Immulina +D3

Immulina +D₃

GENERAL REMARKS

Immulina + D₃ it is further development of Immulina plus. This new product provides the same active compounds as Immulina plus and additionally provides 4.000 international units of Vitamin D3 (100 µg) and 120 µg selenium amount for 2 capsules ia. recommended daily amount of product. Immulina + D₃ — is available in 30 capsules packages only, for the time being.
Immulina + D₃ is a complex preparation. One may say it has three groups of active ingredients that we are trying to characterize hereinafter.

Active Ingredients

First Group of Ingredients

There are two macromolecular compounds in this grup. It is lipopolysaccharide complex LCEPEEN form spirulina extract and β-1,3/1,6 D-glucan from backer's yeast extract. These two ingredients only are immunomodulators and show real immunomodulatory activity. Immunomodulators are active substances applied in immunotherapy. Immunomodulation is a modulation - regulatory adjustment - of immune system. Immunomodulation as part of immunotherapy, in which immune responses are induced, amplified, attenuated, or prevented according to therapeutic goals.

IMMUNOACTIVE SPIRULINA EXTRACT

Spirulina Extract provides a macromolecular lipopolysaccharide compound coded by manufacturer the Danish Company Nordic ImmoTech as LCEPEEN. This product was invented by team of scientists from National Center for Natural Products Research at University of Mississippi under leadership of Dr David S. Pasco, pharmacy professor. Spirulina extract was marketed under Immulina trade name. LCEPEEN complex exhibits outstanding immunomodulatory properties superior than other available immuno-supplements (see figures and tables below).

Swallowed LCEPEEN complex form Immulina is phagocyted by macrophages and dendritic cells (phages of digestive tract) – so called antigen presenting cells. After LCEPEEN digestion APC become activated.

Immulina containing active LECPEEN complex has been compared to crude lipopolysaccharide (LPS) that are component of cell wall of Escherichia coli. Immulina 8-times more effective affects immunity more effectively in comparison to Escherichia coli lipopolysaccharides and 20 times than aloe vera and 25 times than spirulina from which it is derived. This is because Immulina acts on the immune system through TRL-2 receptors*, which have much higher density (more than 2.5 times) on the surface of antigen-presenting cells (dendritic cells) than TLR-4 receptors, through which most substances act affecting immunity. Immulina affects immunity up to 40 times more effectively compared to traditional preparations such as echinacea and β-glucan. Preparations containing reishi and American ginseng extracts show practically only trace effects in comparison to LCEPEEN in Immulina.

Comparison of the potential of various natural activators of the NF-κB factor

Table 1.

* Compound name – all compounds are high molecular weight polysaccharides or lipo-polysaccharides.
** The EC₅₀ value represents the amount (in nanograms) of each of the tested formulations needed to achieve 50% of the maximum activation of nuclear factor NF-κB obtained with LPS.
Crude lipopolysaccharides (LPS) have so far been considered the strongest activator of the nuclear factor NF-κB and the effects of the tested products were related to them. In the tests carried out, it was found that Immulina is more active than lipo-polysaccharides (LPS).
THP monocytes - own line of monocytes developed by the laboratory.

The innate immune response is an evolutionarily older form of immunity than the acquired response. It is fast and quite well targeted, it does not initiate the destruction of its own tissues, but it does not leave a permanent immunological memory. The LCEPEEN complex (from spirulina extract) binds to the appropriate receptors of antigen-presenting cells (patterns recognizing receptors - PRR), which usually leads to the activation of the nuclear transcription factor NF-κB and the increase in the expression of genes encoding pro-inflammatory cytokines and the rapid induction of an immune response.

Effect of a diet containing spirulina extract on the concentration of IgA and INF-γ

In laboratory studies, a diet containing LCEPEEN (lipopolysaccharide complex) from spirulina extract has been shown to increase the concentration of immunoglobulin antibodies of the IgA class and interferon gamma (INF-γ) after a few days. Immunoglobulins* are produced by activated B lymphocytes. mucosal immune response immunoglobulins. Thanks to them, the body protects itself against the penetration of microorganisms (bacteria, viruses) through the mucous membranes.

