Approach to the Patient
Preliminary evidence suggests that hawthorn, L-carnitine or L-propionyl carnitine, and magnesium may be useful adjuvant therapies in the treatment of angina. N-acetyl cysteine (NAC) appears to improve the effectiveness of nitroglycerin, but may cause severe headaches.
Other natural treatments your patient may be using for angina include coenzyme Q10, Coleus forskohlii, khella, oral magnesium, and vitamin E. Also ask your patient about beta-carotene ingestion, which may actually increase angina symptoms. For a full description of potential safety risks with the more common of these substances, see the full herb/supplement articles.
Chromium and coenzyme Q10 may be helpful for individuals taking beta-blockers. Beta-blockers can reduce high-density lipoprotein (HDL) levels as a side effect; chromium supplements may reverse this. Beta-blockers also impair CoQ10-containing enzymes; taking supplemental CoQ10 might therefore be a form of repletion therapy (see the full articles on Chromium and Coenzyme Q10 for more information).
Caution: Patients may need to be counseled that angina is too serious a condition for self-treatment.
Principal Proposed Natural Therapies
(Higher numbers indicate stronger evidence; X modifier indicates contradictory results. See the Introduction for details of the rating scale.)
N-Acetyl Cysteine (NAC) +3X
A 4-month, double-blind, placebo-controlled study of 200 individuals with unstable angina found that the combination of nitroglycerin and NAC was more effective than either drug alone in preventing death, myocardial infarction (MI), or the need for revascularization. 1 The mechanism of action is not clear. Unfortunately, combined treatment was also associated with a high rate of severe headaches. This side effect has been seen in other studies as well. 2 One small study found that NAC helped prevent nitrate tolerance, although another found no benefit. 3,4
For more information, including dosage and safety issues, see the N-Acetyl Cysteine article.
One double-blind study of 60 patients with angina found that treatment for 3 weeks with 180 mg/day of hawthorn extract increased exercise tolerance. 5
For more information, including dosage and safety issues, see the Hawthorn article.
A controlled (but not blinded) study enrolled 200 patients with exercise-induced angina. 6 All were maintained on standard therapy, but one half were also given an additional 2,000 mg/day of L-carnitine and observed for 6 months. The carnitine-treated group showed significant improvements in various cardiac parameters: the most dramatic was ST-segment depression during maximal effort, which fell from 0.5 mm to 0.15 mm in the treated group but did not change significantly in the untreated group ( P<.0001). There were smaller but statistically significant improvements in exercise tolerance, number of premature ventricular contractions (PVCs), maximum cardiac frequency, double cardiac product, and maximum systolic pressure.
Clinical improvement was also marked in the treated group. At the onset of the study, the percentage of patients rated at New York Heart Association (NYHA) class II failure was about 40%, but by the end of the study only 10% were so rated, the rest having improved to stage I. There were no such changes in the control group ( p value not stated). Medication needs also declined significantly in the treated group, as follows: nitroglycerides 60%, other nitro derivatives 40%, nifedipine 33%, diltiazem 47%, beta-blockers 36%, antihypertensives 44%, cardiac glycosides 35%, diuretics 34%, anticoagulants 44%, antiarrhythmics 70%, and hypolipidemics 61%. There were only minor declines in drug use in the control group ( P value not stated). The treated group also showed a decrease in plasma cholesterol from 230 to 208 and of triglycerides from 174 to 154. There was no significant change in the control group. HDL cholesterol did not change significantly in either group.
A smaller but double-blind, placebo-controlled trial enrolled 52 individuals with stable angina and also found benefits. 7 Benefits have also been seen in similar-sized or smaller single- and double-blind studies using propionylcarnitine. 8–11 However, in one comparative study, L-propionylcarnitine appeared to be less effective than diltiazem. 10
For more information, including dosage and safety issues, see the Carnitine article.
A double-blind, placebo-controlled trial of 50 individuals with stable coronary artery disease (CAD) found that supplementation with magnesium at 730 mg daily significantly improved exercise tolerance, apparently by improving endothelial function. 12 In addition, the same research group conducted a 3-month, double-blind, placebo-controlled trial of 42 individuals with CAD and found that magnesium supplementation at 800 to 1,200 mg daily inhibited platelet-dependent thrombus formation. 13 The effect appeared to be independent of platelet aggregation and activation and was additive with aspirin.
For more information, including dosage and safety issues, see the Magnesium article.
