Review of potential risks associated with supplemental dietary exposure to nitrate-containing compounds in swine—a paradox in light of emerging benefits

Calcium nitrate has been reported to benefit reproductive outcomes in sows and their offspring when administered via the feed (15 to 19 mg/kg-body weight [bw]/day) during the periparturient period. Traditionally, dietary nitrate had been considered a methemoglobinemia (MetHb) risk in swine. Similar hazard concerns have existed in humans, but a recent benefit/risk analysis established that nitrate levels associated with well-recognized health benefits outweigh potential risks. A similar benefit/risk perspective in swine was lacking and challenged by sparse published hazard data, often referenced within larger reviews related to all livestock. The objective of this review was to better characterize the potential for adverse health and performance effects reported in the literature for swine consuming nitrate and to provide metrics for evaluating the reliability of the studies reviewed. Supplemental exposure via feed or drinking water was considered for any life stage, dose, and exposure duration. More than 30 relevant studies, including case reports and reviews, examined calcium, potassium, sodium, or unspecified nitrate salts at doses up to 1,800 mg nitrate/kg-bw/day for exposures ranging from 1 to 105 d. The studies primarily evaluated weight gain, blood methemoglobin levels, or vitamin A homeostasis in sows or growing swine. An extensive review of the literature showed reports of adverse effects at low nitrate doses to be of low reliability. Conversely, reliable studies corroborate nitrate intake from feed or drinking water at levels equal to or greater than the European Food Safety Authority’s no-observed-adverse-effect level (NOAEL) for swine of 410 mg nitrate/kg-bw/day, with no MetHb or other adverse effects on reproduction, growth, or vitamin A levels. Using a weight-of-evidence evaluation, we have moderate-to-high confidence that the NOAEL for nitrate supplementation in swine is likely between 600 and 800 mg/kg-bw/day. These levels are several-fold higher than dietary nitrate concentrations (19 mg/kg-bw/day) that are known to benefit birth outcomes in sows. This review elucidates the quality and reliability of the information sources historically used to characterize nitrate in swine feed as a contaminant of concern. Results from this evaluation can assist risk managers (e.g., regulatory officials and veterinarians) in consideration of proposed benefits as well as reassuring swine producers that low-level nitrate supplementation is not anticipated to be a concern.