People’s Journal of Scientific Research / Volume 16 / Issue 1 / Jan-June 2023

Dietary Immunomodulators - An Organic Boom in the

Management of Chronic Diseases

Anwesha Banerjee1, Divya Pandya1, Arpita Maitra1, Kaushik Dutta1, Rekha

Puttanawar1

1Department of Oral Medicine and Radiology, Guru Nanak Instiutute of Dental Sciences and Research, Kolkata,

West Bengal, India

ABSTRACT: Immunology involves all the defence mechanisms occurring in the body after the invasion of

any infectious agent and the ability to resist this infection. The micronutrients like essential

proteins, essential amino acids, vitamins (A, B6, B12, C, D, E and folic acid), fatty acids,

minerals (iron, selenium, zinc and copper) and certain phytochemicals are of prime

importance towards healthy immune system. In addition to these nutritional components,

intestinal microflora and certain bacteria (probiotic bacteria) also play an important role in the

modulation of healthy immune system. There is an ongoing trend of usage of

immunomodulators to combat various chronic diseases like viral diseases, cancers,

inflammatory and autoimmune diseases. This review focuses on various immunomodulators

available in daily dietary meals, its positive and negative effects on immune system and its

role in management of chronic illness as an adjunct to other modalities to achieve positive

health benefits with minimal side effects.

KEY WORDS: cancer; immunity; immunomodulator; organic food; probiotics; vitamins

Address for correspondence : Dr. Anwesha Banerjee, 1-Narendra Nagar, Ankur Apartment, Flat No. 16, Kolkata - 700056

E-mail: dr.anwesha12@gmail.com

Submitted: 27.04.2023, Accepted: 11.05.2023, Published: 26.06.2023

INTRODUCTION:

Nutrition plays an important role in

modulating immune functions. The immune system

needs adequate supply of nutrients to function

properly. Immune functions are indispensable for

defending the body against attack by pathogens or

cancer cells, and therefore it plays a pivotal role in the

maintenance of health. The immune functions are

disturbed by malnutrition, aging, physical and mental

stress or undesirable lifestyle. Therefore, the ingestion

of foods with immune-modulating activities is

considered an efficient way to prevent immune

functions from declining and reduce the risk of

infection or malignancy. Food-derived substances can

modulate either innate or acquired immunity.

Several studies have shown that the

improvement of depressed immune functions by

ingesting foods reduced infection rates and mitigated

the severity of infectious disease.[1] Therefore; food

substances that are capable of enhancing the immune

responses of cancer patients with disturbed/

compromised immune functions are valuable. The

proliferation and metastasis of cancer cells accelerate

when immune functions are disturbed. It has been

found that patients with malignancy have lower

Natural Killer (NK) cell activity than healthy controls

and such persons are subject to higher rates of cancer

incidence, metastasis and aggravation of cancer.[2]

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How to cite this article: Banerjee A, Pandya D, Maitra A, Dutta K,

Puttanawar R. Dietary Immunomodulators - An Organic Boom in the

Management of Chronic Diseases. PJSR. 2023;16(1): 50-59.

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People’s Journal of Scientific Research / Volume 16 / Issue 1 / Jan-June 2023

Banerjee A et al. Dietary Immunomodulators in Management of Chronic Diseases

Mechanism of action of dietary immunomo-

dulators on immune functions:

Basic nutrients-

Fatty acids: Polyunsaturated fatty acids (PUFA), are

important regulators of several cellular functions,

including those related to inflammation and

immunity.[3] Maternal fish oil supplement modifies the

balance between cellular n-3 and n-6 PUFAs within the

foetus and has the capacity to influence neonatal

immune function. It also has potential clinical benefits

and disaccharides like sucrose and lactose[13] and lectins

have capacity to interfere with bacterial and viral

attachment to epithelial cell surfaces within the

alimentary canal, as they contain mucosal

immunoglobulin, secretory IgA. Thus within the

alimentary canal, IgA, lectins, bacteria, viruses and

mucous membrane exist within a delicate equilibrium

which potentially may be perturbed by dietary

saccharides.[14]

in reducing the risk of allergic disease.[4] Dietary 2. Micronutrients-Vitamins

supplementation with fish oil in anti-inflammatory

doses inhibits prostaglandin E2 (PGE2) synthesis by

stimulating peripheral blood monocytes.[ 5 ] This

provides a mechanistic basis for the reduction in take of

Vitamin A:

Vitamin A plays a role in the maintenance of mucosal

surfaces, in the generation of antibody responses, in

haematopoiesis and in the function of T and B

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). lymphocytes, NK cells and neutrophils.[15] The

The onset of action of fish oil is being evident at 12

weeks after commencement. There is no direct dose-

by-dose effect as with the analgesic action of NSAIDs.

Clinical benefits have been observed to last up to 6

weeks after discontinuing therapy.[6] There is evidence

that PUFAs regulate the expression of genes for

cytokines, adhesion molecules, inducible nitric oxide

synthase and other inflammatory proteins.[7] Since the

expression of many of these genes is regulated by the

transcription factor, nuclear factor kappa B (NFkB),

these observations suggest that PUFAs might affect the

activity of this transcription factor.[8]

Aminoacids:

Arginine is a semi-essential amino acid in

mammals. While dietary arginine is not an absolute

requirement under normal conditions, it can become

essential at times of growth and metabolic stress, such

as following trauma, sepsis or burn injuries.[9] Arginine

is required for the normal growth and proliferation of

lymphocytes in vitro.[10] Supplemental arginine also

benefits the innate immune response, with increase in

macrophage and natural killer cell cytotoxicity.[11] In

the setting of protein-calorie malnutrition and tumour

inoculation, supplemental arginine (1% by weight)

reduced the growth rate of the immunogenic

neuroblastoma C1300 and improved host survival

compared with glycine-supplemented controls.[12]

