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Relative bioavailability of copper glycinate (CuGly) vs. copper sulfate (CuSul) as determined by multiple linear regression of phase 2 liver Cu concentrations on total supplemental intake of Cu (g). The data represented are log transformed and adjusted for initial liver Cu values.
Source publication
Sixty Angus (n = 29) and Angus-Sim-mental cross (n = 31) steers, averaging 9 mo of age and 277 kg of initial BW, were used in a 148-d study to determine the bioavailability of copper glycinate (CuGly) relative to feed-grade copper sulfate (CuSO(4)) when supplemented to diets high in S and Mo. Steers were blocked by weight within breed and randomly...
Citations
... Given that bioavailability results vary depending on initial and final Cu status, more work is needed to determine how to best study and apply bioavailability findings to cowherds and feedlots, as cattle can vary widely in Cu status. Hansen et al. (2008) found CuGly had a relative bioavailability of 131% compared to CuSO 4 after feeding 2 mg Mo/kg DM for 120 d, and liver Cu concentrations in control cattle decreased from 262 mg Cu/kg DM to 11 mg Cu/kg DM. After feeding 6 mg Mo/kg DM for an additional 28 d, the relative bioavailability of CuGly was 150% compared to CuSO 4 (Hansen et al., 2008). ...
... Hansen et al. (2008) found CuGly had a relative bioavailability of 131% compared to CuSO 4 after feeding 2 mg Mo/kg DM for 120 d, and liver Cu concentrations in control cattle decreased from 262 mg Cu/kg DM to 11 mg Cu/kg DM. After feeding 6 mg Mo/kg DM for an additional 28 d, the relative bioavailability of CuGly was 150% compared to CuSO 4 (Hansen et al., 2008). The difference between bioavailability determined by Hansen et al. (2008) and the present study may be partially due to the greater liver Cu status of steers in the present study. ...
... After feeding 6 mg Mo/kg DM for an additional 28 d, the relative bioavailability of CuGly was 150% compared to CuSO 4 (Hansen et al., 2008). The difference between bioavailability determined by Hansen et al. (2008) and the present study may be partially due to the greater liver Cu status of steers in the present study. The study conducted by Hansen et al. (2008) utilized steers that had an overall average liver Cu concentration of 256 mg Cu/kg DM, compared to 374 mg Cu/kg DM in the present study. ...
Chelated copper (Cu) sources, such as Cu glycinate (CuGly), may be more bioavailable relative to Cu sulfate (CuSO4) when fed to ruminants under antagonistic pressure. The objective of this study was to determine the bioavailability of CuGly (GemStone Cu; Phibro Animal Health) relative to CuSO4 in steers fed a diet supplemented with 0.3% sulfur and 2 mg molybdenum/kg of dry matter (DM). Sixty Angus crossbred steers (n = 12 per treatment) averaging 288 ± 4.85 kg were enrolled in a 90-d study and fed a corn silage-based diet with one of five Cu supplementation strategies, including no supplemental Cu (CON), 5 or 10 mg supplemental Cu from CuSO4/kg DM, and 5 or 10 mg supplemental Cu from CuGly/kg DM. Steers were housed in pens equipped with GrowSafe feed bunks (GrowSafe Systems Ltd., Airdire, AB, Canada), with six steers per pen. Growth performance, liver Cu, and plasma Cu were analyzed in the MIXED procedure of SAS 9.4 (SAS Inst. Inc, Cary, NC) with orthogonal contrasts to compare CON vs. 5 mg Cu/kg DM, CON vs. 10 mg Cu/kg DM, 5 vs. 10 mg Cu/kg DM, and CuSO4 vs. CuGly. Copper indices were regressed against Cu intake and slopes were calculated using the GLM procedure SAS. Dietary Cu supplementation did not affect steer body weights on days 0, 28, 56, or 90 (P ≥ 0.52), average daily gain, dry matter intake, or gain:feed (P ≥ 0.36). Final plasma Cu concentration did not differ between CON vs. 5 mg Cu/kg DM (P = 0.79), CON vs. 10 mg Cu/kg DM (P = 0.65), or 5 vs. 10 mg Cu/kg DM (P = 0.39). Steers receiving CuSO4 tended to have greater final plasma Cu concentrations than those receiving CuGly (P = 0.08). Initial liver Cu concentration averaged 374 mg Cu/kg DM, which is considered highly adequate. No steers reached deficient Cu status by the end of the 90-d period. Control steers had lesser final liver Cu concentrations than supplemented steers (P ≤ 0.04). Steers receiving 10 mg supplemental Cu/kg DM had greater liver Cu concentrations than those receiving 5 mg supplemental Cu/kg DM (P = 0.01). Copper source had no effect on final liver Cu concentrations (P = 0.57) and based on liver Cu and Cu intake the bioavailability of CuGly was similar to CuSO4 (115%; P = 0.27). The initially high Cu status and the fact that cattle did not become Cu deficient may have impacted the relative bioavailability results, and more research is needed to investigate the role initial Cu status and antagonistic pressure play in the bioavailability of chelated Cu sources.
