Use of melatonin plus citrulline or arginine to mitigate ergot alkaloid-induced vasoconstriction in sheep

Authors: Klotz, James; CHECURA, CELINA - Clemson University; MAY, JOHN - University Of Kentucky; DUCKETT, SUSAN - Clemson University

Submitted to: Animal Feed Science and Technology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/10/2025
Publication Date: 9/17/2025
Citation: Klotz, J.L., Checura, C.M., May, J.B., Duckett, S.K. 2025. Use of melatonin plus citrulline or arginine to mitigate ergot alkaloid-induced vasoconstriction in sheep. Animal Feed Science and Technology. 329. Article 116502. https://doi.org/10.1016/j.anifeedsci.2025.116502.
DOI: https://doi.org/10.1016/j.anifeedsci.2025.116502

Interpretive Summary: Herbivores that graze toxic endophyte-infected tall fescue can consume ergot alkaloids. These toxins prevent overgrazing preserving the plant, but cause fescue toxicosis in livestock. A primary symptom of fescue toxicosis is a chronic vasoconstriction that results in numerous symptoms that characterize the syndrome. Supplementation of melatonin, citrulline, and arginine have all been separately shown to induce relaxation of blood vessels. This study sought to evaluate the efficacy in the supplementation of melatonin, melatonin + citrulline, or melatonin + arginine to offset or mitigate the vasoconstriction caused by ergot alkaloids in sheep. Blood concentrations of citrulline and melatonin were substantially increased and arginine was slightly increased with the dietary supplementation treatments. However, the ergot alkaloid induced vasoconstriction was not moderated by any of the supplementation treatments. The results of this experiment will be important to other researchers that are looking to identify treatments that can easily be implemented by producers to reduce or completely offset the negative effects of fescue toxicosis in grazing livestock production systems.

Technical Abstract: Grazing livestock can encounter ergot alkaloids in wildtype endophyte-infected (E+) tall fescue that can result in fescue toxicosis. Fescue toxicosis, a form of ergotism, causes chronic vasoconstriction in livestock that results in reproductive, digestive, and thermoregulatory issues that negatively impact livestock performance. Melatonin, citrulline, and arginine have all been previously associated with vasodilation. The objective of this experiment was to evaluate the dosing of melatonin, melatonin + citrulline, and melatonin + arginine in sheep as potential supplements to offset the vasoconstriction caused by ergot alkaloids. Eighteen Suffolk ewe lambs were randomly divided across 3 treatments: 1) melatonin (100 ug/kg BW/d; MEL), 2) MEL + citrulline drench (81 mg/kg BW/dose; MEL-CIT) and 3) MEL + arginine drench (81 mg/kg BW/dose; MEL-ARG). Jugular blood samples and Doppler ultrasound measurements of cross-sections of left common carotid artery were taken daily for 12 days. Samples collected on d 1 – 3 were considered baseline values with lambs only receiving TMR. On d 4 – 6, lambs received TMR plus E+ seed (1.77 mg/ewe/d ergovaline + ergovalinine) and on d 7 – 12 lambs received either MEL, MEL+CIT, or MEL+ARG supplemented with the TMR and E+ seed. For all 3 treatments, the supplementation of MEL resulted in a large increase in plasma melatonin on d 7 – 12 compared to d 1 – 6 (P < 0.05). The MEL+CIT resulted in 2- to 3-fold increase in plasma citrulline on d 7 – 12 compared to the other 2 treatment groups (P < 0.05and compared to d 1 – 6 (P < 0.05). Plasma arginine was greater in MEL+CIT and MET+ARG lambs on d 7 and 8 than MEL and in all treatments on d 1 – 6 (P < 0.05). The Doppler measurements demonstrated a steady decline in heart rate associated across days with the initiation of the E+ seed dosing (P < 0.01) and did not differ across treatment groups. Luminal area of the carotid artery decreased with E+ seed dosing (P < 0.01) and did not differ across treatments during d 7 – 12 (P = 0.41). Conversely, time-averaged mean velocity increased with E+ seed dosing (d 4- 6; P < 0.01), then plateaued and did not differ when treatments were administered (d 7 -12). There was no significant effect of treatment on carotid artery blood flow. The successful increase in plasma melatonin, arginine, or citrulline did not offset the vasoconstriction associated with ergot alkaloids. Future research should evaluate dosage level of fescue toxicosis mitigation supplements and consider alternative blood vessels to assess vasoconstriction.