Glutamine is another amino acid having high rate of

utilization by neutrophils, macrophages and

lymphocytes and its levels get elevated in cellular

challenging situations suggesting its importance for

functioning of these cells to mount an efficient immune

response.[3]

Carbohydrates:

Dietary monosaccharides like glucose and fructose

influence of vitamin A and its metabolites on different

aspects of immune function is attributed to its actions

as modulators of gene transcription.[16] Vitamin A

supplementation reduces the morbidity and mortality

from measles and diarrhoeal diseases in infants and

children in developing countries.[17,18] Periodic high-

dose vitamin A supplementation seems to reduce both

morbidity among children born to HIV-infected

mothers[19] and diarrhoeal disease morbidity in HIV

infected children.[20]

Role of Vitamin A in oral diseases:

Vitamin A plays an important role in management

of oral leukoplakia and oral submucous fibrosis. It also

maintains immune defence responses, oral epithelial

integrity, bone growth, normal cell development,

avoids keratinisation of mucous forming cells, allows

cell differentiation, stimulates osteoclasts and permits

normal tooth spacing.[21]

Vitamin C:

It has an inhibitory effect on the expression of

pro-inflammatory cytokines such as interleukin (IL)-6

and tumour necrosis factor alpha (TNF-α) in adult

whole blood cells. It has been postulated that vitamin C

might be an interesting compound for modulation of an

overexuberant immune response.[22]

Role of Vitamin C in oral diseases:

Study conducted by R. Guruprasad et. al in

2014 evaluated the correlation between Serum Vitamin

C and Iron levels in OSMF patients. The level of Serum

Vitamin-C and Iron was significantly decreased in

OSMF patients when compared to controls. They

concluded, that the chemical, thermal and/or

mechanical factors associated with the use of areca nut

may act in conjunction with the Vitamin C and Iron

Banerjee A et al. Dietary Immunomodulators in Management of Chronic Diseases

People’s Journal of Scientific Research / Volume 16 / Issue 1 / Jan-June 2023

deficiency leading to the development of OSMF.

Therapeutic substitution of Vitamin C and Iron may be

recommended in the management of OSMF.[23]

A study conducted by Supriya Bhat et al, in

2017 aimed to estimate the detoxification status of

serum and saliva by assessing the serum and salivary

Vitamin C in oral potentially malignant disorders and

oral cancer. A total of 90 subjects, 30 subjects with oral

potentially malignant disorders, 30 subjects with oral

cancer, and 30 healthy subjects (controls) were

included in the study. The study concluded that the

mean serum and salivary Vitamin C levels were

decreased significantly in potentially malignant

disorders and oral cancer when compared to healthy

subjects.[24]

Vitamin E:

It is the most effective chain breaking, lipid-

soluble antioxidant in cell membranes and plays a

major role in maintaining cell membrane integrity by

limiting lipid peroxidation by reactive oxygen species

(ROS).[25] It can influence a variety of inflammatory

processes by inhibiting the activity of NFk B, required

for maximal transcription of many proteins involved in

inflammatory responses, including several cytokines,

such as IL-1B, IL-2 and TNF-α.[ 26 ] Vitamin E

supplementation in diet enhances antibody production,

lymphocyte proliferation, NK-cell activity, and

macrophage phagocytosis.[27]

Carotenoids:

The bright red, yellow and orange pigments in

various fruits and vegetables are attributed to

Carotenoids. The prevalent ones in the human diet

include beta- carotene, alpha- carotene, beta

cellular biomolecules, including lipids, lipoproteins,

proteins, and DNA. Dosage of 4.8 mg/day orally for 3

months leads to the reversal of dysplastic changes in

leukoplakia and dosage of 16 mg/day leads to

substantial increase in the mouth opening in oral

submucous fibrosis. In vitro studies have shown

lycopene to be twice as potent as β-carotene and ten

times that of α-tocopherol in terms of its singlet oxygen

quenching ability.

Thiamine:

Thiamine is a water-soluble Vitamin B.[22]

Several case control studies have reported significant

associations between thiamine intake and reduced risk

of several cancers including colon, and colorectal.[31,32]

Folate: Folate is a water-soluble vitamin B found

naturally in certain citrus foods called food folate, and

the synthetic form added to fortified foods and

supplements, called folic acid. Several studies

hypothesized that folate supplementation is associated

with a decreased rate of infection, positive effects on

blastogenic response and proliferation of T

lymphocytes, enhanced delayed-type hypersensitivity

r e s p o n s e , e n h a n c e d p h a g o c y t o s i s , a n d

immunoglobulin production. It appears to have no

effect on NK cell function. Immunologically folate

deficiency are likely caused by defects in DNA and

RNA synthesis or methyl metabolism.[22]

Vitamin B-6:

It affects immune function as it plays a role in

the formation of the amino acid cysteine, an important

precursor in glutathione, which is closely associated

cryptoxanthin, lycopene, lutein, and zeaxanthin, with lymphocyte proliferation.[ 33 ] Its potential

having provitamin A activity, and are converted to

retinol, the active form of vitamin A, in the body.[22]

mechanism to reduce cancer risk includes reducing the

disruption of DNA synthesis, repair, and methylation

Lycopene has been shown to have high singlet oxygen associated with inadequate intake.[25] Also it may

quenching capability and has been associated with

anti-tumour promoting activities in various tissues in

animal studies. Association between lycopene intake,

primarily from tomato products is associated with

reduced risk for cancers at all sites.[28] Epidemiological

studies have found significant associations between

higher plasma beta cryptoxanthin and a reduced risk for

reduce cancer cell proliferation and oxidative stress,

suppress nitric oxide, or have antiangiogenic

properties.[34]

Minerals:

Zinc- High content of Zinc (Zn) is present in animal

gastric adenocarcinomas and lung cancer in men.[29,30] protein food.[35] Zn plays a role in T lymphocyte

