Ingredients with a purpose

Vitamin A is actually a group of related fat-soluble compounds. In nature Vitamin A occurs as preformed Vitamin A (most commonly retinyl palmitate) in animal foods and as pro-Vitamin A (most commonly β-carotene) in plants.¹

Vitamin A compounds are essential for vision, immune function, reproduction, and for the integrity and function of the epithelium that lines the airways, blood vessels, gut and is part of the skin.² In mammals, both types of Vitamin A are stored in the liver and then used as necessary by the rest of the body after being converted to retinol.^3,4

We all know that eating carrots helps you see in the dark but at most only 50% of the preformed Vitamin A in carrots is converted into Retinol.⁴ Interestingly, in ancient Greece and Egypt, Ox liver as prescribed as a cure for night blindness.⁵

Interestingly, it is thought that zinc helps to convert provitamin A (from plants) to Retinol that can then be used by the body.⁵ In the body nothing works in isolation. If your zinc is low, you will activate less Vitamin A from plant food.

Given the different forms of Vitamin A, it is now listed as a supplement indicating how much Retinol it will become: RAE = Retinol Activity Equivalents.⁶

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Retinol is obviously central to a healthy of the body but the exact way that Retinol works is still being researched.¹ However, it is known that Retinol controls over 500 genes in the body.⁷
Retinol is essential for:^{2, 8}

• Vision
• Immune function and resistance to viral and other infections
• Reproduction (health and growth of the embryo)
• Physical growth of infants and children
• Integrity and function of the epithelium that lines the airways, blood vessels, gut and is part of the skin
• Function of the gut

Retinol also seems to play a role in glucose and fat metabolism.⁷

While Retinol deficiency is common in developing countries, it is becoming prevalent in areas where excess food is the norm. This is due to the increasing prevalence of Fatty Liver Disease in Western populations. Fatty Liver Disease affects the way the liver metabolizes and stores Vitamin A, making Retinol less available to the rest of the body.³

Your body is an intricate machine, all parts working together.

B-Carotene Actions

Besides being converted to Retinol, Beta Carotene, the pro-Vitamin A found in carrots also has other functions. These include:

• Anti-oxidant functions⁴
• Protection against sunburn⁹
• Protection against cancer¹⁰
• Improving the immune response¹¹

Safety

Too much Vitamin A can cause low-grade fever, headache, fatigue, anorexia, intestinal disturbances, enlarged liver, anemia, hypercalcemia, swellings in the skin, joint and bone pain, and skin changes such as yellowing, dryness, alopecia, and photosensitivity.²

Unless prescribed by a Functional Medical Doctor, supplementing with low doses of Vitamin A that are within the RDA (Recommended Daily Allowance) is suggested.

References

1. Borel P, Desmarchelier C. Genetic Variations Associated with Vitamin A Status and Vitamin A Bioavailability. Nutrients. 2017;9(3):246. doi:10.3390/nu9030246
2. Chea EP, Lopez MJ, Milstein H. Vitamin A. StatPearls. StatPearls Publishing Copyright © 2020, StatPearls Publishing LLC.; 2020.
3. Saeed A, Dullaart RPF, Schreuder T, Blokzijl H, Faber KN. Disturbed Vitamin A Metabolism in Non-Alcoholic Fatty Liver Disease (NAFLD). Nutrients. Dec 29 2017;10(1)doi:10.3390/nu10010029
4. Dawson MI. The importance of vitamin A in nutrition. Curr Pharm Des. Feb 2000;6(3):311-25. doi:10.2174/1381612003401190
5. Braun L, Cohen M. Herbs & Natural Supplements; An evidence-based guide. 3rd ed. Churchill Livingston; 2010.
6. Vitamin A Fact Sheet for Health Professionals National Institutes of Health Office of Dietary Supplements. Updated February 14, 2020. Accessed December 19, 2020, 2020. https://ods.od.nih.gov/factsheets/VitaminA-HealthProfessional/#en5
7. Frey SK, Vogel S. Vitamin A metabolism and adipose tissue biology. Nutrients. Jan 2011;3(1):27-39. doi:10.3390/nu3010027
8. Wiseman EM, Bar-El Dadon S, Reifen R. The vicious cycle of vitamin a deficiency: A review. Crit Rev Food Sci Nutr. Nov 22 2017;57(17):3703-3714. doi:10.1080/10408398.2016.1160362
9. Stahl W, Sies H. β-Carotene and other carotenoids in protection from sunlight. Am J Clin Nutr. Nov 2012;96(5):1179s-84s. doi:10.3945/ajcn.112.034819
10. Xavier AA, Pérez-Gálvez A. Carotenoids as a Source of Antioxidants in the Diet. Subcell Biochem. 2016;79:359-75. doi:10.1007/978-3-319-39126-7_14
11. Milani A, Basirnejad M, Shahbazi S, Bolhassani A. Carotenoids: biochemistry, pharmacology and treatment. British journal of pharmacology. Jun 2017;174(11):1290-1324. doi:10.1111/bph.13625

Vitamin C conjures up images of piles of lemons and oranges in the hulls of ships sailing the world, preventing the feared disease, scurvy. Most mammals make Vitamin C in their bodies from glucose. However, humans, along with primates, guinea pigs and bats do not make Vitamin C and need to get this from their diet.¹ While only 10mg of Vitamin C a day will prevent scurvy, higher doses are required for optimal functioning.²

Scurvy had pretty much vanished from the minds of the population and physicians, but it has started to make a reappearance due to poor diet and over-cooking fruit and vegetables.^{3, 4}

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Vitamin C is a major water soluble anti-oxidant in the body. All of the effects of Vitamin C are due to its anti-oxidant effects,⁵ which not only enables certain enzymes in the body to work but also directly quenches harmful free radicals that can damage cells and tissues.

As a direct anti-oxidant Vitamin C protects the protein, fats, carbohydrates and DNA in the cell that can be damaged by normal cellular metabolism.⁶
This means that Vitamin C helps to guard against almost all chronic illnesses and is also possibly involved the healthy development of the embryo into a full-grown adult human.⁷

Vitamin C may even assist with weight loss.⁸

Vitamin C is also required by at least eight different enzymes in the body that are involved in production of collagen and carnitine as well as the synthesis of norepinephrine and the metabolism of certain types of hormones.⁹

Amongst other effects these Vitamin C dependent enzymes help to:^{5, 10}

• lower histamine (meaning less allergies)
• increase the utilization of creatine (providing more energy)
• increase collagen (strengthening the body)
• make neurotransmitters such as dopamine and norepinephrine (improving mood)

These enzymes are also involved in making red blood cells and when not working correctly are associated with heart disease, diabetes and cancer.⁵

The Common Cold (which includes Corona viruses such as SARS-CoV2)

Vitamin C deficiency impairs immunity and increases susceptibility to infections.¹¹ Furthermore, infections can result in low Vitamin C levels. Supplementing lower doses of Vitamin C may prevent respiratory and other infections, while higher doses are required for treatment.¹¹

Safety

Generally, Vitamin C is well tolerated. It can cause diarrhea at in high doses.²

References

1. Linster CL, Van Schaftingen E. Vitamin C. Biosynthesis, recycling and degradation in mammals. Febs j. Jan 2007;274(1):1-22. doi:10.1111/j.1742-4658.2006.05607.x
2. Braun L, Cohen M. Herbs & Natural Supplements; An evidence-based guide. 3rd ed. Churchill Livingston; 2010.
3. Lipner S. A classic case of scurvy. Lancet. Aug 4 2018;392(10145):431. doi:10.1016/s0140-6736(18)31491-0
4. Parry M. Poor Diet Blamed as Scurvy Reappears in Australia. Independent. November 29, 2016. Accessed December 20, 2020. https://www.independent.co.uk/life-style/health-and-families/health-news/scurvy-reappears-australia-poor-diet-malnutrition-a7444996.html
5. Padayatty SJ, Levine M. Vitamin C: the known and the unknown and Goldilocks. Oral Dis. Sep 2016;22(6):463-93. doi:10.1111/odi.12446
6. Englard S, Seifter S. The biochemical functions of ascorbic acid. Annu Rev Nutr. 1986;6:365-406. doi:10.1146/annurev.nu.06.070186.002053
7. Camarena V, Wang G. The epigenetic role of vitamin C in health and disease. Cellular and molecular life sciences : CMLS. Apr 2016;73(8):1645-58. doi:10.1007/s00018-016-2145-x
8. Johnston CS. Strategies for healthy weight loss: from vitamin C to the glycemic response. Journal of the American College of Nutrition. Jun 2005;24(3):158-65. doi:10.1080/07315724.2005.10719460
9. Granger M, Eck P. Dietary Vitamin C in Human Health. Adv Food Nutr Res. 2018;83:281-310. doi:10.1016/bs.afnr.2017.11.006
10. Johnston CS, Solomon RE, Corte C. Vitamin C depletion is associated with alterations in blood histamine and plasma free carnitine in adults. Journal of the American College of Nutrition. Dec 1996;15(6):586-91. doi:10.1080/07315724.1996.10718634
11. Carr AC, Maggini S. Vitamin C and Immune Function. Nutrients. Nov 3 2017;9(11)doi:10.3390/nu9111211

Vitamin D3, the Sunshine Vitamin, is not really a Vitamin and is more correctly classified as a hormone which is made in body.¹ Of course, the sun’s rays are needed for your body to be able to make Cholecalciferol.

Vitamin D generally refers to related compounds with Vitamin D3 / Cholecalciferol being made in the human body or obtained in the diet is small amounts. Vitamin D2 / Ergocalciferol is either synthetically made or can be obtained from some mushrooms.² Vitamin D from sun, food or supplements (cholecalciferol) is activated in the liver and the kidneys to the active form (calcitriol).¹

Cholecalciferol is also found in fatty fish such as herring, salmon, tuna and sardines, as well as beef, liver, eggs and butter. However, the amount of Vitamin D from animal sources depends on agricultural practices. As an example, in a 2007 study, farmed salmon was found to contain only 25% of the amount of Vitamin D3 found in wild salmon.³

It is now becoming increasingly apparent that sun exposure (without sunscreen) is important for human health. Sun exposure is the most important source of Vitamin D3.⁴ Beyond, Vitamin D3, sun exposure is thought it to have multiple other benefits.⁵ Start low, go slow and get regular sun exposure!

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Vitamin D was first discovered in relation to its effects in preventing rickets⁶ and has traditionally been associated with bone health. It is now known that Vitamin D has a wide range of effects by binding to the Vitamin D receptor which is found throughout the body.⁷

The actions of Vitamin D are summarized in this pictorial.^{6, 8}

Safety

Vitamin D excess can occur if taking high doses. However, this does not occur with sun exposure.⁹ Prolonged intakes of high doses of Vitamin D may lead to tissue and organ damage, especially kidney damage as well as calcifications in blood vessels and around joints.^{1, 10}

In general, keeping your total Vitamin D intake below 4000 iu (100mcg) is unlikely to cause any problems.¹¹ Even better, get your levels tested.

