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Supplement: Arginine Metabolism: Enzymology, Nutrition, and Clinical Significance

Practical Recommendations for Immune-Enhancing Diets^1,2

Nutrition/Infection Laboratory, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215

³To whom correspondence should be addressed. E-mail: bbistria{at}bidmc.harvard.edu.

Immune-enhancing diets contain nutrients that have putative benefits, including arginine, (n-3) fats, glutamine, nucleotides, and structured lipids. Although under most circumstances the systemic inflammatory response is beneficial to the host, improving the eventual outcome of injury, infection, or inflammation, excessive proinflammation (leading to cardiac, hepatic, and mitochondrial dysfunction) or excessive counterinflammation (leading to immune depression) can worsen outcome. In critically ill septic patients, the synthesis of arginine can be exceeded by its catabolism to nitric oxide (NO) and urea, rendering arginine conditionally essential. In patients with sepsis, increased production of NO increases serum nitrite and nitrate levels, whereas levels in patients with trauma and trauma with sepsis are lower than in controls. In septic patients, supplemental arginine might further increase NO levels and be potentially harmful through excessive proinflammation. However, administration of increased amounts of arginine might improve immune function in surgical and trauma patients by increasing NO production in macrophages. When the diet provides at least 1 g of the (n-3) fatty acids eicosapentaenoic and docosahexaenoic acid combined, 2-series eicosanoids (prostaglandins, prostacyclins, thromboxanes) are replaced partially by 3-series eicosanoids, and 4-series leukotrienes are replaced partially by 5-series leukotrienes that are less proinflammatory. Thus, the effects of arginine and (n-3)-fat supplementation might be expected to be complementary—arginine might improve cytokine and NO production in patients with immunodepression, whereas (n-3) fats might be beneficial when there is excessive proinflammation, particularly when supplemental arginine is supplied, by reducing cytokine-induced eicosanoid production.

KEY WORDS: • immune-enhancing diets • arginine • (n-3) fats • clinical outcome

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