Consuming a carotenoid-rich diet may be one of the

ways for reducing the risk of cancer.[22]

Role of Carotene in oral diseases:

Lycopene has been hypothesized to prevent

carcinogenesis and atherogenesis by protecting critical

activation and signal transduction. Zn has been

implicated in the non-covalent interaction of the

cytoplasmic tails of CD4 and CD8 with the tyrosine

kinase p56lck, an essential process in the early steps of

T-cell activation.[36] Zn stimulates autophosphorylation

of tyrosine residues by p56lck and subsequent

Banerjee A et al. Dietary Immunomodulators in Management of Chronic Diseases

People’s Journal of Scientific Research / Volume 16 / Issue 1 / Jan-June 2023

phosphorylation of the T-cell receptor complex oxide (NO) in the presence of iron. This is important,

involving CD45.[ 37 ] Zn-deficient children with because NO is an essential effector molecule produced

acrodermatitis enteropathica (AE) have reduced

numbers of lymphocytes, particularly T-cells, in the

blood and peripheral lymphoid tissues. Decreased

CD4+/ CD8+ cell ratios are also seen. T-cell responses,

such as proliferation in response to mitogens,

cytotoxicity and delayed-type hypersensitivity (DTH),

natural killer cell activity and chemotactic response of

the monocytes are suppressed.[38,39] Controlled trials of

Zn supplementation demonstrated a reduction in the

incidence and duration of acute and chronic diarrhoea

by 25-30 %, and in the incidence of pneumonia by up to

50%.[40]

Role of Zinc in SARS-CoV 2:

It is known that zinc (Zn) possesses a variety of

direct and indirect antiviral properties. Administration

of Zn supplement has a potential to enhance antiviral

immunity, both innate and humoral, and to restore

depleted immune cell function or to improve normal

immune cell function, particularly in immuno-

compromised or elderly patients. Zn may also act in a

synergistic manner when co-administered with the

by macrophages to fight infectious pathogens and

tumour cells.[45] Iron blocks the transcription of

inducible NO-synthase (iNOS or NOSII), the enzyme

responsible for cytokine inducible high-output

formation of NO by hepatocytes or macrophages.[46]

The inhibitory effect of iron toward IFN-γ activity also

affects the Th1/Th2 balance, with Th1 effector

function being weakened, whereas Th2- mediated

cytokine production and function, such as IL-4

activityis increased which is unfavourable during a

malignant disease or an acute infection. B cells are not

prominently affected by iron homeostatic changes,

while NK cells are sensitive to iron homeostatic

imbalances with impaired proliferation in iron

deficiency and overload.[44]

Selenium:

Various milled wheat and corn products may

contain 70% or more of selenium. Cooking appears to

result in little significant loss of selenium in most

foods, but dry heating of cereals may result in

significant reductions in their original selenium

standard antiviral therapy, as was demonstrated in content.[47] A major immune stimulatory effect of

patients with hepatitis C, HIV, and SARS-CoV-1. Zn

may also protect or stabilize the cell membrane that

blocks the virus entry into the cell. It also inhibits viral

replication by alteration of the proteolytic processing

of replicase polyproteins and RNA-dependent RNA

polymerase (RdRp) in rhinoviruses, HCV, and

influenza virus, and diminish the RNA-synthesizing

activity of nidoviruses, that belongs to SARS-CoV-2.

Therefore, it has been hypothesized that Zn

supplements may have potential benefit in prophylaxis

and treatment of COVID-19.[41]

Iron: It is an essential nutrient for cells because of its

role as a cofactor for enzymes in the mitochondrial

respiratory chain and oxidative phosphorylation, in the

citric acid cycle (aconitase), and in DNA synthesis

(ribonucleotide reductase).[42] Iron interferes with

cytokine activities and the cell-mediated immune

effector mechanisms of macrophages, thus altering the

immune response toward invading pathogens.[43] One

central mechanism responsible for this is a direct

inhibitory effect of iron on IFN-γ activity. Iron loading

of macrophages results in an inhibition of IFN-

mediated pathways in macrophages, such as formation

of the pro-inflammatory cytokine, TNF-α and

expression of MHC class II antigen.[44] Part of this

effect results from the reduced formation of nitric

Selenium is by up-regulation of expression of the α and

ß subunits of the IL-2 receptor, which are expressed on

many immune cells and notably on T and B

lymphocytes. This increases the ability of these cells to

respond to IL-2. Stimulation with IL-2 from activated

CD4+ T-helper cells potentiates the cytotoxicity of

killer cells, increases numbers of lymphocytes,

promotes antibody production by B lymphocytes and

improves the responsiveness of immature bone

marrow cells to other cytokines in order to produce

immune-cell precursors.[48] Supplementation with

Selenium appears to reverse the age-related decline in

NK cell function in elderly individuals. The loss of

NK-cell activity is a means by which cancer cells may

evade immune-mediated destruction.[49]

Role of Selenium in oral diseases:

Oral lichen planus (OLP) is a chronic disease

with immune mediated pathogenesis. Selenium (Se),

an antioxidant, plays a role in modulating immunity.

Passant O. Qataya et al, in January, 2020 conducted a

randomized control clinical trial to evaluate two forms

of Selenium (novel topical hydrogel and oral

capsules), solely, in treating erosive OLP based on

clinical evaluation and salivary oxidative stress

markers. Patients were allocated into one of three

groups: group I, topical corticosteroids; group II,

topical Selenium; and group III, systemic Selenium.

