Zinc is an essential bio-element, which plays a fundamental role in a wide range of biochemical processes. This metal is a major component of various proteins and is an important modulator of the immune and nervous systems. It is the second most abundant trace metal in humans after iron and it is the only metal which appears in all enzyme classes.

Zinc is involved in numerous aspects of cellular metabolism. It is required for the catalytic activity of over 300 enzymes and 1000 transcription factors and it plays a role in immune function, protein synthesis, wound healing, DNA synthesis and cell division. Zinc also supports normal growth and development during pregnancy, childhood, and adolescence and is required for proper sense of taste and smell.

In the brain, zinc is stored in specific synaptic vesicles by glutamatergic neurons and can modulate neuronal excitability. It plays a key role in synaptic plasticity and so in learning. Zinc homeostasis also plays a critical role in the functional regulation of the central nervous system. Dysregulation of zinc homeostasis in the central nervous system that results in excessive synaptic zinc concentrations is believed to induce neurotoxicity through mitochondrial oxidative stress (e.g., by disrupting certain enzymes involved in the electron transport chain), the dysregulation of calcium homeostasis, glutamatergic neuronal excitotoxicity, and interference with intraneuronal signal transduction. 1 Reference: Nowak G., Szewczyk B.: Mechanism contributing to antidepressant zinc actions. Pol. J. Pharmacol., 2002, 54, 587–592. PMID: 12866713 2 Reference: Prakash A, Bharti K, Majeed AB (April 2015). "Zinc: indications in brain disorders". Fundam Clin Pharmacol. 29 (2): 131–149. doi:10.1111/fcp.12110. PMID 25659970. S2CID 21141511 3 Reference: https://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/

At the same time, studies have shown a correlation between zinc deficiency and thyroid gland hormone levels. Zinc is necessary for the proper functioning of the enzyme deiodinase, which activates the inactive thyroxine (T4) hormone into a more active form - triiodothyronine (T3), ensuring all thyroid gland functions in the human body. 4 Reference: Maxwell, C., & Volpe, S. L. (2007). Effect of Zinc Supplementation on Thyroid Hormone Function. Annals of Nutrition and Metabolism, 51(2), 188–194. doi:10.1159/000103324

Zinc affects several aspects of the immune system. It is crucial for the normal development and function of innate immune cells, neutrophils and natural killer or NK cells. Zinc deficiency also affects macrophages – large cells that draw in and digest foreign particles. Zinc deficiency affects phagocytosis, intracellular killing and cytokine production. Zinc deficiency negatively affects the growth and function of T and B cells. Zinc’s ability to act as an antioxidant and stabilise membranes suggests that it plays a role in preventing free radical-induced injury during inflammatory processes. 5 Reference: Prasad AS. Zinc in human health: effect of zinc on immune cells. Mol Med. 2008 May-Jun;14(5-6):353-7. doi: 10.2119/2008-00033.Prasad. PMID: 18385818; PMCID: PMC2277319.

Zinc deficiency is characterized by growth retardation, loss of appetite, and impaired immune function. In more severe cases, zinc deficiency causes hair loss, diarrhea, delayed sexual maturation, impotence, hypogonadism in males, and eye and skin lesions. Weight loss, delayed healing of wounds, taste abnormalities, and mental lethargy can also occur. Many of these symptoms are non-specific and often associated with other health conditions; therefore, a medical examination is necessary to ascertain whether a zinc deficiency is present. People at risk of zinc deficiency or inadequacy need to include good sources of zinc in their daily diets.

Groups at Risk of Zinc Inadequacy

1. People with gastrointestinal and other diseases

Gastrointestinal surgery and digestive disorders (such as ulcerative colitis, Crohn’s disease, and short bowel syndrome) can decrease zinc absorption and increase endogenous zinc losses primarily from the gastrointestinal tract and, to a lesser extent, from the kidney. Other diseases associated with zinc deficiency include malabsorption syndrome, chronic liver disease, chronic renal disease, sickle cell disease, diabetes, malignancy, and other chronic illnesses. Chronic diarrhea also leads to excessive loss of zinc.

2. Vegetarians

The bioavailability of zinc from vegetarian diets is lower than from non-vegetarian diets because vegetarians do not eat meat, which is high in bioavailable zinc and may enhance zinc absorption. In addition, vegetarians typically eat high levels of legumes and whole grains, which contain phytates that bind zinc and inhibit its absorption.

3. Pregnant and lactating women

Pregnant women, particularly those starting their pregnancy with marginal zinc status, are at increased risk of becoming zinc insufficient due, in part, to high fetal requirements for zinc. Lactation can also deplete maternal zinc stores.

4. Older infants who are exclusively breastfed

Breast milk provides sufficient zinc (2 mg/day) for the first 4–6 months of life but does not provide recommended amounts of zinc for infants aged 7–12 months, who need 3 mg/day. In addition to breast milk, infants aged 7–12 months should consume age-appropriate foods or formula containing zinc. Zinc supplementation has improved the growth rate in some children who demonstrate mild-to-moderate growth failure and who have a zinc deficiency.

5. People with sickle cell disease

Results from a large cross-sectional survey suggest that 44% of children with sickle cell disease have a low plasma zinc concentration, possibly due to increased nutrient requirements and/or poor nutritional status. Zinc deficiency also affects approximately 60%–70% of adults with sickle cell disease. 

6. Alcoholics

Approximately 30%–50% of alcoholics have low zinc status because ethanol consumption decreases intestinal absorption of zinc and increases urinary zinc excretion. In addition, the variety and amount of food consumed by many alcoholics is limited, leading to inadequate zinc intake. 6 Reference: https://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/  

Zinc in the diet. Adults who are not found or established to be deficient in Zinc are normally required 11 mg for men, 8 mg for women and 11 mg for pregnant women of Zinc per day

Reference Atsauce: https://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/

Zinc supplements have the potential to interact with several types of medications. A few examples are provided below. Individuals taking these medications on a regular basis should discuss their zinc intakes with their healthcare providers.

1. Antibiotics

Both quinolone antibiotics (such as Cipro®) and tetracycline antibiotics (such as Achromycin® and Sumycin®) interact with zinc in the gastrointestinal tract, inhibiting the absorption of both zinc and the antibiotic. Taking the antibiotic at least 2 hours before or 4–6 hours after taking a zinc supplement minimizes this interaction.

2. Penicillamine

Zinc can reduce the absorption and action of penicillamine, a drug used to treat rheumatoid arthritis. To minimize this interaction, individuals should take zinc supplements at least 2 hours before or after taking penicillamine.

3. Diuretics

Thiazide diuretics such as chlorthalidone (Hygroton®) and hydrochlorothiazide (Esidrix® and HydroDIURIL®) increase urinary zinc excretion by as much as 60%. Prolonged use of thiazide diuretics could deplete zinc tissue levels, so clinicians should monitor zinc status in patients taking these medications. 1 Reference: Lomaestro BM, Bailie GR. Absorption interactions with fluoroquinolones. 1995 update. Drug Saf 1995;12:314-33. [PubMed abstract] 2 Reference: Penttilä O, Hurme H, Neuvonen PJ. Effect of zinc sulphate on the absorption of tetracycline and doxycycline in man. Eur J Clin Pharmacol 1975;9:131-4. [PubMed abstract] 3 Reference: Natural Medicines Comprehensive Database. Zinc. 4 Reference: Brewer GJ, Yuzbasiyan-Gurkan V, Johnson V, Dick RD, Wang Y. Treatment of Wilson’s disease with zinc: XI. Interaction with other anticopper agents. J Am Coll Nutr 1993;12:26-30. [PubMed abstract] 5 Reference: Wester PO. Urinary zinc excretion during treatment with different diuretics. Acta Med Scand 1980;208:209-12. [PubMed abstract]

Zinc is found in abundance in the human brain. Patients with depression may have decreased consumption of food sources rich in zinc and consistently low dietary zinc intakes may contribute to depressive symptoms by further lowering available zinc, therefore zinc supplementation may have a potential influence on depressive symptoms. In preclinical studies, single- or long- term treatment with zinc has been shown to have antidepressant-like effects.

