Magnesium is a natural mineral that was discovered in 1755. It is the eighth most abundant element on earth and occurs naturally only in combination with other elements. In nature, it is found in large mineral deposits such as magnesite and dolomite rocks.

Magnesium is required by entire body as it enables muscle contraction, conductivity of nerves. Magnesium keeps a steady heartbeat and strong immune system.

Magnesium is an essential nutrient that is involved in many key metabolic reactions such as energy production, glycolysis, and the synthesis of nucleic acids and proteins. 1 (Reference: ©2016 American Society for Nutrition. Adv Nutr 2016;7:199–201; doi:10.3945/an.115.008524)

Magnesium also plays a role in the active transport of calcium and potassium ions across cell membranes, a process that is important to conductivity of nerves, muscle contraction, and normal heart rhythm. 2 (Reference: Rude RK. Magnesium. In: Ross AC, Caballero B, Cousins RJ, Tucker KL, Ziegler TR, eds. Modern Nutrition in Health and Disease. 11th ed. Baltimore, Mass: Lippincott Williams & Wilkins; 2012:159-75.) 

From a neurological standpoint, magnesium plays an essential role in nerve transmission and neuromuscular conduction. It also has a protective role against excessive excitation that can lead to destruction of neurons (excitotoxicity) and has been implicated in multiple neurological disorders. Due to these important functions within the nervous system, Magnesium is a mineral of intense interest for the potential prevention and treatment of neurological disorders. Current scientific literature reviews the applicability of Magnesium for migraine, chronic pain, epilepsy, Alzheimer’s, Parkinson’s, and stroke, as well as the commonly comorbid conditions of anxiety and depression.

Magnesium is very important for our body but not all people have it in sufficient quantities. Why? The reasons can be quite different. U.S. National Institute of Health lists the following Groups at Risk of Magnesium Inadequacy:

People with gastrointestinal diseases

The chronic diarrhea and fat malabsorption resulting from Crohn’s disease, gluten-sensitive enteropathy (celiac disease), and regional enteritis can lead to magnesium depletion over time. Resection of the small intestine, especially the ileum, typically leads to malabsorption and magnesium loss.

People with type 2 diabetes

Magnesium deficits and increased urinary Magnesium excretion can occur in people with insulin resistance and/or type 2 diabetes. The Magnesium loss appears to be secondary to higher concentrations of glucose in the kidney that increase urine output.

People with alcohol dependence

Magnesium deficiency is common in people with chronic alcoholism. In these individuals, poor dietary intake and nutritional status; gastrointestinal problems, including vomiting, diarrhea, and steatorrhea (fatty stools) resulting from pancreatitis; renal dysfunction with excess excretion of Magnesium into the urine; phosphate depletion; vitamin D deficiency; acute alcoholic ketoacidosis; hyperaldosteronism secondary to liver disease can all contribute to decreased Magnesium status.

Reference https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/#en10

Several types of medications have a potential to interact with Magnesium supplements or affect Magnesium status. A few examples are provided below. People taking these and other medications of these groups on a regular basis should discuss Magnesium intakes with their healthcare providers.

Bisphosphonates

Magnesium-rich supplements or medications can decrease the absorption of oral bisphosphonates, such as alendronate (Fosamax®), used to treat osteoporosis. Magnesium-rich supplements or medications and oral bisphosphonates should be taken at least 2 hours from each other.

Antibiotics

Magnesium can form insoluble complexes with tetracyclines, such as demeclocycline (Declomycin®) and doxycycline (Vibramycin®), as well as quinolone antibiotics, such as ciprofloxacin (Cipro®) and levofloxacin (Levaquin®). These antibiotics should be taken at least 2 hours before or 4–6 hours after a Magnesium-containing supplement.

Diuretics

Chronic treatment with loop diuretics, such as furosemide (Lasix®) and bumetanide (Bumex®), and thiazide diuretics, such as hydrochlorothiazide (Aquazide H®) and ethacrynic acid (Edecrin®), can increase the loss of Magnesium in urine and lead to Magnesium depletion. In contrast, Potassium-sparing diuretics, such as amiloride (Midamor®) and spironolactone (Aldactone®), reduce Magnesium excretion.

Magnesium is possibly one of the most studied substances for people suffering from a migraine or headache. Some studies show that migraine sufferers tend to have lower magnesium levels than those who do not have this problem. Some scientists believe magnesium blocks signals in the brain that lead to migraine with aura or changes in vision and other senses. Studies also reveal that magnesium inhibits certain pain-inducing chemicals. Besides, it seems that lowering of magnesium levels also leads to narrowing of brain blood vessels potentially contributing to migraine.

Migraine’s neurological disorder is characterized by having pain in head and other various symptoms such as nausea, emesis, photophobia, phonophobia, and sometimes visual sensory disorders. Magnesium is a necessary ion for human body and has a crucial role in health and life maintenance. One of the main roles of Magnesium is to conserve neurons electric potential. Therefore, magnesium deficiency can cause neurological complications. Migraine is usually related to low amounts of Magnesium in serum and cerebrospinal fluid. Deficits in magnesium have significant role in the pathogenesis of migraine. Magnesium has been extensively used in migraine prophylaxis and treatment ¹ Ref: Dolati, S., Rikhtegar, R., Mehdizadeh, A., & Yousefi, M. (2019). The Role of Magnesium in Pathophysiology and Migraine Treatment. Biological Trace Element Research. doi:10.1007/s12011-019-01931-z .

In scientific trials participants received daily magnesium supplementation for migraine prevention at varying doses (between 400mg and 1,200mg a day) for a varying period therefore it is difficult to define precisely the amount of magnesium a person needs to prevent migraine and it, most probably, is subject to individual factors (depending on the severity of magnesium deficit in that person).

However, some organisations, like Canadian Headache Association, recommend preventative magnesium therapy for adults and particularly a special dose of elementary magnesium of 600mg per day.

If you notice that magnesium-containing supplements do not alleviate your migraine attacks, it could be due to two underlying causes:

1. Food supplement that you are using has poor bioavailability, meaning that it is not well absorbed. Usually, it is the case with poor quality food supplements which have low value of elemental magnesium (amount of magnesium indicated in a food supplement does not always equal the amount of elemental magnesium in the product) as well as different forms of magnesium has better or worse bioavailability.
2. If diarrhoea appears after taking the daily dose, the food supplement is not absorbed good enough and does not give desirable effect.

Although there is no universally accepted definition, stress can be explained as a complex adaptive biochemical, physiological, psychological and gene expression change in the body (stress response) caused by a stimulus (stressor) and interpreted by the brain as dangerous.

The level of magnesium content in the body is closely related to the level of stress, since both stress and hypomagnesaemia (reduced magnesium in the blood) increase the negative effects of each other. In the case of hypomagnesaemia, as a result of stress, a series of disorders develop, for example, light-sensitive headaches, fibromyalgia (disorders described by widespread muscle and skeletal system pain accompanied by fatigue, sleep, memory disorders, etc.), chronic fatigue syndrome, audiogenic stress, cold stress and physical stress.

The transfer of magnesium from the intracellular (inside the cell) to the extracellular space primarily provides a protective role to mitigate the adverse effects of stress, but prolonged periods of stress lead to progressive magnesium deficiency and adverse health consequences.

A growing number of studies confirm that psychological stress promotes oxidative stress, mainly due to the autooxidation of catecholamines, and psychological stress increases lipid peroxidation, increases markers of DNA oxidative damage, and decreases plasma antioxidant activity. It is important here that magnesium antagonises (counteracts) many of these processes

Ref Ref: Magdalena D. Cuciureanu and Robert Vink. Magnesium and stress, PMID: 29920004 Bookshelf ID: NBK507250;

1. The word "magnesium" comes from the name of the Greek region Magnesia, where compounds of this element occur naturally.
2. Milk of Magnesia, which works as a laxative and to treat indigestion, is a compound of magnesium, hydrogen and oxygen molecules.
3. Don't put out a magnesium fire with water. After spraying the burning magnesium with water, it will start burning even faster, with a sharp flame.
4. Magnesium ions have sour and bitter taste. A small amount of Magnesium gives taste to the mineral water.
5. Magnesium is the 11^th most abundant element in the human body by mass. Magnesium ions are found in every cell of the body.
6. About 60% of the Magnesium in the human body is found in the skeleton, 39% in the muscle tissue, and 1% is extracellular.

Coenzyme Q10 (CoQ10) is a naturally occurring component in living cells. It physiologically acts as a powerful antioxidant, membrane stabilizer and cofactor in the production of adenosine triphosphate (ATP) by oxidative phosphorylation, inhibiting the oxidation of proteins and DNA. 1  (Reference: 2020 Apr 27;9(5):1266. doi: 10.3390/jcm9051266; Clinical Evidence for Q10 Coenzyme Supplementation in Heart Failure: From Energetics to Functional Improvement; Anna Di Lorenzo, Gabriella Iannuzzo, Alessandro Parlato, Gianluigi Cuomo, Crescenzo Testa, Marta Coppola, Giuseppe D'Ambrosio, Domenico Alessandro Oliviero, Silvia Sarullo, Giuseppe Vitale, Cinzia Nugara, Filippo M Sarullo, Francesco Giallauria PMID: 32349341 PMCID: PMC7287951) ATP is a nucleotide with a very important role in the metabolism of living organisms. It is a universal source of energy for biochemical processes in organisms. Accordingly, CoQ10 is important for both metabolic and biochemical processes in the body.

CoQ10 was first approved in 1973 in Japan as a drug for the treatment of patients with heart failure, and it has been used as a drug in some other countries as well. However, in most countries such as the United States and the Europe, CoQ10 has been widely used as a food additive or dietary supplement for maintaining healthy body condition for more than 20 years .

CoQ10 or ubikuinone was known to play a key role in mitochondrial bioenergetics as a carrier of electrons and protons. Subsequent studies showed the presence of CoQ10 in other cell membranes and blood plasma, and its antioxidant role was extensively studied. In addition, recent data suggest that CoQ10 affects the expression of genes involved in the signaling, metabolism and transport of human cells. CoQ10 deficiency is associated with autosomal recessive mutations, mitochondrial diseases, aging-related oxidative stress and carcinogenesis processes, and secondary effects of statin (lipid-lowering drug class). Many neurodegenerative disorders are associated with low levels of CoQ10: diabetes, cancer, fibromyalgia, muscular and cardiovascular diseases. 2 (Reference: Juan Garrido-Maraver, Mario D Cordero, Manuel Oropesa-Avila, Alejandro Fernandez Vega, Mario de la Mata

While many people’s bodies make all the CoQ10 they need, some don’t. The body contains between 500 and 1,500 milligrams of CoQ10, and it decreases with age.

There are no known ideal dosages, as they vary from person to person. Standard dosages for CoQ10 supplements range between 60 and 500 milligrams daily, and the highest recommended daily allowance is around 1,200 milligrams. Possible causes of CoQ10 deficiency:

• Deficiencies of certain vitamins, such as vitamin B6
• Mitochondrial diseases
• Genetic defects affecting CoQ10 production
• Oxidative stress, or an imbalance of free radicals and antioxidants

Some CoQ10 containing foods include:

1.  Organ meats (heart, liver and kidney) contain the highest amounts of CoQ10 per 100 grams. 
2.  Fatty fish, like trout, mackerel, and sardines contain CoQ10. 
3. Meat
4. Soybean products such as tofu, soy milk, and soy yogurt are a valuable source of protein as well as CoQ10 for people who do not eat meat.
5. In addition to many vitamins and minerals, a lot of vegetables and fruits contain CoQ10. Notably, broccoli, spinach, avocados and blackcurrants.

Adults who are not found or established to be deficient in CoQ10 are normally required 90- 200mg of CoQ10 per day.

Reference Pravst, I., Žmitek, K., & Žmitek, J. (2010). Coenzyme Q10 Contents in Foods and Fortification Strategies. Critical Reviews in Food Science and Nutrition, 50(4), 269–280. doi:10.1080/10408390902773037

CoQ10 has been used as a dietary supplement or a drug for more than 30 years. Published data of pre-clinical and clinical safety studies have shown that CoQ10 does not cause serious adverse effects in humans, and it is safe for use as a dietary supplement. Pharmacokinetic studies in animals and humans suggest that exogenous CoQ10 does not influence biosynthesis of CoQ nor does it accumulate into plasma or tissues after cessation of supplementation. 1 (Reference: Hidaka, T., Fujii, K., Funahashi, I., Fukutomi, N., & Hosoe, K. (2008). Safety assessment of coenzyme Q10(CoQ10). BioFactors, 32(1-4), 199–208. doi:10.1002/biof.5520320124

Coenzyme Q10 (CoQ10) is one of the most powerful antioxidants in the body, which also restores other antioxidants in the body and plays an important role in protecting against damage caused by reactive oxygen (reactive oxygen can destroy human cells). CoQ10 is the only known lipid-soluble antioxidant! During chronic migraine, inflammatory processes are formed that interfere with replenishment of antioxidant stores, thus reducing the possibility of getting rid of migraine discomfort. 1 Reference: Parohan, M., Sarraf, P., Javanbakht, M. H., Ranji-Burachaloo, S., & Djalali, M. (2019). Effect of coenzyme Q10 supplementation on clinical features of migraine: a systematic review and dose–response meta-analysis of randomized controlled trials. Nutritional Neuroscience, 1–8. doi:10.1080/1028415x.2019.1572940

CoQ10 is mainly found in the mitochondria of cells and it helps to improve cellular functions thus reducing the inflammation during a migraine. Since migraine and inflammation are interrelated, CoQ10 could mitigate or even prevent migraine-induced headache. 2 (Reference: Dahri, M., Tarighat-Esfanjani, A., Asghari-Jafarabadi, M., & Hashemilar, M. (2018). Oral coenzyme Q10 supplementation in patients with migraine: Effects on clinical features and inflammatory markers. Nutritional Neuroscience, 1–9. doi:10.1080/1028415x.2017.1421039 )

The pathophysiology of the migraine is not fully understood yet, however blood vessel and neuron dysfunction may be explained with oxygen exchange problems which stem from mitochondrial dysfunction. When it comes to problems with mitochondria, at least some part of patients and, taking into account the important role CoQ10 has to play in accumulating mitochondrial energy, CoQ10 could become a good substance for migraine prevention.   2 (Reference: Dahri, M., Tarighat-Esfanjani, A., Asghari-Jafarabadi, M., & Hashemilar, M. (2018). Oral coenzyme Q10 supplementation in patients with migraine: Effects on clinical features and inflammatory markers. Nutritional Neuroscience, 1–9. doi:10.1080/1028415x.2017.1421039 )

1. Fat-soluble, vitamin-like substance that occurs primarily in the mitochondria of practically every cell in the body.
2. It is responsible for generating 95 percent of the human body’s energy.
3. Both natural and synthetic form of CoQ10 is available; ubiquinone is produced through a proprietary bacteria-production process; ubiquinol is manufactured via yeast fermentation.
4. The heart is a remarkable organ as it beats 100,000 times every 24 hours and 2.5 billion times by the age 70, without a single holiday. Consequently, it requires a huge amount of energy. For this reason, nature has placed more CoQ10 in the heart than any other organ.
5. There is a belief, that 50% of overweight patients have low levels of CoQ10. Speeding up metabolism with CoQ10 is a safe way to help in weight loss.
6. Several studies have concluded that supplementing with CoQ10 may improve sperm quality, activity and concentration by increasing antioxidant protection

Feverfew (Tanacetum parthenium L.) belonging to the family Asteraceae (daisies) is a daisy-like perennial plant found commonly in gardens and along roadsides. The name stems from the Latin word febrifugia, “fever reducer.” The first-century Greek physician Dioscorides prescribed feverfew for “all hot inflammations.” Also known as “featherfew,” because of its feathery leaves. It is a short, bushy, aromatic perennial that grows 0.3–1 m in height. Its yellow-green leaves are usually less than 8 cm in length, almost hairless, and pinnate–bipinnate (chrysanthemum-like). Its yellow flowers, which bloom from July to October, are about 2 cm in diameter. They resemble those of chamomile (Matricaria chamomilla), for which they are sometimes confused, and have a single layer of white outer-ray florets. This aromatic plant gives off a strong and bitter odor. Its yellow-green leaves are alternate (in other words the leaves grow on both sides of the stem at alternating levels), and turn downward with short hairs. The small, daisy-like yellow flowers are arranged in a dense flat-topped cluster.

Feverfew (Tanacetum parthenium L.) is a medicinal plant traditionally used for the treatment of fevers, migraine headaches, rheumatoid arthritis, stomach aches, toothaches, insect bites, infertility, and problems with menstruation and labor during childbirth. The feverfew herb has a long history of use in traditional and folk medicine, especially among Greek and early European herbalists. Feverfew has also been used for psoriasis, allergies, asthma, tinnitus, dizziness, nausea, and vomiting. The plant contains a large number of natural substances, but the active principles probably include one or more of the sesquiterpene lactones known to be present, including parthenolide. Other potentially active constituents include flavonoid glycosides and pinenes. It has multiple pharmacologic properties, such as anticancer, anti-inflammatory, cardiotonic, antispasmodic, an emmenagogue, and as an enema for worms. The plant is widely cultivated to large regions of the world and its importance as a medicinal plant is growing substantially with increasing and stronger reports in support of its multifarious therapeutic uses. 1 Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3210009/

No serious side effects have been reported from feverfew use. Side effects can include nausea, digestive problems, and bloating; if the fresh leaves are chewed, sores and irritation of the mouth may occur.