Interferon gamma belongs to a group of 10 interferons - proteins produced and released by body cells in response to the presence of pathogens (e.g. viruses, bacteria, parasites as well as cancer cells) inside the body. Interferons ensure communication between body cells to fight pathogens by triggering defense mechanisms of the immune system. IFN-γ has antiviral properties and plays an essential role as a mediator of the body's immune response, e.g. to infection and cancer.

IMMUNOACTIVE BETA-GLUCAN

β-glucans are high-molecular polysaccharides, i.e. polysaccharides commonly found in the plant world. They are one of the components of the cell wall of many plants, especially cereals and fungi. Depending on their origin, β-glucans have different structures and different properties. In general, they can be divided into two main groups that have been used due to their significant health properties:
(1) Soluble β-glucans derived mainly from cereals (oats, barley, rye, etc.) and
(2) Insoluble β-glucans derived mainly from mushrooms (yeast, shiitake mushroom, oyster mushroom, reishi mushroom, split gill mushroom, etc.)

The first group, showing in its structure short chains with β-bonds in positions (1→3)-(1→4), is soluble in water. This group of β-glucans has outstanding properties influencing the carbohydrate-lipid economy in humans. Their consumption lowers/normalizes lipid (cholesterol) and blood sugar levels.

The second group, showing in its structure long chains with β-bonds in positions (1→3)-(1→6), is insoluble in water. They have immuno-modulating properties. Their consumption supports the natural, non-specific immunity of the body.

These macromolecular β-1,3/1,6-D glucans are a common ingredient in various immuno-modulating preparations used in various clinical situations. Particularly large amounts of β-1,3/1,6-D glucans are found in the cell wall of baker's yeast (Saccharomyces cerevisiae). It is the most immunologically active fraction from the whole group of β-glucans. It is composed of D-glucose molecules linked at the 1,3-position and with D-glucose side chains linked at the 1,6-position. The figure opposite shows the structure of the insoluble β-1,3/1,6-D glucan molecule with a long chain, derived from baker's yeast.

After swallowing, β-glucan particles are phagocytized by macrophages and dendritic cells, i.e. antigen-presenting cells, and through them by the lymphatic tissue of the digestive tract, so called GALT, they stimulate the entire immune system. It was believed that β-glucan participates in the activation of cellular immunity only in this way, and for many years glucan was treated as a non-specific stimulator of macrophages. This is a very important process for the body, because macrophages form the first line of defense and without their optimal activity, the body cannot effectively defend itself. The figure below shows the uptake of β-glucan from the gastrointestinal tract and its effects on the immune system.

It used to be thought that β-glucan could only modulate the immune system when used parenterally, due to the lower systemic bioavailability of oral formulations. However, many studies, both in vitro and in vivo, have revealed that orally administered β-glucan also exerts such an effect. The interaction was discovered through different receptors, explaining the possible modes of action. The effects depend mainly on the origin and structure of β-glucans. At the same time, many clinical trials of insoluble yeast β-glucans administered orally were conducted. The obtained results confirmed the results of previous in vivo studies. Taken together, the results of all the studies clearly indicate that oral administration of yeast β-glucans is safe and has an immune-enhancing effect.

Due to the low systemic availability of oral preparations, it has been thought that only parenterally applied beta-glucans can modulate the immune system. However, several in vivo and in vitro investigations have revealed that orally applied beta-glucans also exert such effects. Various receptor interactions, explaining possible mode ofactions, have been detected. The effects mainly depend on the source and structure of the beta-glucans. In the meantime, several human clinical trials with dietary insoluble yeast beta-glucans have been performed. The results confirm the previous findings ofin vivo studies. The results of all studies taken together clearly indicate that oralintake of insoluble yeast beta-glucans is safe and has an immune strengthening effect.

Review of clinical data by: Stier H, Ebbeskotte V, et al → Immune-modulatory effects of dietary Yeast β-1,3/1,6-D-glucan Nutrition Journal;2014,13:38 (pdf 12 stron).

