Nitroglycerin
  • N-Acetyl Cysteine (NAC) - Possible Benefits and Risks
  • Vitamin C - Supplementation Possibly Helpful
  • Arginine - Supplementation Possibly Helpful
  • Folate - Supplementation Possibly Helpful
  • Vitamin E - Supplementation Possibly Helpful
En Español (Spanish Version)

Nitroglycerin (NTG) is one of the most commonly used treatments for quick relief of anginal pain. Related drugs include isosorbide dinitrate and isosorbide mononitrate.

Possible Benefits and Risks
N-acetyl cysteine (NAC) is a specially modified form of the dietary amino acid cysteine that has various proposed uses.

Nitrates such as nitroglycerin lose some of their effectiveness over time. According to some studies, 1,2 but not all, 3,4 the supplement N-acetyl cysteine might help these drugs work better. However, there's a catch: the combination of NAC and nitroglycerin appears to cause severe headaches. 5,6

Taking NAC with nitroglycerin may be beneficial in some cases. However, unpleasant side effects probably limit the use of this combination.

Note: Angina is too serious a disease for self-treatment. If you have angina, do not take any supplement except on a physician’s advice.

Supplementation Possibly Helpful
Vitamin C may help prevent the development of tolerance to nitrate medications such as nitroglycerin. According to a double-blind study of 48 individuals, use of vitamin C at a dose of 2000 mg three times daily helped maintain the effectiveness of nitroglycerin. 10 These findings are supported by other studies as well. 9,13,14

Note: Angina is too serious a disease for self-treatment. If you have angina, do not take any supplement except on a physician’s advice.

Supplementation Possibly Helpful
According to a small, double-blind, placebo-controlled crossover study, use of arginine (700 mg four times daily) may help prevent tolerance to nitrate medications. 15

Note: Angina is too serious a disease for self-treatment. If you have angina, do not take any supplement except on physician’s advice.

Supplementation Possibly Helpful
A small, double-blind trial suggests that folate supplements (at the high dose of 10 mg daily) may help prevent tolerance to nitrate medications. 11

Note: Angina is too serious a disease for self-treatment. If you have angina, do not take any supplement except on a physician’s advice.

Supplementation Possibly Helpful
A small, double-blind trial suggests that vitamin E at a dose of 200 mg three times daily may help prevent tolerance to nitrate medications. 12

Note: Angina is too serious a disease for self-treatment. If you have angina, do not take any supplement except on a physician’s advice.




Ghio S, de Servi S, Perotti R, et al. Different susceptibility to the development of nitroglycerin tolerance in the arterial and venous circulation in humans. Effects of N-acetylcysteine administration. Circulation. 1992;86:798–802. May DC, Popma JJ, Black WH, et al. In vivo induction and reversal of nitroglycerin tolerance in human coronary arteries. N Engl J Med . 1987;317:805–809. Hogan JC, Lewis MJ, Henderson AH. N-acetylcysteine fails to attenuate haemodynamic tolerance to glycerol trinitrate in healthy volunteers. Br J Clin Pharmacol . 1989;28:421–426. Hogan JC, Lewis MJ, Henderson AH. Chronic administration of N-acetylcysteine fails to prevent nitrate tolerance in patients with stable angina pectoris. Br J Clin Pharmacol . 1990;30:573–577. Iversen HK. N-acetylcysteine enhances nitroglycerin-induced headache and cranial arterial responses. Clin Pharmacol Ther. 1992;52:125–133. Ardissino D, Merlini PA, Savonitto S, et al. Effect of transdermal nitroglycerin or N-acetyl cysteine, or both, in the long-term treatment of unstable angina pectoris. J Am Coll Cardiol. 1997;29:941–947. Watanabe H, Kakihana M, Ohtsuka S, et al. Randomized, double-blind, placebo-controlled study of the preventive effect of supplemental oral vitamin C on attenuation of development of nitrate tolerance. J Am Coll Cardiol. 1998;31:1323–1329. Bassenge E, Fink N, Skatchkov M, et al. Dietary supplement with vitamin C prevents nitrate tolerance. J Clin Invest. 1998;31:67–71. Bassenge E, Fink N, Skatchkov M, et al. Dietary supplement with vitamin C prevents nitrate tolerance. J Clin Invest. 1998;31:67–71. Watanabe H, Kakihana M, Ohtsuka S, et al. Randomized, double-blind, placebo-controlled study of the preventive effect of supplemental oral vitamin C on attenuation of development of nitrate tolerance. J Am Coll Cardiol. 1998;31:1323–1329. Gori T, Burstein JM, Ahmed S, et al. Folic acid prevents nitroglycerin-induced nitric oxide synthase dysfunction and nitrate tolerance: a human in vivo study. Circulation. 2001;104:1119–1123. Watanabe H, et al. Randomized, double-blind, placebo-controlled study of supplemental vitamin E on attenuation of the development of nitrate tolerance. Circulation 1997;96:2545-2550 Daniel TA, Nawarskas JJ. Vitamin C in the prevention of nitrate tolerance. Ann Pharmacother. 2000;4:1193-1197. McVeigh GE, Hamilton P, Wilson M et al. Platelet nitric oxide and superoxide release during the development of nitrate tolerance: effect of supplemental ascorbate. Circulation. 2002;106:208-213. Parker JO, Parker JD, Caldwell RW, et al. The effect of supplemental L-arginine on tolerance development during continuous transdermal nitroglycerin therapy. J Am Coll Cardiol. 2002;39:1199-1203.
Last Reviewed August 2013



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