... In addition to liver concentrations, BSS reduced the concentration of Cu in serum, but the response was of lesser magnitude. Serum Cu concentrations have limited utility in assessing Cu status (Ensley 2020) as circulating Cu concentrations are affected by intestinal absorption of Cu as well as mobilization of stored Cu from the liver, which is tightly regulated by homeostatic mechanisms (Hansen et al., 2008). Previous research has shown that plasma and liver Cu concentrations were not correlated when cattle had liver Cu concentrations > 40 mg/ kg (Claypool et al., 1975). ...
In the Northern Great Plains, cattle may be exposed to water with an elevated sulfate concentration resulting in ruminal hydrogen sulfide (H2S) production and risk of copper deficiency. There are currently few strategies available to help mitigate effects arising from high-sulfate water (HS). The objective of this study was to evaluate the effects of feeding a moderate-forage diet with or without bismuth subsalicylate (BSS; 0.0% vs. 0.4% DM basis) when provided water with a low- (LS; 346 ± 13) or HS (4,778 ± 263 mg/L) concentration on feed and water intake, ruminal H2S concentration, and liver and serum trace-mineral concentrations. Twenty-four Limousin × Simmental cross beef heifers (221 ± 41 kg) were stratified based on initial liver Cu into a completely randomized block design with a 2 × 2 factorial treatment arrangement. Feed and water intake (measured weekly), ruminal H2S concentration (measured on days 42 and 91), liver (measured on days −13 and 91), and serum trace-mineral concentrations (measured on days 1, 28, 56, and 91) were evaluated. Initial liver trace-mineral concentrations were used as a covariate in the statistical model. Water intake tended to be reduced with the inclusion of BSS (P = 0.095) but was not affected by water sulfate (P = 0.40). Water sulfate and BSS did not affect dry matter intake (DMI; P ≥ 0.89). Heifers consuming HS had a ruminal H2S concentration that was 1.58 mg/L more (P < 0.001) than LS. The inclusion of BSS reduced (P = 0.035) ruminal H2S concentration by more than 44% (1.35 vs. 0.75 mg/L). Regardless of the water sulfate concentration, heifers fed BSS had lesser liver Cu concentration (average of 4.08 mg/kg) than heifers not provided BSS, and when not provided BSS, HS had lesser Cu than LS (42.2 vs. 58.3; sulfate × BSS, P = 0.019). The serum concentration of Cu did not differ over time for heifers not provided BSS; whereas, heifers provided BSS had lesser serum Cu concentration on day 91 than on days 28 and 55 (BSS × time, P < 0.001). The liver concentration of selenium was reduced (P < 0.001) with BSS inclusion but the selenium concentration in serum was not affected by sulfate, BSS, or time (P ≥ 0.16). BSS reduced ruminal H2S concentration, but depleted liver Cu and Se. Moreover, sulfate concentration in water did not appear to affect DMI, water intake, or growth, but increased ruminal H2S and reduced liver Cu concentration.
... A redistribution of Copper from the liver to other tissues occurs. The redistribution to the kidney results in increased urinary Copper execration [23]. Since Cu is involved in normalized function of many enzymes, such as cytochrome c oxidase, which is complex IV in mitochondrial electron transport chain, cerulopasmin, Cu/Zn superoxide dismutase, and in amine oxidases. ...
