A Double-blind Block Randomized Clinical Trial on the Effect of Zinc As a Treatment for Diarrhea in Neonatal Holstein Calves Under Natural Challenge Conditions

Diarrhea is the leading cause of death in neonatal calves and contributes to major economic losses. The objective of this double-blind randomized clinical trial was to evaluate the effect of oral inorganic or organic zinc supplementation as a treatment for neonatal diarrhea in calves. Seventy nine 1 to 8 day old male Holstein calves on a California calf ranch were block randomized to one of 3 treatments within 24h from their first onset of diarrhea. Calves received a daily dose of either a placebo composed of 80 mg of zinc-free powder, 381.54 mg of zinc methionine (Met) (equivalent to 80 mg of zinc), or 99.69 mg of zinc oxide (ZO) (equivalent to 80 mg of zinc) in 2L of a zinc-free oral rehydration solution (ORS). Calves were treated once daily until normal fecal consistency or for a maximum of 14 days. Upon enrollment and exit, calves were weighed, and blood, feces, and liver biopsies were collected for trace mineral analysis. Fecal samples at enrollment and exit were tested for E. coli K99, Cryptosporidium spp., rotavirus and coronavirus. Pre-treatment liver zinc concentrations for the 71 calves in the placebo, zinc Met, and ZO treatment groups were 710.6 (SEM=147.7), 852.3 (SEM=129.6), and 750.7 (SEM=202.9)mg/kg dry weight (DW), respectively. Exit liver zinc concentrations for the calves in the placebo, zinc Met, and ZO treatment groups were 728.9 (SEM=182.9), 1141.0 (SEM=423.8), and 636.8 (SEM=81.5)mg/kg dry weight, respectively. Although statistically non-significant, there were clinically important findings identified for each of zinc Met and ZO treatments. Calves treated with zinc Met gained on average 40 g/day during a diarrhea episode compared to a weight loss of 67 g/day on average in the placebo-treated calves (Power 19.9%). Calves treated with ZO had 1.4 times higher hazard of clinical cure compared to calves in the placebo group (Power 5.3%). Calves that were fecal positive to cryptosporidium spp. at enrollment and treated with zinc Met had higher odds of testing negative at exit compared to placebo calves (Odds Ratio (OR)=16.0). In contrast, calves treated with ZO tended to recover (fecal score=1) one day earlier compared to calves treated with a placebo (8.5 d vs. 9.7 d). The current trial identified clinically important findings that warrant further research to investigate zinc's therapeutic effect for calf diarrhea.