People who are sensitive to ragweed and related plants may experience allergic reactions to feverfew.

Do not take feverfew while pregnant because it may affect uterine contractions. Little is known about whether it’s safe to use feverfew while breastfeeding.

Using feverfew topically may cause skin irritation. 1 Reference: https://www.nccih.nih.gov/health/feverfew

Feverfew (Tanacetum parthenium L.) is a well-known plant used in migraine prevention.

Feverfew is a medicinal herb possessing a range of healing properties and ability to alleviate headache that was recognised even in the Middle Ages. The healing properties of the feverfew in migraine pathophysiology is not entirely understood yet. Feverfew extract promotes secretion of serotonin (5-hydroxitriptamine) from platelets facilitated by several aggregation mediators. Physiologically, serotonin is involved in transmission of nerve impulses between neurons. It is also called a neurotransmitter. Serotonin is mainly found in the brain, gastrointestinal tract and platelets. Activity of serotonin in human body is specifically related to smooth muscle activity and impulse transmission between neurons, furthermore, serotonin triggers a sense of happiness and well-being.

Feverfew extracts and pure parthenolide inhibits synthesis of prostaglandins. Since prostaglandins are substances that trigger inflammation and pain, promote exudate (fluid that leaks from blood vessels during inflammation) and fever, the feverfew has beneficial impact on these aspects by preventing or mitigating them. Meanwhile parthenolide has a considerable impact on vasoconstriction and vasodilation mechanisms.

Several clinical studies have confirmed that benefits of feverfew in migraine prevention greatly exceed the risks. No evidence on serious side effects has been gathered from clinical studies and long-term users of this product regarding safety and tolerance of the feverfew. 1 Reference 1: Pfaffenrath, V., Diener, H., Fischer, M., Friede, M., & Henneicke-von Zepelin, H. (2002). The Efficacy and Safety of Tanacetum Parthenium (Feverfew) in Migraine Prophylaxis—a Double-Blind, Multicentre, Randomized Placebo-Controlled Dose-Response Study. Cephalalgia, 22(7), 523–532. doi:10.1046/j.1468-2982.2002.00396.x

Feverfew extracts inhibit 5-HT secretion in platelets by neutralising sulfhydryl groups both in cell and outside it. Sesquiterpenes found in the feverfew contain alpha-methylethylene butyric acetone units that can react with sulfhydryl groups

Feverfew seems to have more than one pathway mechanism of action. Plant extracts affect a number of physiological pathways. Some of these mechanisms were discussed above, for example, inhibition of prostaglandin synthesis, reducing of vessel's smooth muscle spasms and blocking of platelet granule secretion.

The feverfew is known worldwide, for example, Canadian Health Protection Department has granted the Drug Identification Number (DIN) to feverfew product allowing its producer to put a claim that this over-the-counter medication eliminates migraine headache. 2 Reference 2: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3210009/

Feverfew is well researched also in Europe and the European Medicines Agency in its evaluation report on feverfew (EMA/HMPC/48716/2019) has concluded that feverfew is being used for treating migraine and headache with a therapeutic dose of 100 mg of herbs per day.

1. The ancient Greeks called the herb “Parthenium,” supposedly because it was used medicinally to save the life of someone who had fallen from the Parthenon during its construction in the 5^th century BC.
2. Feverfew also was known as “medieval aspirin” or the “aspirin” of the 18^th century
3. In Central and South America, the plant has been used to treat a variety of disorders. The Kallaway Indians of the Andes mountains value its use for treating colic, kidney pain, morning sickness, and stomach ache. Costa Ricans use a decoction of the herb to aid digestion, as a cardiotonic, an emmenagogue, and as an enema for worms. In Mexico, it is used as an antispasmodic and as a tonic to regulate menstruation. In Venezuela, it is used for treating earaches
4. Feverfew also has been planted around houses to purify the air because of its strong, lasting odor, and a tincture of its blossoms is used as an insect repellant and balm for bites. It has been used as an antidote for overindulgence in opium.

Riboflavin was discovered by Blyth in 1872 as a yellow fluorescent pigment in milk, but the vitamin property of this pigment was not established until the early 1930s. Plants and some micro-organisms can synthesize riboflavin; however, it is an essential nutrient for human health and should be obtained from the diet. 1 Reference: https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/riboflavin-vitamin-b2-and-oxidative-stress-a-review/808987B9D15917EC23885EDFF5E17534

Riboflavin, vitamin B2, is a thermally stable, water-soluble vitamin used by the body to metabolize carbohydrates, fats, and protein into glucose for energy. In addition to boosting energy levels, this vitamin functions as an antioxidant for the proper functioning of the immune system, healthy skin, and hair. These effects occur with the help of two coenzymes, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). In riboflavin deficiency, macronutrients like fats, carbohydrates, and proteins cannot be digested to properly maintain the body. Riboflavin is required for normal development, lactation, physical performance, and reproduction.

A healthy digestive system can absorb most of the nutrients from the diet, so it is important to get most of the riboflavin from dietary sources. As already mentioned, Riboflavin has a yellow-green, fluorescent pigment, which causes urine to turn yellow, indicating that the body is absorbing riboflavin. Riboflavin also helps convert tryptophan to niacin, which activates vitamin B6. 2 Reference: https://www.ncbi.nlm.nih.gov/books/NBK470460/ 

Riboflavin deficiency can be caused by insufficient intake of nutrients or pathologies of the endocrine system. Riboflavin deficiency interacts also with deficiency of other B group vitamins. It is naturally occurring in food products such as eggs, dairy products, meat, green vegetables and grains. Antioxidant riboflavin has the same pathway as glutathione. Glutathione is a natural antioxidant created in our bodies, a simple peptide consisting of three amino acids – glycine, cysteine and glutamine. It possesses several vital properties that regulate bodily processes – immunity boosting, energy production, slowing down of cell ageing, lowering cholesterol level. All cells of the body synthesize glutathione but on a daily basis it can be inhibited and reduced by a number of factors, such as poor nutrition, use of drugs, stress, infections. Glutathione aims at neutralising free radicals and liver detoxification because free radicals can contribute to development of several diseases. A reason of deficient riboflavin can be also chronic diarrhoea, liver problems, alcoholism and haemodialysis. 1 Reference: Balasubramaniam, S., Christodoulou, J., & Rahman, S. (2019). Disorders of Riboflavin Metabolism. Journal of Inherited Metabolic Disease. doi:10.1002/jimd.12058

Groups at risk of riboflavin deficiency are:

Athletes. Exercise load strains metabolism therefore riboflavin is consumed excessively.

Pregnant and breastfeeding woman (sometimes also infants). Pregnant or lactating women who rarely consume meats or dairy products are at riboflavin deficiency risk, which can have adverse effects on the health of both mothers and their infants. Riboflavin deficiency during pregnancy, for example, can elevate the risk of preeclampsia.

Vegetarians or vegans and/or persons who consume very little of milk. Those who eat meat and dairy products obtain a substantial proportion of riboflavin from their diets. For this reason, people who live in developing countries and have limited intake of meat and dairy products are exposed to increased riboflavin deficiency risk. Vegans and those who consume little milk in developed countries are also at riboflavin inadequacy risk. 2 Reference: https://ods.od.nih.gov/factsheets/Riboflavin-HealthProfessional/#en40 

Adults who are not found or established to be deficient in Vitamin B2 are normally required 1.3 mg for men, 1.1 mg for women and 1.4 mg for pregnant women of Vitamin B2 per day.

Reference Atsauce: https://ods.od.nih.gov/factsheets/Riboflavin-HealthProfessional/#en12

When supplementing with riboflavin, appropriate amount is five to ten times the daily recommended allowance (1.3 mg for men, 1.1 mg for women and 1.4 mg during pregnancy). No toxic or adverse effects from intake of high riboflavin doses by humans have been reported so far. However, it can be suggested that a high dose of riboflavin could cause an imbalance in the antioxidant state of human body. However, there is no strong evidence in this area, calling for further investigations to clarify the possible adverse effects of high riboflavin intake. 1 Reference: https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/riboflavin-vitamin-b2-and-oxidative-stress-a-review/808987B9D15917EC23885EDFF5E17534

Allergic reaction to this vitamin is rare. However, seek medical help right away if you notice any symptoms of a serious allergic reaction, including rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, troubled breathing. However, this is not a complete list of possible side effects.

Migraine headache usually presents as intense pulsating or stabbing pain in one area of head. Sometimes it is accompanied by aura (transient focal neurological symptoms before or during headache). In case of some types of migraine there is an established causality of mitochondrial dysfunction. Since riboflavin is required for mitochondria to function, researchers are looking at riboflavin as a possible remedy for preventing or treating migraine headache. 1 Reference: Di Lorenzo, C., Pierelli, F., Coppola, G., Grieco, G. S., Rengo, C., Ciccolella, M., … Schoenen, J. (2009). Mitochondrial DNA haplogroups influence the therapeutic response to riboflavin in migraineurs. Neurology, 72(18), 1588–1594. doi:10.1212/wnl.0b013e3181a41269

Several studies have been carried out involving riboflavin as migraine prevention or treatment agent. Some of these studies chose large doses of riboflavin – 400mg and more per day, yet several research have shown that large daily doses of riboflavin are not necessary. Improvements can be seen from as large daily dose as 25mg when administered for 3 months. 2 Reference: Maizels, M., Blumenfeld, A., & Burchette, R. (2004). A Combination of Riboflavin, Magnesium, and Feverfew for Migraine Prophylaxis: A Randomized Trial. Headache: The Journal of Head and Face Pain, 44(9), 885–890. doi:10.1111/j.1526-4610.2004.04170.x

Research in general shows that administering of B2 vitamin for adults may have positive effect on reducing frequency and duration of migraine episodes without serious side effects. Conclusion: riboflavin seems to be safe and well tolerated solution for migraine symptom prevention in adults. 3 Reference: Nazli Namazi, Javad Heshmati, Ali Tarighat-Esfanjani; Supplementation with Riboflavin (Vitamin B2) for Migraine Prophylaxis in Adults and Children: A Review; 2015;85(1-2):79-87. doi: 10.1024/0300-9831/a000225.

1. Riboflavin is easily destroyed when exposed to light. Milk stored in a glass container and exposed to light loses much of its riboflavin content. Opaque plastic jugs and paper cartons protect the riboflavin in milk. Only small amounts of riboflavin are lost in cooking.
2. Out of all of group B vitamins, Riboflavin is probably the most outspoken. It means that you can physically tell if your body has consumed enough Riboflavin as you will notice extra yellow colour of urine if consumption is intense. It is actually the only vitamin that gives you an actual indication of its functioning inside your body! However, due to Riboflavin being water-soluble, your body flushes it out every day, therefore it must be replenished daily.
3. To make Vitamin B2 for food supplements or to add it to foods, industrial companies grow special yeasts, fungi, or bacteria that synthesize a lot of Riboflavin.
4. Riboflavin is yellow or orange-yellow, so it can be useful as a food coloring. Under a blacklight Riboflavin has ultra-green glow.
5. Weight loss increases your need for riboflavin by 60%. More than 20 minutes of cardio exercise 6 days per week increases your need by nearly 60%, too.

Choline is nutrient similar to the B vitamins. It can be made in the liver. It is also found in foods such as meats, fish, nuts, beans, vegetables, and eggs.

Choline is a source of methyl groups needed for many steps in metabolism. The body needs choline to synthesize phosphatidylcholine and sphingomyelin, two major phospholipids vital for cell membranes. Therefore, all plant and animal cells need choline to preserve their structural integrity.

Choline plays an important part in many processes in the body, including:

1. Cell structure: It is needed to make fats that support the structural integrity of cell membranes.
2. Cell messaging: It is involved in the production of compounds that act as cell messengers.
3. Lipid transport and metabolism: It plays an important role in synthesis of substances that are needed for transporting cholesterol away from the liver. Insufficient levels of choline will cause excessive lipid and cholesterol accumulation in the liver.
4. DNA synthesis: Choline and other vitamins, such as B12 and folate, help with a process that’s important for DNA synthesis. 
5. A healthy nervous system: This nutrient is required to make acetylcholine, an important neurotransmitter. It’s involved in memory, muscle movement, regulating heart rhythm and other vital functions.

Humans can produce choline endogenously in the liver, mostly as phosphatidylcholine, but the amount that the body naturally synthesizes is not sufficient to meet human needs. The most common sources of choline in foods are the fat-soluble phospholipids phosphatidylcholine and sphingomyelin as well as the water-soluble compounds phosphocholine, glycerolphosphocholine, and free choline. When these choline-containing compounds are ingested, pancreatic and mucosal enzymes liberate free choline from about half of the fat-soluble forms and some water-soluble forms.

Citicoline is made up of two molecules: cytidine and choline. There is a view that citicoline multiplies a chemical vital for the brain – phosphatidylcholine. This chemical is important for brain functioning. Citicoline may also increase the amount of other chemicals that ensure communication within the brain.

Citicoline and its hydrolysis products (cytidine and choline) play an important role in phospholipid formation that are involved in building and restoring cellular membranes. It drives also important metabolic functions like nucleic acid protein and acetylcholine formation, where acetylcholine contributes to slowing down heart rate, dilation of peripheral blood vessels and lowering of arterial blood pressure, constriction of bronchi, increasing of peristalsis and secretory activity of the gastrointestinal tract. Acetylcholine contributes to memory improvement and counteracts adrenaline. 1 References: Weiss, G. B. (1995). Metabolism and actions of cdpcholine as an endogenous compound and administered exogenously as citicoline. Life Sciences, 56(9), 637–660. doi:10.1016/0024-3205(94)00427-t

Choline deficiency can cause muscle damage, liver damage, and nonalcoholic fatty liver disease (NAFLD or hepatosteatosis). Choline deficiency in healthy, nonpregnant individuals is very rare, possibly because of the contribution of choline that the body synthesizes endogenously. 1 Reference:https://ods.od.nih.gov/factsheets/Choline-HealthProfessional/

Although some people believe that vegetarians and vegans may be at risk of choline deficiencies, there is only mixed evidence to support this.

In fact, some of the foods with the highest choline content include soybeans, potatoes, and mushrooms. Eating a nutritious diet that focuses on whole foods should be enough to prevent deficiency. 2 Reference:https://www.medicalnewstoday.com/articles/327117#deficiency

Adults who are not found or established to be deficient in choline are normally required required 550 mg for men, 425 mg for women of choline per day.

Reference Atsauce: https://ods.od.nih.gov/factsheets/Choline-Health%20Professional/

Choline is not known to have any clinically relevant interactions with medications.   1 Reference:https://ods.od.nih.gov/factsheets/Choline-HealthProfessional/

Stroke is a devastating neurological disorder and third most common cause of death. Usually stroke causes severe disability, high stroke recurrence risk and other unwanted outcomes. Lack or reduction of blood supply after the ischemic stroke causes internal deviation in functions of organs and systems that lead to damage of the nerve cells.

Underlying causes of neuron death both during ageing and progressing loss of neuron structure and functions both acute and chronic are one and the same. These are excessive accumulation of calcium ions and free radicals in the cell, oxidative stress (it appears if too many free radicals are created in the body that harm health and gradually speed up ageing), mitochondrial dysfunction and metabolic disorders that cause acidosis (acidosis reduces the contractility of heart muscle, causes vessel spasms, deteriorates oxygen supply to tissue. Acidosis also leads to breathing rhythm and consciousness disorders, deteriorates blood supply to the brain and kidneys). As a result, cellular signalling mechanisms that include interaction of thousands of diverse molecules through regulating processes from the membrane to the nucleus and back, are completely inhibited. Meanwhile, a cell that died can neither receive nor transmit nor store information, hence human cognitive (mental) functions undergo neurologic deficit.

Cytidine-5′-diphosphocholine (citicoline or CDP-choline), an intermediate in the biosynthesis of phosphatidylcholine, has shown beneficial effects in a number of CNS injury models including cerebral ischemia. Citicoline is composed of two molecules: cytidine and choline. Cytidine and choline separately pass through the BBB, enter brain cells, and act as substrates for intracellular synthesis of CDP-choline.