Banerjee A et al. Dietary Immunomodulators in Management of Chronic Diseases

People’s Journal of Scientific Research / Volume 16 / Issue 1 / Jan-June 2023

Treatment lasted for 6 weeks; patients were clinically

evaluated at baseline, 6 and 12 weeks. Patients in all the

groups showed significant reduction in symptoms after

the treatment. However, group II had significantly

lower pain scores at the end of 12 weeks compared to

the other groups.[50]

Probiotics:

Under normal circumstances, the resident gut

bacteria cause neither pathogenicity nor inflammation

in the host, but instead contribute to health

maintenance, forming a barrier layer against

colonization by pathogens and aiding in nutrient

digestion and assimilation.[51] The resident intestinal

microflora plays important physiological roles like

deconjugating potentially damaging oxidative

metabolites and toxins in the gut; degrading potentially

allergenic food proteins; regulating cholesterol and

triglyceride uptake; increasing vitamin biosynthesis

and providing immunosurveillance signals to limit

intestinal-tract inflammation. Thus, a stable, properly

functioning and active intestinal tract microflora is

essential to the continuance of human health. Among

the most predominant microbes in the human intestinal

tract are the Gram positive lactic acid-producing

genera Lactobacillus and Bifidobacterium.

Lactobacilli and bifidobacteria are also common

fermentative microbes in yoghurt and cheese.[52]

Certain strains of probiotic lactic acid bacteria (LAB)

can prime peritoneal macrophage populations for

enhanced phagocytosis, lysosomal enzyme production

probiotics, that introduce exogenous bacteria into the

human colon, prebiotics stimulate the preferential

growth of a limited number of health-promoting

commensal flora already residing in the colon.[58]

Dietary raffinose suppresses serum immunoglobulin E

response through suppression of Th2-type immune

response against oral antigen in the lymphoid organs

located in or near the intestine.[59]

Food beneficial to the immune system:

Epidemiological and experimental studies

have demonstrated a negative correlation between the

deficinency of diets rich in fruits, and vegetables and

the risks for chronic diseases, such as chronic

inflammation and cancers.[60] Therefore, adequate

supplementation with fruits and vegetables might play

an important role in the control of acute and chronic

diseases via immuno-modulation. Dark coloured fruits

and vegetables have potential in stimulating Th1/Th2

cytokine secretions.[61]

Strawberries, red onions, peppers and spinach:

Strawberry and red onions demonstrate an

immunomodulatory potential via stimulating

splenocyte proliferation.The immuno-modulatory

components in these fruits are correlated with

phenolics, including flavonoids.[61]

Apples:

It one of the main sources of dietary

flavonoids. Apple extracts can significantly inhibit the

and free radical oxidant production.[53] In human TNF-alpha-induced NF-kappa B activation at a dose of

studies, consumption of Lactobacillus rhamnosus

(strain HN001) or Bifidobacterium lactis (strain

HN019) has been demonstrated to up-regulate

peripheral blood NKcell-mediated cytotoxicity against

5 mg/ml.[62]

Carrots, celery and parsley:

Non-toxic doses (20 μg/ml) of these foods and

tumour cells.[ 5 4 ] In addition to anti- allergy their related ingredients might act to affect health as

immunoregulation, probiotics also combat

inflammatorydiseases. Evidences demonstrate that

dietary consumption of immunoregulating LAB might

assist in combating autoimmune diseases, including

immune-stimulating agents, i.e. directly enhancing

lymphocyte activation and/or secreting multipotent

cytokine IFN-γ.[63]

juvenile chronic arthritis.[55] The potential use of Cruciferous vegetables:

probiotics to augment the routine immune signalling

events of the gut microflora, as a means of restoring

vital anti-inflammatory immunoregulatory control

mechanisms is a promising means of combating

inflammatory bowel disease.[56]

Prebiotics:

These are non-digestible food ingredients that

beneficially affect the host by selectively stimulating

the growth and activity of one species or a limited

number of species of bacteria in the colon.[57] Unlike

Increased intake of cabbage, cauliflower,

broccoli, Brussels sprouts, watercress, and mustard

greens, is associated with a decreased risk of several

cancers in human population.[64] This is achieved by

alterations in the activities of metabolic enzymes that

result in reduced carcinogenicity of dietary or

environmental carcinogens, reduction of oxidative

DNA damage levels in human lymphocytes in

increased oxidative stress conditions.[65,66,67]

Banerjee A et al. Dietary Immunomodulators in Management of Chronic Diseases

People’s Journal of Scientific Research / Volume 16 / Issue 1 / Jan-June 2023

Tomato:

Epidemiological and experimental data

suggest that an increased intake of tomato products can

Honey:

The most promising bioactive compounds

found in honey products are the proteins of royal

reduce the risk of cancers, especially prostate, colon, jelly.[77] These proteins may have physiological

and oral cancer. Several evidence suggest that tomato

constituents, such as lycopene, affect immune

functions modulation and antioxidant activity.[68]

Garlic:

Allicin is the active ingredient of freshly

crushed garlic. It significantly inhibits the secretion of

IL-8, INF-γ-inducible protein of 10 kD (IP-10),

monokine induced by INF- γ (MIG) and IL-1b from

intestinal epithelial cells. These cyto-and chemokines

play an important role in the pathogenesis of

inflammatory bowel diseases. Therefore, local

application of allicin may serve as a potential immune-

mediating therapy in inflammatory bowel diseases.[69]

Meta-analyses revealed that increased garlic

consumption diminished the risk of stomach and

colorectal cancers.[70]

Soybeans:

It possesses several traditional phytonutrients

and several bioactive phytochemicals including

flavonoids and saponins, with variety of potential

health benefits, like anti-inflammatory, anti-oxidative,

anti-mutagenicand anticarcinogenic effects.[71-74]

Cereals (rice and wheat):

Lipopolysaccharide (LPS) or LPS-like

components associated with cereal grains play a major

role in IL-10 production from Peripheral Blood

Mononuclear Cells. The ability of various food

products to induce IL-10 production did not always

correlate with the concentrations of LPS in their

extracts. Therefore LPS or LPS mimicking molecules

likely work in concert with other immune stimulatory

or immune regulatory molecules in the cereals, such as

carbohydrate polymers or lectins, to induce robust IL-

10 production. This immune modulatory effect might

explain why most individuals who are at genetic risk

for celiac disease do not acquire celiac disease or

inflammatory bowel disease. [75]