According to recently introduced hypotheses of antidepressant action, one of major goals to be modified by an antidepressant is the NMDA glutamate receptor. The mechanism of antidepressant activity of zinc might be related to its direct antagonism at NMDA receptor. Besides the central nervous system, zinc is also involved in the immune/inflammatory regulation in depressive disorders.

In the hippocampus and cortex, zinc ions regulate synaptic transmission or act as neurotransmitters, modulating many ligand- and voltage-gated ion channels. Disruption of zinc homeostasis in these regions has been implicated in many disturbances in cognition, behavioral and emotional regulation through mechanisms of decreased neurogenesis and neuronal plasticity.

Zinc deficiency has also been implicated in the endocrine pathway of depression. Persistently high levels of cortisol have been implicated in the development of depression via hyperactivity of the hypothalamic–pituitary–adrenal (HPA) axis. Increased plasma cortisol levels could, therefore, potentially mediate the relationship between zinc deficiency and depression.

The relationship between serum zinc levels and depression could be partially explained by reverse causation, whereby depression influences the intake, bioavailability or biological regulation of zinc. Oxidative stress and its accompanying immune-inflammatory response have been linked to the pathophysiology of depression. In response to oxidative stress, levels of pro-inflammatory cytokines (e.g., interleukin 1 (IL-1) and IL-6) increase and, in turn, decrease of the level of albumin and increase the synthesis of metallothioneins. Albumin is the main zinc transporter, and a decrease in albumin coupled with an increase in metallothioneins may compound to decrease serum levels of zinc.

References 1 Reference: Elham Ranjbar, Jamal Shams, Masoumeh Sabetkasaei, Minoo M-Shirazi, Bahram Rashidkhani, Ali Mostafavi, Eiliyaz Bornak, Javad Nasrollahzadeh; Effects of zinc supplementation on efficacy of antidepressant therapy, inflammatory cytokines, and brain-derived neurotrophic factor in patients with major depression; 2 Reference: Pilc A., Kodziñska A., Nowak G.: A role for glutamate in the treatment of anxiety and depression: focus on group I metabotropic glutamate (mGlu) receptors. Drugs Fut., 2002, 27, 753–763. 3 Reference: Jessica Wang, Phoebe Um, Barbra A. Dickerman and Jianghong Liu1; Zinc, Magnesium, Selenium and Depression: A Review of the Evidence, Potential Mechanisms and Implications; Nutrients. 2018 May; 10(5): 584. Published online 2018 May 9. doi: 10.3390/nu10050584

Zinc is an essential element involved in many basic biochemical reactions of the thyroid gland. Zinc is necessary for the production of the hormones triiodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH).

T4 is the main thyroid gland hormone, which is a kind of bodyreserve, while T3 is a much more active hormone. If necessary, one molecule of iodine is separated from T4, and it turns into an active hormone - T3.

This trace element participates in the synthesis of thyrotropin-releasing hormone (TRH) in the hypothalamus and in the synthesis of thyrotropin or thyroid-stimulating hormone (TSH) in the pituitary gland.1

Some studies have shown that zinc deficiency and low zinc concentration in the serum can cause changes in thyroid gland structure and thyroid gland hormone metabolism. Also, studies have shown that taking zinc can increase the concentration of thyroid gland hormones.1

In a study where subjects took zinc supplements, they had improvements in all thyroid gland hormone levels (especially T3) as well as in the rate of metabolism in the state of rest. Another study showed that taking zinc alone or in combination with selenium can improve thyroid gland function in women with hypothyroidism.2

Zinc deficiency can cause hypothyroidism. On the other hand, hypothyroidism can cause zinc deficiency because thyroid gland hormones are needed for zinc absorption. 1 Atsauce: 1) Beserra, J. B., Morais, J. B. S., Severo, J. S., Cruz, K. J. C., de Oliveira, A. R. S., Henriques, G. S., & do Nascimento Marreiro, D. (2021). Relation Between Zinc and Thyroid Hormones in Humans: a Systematic Review. Biological Trace Element Research. doi:10.1007/s12011-020-02562-5 2) Mahmoodianfard, S., Vafa, M., Golgiri, F., Khoshniat, M., Gohari, M., Solati, Z., & Djalali, M. (2015). Effects of Zinc and Selenium Supplementation on Thyroid Function in Overweight and Obese Hypothyroid Female Patients: A Randomized Double-Blind Controlled Trial. Journal of the American College of Nutrition, 34(5), 391–399. doi:10.1080/07315724.2014.926161

Zinc has been found to be an essential trace element for the immune system. However, at the cellular and molecular level, the mechanisms of zinc actions on the immune system are relatively recent and its effects are diverse. 1 Reference: Rink, L. (2000). Zinc and the immune system. Proceedings of the Nutrition Society, 59(04), 541–552. doi:10.1017/s0029665100000781

Adequate levels of zinc in the body are essential for the formation and function of different populations of lymphocytes (the main immune cells), such as the division, maturation and differentiation (development into different forms) of T-cells (or T-lymphocytes); lymphocyte response to mitogens (small bioactive proteins or peptides that induce cells to start dividing or increase the rate of division). At the same time, zinc is important for programming lymphoid and myeloid cell death; gene transcription and biomembrane function. Lymphocytes are one of the types of cells activated by zinc. Zinc is a structural component of various proteins, neuropeptides, hormone receptors and polynucleotides. Zinc deficiency results in rapid and marked atrophy of the thymus, impaired cell-mediated cutaneous sensitivity and lymphopenia. Primary and secondary antibody responses are reduced in zinc deficiency, particularly for those antigens that require T-cell help, such as those in heterologous red blood cells. In addition, antibody response and the generation of splenic cytotoxic T-cells after immunisation are reduced. Zinc also inhibits the production of tumour necrosis factor, which is implicated in the pathophysiology of cachexia and wasting in acquired immune deficiency syndrome. 2 :Reference: Baum MK, Shor-Posner G, Campa A. Zinc status in human immunodeficiency virus infection. J Nutr. 2000 May;130(5S Suppl):1421S-3S. doi: 10.1093/jn/130.5.1421S. PMID: 10801954.

In short, zinc is absolutely essential for the functioning of the thymus and the normal functioning of the immune system. Zinc prevents immunodeficiency by stimulating antibody synthesis and providing antiviral effects.

1. The element was probably named by the alchemist Paracelsus after the German word Zinke and supposedly meant "tooth-like, pointed or jagged" (metallic zinc crystals have a needle-like appearance). Zink could also imply "tin-like" because of its relation to German zinn meaning tin.
2. The oldest known pills were made of the zinc carbonates hydrozincite and smithsonite. The pills were used for sore eyes and were found aboard the Roman ship Relitto del Pozzino, wrecked in 140 BC.
3. Alchemists burned zinc metal in air and collected the resulting zinc oxide on a condenser. Some alchemists called this zinc oxide lana philosophica, Latin for "philosopher's wool", because it collected in wooly tufts, whereas others thought it looked like white snow and named it nix album.
4. Zinc is a natural insect repellent and sun screen, protecting lips and skin.
5. Zinc is 100% recyclable. Over 80% of the zinc available for recycling is currently recycled.

