The present invention relates to an immunostimulating food supplement particularly for use in the treatment of bacterial or viral infections, in reducing tiredness and fatigue and in the protection of cells against oxidative stress.

The immune system is constituted by a complex network of cells, tissues, organs and by the substances that they produce and has the function to protect the body from infectious agents and from cells transformed into tumor cells.

The immune system implements two forms of defense: nonspecific, innate or natural immunity, and specific or adaptive immunity. The former consists of mechanisms that exist prior to an exposure to a foreign agent. The latter develops after birth and is enhanced as a result of contracted infections, thus following exposure to foreign agents. Adaptive immunity involves mechanisms adapted to establish a memory of the encountered agents and of the specific response established.

An adequate intake of nutrients, vitamins, and trace elements is considered fundamental for maintaining levels of normal activity of the components of the immune system. The European Food Safety Authority (EFSA) has evaluated and considers six vitamins (D, A, C, folate, B6, Bl 2) and four minerals (zinc, iron, copper, and selenium) to be essential for the normal function of the immune system. Vitamin C, zinc, selenium, and copper contribute to the normal function of the immune system. Selenium and copper also contribute to the protection of cells from oxidative stress.

A micronutrient deficiency results in a weakening of immune functions by affecting both the innate immune response mediated by T-cells and the adaptive antibody response, causing a dysfunction in the regulation of the host's immune response. In such a circumstance, the host's susceptibility to infections increases, along with the morbidity and mortality rates. In addition, the increase in infections leads to a worsening of micronutrient deficiencies, since it leads to a decrease in the absorption of nutrients and to the alteration of metabolic pathways. These events occur mainly in subjects with eating disorders, smokers, chronic alcoholics, patients with autoimmune diseases, during pregnancy and breastfeeding, and in the elderly.

Therefore, the efficiency of immune defenses depends on the overall physical conditions (pregnancy, debilitation, body weight, etcetera), nutritional status, lifestyle and level of psychophysical stress to which one is exposed. In childhood, the immune system is still partially inefficient, due to immaturity, and expresses its maximum protective potential after puberty, maintaining it throughout adulthood.

After the age of 50-60, the defensive capacity of the immune system begins to decline progressively, since with aging there is a physiological reduction in its functionality, due to senescence of the immunocompetent cells, and therefore the innate and adaptive immune response becomes less effective, resulting in a greater susceptibility to infections. Elderly people are, in fact, more exposed to diseases and less able to react to the attack of pathogenic microorganisms.

However, even in a healthy young person the functionality of the immune system can occasionally fail, especially if one does not follow a healthy and varied diet, which is able to ensure a sufficient energy intake and all the micronutrients that are essential for the proper functioning of the body, such as vitamins (particularly, antioxidants such as A, C and E and those of group B) and mineral salts (especially zinc, characterized by an immune system enhancement action).

Immunostimulants or immuno stimulators are substances capable of stimulating the immune defenses of the body. Nutrients, drugs and plant extracts are immunostimulant substances that allow the prevention of diseases and especially the enhancement of the ability of the body to resist bacterial and viral infections. In many diseases, the decrease in immune defenses can be the cause or the favouring or resulting factor of the disease itself.

In view of the risks associated with deficiencies in the immune function, the aim of the present invention is therefore to provide a food supplement capable of contributing to the strengthening of normal immune defenses.

Within the scope of this aim, an object of the present invention is to provide a food supplement that strengthens the natural defenses of the body against bacterial or viral infections.

Another object of the present invention is to provide a food supplement for use in the protection of cells from oxidative stress.

Moreover, an object of the present invention is to provide a food supplement which helps to reduce symptoms such as tiredness and fatigue.

Not least object of the present invention is to provide a food supplement that is easy to take and has the desired effects in a short time.

This aim and these and other objects which will become better apparent hereinafter are achieved by an immuno stimulating food supplement, comprising:

- ascorbic acid (vitamin C),

- zinc gluconate,

- copper gluconate,

- L-selenomethionine,

- a mixture of nucleotides consisting of adenosine-5'-monophosphate (AMP), cytidine-5'-monophosphate (CMP), uridine-5'-monophosphate (UMP), guanosine-5'-monophosphate (GMP) and inosine-5'-monophosphate (IMP), and optionally one or more excipients.

The aim and objects of the present invention are also achieved by said immunostimulating food supplement for use in the treatment of bacterial or viral infections, in reducing tiredness and fatigue and in the protection of cells against oxidative stress.

Further characteristics and advantages of the invention will become better apparent from the detailed description that follows.

The present invention relates to an immunostimulating food supplement comprising a combination of vitamin C (ascorbic acid) and trace elements (selenium, copper and zinc) which contribute to prevent potential damage caused to cell tissues by reactive oxygen species and support the modulation of immune cell function by regulating transcription factors and influencing the production of cytokines and prostaglandins. The intake of said nutrients promotes the activation of the enhanced innate immune response, mediated by Thl cytokines, consisting in the production of pro- inflammatory cytokines.

