Access the full text.
Sign up today, get DeepDyve free for 14 days.
M. Manangi, M. Vázquez-Añón, J. Richards, S. Carter, R. Buresh, K. Christensen (2012)Impact of feeding lower levels of chelated trace minerals versus industry levels of inorganic trace minerals on broiler performance, yield, footpad health, and litter mineral concentration
The Journal of Applied Poultry Research, 21
I. Bremner, J. Beattie (1995)Copper and zinc metabolism in health and disease: speciation and interactions
Proceedings of the Nutrition Society, 54
(2008)A dose titration comparison of MINTREX® versus ZnSO 4 on performance in broilers with high dietary copper supplementation
Junmei Zhao, R. Shirley, M. Vázquez-Añón, J. Dibner, J. Richards, P. Fisher, T. Hampton, K. Christensen, J. Allard, A. Giesen (2010)Effects of chelated trace minerals on growth performance, breast meat yield, and footpad health in commercial meat broilers
The Journal of Applied Poultry Research, 19
G. Hill, P. Ku, E. Miller, D. Ullrey, T. Losty, B. O’dell (1983)A copper deficiency in neonatal pigs induced by a high zinc maternal diet.
The Journal of nutrition, 113 4
(2015)Champaign (IL): Association of American Feed Control Officials (AAFCO)
K. Wedekind, D. Baker (1990)Zinc bioavailability in feed-grade sources of zinc.
Journal of animal science, 68 3
JD Richards, P Fisher, JL Evans, KJ Wedekind (2015)Greater bioavailability of chelated compared to inorganic zinc in broiler chicks in presence of elevated calcium and phosphorus
Open Access Animal Physiol, 7
P. Schlegel, W. Windisch (2006)Bioavailability of zinc glycinate in comparison with zinc sulphate in the presence of dietary phytate in an animal model with Zn labelled rats.
Journal of animal physiology and animal nutrition, 90 5-6
Paul Oestreicher, Robert Cousins (1985)Copper and zinc absorption in the rat: mechanism of mutual antagonism.
The Journal of nutrition, 115 2
G. Apgar, E. Kornegay, M. Lindemann, D. Notter (1995)Evaluation of copper sulfate and a copper lysine complex as growth promoters for weanling swine.
Journal of animal science, 73 9
J. Richards, P. Fisher, Joseph Evans, K. Wedekind (2015)Greater bioavailability of chelated compared with inorganic zinc in broiler chicks in the presence or absence of elevated calcium and phosphorus
Subcommittee Nutrition, Board Agriculture (2016)Nutrient requirements of poultry
J. Richards, J. Zhao, R. Harrell, C. Atwell, J. Dibner (2010)Trace Mineral Nutrition in Poultry and Swine
Asian-australasian Journal of Animal Sciences, 23
T. Ward, K. Watkins, L. Southern (1994)Interactive effects of dietary copper and water copper level on growth, water intake, and plasma and liver copper concentrations of poults.
Poultry science, 73 8
G. Yi, C. Atwell, J. Hume, J. Dibner, C. Knight, J. Richards (2007)Determining the methionine activity of Mintrex organic trace minerals in broiler chicks by using radiolabel tracing or growth assay.
Poultry science, 86 5
A. Hall, B. Young, I. Bremner (1979)Intestinal metallothionein and the mutual antagonism between copper and zinc in the rat.
Journal of inorganic biochemistry, 11 1
K. Wedekind, A. Hortin, D. Baker (1992)Methodology for assessing zinc bioavailability: efficacy estimates for zinc-methionine, zinc sulfate, and zinc oxide.
Journal of animal science, 70 1
Y. Pang, T. Applegate (2007)Effects of dietary copper supplementation and copper source on digesta pH, calcium, zinc, and copper complex size in the gastrointestinal tract of the broiler chicken.
Poultry science, 86 3
V. Arias, E. Koutsos (2006)Effects of copper source and level on intestinal physiology and growth of broiler chickens.
Poultry science, 85 6
F. Zhao, H. Zhang, Shaohua Hou, Zhe Zhang (2008)Predicting metabolizable energy of normal corn from its chemical composition in adult Pekin ducks.