Citicoline may:

• decrease release of free fatty acids (excessive amounts of free fatty acids reduce insulin sensitivity or cause insulin resistance in tissue (in liver, heart, muscles and adipose tissue));
• restore mitochondrial adenosine triphosphate (ATF) (a nucleotide with very large impact on metabolism of living organisms and universal energy source for biochemical processes taking place in organisms);
• can be efficiently used in the brain cells for membrane lipid synthesis, where not only it increases phospholipid synthesis but also inhibits degradation of phospholipids;
• reduce or prevent impact of ischemia and/or hypoxia;
• reduce and restrict damage of neuron membranes, restore sensitivity and function of intracellular regulation enzymes and limit oedema;
• promote improvement of concentration, learning and memory performance. 1  Reference 1: Gareri, P., Cotroneo, A. M., Castagna, A., Putignano, S., Lacava, R., Monteleone, F., … Fanto, F. (2013). Effectiveness and safety of citicoline in mild vascular cognitive impairment: the IDEALE study. Clinical Interventions in Aging, 131. doi:10.2147/cia.s38420 2 Reference 2: Kay Jorgenson D'Orlando & Bobby W. Sandage Jr. (1995) Citicoline (CDPCholine): Mechanisms of action and effects in ischemic brain injury, Neurological Research, 17:4, 281-284, DOI: 10.1080/01616412.1995.11740327; http://dx.doi.org/10.1080/01616412.1995.11740327

Not only citicoline promotes synthesis of nucleic acid, protein, acetylcholine and other neurotransmitters (biologically active substances that are synthesized in a neuron and is discharged in a synapse; it binds to receptors of other cell and transmits nerve impulse from the synapse to cell), but also reduces formation of free radicals, confirming a view that citicoline at the same time inhibits various steps of ischemic cascades by safeguarding the injured tissues from early or delayed mechanisms that are related to ischemic brain damage. It must be mentioned that citicoline may promote recovery by contributing to synaptic growth and increase neuroplasticity, at the same time reducing neurological deficit and improving behaviour, ability to learn and memory function. 3 Reference 3: Akhlaq A. Farooqui, in Ischemic and Traumatic Brain and Spinal Cord Injuries, 2018; Potential Neuroprotective Strategies for Ischemic Injuries 

1. Not all choline sources are made equally and as much as 50% of the choline we eat may be degraded by bacteria in the gut.
2. Choline is not strictly a vitamin, but is an essential dietary amine. It is, however, known in the literature as vitamin B4.
3. Choline hydroxide is known as choline base. It is hygroscopic and thus often encountered as a colorless viscous hydrated syrup that smells of trimethylamine (TMA). Aqueous solutions of choline are stable, but the compound slowly breaks down to ethylene glycol, polyethylene glycols, and TMA
4. In 1849, Adolph Strecker was the first to isolate choline from pig bile. In 1852, L. Babo and M. Hirschbrunn extracted choline from white mustard seeds and named it sinkaline. In 1862, Strecker repeated his experiment with pig and ox bile, calling the substance choline for the first time after the Greek word for bile, chole, and identifying it with the chemical formula C5H13NO. In 1850, Theodore Nicolas Gobley extracted from the brains and roe of carps a substance he named lecithin after the Greek word for egg yolk, lekithos, showing in 1874 that it was a mixture of phosphatidylcholines.
5. In the early 1930s, Charles Best and colleagues noted that fatty liver in rats on a special diet and diabetic dogs could be prevented by feeding them lecithin, proving in 1932 that choline in lecithin was solely responsible for this preventive effect.

Gotu Kola is a perennial plant native to India, Japan, China, Indonesia, South Africa, Sri Lanka, and the South Pacific. A member of the Apiaceae or carrot family, it has no taste or smell. It is also called pennywort, marsh penny, water pennywort, and sheep rot.

It thrives in and around water. It has small fan-shaped green leaves with white or light purple-to-pink flowers, and small oval fruit. The leaves and stems of the Gotu Kola plant are used as medicine. It can grow like a weed, but its description depends on its location. For example, in shallow water, the leaves float; but in dry areas, the plant develops many roots and thin, tiny leaves. The fan-shaped leaves may be smooth or lobed. Red flowers turn into fruit with a diameter of about 5 mm.

Gotu Kola's main active components are triterpenoids, although the Gotu Kola found in India, Sri Lanka, and Madagascar doesn't have the same properties. Gotu Kola's triterpenes can have a concentration from 1.1-8%, with most concentrations in the middle range.

The plant enhances brain and peripheral circulation, and is said to enhance memory. In the 1880s, the French began using Gotu Kola as part of regular pharmaceutical medicines. 1 References: https://www.mountsinai.org/health-library/herb/gotu-kola https://www.encyclopedia.com/medicine/encyclopedias-almanacs-transcripts-and-maps/gotu-kola

Gotu Kola is typically safe to consume. However, some reported side effects of the herb include: drowsiness, nausea, headaches, dizziness, diarrhea, skin irritation.

Although there is limited research on Gotu Kola’s effect on other medications, it’s possible that it can interfere with prescription or over-the-counter medications. Always consult your doctor before using Gotu Kola.  1 Reference:https://www.webmd.com/diet/health-benefits-gotu-kola#2

Stroke can cause cognitive decline. The frequency of cognitive impairment after an ischemic stroke ranges from 20 to 30%, with an increasing risk in the two years after stroke. In their research, Ballard et al. found that 25% of patients suffered from poststroke dementia, and the risk of poststroke patients developing dementia within the following five years is nine times higher than in the healthy population, especially for cognitive domains such as memory and attention. Management of cognitive impairment following cerebrovascular disease should be aimed at the prevention of secondary strokes and specific treatment for the improvement of cognitive function. Secondary stroke prevention includes control of risk factors such as blood pressure, cholesterol levels, and hyperhomocysteinemia.

One medicinal herb commonly used is Gotu Kola (Centella asiatica). The main group of components in Gotu Kola is the triterpenes including asiaticoside, madecassoside, asiatic acid, and madecassic acid, which have antioxidant, anti-inflammatory, and antiapoptotic properties. This may explain why Gotu Kola has a positive influence on brain plasticity, as well as in increasing the length of dendrites and an enhancement of hippocampal CA3 neuronal dendritic arborization in mice inflicted with neurodegenerative diseases and memory disorders.

Study aimed to determine the improvement of cognitive function in patients with vascular cognitive impairment utilizing the Montreal Cognitive Assessment-Indonesian version (MoCA-Ina) after an intake of Gotu Kola (Centella asiatica) 750 mg/day and 1000 mg/day and of folic acid 3 mg/day for 6 weeks. 1 Reference: Kun Marisa Farhana, Rusdy Ghazali Malueka, Samekto Wibowo, and Abdul Gofir; Effectiveness of Gotu Kola Extract 750 mg and 1000 mg Compared with Folic Acid 3 mg in Improving Vascular Cognitive Impairment after Stroke;  Published online 2016 Jun 1. doi: 10.1155/2016/2795915 PMCID: PMC4908235

1. Historically, Gotu Kola has also been used to treat syphilis, hepatitis, stomach ulcers, mental fatigue, epilepsy, diarrhea, fever, and asthma.
2. The name sheep rot comes from the erroneous belief in Europe that Gotu Kola caused foot rot in sheep.
3. Gotu Kola is noted in India as a very powerful spiritual herb, and Ayurvedic medicine refers to it as Brahmi because it helps obtain knowledge of the spiritual being.
4. Chinese herbalist, Li Ching Yun, is supposed to have lived 256 years from drinking a herbal mixture containing Gotu Kola. An ancient Sinhalese saying, "Two leaves a day will keep old age away," also illustrates Gotu Kola's popularity as an agent for longevity.

Vitamin B9, also called folate or folic acid, is one of 8 B vitamins. All B vitamins help the body convert food (carbohydrates) into fuel (glucose), which is used to produce energy. These B vitamins, often referred to as B-complex vitamins, also help the body use fats and protein. B-complex vitamins are needed for a healthy liver, and healthy skin, hair, and eyes. They also help the nervous system function properly. Folic acid is the synthetic form of B9, found in supplements and fortified foods, while folate occurs naturally in foods. 

All the B vitamins are water-soluble, meaning the body does not store them except for B12 which is stored in liver and used whenever required. Folic acid is crucial for proper brain function and plays an important role in mental and emotional health. It aids in the production of DNA and RNA, the body's genetic material, and is especially important when cells and tissues are growing rapidly, such as in infancy, adolescence, and pregnancy.

One of the most important folate-dependent reactions is the conversion of homocysteine to methionine in the synthesis of S-adenosyl-methionine, an important methyl donor. Another folate-dependent reaction, the methylation of deoxyuridylate to thymidylate in the formation of DNA, is required for proper cell division. An impairment of this reaction initiates a process that can lead to megaloblastic anemia, one of the hallmarks of folate deficiency. 1 References: https://www.mountsinai.org/health-library/supplement/vitamin-b9-folic-acid https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/  

Isolated folate deficiency is uncommon; folate deficiency usually coexists with other nutrient deficiencies because of its strong association with poor diet, alcoholism, and malabsorptive disorders. Megaloblastic anemia, which is characterized by large, abnormally nucleated erythrocytes, is the primary clinical sign of folate or vitamin B12 deficiency. Its symptoms include weakness, fatigue, difficulty concentrating, irritability, headache, heart palpitations, and shortness of breath.

Folate deficiency can also produce soreness in and shallow ulcerations on the tongue and oral mucosa; changes in skin, hair, or fingernail pigmentation; gastrointestinal symptoms; and elevated blood concentrations of homocysteine.

Folate deficiency is rare, but some individuals might have marginal folate status. People with alcohol use disorder frequently have poor-quality diets that contain insufficient amounts of folate. Moreover, alcohol interferes with folate absorption and hepatic uptake, accelerates folate breakdown, and increases its renal excretion

Adults who are not found or established to be deficient in Vitamin B9 are normally required 400 mg (600 mg for pregnant women) of Vitamin B9 per day.

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

Folate supplements can interact with several medications. A few examples are provided below. Individuals taking these medications on a regular basis should discuss their folate intakes with their healthcare providers.

Methotrexate

Methotrexate (Rheumatrex®, Trexall®), used to treat cancer and autoimmune diseases, is a folate antagonist. Patients taking methotrexate for cancer should consult their oncologist before taking folate supplements because the supplements could interfere with methotrexate’s anticancer effects. However, folate supplements might reduce the gastrointestinal side effects of low-dose methotrexate taken for rheumatoid arthritis or psoriasis.

Antiepileptic medications

Antiepileptic medications, such as phenytoin (Dilantin®), carbamazepine (Carbatrol®, Equetro®, Epitol®), and valproate (Depacon®), are used to treat epilepsy, psychiatric diseases, and other medical conditions. These medications can reduce serum folate levels. Furthermore, folate supplements might reduce serum levels of these medications, so patients taking antiepileptic drugs should check with their healthcare provider before taking folate supplements.

Sulfasalazine

Sulfasalazine (Azulfidine®) is used primarily to treat ulcerative colitis. It inhibits the intestinal absorption of folate and can cause folate deficiency. Patients taking sulfasalazine should ask their healthcare provider whether they should increase their dietary folate intake, start taking a folate supplement, or both. 1 Reference:https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/

An elevated homocysteine level has been associated with an increased risk of cardiovascular disease. Folate and other B vitamins are involved in homocysteine metabolism, and researchers have hypothesized that these micronutrients reduce cardiovascular disease risk by lowering homocysteine levels.

Folic acid (and vitamin B12) supplements lower homocysteine levels. However, these supplements do not actually decrease the risk of cardiovascular disease, although they appear to provide protection from stroke. 1 Reference: Xiaobin Wang, Xianhui Qin, Hakan Demirtas, Jianping Li, Guangyun Mao, Yong Huo, Ningling Sun, Lisheng Liu, Xiping Xu (2007). Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. The Lancet, 369(9576), 1876–1882. doi:10.1016/s0140-6736(07)60854-x; https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/

1. Folate and its role in human biochemical functioning was first identified by researcher Lucy Wills in 1931. She found that the nutrient was needed to prevent anemia during pregnancy.
2. Folic acid is so important to human health, it is included in many types of foods, especially breakfast cereal. The process to add a vitamin to other foods is called fortification. So, a cereal that has added vitamins is called fortified.
3. Folic acid is named from a latin word (folium) which means leaf. This comes from the fact that leafy vegetables are very rich in folic acid.
4. Lack of folic acid can also cause a decrease in the amount of red blood cells in the body. This condition is called anemia. The type of anemia caused by folic acid deficiency is called a macrocytic anemia. Macrocytic means "large cells." So, lack of folic acid causes low levels of red blood cells, and the individual red blood cells are really large.
5. Folic acid is actually better absorbed by the body than natural folate, almost twice as efficiently.

Selenium was discovered in 1817 in Gripsholm, a Swedish city, by a Swedish chemist Jacob Berzelius. Selenium is a commonly occurring element in nature. It can be found in the atmosphere, lithosphere, biosphere, and hydrosphere of the Earth. The amount of this element present in nature and in the human organism is very diverse depending on the geographic region and diet.

The total amount of selenium in a human organism is ~3–20 mg.

Selenium is a trace element that is naturally present in many foods, added to others, and available as a dietary supplement. Selenium, which is nutritionally essential for humans, is a constituent of more than two dozen selenoproteins that play critical roles in reproduction, thyroid hormone metabolism, DNA synthesis, and protection from oxidative damage and infection.

Selenium is incorporated into selenoproteins that have a wide range of pleiotropic effects, ranging from anti oxidant and anti-inflammatory effects to the production of active thyroid hormone. In the past 10 years, the discovery of disease associated polymorphisms in seleno protein genes has drawn attention to the relevance of selenoproteins to health. The essential biological importance of selenium is associated with its occurrence in proteins and enzymes. Several selenium-dependent enzymes in which the active center contains selenium in the form of selenocysteine moiety have been identified. The best-characterized selenoenzymes commonly occurring in mammals are glutathione peroxidase, selenoprotein P, and thyroxine 5-deiodinase. Glutathione peroxidase and selenoprotein P catalyze redox reactions. Other enzymatic proteins that are involved in important functions of the organisms are formate dehydrogenase, nicotinic acid hydroxylase, glycine reductase, thiolase, and xanthine dehydrogenase.

Low selenium status has been associated with increased risk of mortality, poor immune function, and cognitive decline.

Higher selenium status or selenium supplementation has antiviral effects, is essential for successful male and female reproduction, and reduces the risk of autoimmune thyroid disease. Prospective studies have generally shown some benefit of higher selenium status on the risk of prostate, lung, colorectal, and bladder cancers, but findings from trials have been mixed, which probably emphasises the fact that supplementation will confer benefit only if intake of a nutrient is inadequate.

The eff ects of selenium on human health are multiple and complex, necessitating further research to optimize the benefits and reduce the risks of this potent trace mineral. 1, Reference: Marek Kieliszek; Selenium–Fascinating Microelement, Properties and Sources in Food; Molecules. 2019 Apr; 24(7): 1298. Published online 2019 Apr 3. doi: 10.3390/molecules24071298 2, Reference: Sunde RA. Selenium. In: Ross AC, Caballero B, Cousins RJ, Tucker KL, Ziegler TR, eds. Modern Nutrition in Health and Disease. 11th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2012:225-37 3 Reference: Rayman, M. P. (2012). Selenium and human health. The Lancet, 379(9822), 1256–1268. doi:10.1016/s0140-6736(11)61452-9

Prolonged selenium deficiency in human organism leads to serious diseases. Deficiency of this element adversely affects the functioning of the cardiovascular system and can be a direct cause of myocardial infarction. It is associated with endemic diseases: Keshan and Kashin-Beck.

As a result of epidemiological studies, it was concluded that moderate deficiency of selenium in daily diet affects the development of diseases resulting from reduced immunity. Selenium deficiency in daily diet can adversely affect the functioning of the nervous system. Among individuals with selenium deficiency, development of depression, or intensification of anxiety is observed; Alzheimer’s disease is also developed. This element is considered to be crucial in reducing the virulence of HIV and in decreasing the progression to full-blown AIDS. Selenium deficiency in pregnant women negatively affects the development of the embryo. Excess of selenium can be toxic to the organism. Acute selenium poisoning is rarely observed. The accurate determination of harmful doses of selenium is difficult because of the occurrence of various chemical forms of this element. A toxic effect on the organism can be exerted by both organic and inorganic forms of selenium. Toxicity of selenium (depends on the dose) is associated with competitive inhibition between selenium and sulfur, leading to the onset of sulfur metabolism (transformation). Selenium may substitute sulfur in amino acids (cysteine and methionine), whereas the inorganic compounds displace sulfur during the synthesis of mercapturic acids and during the reaction of selenites with thiol groups. 2 Reference: Marek Kieliszek; Selenium–Fascinating Microelement, Properties and Sources in Food; Molecules. 2019 Apr; 24(7): 1298. Published online 2019 Apr 3. doi: 10.3390/molecules24071298 

Groups at Risk of Selenium Inadequacy

Selenium deficiency is rare and selenium deficiency in isolation rarely causes overt illness. The following groups are among those most likely to have inadequate intakes of selenium.

1. People living in selenium-deficient regions

People in some countries whose diet consists primarily of vegetables grown in low-selenium areas are at risk of deficiency. The lowest selenium intakes in the world are in certain parts of China, where large proportions of the population have a primarily vegetarian diet and soil selenium levels are very low. Average selenium intakes are also low in some European countries, especially among populations consuming vegan diets. Although intakes in New Zealand were low in the past, they rose after the country increased its importation of high-selenium wheat.

2. People undergoing kidney dialysis

Selenium levels are significantly lower in patients undergoing long-term hemodialysis than in healthy individuals. Hemodialysis removes some selenium from the blood. In addition, hemodialysis patients are at risk of low dietary selenium intakes due to anorexia resulting from uremia and dietary restrictions. Although selenium supplementation increases blood levels in hemodialysis patients, more evidence is needed to determine whether supplements have beneficial clinical effects in these individuals.

3. People living with HIV

Selenium levels are often low in people living with HIV, possibly because of inadequate intakes (especially in developing countries), excessive losses due to diarrhea, and malabsorption. Observational studies have found an association between lower selenium concentrations in people with HIV and an increased risk of cardiomyopathy, death, and, in pregnant women, HIV transmission to offspring and early death of offspring. 3 Reference:https://ods.od.nih.gov/factsheets/Selenium-HealthProfessional/

Selenium in the diet. Adults who are not found or established to be deficient in selenium are normally required 55 mcg (micrograms) for men and for women, but for pregnant women 60 mcg of selenium per day

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

Selenium can interact with certain medications, and some medications can have an adverse effect on selenium levels. One example is provided below. Individuals taking this and other medications on a regular basis should discuss their selenium status with their healthcare providers.

