Introduction
Food, nutrition and health are highly interrelated and consumption of specific nutrients have a profound impact on human health. The amount and type of nutrients consumed are tightly linked to the metabolic system and the immune health and thus, inappropriate nutrient consumption is associated with development of major human diseases due to an immune system not properly functioning (1).Nutrition plays an essential role in the regulation of optimal immunological response, by providing adequate nutrients in sufficient concentrations to immune cells. There is a large number of micronutrients, such as minerals, and vitamins, as well as some macronutrients such as some amino acids, cholesterol and fatty acids demonstrated to exert a very important and specific impact on appropriate immune activity.
But what is the immune system? The immune system serves as the body’s defense mechanism, protecting against pathogens like bacteria, viruses, and harmful substances. It is a network of intricate systems and pathways in the body, that protects us against these harmful microbes as well as certain diseases. It recognizes foreign invaders like bacteria, viruses, and parasites and takes immediate action. Humans possess two types of immunity: innate and adaptive. Innate immunity is a first-line defense from pathogens that try to enter our bodies, achieved through protective barriers. These barriers include:
-Skin that keeps out the majority of pathogens
-Mucus that traps pathogens
-Stomach acid that destroys pathogens
-Enzymes in our sweat and tears that help create anti-bacterial compounds Immune system cells that attack all foreign cells entering the body (2).
Adaptive or acquired immunity is a system that learns to recognize a pathogen. It is regulated by cells and organs in our body like the spleen, thymus, bone marrow, and lymph nodes. When a foreign substance enters the body, these cells and organs create antibodies and lead to multiplication of immune cells (including different types of white blood cells) that are specific to that harmful substance and attack and destroy it. Our immune system then adapts by remembering the foreign substance so that if it enters again, these antibodies and cells are even more efficient and quick to destroy it.
Inflammation is an important, normal first step in the body’s innate immune response. When pathogens attack healthy cells and tissue, a type of immune cell called “mast cells” counterattack and release proteins called histamines, which cause inflammation. Inflammation may generate pain, swelling, and a release of fluids to help flush out the pathogens. The histamines also send signals to discharge even more white blood cells to fight pathogens. However, prolonged inflammation can lead to tissue damage and may overwhelm the immune system. The inflammatory mechanisms that compose the innate immunity are strongly influenced by nutrition, and this interaction, when perturbed, can profoundly affect disease development. The immune system is able to destroy antigens through both innate and adaptive immune cells and finally through antibodies that are specific for each pathogen (3).
What factors can depress our immune system?
- Older age: As we age, our internal organs may become less efficient; immune-related organs like the thymus or bone marrow produce fewer immune cells needed to fight off infections. Aging is sometimes associated with micronutrient deficiencies, which may worsen a declining immune function.
- Environmental toxins (smoke and other particles contributing to air pollution, excessive alcohol): These substances can impair or suppress the normal activity of immune cells.
- Excess weight: Obesity is associated with low-grade chronic inflammation. Fat tissue produces adipocytokines that can promote inflammatory processes . Research is early, but obesity has also been identified as an independent risk factor for the influenza virus, possibly due to the impaired function of T-cells, a type of white blood cell .
- Poor diet: Malnutrition or a diet lacking in one or more nutrients can impair the production and activity of immune cells and antibodies.
- Chronic diseases: Autoimmune and immunodeficiency disorders attack and potentially disable immune cells.
- Chronic mental stress: Stress releases hormones like cortisol that suppresses inflammation (inflammation is initially needed to activate immune cells) and the action of white blood cells.
- Lack of sleep and rest: Sleep is a time of restoration for the body, during which a type of cytokine is released that fights infection; too little sleep lowers the amount of these cytokines and other immune cells.
As we can see from the previous list, a well-functioning immune system depends on various factors, but one of the most crucial is our nutrition. The food we eat affects our weight, body composition and availability of the essential nutrients and bioactive compounds that directly influence the immune system’s development, maintenance, and activity (4) .
But let’s dive more into this.
