L-Citrulline supplements are generally safe for healthy adults but can interact with several medications.Papadia, C., Osowska, S., Cynober, L., & Forbes, A. (2018). Citrulline in health and disease. Review on human studies. Clinical Nutrition, 37(6), 1823-1828. These include medicines for high blood pressure, erectile dysfunction, certain antidepressants, and others. We always recommend talking with your doctor before starting a new supplement if you have any chronic health conditions — especially cardiovascular conditions — or if you take ongoing medications. Citrulline supplements are not recommended for those who are pregnant or nursing.