Other Proposed Natural Therapies
Use of vitamins C or E, folate, or arginine may help prevent nitrate tolerance. 20-26 According to some but not all studies N-acetylcysteine may also help maintain the effectiveness of nitrates; however, it may also increase nitrate-related headaches. 27-29
The herbs khella and Coleus forskohlii are also sometimes recommended, but as yet no meaningful evidence supports their use in angina.
See the article on each individual supplement for a full description of the interactions summarized here.
1. Ardissino D, Merlini PA, Savonitto S, et al. Effect of transdermal nitroglycerin or N-acetylcysteine, or both, in the long-term treatment of unstable angina pectoris. J Am Coll Cardiol. 1997;29:941-947.
2. Iversen HK. N-acetylcysteine enhances nitroglycerin-induced headache and cranial arterial responses. Clin Pharmacol Ther. 1992;52:125-133.
3. Pizzulli L, Hagendorff A, Zirbes M, et al. N-acetylcysteine attenuates nitroglycerin tolerance in patients with angina pectoris and normal left ventricular function. Am J Cardiol. 1997;79:28-33.
4. 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.
5. Hanak T, Bruckel MH. The treatment of mild stable forms of angina pectoris using Crategutt® novo [in German; English abstract]. Therapiewoche. 1983;33:4331-4333.
6. Cacciatore L, Cerio R, Ciarimboli M, et al. The therapeutic effect of L-carnitine in patients with exercise-induced stable angina: a controlled study. Drugs Exp Clin Res. 1991;17:225-235.
7. Cherchi A, Lai C, Angelino F, et al. Effects of L-carnitine on exercise tolerance in chronic stable angina: a multicenter, double-blind, randomized, placebo controlled crossover study. Int J Clin Pharmacol Ther Toxicol. 1985;23:569-572.
8. Bartels GL, Remme WJ, Pillay M, et al. Effects of L-propionylcarnitine on ischemia-induced myocardial dysfunction in men with angina pectoris. Am J Cardiol. 1994;74:125-130.
9. Bartels GL, Remme WJ, den Hartog FR, et al. Additional antiischemic effects of long-term L-Propionylcarnitine in anginal patients treated with conventional antianginal therapy. Cardiovasc Drugs Ther. 1995;9:749-753.
10. Bartels GL, Remme WJ, Holwerda KJ, et al. Anti-ischaemic efficacy of L-propionylcarnitine—a promising novel metabolic approach to ischaemia? Eur Heart J. 1996;17:414-420.
11. Lagioia R, Scrutinio D, Mangini SG, et al. Propionil-L-carnitine: a new compound in the metabolic approach to the treatment of effort angina. Int J Cardiol. 1992;34:167-172.
12. Shechter M, Sharir M, Labrador MJ, et al. Oral magnesium therapy improves endothelial function in patients with coronary artery disease. Circulation. 2000;102:2353-2358
13. Shechter M. The role of magnesium as antithrombotic therapy. Wien Med Wochenschr. 2000;150:343-347.
14. Kamikawa T, Kobayashi A, Yamashita T, et al. Effects of coenzyme Q10 on exercise tolerance in chronic stable angina pectoris. Am J Cardiol. 1985;56:247-251.
15. Bednarz B, Wolk R, Chamiec T, et al. Effects of oral L-arginine supplementation on exercise-induced QT dispersion and exercise tolerance in stable angina pectoris. Int J Cardiol. 2000;75:205-210.
16. Rapola JM, Virtamo J, Haukka JK, et al. Effect of vitamin E and beta carotene on the incidence of angina pectoris. JAMA. 1996;275:693-698.
17. McLean RM. Magnesium and its therapeutic uses: a review. Am J Med. 1994;96:63-76.
18. Maxwell AJ, Zapien MP, Pearce GL, et al. Randomized trial of a medical food for the dietary management of chronic, stable angina. J Am Coll Cardiol. 2002;39:37–45.
19. Bharani A, Ganguli A, Mathur LK, et al. Efficacy of T erminalia arjuna in chronic stable angina: a double-blind, placebo-controlled, crossover study comparing Terminalia arjuna with isosorbide mononitrate. Indian Heart J. 2002;54:170-175.
20. Daniel TA, Nawarskas JJ. Vitamin C in the prevention of nitrate tolerance. Ann Pharmacother. 2000;4:1193-1197.
21. 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.
22. Bassenge E, Fink N, Skatchkov M, et al. Dietary supplement with vitamin C prevents nitrate tolerance. J Clin Invest. 1998;31:67–71.
23. 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.
24. 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.
25. 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.
26. 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.
27. 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.
28. 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.
29. 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.
Last reviewed August 2002 by EBSCO CAM Review Board
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