Poultry science, 87 8
W. Horwitz (1980)Official Methods of Analysis
(2015)AAFCO 2015 Official Publication
W. Horwitz, G. Latimer (2010)Official methods of analysis of AOAC International
Z. Wang, S. Cerrate, C. Coto, Fenglan Yan, P. Waldroup (2007)Evaluation of Mintrex Copper as a Source of Copper in Broiler Diets
International Journal of Poultry Science, 6
F. Yan, P.W. Waldroup (2006)Evaluation of Mintrex Manganese as a Source of Manganese for Young Broilers
International Journal of Poultry Science, 5
Background: The goal of this study was to compare the antagonism of elevated dietary Cu (250 mg/kg) from CuSO on three different Zn sources (ZnSO ·H O; [Zn bis(−2-hydroxy-4-(methylthio)butanoic acid)], Zn(HMTBa) , 4 4 2 2 a chelated Zn methionine hydroxy analogue; and Zn-Methionine), as measured using multiple indices of animal performance in ROSS 308 broilers. Methods: Three experiments were conducted in broiler chicks fed a semi-purified diet. All birds were fed a Zn-deficient diet (8.5 mg/kg diet) for 1 wk, and then provided with the experimental diets for 2 wks. Results: Experiment 1 was a 2 × 2 factorial design with two levels of Cu (8 vs. 250 mg/kg diet from CuSO ) and two Zn sources at 30 mg/kg [ZnSO ·H O vs. Zn(HMTBa) ]. Elevated Cu impaired growth performance only in birds fed ZnSO . 4 2 2 4 Compared to ZnSO ·H O, Zn(HMTBa) improved feed intake (12 %; P < 0.001) and weight gain (12 %, P < 0.001) and the 4 2 2 benefits were more pronounced in the presence of 250 mg/kg diet Cu. Experiment 2 was a dose titration of ZnSO ·H O 4 2 and Zn(HMTBa) at 30, 45, 60, and 75 mg/kg diet in the presence of 250 mg/kg CuSO . Feed:gain was decreased 2 4 and tibia Zn was increased with increasing Zn levels from 30 to 75 mg/kg. Birds fed Zn(HMTBa) consumed more food and gained more weight compared to birds fed ZnSO , especially at lower supplementation levels (30 and 45 mg/kg; interaction P < 0,05). Experiment 3 compared two organic Zn sources (Zn(HMTBa) vs. Zn-Methionine) at 30 mg/kg with or without 250 mg/kg CuSO . No interactions were observed between Zn sources and Cu levels on performance or tissue mineral concentrations. High dietary Cu decreased weight gain (P < 0.01). Tibia Cu and liver Cu were significantly increased with 250 mg/kg dietary Cu supplementation (P < 0.01). No difference was observed between the two Zn sources. Conclusions: Dietary 250 mg/kg Cu significantly impaired feed intake and weight gain in birds fed ZnSO ·H O 4 2 , but had less impact in birds fed Zn(HMTBa) . No difference was observed between the two organic zinc sources. These results are consistent with the hypothesis that chelated organic Zn is better utilized than inorganic zinc in the presence of elevated Cu. Keywords: Antagonism, Broilers, Chelates, Growth, Minerals, Organic, Performance * Correspondence: firstname.lastname@example.org Research and Development, Novus International, 20 Research Park Drive, Saint Charles, MO 63304, USA Full list of author information is available at the end of the article © 2016 Zhao et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Zhao et al. Journal of Animal Science and Biotechnology (2016) 7:13 Page 2 of 9 Background antagonisms in gastrointestinal tract. However, pub- Elevated dietary CuSO (125–250 mg/kg diet) is often lished literature on relative bioavailability of different used in broiler and pig diets as a growth promoter and sources of Zn is mixed. The inconsistencies could be due anti-bacterial agent, possibly by modulating the micro- to differences in the chemical characteristics (and thus bial population within the gastrointestinal tract [1, 2]. bioavailability) between different organic Zn forms. Add- However, high dietary Cu can reduce the bioavailability ing to the complexity of comparing results from different of other important nutrients by forming insoluble com- studies using various forms of Zn is the inconsistency of plexes or by competing for absorption sites. The reciprocal terminology (organic, chelates, complex, etc.) along with antagonism between Zn and Cu is a prime example of the difficulty of characterizing chemical structures. competitive biological interactions between metals due The primary objectives of the experiments reported here to their similar chemical and physical properties [3, 4]. were to investigate the potential antagonism imposed by Excessive Zn supply has been shown to inhibit intestinal high dietary CuSO on Zn bioavailability in broilers, and absorption, hepatic accumulation, and placental transfer to evaluate whether different Zn sources impact the Cu- of Cu, as well as to induce clinical and biochemical signs mediated antagonism. We hypothesized that chelated Zn of Cu deficiency [5, 6]. The intestinal absorption of Zn is more resistant to high Cu antagonism due to their stable was decreased by approximately 20 % when the dietary Cu structure and resistance to interactions with other nutri- intake was increased from 3 to 24 mg/kg diet. The mecha- ents in the gastrointestinal tract. Three Zn sources were nism(s) of Zn and Cu interaction is not well understood, used in the experiments: ZnSO ·H O, Zn(HMTBa) ,and 4 2 2 and the data are controversial to interpret. They compete Zn-methionine (Zn-MET). Zn(HMTBa) is a chelated Zn for uptake sites in the mucosa, and are regulated by the methionine hydroxy analogue [Zn bis(−2-hydroxy-4- same metallothionein protein. In addition, they might (methylthio)butanoic acid)] at 2:1 ratio. To the best of our impact each other’s solubility and binding behavior in knowledge, this is the first report of the evaluation of