Vitamin D is a prohormone belonging to the group of fat-soluble vitamins; it is synthesised in the body when the sun's ultraviolet B (UVB) radiation interacts with a precursor molecule, 7-dehydrocholesterol (7-DHC), in the skin (although in healthy people, the internal production of vitamin D is estimated to account for 90% of the total, a small amount of vitamin D is also received from the diet and additional supplements). Vitamin D is then transported in the blood (bound to vitamin D-binding protein) to the liver, where it is hydroxylated to 25-hydroxyvitamin D (25-(OH)D). 25-(OH)D is further converted to the metabolically active form 1α, 25-dihydroxyvitamin D (1α, 25-(OH)2D), mainly in the kidneys. 1 Atsauces: Muscogiuri, G., Barrea, L., Scannapieco, M., Di Somma, C., Scacchi, M., Aimaretti, G., … Marzullo, P. (2018). The lullaby of the sun: the role of vitamin D in sleep disturbance. Sleep Medicine. doi:10.1016/j.sleep.2018.10.033 10.1016/j.sleep.2018.10.033 Vitamin D regulates the amount and absorption of calcium ions and phosphates in the small intestine, ensures the formation of bones and teeth, and also helps to strengthen the immune system. 2 Atsauces: Mosavat, M., Smyth, A., Arabiat, D., & Whitehead, L. (2020). Vitamin D and sleep duration: Is there a bidirectional relationship? Hormone Molecular Biology and Clinical Investigation, 41(4). doi:10.1515/hmbci-2020-0025

So, for vitamin D to be activated, two metabolic transformations are required - first in the liver - hydrolysis at position 25 (25(OH)D) and then in the kidneys - 1-α-hydrolysis, after which active vitamin D is able to bind to vitamin D receptors to participate in gene transcription and regulated ion (Ca/P) homeostasis.

If we look at the most common forms of vitamin D, D2 (ergocalciferol or calciferol) and D3 (cholecalciferol), it is known that ergocalciferol is mainly obtained from plant sources, formed by UVB radiation in the cell membranes of plants and fungi.

In addition, vitamin D2 is a synthetic molecule that is used to improve food products - added to bread, cereals and dairy products, as well as used in food supplements. Vitamin D3, on the other hand, is obtained from “live” sources, such as fish oil, animal liver and egg yolks. Vitamin D3 is also formed in the skin from provitamin D3 (7-DHC).

Vitamin D deficiency is considered a risk factor for sleep because studies have observed a correlation between vitamin D and sleep duration. Studies of sleep have shown that lower levels of vitamin D are associated with shorter sleep duration in people of all ages. 2 Atsauces: Mosavat, M., Smyth, A., Arabiat, D., & Whitehead, L. (2020). Vitamin D and sleep duration: Is there a bidirectional relationship? Hormone Molecular Biology and Clinical Investigation, 41(4). doi:10.1515/hmbci-2020-0025 .

An important function of vitamin D is to activate T leukocytes, the cells that actually detect and destroy foreign microorganisms such as viruses. This is why all white blood cells (leukocytes) have vitamin D receptors on their surfaces. Vitamin D can modulate the innate and adaptive immune responses. Deficiency of it is associated with increased autoimmunity as well as increased susceptibility to infections. As immune cells in autoimmune diseases are responsive to vitamin D, it has a beneficial effect in controlling these diseases. 3 Reference: Aranow C. Vitamin D and the immune system. J Investig Med. 2011 Aug;59(6):881-6. doi: 10.2310/JIM.0b013e31821b8755. PMID: 21527855; PMCID: PMC3166406.

Vitamin D deficiency can occur for various reasons:

• 1. Your eating habits do not include products that are rich in vitamin D; therefore, you do not get enough vitamin D from food;
• 2. Your body does not absorb enough vitamin D from food (malabsorption);
• 3. You spend little time in sunlight or live in a country with little of it, so the body does not receive enough sunlight;
• 4. Your liver or kidneys cannot convert vitamin D into its active form;
• 5. You are taking medicines that prevent your body from converting or absorbing vitamin D.

Vitamin D deficiency can cause a decrease in bone density, which can contribute to osteoporosis and bone fractures. Individuals with vitamin D deficiency have been observed to have improper and restless sleep, as well as other sleep disturbances.

A severe lack of vitamin D can also cause other diseases. It can cause rickets in children. Rickets is a rare disease that causes the bones to become soft and bend. In adults, severe vitamin D deficiency causes osteomalacia. Osteomalacia causes weak bones, bone pain, and muscle weakness.

Researchers are studying vitamin D for its possible connection to several health conditions, including diabetes, high blood pressure, cancer and autoimmune diseases such as multiple sclerosis.

There are some foods that naturally contain vitamin D: fatty fish (such as salmon, tuna, and mackerel), beef liver, cheese, mushrooms, and egg yolks.

Vitamin D can also be obtained from enriched food products. You can check food labels to see if a food contains vitamin D. Food products that are often supplemented with vitamin D include: milk, breakfast cereals and orange juice.

For adults without vitamin D deficiency, the recommended daily dose of vitamin D is 15 mcg or 600 IU, after the age of 70: 20 mcg or 800 IU.

Excessive amounts of vitamin D are toxic. Because vitamin D increases gastrointestinal calcium absorption, vitamin D toxicity results in express hypercalcemia, hypercalciuria, and high serum 25(OH) levels. Hypercalcemia, in turn, can cause nausea, vomiting, muscle weakness, neuropsychiatric disorders, pain, loss of appetite, dehydration, polyuria, excessive thirst, and kidney stones.

In extreme cases, vitamin D toxicity leads to kidney failure, soft tissue calcification throughout the body (including coronary vessels and heart valves), cardiac arrhythmias, and even death. 1 Atsauce: https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/

When taking additional vitamin D, it can interact with several types of medications. Individuals taking these and other medications regularly should discuss vitamin D use and dosage with their healthcare professional.

Orlistat

The weight-loss drug Orlistat (Xenical® and alli®) in combination with a low-fat diet can reduce vitamin D absorption from food and food supplements, thereby reducing 25(OH)D levels.

Statins

Statin drugs reduce cholesterol synthesis. Because endogenous vitamin D is derived from cholesterol, statins can also reduce vitamin D synthesis. In addition, high intakes of vitamin D, especially from food supplements, may reduce the effects of atorvastatin (Lipitor®), lovastatin (Altoprev® and Mevacor®), and simvastatin (FloLipid™ and Zocor®) because these statins and vitamin D compete with each other and the metabolising enzyme itself.

Steroids

Corticosteroid medications are often prescribed to reduce inflammation: budesonide, prednisolone, prednisone, dexamethasone, hydrocortisone, and methylprednisolone (such as Deltasone®, Rayos®, and Sterapred®). These drugs can reduce calcium absorption and interfere with vitamin D metabolism.

Diuretics of the thiazide group

Thiazide diuretics of the thiazide group (such as Hygroton®, Lozol®and Microzide®) reduce urinary calcium excretion. The combination of these diuretics with vitamin D supplements (which increase intestinal calcium absorption) can cause hypercalcemia, especially in the elderly and those with impaired renal function or hyperparathyroidism.

