens, Slmonell gllinrum, Slmonell enteritidis nd Eimeri. In ddition, the copper sources included copper mino cid complex. As the following chrt shows, sic copper chloride nd the copper mino cid complex were oth etter thn copper sulfte t reducing E. coli numers in ilel contents. Copper source E. coli C. perfringens S. gllinrum S. enteritidis Eimeri % vile dded Cu 1. 1. 1. 1. 79 CuSO4.47.88 1.12.93 76 Intelliond C.31 c.78 c 1.18.9 75 Cu-mino cid.33 c.75 c 1.9 1.11 81 SEM.2.3.4.2 2.3 ANOVA P vlue.1.17.26.36.47 Bcteri t dded Cu (control) set to 1., other numers indicte cteri reltive to control Immune Function And Intestinl Microes The illions of cteri present in the intestinl trct (commensls) hve the dul role of iding digestion while lso forming rrier to protect the niml from pthogenic orgnisms. Minerls re thought to ply key role in regulting these cteri popultions. The lnce etween the
commensl popultion nd the immune system controlling them is essentil. The work descried erlier reveled tht the hydroxy minerl form of copper () - s result of the idel strength of its onds cts throughout the intestinl trct. Thus these minerls re le to ssist in mintining more stle lnce of micro flor nd to llow nutrients to e used for growth rther thn for ttling chllenges. In n ttempt to explore the differences tht vrious minerl forms might hve on the innte immune system, work from Dr. Liz Koutsos s l t Cliforni Polytechnic Stte University, Sn Luis Oispo in 25 reveled lower inflmmtory response etween roilers fed sic copper chloride compred to those fed either copper sulfte or no dditionl copper. The in vitro work showed tht plsm from chicks fed sic copper chloride, s compred to those with no supplementl copper, hd lower inflmmtory profile sed on its ility to dmpen nitric oxide production y mcrophges in response to lipo polyscchride (LPS). The nti-inflmmtory impct of sic copper chloride ws dose-dependent, s higher levels of copper chloride plsm resulted in more dmpened NO responses. 8 Nitric oxide production (µmol/well) 6 4 2 2 4 6 8 1 % plsm from TBCC-fed chicks in cell culture medi (totl 1% plsm in RPMI 164) In vivo work involved using plsm from LPS-chllenged chicks fed sic copper chloride, resulting in lower NO responses y HD11 mcrophges s compred to plsm from LPSchllenged chicks fed no supplementl copper. 4 Unstimulted chick in vivo Stimulted chick in vivo Nitric oxide (µmol/well; 48 h post-lps) 3 2 1 3 7 1 % plsm from TBCC-fed chicks, in cell culture medi (totl of 1% plsm in RPMI medi)
The reserchers theorized tht chicks fed hydroxy copper relesed less inflmmtory cytokines into their lood, presumly due to fewer or less severe pthogen chllenges in the intestines. This my indicte tht copper chloride s etter performnce hs systemic component nd ongoing reserch will determine if this effect is relted to shift in microil ecology or if it is due to direct effect on leucocytes. Summry As in ll fields of scientific inquiry, mnkind s understnding of minerl nutrition continues to evolve. The immense importnce of the huge nd complex colony of commensl orgnisms in the lower gut, nd the interctions etween tht colony nd the host s immune rections is only strting to e understood nd explored. Some of the most recent work with essentil trce minerls shows tht, in ddition to supporting well known systemic functions, minerls ply numer of different roles in ffecting intestinl helth in niml husndry. References 1. Bker, D. H., nd C. B. Ammermn, 1995. Copper iovilility In: C. B. Ammermn, D. H. Bker, nd A. J. Lewis ed. Biovilility of Nutrients: Amino Acids, Minerls, nd Vitmins. Pp 127-156. Acdemic Press. Sn Diego, CA. 2. Beutler, K. T., O. Pndewycz, nd D. L. Brutign. 1998. Equivlent uptke of orgnic nd inorgnic zinc y monkey kidney firolsts, humn intestinl epithelil cells, or perfused mouse intestine. Biol. Trce Elem. Res. 61:19-31. 3. Miles, R. D., S. F. O Keefe, P. R. Henry, C. B. Ammermn, nd X. G. Luo. 1998. The Effect of dietry supplementtion with copper sulfte or trisic copper chloride on roiler performnce, reltive copper iovilility, nd dietry prooxidnt ctivity. Poult. Sci. 77:416-425. 4. Spers, J. W., Kegley, E. B., Mullis, L. A., nd Wise, T. A., Biovilility of Copper From Tri-sic Copper Chloride in Cttle, J. Anim. Sci. 1997 75 (Suppl. 1): 265(Astr.). 5. Hooge, D. M., F. A. Stewrd, nd J. L. McNughton. 2. Biovilility of copper from trisic copper chloride (TBCC ) compred to copper sulfte penthydrte in roiler chicken diets. Poult. Sci. 79(Suppl. 1):97 (Astr.). 6. Luo, X. G.; Ji, F.; Lin, Y. X.; Stewrd, F. A.;Lu, L.;Liu, B. nd Yu, S. X. Effects of dietry supplementtion with copper sulfte or trisic copper chloride on roiler performnce, reltive copper iovilility, nd oxidtion stility of vitmin E in feed. Poult. Sci. 25, 84:888-893. 7. Guo, R., et l., Chemicl chrcteristics nd reltive iovilility of supplementl orgnic copper sources for poultry. J Anim Sci, 21. 79(5): p. 1132-41. 8. Bnks, K. M.; Thompson, K. L.; Jynes, P.; Applegte, T. J. The effects of copper on the efficcy of phytse, growth, nd phosphorous retention in roiler chicks. Poult. Sci. 24, 83, 1335-1341.
9. Bnks, K. M.; Thompson, K. L.; Rush, J. K.; Applegte, T. J. Effects of copper source on phosphorus retention in roiler chicks nd lying hens. Poult. Sci. 24, 83, 99-996. 1. Nziripour, A. nd K.C. Klsing, Effect of dietry copper source nd level on GI copper levels nd ilel E. coli survivl in roiler chicks, in ADSA-PSA-AMPA-CSAS- ASAS Joint Meeting. 21: Denver, CO. 11. Klsing, K.C., Investigting the ntimicroil ction of copper in chicken intestines, internl report, 211. 12. Aris, V. J., nd E. A. Koutsos. 26. Effects of copper source nd level on intestinl physiology nd growth of roiler chickens. Poult. Sci. 85:999-17. 13. Aris, V.J. nd E.K. Koutsos, Dietry copper source nd level led to differences in plsm tht modulte the inflmmtory response in cultured mcrophges, in Experimentl Biology. 25: Sn Diego, CA. 2.8