Research review article by: Kim HS, Hong JT, et al → Stimulatory Effect of β-glucans on Immune Cells Immune Netw.;2011 Aug;11(4):191-195

Active Ingredients

Second Group of Ingredients

Second group of ingredients comprises of vitamins and essential microelements. These ingredients do not enhance immunity per se, but are necessary for a healthy and properly functioning immune system. These vitamins are C and D₃ and microelements are zinc and selenium.

VITAMIN C

Vitamin C or ascorbic acid has been known since 1933, when it was discovered and described by the Hungarian scientist Albert Szent-Györgyi. It is worth mentioning that the concept of a vitamin was introduced just before the First World War by an eminent Polish doctor, Kazimierz Funk. He also discovered the first vitamins. He stated that a certain nitrogen-containing substance (Latin "amine") prevents beriberi - a dangerous disease caused by its lack, i.e. protects life (Latin "vitae"), hence "vitae amine" or vitamin.

One of the main reasons people take vitamin C supplements is to boost their immunity, as vitamin C is involved in many parts of the immune system. Vitamin C helps encourage the production of white blood cells known as lymphocytes and phagocytes, which help protect the body against infection^[1]. Moreover, vitamin C helps these white blood cells function more effectively while protecting them from damage by potentially harmful molecules, such as free radicals.

Vitamin C is an essential part of the skin’s defense system. It’s actively transported to the skin, where it can act as an antioxidant and help strengthen the skin’s barriers^[2]. Studies have also shown that taking vitamin C may shorten wound healing time[^3,4].

What’s more, low vitamin C levels have been linked to poor health outcomes. For example, people who have pneumonia tend to have lower vitamin C levels, and vitamin C supplements have been shown to shorten the recovery time^[5,6].

VITAMIN D

Cholecalciferol (vitamin D3) is a fat-solouble steroid that is synthesized in the skin in the presence of ultraviolet light or obtained from the diet. Vitamin D Has Two Forms of Equal Potency in Humans.

Cholecalciferol is known as vitamin D3 for historical reasons. The chemical structure of vitamin D2 was worked out earlier than that of D3 because of the availability of ergosterol, a sterol derived from fungus. UV light converts ergosterol to ergocalciferol, an analogue of cholecalciferol. It is known as vitamin D2 and equals vitamin D3 in preventing rickets. Ergocalciferol differs from cholecalciferol by a double bond and an extra methyl group.

Cholecalciferol is transferred into clacitrol – the active form – 1,25-dihydroksycholekalcyferol, 1,25(OH)2D3) - by hydroxylation in liver in position 25 and by hydroxylation in position 1α in kidneys.

Cholecalciferol Functions

The major function of 1,25(OH)2D is to regulate calcium homeostasis
other biological activities include regulation of proliferation and differentiation of several cell lines including:

• Keratinocytes – the major cell type of the epidermis (the outer layer of the skin)
• Endothelial cells – that line the interior surface of blood and lymphatic vessels.
• Osteoblasts – the major cellular component of bone that synthesize bone
• Lymphocytes – one of subtypes a white blood cells – the major group of immune cells that comprises of several cell classes

Most of these biological functions are mediated via the vitamin D nuclear receptor (VDR) which acts as a transcription factor regulating transcription of target genes.

ZINC

Zinc affects the functioning of the immune system. It is a complex interaction. Zinc induces the adhesion of monocytes to the endothelium, which intensifies the immune response. Zinc deficiency reduces neutrophil chemotaxis, impairs macrophage-mediated phagocytosis and interferes with the generation of reactive oxygen species. Zinc is required for the interaction between the p581 receptor on NK2 cells and MHC-I3 major complex molecules on target cells, resulting in inhibition of the cytotoxic activity of NK cells. Zinc affects the processes of cell proliferation in the immune system.

Zinc acts as a cofactor for the thymus hormone - thymulin, which induces the differentiation of immature T lymphocytes. Zinc ions also induce the release of IL-1, IL-6, TNF-α and stimulate monocytes.

