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Arginine Therapy for Acute Myocardial InfarctionArginine Therapy for Acute Myocardial Infarction

JAMA. 2006;295(18):2138-2140. doi:10.1001/jama.295.18.2138-b
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AUTHOR INFORMATION

Letters Section Editor: Robert M. Golub, MD, Senior Editor.

ARGININE THERAPY FOR ACUTE MYOCARDIAL INFARCTION

To the Editor: Dr Schulman and colleagues1 examined the effect of 6-month arginine supplementation on the outcome of patients with acute ST-segment elevation myocardial infarction. The premise of the study was that arginine, as a unique precursor for nitric oxide synthesis, would be beneficial in reducing vascular stiffness and other parameters of myocardial function following acute myocardial infarction. The study was stopped prior to enrollment of the targeted number of patients because of lack of cardiovascular efficacy as well as increased mortality in the arginine treatment group. The authors conclude that arginine should not be recommended following acute myocardial infarction. Before accepting this recommendation and dismissing the study premise, several factors need to be considered.

First, the prestudy and poststudy plasma arginine levels suggest poor adherence for ingestion. Arginine levels are highly variable and temporarily reflect intake for a short period. A more accurate measurement for verifying intake would be measurement of plasma ornithine levels, which was not performed. Moreover, whether the commercial arginine product used contained free base or the hydrochloride salt was not stated. Amino acid supplementation has had problems with purity,2 raising similar questions about the arginine preparation.

Second, given the high mortality rates, the lack of detailed data regarding the deaths precludes scientific association. Arginine infusion has been shown to provoke severe hyperkalemia and secondary fatal dysrhythmias.3 4 The 2 cases of sepsis are causally difficult to correlate with arginine ingestion and seem to be contrary to evidence that arginine stimulates the immune system and reduces sepsis.5 6 The case of myocardial rupture and the 2 patients who were found dead, with no provided pathological data, are difficult to relate causally to arginine administration.

Finally, the inclusion of the patient who died of recurrent infarction after the termination of the arginine supplement is questionable unless equally rigorous follow-up was required of all study participants. These deaths, while of concern, do not appear to be connected to the arginine supplementation.

Financial Disclosures: Dr Abumrad reported being a shareholder in Metabolic Technologies, Inc, based in Ames, Iowa, which produces an arginine-containing product that is distributed and sold by Abbott Pharmaceutical Co. Dr Abumrad is not involved in direct sales or marketing of the product. Dr Barbul reported no disclosures.

References
Schulman SP, Becker LC, Kass DA.  et al.  L-Arginine therapy in acute myocardial infarction: the Vascular Interaction with Age in Myocardial Infarction (VINTAGE MI) randomized clinical trial.  JAMA. 2006;29558-64
PubMed
Sternberg EM. Pathogenesis of L-tryptophan eosinophilia myalgia syndrome.  Adv Exp Med Biol. 1996;398325-330
PubMed
Bushinsky DA, Gennari FJ. Life-threatening hyperkalemia induced by arginine.  Ann Intern Med. 1978;89((5 pt 1)):632-634
PubMed
Massara F, Martelli S, Cagliero E.  et al.  The hypophosphatemic and hyperkalemic effect of arginine in man.  J Endocrinol Invest. 1980;3177-180
PubMed
Efron DT, Barbul A. Modulation of inflammation and immunity by arginine supplements.  Curr Opin Clin Nutr Metab Care. 1998;1531-538
PubMed
Luiking YC, Poeze M, Ramsay G, Deutz NE. The role of arginine in infection and sepsis.  JPEN J Parenter Enteral Nutr. 2005;29(1 suppl)  S70-S74
PubMed

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Schulman SP, Becker LC, Kass DA.  et al.  L-Arginine therapy in acute myocardial infarction: the Vascular Interaction with Age in Myocardial Infarction (VINTAGE MI) randomized clinical trial.  JAMA. 2006;29558-64
PubMed
Sternberg EM. Pathogenesis of L-tryptophan eosinophilia myalgia syndrome.  Adv Exp Med Biol. 1996;398325-330
PubMed
Bushinsky DA, Gennari FJ. Life-threatening hyperkalemia induced by arginine.  Ann Intern Med. 1978;89((5 pt 1)):632-634
PubMed
Massara F, Martelli S, Cagliero E.  et al.  The hypophosphatemic and hyperkalemic effect of arginine in man.  J Endocrinol Invest. 1980;3177-180
PubMed
Efron DT, Barbul A. Modulation of inflammation and immunity by arginine supplements.  Curr Opin Clin Nutr Metab Care. 1998;1531-538
PubMed
Luiking YC, Poeze M, Ramsay G, Deutz NE. The role of arginine in infection and sepsis.  JPEN J Parenter Enteral Nutr. 2005;29(1 suppl)  S70-S74
PubMed
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