The cells in our body require energy from food, and immune cells are no exception. One of the best ways to support your immune system is to eat enough. In order to make and support immune cells, your body needs energy, which comes from the food and drinks you put in your body. In addition to fueling immune cells, the different macronutrients and micronutrients offer support on many other levels:
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Work as antioxidants
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Produce antibodies
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Provide structure for immune cells
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Promote growth and activity of immune cells
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Produce white blood cells
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Regulate immune cells responses
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Lower oxidative stress and reduce inflammation
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Synthesis of immune cell DNA and protein
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Repair damaged cells and tissue
The number of studies related to the impact of nutrition on immune system is continuously increasing. The initial studies published were related to nutritional-modulation of the immune function andwere mostly based on the effects of micro and macronutrients . Lately, a wide variety of phytochemicals and other chemical biocomponents found in nutrients has been added to the list of nutritional-immuno-modulators. These biocomponents affect the immune function but are not crucial for maintaining normal cell metabolism and function . Cases in point are several phytochemicals demonstrated to exert impressive positive immune effects (3) .
In light of the strong effects that nutrients have on the immune system, and we will list in the following paragraphs, it can be concluded that a rich-nutrient diet is rigorously required in order to maintain an adequate health status. This is in addition to the fact that nutrients are the main factors for survival, including cell proliferation, specialization, development of tissue and organs growth, energy supply, and the immune defense function (4) .
Moreover, nutritional deficiencies are closely associated with impaired immune response and loss of the host resistance to infection . On the one hand, in less developed regions, malnutrition continues to be a major health problem since it is associated with a higher incidence of morbidity and mortality usually linked with the higher prevalence of bacterial and parasitic infection diseases in these regions . In contrast, developed countries present an inadequate diet consumption, with no real nutritional value, accompanied by excess calories (5) . Therefore, malnutrition due to undernutrition or to consumption of poor diets, deficient in macro- and micronutrients, reduce the effectiveness of the immune system, not only by causing a deterioration of the immune protection but also reducing its efficacy in appropriate elimination of the pathogens, thus making people unprotected to a vast variety of diseases.
To clarify all these aspects, it is essential to understand the meaning of an adequate diet and to recognize the harmful effect of processed foods that impact the immune system. As alluded to earlier, nutrition plays an essential role in the regulation of optimal immunological response, by providing adequate nutrients in sufficient concentrations to the immune cells. In such a manner, the immune system can initiate effective responses against pathogens. In order to avoid chronic inflammation, nutrients stemmed from the diet exert significant effects in initiating this quick response (6) . When the dietary nutrients are insufficient or inefficient, the supply of these elements to the immune system cells is significantly spared and immunity is compromised.
Does an Immune-Boosting Diet Exist?
Different nutrients play different roles in supporting immune health, so there are no “super foods” that can do it all. Therefore, eating enough nutrients as part of a varied diet is required for the health and function of all cells, including immune cells. Diets that are limited in variety and lower in nutrients, such as consisting primarily of ultra-processed foods and lacking in whole organic foods, can negatively affect a healthy immune system . Certain dietary patterns may better prepare the body for microbial attacks and excess inflammation, but it is unlikely that individual foods offer special protection. Each stage of the body’s immune response relies on the presence of many micronutrients. However, there are certain micronutrients such as vitamins and minerals as well as some macronutrients such as specific amino and fatty acids demonstrated to exert a very important and particular impact on immune modulation.
Vitamin C works as an antioxidant but is also involved in the modulation of a wide variety of immune functions by boosting the production and function of white blood cells. Vitamin C is also involved in gene transcription as well as in hydroxylation reactions (7) . Through its main function as an antioxidant, it is capable to defend the body against reactive oxygen species that are the result of the activity of toxins and pollution. It can be found in foods such as :
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Orange, grapefruit,guava, black currant, lemon, lychee
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Broccoli, spinach, tomato, artichoke
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Strawberry, mango, papaya, kiwi.