Vitamin D is a prohormone belonging to the group of fat-soluble vitamins. Although vitamin D has traditionally been shown to be involved in calcium homeostasis and bone health, recent studies have found a positive relationship between vitamin D and sleep. In particular, human clinical trials show that low vitamin D levels are associated with poor quality of sleep and short sleep duration. Vitamin D receptors have been found in brain regions involved in sleep regulation, and vitamin D appears to be involved in regulating the sleep-wake cycle. 1 Atsauce: Muscogiuri, G., Barrea, L., Scannapieco, M., Di Somma, C., Scacchi, M., Aimaretti, G., … Marzullo, P. (2018). The lullaby of the sun: the role of vitamin D in sleep disturbance. Sleep Medicine. doi:10.1016/j.sleep.2018.10.033

As we know, vitamin D plays an important role in bone homeostasis and low levels of this vitamin are significantly correlated with low bone mineral density (BMD). Sleep is an important factor in bone metabolism and studies have found a relationship between sleep duration and BMD. In several

self-assessment studies it was reported that decreased sleep duration is associated with decreased BMD 2 Atsauce: Staab JS, Smith TJ, Wilson M, Montain SJ, Gaffney-Stomberg E. Bone turnover is altered during 72 h of sleep restriction: a controlled laboratory study. Endocrine 2019;65:192–9. and cortical bone thickness.

According to the studies, sleeping less than 5-6 hours is associated with lower BMD and a higher risk of osteoporosis in adults. In children, short sleep duration (<8 h) may be associated with bone mass accumulation disorders during periods of particularly rapid growth. Chronic lack of sleep can directly affect bone metabolism. These discoveries suggest that sleep deprivation may be a risk factor for poorer skeletal health through impaired bone metabolism, may impair bone microarchitecture, and reduce BMD.

In summary, persistent vitamin D deficiency can affect sleep duration, while poor sleep increases the risk of bone fractures and osteoporosis due to impaired bone metabolism.

Vitamin D was used unknowingly to treat infections such as tuberculosis before the advent of effective antibiotics. Tuberculosis patients were sent to sanatoriums where treatment included exposure to sunlight, which was thought to directly kill the tuberculosis. Cod liver oil, a rich source of vitamin D, has also been employed as a treatment for tuberculosis as well as for general increased protection from infections. 1 Reference: Williams C. On the use and administration of cod-liver oil in pulmonary consumption. London Journal of Medicine. 1849; 1:1–18.

The beneficial effects of vitamin D on protective immunity are in part due to its effects on the innate immune system It is known that macrophages recognise lipopolysaccharides (known as endotoxins, which are formed when bacteria are killed) through TLR receptors, which trigger an immune cell response. Engagement of TLRs leads to a cascade of events that produce antimicrobial peptides with potent bactericidal activity that disrupt bacterial cell membranes, such as cathelicidin and beta defensin. 2 Reference: Liu PT, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006; 311(5768):1770–3. PubMed: 16497887

With the direct help of vitamin D, our bodies produce more than 200 antimicrobial peptides, the most potent of which is cathelicidin, a natural broad-spectrum antibiotic. This explains the effectiveness of vitamin D therapy in treating all types of acute respiratory viral infections. 3 Reference: Balla M, Merugu GP, Konala VM, Sangani V, Kondakindi H, Pokal M, Gayam V, Adapa S, Naramala S, Malayala SV. Back to basics: review on vitamin D and respiratory viral infections including COVID-19. J Community Hosp Intern Med Perspect. 2020 Oct 29;10(6):529-536. doi: 10.1080/20009666.2020.1811074. PMID: 33194123; PMCID: PMC7599018.

In general, vitamin D helps reduce viral replication by inducing defensins and cathelicidins, and minimises the total amount of cytokines (biochemically active intercommunicating protein molecules produced by immune cells to act on other immune cells) that injure the lung mucosa in inflammatory pneumonia, and helps increase anti-inflammatory cytokines. 3 Reference: Balla M, Merugu GP, Konala VM, Sangani V, Kondakindi H, Pokal M, Gayam V, Adapa S, Naramala S, Malayala SV. Back to basics: review on vitamin D and respiratory viral infections including COVID-19. J Community Hosp Intern Med Perspect. 2020 Oct 29;10(6):529-536. doi: 10.1080/20009666.2020.1811074. PMID: 33194123; PMCID: PMC7599018.

Β-glucan is a water-soluble dietary fibre obtained from oats, barley, bacteria, yeast, algae, and mushrooms. Cell wall of baker’s yeast, that is, Saccharomyces cerevisiae is most abundant in β-glucan. β-glucan is a water-soluble polysaccharide consisting of glucose units. Glucose monomers are linked via β-(1→3) glycosidic bonds in bacteria and algae whereas glucose monomers are linked via β-(1→3) and β-(1→6) glycosidic bonds in yeast and mushrooms. In oats and barley, glucose monomers are linked via β-(1→4) and β-(1→3) glycosidic bonds. Β-glucan obtained from bacteria and algae shows a linear structure whereas β-glucan extracted from yeast, mushrooms, oats, and barley exhibits a branched structure. Β-glucan synthesis in the cell wall is a complex process because of the identification of a large number of different classes of glucans. Several classes of enzymes are involved in the synthesis of β-glucan. No sharp distinction lies between the insoluble and soluble fractions of β-glucan; however, the water solubility of β-glucan is dependent on its structure.¹

Thus, mushrooms, bacteria and plants produce different glucans with large differences in the proportions and arrangements of their 1→3, 1→4 and 1→6 β-glycosidic bonds; respectively, they are different types of β-glucans. These three types not only differ at the molecular level but also have different effects on the body. Although each of these types of β-glucans can have positive health effects, the benefits vary depending on the type of β-glucan.²

Oat-based β-glucans are notable for promoting heart health and helping manage LDL (bad) cholesterol. They improve metabolic parameters such as dyslipidaemia and insulin resistance.

Although mushroom β-glucans have been shown to have immune health benefits, research indicates that their potency is lower than that of certain well-studied baker’s yeast β-glucans.

Yeast-derived β-glucans act as immune-modulators, particularly by stimulating the innate immune response.³ They usually originate in either baker’s yeast or brewer’s yeast. Even though both are β-(1→3) and β-(1→6) from Saccharomyces cerevisiae, the source matters – the beta-glucans extracted from the cell walls of baker’s yeast have a different molecular pattern from that of brewer’s yeast, which can influence the immune-modulating abilities.

By activating and enhancing immune cells, β-glucans help the body fight off viruses, bacteria, and other pathogens.⁴

However, it is important to choose high-quality β-glucans as they provide biological activity, and the desired mechanism for action in the body. The manufacturing or processing methods used to extract the β-glucans can impact their structure. If the β-glucan’s structure is damaged or altered during the manufacturing process, the result could be a loss of measurable immune health benefits in the finished product.

There is no information on beta-glucan deficiency. Also, there is no specific Recommended Dietary Allowance (RDA) for beta-glucans. However, given that beta-glucans are a fibre, there are recommendations for total fibre intake, and, unfortunately, many people do not get enough fibre in their diet.

The adequate intake of fibre is at least 14 grams of fibre/1000 calories of intake. The recommended amount of fibre varies between women and men – it ranges from 21 to 26 grams of fibre daily for women and 30 to 38 grams daily for men, depending on age.

Beta-glucans are naturally present in various foods. Good sources are oats, barley, sorghum, rye, corn, wheat, rice, mushrooms, seaweed (algae).

The highest concentrations of beta-glucans are found in grains such as barley and oats. Furthermore, this fibre is found in some types of bacteria and mushrooms, including Saccharomyces cerevisiae, which is used to make nutritional yeast, wine, beer and some bakery products. However, this does not mean that alcoholic beverages are a good source of beta-glucans.

No side effects have been reported when beta-glucans are taken orally.

When applied on skin: beta-glucans are safe when used temporarily. For some people they may cause skin irritation and/or rashes.

If taking medication, in some cases there may be a moderate interaction between the medication and beta-glucans.