gastrointestinal tract. Pang and Applegate indicated that the impact of high Cu on the utilization of different Zn high Cu supplementation (250 mg/kg in diet) increased sources in broilers. the percentage of Zn associated with large complexes (>100,000 MW), and decreased the percentage of Zn associated with small complexes (<5,000 MW; P <0.05), Methods thereby suggesting an antagonism between Cu and Zn . The animal protocols for all experiments were approved The association of Zn with smaller complexes might by the Novus International Institutional Animal Care and enhance the potential for absorption due to the larger Use Committee, and complied with all federal and state surface area. statutes ensuring the humane and ethical treatment of ex- Most previous studies of dietary Zn-Cu antagonism perimental animals. Diet formulation and in vivo activities have evaluated inorganic Zn and inorganic Cu. The were performed at the Novus International Research Farm. availability of chelated organic trace minerals (OTM) in ZnSO ·H O was purchased from Sigma-Aldrich (Saint 4 2 the marketplace now offers a potential solution to the Louis, MO USA). Zn(HMTBa) (MINTREX® Zn, Novus inherent limitations associated with the widespread International Inc, Saint Charles, MO USA) is a chelate of commercial practice of employing inorganic dietary CuSO , one Zn with two molecules of 2-hydroxy-4-(methylthio)bu- by reducing and possibly avoiding the antagonism between tanoic acid (HMTBa), and was obtained from Novus Cu and Zn. Results from recent studies indicate that OTM International. Zinc methionine complex (Zn-MET) is might bemoreavailablefor absorption,likelydueto re- the product resulting from complexing a soluble metal duced incidence of antagonistic reactions with other dietary salt with methionine, and was purchased from Zinpro constituents in the gastrointestinal tract [8–10]. The rela- (Eden Prairie, MN USA) . tive bioavailability of a chelated Zn methionine hydroxy Three consecutive experiments were conducted. Experi- analogue [Zn bis(−2-hydroxy-4-(methylthio)butanoic acid; ment 1 was designed to determine whether 250 mg/kg Zn(HMTBa) ] (compared to ZnSO )inbroilerswas dietary Cu from CuSO antagonizes two different Zn 2 4 4 reported to be 161 % based on tibia Zn, and 248 % based sources [ZnSO ·H O vs. Zn(HMTBa) ]. ZnSO ·H O 4 2 2 4 2 on metallothionein mRNA expression . When dietary and Zn(HMTBa) were added at 21.5 mg/kg to achieve Ca and P were increased, a common practice in diets of 30 mg/kg total Zn in the finished feed (the other 8.5 mg/ layers and pets, the relative bioavailability of chelated kg came from feed ingredients). Similar calculations were Zn increased to 441 % (based on μg total tibia Zn). The used in Experiments 2 and 3, such that different Zn authors suggested that the difference in relative bio- sources were added on top of the basal to achieve the tar- availability might be attributed to the fact that chelated geted Zn concentration in the final feed. A total of 288 Zn possesses stronger chemical (coordinate-covalent) ROSS 308 male chicks were randomly divided into four bonds relative to ZnSO and, thus, is more resistant to experimental treatments with six replicate pens per 4 Zhao et al. Journal of Animal Science and Biotechnology (2016) 7:13 Page 3 of 9 treatment and 12 birds per pen. The trial was a 2 × 2 fac- (Experiment 3) analyses. Following the careful removal of torial design with two levels of Cu (8 vs. 250 mg/kg diet muscle and connective tissue, the whole tibia was from CuSO ) and two Zn sources at 30 mg/kg ashed. Tibia Zn and Cu were measured at the Novus [ZnSO ·H O vs Zn(HMTBa) ]. Based on Experiment 1, International Analytical Services Laboratories (Saint 4 2 2 Experiment 2 was designed to compare ZnSO ·H Oand Charles, MO USA) using Inductively Coupled Plasma 4 2 Zn(HMTBa) in a dose titration in the presence of Optical Emission Spectrometry (ICP-OES, Perkin Elmer, 250 mg/kg diet CuSO . A total of 576 ROSS 308 male Shelton, CT USA) following an internally validated chicks were allotted to eight experimental treatments method based on AOAC 985.01 . Tibia Zn and Cu with six replicate pens per treatment and 12 birds per level were reported on a dry ash weight basis, and liver pen. The dietary treatments included either ZnSO · Zn and Cu levels reported on a dry matter basis. H OorZn(HMTBa) added to achieve the following 2 2 dietary levels: 30, 45, 60, and 75 mg/kg Zn. All diets Statistical analyses contained 250 mg/kg diet Cu from CuSO .Based on the In Experiments 1 and 3, data were analyzed with a 2- results of the first two experiments, Experiment 3 was way ANOVA using the General Linear Models (GLM) designed to compare two different organic Zn sources, procedure of SAS (version 9.1; Cary, NC USA). The Zn(HMTBa) and Zn-MET, on performance in the pres- model included the main effects of Zn sources, Cu levels ence of 8 vs. 250 mg/kg CuSO dietary supplementation. (with and without high CuSO ), and their interaction. In A total of 480 day-old ROSS 308 male broilers were al- Experiment 2, data were analyzed with a 2-way ANOVA lotted to four treatments, with 8 replicate pens per using the GLM procedure. The model included the main treatment and 15 birds per pen. The trial was a 2 × 2 effect of two Zn sources [Zn(HMTBa) vs. ZnSO ·H O], 2 4 2 factorial design with two levels of Cu (8 and 250 mg/kg and four different supplementation levels, and their 2-way diet as CuSO ) and two Zn sources [Zn(HMTBa) vs. 4 2 interaction. Means were separated by Fisher’sprotected Zn-MET]at30mg/kg diet. least significant difference