Mushrooms:

Mushroom proteins are potent immune

activators and tumour cell growth inhibitors, mediating

their effects by regulating cytokine secretion and

proliferation, and are mitogens and immune

modulators with therapeutic potential.[76]

functions as suppressors of allergic reactions, as

well.[78]

Dairy products:

Yogurt is one of the best-known foods that

contain probiotics. In human studies, cytokine

production, phagocytic activity, antibody production,

T cell function, and NK cell activity were shown to

increase with yogurt consumption or when cells were

exposed to LAB in vitro. There is evidence that yogurt-

induced immune enhancement is associated with a

lowered incidence of cancer, GI disorders, and allergic

symptoms.[79] Denatured and native whey protein, both

of which have remarkably higher cysteine contents

than do other common edible proteins, may contribute

to the immunostimulatory effects of yogurt. Cysteine

is a rate-limiting component in the biosynthesis of

glutathione. Glutathione i s important for

detoxification of endogenous and exogenous

carcinogens and free radicals and in regulation of

immune functions.[80]

Cheese constitutes another family of milk

derived fermented products and its consumption exerts

a stimulatory effect on immune system functions.[81] In

addition to the bacterial cell components, the

immunomodulatory effect of cheese could also result

from non-bacterial components such as peptides

which in a lyophilized extract of Gouda cheese

suppresses proliferation of cultured human peripheral

blood lymphocytes in vitro and induces apoptosis of

human promyelocytic leukaemia cells.[82]

Detrimental effects of food on the immune system:

Food allergies are caused by immunologic

pathways that include activation of effector cells (mast

cells and basophils) through food specific

immunoglobulin E (IgE) antibodies (IgE-mediated

food allergy), cell-mediated reactions resulting in

subacute or chronic inflammation (non-IgE mediated

food allergies), or combined pathways. IgE-mediated

reactions occur rapidly (within seconds to minutes)

after ingestion of the offending foods. Rarely,

reactions take up to two hours and beyond to

occur.83Manifestations of IgE-mediated food allergy

includeacute urticaria and angioedema, rhino-

conjunctivitis, asthma, nausea, vomiting abdominal

cramps and diarrhoea. However, generalized urticaria

and anaphylaxis can also occur.[84] The oral allergy

syndrome is an IgE mediated hypersensitivity is

Banerjee A et al. Dietary Immunomodulators in Management of Chronic Diseases

People’s Journal of Scientific Research / Volume 16 / Issue 1 / Jan-June 2023

considered as a form of contact allergy to certain

(usually fresh) fruits, nuts and vegetables and seen in

up to 50% of patients with allergic rhinitis to pollen.85

Symptoms are mainly confined to oropharynx, and

include the rapid onset of pruritus involving the lips,

mouth and/or pharynx. Mild swelling of the lips is

common. Symptoms generally subside within minutes

after ingestion ceases. However, progression to

systemic symptoms is thought to occur in

approximately 10% of patients.[83] Over-activation of

the immune system can lead to harmful effects such as

chronic inflammation or autoimmune diseases.

Sometimes, the body begins to manufacture T cells and

antibodies directed against its own cells and organs.

Some individuals develop an exaggerated immune

response to food through developing food allergy

which may be IgE mediated, non-IgE mediated, or

mixed.

CONCLUSION:

Nutrition plays an important role in the

modulation of immune function and the various food

components like proteins, vitamins, fatty acids,

minerals, phytochemicals and probiotics play an

important role in the modulation of immune function

which is directly associated with immunological

tolerance toward diseases.Supplementation with

single or multiple micronutrients may enhance

immune functions even in healthy individuals. On the

other hand, excess amounts of some nutrients may

impair immune functions.

Financial Support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

REFERENCES:

1. Braga M, Vignali A, Gianotti L, Cestari A, Profili M,

Carlo VD. Immune and nutritional effects of early

enteral nutrition after major abdominal operations. Eur J

Surgery.1996;162:105- 12.

2. Imai K, Matsuyama S, Miyake S, Suga K, Nakachi K.

Natural cytotoxic activity of peripheral-blood

lymphocytes and cancer incidence: An 11-year follow-

up study of a general population. Lancet. 2000; 356:

1795-9.

3. Calder PC, Field CJ. Fatty acids, inflammation and

immunity. In: Calder PC, Field CJ, Gill HS, Eds.

Nutrition and Immune Function 1st edition.

NewYork:CAPI publishing. 2002:57-92.

4. Dunstan JA, Mori TA, Barden A, Beilin LJ, Taylor AL,

Holt PG, et al. Fish oil supplementation in pregnancy

modifies neonatal allergen-specific immune responses

and clinical outcomes in infants at high risk of atopy: A

randomized, controlled trial. J Allergy Clin Immunol.

2003;112:1178-84.

5. Mantzioris E, Cleland LG, Gibson RA, Neumann MA,

Demasi M, James MJ. Biochemical effects of a diet

containing foods enriched with n-3 fatty acids. Am J

Clin Nutr. 2000;72:42-8

6. Stamp LK, James MJ, Cleland LG. Diet and rheumatoid

arthritis: a review of the literature. Semin Arthritis

Rheum.2005;35:77-94.

7. Wallace FA, Miles EA, Evans C, Stock TE, Yaqoob P,

Calder RC. Dietary fatty acids influence the production

of Thl- but not Th2-type cytokines. J Leuko Biol.

2001;69:449-57.

8. Xi S, Cohen D, Barve S, Chen LH. Fish oil suppressed

cytokines and nuclear factor kappa B induced by murine

AIDS virus infection. Nutr Res. 2001;21:865-78.