1. Medications that decrease the immune system (Immune-suppressants) interact with beta-glucans.

Beta-glucans can increase the activity of the immune system. Some medications, such as those used after a transplant, decrease the activity of the immune system. Taking beta-glucans along with these medications might decrease the effects of these medications.

2. Medications for high blood pressure (Antihypertensive drugs) interact with beta-glucans.

Oat-based beta-glucans might lower blood pressure. Taking beta-glucans along with medications that lower blood pressure might cause blood pressure to go too low. Monitor your blood pressure closely.

Biologically active, safe and mainly natural immune stimulants have been sought throughout human history. Some of them, such as beta-glucans, are being intensively studied. To date, there are more than 15 000 publications, but the search continues.

Beta-glucan, a natural plant-derived molecule, “modulates” (alters) the immune system by activating every immune cell in the body: macrophages, neutrophils, basophils, NK (natural killer) cells, etc. Specifically, macrophages trigger a range of immune functions that allow the body to produce the most complete, effective and appropriate immune response possible. The activity of the immune cells of the body determines how well the immune system captures and defeats “invaders” that are foreign to the body. Beta-glucan triggers immune cells to be ready to “fight back”.

Basically, beta-glucan is a catalyst that makes the immune system smarter by increasing our body’s defences. When first confronted with a pathogen, the immune system initially reacts quickly and non-specifically, using its innate immune function. Symptoms associated with this response, such as pain and swelling, are the result of the body’s inflammatory response.

This is followed by a slower, specific response to the pathogen by the adaptive side of the immune system. Adaptive immunity involves the part of the immune system that has long-term memory and prevents many pathogens from infecting us more than once.

Immune-modulating molecules, some of which can be ingested, can help the body defend itself against pathogens by adapting the normal immune response so that it responds more effectively when a pathogen is detected.

In particular, beta-glucans derived from yeast affect the inflammatory and antimicrobial activities of neutrophils and macrophages, cells that are part of the innate immune system. There is emerging evidence that yeast beta-glucans may “train” the body’s immune cells to react more effectively when a pathogen is detected.

Training the body’s immune system refers to a newly recognised phenomenon that occurs when innate immune cells encounter specific pieces of microbes (living or non-living), causing the cells to adopt a more effective response to a future threat. In essence, this means that innate immune cells, after experiencing one of these training stimuli, retain a “memory” of the experience that allows them to respond more quickly and effectively when they encounter another pathogen.

A key difference between innate immune training and the traditional immune memory is how broad the trained response is. In traditional immune memory, the immune system encounters a pathogen (for example, measles) through illness or vaccination and the adaptive immune system creates several types of specific molecules to recognise that pathogen (measles) in the future and block the body from becoming infected.

By contrast, in trained immunity, the innate immune system’s encounter with living or non-living microbes (the “trainer” stimuli) adjusts the innate immune response to allow for a more efficient reaction toward pathogens that are not related to the “trainer.” This more general effect is essential for immune defence because it is helpful to have some level of protection from pathogens you have never encountered before.

Trained immunity, induced by an initial encounter with a training stimulus such as yeast beta-glucan, results in an enhanced response to subsequent infections. Several different functions of immune cells are primed for quicker activation from this process including the production of antimicrobial molecules.

The emerging evidence shows that yeast beta-glucan could be a training stimulus for the immune system 1 Ref.: De Marco Castro, E., Calder, P. C., & Roche, H. M. (2020). β‐1,3/1,6‐Glucans and Immunity: State of the Art and Future Directions. Molecular Nutrition & Food Research, 65(1), 1901071. doi:10.1002/mnfr.201901071 . Additionally, some observations from previously published studies investigating the mechanism of action of Wellmune^® are consistent with how an innate immune trainer acts.

To summarise the benefits, beta-glucans may interact positively with the immune system. The potential benefits of beta-glucan for the immune system are:

1) increasing the immune response against colds and influenza (improving protection against colds, influenza and other respiratory infections);

2) reducing seasonal allergy symptoms in some cases (reduced sneezing and nasal stuffiness);

3) reducing inflammation due to intense exercise: several studies show that beta-glucans reduce exercise-related inflammation.

1. Beta-glucans are a polysaccharide sugar derived from yeast, mushrooms or oats. They have antioxidant properties and are skin soothing agents.
2. Investigations into beta-glucans started in the 1960s and 1970s on different continents at the same time. Mainly in the USA and Europe, but also in Asia, mainly in Japan. Research on beta-glucans in Europe and America was based on knowledge of immunomodulatory effects of zymosan, a mixture of polysaccharides isolated from the cell walls of Saccharomyces cerevisiae.
3. In Asian medicine, the consumption of different medicinal mushrooms (e.g., shiitake, maitake, reishi, etc.) has a long tradition. In detailed studies of the biological effects of these mushrooms, especially anti-cancer actions, beta-glucans were found to be a main cause of non-specific immune-modulation.
4. Goro Chihara from Teikyo University in Kawasaki, isolated beta-glucan from mushroom shiitake (Lentinula edodes) and named them lentinan.
5. All sufficiently purified polysaccharide immunomodulators distinguish themselves by very low toxicity.
6. Unlike most other natural products, purified beta-glucans retain their bioactivity, which permits the characterisation of how beta-glucans work on a cellular and molecular level.

The empirical formula of vitamin C is C₆ P₈ O₆. It is a crystalline powder, white or slightly yellow in colour, practically odourless and with a very sour taste. The melting point is 190 degrees Celsius. The active components of the vitamin are normally destroyed by cooking food, especially in the presence of metals such as copper. Vitamin C may be considered the most unstable of all the water-soluble vitamins, but it can withstand freezing. It is easily soluble in water and methanol and oxidises well, especially in the presence of heavy metal ions (copper, iron, etc.). It gradually darkens in contact with air and light. In the absence of oxygen, it can withstand temperatures of up to 100 °C. Vitamin C is an essential element that must be consumed in the diet because the body cannot synthesise it 1 Ref.: Linster, C. L., & Van Schaftingen, E. (2006). Vitamin C. FEBS Journal, 274(1), 1–22. doi:10.1111/j.1742-4658.2006.05607.x . Thus, our body has developed an efficient adaptive system to maintain organic reserves of vitamin C and prevent its deficiency in the case of malnutrition. Dietary vitamin C is absorbed in the reduced form of ascorbic acid through intestinal tissues, via the small intestine, by active transport and passive diffusion via SVCT transporters 1 and 2.

Vitamin C does not have to be digested before absorption. Ideally, about 80–90% of vitamin C consumed is absorbed from the intestines. However, the absorption capacity of vitamin C is inversely related to intake; it tends to reach 80–90% efficiency at quite low levels, but these percentages decrease significantly if the daily intake exceeds 1 gram. Given normal intake with food, 70–90% of vitamin C is absorbed at moderate intakes of 30–180 mg/day, but increases to 98% with very low intakes (less than 20 mg). And vice versa, at doses above 1 g/day, absorption falls to less than 50% The whole process is very fast; the body takes up the required amount in about two hours, and within three to four hours the unused part is removed from the bloodstream. It is even faster for people who consume alcohol or smoke cigarettes, and under stressful conditions. Many other substances and conditions can also increase the body’s need for vitamin C: fever, viral diseases, antibiotics, cortisone, aspirin and other painkillers, exposure to toxins (such as petroleum products, carbon monoxide) and heavy metals (such as cadmium, lead, mercury).

