For most people, arginine has so far appeared to be free of obvious side effects. However, longer-term studies are needed to confirm its safety.

In a double-blind study, supplementation with 9 grams of arginine per day for six months, beginning within 3 to 21 days after a heart attack, resulted in an increase in the mortality rate.⁶ Therefore, people who have recently suffered a heart attack should probably not take large amounts of arginine. Arginine is beneficial for other manifestations of heart disease, such as heart failure and angina. However, because of the potential for arginine to cause adverse effects in heart patients, people with heart disease should consult a doctor before taking arginine.

There have been two case reports of severe allergic reactions following intravenous administration of L-arginine;⁷ however, allergic reactions have not been reported after oral administration.

People with kidney or liver disease should consult their doctor before supplementing with arginine. Some doctors believe that people with herpes (either cold sores or genital herpes) should not take arginine supplements, because of the possibility that arginine might stimulate replication of the virus.

Administration of large amounts of arginine to animals has been found both to promote⁸ and to interfere with cancer growth.⁹ In preliminary research, high intake (30 grams per day) of arginine has increased cancer cell growth in humans.¹⁰ On the other hand, in people with cancer, arginine has been found to stimulate the immune system.¹¹ At this time it remains unclear whether arginine is dangerous or helpful for people with cancer.