Immunonutrition

In critically ill
Emad Zarief MD
Professor of anesthesia and SIC. Assiut faculty of Medicine
Agenda
▪ Immunonutrition
▪ Does it matter ?
▪ Amino Acids
▪ Fatty Acids
▪ Antioxidants
▪ Trace Elements

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“you are what you eat”
Brillat-Savarin et al

• Prior to the 1950s, there was little

recognition of the relationship between
nutrition and immune function.

▪ It is now recognized that, at higher than

essential levels, selected nutrients can
have a pharmacologic effect to prevent or
treat disease.

J. A. Brillat-Savarin, J. Berchoux, and Colnet, Physiologie du Goût,

ou Méditations de Gastronomie Transcendante Paris, Librairie Garnier Frères, 1800.
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• “The use of specific nutritional substrates, called «immunonutrients» having the
ability of modulating specific mechanisms involved in several immune and
inflammatory pathways” .
• The most studied immunonutrients are ω 3 fatty acids, glutamine, sulfur-
containing amino acids, antioxidants, arginine, and nucleotides alone or in
various combinations.

Nutrients 2023, 15, 780.

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PPAR peroxisome proliferator receptor activator
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Nutrients. 2018;10(8).

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Evidence

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World Journal of Surgical Oncology
volume 21, : 183 (2023)

Immunonutrition :arginine, omega-3 fatty acids, nucleotides

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2022

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Conclusion: Short term of preoperative intravenous glutamine 0.4 g/kg/day decreased
the postoperative proBNP level and hospital/ICU stays in mitral valve replacement
surgery. No significant implication was reported upon postoperative human NGAL level
or kidney functions.
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BMC Cancer volume 23: 351 (2023)

• The use of IMN (total of 572 patients) has been shown to

significantly shorten hospital stays and decrease the frequency
of infectious complications in PD patients.
• Early implementation of IMN is recommended for those
undergoing PD.

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2022

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Has an impact on a wide variety of important
clinical outcomes :
• Ventilator free time
• Hospital stay
• Rate of infection
• Mortality rate
J. Parenter. Enter. Nutr. 2020, 44, 742–767.

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Proteins
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Whey
Protein
✓ 9 Essential a a
✓ 3 BCAA

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Whey Protein
• The “gold standard” protein in promoting myofibrillar
protein synthesis (MPS), and this has been attributed
to the high proportion of leucine along with rapid
digestibility and high bioavailability within the plasma
and muscle tissue.
• Helps to prevent cancer cachexia.
Pharmacological research. 2019 Jun 1;144:245-56.

doi.org/10.3390/sym15071313
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Branched Chain AA
• Leucine is the most important BAA
and a key component of muscle
protein.
• Recommended to use of leucine or
leucine-enriched proteins (1.2–6 g
leucine/day) to improve sarcopenia
in elderly individuals

Nutrients. 2019;11(10)

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Conditionally essential
• The most abundant AA in the plasma
• 1ry metabolic fuel for rapidly proliferating cells.
• Plays a central role as a precursor for protein,
nucleotide, and nucleic acid synthesis.
• Activation of autophagy
Nutrients. 2018 Oct 23;10(11):1564

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Conditionally essential
• Improves gut barrier function as well as
lymphocyte function, and this could potentially
↓↓ infectious complications.
• Nitrogen donor for glutathione synthesis may also
help to preserve lean body mass and it is an
important antioxidant.
Crit Care. 2015 Jan 29;19(1):35

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Conditionally essential
• Needs for Gln in metabolic stress is generally
>than Gln endogenous synthesis; hence, it is
conditionally essential
• Gln deficiency → ↑risk of sepsis, MSOF, and
premature death
Nutrition in Clinical Practice,18, 377–385, 2003.

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Arginine
• L-Arginine is the substrate used for NO
production by NOS
• NO→ major endothelial relaxation factor
able to increase vasodilation and ↓↓
arterial blood pressure

Nutrients 2021, 13, 3951

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Nutrients 2021, 13, 3951
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Arginine
• Is a conditionally necessary amino acid.
• Is important for
• Cellular growth
• Gene regulation
• Used carefully in septic patients, as it may
be a source of NO

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Arginine
The 2016 Society of Critical Care Medicine/ASPEN suggest
that immune-modulating enteral formulations (including
arginine and glutamine) should not be used routinely in the
MICU and that these formulations should be reserved for
patients with trauma and perioperative patients in the
surgical ICU (SICU).
J Parenter Enter Nutr. 2016;40(2):159–211.