method when the F test was sig- Birds were housed in stainless steel pens in a thermo- nificant. Mortality data were transformed to square root of statically controlled, electrically heated environment. The mortality + 1 before analysis. Data are presented in natural dimension of each battery pen was 51 × 69 × 35 cm numbers. Pen served as the experimental unit. Effects were (width, length, and height, respectively). Each pen was considered significant at 95 % probability (P ≤ 0.05). provided with water and an individual feeder. All birds were allowed to consume mash feed and water ad libitum. Room temperature was kept at 32 °C for the first two days, Results then reduced until a temperature of 23 °C was reached on Experiment 1 d 17 of age. The light–dark cycle was as follows: on d 0 As shown in Table 2, significant two-way interactions of through d 7, there were 23 h of light and 1 h of darkness Cu level and Zn source were observed on body weight (lights off at 1200 h and on at 0100 h). On d 8 through (P < 0.05) and weight gain (P < 0.05). Compared to 8 mg/kg d 22, there were 20 h of light and 4 h of darkness (lights CuSO , weight gain was decreased 14 % with 250 mg/kg off at 1200 h and on at 0400 h). All birds were fed a com- Cu supplementationinthe ZnSO ·H Ogroups(382vs. 4 2 mon semi-purified Zn-deficient diet (8.5 mg/kg diet) for 328 g), but not in the Zn(HMTBa) groups (404 vs. 390 g). the first week to reduce Zn stores and then were fed the Similar results were observed on final body weight, experimental diets for about 2 wks (basal diet formula, see where 250 mg/kg dietary Cu reduced final body weight in Table 1). A common semi-purified basal diet was used and ZnSO ·H O (465 vs. 407 g) but not in the Zn(HMTBa) 4 2 2 formulated to meet National Research Council (1994) groups (481 vs. 467 g). No interaction was observed on dietary recommendations for all nutrients except for Zn feed intake (P = 0.34, Table 2). For main effect, dietary . Each dietary treatment was then made by adding 250 mg/kg CuSO decreased feed intake 10 % com- different Zn sources and Cu to the common basal. pared to the 8 mg/kg CuSO control groups regardless Methionine activity from Zn(HMTBa) (80 % methio- of Zn source (P < 0.001, Table 2). Compared to ZnSO · 2 4 nine activity) , and Zn-MET (20 % methionine activity) H O, birds fed Zn(HMTBa) consumed 12 % more feed 2 2 was accounted for, and all diets were adjusted to have iso- (P < 0.001). Feed conversion, mortality, and tibia Zn methionine level. were not affected by dietary treatments (P >0.50). In Body weight and feed intake were recorded at begin- summary, dietary Cu from CuSO impaired feed intake ning and the end of each experiment. On d 21 (d 19 for across Zn sources, but decreased weight gain only in Experiment 3), one chick per cage (selected based on birds fed ZnSO ·H O. Compared to ZnSO ·H O, 4 2 4 2 body weight approximating the pen mean) was chosen, Zn(HMTBa) improved weight gain and feed intake, euthanized with CO , and the left tibia (without cartilage and the benefits were more profound with 250 mg/kg cap) and liver (Experiment 3)were collected for Zn and Cu dietary Cu supplementation. Zhao et al. Journal of Animal Science and Biotechnology (2016) 7:13 Page 4 of 9 Table 1 Basal diet formula and nutrient profile (Experiments 1 through 3) Ingredients g/kg Nutrients, g/kg Dextrose 317.5 Metabolize energy, MJ/kg 13.0 Corn starch 158.4 Crude protein 222.6 Soy concentrate, 84 % 152.8 Calcium 9.0 Cellulose 124.3 Total phosphorus 6.2 Soy protein concentrate 110.0 Available phosphorus 4.5 Soybean oil 50 Available amino acid Milo (grain sorghum) 45 Lysine 11.5 Calcium phosphate 14.5 Methionine 6.8 MHA 5.5 Methionine + cystine 8.3 Potassium phosphate 4.8 Calcium carbonate 3.3 Mineral premix 2.5 Choline, 70 % 2.3 Potassium chloride 1.7 Sodium chloride 1.6 Magnesium sulfate heptahydrate 1.4 Threonine 1.1 Vitamin premix 0.6 L-lysine, 78 % 0.6 Sodium bicarbonate 0.3 Tryptophan 0.2 Santoquin-Mix 6 0.1 Silica 1.5 Milo, a draught-tolerant crop also known as grain sorghum, is a food product for humans and livestock feed grain. In the US, the feed grain is mainly for poultry and cattle MHA is the calcium salt of 2-hydroxy-4 methylthio butanoic acid (Novus International), providing 84 % methionine activity. MHA inclusion rate was adjusted to reflect methionine activity provided from Zn(HMTBa) (80 % methionine activity) and Zn-MET (20 % methionine activity) to maintain an equal methionine level across all treatments The mineral premix provided in the final diet (mg/kg): 60 Mn (MnO); 80 Fe (FeSO ·7H O); 8 Cu (CuSO ·5H O); 0.35 I (ED Iodide); 0.15 Se (NaSeO ). Analyzed final 4 2 4 2 3 basal diet Zn was 8.5 mg/kg Vitamin premix provided in the final diet (mg/kg): retinylacetate 10; cholecalciferol 6.25; dl-alpha tocopheryl acetate 90; menadione sodium bisulphate 7; calcium pantothenate 10; cyanocobalamin, 1.4; riboflavin 6.5; niacin 37; biotin 0.15, thiamin monoitrate 2.25; pyridoxine 4.25; and folic acid 0.9 Silica was removed from the diet as different Zn sources were added Experiment 2 birds fed ZnSO ·H O, especially at lower levels of Zn 4 2 As shown in Table 3, significant two-way interactions of Zn supplementation. Less Zn(HMTBa) was needed to source and level were observed on body weight (P = 0.02), achieve similar performance compared to ZnSO ·H O. 4 2 weight gain (P = 0.005), and feed intake (P < 0.001, Table 3). Feed efficiency and tibia Zn increased with increased The superiority of Zn(HMTBa) over ZnSO ·H Owas dietary Zn in the range of 30 to 75 mg/kg. 2 4 2 more pronounced at lower