Cisplatin

Cisplatin, an inorganic platinum chemotherapy agent, is used to treat ovarian, bladder, lung, and other cancers. Cisplatin can reduce selenium levels in hair and serum but whether these reductions have a clinically significant impact is not known. Some small studies have shown that selenium supplementation can reduce cisplatin’s toxicity but the authors of a Cochrane review concluded that the evidence that selenium supplementation alleviates the side effects of chemotherapy is insufficient.

Health Risks from Excessive Selenium

Chronically high intakes of the organic and inorganic forms of selenium have similar effects. Early indicators of excess intake are a garlic odor in the breath and a metallic taste in the mouth. The most common clinical signs of chronically high selenium intakes, or selenosis, are hair and nail loss or brittleness. Other symptoms include lesions of the skin and nervous system, nausea, diarrhea, skin rashes, mottled teeth, fatigue, irritability, and nervous system abnormalities. 1 Reference:https://ods.od.nih.gov/factsheets/Selenium-HealthProfessional/

There are a number of indications that selenium is important to the brain: during selenium depletion the brain receives a priority supply; the turnover rate of some neurotransmitters is altered in selenium deficiency; supplementation with selenium reduced intractable epileptic seizures in children; low plasma selenium concentrations in the elderly were significantly associated with senility and accelerated cognitive decline and brain selenium concentration in Alzheimer’s patients was only 60% of that in controls. Furthermore, the brain is deficient in catalase, thus peroxidation products such as hydrogen peroxide and primary peroxides must be removed by the antioxidant selenoenzymes.

A beneficial effect of selenium status on mood has been shown, at least when selenium status is “marginal”. In three studies, low selenium status was associated with a significantly greater incidence of depression and other negative mood states such as anxiety, confusion, and hostility.

Serum selenium concentrations decline with age. Marginal or deficient selenium concentrations might be associated with age-related declines in brain function, possibly due to decreases in selenium’s antioxidant activity.

Selenium, incorporated into specific seleno-enzymes, is essential to proper thyroid function and protect cells from oxidative damage induced by H2O2 during thyroid hormone synthesis while study has shown that oxidative stress markers are associated with cognitive decline in a highly cognitive functioning population. 

Selenium-dependent glutathione reductase and selenoproteins are important for their antioxidant activity, which is vital for the protection of the organism. Selenium affects the metabolic pathways by changing the activity of selenoproteins and plays a role in cellular defense against oxidative stress. Selenium concentration regulates the expression of selenoproteins. Different selenium concentrations may affect immunity and energy metabolism diversely. Increased levels of stress biomarkers have been reported in depression in recent studies, and this suggests that oxidative stress may be an important factor in the pathogenesis of depression. Selenium may have a protective role against anxiety and depression, possibly due to its protective effect on oxidative stress.

Lastly, selenium could potentially exert antidepressant effects through its modulatory role in various neurotransmitter systems. Selenium has been found to have significant modulatory effects on the dopaminergic, serotonergic, and noradrenergic systems, which are all involved in the physiopathology of depression and other psychiatric illnesses.

References: 1 Reference: Rayman, M. P. (2000). The importance of selenium to human health. The Lancet, 356(9225), 233–241. doi:10.1016/s0140-6736(00)02490-9 2 Reference: Berr, C., Balansard, B., Arnaud, J., Roussel, A.-M., & Alpérovitch, A. (2000). Cognitive Decline Is Associated with Systemic Oxidative Stress: The EVA Study. Journal of the American Geriatrics Society, 48(10), 1285–1291. doi:10.1111/j.1532-5415.2000.tb02603.x 3 Reference: Ruggeri, R. M., D’Ascola, A., Vicchio, T. M., Campo, S., Gianì, F., Giovinazzo, S., … Trimarchi, F. (2019). Selenium exerts protective effects against oxidative stress and cell damage in human thyrocytes and fibroblasts. Endocrine. doi:10.1007/s12020-019-02171-w 4 Reference: Elif Turan and Ozgul Karaaslan; The Relationship between Iodine and Selenium Levels with Anxiety and Depression in Patients with Euthyroid Nodular Goiter; Oman Med J. 2020 Jul; 35(4): e161. Published online 2020 Jul 31. doi: 10.5001/omj.2020.84 5 Reference: Wang, J., Um, P., Dickerman, B., & Liu, J. (2018). Zinc, Magnesium, Selenium and Depression: A Review of the Evidence, Potential Mechanisms and Implications. Nutrients, 10(5), 584. doi:10.3390/nu10050584

Selenium, an essential trace element for humans, has a direct effect on thyroid hormone metabolism and oxidation-reduction processes. The functioning of the thyroid gland is critically dependent on iodine and selenium, in order to ensure that it functions properly. An insufficient amount of selenium in the body is associated with an increased risk of thyroid disease.1

Selenium can be considered the key to the health of the thyroid gland. It is a necessary trace element for the synthesis and functioning of thyroid hormones. The concentration of selenium in the thyroid gland is higher than in any other organ in the body. Selenium works with iodine to activate three different selenium-dependent iodothyronine deiodinases, which can then activate or deactivate thyroid hormones. All three isoforms of deiodinases are selenium-containing enzymes, so dietary or supplemental selenium is essential for triiodothyronine (T3) production. This process (and selenium) is essential for normal growth, development and metabolism.2

Selenium deficiency is associated with hypothyroidism, Hashimoto's disease, an enlarged thyroid gland, thyroid cancer, and Graves' disease.

One study of 1,900 participants found a relationship between serum selenium concentrations and the size of the thyroid gland. A protective effect of selenium against enlarged thyroid gland and thyroid tissue damage was observed. In this particular study, these results were only significant for female participants.3

Another study looked at the effect of selenium on Graves' orbitopathy (when the thyroid gland produces too much thyroid hormone). The researchers compared treatment with selenium to treatment with pentoxifylline (Pentilin), an anti-inflammatory drug. The selenium treatment group reported improved quality of life and slowed the progression of Graves' orbitopathy compared to the pentoxifylline (Pentilin) treatment group.4 1 Atsauce: 1) Wichman, J., Winther, K. H., Bonnema, S. J., & Hegedüs, L. (2016). Selenium Supplementation Significantly Reduces Thyroid Autoantibody Levels in Patients with Chronic Autoimmune Thyroiditis: A Systematic Review and Meta-Analysis. Thyroid, 26(12), 1681–1692. doi:10.1089/thy.2016.0256 2) Triggiani, V., Tafaro, E., Giagulli, V., Sabba, C., Resta, F., Licchelli, B., & Guastamacchia, E. (2009). Role of Iodine, Selenium and Other Micronutrients in Thyroid Function and Disorders. Endocrine, Metabolic & Immune Disorders - Drug Targets, 9(3), 277–294. doi:10.2174/187153009789044392 3) Derumeaux, H., Valeix, P., Castetbon, K., Bensimon, M., Boutron-Ruault, M., Arnaud, J., & Hercberg, S. (2003). Association of selenium with thyroid volume and echostructure in 35- to 60-year-old French adults. European Journal of Endocrinology, 148(3), 309–315. doi:10.1530/eje.0.1480309 4) Marcocci, C., Kahaly, G. J., Krassas, G. E., Bartalena, L., Prummel, M., Stahl, M., … Wiersinga, W. (2011). Selenium and the Course of Mild Graves’ Orbitopathy. New England Journal of Medicine, 364(20), 1920–1931. doi:10.1056/nejmoa1012985

1. For a long time, selenium was considered a toxic element. Poisoning with this element led to the development of severe anemia, bone stiffness, hair loss, and blindness. These symptoms have been observed in humans and animals in areas where the content of this element in the soil was ~1000 times greater in comparison with soils with an average amount of selenium in the other regions of the world.
2. Selenium gets its name from the Greek word "selene," which means "moon." Selene was the Greek goddess of the moon.
3. Selenium is a nonmetal. Like many nonmetals, it exhibits different colors and structures (allotropes) depending on the conditions.
4. Brazil nuts are high in selenium, even if they are grown in soil that is not rich in the element. A single nut provides enough selenium to meet the daily requirement for a human adult.
5. The primary use of selenium is to decolorize glass, to color glass red, and to make the pigment China Red. Other uses are in photocells, in laser printers and photocopiers, in steels, in semiconductors, and in assorted medicinal preparations.
6. Selenium is protective against mercury poisoning.

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.

Gamma-Aminobutyric acid (GABA), discovered in 1950, is an amino acid produced naturally in the brain. GABA functions as a neurotransmitter, facilitating communication among brain cells. GABA’s big role in the body is to reduce the activity of neurons in the brain and central nervous system (CNS), which in turn has a broad range of effects on the body and mind, including increased relaxation, reduced stress, a more calm, balanced mood, alleviation of pain, and a boost to sleep.

Amino acid neurotransmitters are critical for the function of the CNS; they have fast actions, producing responses within few milliseconds playing an important role in brain functions and neurological diseases. 

Under stress conditions certain metabolites, like GABA, are depleted, therefore, additional nutrients are required to replace these metabolites. As the quantities of nutrition vary from one individual to another and the difficulties to obtain these nutrients from food so a better alternative is to consume the required additional nutrients as enriched functional food and/or food supplements.

GABA is synthesised in tissues from glutamic acid via the enzyme glutamic acid decarboxylase (GAD), with pyridoxal-5-phosphate (P5P) acting as a cofactor.

Outside of the CNS, GABA is synthesised by the colonic microflora. As the major inhibitory neurotransmitter, GABA counteracts over excitation in the brain, and has been described as acting like a ‘brake’ on the neuronal circuitry during times of increased stress. Following its release from GABAergic nerve terminals, it acts on both GABA-A and GABA-B receptors, with a net inhibitory effect.

The GABA-A receptors regulate brain excitability and are responsible for GABA’s immediate synaptic inhibitory effects. As low GABA levels are associated with anxiety, depression, insomnia and epilepsy, medications that target these GABA receptors have been developed. There are many pharmaceutical medications, alcohol and psychoactive drugs that produce their anxiolytic, analgesic, anticonvulsant, and sedative effects by modulating GABA-A receptor activity or by blocking the reuptake of GABA by GABA transporter (GAT) proteins.

In addition to its effect on the brain, high doses of GABA (5-10g single dose) have been shown to exert effects on the endocrine system, including increases in plasma growth hormone levels, although the clinical significance of these effects is currently unknown. 1 References: Abdou, A. M., Higashiguchi, S., Horie, K., Kim, M., Hatta, H., & Yokogoshi, H. (2006). Relaxation and immunity enhancement effects of γ-Aminobutyric acid (GABA) administration in humans. BioFactors, 26(3), 201–208. doi:10.1002/biof.5520260305 2 Reference: GABA. Natural Medicines monograph 2014. Viewed 10 Oct 2015, https://naturalmedicines.therapeuticresearch.com/

GABA is likely safe when taken in the amounts commonly found in foods. It is possibly safe when taken in larger amounts as medicine. Doses of up to 1.5 grams daily have been used for up to one month. 

1. Not recommended during pregnancy or lactation.
2. GABA may decrease blood pressure in hypertensive individuals. If you take GABA in addition to taking blood pressure medication, your blood pressure may drop too low.
3. Use with caution in patients taking synthetic GABA agonist medications or herbs that interact with the GABAergic system (e.g. Valeriana officinalis, Hypericum perforatum). If additional sedative/relaxant effects are required, start GABA supplementation slowly and at a low dose.

GABA agonist medications: Baclofen, Zolpidem, Progabide, AZD 3355, Tramiprosate, Gaboxadol, Adipiplon, Arbaclofen Placarbil, Lesogaberan, Muscimol, Phenibut, Zaleplon u.c.

1. Unlike synthetic GABA-agonist drugs, natural GABA is virtually without side effects.

Possible side effects

GABA oral supplements are generally well tolerated by healthy adults. Some people may experience negative side effects, including:

• Gastric distress.
• Nausea.
• Diminished appetite.
• Constipation.
• Burning throat.
• Drowsiness and fatigue.
• Muscle weakness.
• Shortness of breath, at very high doses.

References 1 Reference:https://www.webmd.com/vitamins/ai/ingredientmono-464/gamma-aminobutyric-acid-gaba 2 Reference:https://go.drugbank.com/categories/DBCAT000427 3 Reference:https://www.fxmedicine.com.au/blog-post/gamma-aminobutyric-acid-gaba-monograph

GABA (Gamma-Aminobutyric acid) Deficiency

People with certain medical conditions may have lower levels of GABA. Some of these conditions include:

• Seizure disorders
• Anxiety
• Chronic stress
• Depression
• Difficulty concentrating and memory problems
• Muscle pain and headaches
• Insomnia and other sleep problems
• Low GABA activity is also associated with substance use disorders.

Some people with these conditions take GABA supplements to help manage their symptoms, but GABA is found naturally in varieties of green, black, and oolong tea, as well as in fermented foods including kefir, yogurt, and tempeh. Other foods contain GABA or may boost its production in the body, including whole grains, fava beans, soy, lentils, and other beans; nuts including walnuts, almonds, and sunflower seeds; fish including shrimp and halibut; citrus, tomatoes, berries, spinach, broccoli, potatoes, and cocoa. However, these symptoms have many psychological and physical causes, so you should talk to your doctor before treating them with a supplement. 4 Reference: National Library of Medicine, GABA-transaminase deficiency; https://www.healthline.com/health/gamma-aminobutyric-acid#uses https://www.psychologytoday.com/us/blog/sleep-newzzz/201901/3-amazing-benefits-gaba

More than 300 million people are affected by major depressive disorder (MDD), and limitations in the access to and effectiveness

of MDD treatment have made it the leading cause of disability world-wide. Despite long-standing efforts to identify the pathophysiology of depression, the underlying neurobiological determinants remain largely undefined. The relatively low rate of heritability, approximately 37%, the absence of variants with substantial impact on depression risk, the polygenic nature of depression risk, and the heterogeneity of depression have contributed to the difficulty in identifying genetic determinants of susceptibility. 

Environmental factors, such as trauma and stressful life events, contribute to depression risk through altering brain structure, chemistry, and function. Chronic exposure to social, psychological, or physical stressors provides useful contexts for studying how the brain transduces environmental stress exposure into depression.

The mechanisms underlying the pathophysiology and treatment of depression and stress-related disorders remain unclear, but studies in depressed patients and rodent models are beginning to yield promising insights. These studies demonstrate that depression and chronic stress exposure cause atrophy of neurons in cortical and limbic brain regions implicated in depression, and brain imaging studies demonstrate altered connectivity and network function in the brains of depressed patients. Studies of the neurobiological basis of the these alterations have focused on both the principle, excitatory glutamate neurons, as well as inhibitory GABA interneurons. Dysfunction of the central gamma-aminobutyric system has long been associated with anxiety spectrum disorders. While GABA neurons make up a smaller fraction of the total neuronal population, approximately 15%–20% compared to glutamate, inhibitory neurotransmission and balance with excitatory transmission are critical for normal brain function.

Based on evidence of altered glutamate and functional connectivity, it is not surprising that there is also evidence of disrupted GABA neurotransmission that contributes to the neurobiology of MDD.

Briefly, depression is often associated with decreased GABAergic function, while various antidepressant (AD) manipulations tend to increase it; low GABA function is proposed to be an inherited biological marker of vulnerability for depression; positive modulators of GABA-A receptors can have AD actions, while GABA-A negative modulators often produce depression. There is a large body of evidence to confirm that GABAergic anxiolytic drugs do produce AD effects in patients.

Summarizing, it seems likely that there are overlapping GABAergic mechanisms of anxiety and depression due to: 

1. common neurochemical mechanisms;
2. similar brain structures involved in the regulation of anxiety and depression; 
3. common genetic origins of anxiety and depression; and 
4. overlapping or correlation in neuropsychopharmacological effects of drugs.

Numerous studies have demonstrated a direct correlation between major depressive disorders and significantly decreased GABA concentrations in the brain. This is not to say that GABA deficiency causes depression but that it plays an important role as part of the overall treatment of depression, PMS, ADHD, bipolar disorder, panic, fear, mental blocks, a racing mind and anxiety. Doctors frequently prescribe benzodiazepines for most of these conditions but the major drawback to their use is that they can be addictive. GABA supplementation is not addictive and it is one nutrient that can be used to help facilitate withdrawal from benzodiazepines.

The optimal dose of GABA varies with the need and the individual. The usual anti-anxiety doses for most adults are between 500 and 5000 mg daily in divided doses. 1 Reference: Ronald S. Duman, Gerard Sanacora and John H. Krystal; Department of Psychiatry, Yale University School of Medicine;  Altered Connectivity in Depression: GABA and Glutamate Neurotransmitter Deficit and Reversal by Novel Treatments; DOI:https://doi.org/10.1016/j.neuron.2019.03.013 2 Reference: Kalueff, A. V., & Nutt, D. J. (2007). Role of GABA in anxiety and depression. Depression and Anxiety, 24(7), 495–517. doi:10.1002/da.20262 3 Reference: Dr. Zoltan P. Rona, M.D., M.Sc. Defuse Stress and Calm Nerves Naturally

1. Alcohol is believed to mimic GABA's effect in the brain, binding to GABA receptors and inhibiting neuronal signaling.
2. Alongside GABAergic mechanisms, GABA has also been detected in other peripheral tissues including intestines, stomach, Fallopian tubes, uterus, ovaries, testes, kidneys, urinary bladder, the lungs and liver, albeit at much lower levels than in neurons.
3. In 1883, GABA was first synthesized, and it was first known only as a plant and microbe metabolic product.
4. GABA is also found in plants. It is the most abundant amino acid in the apoplast of tomatoes. Evidence also suggests a role in cell signalling in plants.
5. GABA tea is tea that has undergone a special oxygen-free fermentation process, and as a result has accumulated GABA in tea leaves. This technology has been created in Japan. 