Ascorbic acid is an essential nutrient, which among its many functions contributes to immune defense by supporting both innate and adaptive responses. Numerous in vitro studies have shown that it stimulates both the production and the activity of leukocytes (white blood cells), in particular neutrophils, lymphocytes and phagocytes. Other studies have shown that the intake of ascorbic acid allows the prevention and treatment of respiratory and systemic infections, including colds and pneumonias, especially in immunocompromised or highly stressed individuals.

Preferably, in the immunostimulating food supplement according to the invention ascorbic acid is in a quantity comprised between 25% and 60%, preferably between 35% and 55%, even more preferably 50% by weight on the total weight of the supplement.

Zinc is essential for the normal development and functioning of white blood cells. In the literature, many clinical studies show that the intake of this element determines a significant reduction in the duration of cold symptoms in adults.

Studies conducted on animal models of rats have shown that zinc is involved in the execution of the bactericidal action of the innate immune function. In conditions of zinc (and copper) deficiency, in fact, there is a greater susceptibility to bacterial infections, since the toxic action performed by these elements in high concentrations, against pathogenic agents, is lost. In groups of guinea pigs on a diet with reduced zinc intake, a reduction in the process of phagocytosis by polymorphonuclear cells has been observed. Moreover, clinical studies performed on 20 hemodialysis patients, in order to evaluate lymphocyte blast transformation and granulocyte motility, have shown that a zinc deficiency, resulting in a depletion of zinc in granulocytes, leads to a reduction in granulocyte motility, although abnormal lymphocyte blast transformation has not been demonstrated in vitro.

Preferably, in the immunostimulating food supplement according to the invention, zinc, in the form of zinc gluconate, is in a quantity comprised between 0.1% and 0.45%, preferably between 0.15 % and 0.35%, even more preferably 0.25% by weight on the total weight of the supplement.

Copper is an essential element, useful for the correct functioning of metabolic processes in all organs, in association with amino acids and vitamins. It is the third of the mineral elements most present in the body, it has antiseptic and detoxifying properties and is essential in case of anemias and cardiovascular diseases. Recent studies have shown how much copper is involved in the strengthening of the immune function (it is involved in the processes of defense against infections, as well as against free radicals, which can cause serious damage to tissue cells), in bone formation, in the maturation of blood cells, in the metabolism of lipids, in iron transport, in the contraction of the myocardium and in neurological development. Since copper cannot be produced by the body, it must be taken through the diet.

Copper is an essential micronutrient required for normal immune function. Experiments on animal models (guinea pigs) have shown that a copper deficiency results in increased susceptibility to bacterial infections, although the molecular mechanism underlying this action remains unknown. Copper is used by the host organism as a toxic noxious agent capable of performing a bactericidal action against pathogenic infectious agents.

In particular, studies in animal models and in cell cultures, conducted in order to assess the role of copper in immune response, have confirmed what has been pointed out by recent research on the reduction of interleukin-2 production in conditions of deficiency of said element, which presumably determines in turn a reduction in T cell proliferation. The number of neutrophils in blood is reduced drastically, along with their ability to kill ingested microorganisms, as a result of their reduced ability to generate superoxide anions.

Preferably, in the immunostimulating food supplement according to the invention copper is in the form of copper gluconate in a quantity comprised between 0.05% and 0.4%, preferably between 0.1% and 0.25%, even more preferably 0.2% by weight on the total weight of the supplement.

Selenium is an essential micronutrient that plays an important role in several physiological processes, including the regulation of immune response and inflammation. Exogenous selenium is found incorporated into selenoproteins and in this form stimulates the formation of antibodies and the activity of helper T cells, cytotoxic T cells, and Natural Killer (NK) cells. The mechanisms of intestinal absorption of selenium differ depending on the chemical form of the element. It is mainly absorbed in the duodenum and cecum by active transport through a sodium pump. The recommended daily intake ranges from 60 pg/day for women to 70 pg/day for men.

Selenium deficiency leads to a strong reduction in activation, differentiation and proliferation of immune cells, together with an increase in oxidative stress, impairment of secondary functions such as protein folding and calcium flux, which would allow the performance of the effector functions of cytotoxic immune cells.

Several in vivo scientific studies and clinical studies show that selenium is involved in the processes of modulation of cell function involved in innate and adaptive immunity; specifically, it promotes the proliferation and facilitates the differentiation of CD4+ T lymphocytes into helper- 1 T cells, thus supporting acute cellular immune response, while the excessive activation of the immune system and the consequent host tissue damage are counteracted by directing the macrophages towards the M2 phenotype. Numerous scientific evidences show that the exogenous supply of selenium determines a significant increase in the cytotoxicity of helper T lymphocytes in the mouse, of NK lymphocytes and of macrophages activated by lymphokines. These effects were not associated with changes in endogenous levels of interleukin- 1, interleukin-2 or interferon-gamma, and therefore they were correlated with the ability of selenium to cause an increase in the expression of the alpha (p55) and/or beta (p70/75) subunits of the interleukin-2 receptor (IL-2R) on the surface of said lymphocytes, therefore to cause an increase in the proliferation and clonal expansion of their cell precursors.