The object of this study were to evaluate the effect of molybdate and sulfate overload alone or in combination overload intake on copper outcome with regard toxicopathological changes in mature male rats. Twenty eight adult male rats were housed and arbitrarily divided into four equal groups (seven rat/group) and treated as follows for 60 days: control received distilled water, groups T1 received sodium molybdate 50 mg/kg B.W and T2: given orally 500 mg/kg B.W of sodium sulfate and T3 group were given sodium molybdate and sodium sulfate in combination at half dose in comparison with T1 and T2 doses. The blood tests results, which included Red Blood Cell count, hemoglobin concentration and Packed Cell Volume % that conducted a after one month and at the end of the experiment showed a significant reductions in general but were more in T1 group followed by T2 group, while T3 group showed less decline than that recorded in each of T1 and T2 groups. These functional changes were accompanied by structural changes in the hepatic and renal tissues. Histopathological changes following molybdate (50 mg/kg B.W) exposure were manifested by extensive areas of necrosis, hemorrhage, and hyperplasia of bile ductules. Besides focal area of necrosis and suppurative granuloma observed in livers of rats received 500 mg/kg B.W of sodium sulfate, mild infiltrate of mononuclear cell within the hepatic parenchyma, suppurative granuloma and proliferation of kupffer’s cells with hyperplasia of bile ductules seen in liver of rats received combination of them at half dose. While section of kidney from T1 group showed marked fibrous thickening of the capsule, severe cortical hemosiderosis with infiltrate of plasma cell and neutrophils, While in T2 group showed atrophy of glomerular tuft, focal interstitial mononuclear cells infiltration with deposition of hyaline cast. The histological changes revealed that renal damage was also observed in T3 group but at a little degree, depending on the result of this study it can be concluded that molybdate and sulfate alone and in combination succeeded to induce copper deficiency with severe changes in hematological and histopathological parameters in rats.
... [56] state that copper and zinc combined with amino acids, accumulate in the liver at higher levels in sheep. Hansen et al. [57] reported that copper glycinate showed signi cant (p < 0.01) bioavailability in calves with high levels of sulfur and molybdenum in their diets, while Nockels et al. [58] reported that copper-lysine accumulated in the body at a higher level in calves. ...
In this study, organic copper and zinc minerals, which were reduced by 25% of the inorganic copper (Cu) and inorganic zinc (Zn) levels recommended for sheep, were determined by the lambs live weight, scrotum length, scrotum circumference, testis length, testicular diameter, the effects on serum, fleece, and stool mineral levels, semen delivery age, and the histological structure of testis were investigated. Depending on their nutrition with organic or inorganic minerals, male lambs born from sheep were divided into two groups, one organic and the other inorganic given a ration containing copper and zinc minerals. 5.25 mg/kg DM copper-chelate (2-hydroxy-4-methylthiobutyrate) and 15.0 mg/kg DM zinc-chelate were given to the experimental group, and 7 mg/kg DM copper-sulfate and 20 mg/kg DM zinc-sulfate were given to the control group. At the end of the experiment, it was determined that the difference between the live weight, scrotum length and circumference, testicular length and diameter, and the mean age of sperm delivery with 50% motility were not statistically significant. It was determined that the mean values of serum copper, serum zinc, and fleece zinc were numerically higher in the experimental group, and the average fleece copper value was significantly higher in the experimental group. At the end of the experiment, the mean fecal copper level and the mean fecal zinc level were found to be significantly lower in the experimental group. Moreover, it was determined that the height of the tubular epithelium was higher in the experimental group. Although organic copper and organic zinc were given at lower levels, it was determined that they showed similar results with inorganic copper and inorganic zinc and even better in terms of some parameters.
... In beef cows, plasma Cu concentrations did not decrease below normal concentrations until liver Cu concentrations were less than 40 mg/kg of DM (Claypool et al., 1975). Studies in growing cattle indicate that plasma Cu concentrations do not decrease substantially until liver Cu is less than 20 mg/kg of DM (Phillippo et al., 1987;Hansen et al., 2008). Liver Cu is affected by dietary Cu, age, species, and breed and possibly by sex and gestation. ...
... Using this definition liver Cu less than 7 mg/kg of DM indicates a high risk, and concentrations of 7 to 20 mg/kg of DM suggest a possible risk for disorders that respond to Cu supplementation. In growing cattle liver Cu concentrations of approximately 10 mg/kg of DM or lower have been associated with reduced growth rate, compared with Cusupplemented animals (Phillippo et al., 1987;Hansen et al., 2008). The growth response to Cu supplementation is most evident in cattle fed diets high in Mo and S (Phillippo et al., 1987). ...
... Some research with organic forms of copper suggests higher absorption than from Evaluation of Trace Mineral Sources copper sulfate during stress 24 or in situations where dietary molybdenum and sulfur are high. 25 In contrast other studies have found no differences in bioavailability of copper from organic sources and copper sulfate. 26,27 Studies in lambs 28 and cattle 24 indicated that apparent absorption of zinc from zinc methionine and inorganic zinc oxide or zinc sulfate was similar. ...
