Copper sulfate and Phytase

Blavi L, Solà D, Monteiro A, Pérez JF, Stein HH. Inclusion of dicopper oxide instead of copper sulfate in diets for growing-finishing pigs results in greater final body weight and bone mineralization, but reduced accumulation of copper in the liver. J Anim Sci. 2021 Jun 1;99(6):skab127. PMC free article

We at CopperOne would like to say that the leading dietary copper supplement, cupric sulfate (CuSO₄), was compared side by side with cuprous nicotinic acid and the latter was found to be superior in a large species that resembles humans. This is dimply not the case. A team from France, Spain, and the United states compared cuprous oxde (C₂O) with CuSO₄ in the feed of finishing pigs. Our original thought was that these experiments were conducted because the authors considered cuprous copper more bioavailable. The concern was that Cu²⁺ is an inhibitor of an enzyme called phytase, which which makes phosphate found in the plant compound phytic acid more bio available. The featured image came from Bacillus amyloliquefaciens. Pytase binds Ca²⁺ as part of the process of removing phosphates from the plant compound phytic acid. Since the enzyme phytase is a widely used feed supplement to increase the bio availability of phosphate of plant feed in farm animals, Blavi and coauthors are proposing that Cu²⁺ supplements may affect bone mineralization by preventing the absorption of phosphate from phytic acid.. Their concerns were also centered around Cu²⁺ binding to phytic acid more so than Cu²⁺ binding to Ca2+ sites on supplemental phytase.

1. The Diet

As pigs grow, their nutritional needs change. This study used slightly different feeding schemes for different stages of growth. At the end of each stage, a representative pig of the group was slaughtered and analyzed for bone mineral content and other parameters.

• Phase 1, days 1 to 26
• phase 2, days 26 to 61
• phase 3, days 61 to 96
• phase 4, days 96 to 116.

Note that the pigs are already being supplemented with niacin. In an actual farm setting, why not use cuprous nicotinic acid instead of di cuprous oxide?

2. The diets

The take home message is that the diets are pretty similar.

3. Weight gain

The 250 mg/kg Cu₂O supplemented pigs (superscript “a”)gained more weight in all four phases than the controls(superscripts “b” and “c”) . Pigs on the 250 Cu₂O gained more weight in phases 3 and 4 than their 250 CuSO₄ counter parts.

Perhaps the other main point of Table 2 is that the pigs on Cu₂O were not eating more than the pigs on the CuSO₄.

4. Other meat industry parameters, no difference

Note that these pigs already had supplemental copper in their diets by way of the mineral/vitamin mix in Table 1. Additional copper made no difference in these parameters.

5. 250mg/kg Cu is too much?

This may not have been what the authors were considering at first, but look at the numbers. Going from 125 to 250 mg/kg Cu in the diet increases copper in the liver over 10x in Phase 1. In Phase 4 the increase is not as dramatic. Less copper accumulates in the liver in the 250 Cu₂O group. Export in the bile is naturally much greater than in the control group. By Phase 4 more Cu⁺ was being exported in the bile in the Cu₂O group than in the CuSO₄ group. Was this because the ATP7B export pump uses Cu⁺. We can only speculate at this point.Mutations in ATP7B define Wilson’s Disease, which is defined by copper poisoning by failure to export excess in the bile.

Why the spleen was examined was not entirely clear. The spleen may play a role in the immune system and processing of damaged red blood cells, but its role in copper handling is less clear. Perhaps the spleen was simply in the abdominal cavity neighborhood. At the potentially toxic copper concentration of 250mg/kg, the copper content of the spleen was statistically the same as the control in the 250 Cu₂O group but elevated in the CuSO₄ group.

6 Bone mineralization

Table 6 has been divided into two sections just because there are two points to be made by the information by this table. Recall our first issue with CuSO₄ is that it might bind to phytase and decrease the pigs’ ability to make use of phosphate bound to phytic acid in the soy and corn they were consuming. Bone is composed of collagen fibers with hydroxyapatite deposits. Hydroxyapatite is calcium and phosphate. No changes were seen in the percentages of calcium and phosphate in the bone ash. One would expect that burning the bone to ash would remove all traces of collagen.

The total amount of noncombustible (ash) in the bone is greatest in the 250 Cu₂O treatment. Calcium data is a bit more ambiguous. We can say that 250 Cu₂O is better than 250 CuSO₄ but we cannot say Cu₂O is better than the control diet with no additional copper. The bone phosphate data confirm the investigators’ concern that CuSO₄ is inhibiting phytase. 250 Cu₂O treated pigs have (statistically) the same phosphate content in their bones as the control group of pigs.

Moving on to the copper and zinc component of Figure 6 things get more complicated and interesting. It is assumed mg/kg means mg/kg bone ash and that mg/kg means mg/kg non combusted bone.

Note that both copper compounds decrease the amount of zinc (in bone ash?) in Phase 1 but not Phase 4.

What did the authors discuss and conclude?

They mentioned that Cu is absorbed by the intestine in the +1 oxidation state rather than the +2 state. They discussed Cu₂O being less water soluble than CuSO₄, less likely to dissolve, dissociate into ions, and form complexes with phytic acid. The intestinal pH was also discussed somewhat. The authors also discussed some previous studies that we may look into some more. Their review of the literature led them to conclude that hepatic copper is a good indicator of copper absorbed in farm animals. We at CopperOne would probably be speculating too much if we proposed Cu²⁺ could get stuck in the liver and never transported out of the liver on ceruloplasmin. Certainly more copper got incorporated into the spleen in CuSO₄ fed pigs, see figure 5. This is a very interesting study that has given us a lot to think about.