levels of Zn supplementation. Birds achieved maximal performance at 45 mg/kg Zn Experiment 3 supplementation from Zn(HMTBa) , and no further No interactions between Cu levels and Zn sources were improvement was observed at levels above that (Table 3). observed on performance (P > 0.25; Table 4). No differ- In contrast, performance was linearly improved in birds ences were observed on feed intake, feed efficiency, and fed Zn from ZnSO ·H O from 30 to 75 mg/kg, with the mortality among treatments (P > 0.25, Table 4). Similar 4 2 best performance at the highest level. Feed:gain was de- to experiment 1, birds fed 250 mg/kg CuSO gained less creased and tibia Zn was increased with increased Zn weight and were lighter compared to birds fed 8 mg/kg level regardless of the source (main effect, P <0.05). No CuSO (main Cu effect, P < 0.05). Tibia Zn and liver Zn differences were observed on tibia Zn or mortality be- were not different among treatments (P > 0.50, Table 5). tweenZnsources (P>0.05).Insummary,birdsfed Dietary Cu supplementation significantly increased bone Zn(HMTBa) ate more and gained more compared to and hepatic Cu level, regardless of Zn sources (P < 0.001, 2 Zhao et al. Journal of Animal Science and Biotechnology (2016) 7:13 Page 5 of 9 Table 2 Effects of Zn sources and CuSO on growth performance and tibia Zn in broilers (Experiment 1) Cu levels, mg/kg Zn Source, 30 mg/kg D7 BW, D21 BW, Gain, Feed Intake, Feed:gain Mortality, % Ash based tibia Zn, g/bird g/bird g/bird g/bird mg/kg a b 8 ZnSO 83 465 382 523 1.372 2.78 148 b c 250 ZnSO 78 407 328 456 1.389 1.39 158 a a 8 Zn(HMTBa) 77 481 404 569 1.407 5.55 170 a ab 250 Zn(HMTBa) 78 467 390 528 1.355 2.78 150 SEM 2 8 7 13 0.027 2.26 14 Main effect means Cu level 8 79 473 393 546 1.390 4.167 159 250 78 437 359 492 1.372 2.083 154 Zn source ZnSO 80 436 355 489 1.381 2.083 153 Zn(HMTBa) 77 474 397 548 1.381 4.165 160 2x2 factorial arrangement, P value Zn sources – <0.001 <0.001 <0.001 0.980 0.368 0.597 Cu level – <0.001 <0.001 <0.001 0.515 0.367 0.722 Zn Source * Cu level – 0.012 0.011 0.334 0.208 0.762 0.298 A total of 288 ROSS 308 male birds were used, with six cages per treatment and 12 birds per pen Tibias were collected from one bird per pen, total of six birds per treatment a,b,c Means within a column with no common superscripts differ (P < 0.05) Table 5). Liver Cu was increased greater than 10 fold with to a crystalline amino acid, casein-dextrose, or egg white 250 mg/kg Cu supplementation. In summary, 250 mg/kg diet which are devoid of phytate. Cu decreased weight gain and significantly increased liver The reciprocal antagonisms between dietary Zn and and tibia Cu concentration. No difference was observed Cu are well known. For example, high dietary Cu (204 mg between the two Zn sources. Cu/kg for 10 d) retarded growth performance in turkey poults . Hall et al. reported a 20 % decrease in Zn ab- Discussion sorption when dietary Cu was raised from 3 to 24 mg/kg The data reported here are consistent with the hypoth- in rats . The mechanism(s) by which Cu antagonizes Zn esis that chelated organic Zn forms are more efficient, is not well understood, although it has been postulated compared to an inorganic zinc salt, in their abilities to that these antagonisms are due to their similar chemical overcome the antagonism mediated by elevated dietary and physical properties . It seems unlikely that Cu-Zn Cu. Collectively, the data from our study indicate that a interaction occurs at a systemic level, because a) the chelated form of Zn [Zn(HMTBa) ]outperforms the absorption of these two metals occurs via different inorganic ZnSO ·H O, in the context of high dietary transporters, b) their functions and metabolism are quite 4 2 Cu-mediated antagonism in broiler chicks. Similarly, different, and c) they do not share common storage Richards et al. recently reported that Zn(HMTBa) is proteins except metallothionein . more bioavailable than ZnSO and the difference is Dietary 250 mg/kg Cu significantly impaired feed in- 4, greater under conditions of elevated dietary Ca and P take and weight gain in birds fed ZnSO ·H O but had 4 2 supplementation . little or no impact in birds fed Zn(HMTBa) . Computer To the best of our knowledge, this is the first report modeling analyses suggest that the interaction between demonstrating that high dietary Cu in broilers antago- HMTBa and Zn (at a 2:1 molar ratio) is more stable over a nizes, to differing degrees, different dietary sources of Zn. range of physiological pH values compared to the inter- We used a soy isolate/soy concentrate diet to assess the action between methionine and Zn (at a 1:1 molar ratio) relative performance differences between zinc sources in (unpublished observations). In turn, Zn(HMTBa) would chicks. The use of such a diet is an accepted model to as- be predicted to be more stable in solution than Zn-MET, sess relative bioavailability or performance differences be- and less susceptible to dietary antagonisms over the vari- tween Zn sources . The presence of phytate and fiber able pH range found in the gastrointestinal tract. Thus, (similar to corn-soybean meal diets) makes this semi- the inherent physicochemical features of Zn(HMTBa) purified diet more relevant to commercial diets compared might contribute to greater overall bioavailability and Zhao et al. Journal of Animal Science and Biotechnology (2016) 7:13 Page 6 of 9 Table 3 Effects of Zn sources with high dietary CuSO on performance and tibia Zn in broilers (Experiment 2) Zn level, mg/kg Zn Source CuSO , D7 BW, D21 BW, Gain, Feed Intake, Feed:gain