References

1. Braun L, Cohen M. Herbs & Natural Supplements; An evidence-based guide. 3rd ed. Churchill Livingston; 2010.
2. Nowson CA, McGrath JJ, Ebeling PR, et al. Vitamin D and health in adults in Australia and New Zealand: a position statement. Med J Aust. Jun 18 2012;196(11):686-7. doi:10.5694/mja11.10301
3. Lu Z, Chen TC, Zhang A, et al. An evaluation of the vitamin D3 content in fish: Is the vitamin D content adequate to satisfy the dietary requirement for vitamin D? The Journal of steroid biochemistry and molecular biology. Mar 2007;103(3-5):642-4. doi:10.1016/j.jsbmb.2006.12.010
4. Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G. Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects. Physiol Rev. Jan 2016;96(1):365-408. doi:10.1152/physrev.00014.2015
5. van der Rhee HJ, de Vries E, Coebergh JW. Regular sun exposure benefits health. Med Hypotheses. Dec 2016;97:34-37. doi:10.1016/j.mehy.2016.10.011
6. Türkmen AS, Kalkan I. Vitamin D Deficiency in Children: Health Consequences and Prevention. 2018:471-492.
7. Pike JW, Christakos S. Biology and Mechanisms of Action of the Vitamin D Hormone. Endocrinol Metab Clin North Am. Dec 2017;46(4):815-843. doi:10.1016/j.ecl.2017.07.001
8. Zittermann A, Gummert JF. Nonclassical Vitamin D Actions. Nutrients. 2010;2(4):408-425.
9. Sizar O, Khare S, Goyal A, Bansal P, Givler A. Vitamin D Deficiency. StatPearls. StatPearls Publishing
   Copyright © 2020, StatPearls Publishing LLC.; 2020.
10. Razzaque MS. Can adverse effects of excessive vitamin D supplementation occur without developing hypervitaminosis D? The Journal of steroid biochemistry and molecular biology. Jun 2018;180:81-86. doi:10.1016/j.jsbmb.2017.07.006
11. Vitamin D Fact Sheet for Health Professionals. NIH National Institutes of Health Office of Dietary Supplements Accessed December 8, 2020. https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/#ref

Tocotrienols are part of the greater Vitamin E family. Vitamin E was first named the “anti-sterility” vitamin as it was found that it was necessary for rats to maintain their fertility.¹

Vitamin E consists of eight different molecules: four in the tocopherol family and four in the tocotrienol family. Vitamin E is found in both plant and animal foods with rich sources including nuts and seeds, cold-pressed vegetable oils, avocado, olive oil, egg yolk, liver, milk and butter.^2-4 Given it’s widespread occurrence in nature, Vitamin E deficiency is rare and is usually related to other conditions resulting in poor absorption.³

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Vitamin E is a major fat-soluble anti-oxidant5 and is part of the “anti-oxidant network.”6 Once Vitamin E has acted as an anti-oxidant, itself becoming a free radical, it is recycled by Vitamin C or other antioxidants such as glutathione back to its functional state.7

The Anti-oxidant Network:

Tocotrienols

Alpha tocopherol is the most abundant type of Vitamin E and most research has been done on this molecule. However, the importance of other types of Vitamin E, especially the tocotrienols is now being highlighted.8 Tocotrienols are much less abundant in food, mainly found in annatto seed, palm oil, barley and rice bran.4, 9 Tocotrienols have been shown to have distinct effects separate from tocopherols, including:^{4, 9, 10}

• Anti-cancer effects
• Anti-inflammatory effects
• Nerve and brain protection
• Cholesterol lowering effects
• Lowers blood pressure
• Possible anti-obesity effects
• Greater anti-oxidant affect when compared to tocopherols

Furthermore, alpha tocopherol found in most Vitamin E and multivitamin supplements, seems to inhibit the effect of tocotrienols.¹¹ It is for this reason and the fact that alpha tocopherol deficiency is very rare, Omic as included only tocotrienols in its Balance formula.

Safety

High dose tocopherol supplementation may lead to gastric upset, headache, visual changes and increased bleeding.¹² Tocotrienols have been grouped into Vitamin E as a whole and do not have a Recommended Dietary Allowance outside of Vitamin E. Early clinical studies have found tocotrienol supplementation to be well tolerated.^{13, 14}

References

1. Niki E, Traber MG. A history of vitamin E. Ann Nutr Metab. 2012;61(3):207-12. doi:10.1159/000343106
2. Caporaso N, Savarese M, Paduano A, Guidone G, De Marco E, Sacchi R. Nutritional quality assessment of extra virgin olive oil from the Italian retail market: Do natural antioxidants satisfy EFSA health claims? Journal of Food Composition and Analysis. 2015/06/01/ 2015;40:154-162. doi:https://doi.org/10.1016/j.jfca.2014.12.012
3. Braun L, Cohen M. Herbs & Natural Supplements; An evidence-based guide. 3rd ed. Churchill Livingston; 2010.
4. Colombo ML. An update on vitamin E, tocopherol and tocotrienol-perspectives. Molecules. Mar 24 2010;15(4):2103-13. doi:10.3390/molecules15042103
5. Constantinescu A, Han D, Packer L. Vitamin E recycling in human erythrocyte membranes. The Journal of biological chemistry. May 25 1993;268(15):10906-13.
6. Sen CK, Packer L. Thiol homeostasis and supplements in physical exercise. Am J Clin Nutr. Aug 2000;72(2 Suppl):653s-69s. doi:10.1093/ajcn/72.2.653S
7. Vatassery GT. In vitro oxidation of alpha-tocopherol (vitamin E) in human platelets upon incubation with unsaturated fatty acids, diamide and superoxide. Biochim Biophys Acta. Nov 6 1987;926(2):160-9. doi:10.1016/0304-4165(87)90233-9
8. Jiang Q. Natural Forms of Vitamin E as Effective Agents for Cancer Prevention and Therapy. Adv Nutr. Nov 2017;8(6):850-867. doi:10.3945/an.117.016329
9. Fukui K. Neuroprotective and Anti-Obesity Effects of Tocotrienols. J Nutr Sci Vitaminol (Tokyo). 2019;65(Supplement):S185-s187. doi:10.3177/jnsv.65.S185
10. Sen CK, Khanna S, Rink C, Roy S. Tocotrienols: the emerging face of natural vitamin E. Vitam Horm. 2007;76:203-61. doi:10.1016/s0083-6729(07)76008-9
11. Shibata A, Nakagawa K, Tsuduki T, Miyazawa T. α-Tocopherol suppresses antiangiogenic effect of δ-tocotrienol in human umbilical vein endothelial cells. J Nutr Biochem. Apr 2015;26(4):345-50. doi:10.1016/j.jnutbio.2014.11.010
12. Medina J, Gupta V. Vitamin E. StatPearls. StatPearls Publishing
    Copyright © 2020, StatPearls Publishing LLC.; 2020.
13. Ghani SMA, Goon JA, Azman N, Zakaria SNA, Hamid Z, Ngah WZW. Comparing the effects of vitamin E tocotrienol-rich fraction supplementation and α-tocopherol supplementation on gene expression in healthy older adults. Clinics (Sao Paulo). Mar 7 2019;74:e688. doi:10.6061/clinics/2019/e688
14. Meganathan P, Jabir RS, Fuang HG, et al. A new formulation of Gamma Delta Tocotrienol has superior bioavailability compared to existing Tocotrienol-Rich Fraction in healthy human subjects. Sci Rep. Sep 1 2015;5:13550. doi:10.1038/srep13550

Vitamin B1 (Thiamin) was the first B Vitamin to be identified.¹ It is found in lean pork and other meats, wheat germ, liver, eggs, fish, legumes and whole grains.² Thiamin is destroyed by processing as indicated by the fact that the Vitamin B1 deficiency illness, Beriberi reached a peak in Japan in the 17th century when the population changed from eating unpolished rice to eating white rice.

Thiamin cannot be made in the body and the body only stores a small amount Thiamin, meaning an almost continuous supply is necessary and deficiency can develop after 14 days of restricted intake.³ This can occur not only in those with restricted access to food but can also occur with alcohol abuse, persistent vomiting and where absorption is decreased such as those who have undergone bariatric surgery.⁴

Unfortunately, while Thiamin is readily available in food, our penchant for processed foods, has led to a surprisingly high incidence of Thiamin deficiency.² Cooking and canning can lead to the loss of 85% of the Thiamin in food.³ Furthermore, the more refined carbohydrates that are eaten, the higher the requirement for Thiamin intake. So, for those eating a processed high carbohydrate diet, there is a significantly increased likelihood of Thiamin deficiency.⁵

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Thiamine is involved in a number of enzymes, most of which are involved in the production of the energy molecule, ATP, where Thiamin works closely with Magnesium.^{1, 5} Thiamin is also crucial to the synthesis of DNA, the metabolism of amino acids and is part of the anti-oxidant processes in the cell,⁶ due to its role in the NADHP production.⁴

Many organ systems are dependent on Thiamin for functioning.⁴ The brain, in particular, needs the ATP that Thiamin helps to create. Adequate Thiamin is required for mood, sleep, energy and memory.⁵ It is also crucial to the optimum functioning of the heart and vision,¹ and the peripheral nervous system, helping you keep your balance.³

Safety

Thiamine is generally well tolerated and there are no known adverse effects.⁷

References

1. Mallat J, Lemyze M, Thevenin D. Do not forget to give thiamine to your septic shock patient! J Thorac Dis. Jun 2016;8(6):1062-6. doi:10.21037/jtd.2016.04.32
2. Lonsdale D. Thiamin. Adv Food Nutr Res. 2018;83:1-56. doi:10.1016/bs.afnr.2017.11.001
3. Braun L, Cohen M. Herbs & Natural Supplements; An evidence-based guide. 3rd ed. Churchill Livingston; 2010.
4. Martel J, Kerndt C, Franklin D. Vitamin B1 (Thiamine). 2020:PMID: 29493982.
5. Dhir S, Tarasenko M, Napoli E, Giulivi C. Neurological, Psychiatric, and Biochemical Aspects of Thiamine Deficiency in Children and Adults. Mini Review. Frontiers in Psychiatry. 2019-April-04 2019;10(207)doi:10.3389/fpsyt.2019.00207
6. Depeint F, Bruce W, Shangari N, Mehta R, O’Brien P. Mitochondrial function and toxicity: Role of the B vitamin family on mitochondrial energy metabolism. Chemico-biological interactions. 11/01 2006;163:94-112. doi:10.1016/j.cbi.2006.04.014
7. Wiley KD, Gupta M. Vitamin B1 Thiamine Deficiency. StatPearls. StatPearls Publishing

Vitamin B2 (Riboflavin) was first discovered in milk, as the compound providing the yellow-white tinge.¹

Riboflavin works in concert with the other B Vitamins and is critical for a wide-range of processes in the body.² Therefore, it is essential to maintaining health and function. Luckily, Riboflavin is found in many foods including animal foods such as organ meats, chicken, fish, eggs and dairy as well as plant foods such as green vegetables and to a lesser extent grains (unless these are fortified with B2). Processing such as blanching, fermenting, cooking, and adding bicarb to green vegetables will also destroy Riboflavin.¹

Deficiency of Riboflavin is more likely to occur in those with poor absorption, high alcohol intake and those on restricted diets, such as vegan diets and often occurs in teenage girls and the elderly.² An increased requirement for Riboflavin is found in athletes, pregnancy and lactation, infants and growing children meaning that these individuals are more likely to become deficient in Riboflavin if their dietary intake is marginal.^{2, 3}