Crocus, genus of about 75 low-growing cormose species of plants of the iris family (Iridaceae). Crocuses are native to the Alps, southern Europe, and the Mediterranean area and are widely grown for their cuplike blooms in early spring or fall. Spring-flowering plants have a long floral tube that allows the ovary to remain belowground, sheltered from climatic changes. The flowers close at night and in dull weather. Saffron, used for dye, seasoning, and medicine, is the dried feathery orange tip of the pistils of the lilac or white, autumn-flowering saffron crocus (Crocus sativus) of western Asia. Saffron crocus generally blooms with purple flowers in the autumn. The plant grows about 10 to 30 cm high.

Saffron is the dried elongated stigmas and styles of the blue-purple saffron crocus. Saffron stigmas contain four major bioactive compounds: crocins (family of six mono-glycosyl or di-glycosyl polyene esters), crocetin (a natural carotenoid dicarboxylic acid precursor of crocin), picrocrocin (monoterpene glycoside precursor of safranal and product of zeaxanthin degradation) and safranal. It appears that crocin and safranal inhibit reuptake of dopamine, norepinephrine, and serotonin. Saffron has the potential to enhance mental health through its antidepressant properties and, in a recent meta-analysis, was confirmed to be effective for the treatment of depression. 1 Atsauce: https://www.britannica.com/plant/Crocus#ref172302 2 Reference: Lopresti, A. L., & Drummond, P. D. (2014). Saffron (Crocus sativus) for depression: a systematic review of clinical studies and examination of underlying antidepressant mechanisms of action. Human Psychopharmacology: Clinical and Experimental, 29(6), 517–527. doi:10.1002/hup.2434   3 Mazidi, M., Shemshian, M., Mousavi, S. H., Norouzy, A., Kermani, T., Moghiman, T., … Ferns, G. A. A. (2016). A double-blind, randomized and placebo-controlled trial of Saffron (Crocus sativus L.) in the treatment of anxiety and depression. Journal of Complementary and Integrative Medicine, 13(2). doi:10.1515/jcim-2015-0043

When taken by mouth: Saffron is likely safe in food amounts and when taken as a medicine for up to 26 weeks. Some possible side effects include dry mouth, anxiety, agitation, drowsiness, low mood, sweating, nausea or vomiting, constipation or diarrhea, change in appetite, flushing, and headache. Allergic reactions can occur in some people.

Taking large amounts of saffron by mouth is possibly unsafe. High doses of 5 grams or more can cause poisoning. Doses of 12-20 grams can cause death.

Pregnancy and breast-feeding: Taking saffron by mouth in amounts larger than what is normally found in food is likely unsafe. Larger amounts of saffron can make the uterus contract and might cause a miscarriage.

There isn't enough reliable information to know if saffron is safe to use when pregnant or breast-feeding. Stay on the safe side and stick to food amounts.

Bipolar disorder: Saffron seems to be able to affect mood. There is a concern that it might trigger excitability and impulsive behavior (mania) in people with bipolar disorder. Don't use saffron if you have this condition.

Allergies to Lolium, Olea (includes olive), and Salsola plant species: People who are allergic to these plants might also be allergic to saffron.

Interactions. When used as a supplement, saffron may cause problems for people on blood pressure medicine or blood thinners. Check with your doctor before using it if you are taking medication. 1 Atsauce: www.webmd.com/vitamins/ai/ingredientmono-844/saffron

Depressive disorder is one of the most prevalent psychiatric diseases and has been estimated to affect up to 21% of the world’s population. Majority of patients are often reluctant to take synthetic antidepressant drugs in their appropriate doses because of the anticipated side effects such as the inability to drive a car, dry mouth, constipation, and libido. Hence, plant extracts are some of the most attractive sources of new drugs and have been shown to produce a better result with low side effects in the treatment of depression. 

The benefits of saffron as an antidepressant are well-documented. Almost 150 volatile and nonvolatile compounds are obtained from the chemical analysis of this plant. Fewer than 50 constituents elucidated and identified so far showed phytochemical characteristics.

Crocin and saffron extract had been revealed to prevent memory and spatial learning impairment because of chronic-induced stress. Prophylactic property of saffron against memory deficiency had been proposed to occur as the result of the correlation between the antioxidant activity of saffron and the impairment because of oxidative stress. Akhondzadeh et al., in 2004, had shown saffron extract to be equally efficient to imipramine during double-blind and randomized trial conducted over 6 weeks. The dried saffron petal also had been revealed to be effective in mild-to-moderate depression based on 6 weeks of double-blind randomized clinical trials. Crocin (30 mg/day), the main antioxidant constituent of saffron stigmas, was shown to amplify the effects of selective serotonin reuptake inhibitors in treating patients with mild-to-moderate depression with the absence of substantial side effects based on the observation of 4 weeks of randomized, double-blind, prospective, placebo-controlled pilot clinical trial with 40 patients of major depressive disorder.

Another study (in this double-blind, placebo-controlled and randomized trial, patients were randomly assigned to receive capsule of petal of C. sativus 30 mg/day (BD) (Group 1) and capsule of placebo (BD) (Group 2) for a 6-week study) showed that patients with mild-to-moderate depression receiving petal of C. sativus experienced statistically significant benefits in their mood after 6 weeks treatment. The clinical relevance of these findings was emphasized by the improvements seen in the Hamilton Depression Rating Scale measures in the saffron group. Moreover, there were no significant differences in the two groups in terms of observed side effects. It has been reported that stigma of C. sativus has antidepressant effect by at least three clinical trials (Akhondzadeh et al., 2004, 2005; Noorbala et al., 2005). 1 Reference: Mohammad J. Siddiqui, Mohammed S. M. Saleh, Siti N. B. Binti Basharuddin, Siti H. Binti Zamri, Mohd H. bin Mohd Najib, Muhammad Z. bin Che Ibrahim, Nur A. binti Mohd Noor, Hanin N. Binti Mazha, Norazian Mohd Hassan, and Alfi Khatib; Saffron (Crocus sativus L.): As an Antidepressant; J Pharm Bioallied Sci. 2018 Oct-Dec; 10(4): 173–180. doi: 10.4103/JPBS.JPBS_83_18 2 Reference: Akhondzadeh S, Fallah-Pour H, Afkham K, Jamshidi AH, Khalighi-Cigaroudi F. Comparison of Crocus sativus L. and imipramine in the treatment of mild to moderate depression: a pilot double-blind randomized trial [ISRCTN45683816] BMC Complement Altern Med. 2004;4:12. 3 Reference: Esmail Moshiria, Afshin Akhondzadeh Bastib, Ahamad-Ali Noorbalac, Amir-Hossein Jamshidid, Seyed Hesameddin Abbasie, Shahin Akhondzadeh; Crocus sativus L. (petal) in the treatment of mild-to-moderate depression: A double-blind, randomized and placebo-controlled trial; Phytomedicine 13 (2006) 607–611

1. Saffron crocus smells a little like vanilla and spice, and the dried stigmas add a distinct flavor to foods like Spanish paella, rice dishes, and bouillabaisse. 
2. The origin of the word saffron is the French term “Safran,” which was derived from the Latin word “safranum” and yellowish in color, phytochemical analysis have revealed that the color is mainly because of the degraded carotenoid compounds, crocin and crocetin.
3. The stigma of saffron has been used as a medicine over 3600 years ago. Saffron was used in various opioid preparations for pain relief (sixteenth to nineteenth centuries). Also, saffron has been used in coloring tunics in the region of Spain and by the Babylonian culture around 2400 BC.
4. At a retail price of up to $11 000 per kg, it is the world’s most expensive spice, reflected by the labour intensiveness associated with its production. Each of the flowers has three red-colored stigma, and one stigma of saffron weighs approximately 2 mg. 150 000 crocus blossoms or 450 000 hand-picked stigmas to produce just 1 kg of this unique spice.
5. Quantities of 10 g or more can cause an abortion and the lethal dose in human is 20 g
6. Saffron is used for depression in Persian traditional medicine. Indeed, it is a Persian herb with a history as long as the Persian Empire itself.

Passiflora (Passiflora incarnata L.) or the passion flower is cultivated to obtain raw materials for pharmaceutical needs.Passiflora incarnata is one of the best-documented species of the Passiflora genus with medicinal properties. Both the plant as a whole, and blossoms and fruits are used for medicinal purposes.

The valuable properties and side effects of passiflora have long been studied in various medicinal preparations. Considering the fact that this plant has unique pharmacological properties, it is becoming increasingly popular lately.

Passiflora is a source of alkaloids, phenolic compounds, flavonoids and cyanogenic glycosides. The primary phytochemicals of passiflora are flavonoids (apigenin, luteolin, quercetin, and kaempferol) and flavonoid glycosides (vitexin, isovitexin, orientin, and isoorientin).1

The C-glycosylated flavonoids and isovitexin found in passiflora modulate GABAA receptors through their benzodiazepine binding sites and simultaneously create effects characteristic for anxiolytic means and the effect of cognitive improvement.2

On 25 March 2014, the European Medicines Agency published aherbal monograph on Passiflora incarnata, thereby recognising its status as a medicinal product.3

Passiflora incarnata is important in the plant-based medicinal treatment of anxiety or nervousness, generalised anxiety disorder, opiate withdrawal symptoms, insomnia, neuralgia, convulsions, spasmodic asthma, UDHS, palpitations, heart rhythm abnormalities, hypertension, sexual dysfunction, and menopause.

Despite the shortcomings of our understanding of neurophysiological processes, it is being increasingly recognisedthat neuropsychiatric conditions connected with depression and anxiety in the central nervous system relate to the balance between chemical excitation and inhibition. One mechanism involves the γ-aminobutyric acid (GABA) system.4 Therefore, the effects of Passiflora incarnata dry extract on the GABA system in vitro were investigated. Studies have shown that many of the pharmacological effects of Passiflora incarnata are related to modulation of the GABA system, including affinity (the ability of a substance to form a compound with another substance) for GABAA and GABABreceptors and effects on GABA uptake. The anxiolytic activities of polyphenols and flavones in passiflora can be partially attributed to their anti-irritant and antioxidant effects due to their specific structures. In addition, a significant number of these compounds have been proven to have anxiolytic properties through the activation of GABAA receptors.5 1 Atsauce: 1) Janda, K., Wojtkowska, K., Jakubczyk, K., Antoniewicz, J., & Skonieczna-Żydecka, K. (2020). Passiflora incarnata in Neuropsychiatric Disorders—A Systematic Review. Nutrients, 12(12), 3894. doi:10.3390/nu12123894 2) Oliveira, D. R. de, Todo, A. H., Rêgo, G. M., Cerutti, J. M., Cavalheiro, A. J., Rando, D. G. G., & Cerutti, S. M. (2018). Flavones-bound in benzodiazepine site on GABA A receptor: Concomitant anxiolytic-like and cognitive-enhancing effects produced by Isovitexin and 6-C-glycoside-Diosmetin. European Journal of Pharmacology, 831, 77–86. doi:10.1016/j.ejphar.2018.05.004 3) https://www.ema.europa.eu/en/medicines/herbal/passiflorae-herba 4) Fonseca, L. R. da, Rodrigues, R. de A., Ramos, A. de S., da Cruz, J. D., Ferreira, J. L. P., Silva, J. R. de A., & Amaral, A. C. F. (2020). Herbal Medicinal Products from Passiflora for Anxiety: An Unexploited Potential. The Scientific World Journal, 2020, 1–18. doi:10.1155/2020/6598434 5) Sita Sharan Patel, Neelesh Kumar Verma, Karunakaran Gauthaman; Passiflora Incarnata Linn: A Review on Morphology, Phytochemistry and Pharmacological Aspects; Phcog Rev. Vol, 3, Issue 5, 186-192, 2009

Side effects are sometimes observed when using products containing passiflora . The most common side effects are:

• • dizziness;
• • drowsiness;
• • confusion;
• • nausea;
• • vomiting;
• • low blood pressure;
• • abnormal heartbeat and rhythm.

Passiflora should be used with caution if you are already taking any sedative medications, such as alprazolam (Xanax), lorazepam (Ativan), temazepam (Restoril), and zolpidem (Ambien), because using them concurrently with passiflora increases the risk of excessive drowsiness and sedation.

Passiflora should be used cautiously together with blood pressure medications such as enalapril (Vasotec), losartan (Cozaar), atenolol (Tenormin), amlodipine (Norvasc), and furosemide (Lasix). Passiflora has a blood pressure-lowering effect, and taking blood pressure medications in combination with passiflora can lower your blood pressure more than necessary.

If you are taking any medications and have questions about the compatibility of these medications with passiflora, consult your doctor before using this product.

Passiflora is not recommended for women during pregnancy and breast-feeding.

Stress is a natural body reaction. It can be caused by factors of a physical (hunger, thirst, infection) and/or psychological nature (perceived threats, anxiety or concern), i.e., stress factors. Stress is associated with cell irritation. Physiologically, the body's response to stress causes an immediate activation of the adrenergic system and the sympathetic-adrenomedullary axis (SAM axis), followed by the hypothalamic-pituitary-adrenal axis (HPA axis). Chronic, long-term stress is a pathological condition that can impair concentration and memory, and lead to affective disorders such as depression, schizophrenia, and post-traumatic stress disorder. Passiflora incarnata is one of the plant-based remedies used to reduce the effects of stress. A study in rats demonstrated that a long-term use of passiflora was associated with reduced stress levels and, consequently, increased motivation to act and improved motor activity. The beneficial effects of passiflora on memory function have also been confirmed.

Stress can affect the quality of sleep and cause insomnia. The use of passiflora in people with chronic insomnia can have a therapeutic effect in the case of sleep disorders, memory loss and degenerative brain disease. Passiflora, due to its calming effect, can also be useful in anxiety, restlessness, insomnia and depressive conditions.1

The most commonly used drugs for anxiety include the anxiolytics benzodiazepine and buspirone, as well as various antidepressants, which can cause side effects and tolerability problems.

In a study2 setting a hypothesis that the oral use of Passiflora incarnata would be an effective anxiolytic agent with limited effects on anaesthesia and recovery, the effect of passiflora (500 mg) on anxiety in preoperative patients was demonstrated. Conclusion: In outpatient surgery, peroral administration ofPassiflora incarnata as premedication reduces anxiety without inducing sedation (drowsiness).

Passiflora incarnata at 500 mg/day provides a safe and effective anxiolytic effect without impairing psychomotor functions. 1 Atsauce: 1) Janda, K., Wojtkowska, K., Jakubczyk, K., Antoniewicz, J., & Skonieczna-Żydecka, K. (2020). Passiflora incarnata in Neuropsychiatric Disorders—A Systematic Review. Nutrients, 12(12), 3894. doi:10.3390/nu12123894; 2) Movafegh, A., Alizadeh, R., Hajimohamadi, F., Esfehani, F., & Nejatfar, M. (2008). Preoperative Oral Passiflora Incarnata Reduces Anxiety in Ambulatory Surgery Patients: A Double-Blind, Placebo-Controlled Study. Anesthesia & Analgesia, 106(6), 1728–1732. doi:10.1213/ane.0b013e318172c3f9

L-theanine (γ-glutamylethylamide) is a derivative of L-glutamic acid, an amino acid most associated with tea leaves (Camellia sinensis L.). It has a similar chemical structure to glutamate (a neurotransmitter involved in more than 90% of all synaptic connections in the human brain). Upon reaching the brain, L-theanine turns into an active neurotransmitter, which ensures the transmission of intercellular nerve impulses and effectively affects the processes of inhibition and relaxation. In other words, your mood, concentration, sleep pattern, appetite and alertness are mainly influenced by various neurotransmitters - endogenous chemicals that transmit a signal from a neuron to a target cell through a synapse, including GABA (gamma-amino butyric acid), serotonin and dopamine, as well as brain function inhibitory hormones such as cortisol and corticosterone. When you're under stress, cortisol and corticosterone levels rise, resulting in reduced brain function.1

To prevent this, L-theanine enhances the action of neurotransmitters such as GABA, thus reducing the level of excitatory brain chemicals - cortisol and corticosterone - and promoting relaxation. Elevated levels of cortisol and corticosterone not only cause anxiety, but also affect various other brain functions such as spatial learning and memory.

Currently, four types of electromagnetic waves are known in the human brain: beta, alpha, theta and delta waves. Each has its own frequency range and is associated with a different activity, for example theta waves are associated with sleepiness and alpha waves with relaxation. Alpha brain waves are considered a measure of relaxation. Their action is associated with increased creativity, better performance under stress, better learning and concentration, and reduced anxiety. L-theanine increases the activity of alpha waves, thereby relaxing the activity of the brain.1; 2As you continue to relax, alpha waves begin to dominate the entire brain. The lack of these waves is caused by stress, illness, anxiety. 1 Atsauces: 1) Eschenauer, G. (2006). Pharmacology and therapeutic uses of theanine. American Journal of Health-System Pharmacy, 63(1), 26–30. doi:10.2146/ajhp050148 2) Gomez-Ramirez, M., Kelly, S. P., Montesi, J. L., & Foxe, J. J. (2008). The Effects of l-theanine on Alpha-Band Oscillatory Brain Activity During a Visuo-Spatial Attention Task. Brain Topography, 22(1), 44–51. doi:10.1007/s10548-008-0068-z

L-theanine is generally considered safe to use. It is not associated with serious adverse effects.