Mortality, % Ash based tibia Zn, mg/kg g/bird g/bird g/bird g/bird mg/kg d d c 30 ZnSO 250 78 406 328 455 1.388 1.54 158 bc bc a 45 ZnSO 250 78 488 411 550 1.341 1.39 219 ab ab a 60 ZnSO 250 76 501 425 557 1.315 0.00 256 a a a 75 ZnSO 250 78 515 438 571 1.307 0.00 263 c c b 30 Zn(HMTBa) 250 78 468 390 527 1.355 2.78 150 a a a 45 Zn(HMTBa) 250 80 519 440 571 1.302 0.00 228 ab a a 60 Zn(HMTBa) 250 80 514 434 566 1.304 1.24 271 a a a 75 Zn(HMTBa) 250 77 519 441 572 1.300 1.24 267 SEM 2 9 8 8 0.020 1.16 12 Main effect means Zn source ZnSO 78 475 396 531 1.345 1.111 208 Zn(HMTBa) 78 500 422 561 1.333 2.220 217 Zn level a c 30 78 455 376 519 1.381 3.125 157 b b 45 79 504 425 561 1.321 0.694 224 b a 60 78 507 429 561 1.309 0.694 263 b a 75 77 517 439 572 1.303 0.694 265 2 × 4 factorial arrangement, P value Zn level – <0.001 <0.001 <0.001 0.004 0.549 <0.001 Zn Source – <0.001 <0.001 <0.001 0.102 0.403 0.569 Zn source * level – 0.021 0.005 <0.001 0.827 0.549 0.833 A total of 576 ROSS 308 male chicks were allotted to eight treatments with six replicate cages per treatment and 12 birds per cage. Tibias were collected from one bird per pen, total six birds per treatment a-d Means within a column with no common superscripts differ (P < 0.05) superior performancecompared to the ZnSO ·H O commercial diets or phytate-containing diets, absorption 4 2 evaluated here. Collectively, the data reported here indicate of organic sources of minerals are depressed, but to a that Zn(HMTBa) was less susceptible to Cu-mediated lesser extent than inorganic sources. For example, it was antagonism compared to ZnSO ·H O. Furthermore, demonstrated by Wedekind et al. that the inflection point 4 2 bioavailability experiments using tissue zinc levels and or breakpoint varies among Zn sources . The break- zinc-responsive gene expression as indicators of bio- point or inflection point for bone Zn was determined to availability have shown that Zn(HMTBa) exhibits be 54, 60 and 65 mg total Zn per kg/diet for Zn-MET, greater relative bioavailability than these other sources ZnSO and ZnO, respectively for birds fed a corn-SBM [11, 17, 18]. diet. Their studies also showed an inflection point for In experiments such as these, careful consideration must weight gain for ZnSO for chicks fed a soy isolate diet to be given to the response range of the outcome measures occur at 33 mg Zn/kg diet . Comparison of Zn sources (eg weight gain, tissue Zn, etc.). Differences between Zn above the inflection point would result in an underestima- sources can only be determined at low intakes (below tion of the bioavailability or performance difference that the requirement or inflection point). Homeostatic physio- may truly exist between Zn sources. These findings were logical mechanisms preclude the demonstration of differ- confirmed in our studies. Marked differences between ences between Zn sources, once the supplementation level Zn(HMTBa) and ZnSO ·H Owere observedat 30 and 2 4 2 is above the inflection point [8, 11, 19]. At deficient intake, 45 mg Zn/kg diet, but not at higher levels. In the presence Zn absorption is maximized. Bioavailability is significantly of excess Cu (250 mg Cu/kg diet), the requirement or in- dependent on the degree of absorption. In purified diets, flection point for weight gain, although not defined in this in the absence of phytate, antagonisms, or a challenge study, is likely higher than the 33 mg Zn/kg determined (lipopolysaccharides, etc.), there is little difference in by Wedekind et al., wherein no excesses of Ca or Cu were utilization between organic and inorganic sources. In present . Zhao et al. Journal of Animal Science and Biotechnology (2016) 7:13 Page 7 of 9 Table 4 Effects of organic Zn sources and high dietary CuSO on growth performance in broilers (Experiment 3) CuSO , mg/kg Zn source, 30 mg/kg D8 BW, g/bird D19 BW, g/bird Gain, g/bird Feed Intake, g/bird Feed:gain Mortality, % 8 Zn(HMTBa) 83 375 336 457 1.362 1.67 250 Zn(HMTBa) 82 367 328 438 1.336 0.83 8 Zn-MET 81 374 335 457 1.364 1.67 250 Zn-MET 80 356 317 447 1.408 2.50 SEM 1 4 4 12 0.030 1.39 Main effect means Cu level a a 8 82 375 335 457 1.363 1.77 b b 250 82 361 332 442 1.372 1.77 Zn source Zn(HMTBa) 82 371 332 447 1.349 1.25 Zn-MET 81 365 326 452 1.385 2.18 2 × 2 factorial arrangement, P value Zn source – 0.187 0.198 0.703 0.217 0.553 Cu level – 0.004 0.005 0.227 0.759 1.000 Zn Source* Cu level – 0.292 0.271 0.696 0.245 0.554 A total of 288 ROSS 308 male birds were used, with six cages per treatment, and 12 birds per pen a,b Means within a column with no common superscripts differ (P < 0.05) Our study had some limitations and strengths. A limi- these geographic areas, so the level used in this study tation of this study was the amount of dietary Cu se- might not be relevant for these regions. However, the lected for the elevated Cu condition. For environmental mineral antagonism demonstrated in our studies is still reasons, the European Union and China restrict the important, since antagonism could potentially happen at maximum amount of Cu in animal feed. The 250 mg/kg lower levels of Cu supplementation, and 250 mg/kg diet- diet CuSO is above the maximum allowed levels in ary Cu is a level used commercially in the United States. Table 5 Effects of Zn sources and dietary CuSO on tissue mineral content (Experiment 3) Cu levels, mg/kg Zn sources, Tibia Zn (ash based), Tibia Cu (ash based), Liver Zn (dry wt. based), Liver Cu (dry wt. based), 30 mg/kg mg/kg mg/kg mg/kg mg/kg 8 Zn(HMTBa) 143 6.5 104 13.5 250 Zn(HMTBa) 154 11.8 69 169.7 8 Zn-MET 140 6.0 93 13.3 250 Zn-MET 147 