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In the body Riboflavin is converted into to coenzymes (FMN and FAD).⁴ It is through these enzymes that Riboflavin exerts most of its effects. Riboflavin plays an important role in:^{2, 4, 5}

• Energy production from fat and carbohydrate, making ATP
• Anti-oxidant capacity of cells, partially by recycling glutathione the master anti-oxidant
• Regulation of neuro-transmitters such as dopamine and norepinephrine
• The normal breakdown of purines from DNA and RNA
• Activation and / or metabolism of other B Vitamins such as folate (B9), niacin (B3) pyridoxine (B6), cobalamin (B12), as well as that of Vitamin K and Vitamin D
• Iron absorption
• Anti-inflammatory systems
• Normal break down of medications

Interestingly a normal thyroid function is required for Riboflavin to work optimally.¹ In the body, no one compound or system works in isolation.
As all our cells require energy, Riboflavin is involved in a large number of biological processes as indicated in the pictorial.^{1, 6}

Safety

Unless taken repeatedly in massive doses, riboflavin is safe with few adverse effects as excess Riboflavin is excreted in the urine.⁷

References

1. Pinto JT, Zempleni J. Riboflavin. Adv Nutr. Sep 2016;7(5):973-5. doi:10.3945/an.116.012716
2. Braun L, Cohen M. Herbs & Natural Supplements; An evidence-based guide. 3rd ed. Churchill Livingston; 2010.
3. Powers HJ. Riboflavin (vitamin B-2) and health. Am J Clin Nutr. Jun 2003;77(6):1352-60. doi:10.1093/ajcn/77.6.1352
4. Riboflavin. Monograph. Altern Med Rev. Dec 2008;13(4):334-40.
5. Thakur K, Tomar SK, Singh AK, Mandal S, Arora S. Riboflavin and health: A review of recent human research. Crit Rev Food Sci Nutr. Nov 22 2017;57(17):3650-3660. doi:10.1080/10408398.2016.1145104
6. Suwannasom N, Kao I, Pruß A, Georgieva R, Bäumler H. Riboflavin: The Health Benefits of a Forgotten Natural Vitamin. Int J Mol Sci. Jan 31 2020;21(3)doi:10.3390/ijms21030950
7. Peechakara BV, Gupta M. Vitamin B2 (Riboflavin). StatPearls. StatPearls Publishing

Vitamin B3 encompasses a number of molecules with similar sounding names nl. Niacin, Nicotinic acid, Nicotinamide, Niacinamide and Nicotinamide Riboside. While not strictly correct, the term Niacin is generally used to refer to all of these compounds except Nicotinamide Riboside.¹ The name Niacin is derived from its discovery as a byproduct of nicotine metabolism.¹

Vitamin B3 was initially known as the anti-Pellagra factor. The disease, Pellagra, described as diarrhea, dermatitis, dementia and death ravaged Europe and the Southern regions of the US in the early 20th century until Vitamin B3 deficiency was discovered to be its cause and thus easily treatable.² Pellagra reached epidemic levels following the introduction of corn as a staple food. Milk and meat were then found to prevent Pellagra. Interestingly, while corn does contain Niacin it bound to proteins and largely unavailable. However when corn is soaked in alkaline “lime-water” in traditional Latin American cooking, the Niacin is released.³

In the diet, Niacin is found in organ and muscle meat, poultry, yeast, legumes, wheat bran and corn. Although milk only contains trivial amounts of Niacin, it does contain Tryptophan that can be converted into Niacin in the body,¹ as well as a different form of Vitamin B3 called Nicotinamide Riboside.⁴ As previously stated the Niacin is grains is unavailable to the body unless the grains soaked in an alkaline solution prior to cooking.¹
The body will also make Niacin from the essential amino acid Tryptophan found in protein foods.¹ However, this process is not very efficient, producing low levels of Niacin only.³

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In the body all the forms of Niacin are converted to NAD (Nicotinamide adenine dinucleotide) and NADPH (Nicotinamide adenine dinucleotide phosphate).³ These molecules are central to life.
NAD and NADPH are crucial to:^{2, 3, 5}

• Energy generation – which is required by every cell to do its work
• Cellular metabolism via redox reactions – the cycling of electrons and hydrogen ions which is how cells get their work done, whether it is digesting lunch or growing new neurons
  • NAD is required to regenerate Glutathione, the master anti-oxidant
• Sirtuin function; these are important proteins in the cell that
  • Repair DNA
  • Regulate metabolism in response to energy availability
  • Increase mitochondria (energy “factories” in cells)
  • Promote the use of fat for fuel
  • Support optimal glucose metabolism and the normal breakdown of proteins
  • Protect against oxidative stress
  • Decrease inflammation
• Epigenetic regulation: “turning” genes on and off depending on what is happening in the environment of the cells.

Effects

Given all the above it can get very confusing. Suffice it to say that Niacin, via NAD and NADPH rule the body. Suboptimal NAD and thus Niacin is involved in any age-related condition from heart disease to arthritis to dementia to cancer. Niacin is also important in a sub-group of individuals with mental health conditions and is important for skin health.

They are involved in the:^{1-3, 6, 7}

• Normal breakdown of fats, carbohydrate, alcohol and protein for fuel
• Production of fatty acids necessary for a multitude of biological processes
• Production certain hormones, bile and cholesterol (Let’s not be deceived, if you had no cholesterol, you would not be a living person. Furthermore, high doses of Niacin are actually used to lower the cholesterol in the blood).
• Production of Nucleic acids, the building blocks of DNA
• Regeneration of components of detoxification and anti-oxidant systems in the cells
• Immune system regulation
• Cells cycle of life; NAD basically tells a cell when to die (apoptosis). This is very important as old cells that are not functioning well, harm the body.
• Protection of nerves
• Decreases inflammation

Safety

As can be expected Vitamin B3 as a supplement or medication comes in a variety of forms. When taken in low doses Vitamin B3 is safe. However, it can cause uncomfortable flushing. This is particularly true of Nicotinic Acid. Extended-release forms of Nicotinic Acid cause less flushing but in high doses can cause liver damage. Niacinamide, the form used in Omic Balance serves to correct nutritional deficiency and is unlikely to cause any side-effects.⁸

This review does not cover the use of high-dose, supraphysiological (pharmaceutical) Niacin which is used a treatment mainly for high cholesterol.⁹

References

1. Braun L, Cohen M. Herbs & Natural Supplements; An evidence-based guide. 3rd ed. Churchill Livingston; 2010.
2. Jacobson MK, Jacobson EL. Vitamin B3 in Health and Disease: Toward the Second Century of Discovery. Methods Mol Biol. 2018;1813:3-8. doi:10.1007/978-1-4939-8588-3_1
3. Kirkland JB, Meyer-Ficca ML. Niacin. Adv Food Nutr Res. 2018;83:83-149. doi:10.1016/bs.afnr.2017.11.003
4. Trammell SA, Yu L, Redpath P, Migaud ME, Brenner C. Nicotinamide Riboside Is a Major NAD+ Precursor Vitamin in Cow Milk. The Journal of nutrition. 2016;146(5):957-963. doi:10.3945/jn.116.230078
5. Kupis W, Pałyga J, Tomal E, Niewiadomska E. The role of sirtuins in cellular homeostasis. J Physiol Biochem. Sep 2016;72(3):371-80. doi:10.1007/s13105-016-0492-6
6. Benavente CA, Schnell SA, Jacobson EL. Effects of niacin restriction on sirtuin and PARP responses to photodamage in human skin. PloS one. 2012;7(7):e42276. doi:10.1371/journal.pone.0042276
7. Xu XJ, Jiang GS. Niacin-respondent subset of schizophrenia – a therapeutic review. Eur Rev Med Pharmacol Sci. 2015;19(6):988-97.
8. MacKay D, Hathcock J, Guarneri E. Niacin: chemical forms, bioavailability, and health effects. Nutr Rev. Jun 2012;70(6):357-66. doi:10.1111/j.1753-4887.2012.00479.x
9. Romani M, Hofer DC, Katsyuba E, Auwerx J. Niacin: an old lipid drug in a new NAD(+) dress. J Lipid Res. Apr 2019;60(4):741-746. doi:10.1194/jlr.S092007

Vitamin B 5 (Pantothenic acid) was discovered in 1933 and was named after the Greek word panthos, meaning everywhere. This is due to the fact that Pantothenic acid is everywhere in food A classic deficiency state for Pantothenic acid is not known.¹

Pantothenic acid from food is concentrated in meats, especially liver, egg yolk, beans, peanuts, avocado, mushrooms and apricots.² Generally Pantothenic acid is sufficient in the diet, but suboptimal levels have been found in lower socioeconomic groups, adolescents and the elderly, as well as in women using oral contraceptives.¹

Given its widespread availability it has been difficult for researchers to study what happens when there is not enough Pantothenic acid in the body. Most notably vague symptoms such as fatigue, depression, poor sleep and “burning feet syndrome” are described.^{3, 4}

Actions

In the body Pantothenic acid works mainly by its incorporation into two proteins, CoA (co-enzyme A) and Acyl carrier protein.¹ These two proteins are central to a number of important biological processes listed below. Magnesium is essential in Pantothenic acid being made into CoA.¹ So, even if you are getting enough Pantothenic acid in your diet but you are not getting enough Magnesium, you can become relatively deficient in the actions of Pantothenic acid.

CoA and Acyl carrier protein which are made up of Pantothenic acid and β-alanine is central to:^{1, 3, 5}

• Energy production – note that most of the other B Vitamins are crucial here too; nothing in the body happens in isolation.
• Normal production and breakdown of fats and proteins
• Production of Vitamin D, sex hormones, melatonin, cortisol, and cholesterol
• Production of Acetylcholine and other neurotransmitters, making Pantothenic acid important in memory and learning, as well as mood and sleep.
• Production of ketones
• Formation of red blood cells
• Regulates inflammation and immune activity
• Control of cell growth
• Enhancement of insulin sensitivity

Other roles for Pantothenic acid have been described and include wound healing, liver detoxification and joint health.³

Pantothenic acid is in many foods and everywhere in the body.

Safety

Pantothenic acid is considered to be relatively safe. Occasional mild stomach discomfort has been described.⁶

References

1. Kelly GS. Pantothenic acid. Monograph. Altern Med Rev. Sep 2011;16(3):263-74.
2. Braun L, Cohen M. Herbs & Natural Supplements; An evidence-based guide. 3rd ed. Churchill Livingston; 2010.
3. Gheita AA, Gheita TA, Kenawy SA. The potential role of B5: A stitch in time and switch in cytokine. Phytother Res. Feb 2020;34(2):306-314. doi:10.1002/ptr.6537
4. Tahiliani AG, Beinlich CJ. Pantothenic acid in health and disease. Vitam Horm. 1991;46:165-228. doi:10.1016/s0083-6729(08)60684-6
5. Kennedy DO. B Vitamins and the Brain: Mechanisms, Dose and Efficacy–A Review. Nutrients. Jan 27 2016;8(2):68. doi:10.3390/nu8020068
6. Sanvictores T, Chauhan S. Vitamin B5 (Pantothenic Acid). StatPearls. StatPearls Publishing

Vitamin B6, B9, B12 and Methylation

This is big one and going past biochemistry will not suffice. Vitamin B6, Vitamin B9 (folate) and Vitamin B12 are intimately linked in the body in a biological processes called Methylation.¹ As previously stated all micronutrients work together. It is thus difficult, if not impossible, to research the exact effects of one single nutrient.

