Effects of Diet and Immunomodulation in Children

Investigators reviewed dietary macro- and micronutrients that affect the immune system and provided recommendations on immunomodulation in children.

Due to the complex interactions between diet, microbiome, and epigenetic influences, nutrition counseling in children should start early in life and stress the importance of foods with immune-modulating effects to promote healthy eating, according to study results published in the Journal of Pediatric Gastroenterology and Nutrition.

A pair of investigators from Italy and the United Kingdom reviewed dietary macro- and micronutrients that affect the immune system and used this information to provide recommendations on immunomodulation in children. As an imbalanced diet may result in suboptimal immune function due to macro- and micronutrient insufficiency, the authors highlighted the role of each nutrient and its effect on immunomodulation.


Protein deficiencies can lead to an array of immune dysfunctions and higher risk for infections. Some negative effects of protein deficiency include impaired gastrointestinal barrier function, loss of lymphoid tissue, altered intestinal microbiota, and negative effects on hematopoietic and lymphoid organs. Amino acids like arginine and glutamine are essential for immune system function. Arginine is needed for cardiovascular and immune system functioning, as well as wound healing, while some roles of glutamine include lymphocyte proliferation, cytokine production, and macrophage and neutrophil activity.

Children eating a healthy, balanced diet do not need glutamate supplementation; therefore, appropriate protein intake during the rapid growth period in child development, especially the first years of life and puberty, is essential to maintaining immune function.


Dietary lipids, namely polyunsaturated fatty acids (PUFA), such as docosahexaenoic acid (DHA) and omega-3 PUFAs are important modulators of innate and adaptive immunity. DHA can inhibit inflammatory response via mediators. Adequate dietary intake of eicosapentaenoic acid (EPA) and DHA, which suppress inflammatory response by reducing the expression of arginase, should be considered 250 mg for children 2 years and older in 1 or more servings. During the first 2 years of life, only 100 mg of DHA per day are necessary. Although dietary sources of DHA can be found in oily fish, this should be limited to one serving per week to avoid mercury poisoning.

Lastly, conjugated linoleic acid (CLA), an omega-6 fatty acid that can be found in cow’s milk, dairy products, and breast milk, can also modulate immune function. CLA produces cytokines, eicosanoids, and nitric oxide; it has also been shown to have a protective effect on the development of atopic manifestations in infants.

Dietary Prebiotics

Typically present in the diet are nondigestible carbohydrates, often in the form of dietary prebiotics, which influence the makeup and activity of the microbiota of the intestines. “The mechanism by which prebiotics have a beneficial effect on the functioning of the immune system has not yet been fully understood,” the authors noted. However, some hypothesized effects include increased short-chain fatty acid production, modulation of mucin production, increased number of lymphocytes and leukocytes in gut-associated lymphoid tissue and peripheral blood, and the stimulation of phagocytic function of inflammatory macrophages. These dietary prebiotics can be found in edible plants.


Vitamins and minerals play important roles in innate and adaptive immune responses. “[H]owever, in conditions associated with a systemic inflammatory response, interpretation of vitamin and trace element concentrations in blood can be misleading in clinical practice,” the researchers wrote. Some important vitamins that act as immunomodulators include vitamins A, B6, B9, B12, C, D, and E.

Trace Elements

Normal levels of zinc are important for maintaining the immune system, with deficiencies being linked to diarrhea and respiratory infections. In children aged 2 to 60 months in low- and middle-income countries, zinc plays a significant role in the prevention of respiratory infections. Several dietary resources such as plant foods (eg, whole grains and certain nuts) and animal-derived foods (eg, red meat, fish, and cheese) are also sources of dietary zinc.

Copper has bactericidal properties and is needed for cell-mediated immunity and specific antibody formation. Copper supports macrophages, T helper cells, B cells, neutrophils, and natural killer cells. Deficiency in copper can leave children susceptible to bacterial infections. Dietary copper can be acquired from liver, fish, aged cheeses, nuts, and cocoa.

Selenoproteins needed for immune function require selenium. Function of mitogen-activated protein kinase, nuclear factor kappa B (NF-kB), and proliferator-activated receptor gamma-dependent regulation of proinflammatory mediators are tied to selenium. Deficiency in selenium is linked to sepsis in intensive care patients. Supplementation in preterm infants can decrease the risk for nosocomial sepsis. Dietary selenium can be found in liver, meat, and fish. Due to low levels of selenium in agricultural soil in certain areas of Europe, some populations may have lower selenium intake.

Iron plays an important role in the proliferation and maturation of immune cells, especially in lymphocytes. Iron deficiency is common and diagnosed as serum ferritin levels lower than 12 μg/L for children aged less than 5 years and below 15 μg/L for children aged 5 years or more. Deficiency in iron can lead to decreased response to infections, fatigue, and response to metabolic stress, reduced cognitive functions, and growth impairments. Combined iron and vitamin A supplementation may reduce the incidence of diarrhea- and respiratory-linked illnesses. Heme iron can be found in meat, which contributes to 20% of the intake, while nonheme iron can be found in vegetables and dairy products; however, this form of iron is not as well absorbed as heme iron. Consuming vitamin C simultaneously can help improve iron absorption. Foods rich in iron include meat, egg, grains, legumes, and some vegetables.

“More information regarding the optimal dietary intake (and blood/plasma levels) to achieve an immunoregulatory action of these nutrients are desirable,” the authors noted. “Well-designed intervention studies, investigating the effects of whole dietary pattern on the immune system, are needed,” the researchers added.


Verduci E, Köglmeier J. Immunomodulation in children: the role of the diet. J Pediatr Gastroenterol Nutr. 2021;73(3):293-298. doi:10.1097/MPG.0000000000003152