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reatine
• Supports anabolism by ↑↑ the
expression of growth factors like insulin growth
factor 1 and the phosphorylation of signaling
proteins cellular growth .
• Improves muscle mass and enhance exercise
capacity.
Exp Gerontol. 2014;53:7–15

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L - carnitine
• L-Carnitine is an indispensable factor in the
energy production of cells that are synthesized
from lysine and methionine.
• Dose in ICU up to 3 g L-carnitine per day

Yahyapoor et al. Trials (2023) 24:3

doi.org/10.1186/s13063-022-07010-4

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L - carnitine
• L-carnitine supplementation can significantly
↓↓inflammatory biomarkers CRP, IL-6TNF-α.
• ↓↓ sequential organ failure assessment score
(SOFA) in septic patients, and L-carnitine
supplementation leads to a reduction in the
28-mortality rate

doi.org/10.1186/s13063-022-07010-4

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Polyunsaturated
Fatty Acids
Omega 3

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Polyunsaturated
Fatty Acids
• Energy sources
• Structure and physical
properties of cell
membranes
• Precursors of bioactive
lipid metabolites

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Polyunsaturated
Fatty Acids
• ω3-PUFAs ↓↓sarcopenia in
advanced cancer, aging, and
chronic diseases.
• of 3 g/day of EPA + DHA
is beneficial for muscle
health in older adults

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Antioxidants
Vitamins
Trace e.

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Antioxidants
Critical illness →deficits in
antioxidants due to:

• Redistribution from blood to tissues

• Increased losses
• Decreased nutritional intake

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Antioxidants
• ..Antioxidant includes:
• Enzymes (superoxide dismutase, glutathione
peroxidase),
• Trace elements (Se, Zn),
• Vitamins (vit C, E, beta-carotene)
• Sulfhydryl group donors (glutathione)

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j Parenter Enteral Nutr. 2023;47:S38–S49

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Antioxidants
Trace elements such as:
copper, iron, manganese, selenium, and zinc
act as important cofactors of antioxidative
enzymes, for example, catalase, glutathione
peroxidase, and superoxide dismutase.
j Parenter Enteral Nutr. 2023;47:S38–S49

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j Parenter Enteral Nutr. 2023;47:S38–S49

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Antioxidants
• Vitamins E, C, and D, and beta‐carotene
(pro‐vitamin A)
• Regulate nonenzymatic antioxidative
reactions by:
• Directly scavenging, inactivating, and
eliminating radicals and interrupting
oxidative (chain‐) reactions.
j Parenter Enteral Nutr. 2023;47:S38–S49

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Antioxidants
• Metanalysis→ supplementation of combined
antioxidants was associated with
• ↓ ↓ in overall mortality
• ↓ ↓ duration of mechanical ventilation,
• ↓ ↓ overall infectious complications,
• no effects on ICU or hospital length of stay (LOS).

Clin Nutr. 2021;40(3):740‐750

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Vitamin C

j Parenter Enteral Nutr. 2023;47:S38–S49

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Vitamin D

j Parenter Enteral Nutr. 2023;47:S38–S49

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Vitamin D
• Currently, in ICU patients, Vit D is ESPEN recommendation in severely
deficient patients with levels < 12.5 ng/mL within the first week after
ICU admission
• Vitamin D supplementation may play a useful role in alleviating muscle
loss both during and post-critical care hospitalization.
• It has immunomodulation properties essential to critically ill patients

Nutrition, 61, 2019, 173-178,

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Final Words
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Final Words
• Immunonutrition is usually under looked.
• Overdose of such agents is usually not needed.
• BCAA namely leucine + physical activity for
avoidance of sarcopenia.
• Glutamine and arginine to be cautiously used
during sepsis

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Final Words
• Still a lot of debates regarding the use of high
dose Vit C and D in ICU and sepsis.
• Antioxidants are very crucial during critical
illness and for any patients receives oxygen
therapy

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Thank You
[email protected]
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