For instance, supplementing with B6, B9, and B12 has had mixed results in showing clinical efficacy. However for these three vitamins to be effective, not only do the six other essential B Vitamins need to be present in adequate amounts but so do essential minerals such as Magnesium and Zinc.² Furthermore the functions of micro-nutrients are affected by metabolic processes such as the amount of inflammation present in the body, so more or less of the nutrient may be required.³

This is one reason why nutritional studies seem to be so confusing. However, what is being discovered is more detail about the biochemical pathways where micronutrients exert their essential effects. Thus, combing knowledge of the effect of the nutrient in human biochemistry with research into the effects of the nutrient in humans is important to furthering our understanding.

Dietary Sources

Vitamin B6: Pyridoxine

Vitamin B6 is essential to all living organisms and widely distributed in plant and animal foods with the bio-availability from animal foods being 10% greater than that from plant foods.¹ Good sources include fish, organ meats, legumes, wheatgerm, eggs, nuts potatoes and bananas. Up to 40% can be lost in cooking.⁴

A certain amount of Vitamin B6 is also made in the bowel by the gut bacteria. It is not known how much this contributes to overall Vitamin B6 requirements.⁵

Vitamin B9: Folate

Folate, although named for leafy vegetables, is found in virtually all foods including green leafy vegetables, nuts, legumes, grains, and meat. In fact organ meats such as liver and kidney are especially rich in folate, while the highest concentrations are found in yeast, spinach, liver, peanuts kidney beans, Brussel sprouts and broccoli.^{4, 6}

However, dietary intake of folates is generally lower than recommended. Furthermore as much as 30% is lost in processing and cooking.⁷

Vitamin B12: Cobalamin

Vitamin B12 is essential in the human diet. It is synthesized by bacteria. Animals then ingest the bacteria and incorporate the B12 into their flesh, organs, eggs, and milk, which are then eaten by humans. Plants supply very trivial amounts of Vitamin B12.⁸

The uptake of Vitamin B12 is dependent on sufficient stomach acid and a protein produced in the stomach known as Intrinsic Factor.⁸

Methylation

Methylation has been in the very prominent in the nutritional medicine, biohacking and alternative medicine circles in the last few years. This is likely due to the increasing availability of genetic testing and purported increase in variances in the MTHFR (methylenetetrahydrofolate reductase) gene.

Please forget about MTHFR

Please forget about MTHFR. Unless you are being treated by a Functional Medicine physician who has had specific training in methylation, focusing on this enzyme can leave you with imbalanced methylation and methyl trapping which can result in significant problems.^{9, 10} Furthermore methylation is much more than MTHFR and Folate is much more than 5-MTHF.

What is Methylation?

Methylation, also called one-carbon metabolism, is a collection of reactions and cycles that generates methyl groups.⁵

Methyl is the chemical name for CH₃. This structure contains one carbon atom and three hydrogen atoms. When Methyl is passed from one compound in the cell to another, changing the structure of both compounds, that is called methylation.

The point of methylation is to make and recycle “methyl groups.” Methyl groups are structures that contain methyl. Methyl groups are involved in almost every reaction in the body. The methylation cycle functions as carriers of methyl groups, allowing them to be manipulated to support the metabolic processes in the cell.¹¹

Methylation Cycle

The methylation pathway is highly associated with Vitamin B12, folate and Vitamin B6. However, Vitamin B3, Vitamin B2, Zinc and Magnesium are also required. Furthermore, many other factors such as stress, exercise, smoking, alcohol, and toxins will also affect methylation.

The central pathway of the methylation cycle changes Homocysteine into Methionine with the help of folate and Vitamin B12. Methionine then goes on to make SAM (S-adenosyl-methionine). SAM is considered the universal methyl donor or methyl group. After Methionine makes SAM it is recycled back into Homocysteine.

One sign that the methylation cycle is not working properly is an elevated Homocysteine. While Homocysteine can be broken down by a different pathway, an elevated blood Homocysteine is used as a proxy for the methylation cycle.

Elevated Homocysteine (proxy for suboptimal methylation) is associated with:^11-14

• Vascular disease including coronary artery disease and stroke
• Cognitive decline
• Insulin resistance
• Pregnancy complications
• Blood clots
• Cancer
• Parkinson’s disease

Methyl Groups / Donors

Methyl groups are required for:^{7, 11, 15-17}

• Synthesis of DNA precursors
• Gene regulation
• Maintaining antioxidant status
• Synthesizing fats (phospholipids) for incorporation into the cell wall
• Synthesis of neurotransmitters such as epinephrine, serotonin and dopamine
• Protection of nerves
• Balance of amino acids such as glycine and methionine
• Synthesis of creatine (an energy molecule)
• Synthesis of choline (important for cell membranes and brain function)
• Immune function
• Production of glutathione (master anti-oxidant)
• Energy production

As can be seen by this list, methylation groups are involved in just about all functions in the cell. Thus, if any of the nutrients involved are insufficient, methylation will be affected. The result affect is likely to be the same, whether it is for instance low Vitamin B12 or low folate.

Epigenetics / Gene regulation

We are constantly being told that our lifestyle, particularly our diet, turns genes on and off making us either more or less healthy. The nutrients in our diet do this is through the methylation cycle.

As we have said, the methylation cycle is dependent on Vitamin B12, Vitamin B6, folate, other B Vitamins, minerals, and protein. All of these nutrients affect the function of the methylation cycle and thus the production of SAM.

One of SAM’s roles is to attach to histones, the proteins that support and regulate DNA. When SAM attaches to a histone, methylating the histone, this will result either in the expression or not of a particular gene. The levels of SAM affect the amount of methylation of the histone.¹⁵ Thus, nutrients in food affect methylation which turns genes on and off.

If the “wrong” genes are turned on or off, diseases such as diabetes, obesity, cancer, heart disease and aging may be result.¹⁵

Vitamin B6

Actions

Vitamin B6 is a group of compounds that can be converted to the coenzyme Pyridoxal 5’ Phosphate (p5P), the biologically active form of Vitamin B6.⁵ Coenzymes help the biological processes in the body to work. Vitamin B6 is one of the most central molecules in the cells of all living things, impacting overall physiology.¹⁷

In the body most Vitamin B6 is found in the muscle where it is associated with the regulation of glycogen (glucose stores).⁵

Co-factor

Vitamin B6 is a co-factor in more than 140 biochemical reactions.¹⁶

These include: ^{1, 5, 16, 17}

• amino acid breakdown and synthesis
• synthesis of long-chain omega 3 & 6 fatty acids
• methylation reactions
• storage and metabolism glycogen, thereby having a role in glucose metabolism
• formation of Hemoglobulin (the oxygen carrying molecule in blood)
• synthesis of neurotransmitters serotonin, dopamine, epinephrine, and GABA
• breakdown of Homocysteine
• healthy immune function

Anti-oxidant

Interestingly Vitamin B6 has been shown to have a greater anti-oxidant effect than Vitamin C. However, this needs to be further researched in humans.¹⁶

Protects against AGE formation

Advanced glycation end-products (AGEs) form when high levels of glucose are present in the cells. These AGEs cause problems with the proper functioning of the cells and create oxidative stress. This is part of the way that Diabetes can cause damage to kidneys and eyes. Vitamin B6 may help prevent the formation of AGEs.¹⁸

Effects

Beside Vitamin B12 and folate, the actions of Vitamin B6 are intricately linked to Vitamin B2, B3 and zinc. If any of these nutrients are insufficient, Vitamin B won’t work adequately.¹

Marginal Vitamin B6 status, independent of Homocysteine (the byproduct of methylation), has been associated with an increased risk of:^{5, 19}

• Stroke
• Heart disease
• Blood clots
• Cancer
• Diabetes
• Inflammation
• Dermatitis
• Anemia
• Inflammation e.g. in Rheumatoid arthritis
• Depression
• Confusion
• Seizures (severe cases of B6 deficiency)

Vitamin B6 may be helpful for those with schizophrenia or autism. It may also help with memory.¹⁷ Supplementing with Vitamin B6 has been shown to improve immune function.¹⁹

Safety

High levels of Vitamin B6 supplementation (>500mg) have been associated with neuropathy (tingling in the limbs) which is reversible on stopping the Vitamin B6.²⁰

Vitamin B 9: Folate

Metabolism

Folate has two main interlinked actions:

• Methylation
• Production of DNA building blocks (Purines)

It is very important to define what we mean by folate. Folate, folic acid, folinic acid and 5-methyltetrahydrofolate are not the same thing.

Folate, folic acid, folinic acid and 5-methyltetrahydrofolate are not the same thing

Folate is the umbrella term used to describe all the members of the Vitamin B9 family, including folic acid, folinic acid, tetrahydrofolate and methylfolate.⁷

Folinic acid (5-formyl THF) is found naturally in food and does not need to be activated like Folic acid does.⁷

Tetrahydrofolate (THF) is the biologically active form of folate.¹¹ It can be metabolised down either of folate’s biological pathways.

5-MTHF (methylfolate) is the most abundant type of folate in the blood and is catalyzed from THF by MTHFR (Methylene tetrahydrofolate reductase) mentioned earlier. MTHFR is critical to the function of folate in the methylation cycle. However, 5-MTHF is not the only biologically active form of folate in the body.⁷ 5-MTHF is involved in methylation reactions, whereas other active forms are involved in DNA replication and repair.⁷

Methylfolate is used in the methylation cycle. Enabled by Vitamin B12, Methylfolate metabolizes homocysteine into methionine and ends up back as Tetrahydrofolate (THF). THF can then go on to be used in the production of the purines for DNA or be activated to Methylfolate again by MTHFR.²¹

In those with a MTHFR mutation, extra supplementation with 5-MTHF may be required at times but this is best done under the supervision of a trained Functional Medicine physician.

Folic acid is a synthetic form of Vitamin B9 rarely found in nature. It is however extensively used in supplements and food fortification.⁷

Folic acid needs to be reduced (activated) before it can be used by the body. Folic acid is activated by an enzyme called DHFR (dihyrofolate reductase). Unfortunately, this enzyme is decreased by medications, including antibiotics and immune suppressants, as well as naturally occurring compounds such as EGCG in tea, Quercetin and Naringin in citrus.^{22, 23} When this enzyme is decreased, it may lead to folate deficiency, even when taking folic acid. Even under normal circumstances, this enzyme can also become “full” very quickly, leading to a backup of folic acid.⁷ This unmetabolized folic acid has raised concern amongst researchers about its effect on biological function.²⁴ Counter to this, the risks of folic acid supplementation is said to be outweighed by the benefits.²⁵

This is one reason why Omic went to great lengths to source Folinic acid rather than use the cheap Folic acid or the trendy 5-MTHF versions of folate.