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Kale, bell pepper, Brussels sprouts, snow peas, green chili, kohlrabi, parsley
Vitamin D is both a nutrient we eat and a hormone our bodies make. It has long been known to help the body absorb and retain calcium and phosphorus and is critical for building bone. Additionally, recent studies show that vitamin D can modulate the immune response in our body, reduces cancer cell growth, help control infections and reduce inflammation. Deficiency has been linked to increased susceptibility to respiratory infections and osteomalacia/osteoporosis. Our body can synthesize vitamin D when our skin is exposed to the sun, which is the primary natural source of vitamin D, but many people have insufficient levels because they live in places where sunlight is limited in winter, or because they have limited sun exposure due to being inside much of the time. Foods that contain significant quantities are:
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Salmon, tuna
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Mushroms
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Beef liver
Vitamin A works as an antioxidant and additionally helps in the production of white blood cells while regulating the immune cell responses. Deficiency of this vitamin affects processes related to appropriate cytokines release and antibody production. Additionally, vitamin A deficiency is associated with a reduced production of natural killer cells, monocytes or macrophages, and impaired maturation and proliferation of T- and β-lymphocytes and supports the integrity of skin and mucosal barriers, the first line of defense against pathogens. Vitamin A supplementation cuts down morbidity and mortality in various infectious diseases. Found in foods like:
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Carrot, bell pepper, artichoke
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Sweet potato, pumpkin, squash, russet potato
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Spinach, kale, cooked collards, cooked turnip green, chard, lettuce
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Mango, papaya, apricot, cantaloupe, red grapes, watermelon, tangerine, nectarine, guava, passion fruit
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Beef, lamb, goose liver
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Bluefin tuna, trout
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Goat, limburger, cheddar, blue, and feta cheeses
Vitamins B1, B2, B3, B6 and B12 are water soluble vitamins in charge to carry out essential, inter-related roles for appropriate cellular functioning and additionally help the body make healthy red blood cells and aid in maintaining the lymphatic system. These vitamins act as efficient co-enzymes in a vast array of catabolic and anabolic enzymatic reactions and they are essential cofactors for many important cellular metabolic pathways that assist our immune response. They can be found in foods as:
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Legumes, beans
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Spinach, kale, arugula, asparagus, turnip greens, romaine lettuce, Brussels sprouts, broccoli, beets
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Orange, grapefruit, lemon, lime, papaya, banana, avocado
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Peanuts, sunflower seeds
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Wheat germ
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Poultry and meat products.
Selenium is involved in the functioning of the thyroid metabolism and the cardiovascular system as well as in ensuring a functional immune system and preventing cancer. It promotes the growth and activity of immune cells while lowers oxidative stress and inflammation. Found in:
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Seafood, poultry
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Cottage cheese
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Whole grains, including whole grain breads and pasta, brown rice, barely, quinoa, rye, millet
Zinc is responsible for the inflammatory cytokines number reduction and promotes growth and activity of immune cells. Zinc deficiency is associated with impaired immune function and slower wound healing.
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Nuts, cashews
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Oysters and shellfish
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Chickpeas
Iron supports the proliferation of immune cells and the production of enzymes that fight infections and carries oxygen to immune cells. Found in :
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Red meat, chicken, turkey
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Canned light tuna, sardines
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Clams, oysters
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Beans
Macronutrients:
Amino Acids: Besides micronutrients, macronutrients, such as proteins and amino acids, also play an important role in the activity of the immune system. Proteins are formed from amino acids that are essential in the construction of other proteins among which antibodies and cytokines that are typical proteins belonging to the immune system . Essential amino acids from protein-rich foods like poultry, fish, and tofu are critical for building immune cells and antibodies (7) . Amino acids such as L-arginine and L-tryptophan are responsible and critical for macrophages’ appropriate immune activity. The decline of protein metabolism that is related to the diminishing concentration of certain amino acids, leads to the endoplasmic reticulum (ER) stress. As a result, the T cells which produce pro-inflammatory cytokines are activated . For example, the deficiency of Arginine is correlated with reduced T cell ability to trigger tumor immunity (14) .
Healthy Fats: Polyunsaturated fatty acids (PUFAs) are essential fatty acids that contain more than one double bond in their backbone. PUFAs are divided into two main groups: Omega-3s and omega-6s. Together with cholesterol, PUFAs are essential for cell membrane integrity, development and maintenance in the homeostasis of cell function. Omega-3 fatty acids, found in fatty fish, walnuts, and flaxseeds, reduce inflammation and promote a balanced immune response. Omega-3s from the PUFAs group are involved in anti-inflammatory reactions through the inhibition of ARA from the membrane, which is the main precursor for pro-inflammatory eicosanoids (9) . They are capable to modulate immune and inflammatory responses through intensity and duration. On the one hand, pro-inflammatory effects are linked to fever, vasodilatation and intensification of pain. On the other hand, they could have anti-inflammatory effects by blocking natural killer activity and lymphocyte proliferation. However, most importantly is the ratio between the 2 groups of PUFAs. Simopoulos, tried to shade light in this regards and proposed that a low omega-6/omega-3 ratio in women is responsible for the decrease in breast cancer risk. She additionally concluded that a lower ratio is associated with a general decrease in very common chronic diseases in the Western society (10) .