Several trace mineral sources, including inorganic, numerous organic, and hydroxychloride sources, are available for dietary supplementation or inclusion in a free-choice supplement. Inorganic forms of copper and manganese differ in their bioavailability. Although research results have been variable, organic and hydroxychloride trace minerals are generally considered more bioavailable than inorganic sources. Research indicates that fiber digestibility is lower in ruminants fed sulfate trace minerals compared with hydroxychloride and some organic sources. Compared with free-choice supplements, individual dosing with rumen boluses or injectable forms ensures that each animal receives the same quantity of a trace mineral.
... ATP7A transports copper to the portal vein and then through serum proteins such as albumin for transportation to the liver. When copper ions exceed standard requirements, they are bound to metallothionein 1 (MT1) and metallothionein 2 (MT2) and stored in liver cells (45). ATPase copper transporting beta (ATP7B) primarily functions in the efflux of copper ions from cells (46). ...
As an essential nutrient, copper’s redox properties are both beneficial and toxic to cells. Therefore, leveraging the characteristics of copper-dependent diseases or using copper toxicity to treat copper-sensitive diseases may offer new strategies for specific disease treatments. In particular, copper concentration is typically higher in cancer cells, making copper a critical limiting nutrient for cancer cell growth and proliferation. Hence, intervening in copper metabolism specific to cancer cells may become a potential tumor treatment strategy, directly impacting tumor growth and metastasis. In this review, we discuss the metabolism of copper in the body and summarize research progress on the role of copper in promoting tumor cell growth or inducing programmed cell death in tumor cells. Additionally, we elucidate the role of copper-related drugs in cancer treatment, intending to provide new perspectives for cancer treatment.
... An alternative to ITM supplementation is the use of organic sources of TM (OTM), which comprise chelates between the mineral and an organic molecule. The structure of OTM is expected to avoid most unwanted chemical reactions in the gastrointestinal tract and improve the bioavailability of supplementary TM for intestinal absorption, enhancing the TM status in circulation and in tissues (Cao et al., 2000;Spears, 2003;Wright and Spears, 2004;Hansen et al., 2008;Pal et al., 2010;Galbraith et al., 2016). Thus, a more effective supplementation with TM in the diet is expected to improve antioxidant capacity and immune function, potentially decreasing the incidence of postpartum diseases and enhancing feed intake, which in turn would reduce the occurrence of metabolic problems and improve overall performance of dairy cows. ...
Our objectives were to evaluate the effects of complete replacement of supplementary inorganic salts of trace minerals (ITM; Co, Cu, Mn, Zn sulfates and Na selenite) by organic trace minerals (OTM; Co, Cu, Mn, Zn proteinates and selenized yeast) in both pre- and postpartum diets on TM concentrations in body fluids and liver, antioxidant and inflammation biomarkers in blood, and postpartum health of dairy cows. Pregnant cows were blocked by parity and BCS and randomly assigned to ITM (n = 136) or OTM (n = 137) 45 d before expected calving. Both groups received the same pre- and postpartum diets except for the source of supplementary TM. The day of calving was considered study d 0 and blood was collected on d -45, -21, -14, -10, -7, -3, 0, 3, 7, 10, 14, 23, 65 and 105 for analyses of TM and biomarkers. Concentrations of TM were also investigated in liver (d 105), milk (d 7, 23, 65, 105), urine (d -21, 21, 65, 105), ruminal fluid and feces (d -21, 21, 65). Incidence of clinical and subclinical health conditions were evaluated. Complete replacement of ITM by OTM resulted in greater concentration of Se in serum (0.084 vs. 0.086 µg/mL; P<0.01), milk (0.24 vs. 0.31 µg/g; P<0.01), and ruminal fluid (0.54 vs. 0.58 µg/g; P=0.06), and reduced concentration of Se in urine (1.54 vs. 1.23 µg/g; P<0.01). For concentration of Co in serum, an interaction between treatment and time was detected (P<0.01). Cows supplemented with OTM had greater concentrations of Co on d -7 and 0 (0.30 vs. 0.33 ng/mL; P<0.01) but lower concentrations of Co on d 23, 65, and 105 (0.34 vs. 0.31 ng/mL; P<0.05), in addition to reduced concentration of Co in feces (1.08 vs. 0.99 µg/g; P=0.04) and, for multiparous only, in urine (0.019 vs. 0.014 µg/g; P<0.01). Cows supplemented with OTM had lower postpartum concentrations of glutamate dehydrogenase (20.8 vs. 17.8 U/L; P<0.05) and higher albumin on d -10 (36.0 vs. 36.7 g/L; P=0.04) and 23 (36.9 vs. 37.6 g/L; P=0.03) relative to calving. Primiparous cows fed OTM had lower concentration of ceruloplasmin in plasma (55 vs. 51 mg/L; P≤0.05). Cows supplemented with OTM had less incidence of lameness (14 vs. 7%; P=0.05), elevated NEFA (61 vs. 44%; P<0.01), and multiple metabolic problems (35 vs. 20%; P<0.01). Despite the lack of differences in Cu, Mn, and Zn concentrations and antioxidant capacity, complete replacement of ITM by OTM altered concentrations of Se and Co, supported liver and hoof health, and reduced the risk of postpartum elevated NEFA.