In food, folate is found as 5-MTHF and Folinic acid.^{6, 7}

Effects

Given folate’s wide distribution in food, folate deficiency usually occurs from a generally poor diet rather than form a poor intake of any single food. Folate deficiency also rarely exists in a pure state.⁶

The main indicator of Folate deficiency is a specific type of anemia called megaloblastic anemia. However, this may also be due to Vitamin B12 deficiency, or both.⁶ Pointing to specific folate deficiency the incidence of neural tube defects has decreased dramatically with the introduction of folic acid supplementation in early pregnancy.²⁵

Other conditions associated with folate deficiency are:^{6, 7}

• Cardiovascular disease
• Colorectal cancer
• Cognitive dysfunction
• Psychiatric diseases
• Degeneration of ulcerative colitis
• Complicates of pregnancy

Safety

Because folate and Vitamin B12 are so closely linked, doctors are taught to always supplement Vitamin B12 when supplementing folate or to at least regularly check levels of Vitamin B12. Failure to do so, can lead to significant Vitamin B12 deficiency leading to irreversible mental, neurological and blood cell abnormalities. This has been described as being due to the methylfolate trap,⁸ or to folates oxidizing and inactivating Vitamin B12 especially in the elderly.²⁶

This effect is borne out by a study indicating that high levels of folate in the presence of low levels of Vitamin B12 are associated with higher rates of dementia than with low levels of Vitamin B12 on its own.²⁷

It is also possible that the fortification of bread and cereals with folate has led to increasing symptoms of Vitamin B12 deficiency.²⁶

It is unwise to consume high doses of any micronutrient except under the supervision of a trained Functional Medicine physician. However, It has been stated that no dose of folate can be considered truly safe in the presence of untreated (minor) Vitamin B12 deficiency, which may be difficult diagnose.⁶

The addition of Vitamin B6 and Vitamin B12 (and probably the other B Vitamins and essential minerals) to folate supplementation is likely to be far more beneficial, than supplemental folate, in any form, on its own.

Vitamin B12: Cobalamin

Vitamin B12 has only two actions but has multiple effects and is essential to the normal functioning of all cells.⁴ Inside the cells, Vitamin B12 exists in two forms. These are:

• Methylcobalamin directly involved in the methylation cycle where it helps folate to metabolize homocysteine into methionine and then recycles folate back to THF to make the DNA purines. Thus, if either Vitamin B12 or folate is deficient, the symptoms will be the same.
• Adenosylcoblamin helps to shuttle amino acids (including Alpha-Ketobutyric acid, a breakdown product of Homocysteine), and fatty acids into the Krebs cycle where they are made into energy. It is does this via the enzyme Methylmalonyl-CoA mutase.²⁸

Through the two actions described above, Vitamin B12 is integral to:^{8, 14, 21, 29}

• Normal red blood cell production and function; like folate, Vitamin B12 deficiency classically causes megaloblastic anemia
• Healthy nerves and brain, with deficiency associated with problems with balance, memory, personality changes and mood effects ranging from mild depression to psychosis
• Healthy cardiovascular function
• Energy
• Healthy skin and mucous membranes such as mouth and tongue
• Healthy nails and hair
• Healthy bone formation
• Healthy hearing and vision
• Normal childhood development
• Normal fertility

Deficiency states of Vitamin B12 take much longer to appear than folate deficiency. Given how closely these two Vitamin work together, it is no wander that Vitamin B12 deficiency is often misdiagnosed as folate deficiency.³⁰ Unfortunately if folate is prescribed without Vitamin B12 this can make matters worse.⁸

Vitamin B12 deficiency is common across the world.²¹ It can be caused by low dietary intake of Vitamin B12 such is in veganism. This is particularly a problem in breast-fed infants of vegan mothers, where Vitamin B12 is critical for development.¹⁴

Vitamin B12 deficiency can also be caused by gut issues such as colitis and gastritis, following gastrectomy and in those with Pernicious Anemia. Pernicious anemia is an auto-immune disease that causes destruction of the stomach cells that produce Intrinsic Factor that is necessary for the absorption of Vitamin B12. Drugs that reduce stomach acid and alcohol will also reduce Vitamin B12 absorption.⁸ The anesthetic gas nitrous oxide (laughing gas) inactivates Vitamin B12. This is generally not a problem except in susceptible individuals and in repeated use of laughing gas.²¹

Medications such as Metformin and stomach acid inhibitors will decrease Vitamin B12 absorption.³¹

Safety

Vitamin B12 supplementation has been found to be safe and with adverse effects. As such an upper limit has not been set.³¹

References

1. Mackey AD, Davis, S.R., Gregory III, S.F. Vitamin B6. In: Shils M, ed. Modern Nutrition in Health and Disease. 10th ed. Lippincott Williams & Wilkins; 2006.
2. Kennedy DO. B Vitamins and the Brain: Mechanisms, Dose and Efficacy–A Review. Nutrients. Jan 27 2016;8(2):68. doi:10.3390/nu8020068
3. Ford ES, Liu S, Mannino DM, Giles WH, Smith SJ. C-reactive protein concentration and concentrations of blood vitamins, carotenoids, and selenium among United States adults. Eur J Clin Nutr. Sep 2003;57(9):1157-63. doi:10.1038/sj.ejcn.1601667
4. Braun L, Cohen M. Herbs & Natural Supplements; An evidence-based guide. 3rd ed. Churchill Livingston; 2010.
5. da Silva VR, Gregory JF. Chapter 13 – Vitamin B6. In: Marriott BP, Birt DF, Stallings VA, Yates AA, eds. Present Knowledge in Nutrition (Eleventh Edition). Academic Press; 2020:225-237.
6. Carmel R. Folic Acid. In: Shils M, ed. Modern Nutrition in Health and Disease. 10th ed. Lippincott Williams & Wilkins; 2006.
7. Scaglione F, Panzavolta G. Folate, folic acid and 5-methyltetrahydrofolate are not the same thing. Xenobiotica. May 2014;44(5):480-8. doi:10.3109/00498254.2013.845705
8. Carmel R. Cobalamin (Vitamin B12). In: Shils M, ed. Modern Nutrition in Health and Disease. 10th ed. Lippincott Williams & Wilkins; 2006.
9. Chanarin I, Deacon R, Lumb M, Perry J. Cobalamin and folate: recent developments. J Clin Pathol. Apr 1992;45(4):277-83. doi:10.1136/jcp.45.4.277
10. Marotta DA, Kesserwani H. Nitrous Oxide Induced Posterior Cord Myelopathy: Beware of the Methyl Folate Trap. Cureus. Jul 21 2020;12(7):e9319. doi:10.7759/cureus.9319
11. Ducker GS, Rabinowitz JD. One-Carbon Metabolism in Health and Disease. Cell metabolism. Jan 10 2017;25(1):27-42. doi:10.1016/j.cmet.2016.08.009
12. Pizzorno J. Homocysteine: Friend or Foe? Integr Med (Encinitas). Aug 2014;13(4):8-14.
13. Setola E, Monti LD, Galluccio E, et al. Insulin resistance and endothelial function are improved after folate and vitamin B12 therapy in patients with metabolic syndrome: relationship between homocysteine levels and hyperinsulinemia. Eur J Endocrinol. Oct 2004;151(4):483-9. doi:10.1530/eje.0.1510483
14. Volkov I. The critical role of vitamin B12. Phys Sportsmed. 2008;36(1):34-41. doi:10.3810/psm.2008.12.9
15. Mentch SJ, Locasale JW. One-carbon metabolism and epigenetics: understanding the specificity. Ann N Y Acad Sci. Jan 2016;1363(1):91-8. doi:10.1111/nyas.12956
16. Mooney S, Leuendorf JE, Hendrickson C, Hellmann H. Vitamin B6: a long known compound of surprising complexity. Molecules. Jan 12 2009;14(1):329-51. doi:10.3390/molecules14010329
17. Parra M, Stahl S, Hellmann H. Vitamin B₆ and Its Role in Cell Metabolism and Physiology. Cells. Jul 22 2018;7(7)doi:10.3390/cells7070084
18. Metz TO, Alderson NL, Thorpe SR, Baynes JW. Pyridoxamine, an inhibitor of advanced glycation and lipoxidation reactions: a novel therapy for treatment of diabetic complications. Arch Biochem Biophys. Nov 1 2003;419(1):41-9. doi:10.1016/j.abb.2003.08.021
19. Ueland PM, McCann A, Midttun Ø, Ulvik A. Inflammation, vitamin B6 and related pathways. Mol Aspects Med. Feb 2017;53:10-27. doi:10.1016/j.mam.2016.08.001
20. Abosamak NER, Gupta V. Vitamin B6 (Pyridoxine). StatPearls. StatPearls Publishing Copyright © 2020, StatPearls Publishing LLC.; 2020.
21. Green R, Allen LH, Bjørke-Monsen AL, et al. Vitamin B(12) deficiency. Nat Rev Dis Primers. Jun 29 2017;3:17040. doi:10.1038/nrdp.2017.40
22. Sánchez-del-Campo L, Sáez-Ayala M, Chazarra S, Cabezas-Herrera J, Rodríguez-López JN. Binding of natural and synthetic polyphenols to human dihydrofolate reductase. Int J Mol Sci. Dec 18 2009;10(12):5398-410. doi:10.3390/ijms10125398
23. Aslan E, Adem S. Investigation of the effects of some drugs and phenolic compounds on human dihydrofolate reductase activity. J Biochem Mol Toxicol. Mar 2015;29(3):135-9. doi:10.1002/jbt.21677
24. Maruvada P, Stover PJ, Mason JB, et al. Knowledge gaps in understanding the metabolic and clinical effects of excess folates/folic acid: a summary, and perspectives, from an NIH workshop. Am J Clin Nutr. Nov 11 2020;112(5):1390-1403. doi:10.1093/ajcn/nqaa259
25. van Gool JD, Hirche H, Lax H, De Schaepdrijver L. Folic acid and primary prevention of neural tube defects: A review. Reprod Toxicol. Sep 2018;80:73-84. doi:10.1016/j.reprotox.2018.05.004
26. Solomon LR. Advanced age as a risk factor for folate-associated functional cobalamin deficiency. J Am Geriatr Soc. Apr 2013;61(4):577-82. doi:10.1111/jgs.12155
27. Moore EM, Ames D, Mander AG, et al. Among vitamin B12 deficient older people, high folate levels are associated with worse cognitive function: combined data from three cohorts. J Alzheimers Dis. 2014;39(3):661-8. doi:10.3233/jad-131265
28. Manoli I, Venditti C. Methylmalonic Acidemia. 2005.
29. Smith AD, Warren MJ, Refsum H. Chapter Six – Vitamin B12. In: Eskin NAM, ed. Advances in Food and Nutrition Research. Academic Press; 2018:215-279.
30. Carmel R, Karnaze DS. Physician response to low serum cobalamin levels. Arch Intern Med. Jun 1986;146(6):1161-5.
31. Vitamin B12. NIH National Institutes of Health Office of Dietary Supplements. Updated March 30, 2020. Accessed January 6, 2021, https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/

Biotin is a water-soluble B vitamin, also known as Vitamin B7. It is essential to human health affecting energy production, the synthesis of fatty acid compounds essential to all aspects of life, the breakdown of certain amino acids and fatty acids and the normal functioning of the brain.¹ It is important for normal human health, growth and development.²

Humans cannot make Biotin and need to include this in their diet. Biotin is also made in the human gut by the gut microbes, though how much this source contributes to our Biotin needs is not known.² Biotin is found in good amounts in chicken and beef liver, egg yolk, salmon, pork, sunflower seeds and almonds.³

Biotin is recycled in the body and frank deficiency is rare⁴, occurring in specific genetic disorders that are usually diagnosed at birth.¹

However marginal biotin deficiency does occur² and is particularly important in women who are pregnant.⁵ Biotin deficiency can occur in those who consume raw egg white for long periods,⁴ or those who may have decreased absorption such as in alcoholism and inflammatory bowel conditions and those on long-term epilepsy drugs²

Actions

Biotin in food is bound to protein and needs to be freed by the digestive process for use in the body. It has two main mechanisms of actions in the body.

