In a double-blind trial, sustained-release ISMN plus oral NAC (2,400 mg twice per day) for two days led to significantly longer exercise time than ISMN plus placebo.¹ This outcome suggests that NAC may have increased the efficacy of ISMN. There were no differences in side effects between the two groups.

Some persons taking nitroglycerin or isosorbide mononitrate may find that it loses efficacy over time. This is because the body adapts to the drug, a process known as developing tolerance. One study found that taking 2 grams three times daily of vitamin C can decrease this effect when nitroglycerin patches are simultaneously used.² Similar benefits have been confirmed in another study.³ However, it should be noted that it is also possible to avoid tolerance to these drugs by simply changing the dosing schedule. People taking ISMN or nitroglycerin should talk with their pharmacists about avoiding drug tolerance.