The most common side effects of L-theanine are headache, nausea, and irritability.1 However, nausea appears to be primarily associated with L-theanine intake through green tea rather than supplements. Similarly, the side effect of irritability has been associated with the double use of caffeine and L-theanine. 1 Atsauce: 1) Giesbrecht T, Rycroft JA, Rowson MJ, De bruin EA. The combination of L-theanine and caffeine improves cognitive performance and increases subjective alertness. Nutr Neurosci. 2010;13(6):283-90.

If your usual answer to the question “How are you?” is “Tense –work never ends” or “I can't get anything done”, you may want to supplement your daily routine with L-theanine to reduce your stress and anxiety symptoms.1

L-theanine is associated with anti-anxiety effects by inhibiting the excitation of cortical neurons. Stress is our body's natural response to danger. For example, when you see a bear in the forest, your sympathetic nervous system is activated, hormones are released, your heart beats faster, your hands sweat, your mouth becomes dry, etc. However, you can also activate your sympathetic nervous system accidentally, so to speak, “unnecessarily”, and this can become a problem.

At best, the effects of stress can result in unpleasant, sweaty palms. At worst, you may suffer from chronic stress and related physiological reactions, such as increased heart rate and blood pressure, or weakened immunity.

Students are also under regular stress. Stress increases the level of the hormone corticosterone, and as a result, the brain cannot function as it is supposed to. Consequently, learning becomes ineffective. It was proven in the study2 that the use of L-theanine ensured a faster simple reaction time, faster numerical working memory reaction time, and improved sentence test accuracy. Self-assessments of persons such as “headache” and “fatigue” were reduced.

This proves that by reducing levels of the hormone corticosterone, L-theanine protects cognitive abilities from potential disorders that could occur due to high levels of the stress hormone.

Researchers have established3 that L-theanine helps in regulating high blood pressure, thus helping people to keep it at a healthy level in stressful situations.

If you suffer from stress-induced insomnia, L-theanine can help. A team of researchers conducted a study4 to investigate the ability of L-theanine to improve sleep quality. A study shows that taking 200 mg of L-theanine before bed improves sleep quality, not sedation, but anxiolysis. As L-theanine does not induce daytime drowsiness; its use can be beneficial at any time of the day.

L-theanine improves sleep quality in a number of ways. First, the amino acid enables a person to relax better and become less anxious. With the stimulation of relaxation and reduced stress, you can fall asleep easier and faster. By reducing anxiety and promoting relaxation, L-theanine helps you go through the entire normal sleep cycle, including the much-needed deep REM phase, for complete mind and body rejuvenation. 1 Atsauce: 1) Kimura, K., Ozeki, M., Juneja, L. R., & Ohira, H. (2007). l-Theanine reduces psychological and physiological stress responses. Biological Psychology, 74(1), 39–45. doi:10.1016/j.biopsycho.2006.06.006 2) Haskell, C. F., Kennedy, D. O., Milne, A. L., Wesnes, K. A., & Scholey, A. B. (2008). The effects of l-theanine, caffeine and their combination on cognition and mood. Biological Psychology, 77(2), 113–122. doi:10.1016/j.biopsycho.2007.09.008 3) Rogers, P. J., Smith, J. E., Heatherley, S. V., & Pleydell-Pearce, C. W. (2007). Time for tea: mood, blood pressure and cognitive performance effects of caffeine and theanine administered alone and together. Psychopharmacology, 195(4), 569–577. doi:10.1007/s00213-007-0938-1 4) Rao, T. P., Ozeki, M., & Juneja, L. R. (2015). In Search of a Safe Natural Sleep Aid. Journal of the American College of Nutrition, 34(5), 436–447. doi:10.1080/07315724.2014.926153

Vitamin B6 (pyridoxine) was discovered in 1934. It is a water-soluble substance that transforms into the most important coenzymes in the body. Vitamin B6 in the form of a coenzyme fulfils various functions in the body and is extremely versatile, involved in more than 100 enzyme reactions, mainly related to protein metabolism.

Vitamin B6 has three naturally occurring forms: pyridoxine, pyridoxal, and pyridoxamine, all of which transform into their active forms in the body, namely, coenzyme pyridoxal 5-phosphate (PLP or P5P). PLP mainly serves as a coenzyme in the metabolism of amino acids, proteins, carbohydrates and lipids, in addition to the synthesis of neurotransmitters (biologically active substances that are synthesised in the neuron and released in the synapse; when they bind to the receptors of another cell, they transmit the nerve impulse from the synapse to the cell). It is also involved in glycogenolysis and gluconeogenesis.1

Pyridoxine, pyridoxamine, and pyridoxal absorb fast from food and oral drugs and dietary supplements into the mucosal cells of the small intestine, whereas their phosphorylated analogues are first dephosphorylated and then absorbed.

Vitamin B6 has a significant and selectively modulating effect on central serotonin and GABA production2. GABA is a chemical found in the brain and an inhibitory neurotransmitter. Read more about GABA here. It helps to calm the nervous system by blocking certain impulses between nerve cells, slowing down the activity of the brain, thus it has a calming effect that can help reduce stress, anxiety and fear.

Biochemically, in partial vitamin B6 deficiency, some enzymes may be affected more than others, leading to the greater attenuation of certain neurotransmitters and thus disrupting the balance between different neurotransmitter levels.3 Accordingly, causing neurological disorders such as cognitive impairment, convulsive seizures, depression and even premature neuronal ageing (CNS effects).

So, the most important function of vitamin B6 is that it acts as a coenzyme in the synthesis of neurotransmitters necessary for synaptic transmission (for example, dopamine, serotonin, GABA) and performs a neuroprotective role based on its importance in the glutamatergic system. 1 References: 1) NourEldin R. Abosamak, Vikas Gupta; Vitamin B6 (Pyridoxine); In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan.; 2022 May 23. PMID: 32491368 Bookshelf ID: NBK557436; 2) McCarty M.F. High-dose pyridoxine as an 'anti-stress' strategy. Med. Hypotheses. 2000 May;54(5):803–807. doi: 10.1054/mehy.1999.0955.PMID:1085969 3) Calderón‐Ospina, C. A., & Nava‐Mesa, M. O. (2019). B Vitamins in the nervous system: Current knowledge of the biochemical modes of action and synergies of thiamine, pyridoxine, and cobalamin. CNS Neuroscience & Therapeutics. doi:10.1111/cns.13207

Vitamin B6 deficiency can be clinically observed as seborrheic dermatitis, microcytic anaemia, tooth decay, glossitis, epileptiform seizures, peripheral neuropathy, electroencephalographic abnormalities, depression, confusion, and weakened immune function.1

Vitamin B6 deficiency is relatively rare, but some people may have low levels of vitamin B6.

People who may be deficient in vitamin B6:

People with impaired kidney function, including those with chronic kidney failure, those receiving maintenance kidney dialysis, those who have had a kidney transplant, often have low levels of vitamin B6.

People with rheumatoid arthritis often have low levels of vitamin B6 in their blood, and these levels tend to decrease as the disease progresses. This low level of vitamin B6 is associated with the inflammation caused by the disease. Although the additional intake of vitamin B6 can normalise blood levels of vitamin B6 in patients with rheumatoid arthritis, it does not, however, suppress the production of inflammatory cytokines and it does not reduce the levels of inflammatory markers, either.

Patients with celiac disease, Crohn's disease, ulcerative colitis, inflammatory bowel disease, and other malabsorption autoimmune disorders typically have low levels of vitamin B6.

People who are dependent on alcohol tend to have very low vitamin B6 concentration levels in the plasma. Alcohol produces acetaldehyde, which reduces net B6 production in cells and competes with pyridoxal 5-phosphate for protein binding. As a result, pyridoxal 5-phosphate may make cells more susceptible to hydrolysis by membrane-bound phosphatase. People with alcohol addiction would be advised to take vitamin B6 supplements regularly.

Adults with no known or confirmed vitamin B6 deficiency normally need 1.3 mg of vitamin B6 per day (pregnant women 2 mg).

1 Reference: 1) NourEldin R. Abosamak, Vikas Gupta; Vitamin B6 (Pyridoxine); In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan.; 2022 May 23. PMID: 32491368 Bookshelf ID: NBK557436; 2) https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/

High intakes of vitamin B6 from food sources have not been reported to cause adverse effects; however, the long-term use of 1-6 g of oral pyridoxine per day for 12-40 months may cause severe and progressive sensory neuropathy. Degeneration of peripheral nerve fibres and their myelin, as well as spinal canals, causes the bilateral loss of peripheral sensation or hyperaesthesia, accompanied by pain in the extremities, ataxia (impaired movement coordination and balance), and loss of balance. The condition gradually regresses after stopping the use of additional vitamin B6 until normal activity is restored.1 Higher doses may cause testicular atrophy and reduced sperm motility.

Drug interactions

Vitamin B6 can interact with certain medications and several types of medications can negatively affect vitamin B6 levels. Let's cite some examples. Individuals who regularly take these and other medications should discuss their vitamin B6 use with their health care providers.

Cycloserine (Seromycin®) is a broad-spectrum antibiotic used to treat tuberculosis. In combination with pyridoxal phosphate, cycloserine increases the urinary excretion of pyridoxine. Urinary excretion of pyridoxine may exacerbate the convulsions and neurotoxicity associated with cycloserine. Supplemental pyridoxine intake may help prevent these adverse consequences.

Some antiepileptic drugs, including valproic acid (Depakene®, Stavzor®), carbamazepine (Carbatrol®, Epitol® and others), and phenytoin (Dilantin®) increase vitamin B6 catabolism (a set of metabolic processes that break down molecules into smaller units that are oxidised to release energy) rate, resulting in decreased B6 concentrations and the development of hyperhomocysteinemia. High homocysteine levels in antiepileptic drug users can increase the risk of epileptic seizures, including stroke, and reduce the ability to control seizures. In addition, patients typically take antiepileptic drugs for years, increasing the risk of chronic vascular toxicity.

Theophylline (Aquaphyllin®, Elixophyllin®, Theolair®, Truxophyllin®, etc.) can prevent or treat shortness of breath, wheezing, and other breathing problems caused by asthma, chronic bronchitis, emphysema, and other lung diseases. Patients treated with theophylline often have low plasma concentrations of vitamin B6, which may contribute to theophylline-related neurological and central nervous system side effects, including seizures. 1 Reference: Lheureux P, Penaloza A, Gris M. Pyridoxine in clinical toxicology: a review. Eur J Emerg Med. 2005 Apr;12(2):78-85. https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/

In the most recent studies, researchers have looked for a link between mood disorders such as depression and anxiety, stress, and vitamin B6 use. For example, an eight-week phase IV randomised controlled trial found that a combination of magnesium and vitamin B6 was able to provide increased physical activity in daily life and a significant reduction in stress in healthy people with severe stress and anxiety and low magnesium levels.1

Taking the results of various studies into account, it can be concluded that vitamin B6 actively helps to reduce the symptoms characteristic of depression and anxiety, making this vitamin an important addition to everyday life. Another important consideration in favour of vitamin B6 is that while benzodiazepines (such as diazepam, phenazepam, etc.) are effective in treating anxiety and similar conditions, they also have a number of side effects, including but not limited to addiction, rebound anxiety, memory disorders and withdrawal syndrome. 1 Reference: 1) Noah L., et al. Effect of magnesium and vitamin B6 supplementation on mental health and quality of life in stressed healthy adults: post-hoc analysis of a randomised controlled trial. Stress Health. 2021; 37:1000–1009.

L-tyrosine is a replaceable (non-essential) aromatic amino acid that serves as a raw material in the body for the synthesis of various other substances, for example, it is a precursor for the synthesis of the thyroid gland hormone thyroxine (T4) (produced by iodination of tyrosine), the pigment melanin and other biologically active substances such as catecholamines - epinephrine (adrenaline), norepinephrine (noradrenaline) and dopamine. These are very important biologically active substances that are synthesised in the neuron and released in the synapse; binding to the receptors of another cell, they transmit a nerve impulse from the synapse to the cell (neurotransmitters), which are closely related to the corresponding concentration of L-tyrosine in the body.

L-tyrosine is part of many natural proteins, including enzymes. In the body, L-tyrosine is synthesised from phenylalanine with the help of the enzyme phenylalanine-4-hydroxylase.

How does tyrosine work in our body? First, the thyroid gland absorbs iodine from food. Once these iodine molecules are oxidised, they are ready to attach to the tyrosine found in thyroglobulin (a protein produced by the thyroid gland). When iodine and tyrosine combine, they create thyroid gland hormone precursors, monoiodotyrosine (T1) and diiodotyrosine (T2). T1 and T2 then combine to form the thyroid gland hormones triiodothyronine (T3; thyroglobulin with three iodine molecules) and thyroxine (T4, thyroglobulin with four iodine molecules). T4 and T3 are the primary thyroid gland hormones that are essential for regulating metabolic processes throughout the body.

So, to summarise the roles of tyrosine in the body, the following should be mentioned:

A lack of tyrosine can cause thyroid gland dysfunction, such as hypothyroidism, as well as cause depression or increased nervousness due to impaired catecholamine synthesis.

L-Tyrosine is considered safe in most doses, but you should still consult your doctor before using it if you are taking any medications. It can interact with medications, including some medications used to treat thyroid gland disorders or depression.

Monoamine oxidase inhibitors (MAOIs) - Tyrosine can cause serious increases in blood pressure in people taking antidepressants known as MAOIs. This rapid rise in blood pressure, also called a “hypertensive crisis,” can lead to a heart attack or stroke. People taking MAOIs should avoid foods and supplements that contain tyrosine. For instance:

Levodopa - Tyrosine should not be used at the same time as levodopa, a medicine used to treat Parkinson's disease. Levodopa may interfere with the absorption of tyrosine.

In some cases, extra use of tyrosine can cause insomnia, restlessness, palpitations, headaches, stomach disorders and heartburn.

Because tyrosine is involved in the production of thyroid gland hormones, you should not take it if you have been diagnosed with a thyroid disorder such as hyperthyroidism or Graves' disease.

The recommended daily dietary allowance (RDA) for tyrosine is 25 mg per kilogram of body weight.1 Assuming that a person receives half of the required amino acid, this amounts to 12.5 mg per kg. Thus, a person weighing 70 kg should consume about 875 mg of tyrosine per day, which is the amount used to calculate the RDA. Tyrosine is found in a variety of foods, such as peanuts, fish, chicken, turkey, soy, eggs, and cottage cheese. It is also in pumpkin seeds, oats, wheat, beans, sesame seeds, avocados, and bananas. 1 Atsauce: George M. Kapalka, in Nutritional and Herbal Therapies for Children and Adolescents, 2010

Hypothyroidism, or reduced thyroid function, means that the thyroid gland produces insufficient amounts of important hormones that have an impact on all metabolic processes.  The most common causes of hypothyroidism are chronic autoimmune thyroiditis, the use of various medications, radiation therapy, and thyroid surgery. It should also be taken into account that people are reluctant to use sea vegetables, such as kelp, in their diet, as well as because of the taste, people prefer salt without iodine addition, which is also the reason why iodine deficiency is becoming more and more common.

The most common symptoms of hypothyroidism are fatigue, increased sensitivity to cold, dry skin, brittle hair, a person looking much older than they actually are. Women often have irregular menstruation, cognitive disorders, depression.

It has also been shown that people with thyroid disease, whether hyperthyroid or hypothyroid, have very fluctuating tyrosine levels in the blood serum, and those with hypothyroidism (low thyroid hormone levels) usually have lower than normal blood tyrosine levels.

Combined with the proven fact that the use of medications (for example, levothyroxine, a synthetic thyroid gland hormone used to treat thyroid diseases and disorders) improves the metabolism of tyrosine in the liver, it may be worth consulting a doctor and considering the possibility to supplement everyday life with both thyroid medication and tyrosine (either by following a special diet or using nutritional supplements).

If you choose to supplement your everyday life with L-tyrosine, remember that it is more effective to use it together with other minerals that can improve thyroid function, such as zinc and selenium. Zinc helps to improve the conversion of thyroxine (T4) to triiodothyronine (T3) in hypothyroid patients with insufficient thyroid function. Selenium, on the other hand, helps reduce thyroid antibodies and is also involved in the conversion of T4 to T3.

Among the 66 species of kelp, Fucus vesiculosus is one of the most prominent in the shallow waters of the Arctic region - the Atlantic Ocean, the North Pacific Ocean, the Barents, White, Norwegian, Baltic and Irminger seas. These algae dominate shallow water macroalgal populations at depths of 0.5-4 m in marine waters. They are used not only in food, but also in cosmetics, biological fertilisers, animal feed and the pharmaceutical industry.1

Fucus vesiculosus contains a range of health-promoting compounds such as fucoidans, polyphenols, fucoxanthin and a source of essential minerals, including iodine, which is highly bioavailable, and selenium, which plays a key role in regulating thyroid gland function. Bladderwrack is particularly rich in iodine and is used as a natural source of iodine, which is organically incorporated into cellular metabolism.