9. Duff MD, Daly JM. Arginine and immune function. In:

Calder PC, Field CJ, Gill HS (eds). Nutrition and

Immune Function. 1st edition. NewYork: CAPI

publishing. 2002:93-108.

10. Efron DT, Kirk SJ, Regan MC, Wasserkrug HL, Barbul

A. Nitric oxide generation from L-arginine is required

for optimal peripheral blood DNA synthesis.

Surgery.1991;110:327-34

11. Reynolds JV, Daly JM, Zhang, S, Evantash E, Shou J,

Sigal R, et al. Immunomodulatory effects of arginine.

Surgery.1988;104:142-51.

12. Reynolds JV, Daly JM, Shou J, Sigal R, Ziegler MM,

Naji A. Immunological effects of arginine in tumor-

bearing and non- tumor- bearing hosts. Ann

Surgery.1990;211:202-10.

13. Kidd G, Devorak J. Trehalose is a sweet target for

agbiotech. Biotechnol. 1994;12:1328-9.

14. Kilpatrick DC. Immunological aspects of the potential

role of dietary carbohydrates and lectins in human

health. Eur J Nutr. 1999;38:107-17.

15. Semba RD, Lyles CM, Margolick JB, Caiaffa WT

Farzadegan II, Cohn S, et al. Vitamin A supplementation

and human immunodeficiency virus load in injection

drug users. J Infect Dis.1998;177:611-6.

16. McLaren DS, Frigg M. Sight and life. Manual on vitamin

A deficiency disorders. 2nd edition, Task Force Sight

and Life, Basel 2001, Switzerland

17. Markowitz L, Nzilambi N. Driskell WJ, Sension MG,

Rovira EZ, Nieburg R, et al. Vitamin A levels and

mortality among hospitalized measles patients,

Kinshasa, Zaire. J Tropical Pediatr.1989;35:109-12.

18. Schaumberg DA, O'Connor J, Semba RD. Risk factors

for xerophthalmia in the Republic of Kiribati. Eur J

Nutr1996;50:761-4.

19. Coutsoudis A, Bobat RA, Coovadia HM, Kuhn L, Tsai

W Y, S t e i n Z A . T h e e f f e c t s o f v i t a m i n A

supplementation on the morbidity of children born to

HIV-infected women. Am J Pub Health.1995;85:1076-

81.

Banerjee A et al. Dietary Immunomodulators in Management of Chronic Diseases

People’s Journal of Scientific Research / Volume 16 / Issue 1 / Jan-June 2023

20. Fawzi WW, Mbise RL, Hertzmark E, Fataki MR, Herrera

MG, Ndossi G, et al. A randomized trial of vitamin A

supplements in relation to mortality among human

immunodeficiency virus-infected and uninfected

children in Tanzania. Pediatr Infect Dis J.1999;18:127-

21. Enwonwu C.O., Phillips R.S., Falker W.A. Jr. Nutrition

and oral infectious diseases: state of the science.

CompendCont Edu Dent. 2002;23(5):431-4

22. Härtel C, Puzik A, Göpel W, Temming P, Bucsky P,

Schultz C. Immunomodulatory effect of Vitamin C on

intracytoplasmic cytokine production in neonatal cord

blood cells. Neonatology.2007;91:54-60.

23. Guruprasad R,NairPP,SinghM,Singh M P,Jain A. Serum

vitamin c and iron levels in oral submucous

fibrosis.Indian J Dent.2014;5:81-5

24. Bhat S, Babu SG, Bhat SK, Castelino RL, Rao K, Madi

M. Status of Serum and Salivary Ascorbic Acid in Oral

Potentially Malignant Disorders and Oral Cancer.

Indian J Med Paediatr Oncol. 2017;38(3):306-310.

25. Hughes D. Antioxident vitamins and immune function.

In: Calder PC, Field CJ, Gill HS, eds. Nutrition and

immune function. 1st edition. NewYork: CAPI

publishing.2002:171-91.

26. Lavrovsky Y, Chatterjee B, Clark RA, Roy AK. Role of

redox-regulated transcription factors in inflammation,

ageing and age-related diseases. Exp Gerontol.2000;

35:521-32.

27. Meydani SN, Beharka AA. Recent developments in

vitamin E and immune response. Nutr Rev.

1998;56:549-58.

28. Nishino H, Murakoshi M, Ii MT, Takemura M, Kuchide

M, Kuchide M, et al. Carotenoids in cancer

chemoprevention. Cancer and Metastasis Rev.2002;

21:257-64.

29. Jenab MRE, Ferrari P, Friesen M, Sabate J, Norat T,

Slimani N, et al. Plasma and dietary carotenoid, retinol

and tocopherol levels and the risk of gastric

adenocarcinomas in the European prospective

investigation into cancer and nutrition. Br J

Cancer.2006;95:406-15.

30. Ito YK, Wakai K, Suzuki K, Ozasa Y, Watanabe N, Seki

M, et al. Lung cancer mortality and serum levels of

carotenoids, retinol, tocopherols, and folic acid in men

and women: a case-control study nested in the JACC

study. J Epidemiol. 2005;15:5140-9.

31. Slattery ML, Potter JD, Coates A, Ma KN, Berry TD,

Duncan DM, et al. Plant foods and colon cancer: an

assessment of specific foods and their related nutrients

(United States). Cancer Causes Control.1997;8:575-90.

32. Jedrychowski WK, Steindorf T, Popiela T, Wahrendorf J,

Tobiasz-Adamczyk B, Kulig J, et al. Alcohol

consumption and the risk of colorectal cancer at low

l e v e l s o f m i c r o n u t r i e n t i n t a k e . M e d S c i

Monit.2002;8:357-63.

33. Grimble RF. Effect of antioxidative vitamins on immune

function with clinical applications. Int J VitamNutr

Res.1997;67:312-20.