In fact, the white blood cell concentration of vitamin C can reach up to 80% of the plasma concentration of vitamin C. However, the body has a limited storage capacity for vitamin C. It is most often maintained in the adrenal glands (about 30 mg), pituitary gland, brain, eyes, ovaries, and testicles. Vitamin C is also found in the liver, spleen, heart, kidneys, lungs, pancreas and muscles, although in smaller amounts. Plasma concentration of vitamin C increases with increasing intake, but only up to a certain limit. Any dose of 500 mg or more is normally removed from the body. Unused vitamin C is removed from the body or first converted to dehydroascorbic acid. This oxidation mainly happens in the liver and also in the kidneys.

Pharmacokinetic experiments demonstrated that plasma vitamin C concentration is tightly controlled by three primary mechanisms: intestinal absorption, tissue transport, and renal reabsorption 100% absorption efficiency is observed with oral intake of vitamin C in doses of up to 200 mg at one time. Once plasma vitamin C concentrations reach saturation, additional vitamin C is largely excreted in the urine.

The first symptoms of vitamin C deficiency in the body are weakness and fatigue, muscle and joint pain, rapid bruising, and rashes in the form of small red-blue spots. Other symptoms include dry skin, swollen and discoloured gums, bleeding gums, wound healing, frequent colds, tooth loss and weight loss.

In 2013, the European Scientific Committee on Food stated that the average vitamin C requirement for a healthy level is 90 mg/day for men and 80 mg/day for women. The ideal amount for most people is around 110 mg/day for men and 95 mg/day for women. According to the group of experts, these levels were sufficient to balance the metabolic losses of vitamin C and to maintain plasma ascorbate concentrations at around 50 µmol/L.

Smokers are recommended to take 35 mg/day more than non-smokers because they are exposed to increased oxidative stress caused by cigarette smoke toxins and generally have lower vitamin C levels in the blood.

Reference https://ods.od.nih.gov/factsheets/VitaminC-HealthProfessional/

It is currently recommended to avoid doses of vitamin C higher than 2 g/day to avoid side effects (bloating and osmotic diarrhoea). It is believed that excessive consumption of ascorbic acid can cause several problems (e.g., birth defects, cancer, atherosclerosis, increased oxidative stress, kidney stones); however, none of these alleged adverse health effects have been confirmed in subsequent studies, and there is no reliable scientific evidence. Although, there is scientific evidence that high levels of vitamin C (up to 10 g/day in adults) are toxic or detrimental to health. Gastrointestinal side effects are usually not serious and normally disappear when high doses of vitamin C are reduced. The most common symptoms of vitamin C overdose are diarrhoea, nausea, abdominal pain and other gastrointestinal problems.

Some medicines can lower vitamin C levels in the body: oral contraceptives, high doses of aspirin. Taking vitamin C, vitamin E, beta-carotene and selenium at the same time can reduce the effectiveness of cholesterol-lowering drugs and niacin. Vitamin C also interacts with aluminium, which is part of most antacids, so a break between their use is necessary. In addition, there is some evidence that ascorbic acid may reduce the effectiveness of some cancer and AIDS drugs.

Vitamin C (ascorbic acid) plays an important role in the normal functioning of the immune system and its use in preventing and/or treating infections has strongly attracted the interest of physicians and investigators for almost a century. It is well known that vitamin C deficiency leads to increased vulnerability to infections. 1 Ref.:Hemilä, H. (2017). Vitamin C and Infections. Nutrients, 9(4), 339. doi:10.3390/nu9040339

In the 1970s, Linus Pauling proposed that vitamin C could successfully treat and/or prevent the common cold. 2 Ref.:Pauling L. The significance of the evidence about ascorbic acid and the common cold. Proc Natl Acad Sci U S A 1971;68:2678-81. The results of further controlled studies have been inconsistent, leading to confusion and controversy, although public interest in the subject remains high.

One study 3 Ref.:Douglas RM, Hemilä H, Chalker E, Treacy B. Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev 2007;(3):CD000980 examined placebo-controlled trials of 200 mg of vitamin C per day taken continuously as prophylactic treatment or after the appearance of cold symptoms. Prophylactic vitamin C intake did not generally reduce the risk of common cold. However, in studies involving marathon runners, skiers and soldiers exposed to extreme exercise and/or cold environments, prophylactic vitamin C intake of 250 mg/day to 1 g/day reduced the occurrence of common colds by 50%. In the general population, Prophylactic supplementation with vitamin C reduced the duration of the common cold in both adults by 8% and children by 14%. When taken after the occurrence of cold symptoms, vitamin C had no effect on the duration or severity of colds.

However, vitamin C has generally been shown to regulate the immune system due to its antioxidant properties and its role in the synthesis of collagen, which is needed to stabilise epithelial barriers. Additionally, it impacts phagocytic function and has an immune-stimulatory effect on lymphocyte cells. Vitamin C is highly concentrated in leukocytes and is used rapidly during infection. In fact, it has been defined as a stimulant of leukocyte functions, especially of neutrophil and monocyte movement. High vitamin C levels in neutrophils are necessary to counteract the extremely high levels of oxidative stress, which includes damage to cellular DNA and cell bodies caused by molecules known as reactive oxygen species (ROS), also known as “free radicals”. The antioxidant balance is an important determinant of immune function and immune cells are particularly sensitive to changes in this balance. 4 Ref.:Maggini, S., Wenzlaff, S., & Hornig, D. (2010). Essential Role of Vitamin C and Zinc in Child Immunity and Health. Journal of International Medical Research, 38(2), 386–414. doi:10.1177/147323001003800203

Also, vitamin C has good synergy with immune-boosting substances such as beta-glucans. The potent immune-stimulatory effects of beta-glucans are well established, with recent studies showing that some additional bioactive molecules have synergistic effects when combined with glucan. First, several scientific studies have confirmed the beneficial effects of taking glucan in combination with vitamin C. 5 Ref.:Vaclav Vetvicka, Jana Vetvickova; Combination of glucan, resveratrol and vitamin C demonstrates strong anti-tumor potential Anticancer Res. 2012 Jan;32(1):81-7. The main reason for the synergistic effect of vitamin C could be the fact that vitamin C stimulates the same type of immune responses as glucan.

Accordingly, we can conclude that vitamin C is an essential antioxidant and plays an important role as a cofactor (helps catalyse biochemical reactions) and modulator of various immune system pathways. 6 Ref.:Milani, G. P., Macchi, M., & Guz-Mark, A. (2021). Vitamin C in the Treatment of COVID-19. Nutrients, 13(4), 1172. doi:10.3390/nu13041172

1. In the 1940s, Doctor Frederick Klener cured chickenpox, tetanus, mumps, measles and poliomyelitis using vitamin C therapy.
2. Vitamin C is excellent for collagen repair. It helps the skin look better and relieves bone pain.
3. Scurvy was a disease that most sailors had to deal with. For a long time, nobody knew how to treat this disease. Around 1747, a breakthrough came. A doctor managed to cure 12 sick sailors with citrus fruits. It was the only effective treatment and eventually gave the sailors the nickname “sour”. It originated from sucking on limes during a voyage to prevent illness.
4. Vitamin C is necessary for proper fat metabolism. Basically, it allows the body to use fat as fuel. It has also been proven that vitamin C can help reduce appetite.
5. Vitamin C, instant coffee and soda can be used to develop black-and-white films.
6. Humans, primates and guinea pigs are the only mammals that cannot produce vitamin C in their own bodies.

