Topic of the Month

Micronutrients and the immune system

February 1, 2014

The task of the immune system is to protect the organism against harmful external influences, e.g., microorganisms. One consequence of an immune reaction is inflammation, which serves to remove foreign bodies or pathologically altered cells. However, if the immune reaction is not appropriate it may lead to undesirable effects, including increased vulnerability to infections if immune function is diminished, or allergies, autoimmune diseases and chronic inflammation in the case of hyperfunction. To fulfill its many and various protective and signaling functions, the immune system relies on the adequate availability of micronutrients. Potential deficiencies can affect both unspecific (innate) and specific (acquired) immunity.

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A person’s psychological state, as well as their physical condition, greatly influences immune system activity. Chronic (inflammatory) diseases or frequent physical exertion (work or sports) can lead to permanently elevated immune system activity and incre- ase the requirement for micronutrients. Vitamins, trace elements and omega-3 fatty acids, in particular, are indispensable for the synthesis of components of the immune defense system (including immunoglobulins, cytokines and enzymes). Thanks to their antioxidant and/or anti-inflammatory properties they ensure optimum functionality or regulate immune cell processes. The nutrients collaborate and complement each other in the diverse pro- cesses of the immune system.

Antioxidant vitamins

As a fat-soluble antioxidant, vitamin E can protect lipids – which are the building blocks of cell membranes – against attack by free radicals (e.g., highly reactive oxygen compounds). These free radicals occur in the body as a result of metabolic processes like immunological reactions and the effect of environmental influ- ences. Experimental findings indicate that vitamin E can also stimulate the immune system directly (1): the vitamin acts primarily on the mast cells (mastocytes), which belong to the leukocyte (white blood cell) group (2) and play a special role in wound healing, in warding off pathogens and in allergies. Mast cells are acti- vated by oxidized lipoproteins that occur under the influence of pro-inflammatory signaling molecules (cyto- kines). These cells then release signaling molecules which in particular encourage allergic inflammatory pro- cesses. Vitamin E is thought to influence these processes on several levels. In the first place, thanks to its antioxidant properties vitamin E can limit the oxidation of lipoproteins and hence prevent the excessive pro- duction and activation of mast cells. In this way the vitamin can combat overreactions of the immune system and allergic reactions. Moreover, vitamin E reduces the formation of pro-inflammatory cytokines that are produced by macrophages (scavenger cells) and their precursor cells (monocytes) (3). Additionally, vitamin E appears to act directly on T cells (white helper cells) and is therefore able to reduce inflammation (4).

The antioxidant vitamin C can also support the immune system and reduce the severity of allergic reactions (5). Its mode of action on the immune system has been only partially researched. As a water-soluble anti- oxidant it can prevent oxidative damage inside immune cells caused by reactive oxygen species which are released in greater quantities on activation of the immune response (6). Infections reduce the concentration of vitamin C in immune cells. Vitamin C also appears to act directly on the cellular (immune cell) and hum- oral (plasma proteins such as antibodies) components of the immune system (7). Hence the vitamin can promote activity by the white blood cells (leukocytes, lymphocytes, T cells) and macrophages, prolonging their function, and can stimulate the release of the signaling molecule interferon, which is involved in the defense against viruses. Vitamin C also accelerates the decomposition of histamine in the blood. As a signa- ling molecule, histamine is substantially involved in the development of cold symptoms in terms of inflam- matory reactions (2). Although targeted consumption of vitamin C does not, in general, appear to afford protection against colds, some studies do indicate that the vitamin can reduce the duration and severity of infections of the upper respiratory tract (8). In particular, people who do hard physical work over short periods of time and/or are exposed to low temperatures for lengthy periods could combat colds with regular consumption of vitamin C. Taking 200 mg of vitamin C per day could alleviate the symptoms of acute respi- ratory infections in the elderly (9).

The effect of beta-carotene on the immune system is based essentially on its properties as a fat-soluble antioxidant. Reactive oxygen species are formed extensively during inflammatory processes intended to render germs harmless. Beta-carotene, working together with other antioxidants, can ensure balanced regulation of oxidative processes, so that infectious germs can be fought without allowing an excess of free radicals to damage the immune cells (10). How beta-carotene and other carotenoids could directly streng- then cellular and humoral immune defense is as yet unclear and requires further research (11). One ran- domized controlled study with post-menopausal women was able to show that daily consumption of a combi- nation of beta-carotene, lutein and lycopene or only one of these carotenoids was able to protect lympho- cytes against damage to their genetic substance (DNA) (12).

Vitamin A

Vitamin A (retinol) is important for the development and protection of skin and the mucous membranes that represent the first line of defense against pathogens. Vitamin A is also important for acquired immune sys- tem functioning (13). Hence retinoic acid is needed for the activity of diverse immune cells, such as the divi- sion, growth and the differentiation of T cells (14, 15). Vitamin A also plays a key role in the transport of T cells to tissue and in T-cell-dependent antibody reactions (16), as well as in lymphocyte maturation (17). A lack of vitamin A has been linked to a diminished ability to fend off infectious germs (18) and to an increased susceptibility to respiratory infections (19). Studies indicate that targeted consumption of vitamin A can redu- ce inflammatory processes, for example in the lung and the bronchial tubes (20).