10.2 57 128.2 SEM 8 0.8 24 19.8 Main effect means Cu level b b 8 141 6.23 98 13.4 a a 250 150 11.0 63 150 Zn source Zn(HMTBa) 148 9.14 86 91.6 ZnSO 143 8.11 75 70.8 2 × 2 factorial arrangement, P value Zn source 0.543 0.229 0.653 0.296 Cu level 0.231 <0.001 0.168 <0.001 Zn Source* Cu level 0.780 0.513 0.981 0.301 One bird per pen was killed for tissue collection, total of six birds per treatment a,b Means within a column with no common superscripts differ (P < 0.05) Zhao et al. Journal of Animal Science and Biotechnology (2016) 7:13 Page 8 of 9 Organic trace minerals, in general, and Zn(HMTBa) , broiler industry. However, this could result in additional specifically, offer an alternative solution to address the antagonisms along with excess nutrient excretion to the challenge of providing required dietary minerals, at environment. Organic trace minerals have the potential lower levels, to meet animal nutritional requirements advantage of providing dietary minerals that are more while avoiding potential antagonism with other nutri- bioavailable. Consequently, less mineral is required to ents. Furthermore, in Experiment 2, differences between achieve a similar performance level compared to inorganic two Zn sources were only observed at 30 and 45 mg/kg, trace minerals [21, 22]. However, not all OTMs are equally not at 60 and 75 mg/kg. This suggests that the Zn re- capable of avoiding these antagonisms, and thus do not quirement (in the presence of 250 mg/kg Cu) is between always provide equivalent bioavailability. More research 45 and 60 mg/kg. In future studies, dietary Zn supple- is needed to fully decipher the mode of action of OTMs mentation should be chosen below the inflection point, and their benefits, compared to inorganic sources of to more sensitively assess bioavailability differences Zn, along with understanding the differences among among different Zn sources. Finally, in future studies, different OTMs. biological function parameters should be measured to understand how Cu antagonizes Zn, along with the Conclusions physiological consequences of that antagonism. For ex- Dietary 250 mg/kg Cu significantly impaired feed intake ample measurement of metallothionein, collagen, and and weight gain in birds fed ZnSO ·H O and had little 4 2 immune function have served as reliable indices in pre- or no impact in birds fed Zn(HMTBa) . No significant vious studies. More research is needed to understand differences were observed between Zn(HMTBa) and the biological consequences of Cu-Zn antagonism in Zn-Met. addition to performance and mineral storage in tissues. The statistical design of our studies and the use of an Abbreviations MW: molecular weight; OTM(s): organic trace mineral(s); Zn(HMTBa) : experimental basal diet containing phytate were some of [Zn bis(−2-hydroxy-4-(methylthio)butanoic acid)] at 2:1 ratio; Zn-MET: zinc the strengths of our studies. A factorial design offers ad- methionine. vantages over one-way ANOVA studies. There is more power to measure main effects as well as the ability to Competing interests measure interactions. Significant interactions or trends KJW, FY, PF, JLE, TRH, and MV-A are employees of Novus International, which manufactures and markets organic trace mineral products including zinc were observed in all three experiments which demonstrated chelated to hydroxymethylthiobutyric acid [Zn(HMTBa) ; MINTREX® Zn]. JZ, the improved performance of chelated Zn(HMTBa) vs RBS, and JJD were employees of Novus during the course of the study and ZnSO ·H O in the presence of elevated Cu. The presence analysis of the data; JJD is currently a paid consultant of Novus. 4 2 of phytate, common in cereals and grains, is an important Authors’ contributions antagonist that reduces Zn bioavailability. In the presence JZ participated in the 1) design of the study, 2) execution of the experiments, of antagonisms(ie,phytate,fiber, elevatedCu, Ca,P,etc.), 3) analyses of the data, 4) interpretation of the data, and 5) preparation of the bioavailability differences between OTM and ITM are in- manuscript; JZ is the guarantor of the data and other content in this manuscript. RBS participated in the 1) design of the study, 2) execution of creased . The presence of elevated Cu and phytate are the experiments, 3) analyses of the data, 4) interpretation of the data. JJD conditions that are relevant to diets fed commercially to participated in the 1) design of the study, 2) execution of the experiments, poultry and livestock. The advantages of the Zn(HMTBa) 2 3) analyses of the data, 4) interpretation of the data, and 5) preparation of the manuscript. KJW participated in the 1) design of the study, 2) execution of chelate demonstrated in our study under conditions of ele- the experiments, 3) analyses of the data, 4) interpretation of the data, and 5) vated Cu has also been demonstrated under other antagon- preparation of the manuscript. FY participated in the 1) analyses of the data, istic conditions (eg, elevated Ca and P) . Bioavailability 2) interpretation of the data, and 3) preparation of the manuscript. PF participated in the 1) execution of the experiments. THR participated in of Zn(HMTBa) , relative to ZnSO ·H O was 161 % (total 2 4 2 the 1) execution of the experiments. JLE participated in the 1) interpretation of bone Zn) and 248 % (metallothionein) in the presence of the data and 2) preparation of the manuscript. MV-A participated in the typical Ca and P (0.82 % Ca and 0.47 % available P). How- 1) design of the study, 2) analyses of the data, 3) interpretation of the data, and 4) preparation of the