34. Matsubara K, Komatsu S, Oka T, Kato N. Vitamin B6-

mediated suppression of colon tumorigenesis, cell

proliferation, and angiogenesis ( Review). J

NutrBiochem.2003;14:246-50.

35. Shrimpton R, Gross R, Darnton-Hill J, Young M. Zinc

deficiency: what are the most appropriate

interventions?. Br Med J.2005;330:347-9.

36. Turner JM, Brodsky MH, Irving BA, Levin SD,

Perlmutter RM, Littman DR. Interaction of the unique

N-terminal region of tyrosine kinase p56kk with

cytoplasmic domains of CD4 and CDS is mediated by

cysteine motifs. Cell.1990;60:755-65.

37. Zalewski RD. Zinc and immunity: implications for

growth, survival and function of lymphoid cells. J Nutr

Immunol.1996;4:39-80.

38. Prasad AS. Effects of zinc deficiency on immune

functions. J Trace Elements in Exp Med.2000;13:1- 20.

39. Shankar AH, Prasad AS. Zinc and immune function: the

biological basis of altered resistance to infection. Am J

Clinic Nutr.1998;68:447-63.

40. Ruel MT, Ribera JA, Santizo MC, Lonnerda B, Brown

KH. Impact of zinc supplementation on morbidity from

diarrhea and respiratory infections among rural

Guatemalan children. Pediatrics.1997;99:808-13.

41. Kumar A, Kubota Y, Chernov M, Kasuya H. Potential

role of zinc supplementation in prophylaxis and

treatment of COVID-19. Med Hypotheses.2020;144.

42. Templeton D, editor. Molecular and cellular iron

transport. 1st edition. New York: Marcel Decker

Inc.2002:468–87.

43. Weiss G. Iron. In: Hughes DA, Darlington LG, Bendich

A, eds. Diet and human immune function. Totowa:

Humana Press.2004:203-15.

44. Weiss G, Fuchs D, Hausen A, Reibnegger G, Werner ER,

Werner-Felmayer G, et al. Iron modulates interferon-γ

effects in the human myelomonocytic cell line THP-1.

Exp Hematol.1992;20:605-10.

45. MacMicking J, Xie QW, Nathan C. Nitric oxide and

macrophage function. Ann Rev Immunol.1997;15:323-

50.

46. Weiss G, Werner-Felmayer G, Werner ER, Grünewald K,

Wachter H, Hentze MW. Iron regulates nitric oxide

synthase activity by controlling nuclear transcription. J

Exp Med.1994;180:969-76.

47. Young VR, Nahapetian A, Janghorbani M. Selenium

bioavailability with reference to human nutrition. Am J

Clin Nutr.1982;35:1076-88.

48. McKenzie RC, Arthur JR, Beckett GJ. Selenium and the

regulation of cell signalling, growth and survival:

molecular and mechanistic aspects. Antioxid Redox

Signal.2002;4:339-51.

49. Ravaglia G, Forti R, Maioli F, Bastagli L, Facchini A,

Mariani E, et al. Effect of micronutrient status on natural

killer cell immune function in healthy free-living

subjects aged > 90. Am J Clin Nutr.2000;71:590-8.

50. Qataya, PO, Elsayed, NM, Elguindy, NM, Ahmed Hafiz,

M, Samy, WM. Selenium: A sole treatment for erosive

oral lichen planus (Randomized controlled clinical

Banerjee A et al. Dietary Immunomodulators in Management of Chronic Diseases

People’s Journal of Scientific Research / Volume 16 / Issue 1 / Jan-June 2023

trial). Oral Dis.2020;26:789– 804.

51. Salminen S, Ponley C, PourronRuanlt M, Cummings JH,

Franck A, Gibson GR, et al. Functional food science and

gastrointestinal physiology and function. Br J

Nutr.1998;80:9147-71.

52. Gill HS, Cross ML. Pobiotics and immune functions. In:

Calder PC, Field CJ, Gill HS, eds. Nutrition and immune

function, 1st edition. NewYork: CAPI publishing.

2002:251-72.

53. Majamaa H, Isolauri E, Saxelin M and Vesikarit C.

Lactic acid bacteria in the treatment of acute rotavius

gastroenteritis. J PediatrGastroentrolNutr.1995;20:333-

54. Matuzaki T, Chin J. Modulating immune responses with

probiotic bacteria. Immunol Cell Biol.2000;78:67-73.

55. Malin M, Verronen P, Mykkanen H, Salminen S, Isolauri

E. Increased bacterial urease activity in faeces in

juvenile chronic arthritis: Evidence of altered intestinal

microﬂora?. Br J Rhematol.1996;35:689-94.

56. Gionchetti P, Rizzello F, Venturi A, Campieri M.

Probiotics in infective diarrhoea and inﬂammatory

bowel diseases. J Gastroenterol Hepatol.2000;15:489-

93.

57. Gibson GR, Roberfroid MB. Dietary modulation of the

human colonic microbiota: introducing the concept of

prebiotics. J Nutr.1995;125:1401-12.

58. Roberfroid MB. Prebiotics: preferential substrates for

speciﬁc germs? Am J Clin Nutr.2001;73:406-9.

59. Nagura T, Hachimura S, Hashiguchi M, Ueda Y, Kanno

T, Kikuchi H, et al. Suppressive effect of dietary

rafﬁnose on T-helper 2 cell-mediated immunity. Br J

Nutr.2002;88:421-6.

60. Chen PN, Chu SC, Chiou HL, Kuo WH, Chiang CL,

Hsieh YS. Mulberry anthocyanins, cyanidin 3-

rutinoside and cyanidin 3-glucoside, exhibited an

inhibitory effect on the migration and invasion of a

human lung cancer cell line. Cancer Lett. 2006;

235:248-59.

61. Lin JY, Tang CY. Total phenolic contents in selected fruit

and vegetable juices exhibit a positive correlation with

interferon-g, interleukin-5, and interleukin-2 secretions

using primary mouse splenocytes. J Food Compos

Anal.2008;21:45-53.