Glutamine is the most abundant and versatile free-form (already broken down and easily absorbed) α-amino acid in our bodies. In the body, glutamine is formed from glutamic acid by the action of the enzyme glutamine synthetase, which binds ammonia. Glutamine is an important component of nitrogen metabolism. Like arginine, glutamine is a biochemical nitrogen donor, forming other amino acids, purines and pyrimidines. 1 Ref.: https://en.wikipedia.org/wiki/Glutamine For instance, in vitro and in vivo studies have determined that glutamine is an essential nutrient for tissue development and for the formation of the main new immune cells, lymphocytes. Glutamine helps produce cytokines – biochemically active protein molecules that are produced by cells of the immune system to affect other immune cells. These cytokines activate or modulate cells of the innate immune system (macrophages, dendritic cells, natural killer cells) and also epithelial cells. 2 Ref.: Cruzat, V., Macedo Rogero, M., Noel Keane, K., Curi, R., & Newsholme, P. (2018). Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation. Nutrients, 10(11), 1564. doi:10.3390/nu10111564 The immune cells consume glutamine both when the body is healthy and during illness, and this consumption is similar to or greater than that of glucose.

Glutamine is involved in various biochemical processes. Some provide energy, serving as a precursor for amino acid synthesis, a nitrogen donor for nucleic acid formation, helping to synthesise intracellular proteins and acting as essential support in the acid-base balance. 3 Ref.: De Oliveira, D. C., da Silva Lima, F., Sartori, T., Santos, A. C. A., Rogero, M. M., & Fock, R. A. (2016). Glutamine metabolism and its effects on immune response: molecular mechanism and gene expression. Nutrire, 41(1). doi:10.1186/s41110-016-0016-8

Glutamine is also a potential precursor for the synthesis of N-acetyl-glucosamine and N-acetyl-galactosamine, which may play a crucial role in the synthesis of intestinal mucin (a glycoprotein) and thus in maintaining a passive barrier against bacterial invasion. 4 Ref.: Khan J, Iiboshi Y, Cui L, Wasa M, Sando K, Takagi Y, Okada A. Alanylglutamine-supplemented parenteral nutrition increases luminal mucus gel and decreases permeability in the rat small intestine. JPEN J Parenter Enteral Nutr. 1999;23:24–31.

Basically, it is “food” for enterocytes (the cells that make up the small intestine), helping to heal intestinal inflammation. It is ideal for autoimmune diseases, which are often aggravated by inflammatory bowel disease. Additional use of glutamine has been shown to relieve psoriasis, eczema and joint pain. If inflammatory markers are detected in a gut microbiome test, glutamine may help.

Medications used to prevent seizures (Anticonvulsants) interact with glutamine.

Glutamine may increase the risk of seizures in some people. Therefore, taking glutamine may decrease the effects of medications used to prevent seizures.

When taken orally, glutamine is likely safe when used in doses of up to 40 grams daily. Side effects are generally mild and might include bloating, nausea, dizziness, heartburn, and stomach pain.

Glutamine can increase the risk of brain function issues in people with advanced liver disease. Consult your healthcare professional if you have any advanced liver disease.

Bipolar disorder: glutamine might increase the risk of mania or hypomania in people with this condition.

Monosodium glutamate (MSG) sensitivity: if you are sensitive to MSG, you might also be sensitive to glutamine because the body converts glutamine to glutamate.

Nutrients can impact and regulate cellular metabolism and cell function which is particularly important for the activation and function of diverse immune subsets. Among the critical nutrients for immune cell function and fate, glutamine is possibly the most widely recognised immune-nutrient, playing key roles in the TCA cycle (tricarboxylic acid cycle – cellular respiration involving a series of chemical reactions that release stored energy), heat shock protein responses and antioxidant systems.

If speaking of immunity, we must not forget the intestinal tract. Why? For many years, the gut was only studied as an organ for digestion, nutrient absorption and fermentation. However, now we know that the intestinal tract is a complex organ performing a variety of critical physiological functions. The intestinal mucosa not only contains a secretion but also immune and neuroendocrine cell-absorbing enterocytes (an epithelial cell in the intestinal mucosa that mainly absorbs nutrients). One layer of epithelium covering the gastrointestinal tract creates a selective barrier to prevent harmful substances such as toxins, allergens and pathogens from entering the large circulatory tract. 1 Ref.: De Oliveira, D. C., da Silva Lima, F., Sartori, T., Santos, A. C. A., Rogero, M. M., & Fock, R. A. (2016). Glutamine metabolism and its effects on immune response: molecular mechanism and gene expression. Nutrire, 41(1). doi:10.1186/s41110-016-0016-8

From this perspective, we can understand the important role of glutamine. Glutamine is the main energy substance of enterocytes. Rapidly dividing cells need glutamine, which serves as a nitrogen donor, for amino acids, purine and pyrimidine by acting on carbamoyl phosphate synthetase. 2 Ref.: Lobley GE, Hoskin SO, McNeil CJ. Glutamine in animal science and production. J Nutr. 2001;131:2525S–31

Based on this, glutamine is generally included on the list of “immune elements” that have biological effects.

Conclusion: glutamine is required by the cells of the immune system both as a primary fuel and as a carbon and nitrogen donor for nucleotide precursor synthesis. In vivo studies have demonstrated that glutamine is essential for optimal immune cell functioning for monocytes, lymphocytes and neutrophils. A number of studies of patients have shown improved infectious morbidity when receiving glutamine. 3 Ref.: Andrews, F. J., & Griffiths, R. D. (2002). Glutamine: essential for immune nutrition in the critically ill. British Journal of Nutrition, 87(S1), S3. doi:10.1079/bjn2001451

1. Cabbage and beetroot contain high concentrations of glutamine. Other dietary sources include fish, beans and dairy products.
2. Unlike protein or creatine, glutamine does not directly help build muscle mass.
3. If you happen to spend more time in the gym, glutamine helps in recovering from muscle soreness and fatigue, thus reducing the “recovery” time between workouts.
4. Having enough glutamine in your body promotes good ‘mucosal integrity’ of the gut – which means it has a strong defence against irritants, such as from alcohol or drugs such as aspirin.
5. It is best to take L-glutamine about 10-15 minutes before a meal on an empty stomach and take it 2–3 times per day (so before meals 2–3 per day) to provide support evenly and consistently.
6. However, glutamine should not be taken with anything hot such as coffee, tea, soup or broth. The main reason is that high temperatures can denature (take away the natural properties) or damage the amino acids.

Black elder (Sambucus nigra L.) is one of many species of elderberry. The black elder is an up to 6 m tall tree or shrub. It has creamy-white flowers in shield-like clusters and black-purple stone fruits with three stones. The flowers bloom in June and July. The oppositely arranged leaves are pinnate with 3, 5 or 7 leaflets. The natural range is southern Europe, North Africa and the Middle East. 1 Ref.: https://en.wikipedia.org/wiki/Sambucus_nigra

Elderberries contain many active chemicals with pharmacological activity, including anthocyanins (mainly cyanidin 3-glucoside and cyanidin 3-sambubioside), which have been shown to strengthen the immune system and show antiviral activity. 2 Ref.: Hawkins, J., Baker, C., Cherry, L., & Dunne, E. (2019). Black elderberry (Sambucus nigra) supplementation effectively treats upper respiratory symptoms: A meta-analysis of randomized, controlled clinical trials. Complementary Therapies in Medicine, 42, 361–365. doi:10.1016/j.ctim.2018.12.004  Oral use of elderberry has resulted in plasma levels of these anthocyanins.

Other components include vitamins and minerals in small amounts and carbohydrates such as pectin and up to 7.5% glucose and fructose.

Elderberry contains diversely bioactive ingredients, such as (poly)phenolic compounds and terpenoid compounds. Polyphenols, known for their free radical scavenging activity, together with anthocyanins are the most important groups of bioactive compounds present in elderberry in relatively high concentrations.