1. Co-factor in enzymes related to glucose, fat and protein metabolism important in energy metabolism, glucose regulation and protein metabolism.
2. Regulates a number of different genes.

This means that biotin is important in parts of the body that require a high turn-over of cells, including hair, skin and nails.

It is also essential to brain function for energy and mood.

Safety

An upper limit for Biotin has not been established and high doses of Biotin do not seem to be associated with any problems.⁶ However, be aware that high dose Biotin supplementation may interfere with laboratory tests.⁵

References

1. León-Del-Río A. Biotin in metabolism, gene expression, and human disease. J Inherit Metab Dis. Jul 2019;42(4):647-654. doi:10.1002/jimd.12073
2. Said HM. Biotin: biochemical, physiological and clinical aspects. Subcell Biochem. 2012;56:1-19. doi:10.1007/978-94-007-2199-9_1
3. Staggs CG, Sealey WM, McCabe BJ, Teague AM, Mock DM. Determination of the biotin content of select foods using accurate and sensitive HPLC/avidin binding. J Food Compost Anal. Dec 2004;17(6):767-776. doi:10.1016/j.jfca.2003.09.015
4. Mock D. Biotin. In: Shils M, Shike, M., Ross, A., Caballero, B., Cousins, R., ed. Modern Nutrition in Health and Disease. Lippincott Williams & Wilkins; 2006.
5. Mock DM. Biotin: From Nutrition to Therapeutics. J Nutr. Aug 2017;147(8):1487-1492. doi:10.3945/jn.116.238956
6. Biotin. National Institutes of Health Office of Dietary Supplements. Updated June 3, 2020. Accessed December 29, 2020, 2020. https://ods.od.nih.gov/factsheets/Biotin-HealthProfessional/

Vitamin K has for many years been considered a single fat-soluble Vitamin. However, new research is now leading to the acceptance that Vitamin K can be divided into two main groups, Vitamin K1 and Vitamin K2.¹ Unlike other fat soluble vitamins, the body does not store Vitamin K.²

Vitamin K1: Phylloquinone

The role of Vitamin K1 is well known as preventing excessive bleeding. Vitamin K1 is so important in the body that is able to compensate for low dietary intake by recycling Vitamin K1 multiple times.³ Vitamin K1 is found in green leafy vegetables such as collards, spinach and salad greens.⁴ Furthermore, there is some suggestion that Vitamin K1 can be made in the gut by gut bacteria. Except in newborns, it is therefore very rare to become deficient in Vitamin K1.⁴

For this reason, Vitamin K1 is not included in the Omic Balance.

Vitamin K2: Menaquinone

It is only recently that Vitamin K2 became to be known for its role in modulating calcium. Research is continuing into the widespread functions of this Vitamin.⁵ As far as is known, there is no recycling pathway for Vitamin K2 and adequate amounts must be consumed in the diet. Herbivores can convert Vitamin K1 to Vitamin K2 efficiently but humans only convert a small amount.⁶ Certain forms for Vitamin K2 may be synthesized in the gut but the availability of this source from the gut bacteria is unkown.⁷

It is apparent that Vitamin K2 deficiency is very common.⁵ Factors which contribute to this deficiency include low fat diets, preservatives and the use of transfats.^{1, 8}

Vitamin K2 is divided into sub-types:⁹

• Short-chain: MK-4
• Long-chain: MK-7, MK-8, MK-9

MK-7 is the most efficiently absorbed of all the Menaquinones and has a longer action that MK-4.¹⁰

Vitamin K2 in the Diet

Vitamin K2 is not found in plants but is high in animal products. However, Vitamin K2 is made by bacteria and is found in certain fermented plant foods such as Sauerkraut and Natto. Not all bacteria make Vitamin K2 and not all fermented foods contain Vitamin K2. Natto is soybean that has been fermented with the Bacillus natto bacteria and is very high in Vitamin K2.⁹ It can be challenging to eat for those who have not grown up with it!

Dairy products are the 2^nd richest sources of Vitamin K2, followed by egg yoks, beef and salmon.⁹

Vitamin K2 is one of the best illustrations of how we are not just what we eat, we are what our animals eat.

While further research is necessary it appears that animals that eat a natural, grass-based diet will produce Vitamin K2 in their livers from the chlorophyll (green pigment) in the plants that they eat. This Vitamin K2 then makes its way to the milk and eggs that the animals produce. Grain-fed cattle and poultry do not produce sufficient Vitamin K2.¹¹

Actions

Enzyme activation

Both types of Vitamin K work mainly by activating enzymes, called carboxylases, that then go on to activate certain proteins.

Vitamin K1 mainly activates proteins that regulate blood clotting.⁴

Vitamin K2 actives proteins that regulate calcium metabolism. The beauty of these proteins is that they help to put calcium into bone and stop calcium being put into blood vessels, cartilage, and other soft tissues.⁹

Antioxidant

Emerging research indicates that Vitamin K2 displays anti-oxidant activity greater than that of Vitamin E and Co-enzyme Q 10, helping to protect cell membranes and prevent neurons from damage.¹²

Energy

Vitamin K2 may even have a role in mitochondrial health and ATP (energy) generation, although a lot more research is needed here.¹³

Effects

As can be seen by the above actions, Vitamin k2 has a vast number of effects in the body. There is now good evidence that Vitamin K2:⁹

• Protects against cardiovascular disease and may even reverse hardening of the arteries
• Improves bone quality (not density) and decreases risk of fractures
• Decreases the risk of Diabetes by increasing insulin production

Early research indicates that Vitamin K2 may:^{1, 5, 14-16}

• Protect against cancer
• Improve liver and kidney function
• Modulate the immune system
• Protect against neurological degeneration, improving cognition
• Improve glucose and fat metabolism, decreasing weight, fat deposits and waist circumference in humans
• Protect against arthritis – osteoarthritis (wear and tear) and inflammatory arthritis (auto-immune)
• Inhibit kidney stones
• Regulate estrogen
• Prevent wrinkles due to its effect in elastin
• Be crucial in the normal growth of infants and children
• Improve dental health

Safety

No official RDI (reference daily intake) exists for Vitamin K2 at present.⁹ Suggested maximum dosages for MK-7 of 10mg are evidence of the safety of supplementing this Vitamin.¹⁰ Very few adverse effects have been reported with long-term use of MK-7. The most commonly reports were those of mild gastric upset.¹⁰

Those taking Warfarin need to check with their prescriber about using Vitamin K2 supplements.¹

References

1. Schwalfenberg GK. Vitamins K1 and K2: The Emerging Group of Vitamins Required for Human Health. Journal of nutrition and metabolism. 2017;2017:6254836. doi:10.1155/2017/6254836
2. Fusaro M, Crepaldi G, Maggi S, et al. Vitamin K, bone fractures, and vascular calcifications in chronic kidney disease: An important but poorly studied relationship. Journal of endocrinological investigation. 11/01 2010;34:317-23. doi:10.3275/7353
3. Tie JK, Stafford DW. Functional Study of the Vitamin K Cycle Enzymes in Live Cells. Methods Enzymol. 2017;584:349-394. doi:10.1016/bs.mie.2016.10.015
4. Suttie JW. Vitamin K1. In: Shils M, ed. Modern Nutrition in Health and Disease. 10th ed. Lippincott Williams & Wilkins; 2006.
5. Cranenburg EC, Schurgers LJ, Vermeer C. Vitamin K: the coagulation vitamin that became omnipotent. Thromb Haemost. Jul 2007;98(1):120-5.
6. Shearer MJ, Fu X, Booth SL. Vitamin K nutrition, metabolism, and requirements: current concepts and future research. Adv Nutr. Mar 1 2012;3(2):182-95. doi:10.3945/an.111.001800
7. McCann A, Jeffery IB, Ouliass B, et al. Exploratory analysis of covariation of microbiota-derived vitamin K and cognition in older adults. Am J Clin Nutr. Dec 1 2019;110(6):1404-1415. doi:10.1093/ajcn/nqz220
8. Booth SL, Lichtenstein AH, O’Brien-Morse M, et al. Effects of a hydrogenated form of vitamin K on bone formation and resorption. Am J Clin Nutr. Dec 2001;74(6):783-90. doi:10.1093/ajcn/74.6.783
9. Halder M, Petsophonsakul P, Akbulut AC, et al. Vitamin K: Double Bonds beyond Coagulation Insights into Differences between Vitamin K1 and K2 in Health and Disease. Int J Mol Sci. Feb 19 2019;20(4)doi:10.3390/ijms20040896
10. Marles RJ, Roe AL, Oketch-Rabah HA. US Pharmacopeial Convention safety evaluation of menaquinone-7, a form of vitamin K. Nutr Rev. Jul 1 2017;75(7):553-578. doi:10.1093/nutrit/nux022
11. Rheume-Bleue K. Vitamin K2 and the Calcium Paradox. Harper Collins Publishers Ltd; 2012.
12. Li J, Wang H, Rosenberg PA. Vitamin K prevents oxidative cell death by inhibiting activation of 12-lipoxygenase in developing oligodendrocytes. J Neurosci Res. Jul 2009;87(9):1997-2005. doi:10.1002/jnr.22029
13. Bhalerao S, Clandinin TR. Cell biology. Vitamin K2 takes charge. Science. Jun 8 2012;336(6086):1241-2. doi:10.1126/science.1223812
14. Otsuka M, Kato N, Ichimura T, et al. Vitamin K2 binds 17beta-hydroxysteroid dehydrogenase 4 and modulates estrogen metabolism. Life Sci. Apr 8 2005;76(21):2473-82. doi:10.1016/j.lfs.2004.12.020
15. Gheduzzi D, Boraldi F, Annovi G, et al. Matrix Gla protein is involved in elastic fiber calcification in the dermis of pseudoxanthoma elasticum patients. Lab Invest. Oct 2007;87(10):998-1008. doi:10.1038/labinvest.3700667
16. Southward K. A hypothetical role for vitamin K2 in the endocrine and exocrine aspects of dental caries. Med Hypotheses. Mar 2015;84(3):276-80. doi:10.1016/j.mehy.2015.01.011

Magnesium – If you are a woman, chances are you will immediately think of chocolate. Magnesium is why you need chocolate; and you are partially right.

