Nitroglycerin dilates blood vessels by relaxing the smooth muscles surrounding them, increasing blood flow. Nitroglycerin is used to treat or prevent chest pain in people with angina pectoris and to treat instances of congestive heart failure.
Vitamin C may help maintain the blood vessel dilation response to nitroglycerin. A double-blind study found that individuals taking 2 grams of vitamin C three times per day did not tend to develop nitroglycerin tolerance over time compared to those taking placebo.1 In another controlled clinical trial, similar protection was achieved with 500 mg three times daily.2
People using long-acting nitroglycerin can avoid tolerance with a ten- to twelve-hour hour nitroglycerin-free period every day. People taking long-acting nitroglycerin should ask their prescribing doctor or pharmacist about preventing nitroglycerin tolerance.
Continuous nitroglycerin use leads to development of nitroglycerin tolerance and loss of effectiveness. Intravenous (iv) N-acetyl cysteine (NAC), during short-term studies of people receiving continuous nitroglycerin, was reported to reverse nitroglycerin tolerance.3 , 4 In a double-blind study of patients with unstable angina, transdermal nitroglycerin plus oral NAC (600 mg three times per day) was associated with fewer failures of medical treatment than placebo, NAC, or nitroglycerin alone. However, when combined with nitroglycerin use, NAC has led to intolerable headaches.5 , 6 In two double-blind, randomized trials of angina patients treated with transdermal nitroglycerin, oral NAC 200 mg or 400 mg three times per day failed to prevent nitroglycerin tolerance.7 , 8
1. Watanabe H, Kakihana M, Sadanori O, Sugishita Y. 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;31:1323–9.
2. Bassenge E, Fink N, Skatchkov M, Fink B. Dietary supplement with vitamin C prevents nitrate tolerance. J Clin Invest 1998;102:67–71.
3. 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.
4. 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;317:805–9.
5. Iversen HK. N-acetylcysteine enhances nitroglycerin-induced headache and cranial artery response. Clin Pharmacol Ther 1992;52:125–33.
6. 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;29:941–7.
7. Hogan JC, Lewis MJ, Henderson AH. N-acetylcysteine fails to attenuate haemodynamic tolerance to glycerol trinitrate in healthy volunteers. Br J Clin Pharmacol 1989;28:421–6.
8. 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;30:573–7.
Last Review: 05-01-2013
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