Recent studies 3 Ref.: Liu D, He XQ, Wu DT, Li HB, Feng YB, Zou L, Gan RY. Elderberry (Sambucus nigra L.): Bioactive Compounds, Health Functions, and Applications. J Agric Food Chem. 2022 Apr 13;70(14):4202-4220. doi: 10.1021/acs.jafc.2c00010. Epub 2022 Mar 29. PMID: 35348337 report that some food processing methods can affect the content of bioactive compounds in elderberry, and that the chemical composition depends on various factors such as location, stage of ripening and climatic conditions. 4 Ref.: Młynarczyk K, Walkowiak-Tomczak D, Łysiak GP. Bioactive properties of Sambucus nigra L. as a functional ingredient for food and pharmaceutical industry. J Funct Foods. 2018 Jan;40:377-390. doi: 10.1016/j.jff.2017.11.025. Epub 2017 Dec 22. PMID: 32362939; PMCID: PMC7185606 For instance, the method of production of the juice, which is widely used in both food supplements and syrups, influences the content of bioactive compounds. Elderberry juices processed using enzymatic treatment (pectinolysis) demonstrated a lower average content of most investigated phenolic compounds compared to the juices produced without enzymatic treatment. Therefore, when choosing supplements with elderberry juice or extract, consider the standardisation of the active substances (polyphenols and anthocyanins). Elderberry exhibits various health functions in vitro and in vivo, including antioxidant, anti-inflammatory, anticancer, anti-influenza, antimicrobial, antidiabetic, cardiovascular protective, and neuroprotective activities. 3 Ref.: Liu D, He XQ, Wu DT, Li HB, Feng YB, Zou L, Gan RY. Elderberry (Sambucus nigra L.): Bioactive Compounds, Health Functions, and Applications. J Agric Food Chem. 2022 Apr 13;70(14):4202-4220. doi: 10.1021/acs.jafc.2c00010. Epub 2022 Mar 29. PMID: 35348337 However, elderberry is mainly used to treat common cold symptoms: fever, cough, stuffy nose, runny nose and flu, as well as preventively to strengthen the immune system. 4 Ref.: Młynarczyk K, Walkowiak-Tomczak D, Łysiak GP. Bioactive properties of Sambucus nigra L. as a functional ingredient for food and pharmaceutical industry. J Funct Foods. 2018 Jan;40:377-390. doi: 10.1016/j.jff.2017.11.025. Epub 2017 Dec 22. PMID: 32362939; PMCID: PMC7185606

Elderberry bark, unripe berries, and seeds contain small amounts of substances known as lectins, which can cause stomach problems if consumed excessively. 1 Ref.: https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-sambucus-nigra-l-fructus_en.pdf In addition, the elderberry plant contains substances called cyanogenic glycosides that can release cyanide in some circumstances. This is a toxin also found in apricot seeds and almonds 2 Ref.: Ulbricht C, Basch E, Cheung L, Goldberg H, Hammerness P, Isaac R, Khalsa KP, Romm A, Rychlik I, Varghese M, Weissner W, Windsor RC, Wortley J. An evidence-based systematic review of elderberry and elderflower (Sambucus nigra) by the Natural Standard Research Collaboration. J Diet Suppl. 2014 Mar;11(1):80-120. doi: 10.3109/19390211.2013.859852. Epub 2014 Jan 10. PMID: 24409980 . However, its content is not high – 3% of the estimated lethal dose for a person weighing 60 kg, or more precisely 3 mg per 100 grams of fresh berries and 3–17 mg per 100 grams of fresh leaves.

However, it is important to know that commercial preparations and cooked berries do not contain cyanide. Symptoms of eating uncooked berries, leaves, bark or elderberry roots include nausea, vomiting and diarrhoea.

Elder is not known to have severe, serious or moderate drug interactions. Do not use preparations containing elder if an allergic reaction has been observed.

Elderberry extract is shown to be effective in mitigating the duration and severity of flu symptoms in several strains of influenza viruses. 1 Ref.: Porter RS, Bode RF. A Review of the Antiviral Properties of Black Elder (Sambucus nigra L.) Products. Phytother Res. 2017 Apr;31(4):533-554. doi: 10.1002/ptr.5782. Epub 2017 Feb 15. PMID: 28198157  A study of 312 air travellers taking capsules containing 300 mg of elderberry extract three times per day found that those who got sick experienced a shorter duration of illness and less severe symptoms. 2 Ref.: Tiralongo E, Wee SS, Lea RA. Elderberry Supplementation Reduces Cold Duration and Symptoms in Air-Travellers: A Randomized, Double-Blind Placebo-Controlled Clinical Trial. Nutrients. 2016 Mar 24;8(4):182. doi: 10.3390/nu8040182. PMID: 27023596; PMCID: PMC4848651

Studies 3 Ref.: Chatterjee A, Yasmin T, Bagchi D, Stohs SJ. Inhibition of Helicobacter pylori in vitro by various berry extracts, with enhanced susceptibility to clarithromycin. Mol Cell Biochem. 2004 Oct;265(1-2):19-26. doi: 10.1023/b:mcbi.0000044310.92444.ec. PMID: 15543930 4 Ref.: Krawitz C, Mraheil MA, Stein M, Imirzalioglu C, Domann E, Pleschka S, Hain T. Inhibitory activity of a standardized elderberry liquid extract against clinically-relevant human respiratory bacterial pathogens and influenza A and B viruses. BMC Complement Altern Med. 2011 Feb 25;11:16. doi: 10.1186/1472-6882-11-16. PMID: 21352539; PMCID: PMC3056848 have shown that elderberry is effective against a variety of pathogens, such as Helicobacter pylori (can cause stomach ulcers, abdominal pain, nausea), Streptococcus pyogenes (the most common bacterial cause of pharyngitis), Streptococci group C and G, Branhamella catarrhalis (can cause infections of the human respiratory system, middle ear, eyes, central nervous system and joints) and Haemophilus influenza (can cause pneumonia, otitis, sinusitis, laryngotracheitis, bronchitis).

The immune-modulatory effect of standardised elderberry extract against leishmaniasis and malaria infections was found to delay disease progression. 5 Ref.: Waknine-Grinberg, J., El-On, J., Barak, V., Barenholz, Y., & Golenser, J. (2009). The Immunomodulatory Effect of Sambucol on Leishmanial and Malarial Infections. Planta Medica, 75(06), 581–586. doi:10.1055/s-0029-1185357

Black elder has many bioactive constituents beneficial for general health and associated with the alleviation of a wide range of health disorders; accordingly, elder is promising for the treatment of low-risk influenza and other viruses and non-viral pathogens – and possibly also as a prophylactic agent for acute viral infections. 1 Ref.: Porter RS, Bode RF. A Review of the Antiviral Properties of Black Elder (Sambucus nigra L.) Products. Phytother Res. 2017 Apr;31(4):533-554. doi: 10.1002/ptr.5782. Epub 2017 Feb 15. PMID: 28198157

1. The elder tree was once considered sacred because it protected against many dangers and misfortunes – fires, evil people, even robbers and, of course, many diseases and illnesses.
2. Elder is considered mature after 3–4 years. Elderberries are not suitable for mechanical harvesting because they are difficult to separate from the stems, but in some countries, they are harvested using machinery designed for other berry crops and adapted to the elderberry.
3. The history of Elderberry dates all the way back to 400 BC, when Hippocrates, the “Father of Medicine”, called the elder tree his “medicine chest”.
4. Elder flowers, berries and leaves are excellent sources of antioxidants. For example, one of the anthocyanins found in the berries has 3.5 times the antioxidant power of vitamin E.
5. Elderberries may reduce levels of uric acid in the blood. Elevated uric acid is linked to increased blood pressure and negative effects on heart health.