Alginic acid found in kelp (up to 35% of dry mass) is known in the food industry. It serves as an ingredient in soups and soup mixes as an emulsifier, thickener and stabiliser. On the other hand, preparations based on alginates (salts of alginic acid) are used to treat heartburn and gastric acid reflux.2 Alginic acid stimulates phagocytosis, thereby increasing the antimicrobial, antiviral and antifungal activity of cells; binds the excess amount of immunoglobulin E, due to which allergy develops; promotes the synthesis of immunoglobulin A (antibodies), which increases the body's resistance to microbes. Likewise, thanks to alginic acid, Fucus vesiculosus lowers blood pressure, removes harmful radionuclides and heavy metals and weakens body intoxication.

Another important component of Fucus vesiculosus is fucoidans. Fucoidans are polysaccharides from the Fucus family, compounds unique to brown algae (kelp). Various pharmacological effects of fucoidans have been reported, including antioxidant, anti-obesity, antidiabetic, antiageing, antimicrobial, anticancer (by modulating the host immune system and inhibiting tumour angiogenesis), anticoagulant, and anti-inflammatory effects.1

Fucus vesiculosus reduces the activity of trans-sialidase in the blood, an enzyme associated with cholesterol accumulation, by as much as 36%.3 This may be useful in patients with hypothyroidism, as slow metabolism is associated with the excessive accumulation of lipids and glucose.

Summing up the valuable qualities of Fucus vesiculosus, it should be mentioned that it effectively cleanses the body of slags and toxins, as well as maintains the health of the endocrine system. Recommended for hypothyroidism, blood circulation disorders, poisoning with heavy metal salts. Fucus vesiculosus slows down the development of atherosclerosis, and reduces the level of cholesterol in the blood. Bladderwrack polysaccharides swell, increase their volume and irritate the intestinal mucosa, thereby stimulating peristalsis, promoting intestinal cleansing, which is used to reduce weight in obese people. Polysaccharides bind toxins, remove them from the body. Bladderwrack alginates remove heavy metals and radionuclides from the body. Bladderwrack contains more trace elements than land plants. 1 Atsauces: 1) Ekaterina D. Obluchinskaya, Olga N. Pozharitskaya, Denis V. Zakharov, Elena V. Flisyuk, Inna I. Terninko, Yulia E. Generalova, Irina E. Smekhova, and Alexander N. Shikov; The Biochemical Composition and Antioxidant Properties of Fucus vesiculosus from the Arctic Region; Mar Drugs. 2022 Mar; 20(3): 193.; doi: 10.3390/md20030193 2) Mandel, Daggy, Brodie, & Jacoby. (2000). Review article: alginate-raft formulations in the treatment of heartburn and acid reflux. Alimentary Pharmacology and Therapeutics, 14(6), 669–690. doi:10.1046/j.1365-2036.2000.00759.x 3) Aksenov, D. V., Kaplun, V. V., Tertov, V. V., Sobenin, I. A., & Orekhov, A. N. (2007). Effect of plant extracts on trans-sialidase activity in human blood plasma. Bulletin of Experimental Biology and Medicine, 143(1), 46–50. doi:10.1007/s10517-007-0013-2

There are no clinical studies supporting the safety of Fucus vesiculosus, but based on the use of Fucus as a traditional food, moderate consumption of the seaweed is generally considered safe. Seaweed can be exposed to chemical contamination present in the water in which it is harvested, so its origin and manufacturer's quality requirements are of particular importance. Cases of Fucusnephrotoxicity, possibly due to arsenic contamination, have been reported. Therefore, pay attention if products containing algae are unusually cheap or are not registered with food safety authorities.

Due to the limited number of studies, there are no well-defined recommendations for daily doses of bladderwrack; however, mostly, it is recommended not to exceed 500 mg daily.

Pregnancy and breastfeeding period: Fucus vesiculosus is probably not safe to use during pregnancy or breastfeeding unless prescribed by a doctor.

Allergy to iodine: Fucus vesiculosus can contain large amounts of iodine, which can cause an allergic reaction in sensitive people. Do not use them as a food product in excessive amounts, but it can be used as a dietary supplement in controlled amounts.

Surgery: Fucus vesiculosus can slow down blood clotting. This can cause additional bleeding during and after surgery. Tell your doctor how much algae you are taking and, if necessary, stop taking Fucus vesiculosus at least 2 weeks before surgery if your doctor tells you to.

Drug interactions:

Be careful if you use:

Taking Fucus vesiculosus together with lithium may increase the risk of changes in thyroid gland function.

Taking Fucus vesiculosus with medicines for a hyperactive thyroid gland can change the effects of these medicines.

Fucus vesiculosus can slow down blood clotting. Taking them with medicines that also slow down blood clotting can increase the risk of bruising and bleeding.1 1 Atsauce: 1) https://medlineplus.gov/druginfo/natural/726.html

In our latitudes, a common phenomenon is a reduced thyroid function, or hypothyroidism. Almost every third or fourth woman has it. Women are more affected by this problem, because the function of the thyroid gland and its activity is influenced by the psycho-emotional state. The thyroid gland is very sensitive to adrenaline and the stress hormone cortisol. Typical signs of hypothyroidism are freezing (intolerance to cold), fluid retention, and it is especially evident in premenopausal age.1

The body of a healthy adult contains 15 to 20 mg of iodine, of which 70 to 80% is located in the thyroid gland. In the case of a chronic iodine deficiency, the iodine content in the thyroid gland may fall below 20 µg. If a sufficient amount of iodine is available to the body, then the thyroid gland “uses” about 60 µg of iodine per day to balance its loss and maintain the synthesis of thyroid hormones; accordingly, iodine is an essential component of the hormones produced by the thyroid gland.2

The body does not produce iodine, so it is essential to consume foods that contain iodine or to take iodine with food additives or nutritional supplements. Iodine is found in a variety of foods, however seafood has a higher iodine content because marine plants and animals are able to concentrate iodine from seawater. Iodine is found in large quantities in organic form in algae, incl. Fucus vesiculosus . If the body does not have enough iodine, it cannot produce enough thyroid gland hormones. Thus, iodine deficiency can cause thyroid gland enlargement, hypothyroidism, and intellectual disability in infants and children whose mothers were iodine deficient during pregnancy.3 Strict vegans are especially at risk because their daily food intake is limited.4

Fucus vesiculosus contains the flavonoid fucoxanthin and is reported to have the highest antioxidant activity among edible seaweeds. Fucus vesiculosus, rich in minerals and halides including iodine, has shown beneficial effects in the treatment of thyroid gland dysfunction such as Hashimoto's disease and sub-clinically

hypothyroidism. Fucus also has the ability to reduce the activity of trans-sialidase in the blood, which is associated with the accumulation of cholesterol. This may be important in hypothyroid patients whose metabolism is associated with hyperlipidemia.5 1 Atsauce: 1) https://nra.lv/veseliba/181158-veseliba-vairogdziedzera-disfunkcija-21-gadsimta-pandemija.htm 2) Zimmermann, M. B. (2009). Iodine Deficiency. Endocrine Reviews, 30(4), 376–408. doi:10.1210/er.2009-0011 10.1210/er.2009-0011 3) https://www.thyroid.org/iodine-deficiency/ 4) Lightowler HJ, Davies GJ. Iodine intake and iodine deficiency in vegans as assessed by the duplicate-portion technique and urinary iodine excretion. Br J Nutr 1998;80(6):529-535. 5) Jill Stansbury,Paul Saunders, David Winston; Promoting Healthy Thyroid Function with Iodine, Bladderwrack, Guggul and Iris; ©2012, Jill Stansbury, ND Journal Compilation ©2012, AARM; DOI 10.14200/jrm.2012.1.1008

Lavender is a perennial plant of the Labiatae family with thousands of years of history. It is a small, fragrant shrub that reaches a maximum height of 80 centimetres and is both a nectar plant and an essential oil plant. Lavender has oppositely arranged, grey-green, lanceolate leaves with a curled edge. The flowers are double-lipped, blue or violet-blue, arranged in false spikes, which in turn form a spike at the end of the inflorescence.

The lavender genus includes up to 47 species. Under natural conditions, lavender grows in North and East Africa, Australia, the Arabian Peninsula, India, the Canary Islands and Southern Europe. However, as a crop it is found all over the world.

Looking at the great variety of species, three main types can be distinguished: English, Spanish and French lavender. Although they share many similarities, French and English varieties can be distinguished by appearance, growth habit, flowering time, fragrance and use.

English or “true” lavender (Lavandula officinalis angustifolia) is more dense, with a fuller flower, and it is this lavender species that is mostly used for medicinal purposes.

Its flowers contain 3% essential substances, anthocyanins, phytosterols, sugars, minerals and tannins. The qualitative and quantitative composition of lavender essential oil is variable and depends on the genotype, place of growth, climatic conditions, propagation and morphological features. Lavender essential oil contains more than 300 different chemical compositions, the main of which is linalool (the amount varies from 9.3% to 68.8% and has the following medicinal properties: anti-inflammatory, anticonvulsant, relaxant, analgesic, sedative, antidepressant, anti-stress agent and anxiolytic agent), linalyl acetate (amount varies from 1.2% to 59.4%), lavandulyl acetate, ocimene, cineole and terpinen-4-ol. 1 Atsauces: Prusinowska, R., & Śmigielski, K. B. (2014). Composition, biological properties and therapeutic effects of lavender (Lavandula angustifolia L). A review. Herba Polonica, 60(2), 56–66. doi:10.2478/hepo-2014-0010

Lavender essential oil has good antioxidant and antimicrobial activities when applied to the skin, as well as significant positive effects on the digestive and nervous systems when taken orally.

Linalool and linalyl acetate are thought to be the main components of lavender oil, which could be related to sleep-promoting effects by modulating the effects of glutamate and GABA. 2 Atsauces: Kim, J., Lee, S. L., Kang, I., Song, Y. A., Ma, J., Hong, Y. S., … Kim, J. E. (2018). Natural Products from Single Plants as Sleep Aids: A Systematic Review. Journal of Medicinal Food, 21(5), 433–444. doi:10.1089/jmf.2017.4064

Lavender has been shown to act as an anxiolytic aid (anxiety reliever) and as a sedative aid to increase body relaxation and resting, thereby promoting sleep.

Lavender interacts with the neurotransmitter GABA (a chemical naturally produced in the nervous system that allows nerve cells to communicate with each other and a lack or excess of which can cause a variety of mood disorders) to help calm the brain and nervous system, reducing agitation, anger, aggression and anxiety. Lavender also works as a pain reliever.

The toxicity of lavender oil is not a concern. Components such as linalool and linalyl acetate are not mutagenic. 1 Atsauce: https://www.ema.europa.eu/en/documents/herbal-report/draft-assessment-report-lavandula-angustifolia-mill-aetheroleum-lavandula-angustifolia-mill-flos_en.pdf]] Given that lavender is also used in food, it is also safe when used as medicine. Side effects may include constipation, diarrhoea and headache.

Be careful when using sedative medications (central nervous system depressants) with lavender because they interact.

Lavender can cause drowsiness and slow breathing. Sedatives (medications) can also cause drowsiness and decelerated breathing. Taking lavender with sedative medications can cause breathing problems and/or excessive drowsiness.

Insomnia is one of the most common sleep disorders among the population. This disorder is also among the most frequent complaints in primary health care centres. Lavender is called a “brain broom” in various Eastern traditional medicines, because it is able to “clean” the head in the same way that a broom sweeps a room of debris. It is one of the most commonly used herbs for patients with sleep disorders.

According to the European Medicines Agency assessment report 1 Atsauce:  2" https://www.ema.europa.eu/en/documents/herbal-report/draft-assessment-report-lavandula-angustifolia-mill-aetheroleum-lavandula-angustifolia-mill-flos_en.pdf]]

EMA/HMPC/143183/2010, lavender oil acts as a sedative aid and promotes sleep. Separate studies have shown that individuals reported greater alertness and vigour the morning after exposure to lavender, as well as an increase in non-REM, or slow, light sleep, and a decrease in rapid eye movement (REM) sleep, and its duration.

At the same time, the time before waking up after first falling asleep (waking up after the beginning of sleep) increased. 2 Atsauce: Goel, N., Kim, H., & Lao, R. P. (2005). An Olfactory Stimulus Modifies Nighttime Sleep in Young Men and Women. Chronobiology International, 22(5), 889–904. doi:10.1080/07420520500263276

Plants and herbal medicines for the treatment of various sleep disorders have been used for medicinal purposes for centuries - including lavender. Various, complex biochemical processes in the brain provide us with sleep, incl. interaction with GABAergic signals.

As the main inhibitory neurotransmitter, GABA helps maintain the overall balance of neuronal excitation and inhibition in the central nervous system and plays one of the key roles in brain development and function. More than 20% of all neurons in the brain are thought to be GABAergic. Three different GABA receptors: GABAA, GABAB and GABAC are involved in the regulation of sleep and arousal (although to varying degrees). The most commonly used sleeping pills act directly on the GABA systems, ​especially benzodiazepine. 3 Atsauce: Bruni, O., Ferini-Strambi, L., Giacomoni, E., & Pellegrino, P. (2021). Herbal Remedies and Their Possible Effect on the GABAergic System and Sleep. Nutrients, 13(2), 530. doi:10.3390/nu13020530

Lavender's active ingredients can bind glutamate N-methyl-D-aspartate receptors (NMDA) and serotonin transporters. The NMDA receptor is believed to be crucial for the control of synaptic plasticity and to mediate memory function. Sleep-promoting GABAergic neurons are a major target for the pharmacological treatment of insomnia.

It must be said that despite the availability of several sleep medications, side effects are still a problem and there is still a demand for safer insomnia treatment options. Studies show that several substances of plant origin, incl. found in lavender, can act as sleep inducers by modulating GABAergic signalling in the brain. The safety and wide acceptance (absence of side effects) of herbal products among patients is a strong argument for preferring herbs over industrially produced drugs.

Hopkins and Cole discovered tryptophan at the beginning of the twentieth century after isolating it from the casein protein, while Ellinger and Flamand determined its molecular structure shortly thereafter. L-tryptophan (i.e., tryptophan) is one of the eight essential amino acids (amino acids that cannot be synthesised by the human body and must be obtained from the diet). 1 Atsauces: Richard, D. M., Dawes, M. A., Mathias, C. W., Acheson, A., Hill-Kapturczak, N., & Dougherty, D. M. (2009). L-Tryptophan: Basic Metabolic Functions, Behavioral Research and Therapeutic Indications. International Journal of Tryptophan Research, 2, IJTR.S2129. doi:10.4137/ijtr.s2129

So L-tryptophan is a unique protein amino acid that has an indole ring. Indole is a typical nitrogen heterocyclic aromatic compound, widely distributed in our daily products and natural environment. The indole ring is present in many alkaloids, phytohormones, plant flower oils, pigments and proteins. Because the indole nucleus has a wide spectrum of biological activities, it is widely used in the pharmaceutical industry.

After L-tryptophan enters various tissues and cells of the body, it is included in protein metabolism and synthesis, and it can also participate in various metabolic processes depending on the expression of specific enzyme activities in the tissues. 2 Atsauces: Palego, L., Betti, L., Rossi, A., & Giannaccini, G. (2016). Tryptophan Biochemistry: Structural, Nutritional, Metabolic, and Medical Aspects in Humans. Journal of Amino Acids, 2016, 1–13. doi:10.1155/2016/8952520  

L-tryptophan is the only precursor of peripherally and centrally produced serotonin. 3 Atsauces: Jenkins, T., Nguyen, J., Polglaze, K., & Bertrand, P. (2016). Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis. Nutrients, 8(1), 56. doi:10.3390/nu8010056 Serotonin regulates the balance of the nervous system, mental stability, mood and also sleep. On the other hand, melatonin is synthesised from serotonin. As the “output material” of melatonin, serotonin helps regulate sleep cycles and the internal clock. It has been proven that melatonin plays a decisive role in the quality of sleep.  Melatonin is a biologically active substance that is formed in our brain during the night (darkness) and regulates the biorhythms of our body - the cycle of sleep and wakefulness. 2 Atsauces: Palego, L., Betti, L., Rossi, A., & Giannaccini, G. (2016). Tryptophan Biochemistry: Structural, Nutritional, Metabolic, and Medical Aspects in Humans. Journal of Amino Acids, 2016, 1–13. doi:10.1155/2016/8952520 Both melatonin and serotonin are formed from the essential amino acid L-tryptophan, which we can only take in through food or food supplements. Significant amounts of L-tryptophan can be found in various types of cheese and meat.

Food supplements containing L-tryptophan are safe as long as they are not taken on a long-term basis. L-Tryptophan can cause someside effects such as drowsiness, stomach pain, vomiting, diarrhoea, headache, blurred vision, dizziness, palpitations and more.

L-tryptophan can interfere with the effects of many different drugs. Do not take L-tryptophan if you are taking antidepressants known as selective serotonin reuptake inhibitors (SSRIs), MAO inhibitors, tricyclic antidepressants, and atypical antidepressants. This can lead to a life-threatening condition called serotonin syndrome. Symptoms of serotonin syndrome include:

• • Extreme anxiety
• • Heart palpitations
• • Delirium
• • Severe muscle spasms
• • Increased body temperature

L-tryptophan supplements are not recommended for pregnant women.

Consult your doctor before taking L-tryptophan if you have cirrhosis of the liver.