62. Yoon H, Liu RH. Effect of selected phytochemicals and

apple extracts on NF-kappaB activation in human

breast cancer mcf-7 cells. J Agric food chem.2007;

55(8):3167-73.

63. Cherng JM, Chiang W, Chiang LC. Immunomodulatory

activities of common vegetables and spices of

Umbelliferae and its related coumarins and ﬂavonoids.

Food Chem.2008;106:944-50.

64. Brennan P, Hsu CC, Moullan N, SzeszeniaDabrowska

N, LissowskaJ, Zaridze D, et al. Effect of cruciferous

vegetables on lung cancer in patients stratiﬁed by

genetic status: a mendelian randomisation approach.

Lancet.2005;366:1558-60.

65. Kassie F, Laky B, Gminski R, MerschSundermann V,

Scharf G, Lhoste E, et al. Effects of garden and water

cress juices and their constituents, benzyl and phenethyl

isothiocyanates, towards benzo (a) pyrene-induced

DNA damage: a model study with the single cell gel

electrophoresis/Hep G2 assay. Chem Biol Interact.

2003;142:285-96.

66. Verhagen H, Poulsen HE, Loft S, van Poppel G, Willems

MI, van Bladeren PJ. Reduction of oxidative DNA-

damage in humans by brussels sprouts. Carcinogenesis.

1995;16:969-70.

67. Gill CI, Haldar S, Porter S, Matthews S, Sullivan S,

Coulter J, et al. The effect of cruciferous and

leguminous sprouts on genotoxicity, in vitro and in

vivo. Cancer Epidemiol Biomarkers Prev. 2004;13:

1199-205.

68. Briviba K, Kulling SE, Möseneder J, Watzl B,

Rechkemmer G, Bub A. Effects of supplementing a

low-carotenoid diet with a tomato extract for 2 weeks on

endogenous levels of DNA single strand breaks and

immune functions in healthy nonsmokers and smokers.

Carcinogenesis.2004;25:2373-8.

69. Lang A, Lahav M, Sakhnini E, Barshack I., Fidder HH,

Avidan B, et al. Allicin inhibits spontaneous and TNF-a

induced secretion of proinﬂammatory cytokines and

chemokines from intestinal epithelial cells. Clin

Nutr.2004;23:1199- 208.

70. Fleischer DM, Conover-Walker MK, Christie L, Burks

AW, Wood RA. The natural progression of peanut

allergy: resolution and the possibility of recurrence. J

Allergy Clin Immunol.2003;112:183-9.

71. Yamaki K, Kim DH, Ryu N, Kim YP, Shin KH, Ohuchi

K. Effects of naturally occurring isoﬂavones on

prostaglandin E2 production. Planta Medica.

2002;68:97-100

72. Cos P, Ying L, Calomme M, Hu JP, Cimanga K, Van Poel

B, et al. Structure- activity relationship and

classiﬁcation of ﬂavonoids as inhibitors of xanthine

oxidase and superoxide scavengers. J Natural

Products.1998;61:71-6.

73. Sangwan NS, Shanker S, Sangwan RS, Kumar S. Plant

derived products as antimutagens. Phytotherapy

Res.1998;12:389-99.

7 4 . D i x o n R A , F e r r e i r a D . G e n i s t e i n .

Phytochemistry.2002;60:205-11.

7 5 . Ya m a z a k i K , M u r r a y J A , K i t a H . I n n a t e

immunomodulatory effects of cereal grains through

i n d u c t i o n o f I L - 1 0 . J A l l e r g y C l i n

Immunol.2008;121:172-8.

76. Ye M, Liu JK, Lu ZX, Zhao Y, Liu SF, Li LL, et al.

Grifolin, a potential antitumor natural product from the

mushroom Albatrellusconﬂuens, inhibits tumor cell

growth by inducing apoptosis in vitro. FEBS

Letters.2005;579:3437-43.

77.

Kohno K, Okamoto I, Sano O, Arai N, Iwaki K, Ikeda M,

et al. Royal jelly inhibits the production of

proinﬂammatory cytokines by activated macrophages.

BiosciBiotechnolBiochem. 2004;68:138-45.

78. Okamoto I, Taniguchi Y, Kunikata T, Kohno K, Iwaki K,

Ikeda M, et al. Major royal jelly protein 3 modulates

Banerjee A et al. Dietary Immunomodulators in Management of Chronic Diseases

People’s Journal of Scientific Research / Volume 16 / Issue 1 / Jan-June 2023

immune responses in vitro and in vivo. Life

Sci.2003;73:2029-45.

79. Meydani SN, Ha WK. Immunologic effects of yogurt.

Am J Clin Nutr.2000;71:861-72.

80. Yamauchi A, Bloom ET. Requirement of thiol

compounds as reducing agents for IL-2-mediated

induction of LAK activity and proliferation of human

NK cells. J Immunol.1993;151:5535-44.

81. Durrieu C, Degraeve P, Chappaz S, MartialGros A.

Immunomodulating effects of watersoluble extracts of

traditional French Alps cheeses on a human T-

lymphocyte cell line. Int Dairy J.2006;16:1505-14.

82. Meisel H, Gunther S. Food proteins as precursors of

peptides modulating human cell activity.

Nahrung.1998;42:175-6.

83. Meisel H, Gunther S. Food proteins as precursors of

peptides modulating human cell activity.

Nahrung.1998;42:175-6.

84. Green TD, LaBelle VS, Steele PH, Kim EH, Lee LA,

Mankad VS, et al. Clinical Characteristics of Peanut-

Allergic Children: Recent Changes. Pediatrics.

2007;120:1304-10.

85. Sicherer SH, Sampson HA. Food allergy. J Allergy Clin

Immunol.2006;117:470-5.