short commentary

Essential Amino Acids as Immunonutrition in Critical Illness: Time for Trials?

Aquilani Roberto1, Iadarola Paolo1, Boschi Federica2*

1Department of Biology and Biotechnology, The University of Pavia, Pavia, Italy

2Department of Pharmaceutical Sciences, The University of Pavia, Pavia, Italy

*Corresponding author: Boschi Federica, Department of Pharmaceutical Sciences, The University of Pavia, Viale Taramelli,12- 27100 Pavia, Italy

Received Date: 04 November, 2022

Accepted Date: 14 November, 2022

Published Date: 17 November, 2022

Citation: Roberto A, Paolo I, Federica B (2022) Essential Amino Acids as Immunonutrition in Critical Illness: Time for Trials?. J Vaccines Immunol 7: 180. DOI:

Short Commentary

The derangement of both innate and adaptive immune responses of patients in the intensive care unit (ICU) led to the use of Immuno Nutrition Formula (INF) to reduce the risk of infection complications. While the observed findings might appear beneficial to high-risk surgical patients, they do not support the routine use of INF in medical ICU patients. In our opinion the inconsistent results from clinical trials might be due to the lack of Amino Acids (AA), in particular the Essential Amino Acids (EAAs), that patients receive either from a general nutrition support and from INF formula which does not contain EAAs.

To influence all aspects of leukocyte activities patients should be adequately supplied with all AAS [1,2]. However, most ICU patients receive an average of 0.7 g /Kg /d proteins, which is far lower than the recommended amount. This means that a patient weighing 70 Kg receives a maximum of only 16-20 gr EAAs/d, the amount approximatively contained in 240gr lean beef meat. The influences of AAs on the immune response have been documented in both in vitro and in vivo studies under physiological and clinical conditions (see Table). In extreme synthesis, adequate AA/EAA intake/provision is essential to leukocytes for the synthesis of cytotoxic proteins by T lymphocytes, antibodies by B lymphocytes and cytokines [3].

Griffith et al. [4] have shown that the intake of lysine reduces the transport of arginine into the virus of Herpes simplex thus leading to a depletion of polyamines, which are important for the growth of the virus. The EAA phenylalanine influences the immune response [5] both directly and indirectly; directly by regulating nitric oxide synthesis with leukocytes, and indirectly by its conversion to tyrosine. The latter leads to the formation of catecholamines, which stimulate the process of differentiation, proliferation of Th1 and B cells. Tyrosine, moreover, leads to the formation of dopamine which induces the production of anti-inflammatory mediators by leukocytes. The metabolism of the EAA methionine produces polyamines, which are important for the proliferation and differentiation of lymphocytes [6]. The EAA tryptophan is important for immunity in cancer, in which tryptophan plays a key role for an adequate cancer cell immune response. Indeed, tryptophan depletion suppresses the T cell response to cancer-specific antigens and causes tumour growth [7].

Given the huge influences on immune cell function of AAs and, in particular, of EAAs, we strongly believe that time has come to undertake appropriate trials targeting the effectiveness of adequate supplementation of EAAs with or without standard INF to enhance patient immune response and to reduce the risk for and shorten the duration of infection in critical patients. In addition, EAAs supplementation would increase the high-quality nitrogen provided to patients.

The following Table lists some human studies that report the immune response and beneficial clinical effects of administering BCAAs or EAAs mixture:


AA type


Cirrhosis [8]


Enhanced function of myeloid dendritic cells

Postsurgery subjects [9]


Blood lymphocyte counting higher than in controls

Postacute elderly patients [10,11]


30% reduction of nosocomial infections and reduced serum C-Reactive Protein

Postintensive severe brain injury patients [12]


23% reduction of nosocomial infections and reduced serum C-Reactive Protein (but not significant)

Elderly malnourished subjects [13]


Increase of mitochondrial bioenergetics in peripheral blood mononuclear cells


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  7. Hou Y, Yin M, Sun F, Zhang T, Zhou X, et al. (2014) A Metabolomics Approach for Predicting the Response to Neoadjuvant Chemotherapy in Cervical Cancer Patients. Mol Biosyst 10: 2126-2133.
  8. Kakazu E, Ueno Y, Kondo Y, Fukushima K, Shiina M, et al. (2009) Branched Chain Amino Acids Enhance the Maturation and Function of Myeloid Dendritic Cells Ex Vivo in Patients with Advanced Cirrhosis. Hepatology 50: 1936-1945.
  9. Nuwer N, Cerra FB, Shronts EP, Lysne J, Teasley KM, et al. (1983) Does Modified Amino Acid Total Parenteral Nutrition Alter Immune-Response in High Level Surgical Stress. JPEN J Parenter Enteral Nutr 7: 521-524.
  10. Aquilani R, Zuccarelli GC, Dioguardi FS, Baiardi P, Frustaglia A, et al. (2011) Effects of Oral Amino Acid Supplementation on Long-Term-Care-Acquired Infections in Elderly Patients. Arch Gerontol Geriatr 52: e123-128.
  11. Aquilani R, Zuccarelli GC, Maestri R, Boselli M, Dossena M, et al. (2021) Essential Amino Acid Supplementation Is Associated with Reduced Serum C-Reactive Protein Levels and Improved Circulating Lymphocytes in Post-Acute Inflamed Elderly Patients. Int J Immunopathol Pharmacol 2021.
  12. Boselli M, Aquilani R, Baiardi P, Dioguardi FS, Guarnaschelli C, et al. (2012) Supplementation of Essential Amino Acids May Reduce the Occurrence of Infections in Rehabilitation Patients with Brain Injury. Nutr Clin Pract 27: 99-113.
  13. Buondonno I, Sassi F, Carignano G, Dutto F, Ferreri C, et al. (2020) From Mitochondria to Healthy Aging: The Role of Branched-Chain Amino Acids Treatment: MATeR a Randomized Study. Clin Nutr 39: 2080-2091.

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