Cholesterol in food is often misunderstood. In reality cholesterol is needed for all cellular membranes, making its biosynthesis and regulatory pathways ubiquitous across cell types, including immune cells. Recent studies have underlined an emerging role for cholesterol as an important modulator of innate and adaptive immunity activity. There are mainly two types of cholesterol the high-density lipoprotein (HDL) or “good” cholesterol, and low-density lipoprotein (LDL) or “bad” cholesterol. If there is too much LDL cholesterol in the blood, it builds up in the walls of the blood vessels, causing them to narrow and stiffen. A buildup of LDL cholesterol reduces blood flow and can increase the risk of heart attack or stroke. HDL cholesterol can move LDL cholesterol from the blood to the liver, which breaks it down for disposal as waste. HDL cholesterol is referred to as good cholesterol because it reduces the level of cholesterol in the blood. Higher HDL levels are linked to a reduced risk of heart attack and heart disease. Foods that can raise HDL cholesterol are :
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Olive Oil
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Nuts
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Fatty Fish
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Seeds
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Cocoa and Dark Chocolate
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Avocado
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Legumes and Beans
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Fruits and Vegetables
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Whole Grains
Gut Health and Immunity
It would be a big mistake to analyse the relation between the food we eat and our immune system , without mentioning the gut. The gut plays a pivotal role in immunity, as approximately 70% of the immune system resides in the gastrointestinal tract. The human gut is home to trillions of microorganisms, collectively known as the gut microbiome. These microorganisms—bacteria, fungi, viruses, and other microbes—play an integral role in maintaining health by interacting closely with immune cells to regulate their activity.
The diet plays a large role in determining what kinds of microbes live in our intestines. A typical Western diet high in refined sugar and processed foods can promote disturbances in healthy intestinal microorganisms, resulting in chronic inflammation of the gut, which is associated with suppressed immunity (12) . A high-fiber plant-rich diet with plenty of fruits, vegetables, whole grains, and legumes appear to support the growth and maintenance of beneficial microbes (13) . Certain helpful microbes break down fibers into short chain fatty acids, which have been shown to stimulate immune cell activity. Probiotic foods contain live helpful bacteria, and prebiotic foods contain fiber and oligosaccharides that feed and maintain healthy colonies of those bacteria. Therefore, a diet containing probiotic and prebiotic foods may be beneficial.
Probiotic foods include kefir, yogurt with live active cultures, fermented vegetables sauerkraut, tempeh kombucha tea, kimchi and miso.
Prebiotic foods include garlic, onions, leeks, asparagus, Jerusalem artichokes, dandelion greens, bananas, and seaweed. However, a more general rule is to eat a variety of fruits, vegetables, beans, and whole grains for dietary prebiotics.
Conclusion
The relationship between food and the immune system is profound and multifaceted. A balanced diet rich in vitamins, minerals, and other bioactive compounds provides the foundation for a robust immune system, while poor dietary choices can weaken it and increase vulnerability to diseases. Recognizing the pivotal role of nutrition in immune health empowers individuals to make informed food choices, fostering not only immunity but also overall well-being. As science continues to uncover the intricate connections between diet and immunity, one thing remains clear: Hippocrates, the “father of medicine” knew it al along when thousands of years ago suggested : “Let food be thy medicine and medicine be thy food“.
References
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- Simopoulos A. The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother. (2002) 56:365–79. 10.1016/s0753-3322(02)00253-6.
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- Caballero S, Pamer EG. Microbiota-mediated inflammation and antimicrobial defense in the intestine. Annual review of immunology. 2015 Mar 21;33:227-56.
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- Szefel J, Danielak A, Kruszewski W. Metabolic pathways of L-arginine and therapeutic consequences in tumors. Adv Med Sci. (2019) 64:104–10. 10.1016/j.advms.2018.08.018.
- Rubio-Patiño C, Bossowski J, De Donatis G, Mondragón L, Villa E, Aira L, et al. Low-protein diet induces IRE1α-dependent anticancer immunosurveillance. Cell Metab. (2018) 27:828.e–42.e. 10.1016/j.cmet.2018.02.009.
- Szefel J, Danielak A, Kruszewski W. Metabolic pathways of L-arginine and therapeutic consequences in tumors. Adv Med Sci. (2019) 64:104–10. 10.1016/j.advms.