Always tell your doctor about any food supplements you take, including natural and over-the-counter supplements. In this way, your doctor can check for possible side effects or interactions with any medications.

Atsauce Atsauce: https://www.webmd.com/vitamins-and-supplements/l-tryptophan-uses-and-risks

The main role of L-tryptophan in the human body is a part of protein synthesis. Because tryptophan is found in the lowest concentration of all the amino acids in the body, it is relatively lessavailable and it is considered to play a decelerating role in protein synthesis. Tryptophan is also a precursor of two important metabolic processes: kynurenine synthesis and serotonin synthesis (substance involved in the reaction resulting in the formation of the target substance - an intermediate member of the metabolic pathway). 1 Atsauce: Sainio EL, Pulkki K, Young SN. L-tryptophan: Biochemical, nutritional and pharmacological agents. Amino Acids. 1996;10:21–47.

Accordingly, serotonin is synthesised from the irreplaceable amino acid in the human body - L-tryptophan, while serotonin regulates mood, improves sleep quality and appetite. It is important that serotonin also participates in the regulation of dopamine - if it is lacking, it promotes its release, if there is too much dopamine - it helps to slow down its release. Low serotonin levels are thought to be closely related to depression, anxiety, sleep disorders, weight gain, and other health problems. If there is a deficiency of serotonin in the body, then the person's mood deteriorates, pessimism and apathetic mood increases, as a result of which the desire to do something disappears.

Several laboratories have demonstrated the positive effect of L-tryptophan on sleep quality 2 Atsauce: Hartmann, E. (1982). Effects of L-tryptophan on sleepiness and on sleep. Journal of Psychiatric Research, 17(2), 107–113. doi:10.1016/0022-3956(82)90012-7 , as well as the fact that tryptophan reduces the time it takes to fall asleep in patients with mild insomnia or those who take a long time to fall asleep. 3 Atsauce: Simon N. Young:  Is tryptophan a natural hypnotic?; Journal of Psychiatry & Neuroscience; 2003 Mar; 28(2): 160; PMCID: PMC161739

Tryptophan has not been found to have any effect on next-day alertness. In patients with moderate to severe insomnia, tryptophan is not as effective as standard sleep aids.

In general, we can say that serotonin regulates the balance of the nervous system; mental stability, mood and also sleep, is the “raw material” for melatonin. In turn, it has been proven that melatonin plays a decisive role in the quality of sleep.  Both melatonin and serotonin are formed from the essential amino acid L-tryptophan, which we can only get through food or food supplements.

However, when tryptophan is ingested as part of the diet, it is joined by other large neutral amino acids that compete for the system that transports them all to the brain. As a result, dietary tryptophan intake, unlike tryptophan in the form of food supplements, does not increase tryptophan levels in the brain. Thus, the popular myth that a glass of milk before bed has a calming effect because it contains tryptophan is false. 3 Atsauce: Simon N. Young:  Is tryptophan a natural hypnotic?; Journal of Psychiatry & Neuroscience; 2003 Mar; 28(2): 160; PMCID: PMC161739

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.

California poppies are plants of the Eschscholzia genus of the poppy family (Papaveraceae). Depending on the place of growth, they are divided into two large subspecies E.californica subsp. californica and E. californica subsp. Mexican.

The natural range of the California poppy is the United States (states: California, Oregon, Washington, Nevada, Arizona, New Mexico) and Mexico (States: Sonora and Baja California), but as an ornamental plant it is distributed throughout the world.

The California poppy is an annual (in places where it does not grow naturally) or a perennial 130-152 cm tall plant. The flowers are yellow to orange in colour. It blooms from February to September (in the natural distribution areas) and the flowers have a specific aroma.

Californian poppy leaves are said to have been used by the Indians as a medicine, and the pollen - in cosmetics. The seeds, on the other hand, can be used in cooking.

California poppies are known for their calming, anti-anxiety and sleep-inducing effects. This effect is associated with protopine and allocryptopine. Both alkaloids act as weak stimulants - GABA receptor initiators (agonists) and as acetylcholinesterase inhibitors preventing the breakdown of acetylcholine (ACh) and increasing the duration of action and the level of ACh at the nerve endings, called synapses.[[1:: Atsauces: Fedurco, M., Gregorová, J., Šebrlová, K., Kantorová, J., Peš, O., Baur, R., … Táborská, E. (2015). Modulatory Effects of Eschscholzia californica Alkaloids on Recombinant GABAA Receptors. Biochemistry Research International, 2015, 1–9. doi:10.1155/2015/617620]] Another aporphine alkaloid isolated from this plant, namely N-methyllaurotetanine (NMT), acts as a serotonin 5HT 1A R receptor blocker (antagonist). 2 Atsauces: S. Gafner, B. M. Dietz, K. L. McPhail et al., “Alkaloids from Eschscholzia californica and their capacity to inhibit binding of [3H]8-hydroxy-2-(di-N-propylamino) tetralin to 5-HT1A receptors in vitro” Journal of Natural Products, vol. 69, no. 3, pp. 432–435, 2006 .Protopine and allocryptopine have been found to block the human serotonin and noradrenaline transporters (hSERT and NERT) and have antidepressant-like effects. 1 Atsauces: Fedurco, M., Gregorová, J., Šebrlová, K., Kantorová, J., Peš, O., Baur, R., … Táborská, E. (2015). Modulatory Effects of Eschscholzia californica Alkaloids on Recombinant GABAA Receptors. Biochemistry Research International, 2015, 1–9. doi:10.1155/2015/617620

In addition to the mentioned alkaloids, California poppies also contain other active components: alkaloids - cryptopine and chelidonine, as well as flavonoids and glycosides.

California poppies have no narcotic effects and are completely safe to use. It is not an opiate family plant. If the opium poppy has a disorientating effect, the California poppy has a normalising effect on human physiology and psychology. Alkaloids have a calming and relaxing effect on the body and mind, but they work gently.

California poppy is safe for most people when taken correctly perorally for up to three months. There is not enough research on the safety of long-term use of the California poppy.

If surgical intervention is planned: California poppies act on the central nervous system, causing drowsiness and other symptoms. There is a possibility that the California poppy may excessively slow down the central nervous system when used with anaesthesia and/or other drugs used during and after surgery. Stop using California poppy preparations at least 2 weeks before the scheduled surgery.

INTERACTION

Sedative medications (benzodiazepines and CNS depressants)

Interaction assessment: Moderate. Be careful when using this combination. Talk to your health care professional.

California poppies can cause drowsiness. Taking California poppy along with sedative medications can cause excessive drowsiness.

Some of these sedative medications include clonazepam (Klonopin), diazepam (Valium), lorazepam (Ativan), phenobarbital (Donnatal), zolpidem (Ambien), and others.

California poppy is not recommended for:

Insomnia is defined as difficulty falling asleep or staying asleep that is caused by the effects of the day's events and is not related to environmental conditions or insufficient duration of sleep. In the international classification of sleep disorders, insomnia is considered chronic if it persists for a long time - at least three months with a frequency of at least three times a week. In other cases, insomnia is defined as temporary and can be considered corrective, acute, or anxiety-related insomnia.

The Committee on Herbal Medicinal Products (HMPC) and the European Medicines Agency (EMA) have concluded that California poppy can be used to relieve mild symptoms of mental stress and as a sleeping aid. 1 Atsauce: https://www.ema.europa.eu/en/medicines/herbal/eschscholziae-herba]]

The sedative and anxiolytic properties of California poppy have been demonstrated in several preclinical studies. With the use of this herb, an increase in sleep time and a decrease in motor activity during sleep were observed. 2 Atsauce:  Abdellah, S. A., Berlin, A., Blondeau, C., Guinobert, I., Guilbot, A., Beck, M., & Duforez, F. (2019). A combination of Eschscholtzia californica Cham. and Valeriana officinalis L. extracts for adjustment insomnia: A prospective observational study. Journal of Traditional and Complementary Medicine. doi:10.1016/j.jtcme.2019.02.003

The chemical composition of California poppy, like all other representatives of the poppy family, is rich in alkaloids, ​especially protopine, berberine, allocryptopine, escholtzine, and californidine. Flavonoids, especially rutose, have been found in the plant. California poppy contains various carotenoids, such as zeaxanthin, which determine the colour of the plant.

The medicinal properties are related to the alkaloids contained in its chemical composition. Thanks to the alkaloids, California poppy has a calming, antispasmodic and even analgesic effect on the human body.

With the help of California poppy, you can normalise sleep, get rid of insomnia, and the slightly antispasmodic and sedative effect of alkaloids allows the use of the plant extract for the treatment of psychological and physical problems and nervous disorders.

Calcium is the mineral that is mostly associated with healthy bones and teeth, although it also plays an important role in blood clotting, helping muscles to contract. At the same time, calcium regulates a normal heart rhythm and ensures nerve functions, as well as participates in the regulation of hormone activity, reduces neuromuscular excitement, participates in the absorption and use of vitamin B12. About 99% of the calcium in the body is in the bones, with the remaining 1% in the blood, muscles and other tissues. 1 Atsauces: Bruder J. M., Guise T. A., Mundy G. R. Mineral metabolism. In: Endocrinology & Metabolism, 4th ed., P. Felig, L. A. Frohman (eds.); Chapter 22, p. 1079 – 1159, 2001.

There are three forms of calcium in the blood plasma: 41% is bound to proteins and in this way it cannot cross the capillary membrane; 9% is in combination with anions and interstitial (tissue) fluid, able to cross the capillary membrane and 50% is ionised and able to cross the capillary membrane.  Calcium plays an important role in cellular and extracellular fluid exchange. Calcium ions are necessary in the transmission of nerve impulses.

In neurons, calcium is a key element and it performs multiple tasks. It helps spread electrical signals along axons (nerve cell projections conducting nerve impulses to other nerve cells). It activates synaptic connections to carry neurotransmitters (transmit nerve impulse from synapse to cell) into synapses. Calcium is also involved in memory formation, metabolism and cell growth.

All cells from primitive unicellular organisms to highly differentiated neurons in the cerebral cortex depend on calcium metabolism. This element is important in living organisms, especially in cell physiology, where the movement of Ca2+ in and out of the cytoplasm acts as a signal for many cellular processes. 2 Atsauces: Kumar V., Abbas A. K., Fausto N. Robbins and Cotran pathologic basis of disease. 7th ed. 2005; p. 1183 – 1189.

In food supplements, calcium is found in various forms, where each of the compounds contains a different amount of calcium, or the basic substance, elemental calcium. The following forms of calcium are most commonly used in food supplements:

• • Calcium carbonate (40% elemental calcium)
• • Calcium citrate (21% elemental calcium)
• • Calcium lactate (13% elemental calcium)
• • Calcium gluconate (9% elemental calcium)

Calcium carbonate contains significantly more elemental calcium than other compounds, but requires an acidic food or drink to absorb it. The acid in calcium citrate, on the other hand, promotes the absorption of the compound in an environment of reduced acidity and may be more effective in people taking antacids.

Long-term calcium deficiency can cause changes in teeth (teeth can suddenly become more sensitive, softer and more easily injured; it may be the case that the tooth simply breaks when biting on harder food), cataracts, changes in the brain and osteoporosis, which causes brittle bones.

Symptoms of calcium deficiency:

A person with calcium deficiency may experience:

• • muscle pain, cramps and spasms,
• • pain in the thighs and arms when walking or moving,
• • numbness and tingling in the arms, legs and feet and around the mouth.

These symptoms may come and go, but they do not, however, tend to disappear with activity. More extreme sensations may indicate a more severe deficiency, which can lead to: seizures, arrhythmia, and even death.

Low calcium levels can cause extreme fatigue, which includes a lack of energy and a general feeling of sluggishness. It can also cause insomnia. Fatigue associated with calcium deficiency can also include dizziness and double vision, characterised by a lack of focus, oversight, and confusion.

Prolonged calcium deficiency can cause:

• • dry skin
• • dry, broken or brittle nails
• • brittle hair
• • alopecia, which causes hair loss in the form of spots
• • eczema or skin inflammation that can cause itchy or dry spots
• • psoriasis

Bones store calcium well, but they need high levels of calcium to be strong. If total calcium levels are low, the body can divert some ofthe calcium from the bones to processes needed by the body, making them brittle and prone to fracture.

Over time, too little calcium can cause osteopenia, a decrease in bone mineral density. This can lead to osteoporosis, which makes the bones thinner and more vulnerable to fractures, as well as pain and postural problems.

Some studies suggest that calcium deficiency may be associated with mood disorders, including depression.

Anyone who suspects that calcium deficiency is contributing to depressive symptoms should consult a doctor. After checking your calcium levels, your doctor may recommend additional calcium intake.

For the body to use calcium, it is worth knowing some nuances:

• • together with calcium, vitamin D is needed - both help each other fulfil their functions;
• • in order for calcium to strengthen bones and teeth, sufficient phosphorus must be taken;
• • appropriate enzymes are needed in the gastrointestinal tract, which dissolve the ingested calcium;
• • excessive use of coffee or salt promotes the release of calcium from the body;
• • bone robbers include oxalic acid present in certain vegetables such as rhubarb and spinach;
• • cocoa and black tea negatively affect the absorption of calcium in the body;
• • a large amount of sugar, salt, phosphates and fat in the diet has a negative effect on calcium absorption. Fast snacks, ready-made meals, meat and sausage products contain a particularly large amount of phosphates, so their consumption should be moderate;
• • absorption is hindered by fatty and greasy food, white bread, wheat bran. Absorption can be enhanced by vitamin C and products containing it;
• • any disease of a gastroenterological nature reduces the ability to absorb calcium.

Some foods that are rich in calcium: dairy products such as milk, cheese and yoghurt; beans; figs; broccoli; tofu; soy milk and spinach.

Adults who have not been observed to have a calcium deficiency need 1,000 mg of calcium per day, persons over 51 years of age - 1,200 mg per day.

There is an inverse relationship between calcium intake and absorption. Calcium absorption from food is about 45% when 200 mg/day is taken, but only 15% when intake exceeds 2,000 mg/day. Age can also affect the absorption of calcium taken in from food. Dietary absorption of calcium is as high as 60% in infants and young children, who need significant amounts to build bone, but this drops to about 25% in adulthood and continues to decline with age.

Bloating, gases and constipation may be observed when taking calcium supplements. Very high doses of calcium can cause kidney stones. 1 Atsauce: https://www.webmd.com/diet/supplement-guide-calcium;

Interaction. If you regularly take any prescription or over-the-counter medications, ask your doctor if it is safe to take extra calcium supplements. Calcium can interact with medications for treating heart disease, diabetes, epilepsy, and other diseases. High doses of vitamin D can lead to dangerously high calcium levels. High doses of calcium can also prevent your body from absorbing minerals such as iron and zinc. Try to take calcium one to two hours before or after taking other food supplements or medications. If you happen to take calcium at the same time as other medications or food supplements, they may interact with these products and they will be excreted from your body without being absorbed.

Calcium supplements can interact or interfere with certain medications, and some medications can lower calcium levels in the body. Here are some examples:

Risks. If you have kidney disease, heart problems, sarcoidosis, or bone tumours, do not take calcium supplements unless directed by your doctor.

Overdose. High levels of calcium in the blood can cause nausea, dry mouth, stomach pain, irregular heartbeat, confusion and even death. 1 Atsauce: https://www.webmd.com/diet/supplement-guide-calcium;

Calcium is directly related to our sleep cycles. In one study published in the European Neurology Journal, researchers found that calcium levels in the body are higher during some of the deeper stages of sleep, such as the rapid eye movement (REM) phase. The study concluded that sleep disorders, specifically a lack of REM deep sleep or disturbed REM sleep, are associated with calcium deficiency. Normal sleep patterns were restored after blood calcium levels normalised. 1 Atsauce: https://www.medicalnewstoday.com/releases/163169#1]]

Calcium helps the brain to use the amino acid tryptophan to produce the sleep-inducing substance melatonin.

If the body lacks calcium, nerve impulses may be inhibited and unstable, leading to excessive anxiety or stress. In addition, the nervous system will encounter many obstacles in its operation: the contraction of the heart will be disturbed and the function of muscle reflexes will change. If calcium deficiency is prolonged, insomnia, difficulty falling asleep, poor sleep and frequent awakening will be observed.

Calcium deficiency can cause other related diseases, such as peptic ulcers, which also seriously affect sleep. Lack of calcium stimulates the increase of stomach acid; long-term increased acid will cause damage to the stomach lining, and even ulcers. This process is often accompanied by symptoms such as heartburn, nausea and nighttime stress that causes insomnia.

At the same time, it should be mentioned that there is a close relationship between vitamin D levels and calcium levels, where calcium levels regulate the formation of the deep sleep phase, while the classical functions of vitamin D include intestinal calcium transport and bone mineralisation, which are essential for calcium homeostasis. It is possible that sleep disorders in the case of vitamin D deficiency may be related to altered calcium levels. Lower calcium level in the serum may be associated with more impaired sleep-wake control and rest-activity rhythms. [[2:: Atsauce: Yi-Seon Jeon, Seungyeong Yu, Chaeyeon Kim, Hyuk Joo Lee, In-Young Yoon and Tae Kim1 “Lower Serum Calcium Levels Associated with Disrupted Sleep and Rest–Activity Rhythm in Shift Workers”; Nutrients. 2022 Aug; 14(15): 3021.; Published online 2022 Jul 22. doi: 10.3390/nu14153021]]

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.