manuscript. All authors read and approved the ever, in the presence of elevated Ca and P (1.2 % Ca; 1 % final version of manuscript. available P) bioavailability of Zn(HMTBa) , relative to ZnSO ·H O was even greater: 441 % (total bone Zn) and 4 2 Acknowledgments 426 % (metallothionein) . The authors gratefully acknowledge the participation, expertise, and The use of high dietary CuSO as a growth promoter dedication of the entire staff of the Novus Research Farm. is common practice in both the broiler and swine indus- Author details tries in North America and some other geographical 1 Research and Development, Novus International, 20 Research Park Drive, areas. The bioavailability of other nutrients (Zn and P) Saint Charles, MO 63304, USA. Current affiliation: Poultry Technical Services, Adisseo USA, Alpharetta, GA 30022, USA. should be considered when high CuSO is used. One practical strategy is to increase the level of addition of Received: 10 June 2015 Accepted: 18 February 2016 these other nutrients as is often practiced in today’s Zhao et al. Journal of Animal Science and Biotechnology (2016) 7:13 Page 9 of 9 References 1. Apgar GA, Kornegay ET, Lindemann MD, Notter DR. Evaluation of copper sulfate and a copper lysine complex as growth promoters for weanling swine. J Anim Sci. 1995;73:2640–6. 2. Arias VJ, Koutsos EA. Effects of copper source and level on intestinal physiology and growth of broiler chickens. Poult Sci. 2006;85:999–1007. 3. Bremner I, Beattie JH. Copper and zinc metabolism in health and disease: speciation and interactions. Proc Nutr Soc. 1995;54:489–99. 4. Oestreicher P, Cousins RJ. Copper and zinc absorption in the rat: mechanism of mutual antagonism. J Nutr. 1985;115:159–66. 5. Hall AC, Young BW, Bremner I. Intestinal metallothionein and the mutual antagonism between copper and zinc in the rat. J Inorg Biochem. 1979;11:57–66. 6. Hill GM, Ku PK, Miller ER, Ullrey DE, Losty TA, O’Dell BL. A copper deficiency in neonatal pigs induced by a high zinc maternal diet. J Nutr. 1983;113:867–72. 7. Pang Y, Applegate TJ. Effects of dietary copper supplementation and copper source on digesta pH, calcium, zinc, and copper complex size in the gastrointestinal tract of the broiler chicken. Poult Sci. 2007;86:531–7. 8. Wedekind KJ, Hortin AE, Baker DH. Methodology for assessing zinc bioavailability: efficacy estimates for zinc-methionine, zinc sulfate, and zinc oxide. J Anim Sci. 1992;70:178–87. 9. Yan F, Waldroup PW. Evaluation of MINTREX® manganese as a source of manganese for young broilers. Int J Poult Sci. 2006;5:708–13. 10. Wang Z, Cerrate S, Coto C, Yan F, Waldroup PW. Evaluation of MINTREX® copper as source of copper in broiler diets. Int J Poult Sci. 2007;6:308–13. 11. Richards JD, Fisher P, Evans JL, Wedekind KJ. Greater bioavailability of chelated compared to inorganic zinc in broiler chicks in presence of elevated calcium and phosphorus. Open Access Animal Physiol. 2015;7:1–14. 12. AAFCO Committees. AAFCO 2015 Official Publication. Champaign (IL): Association of American Feed Control Officials (AAFCO); 2015. 13. National Research Council (U.S.), Subcommittee on Poultry Nutrition. Nutrient requirements of poultry. 9th ed. Washington: National Academy Press; 1994. 14. Yi GF, Atwell CA, Hume JA, Dibner JJ, Knight CD, Richards JD. Determining the methionine activity of Mintrex organic trace minerals in broiler chicks by using radiolabel tracing or growth assay. Poult Sci. 2007;86:877–87. 15. International AOAC. Official methods of analysis of AOAC International. 18th ed. Gaithersburg: AOAC International; 2005. 16. Ward TL, Watkins KL, Southern LL. Interactive effects of dietary copper and water copper level on growth, water intake, and plasma and liver copper concentrations of poults. Poult Sci. 1994;73:1306–11. 17. Manangi MK, Vazquez-Añon M, Richards JD, Carter S, Buresh RE, Christensen KD. Impact of feeding lower levels of chelated trace minerals vs. industry levels of inorganic trace minerals on broiler performance, yield, foot pad health, and litter mineral concentration. J Appl Poul Res. 2012;21:881–90. 18. Richards JD, Zhao J, Harrell RJ, Atwell CA, Dibner JJ. Trace mineral nutrition in poultry and swine. Asian-Aust J Anim Sci. 2010;23:1527–34. 19. Schlegel P, Windisch W. Bioavailability of zinc glycinate in comparison with zinc sulphate in the presence of dietary phytate in an animal model with Zn labelled rats. J Anim Physiol Anim Nutr (Berl). 2006;90:216–22. 20. Wedekind KJ, Baker DH. Zinc bioavailability in feed-grade sources of zinc. J Anim Sci. 1990;68:684–9. 21. Zhao J, Shirley RB, Vazquez-Añon M, Dibner JJ, Richards JD, Fisher P, et al. Effects of chelated trace minerals on growth performance, breast meat yeld, amd footpad health in commercial meat broilers. J Appl Poul Res. 2010;19:365–72. 22. Zhao J, Shirley RB, Hampton TR, Richards JD, Harrell RJ, Dibner JJ, et al. A dose titration comparison of MINTREX® versus ZnSO on performance in Submit your next manuscript to BioMed Central broilers with high dietary copper supplementation. Poult Sci. 2008;87:51–2. and we will help you at every step: • We accept pre-submission inquiries • Our selector tool helps you to ﬁnd the most relevant journal • We provide round the clock customer support • Convenient online submission • Thorough peer review • Inclusion in PubMed and all major indexing services • Maximum visibility for your research Submit your manuscript at www.biomedcentral.com/submit
Journal of Animal Science and Biotechnology – Springer Journals
Published: Feb 29, 2016
Access the full text.
Sign up today, get DeepDyve free for 14 days.