Magnesium is the 8^th most abundant element in the earth’s crust and the 2^nd most abundant in sea.¹ Magnesium is mainly found in mineral deposits as a Magnesium carbonate and Dolomite. It is essential to all living organisms, with the most biologically available Magnesium from the ocean.²

Despite Magnesium being rather ubiquitous in the environment, there is no food that provides a particularly high amount.³ Chlorophyll (thus green vegetables) are a major source of Magnesium, followed by nuts, seeds, cocoa and unprocessed grains. Legumes, fruit, fish, and meat have lower levels, while, except for milk, dairy is generally a poor source of Magnesium. Potatoes also contain a moderate amount of Magnesium.³

Refining grains and cooking, lowers the amount of Magnesium.^{2, 4} For example, 80% of Magnesium is lost when turning wheat into flour.⁴

Magnesium intakes for most of the population of the United States and Europe are below the recommended amounts and are declining. This is likely to be due to the increasing use of fertilizers and processed foods²

Actions

Magnesium is the 4^th most common mineral in the body after calcium, sodium and potassium.⁵ 60% of Magnesium in the body is found in bone, followed by 30-40% in muscle and soft tissue and 1% outside of the cells (e.g. in the blood).⁶

Magnesium’s main role in the body is closely linked to ATP, the body’s energy molecule.¹ As ATP is required for everything your body does, so is Magnesium. You need to walk, you need Magnesium; you need to digest, you need Magnesium; you need to think, you need Magnesium! You get the picture.

Magnesium is also important in the stabilization and function of your DNA and cell membranes. As “natures Calcium Channel Blocker,” it also helps your heart muscle work properly. In addition there are also over 300 different enzyme systems where Magnesium is critical.¹

Insufficient magnesium is associated with chronic disease such as Diabetes, Alzheimer’s disease, heart disease, stroke, migraine, osteoporosis, depression, ADHD, asthma, muscle cramps, eczema. painful periods, poor sleep, and possibly cancer. Diabetes and pre-diabetes are particularly relevant as Magnesium deficiency leads to Diabetes and Diabetes causes loss of Magnesium in the urine.^{2, 5}

Many commonly used pharmaceuticals also cause a loss of Magnesium in the urine. These include diuretics, drugs used for indigestion, antibiotics, and steroids. Alcohol consumption will also increase the loss of Magnesium in the urine.^{2, 5}

As you can see below Magnesium is life.^{1, 2, 5, 7}

Safety

The most common adverse reaction to Magnesium is diarrhea and gastric irritation. This can be managed by decreasing the dose or splitting the dose to two or three times per day.⁸ Although rarely seen, taking very high doses of Magnesium especially in those with kidney failure can be fatal,⁹ so it is best to stick to recommended doses.

References

1. Rude RK, Shils, M.E. Magnesium. In: Shils M, ed. Modern Nutrition in Health and Diseassse. 10th ed. Lippincott Williams & Wilkins; 2006.
2. Gröber U, Schmidt J, Kisters K. Magnesium in Prevention and Therapy. Nutrients. Sep 23 2015;7(9):8199-226. doi:10.3390/nu7095388
3. Volpe SL. Magnesium in disease prevention and overall health. Adv Nutr. May 1 2013;4(3):378s-83s. doi:10.3945/an.112.003483
4. Ahsan SK. Magnesium in health and disease. J Pak Med Assoc. Aug 1998;48(8):246-50.
5. Schwalfenberg GK, Genuis SJ. The Importance of Magnesium in Clinical Healthcare. Scientifica (Cairo). 2017;2017:4179326. doi:10.1155/2017/4179326
6. Romani A. Magnesium in Health and Disease. Metal ions in life sciences. 11/18 2013;13:49-79. doi:10.1007/978-94-007-7500-8_3
7. Boyle NB, Lawton C, Dye L. The Effects of Magnesium Supplementation on Subjective Anxiety and Stress-A Systematic Review. Nutrients. Apr 26 2017;9(5)doi:10.3390/nu9050429
8. Braun L, Cohen M. Herbs & Natural Supplements; An evidence-based guide. 3rd ed. Churchill Livingston; 2010.
9. Schelling JR. Fatal hypermagnesemia. Clin Nephrol. Jan 2000;53(1):61-5.

Zinc is the 2^nd most abundant trace element in the body and is found in all tissues and body fluids.¹ Although Zinc is widespread in the body, it is not stored in the body, meaning Zinc needs to be adequate in the diet. Zinc is considered a type II nutrient which are building blocks in the body, required for the synthesis of any new tissue.²

85% of the Zinc in the body is found in the muscle and bones, 11% in the skin and liver and the rest in all other tissues especially in the eye and prostate.³

Zinc in the Diet

Zinc is found in a wide range of foods including meat, liver, eggs, seafood, nuts, legumes and whole grains. However, sufficient intake of dietary Zinc intake does not guarantee adequate Zinc. This is because Zinc in plant foods is tightly bound to phytates, making Zinc much less available. Furthermore, Calcium may inhibit the absorption of Zinc. However, the amount of animal protein does correlate to the amount of Zinc absorption.² Fermenting or sprouting of plants foods may help to improve Zinc bioavailability.⁴

Actions

Zinc has three effects in the body. Don’t let this fool you, those three actions produce a multiplicity of effects.

1. Enzymatic / Catalytic

Zinc is said to be required for about 300 different enzymes and hence metabolic processes in the body. However, there is no one pathway that defines the function of Zinc, making it complex for researchers to study.⁴

2. Structural

Zinc forms part of proteins call zinc fingers. These Zinc fingers help to form the structure of critical proteins in our cells and are as such involved in many different functions. They help to translate our genetic code from DNA to an actual protein structure such as in the development of blood cells. Zinc fingers also have roles in the walls of cells and the binding and transporting of fats.⁵

3. Regulatory

Zinc is involved in activation of thousands of genes⁶ and in the functioning of neurons and hormones.^{1, 4} It is essential in the regulation of the immune system.⁷

Given its ubiquitous nature, one could say that zinc is indirectly required for most processes in the body. The dominant effects of Zinc are shown in the pictorial below.^{1, 3, 8-12}

Safety

Zinc toxicity can occur if Zinc is taken in a large dose all at once or if taken at too high a dose over a long period. This effects include everything from nausea to reduced immune function and reduced HDL “good” cholesterol. It is recommended that the upper limit for Zinc supplementation in adults is 40mg.¹³

References

1. Livingstone C. Zinc: physiology, deficiency, and parenteral nutrition. Nutr Clin Pract. Jun 2015;30(3):371-82. doi:10.1177/0884533615570376
2. Braun L, Cohen M. Herbs & Natural Supplements; An evidence-based guide. 3rd ed. Churchill Livingston; 2010.
3. Chasapis C, Loutsidou A, Spiliopoulou C, Stefanidou M. Zinc and human health: An update. Archives of toxicology. 11/10 2011;86:521-34. doi:10.1007/s00204-011-0775-1
4. King JC, Cousins, R.J. Zinc. In: Shils M, ed. Modern Nutrition in Health and Disease. 10th ed. Lippincott Williams & Wilkins; 2006.
5. Laity JH, Lee BM, Wright PE. Zinc finger proteins: new insights into structural and functional diversity. Curr Opin Struct Biol. Feb 2001;11(1):39-46. doi:10.1016/s0959-440x(00)00167-6
6. McClung JP. Iron, Zinc, and Physical Performance. Biol Trace Elem Res. Mar 2019;188(1):135-139. doi:10.1007/s12011-018-1479-7
7. Wessels I, Maywald M, Rink L. Zinc as a Gatekeeper of Immune Function. Nutrients. Nov 25 2017;9(12)doi:10.3390/nu9121286
8. Baltaci AK, Mogulkoc R, Baltaci SB. Review: The role of zinc in the endocrine system. Pak J Pharm Sci. Jan 2019;32(1):231-239.
9. Fukunaka A, Fujitani Y. Role of Zinc Homeostasis in the Pathogenesis of Diabetes and Obesity. Int J Mol Sci. Feb 6 2018;19(2)doi:10.3390/ijms19020476
10. Cherasse Y, Urade Y. Dietary Zinc Acts as a Sleep Modulator. Int J Mol Sci. Nov 5 2017;18(11)doi:10.3390/ijms18112334
11. Bao B, Prasad AS, Beck FW, et al. Zinc decreases C-reactive protein, lipid peroxidation, and inflammatory cytokines in elderly subjects: a potential implication of zinc as an atheroprotective agent. Am J Clin Nutr. Jun 2010;91(6):1634-41. doi:ajcn.2009.28836 [pii]
    10.3945/ajcn.2009.28836 [doi]
12. Sawada T, Yokoi K. Effect of zinc supplementation on mood states in young women: a pilot study. Eur J Clin Nutr. 2010;64(3):331-333.
13. Zinc. National Institutes of Health Office of Dietary Supplements. Updated July 15, 2020. Accessed December 31, 2020, 2020. https://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/

Calcium is the 5^th most abundant element in the earth and its atmosphere.¹ Calcium is what makes limestone, marble, coral, pearls, sea-shells, egg-shells, antlers and bone. Calcium can be found both in solid form and dissolved in water. It is part of sea water, fresh water and soil.¹ Human adults contain around 1kg of calcium. More the 99% of this is in bones and teeth with the rest in the tissues and fluid surrounding the cells, and the smallest amount being in the blood.²

Calcium is essential to human life and must be taken in through the diet. Early humans derived Calcium from roots, tubers, nuts and beans and were able to obtain around 1500mg per day from these sources. After the agricultural revolution, grains became the dominant food source. Grains (being the fruit of the plant), accumulate the least amount of Calcium in the plant, leading Humans to by necessity use dairy to obtain sufficient Calcium.

Dairy remains the main dietary source of Calcium in Western populations,³ with a large number of the world’s population obtaining less than required amounts of Calcium in the diet.³ Furthermore some plant constituents decrease plant (but not dairy) Calcium from being absorbed. In particular, Oxalate found in high amounts in Spinach, binds Calcium in the gut, meaning it cannot be absorbed.⁴ Other vegetables such as broccoli and kale to provide Calcium, but a large amount does need to be eaten to obtains sufficient Calcium.⁵

Actions & Functions

Calcium has a unique structure, allowing it to be easily incorporated into proteins, where it stiffens the protein molecule and stabilizes its structure.¹ As a molecule, Calcium has a number of actions that result in a vast array of physiological functions.² Without calcium, nothing would work.

Structure

Calcium provides mass, hardness, and strength to bones and teeth.¹ The bones also act as a store of Calcium that the body can draw on when necessary.

Obviously, if you are not getting enough Calcium in your diet, and your body keeps drawing on the Calcium in your skeleton, this will lead to Osteoporosis (soft bones).⁶

Here the importance of other micro-nutrients is illustrated. Nothing works in isolation. For healthy bones, not only is Calcium critical, but so is Magnesium, Vitamin D and Vitamin K2.^{7, 8}

Messenger / Signaling Molecule¹

The body keeps tight control of Calcium availability. Most Calcium is actively kept outside the cell. There is 10 000 times as much Calcium outside the cell, in the extracellular fluid than there is inside the cell, creating what is known as the Calcium gradient. This allows proteins and enzymes to remain dormant until Calcium is allowed into the cell.

The following illustration is a very simplified pictorial of one of the ways Calcium works as a signalling molecule.