... Cattle offered either organic or inorganic Cu did not differ in growth rate or Cu status [12,13]. The bioavailability of Cu lysine and Cu sulfate were similar in vitro [14], and the bioavailability of Cu glycinate was greater than that of Cu sulfate in diets with high sulfur and molybdenum contents [15]. ...
Copper (Cu) is essential for the health of livestock, however, the optimal source and level of dietary Cu for yaks are uncertain. To fill this important gap, we designed an in vitro study to examine the effects of three Cu sources, namely Cu methionine (Met-Cu), Cu chloride (CuCl2) and tribasic Cu chloride (TBCC), at five levels, namely 5, 10, 15, 20 and 25 mg/kg DM (includes Cu in substrate), on rumen fermentation in yaks. In vitro dry matter degradability (IVDMD) and amylase activity were greater (p < 0.05) with added Met-Cu than the other two Cu sources, and ammonia nitrogen (NH3-N), microbial protein (MCP) and propionate contents were greater with Met-Cu and CuCl2 than with TBCC. Total gas production and lipase activity were greater with Met-Cu and TBCC than CuCl2 (p < 0.05), which meant that the metabolizable energy yield was greater in the two former Cu sources than the latter, but CH4 production did not differ (p = 0.92) among Cu sources. IVDMD and lipase activity were greatest (p < 0.05) at 15 mg Cu/kg DM in the substrate and MCP, isobutyrate, butyrate and isovalerate contents, and amylase and trypsin activities were greatest or second greatest at 10 and 15 mg Cu/kg DM. It was concluded that Met-Cu was the best source of Cu and 10 to 15 mg Cu/kg DM was the optimal level for yaks, at least under in vitro conditions.
... Differences in chemical characteristics between the organic sources (lysine vs. proteinate) may in part explain the difference while response criteria also differed (apparent absorption vs. plasma Cu) [198]. A more recent study using Cu glycinate relative to feed-grade Cu sulphate found the organic form was more available than the inorganic sulphate when supplemented to diets high in S and Mo [199]. ...
... The pH-dependent solubility of organic compounds could explain some differences in the experimental results. Higher bioavailability in comparison with Cu sulphate was found when feeding diets with high molybdenum and sulphur in Cu chelate [175] and Cu glycinate [199]; however, another experiment with high Mo and S showed similar bioavailability to Cu sulphate with Cu proteinate [203]. Van den Top summarised the results of a selection of bioavailability trials in 2005 with different Cu sources for ruminants and concluded that the evidence was not fully in agreement at that time. ...
The importance of dietary supplementation of animal feeds with trace minerals is irrefutable, with various forms of both organic and inorganic products commercially available. With advances in research techniques, and data obtained from both in-vitro and in-vivo studies in recent years, differences between inorganic and organic trace minerals have become more apparent. Furthermore, differences between specific organic mineral types can now be identified. Adhering to PRISMA guidelines for systematic reviews, we carried out an extensive literature search on previously published studies detailing performance responses to trace minerals, in addition to their corresponding relative bioavailability values. This review covers four of the main trace minerals included in feed: copper, iron, manganese and zinc, and encompasses the different types of organic and inorganic products commercially available. Their impact from environmental, economic, and nutritional perspectives are discussed, along with the biological availability of various mineral forms in production animals. Species-specific sections cover ruminants, poultry, and swine. Extensive relative bioavailability tables cover values for all trace mineral products commercially available, including those not previously reviewed in earlier studies, thereby providing a comprehensive industry reference guide. Additionally, we examine reasons for variance in reported relative bioavailability values, with an emphasis on accounting for data misinterpretation.