At the cellular level, zinc improves the stability of the cell membrane. It is necessary for the activation (translocation) of the C5 protein kinase. It itself can bind to a specific membrane receptor and affects the fluidity of the lipid layer. At the level of the cell nucleus, it can influence gene expression through structural stabilization and functional regulation of various immunologically important transcription factors, e.g. NF-κB6. It should be noted that in vitro studies have shown that too high doses of zinc can inhibit the function of T lymphocytes and the production of IFN-α. For this reason, when supplementing with zinc, it is necessary to adjust the doses of this element to the needs.

SELENIUM

Selenium (Se), supplied in food, is an essential micronutrient that affects various areas of our health, in particular ensuring an optimal response of the immune system. Selenium performs its biological effect by incorporating into special proteins, the so-called seleno-protein and is involved in the regulation of oxidative stress, redox reactions and other key cellular processes in almost all tissues, including those responsible for the innate and adaptive response of the immune system.

Third Group of Ingredients

The third group represents acerola fruit extract providing natural vitamin C together in complex with rutoside i.a. rutin and hesperidin.

ACEROLA FRUIT EXTRACT

Acerola (previously M. punicifolia) is native to the West Indies. It also is found in northern South America, Central America, Texas, and Florida. This small shrub or tree has 5-petaled flowers ranging from pink to white in color. Acerola fruit is a bright red cherry-like fruit containing several small seeds. Mature fruits are soft and pleasant tasting. They contain 80 percent juice. The fruits deteriorate rapidly once removed from the tree.

RUTOSIDE

Rutoside (łac. rutosiduae) – is a group of chemical compounds that belongs to flavonoid glycosides group and is present in many plants. Falvonoids play function as colours, antioxidants and natural insecticides and fungicides protecting plant from insects and fungi. Most of them are pigments deposited in external plant tissues (skin, peel, and husk) giving intense colour and protection from harmful UV radiation. Rutin and hesperidin belong to rutoside.

Rutoside demonstrate antioxidant properties and as majority of flavonoids have vascular protective activity, reduce micro-vascular permeability, and anti swelling property. Rutoside protect from free radicals formation, slow down and reduce oxidation of vitamin C (thus prolog its action), reduce cytotoxicity of oxidized cholesterol, and demonstrate anti inflammatory properties.

RUTIN

Rutin is the major representative of rutoside. It was primarly established in a shrubby plant common rue (lat. Ruta graveolens). Rutin is a citrus flavonoid glycoside found in many plants including buckwheat, the leaves and petioles of Rheum species, and asparagus. Tartary buckwheat seeds have been found to contain more rutin (about 0.8–1.7% dry weight) than common buckwheat seeds (0.01% dry weight). Rutin is one of the primary flavonols found in 'clingstone' peaches. It is also found in green tea infusions.

Rutin demonstrate several health benefits. Rutin is most commonly used for swelling in the arms or legs caused by damage to the lymph system (lymphedema) and osteoarthritis. It is also used for autism, or on the skin for sun protection, but there is no good scientific evidence to support these uses. Rutin supports immune system.

HESPERIDIN

Hesperidin is another representative of rutoside. Hesperidin is a plant yellow colour that belongs to flavonoids. It is found most of all in citrus fruits (sweet oranges, lemons and also many others yellow and/or red fruits). Fruit skin, seeds and pulp of these fruits are used as a hesperidin source for pharmaceutic and cosmetic preparations.

Hesperidin exhibits several pharmacological actions such as antihyperlipidemic, cardioprotective, antihypertensive, antidiabetic activities, which are mainly attributed to an antioxidant defence mechanism and suppression of pro-inflammatory cytokine production. Various randomized crossover trials have shown the beneficial effects of hesperidin, which mainly results from anti-inflammatory and anti-atherogenic actions. Hesperidin supports immune system.

Hesperdin is often used together with diosmine in preparations targeting vascular health.

One can read more about hesperidin → Evaluating the bioactive effects of flavonoid hesperidin – A new literature data survey