B vitamins

Vitamins B2, B6, B12 and folic acid (vitamin B9) appear to be able to enhance the function of immune cells such as T and B lymphocytes or macrophages (21). A lack of vitamin B2 impairs the ability of macrophages to adhere to microorganisms (22). Vitamin B6 is involved in the production of antibodies and in cellular im- mune defense (23, 24) and has further proved beneficial in the treatment of inflammatory infections of the respiratory tract (25). Damage to the DNA of mononuclear leukocytes identified in children with vitamin B12 deficiency and their mothers has been reversed by the administration of vitamin B12 injections (26).

A deficiency of folic acid can also weaken the immune system (27), for example by impeding the formation of antibodies or new immune cells (28). Folic acid regulates the blood concentration of the amino acid homo- cysteine, which in large amounts can damage cells. High homocysteine levels are often found in patients with chronic immune-dependent diseases like rheumatoid arthritis or psoriasis (29) and treatment with folic acid has been recommended for patients with chronic inflammatory skin diseases.

Vitamin D

Vitamin D modulates the function of the innate and of the acquired immune system and is particularly effec- tive in combating excessive infectious and inflammatory reactions (2). Many immune cells appear to need vitamin D for their development and function (30); they possess vitamin D receptors (31). Vitamin D reinfor- ces the activity of macrophages and monocytes brought into play by the body to fight microorganisms. Fur- ther, it appears to be crucial to the control of infection, because it increases the blood concentration of the body’s own antimicrobial proteins (e.g., alpha- and beta-defensin). Moreover, vitamin D activates enzymes in T and B lymphocytes.

Epidemiological studies found an association between low blood levels of vitamin D and an elevated risk for various autoimmune diseases like multiple sclerosis (32) or type-1 diabetes (33). Both epidemiological and clinical studies have shown that low blood levels of vitamin D are associated with an up to 40% higher risk of developing respiratory tract infections (34,35) or influenza (36). In one randomized controlled study of pa- tients with a weakened immune system it was possible to demonstrate that daily administration of 4,000 I.U. of vitamin D3 for a period of one year significantly reduced the incidence of recurrent respiratory tract infec- tions (37).

Omega-3 fatty acids

The strength of the immune system is also dependent on a sufficient supply of the omega-3 fatty acids eico- sapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which play an essential role in the regulation of inflammation (38). Whilst omega-3 fatty acids form the basic substances for the production of anti-inflamma- tory, hormone -like icosanoids, omega-6 fatty acids (essentially arachidonic acid) are used for the synthesis of pro-inflammatory icosanoids. If the body is supplied with sufficient amounts of eicopentaenoic acid, the concentration of arachidonic acid diminishes and with it the amount of pro-inflammatory icosanoids (39, 40). As a consequence the formation of pro-inflammatory cytokines is reduced, as is the production of reactive oxygen compounds, high concentrations of which can damage immune cells. Pro-inflammatory cytokines, which include interferons, interleukin-1 (IL-1) and tumor necrosis factor (TNF), are important components of the immune defense system. However, when present in high concentrations they can give rise to excessive, pathological inflammatory reactions. Randomized controlled studies have shown that patients with rheuma- toid arthritis benefit from targeted consumption of omega-3 fatty acids in fish oil. Swelling went down, pain was diminished and morning stiffness reduced, and they needed less medication (non-steroidal anti-inflam- matories) (41, 42).

Trace elements

The effect of iron on the immune system depends in particular on its concentration in the blood. Iron defici- ency has been linked to several reversible functional disorders of the immune system (43), for example pro- inflammatory processes (44). In one intervention study with anemic children, fewer infections were observed after targeted administration of iron (43). On the other hand, the immune system attempts to deny microbes the iron they need to survive as a way of fighting the germs (45). In any case, sustained consumption of large doses of iron should be avoided.

Zinc influences immune defense in various ways. As an antioxidant it protects immune cells against oxida- tive damage from reactive oxygen compounds. It fulfils this function particularly consistently in synergy with vitamin C (46). In addition, zinc promotes the growth, maturation and activity of numerous immune cells such as the B and T lymphocytes and natural killer cells (47, 48), and functions as a signaling molecule for defense cells (49). A severe lack of zinc can massively reduce the activity of immune cells and the produ- ction of antibodies. However, even a slight zinc deficit can make older people, in particular, more susceptible to virus infections and allergic diseases (50). Several studies have shown that balancing zinc deficits by targeted administration can redress this susceptibility and strengthen the immune system. Another study provided evidence that food supplementation with zinc can reduce the incidence of acute infections of the lower airways in children by 15% (51). One meta-analysis came to the conclusion that zinc can reduce the symptoms, severity and duration of a cold if it is taken orally within 24 hours of the appearance of the first symptoms (52).

Selenium acts on the one hand as an antioxidant to protect against the reactive oxygen molecules which are formed during immunological processes and, in high concentrations, can cause oxidative damage to the immune cells. On the other hand, selenium plays an important role in the regulation of the immune system and of inflammatory processes (53). In particular as a component of the selenoproteins it regulates signal transmission and the function of immune cells, e.g., the activation of natural killer cells and the formation of signaling molecules (cytokines). Selenium deficiency can contribute to an increase in susceptibility to bac- terial infections or viral infections like influenza (54) and to an elevated risk of complications from infections (55).

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