Evidence for oral agmatine sulfate safety – A 95-day high dosage pilot study with rats

• Published in: Food and chemical toxicology 2013-12, Vol.62, p.758-762
• Main Authors: Gilad, Gad M., Gilad, Varda H.
• Format: Article
• Language: English
• Subjects: abnormal behavior; absorbed dose; Administration, Oral; adults; agmatine; Agmatine - administration & dosage; Agmatine - adverse effects; Agmatine - analogs & derivatives; Agmatine treatment; Animals; arginine; Behavior, Animal - drug effects; Biological and medical sciences; Blood pressure; Blood Pressure - drug effects; body weight; Body Weight - drug effects; cages; clinical trials; Dietary ingredients; disease models; Dose-Response Relationship, Drug; Drinking - drug effects; drinking water; feces; Female; fur; Male; Medical sciences; necropsy; Neuroprotection; oral administration; Pilot Projects; Rats; Rats, Wistar; Toxicity Tests, Subchronic; Toxicology; urination; Wistar rats
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2013.10.005

•Safety assessment of agmatine, decarboxylated arginine, is required as interest in its therapeutic potential increases.•A pilot study assesses the general safety of a 95-day high dosage treatment with oral agmatine sulfate in laboratory rats.•Results suggest that a high dosage, sub-chronic oral agmatine sulfate treatment may be safe in laboratory rats.•The study further highlights the therapeutic potential of agmatine. Agmatine, decarboxylated arginine, exerts beneficial effects in various experimental disease models. Clinical trials indicate the safety and effectiveness of short-term (up to 21days) high dose regimens of oral agmatine sulfate, but longer term studies are lacking. This pilot study undertook to assess the safety of a longer term high dosage oral agmatine sulfate in laboratory rats. Adult Wistar rats consumed 5.3g/l agmatine sulfate in their drinking water for 95days, a regimen estimated to result in a daily dosage of absorbed agmatine of about 100mg/kg. Animals’ body weight, water consumption and blood pressure were periodically measured, and general cage behavior, fur appearance, urination and feces appearance monitored. These parameters were also determined at 20days after treatment cessation (day 115). On days 95 and 115, animals were euthanized for gross necropsy assessment. Agmatine-treated rats showed slight, but significant reductions in body weight and blood pressure, and reduced water consumption during treatment, which recovered completely within 20days after treatment cessation. Otherwise, no abnormal behaviors or organ pathologies were observed. These findings are first to suggest apparent safety of sub-chronic high dosage dietary agmatine sulfate in laboratory rats, thus lending further support to the therapeutic applications of agmatine.