Preferably, in the immunostimulating food supplement according to the invention selenium, in the form of L-selenomethionine, is in an amount comprised between 0.005% and 0.02%, preferably between 0.05% and 0.015%, even more preferably 0.01% by weight on the total weight of the supplement.

A further ingredient of the immunostimulating food supplement of the invention is a mixture of nucleotides. Nucleotides are molecules constituted by a nitrogen base, a sugar and a phosphate group. These are phosphate esters of nucleosides which contain a sugar bound through a glycosidic bond to purine (adenine and guanine) and pyrimidine (cytosine, uracil) bases to form adenosine monophosphate (AMP), guanosine monophosphate (GMP), cytosine monophosphate (CMP), and uridine monophosphate (UMP), respectively. Purine and pyrimidine nucleotides are the main components of cells that constitute the monomeric units of DNA and RNA and function in all the cellular processes. Nucleotides constitute a functional ingredient that contributes to the improvement of immune function and response, promotes the prevention of infections in immunocompromised subjects and the strengthening of the activity of the bacterial flora at the gastrointestinal level, and stimulates the metabolism of unsaturated fatty acids, in adults and children.

Fast-growing tissues such as lymphoid cells, as well as intestinal epithelium, require exogenous sources of purine and pyrimidine bases for de novo synthesis of nucleotides; these food sources of nucleotides contribute to the pool of nucleotides in tissues, optimizing their metabolic function. In this sense, nucleotides can be considered conditionally essential nutrients.

Preferably, in the immunostimulating food supplement according to the invention the mixture of nucleotides consisting of adenosine-5'- monophosphate (AMP), cytidine-5'-monophosphate (CMP), uridine-5'- monophosphate (UMP), guanosine-5'-monophosphate (GMP) and inosine- 5'-monophosphate (IMP) is in a quantity comprised between 5% and 15%, preferably between 8% and 13%, even more preferably 12.5% by weight on the total weight of the supplement.

The nucleotides may be in acid form or in the form of a nutraceutically acceptable salt that is therefore suitable for human consumption, preferably a sodium salt.

For example, in a preferred embodiment of the immunostimulating food supplement according to the invention, the mixture of nucleotides consists of adenosine-5'-monophosphate in acid form, cytidine-5'- monophosphate in acid form, uridine-5 '-monophosphate (UMP) sodium salt, guanosine-5'-monophosphate (GMP) sodium salt and inosine-5'- monophosphate (IMP) sodium salt in a quantity comprised between 5% and 15%, preferably between 8% and 13%, even more preferably 12.5% by weight on the total weight of the supplement.

The food supplement according to the invention may further be formulated with nutraceutically acceptable excipients known to the person skilled in the art. The excipients may be, for example, one or more of hydroxypropylmethylcellulose, microcrystalline cellulose, maltodextrins, silica, and magnesium stearate.

In a preferred embodiment, the immuno stimulating food supplement according to the invention comprises, more preferably consists essentially of, even more preferably consists of:

- 50% by weight on the total weight of the supplement of ascorbic acid,

- 2.5% by weight on the total weight of the supplement of zinc gluconate,

- 2% by weight on the total weight of the supplement of copper gluconate,

- 0.1% by weight on the total weight of the supplement of L- selenomethionine,

- 12.5% by weight on the total weight of the supplement of a mixture of nucleotides consisting of adenosine-5'-monophosphate, cytidine-5'- monophosphate, uridine-5 '-monophosphate, guano sine- 5 '-monophosphate and inosine-5'-monophosphate,

- 36.95% by weight on the total weight of the supplement of a mixture of excipients comprising hydroxypropylmethylcellulose, microcrystalline cellulose, maltodextrins, silica, and magnesium stearate.

Preferably, the immuno stimulating food supplement according to the invention may be formulated in tablet form preferably in a dosage of 1g.

Another aspect of the present invention relates to the immunostimulating food supplement according to the invention for use in the treatment of bacterial or viral infections, in reducing tiredness and fatigue and in the protection of cells against oxidative stress.

Within the scope of said aspect, the present invention also relates to a method for treating bacterial or viral infections, reducing tiredness and fatigue, and protecting cells against oxidative stress by administering to a subject in need thereof an immunostimulating food supplement as described herein.

In practice it has been found that the immunostimulating food supplement according to the invention is effective in contributing to immune defense by supporting both innate and adaptive responses, by virtue of the combined action of its active ingredients.

The disclosures in Italian Patent Application No. 102020000032717, from which this application claims priority, are incorporated by reference.