1. A cell is activated e.g. a muscle fiber receives a nerve stimulus to contract
2. The usually closed calcium channel that runs between the extra-cellular flood (fluid between the cells that contains calcium) and the inside of the cell opens up
3. Calcium flows into the cell
4. Calcium binds to activator proteins which in turn release calcium from storage vesicles inside the cell; this raises the concentration of calcium in the cell
5. Contraction complex is activated
6. Calcium pump, extrudes calcium from the cell and it returns to its resting state

This messenger function is not just involved in the contraction of muscle, it is critical to multiple aspects of the normal functioning of the body. A few examples are listed here:^{1, 2, 9-11}

• Secretion of hormones such as Aldosterone from the Adrenals. This hormones regulates the salt and water balance in your blood.
• Secretion of Insulin from the Pancreas. This is obviously important to health blood glucose metabolism
• Switching nerves and muscle “on and off”
• Healthy functioning of the brain such as memory, learning and the sleep/wake cycle
• Normal mental health and neurotransmission
• Healthy heart function
• Healthy blood pressure
• Healthy liver and kidney function
• Healthy joints
• Normal immune function (supporting normal immune cell proliferation)
• Normal fertilization
• Balanced autophagy (recycling of dead cells)
• Prevention of certain cancers
• Normal gall bladder function
• Maintaining a healthy weight and metabolism

Activation of Enzymes

Some enzymes are activated and stabilized irrespective of the amount of Calcium in the cell. These include:

• Proteases that break down food in the digestive system into proteins and amino acids that are then incorporated into new molecules to help the body work¹²
• Dehydrogenases that are involved in multiple pathways, including the production of ATP, the energy molecule in the body and the breakdown of alcohol.^{13, 14}
• Normal blood clotting

Safety

As previously mentioned, the body keeps the amount of available Calcium under strict control. Furthermore, you have a huge store of Calcium that your body can add to or take away from, namely your bones.

Given the widespread importance of this mineral, Calcium is strongly regulated via multiple pathways including Vitamin D, phosphorus levels and hormones from the Thyroid and Parathyroid.¹⁵

If more Calcium is required than is being consumed in the diet, the body will use the Calcium that is in the bone. Occasionally, even if you are getting the right amount of Calcium, these mechanism may be dysfunctional leading to conditions such as Osteoporosis or Hypercalcemia (elevated levels of blood Calcium) and Kidney stones. However, while Calcium is often blamed for these conditions, it is very unlikely to be related to the amount of calcium in the diet or supplements. These conditions are more likely due to other conditions such as low Vitamin D or high Oxalate intake.

High Calcium is in effect never due to an overconsumption of Calcium in the diet. However high Calcium can rarely occur when massive amounts of Calcium supplements are consumed such as Calcium carbonate for the treatment of stomach ulcers.¹

Calcium deposits

The calcification that may occur in soft-tissue, such as in your shoulders, is related to injury not to the amount of Calcium in your diet.¹

Kidney Stones

The majority of kidney stones consist of the Calcium and Oxalate in the urine that have combined to form stones. Increasing Calcium in the diet actually helps to decrease the incidence of kidney stones, as Calcium binds with Oxalate in the gut, preventing the Oxalates from getting to the urine.¹⁶

Hardening of the Arteries

The “Calcium is good for your bones and bad for your heart” debates continues. However, emerging research again indicates that it is not the Calcium that is the problem. It is becoming apparent that Vitamin K2 (also called Menaquinone) is important in Calcium metabolism. Vitamin K2 actives enzymes that prevent calcification in blood vessels, while at the same time increasing calcification of bone.^{17, 18}

Take-home safety for Calcium supplements

High calcium supplements may cause constipation, particularly if in the Calcium carbonate form. Calcium may inhibit the absorption of zinc and iron, although this is not fully established.¹⁹

References

1. Weaver CM, Heaney, R.P. Calcium. In: Shils M, ed. Modern Nutrition in Health and Disease. 10th ed. Lippincott Williams & Wilkins; 2006.
2. Peacock M. Calcium metabolism in health and disease. Clin J Am Soc Nephrol. Jan 2010;5 Suppl 1:S23-30. doi:10.2215/cjn.05910809
3. Balk EM, Adam GP, Langberg VN, et al. Global dietary calcium intake among adults: a systematic review. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2017;28(12):3315-3324. doi:10.1007/s00198-017-4230-x
4. Heaney RP, Weaver CM. Oxalate: effect on calcium absorbability. Am J Clin Nutr. Oct 1989;50(4):830-2. doi:10.1093/ajcn/50.4.830
5. Weaver CM, Proulx WR, Heaney R. Choices for achieving adequate dietary calcium with a vegetarian diet. Am J Clin Nutr. Sep 1999;70(3 Suppl):543s-548s. doi:10.1093/ajcn/70.3.543s
6. Cashman KD. Calcium intake, calcium bioavailability and bone health. Br J Nutr. May 2002;87 Suppl 2:S169-77. doi:10.1079/bjnbjn/2002534
7. Capozzi A, Scambia G, Lello S. Calcium, vitamin D, vitamin K2, and magnesium supplementation and skeletal health. Maturitas. Oct 2020;140:55-63. doi:10.1016/j.maturitas.2020.05.020
8. Maresz K. Proper Calcium Use: Vitamin K2 as a Promoter of Bone and Cardiovascular Health. Integr Med (Encinitas). Feb 2015;14(1):34-9.
9. Berridge MJ. The Inositol Trisphosphate/Calcium Signaling Pathway in Health and Disease. Physiol Rev. Oct 2016;96(4):1261-96. doi:10.1152/physrev.00006.2016
10. Pannu PK CE, Soares MJ. Calcium and Vitamin D in Obesity and Related Chronic Disease. Adv Food Nutr Res. 2015;77:57-100. doi:0.1016/bs.afnr.2015.11.001
11. Cheng L, Hu D, Jiang W. Dietary calcium intake and the risk of metabolic syndrome: evidence from observational studies. Public Health Nutr. Aug 2019;22(11):2055-2062. doi:10.1017/s1368980019000247
12. López-Otín C, Bond JS. Proteases: multifunctional enzymes in life and disease. The Journal of biological chemistry. Nov 7 2008;283(45):30433-7. doi:10.1074/jbc.R800035200
13. Edenberg HJ, McClintick JN. Alcohol Dehydrogenases, Aldehyde Dehydrogenases, and Alcohol Use Disorders: A Critical Review. Alcohol Clin Exp Res. Dec 2018;42(12):2281-2297. doi:10.1111/acer.13904
14. Gray LR, Tompkins SC, Taylor EB. Regulation of pyruvate metabolism and human disease. Cellular and molecular life sciences : CMLS. Jul 2014;71(14):2577-604. doi:10.1007/s00018-013-1539-2
15. Fleet JC. The role of vitamin D in the endocrinology controlling calcium homeostasis. Mol Cell Endocrinol. Sep 15 2017;453:36-45. doi:10.1016/j.mce.2017.04.008
16. Curhan GC, Willett WC, Rimm EB, Stampfer MJ. A prospective study of dietary calcium and other nutrients and the risk of symptomatic kidney stones. N Engl J Med. Mar 25 1993;328(12):833-8. doi:10.1056/nejm199303253281203
17. Wasilewski GB, Vervloet MG, Schurgers LJ. The Bone-Vasculature Axis: Calcium Supplementation and the Role of Vitamin K. Front Cardiovasc Med. 2019;6:6. doi:10.3389/fcvm.2019.00006
18. Cozzolino M, Fusaro M, Ciceri P, Gasperoni L, Cianciolo G. The Role of Vitamin K in Vascular Calcification. Adv Chronic Kidney Dis. Nov 2019;26(6):437-444. doi:10.1053/j.ackd.2019.10.005
19. Calcium. National Institutes of Health Office of Dietary Supplements. Updated 2020, March 26. Accessed 2021, Jan 3, 2021. https://ods.od.nih.gov/factsheets/Calcium-HealthProfessional/

The mineral we commonly use to clean wounds, in the form of the antiseptic, Betadine, is central to the inner workings of the body.

Most of the earth’s Iodine is found in the ocean. Iodine was initially described by a French chemist making gunpowder from seaweed. It was identified in the 17^th century and was named after the Greek word for violet.¹

How humans get iodine

Iodine is solid that becomes a vapor at room temperature. It evaporates from the sea, reaching the earth with rain, then flowing back to the sea with runoff. Organisms in the sea such as micro- and macro-algae help to concentrate that iodine that eventually makes it to the soils.² Just another reason to make sure our oceans are healthy and not contaminated with plastic and masks. The sun also releases iodine from the ocean.

Plants take up a small amount of iodine from the soil through their roots and may also absorb iodine from the atmosphere². However, the iodine is plants is generally not sufficient for mammalian health. Except when eating large amounts of kelp,³ those following a vegan diet are generally insufficient in Iodine.⁴ Interestingly in sheep studies in New Zealand where it was found that eating soil was a better source of Iodine for lambs than eating the plants from the same soil.⁵

Some plants release iodine back into the atmosphere. Interestingly, microorganisms in soil such as bacteria and fungi help to release Iodine from the soils that then makes its way back up into the atmosphere.² Keeping soils healthy by not killing these microorganisms with pesticides such as Roundup is imperative in keeping us healthy.

The sufficiency of iodine in the soil varies considerably, low amounts of in mountainous areas such as the Himalayas, Alps and Andes typically and in areas with frequent flooding and glaciation, which leeches iodine out of the soil.⁶ However it has been estimated that 50% of Europe is Iodine deficient and that the iodine intake in the United States and Australia is dropping.¹

Iodine deficiency is one of the most common nutrient deficiencies.⁷ Humans get their iodine from food, and occasionally water. Good sources of iodine are seaweed and seafood. Iodine can also be obtained from dairy where the animal has fed on iodine rich plants, the animal feed has been enriched by iodine or the milk vats and animal teats have been cleaned with iodine. Eggs, where the chickens have been fed iodine-rich feed is also a good source. However, it is only since the large-scale introduction of iodized salt that the overt problems of Iodine deficiency such as Cretinism have significantly diminished.^{1, 2, 8} However, possibly given the drive to decrease salt intake, insufficient iodine levels are increasingly being seen in the US.⁹

Actions

Iodine is of course, necessary for the thyroid gland to produce Thyroid Hormone (T4)⁶. Thyroid hormone is essential to the function all cells. In severe cases, an Iodine deficiency manifests as goiter and overt hypothyroidism. Iodine is crucial in pregnancy and lactation for the development of the fetal brain, as well as in childhood and adolescence for normal physical and cognitive growth.⁶

However even marginal iodine deficiency and a slightly reduced thyroid function can prevent you from functioning at your best. Without adequate Thyroid hormone everything slows down: your metabolism, your brain, your liver, your digestion, and your mood etc.

Thyroid and thus Iodine, appear to directly affects the brain and how well it works throughout human lifespan.⁷ While, the exact mechanisms are being figured out, this is thought to be through genetic expression and neurotransmission.

Safety

When taken in recommended amounts, Iodine is safe. However there are reports of Iodine toxicity where naturally high levels of iodine are found in water, especially if an individual adds iodized salt to their diet.¹⁰ High dose of iodine may cause over- or under-activity of the thyroid.¹¹

References

1. Zimmermann MB. Iodine deficiency. Endocr Rev. Jun 2009;30(4):376-408. doi:10.1210/er.2009-0011
2. Fuge R, Johnson C. Iodine and human health, the role of environmental geochemistry and diet, a review. Applied Geochemistry. 09/01 2015;63doi:10.1016/j.apgeochem.2015.09.013
3. Becker DV, Braverman LE, Delange F, et al. Iodine supplementation for pregnancy and lactation-United States and Canada: recommendations of the American Thyroid Association. Thyroid. Oct 2006;16(10):949-51. doi:10.1089/thy.2006.16.949
4. Leung AM, LaMar A, He X, Braverman LE, Pearce EN. Iodine Status and Thyroid Function of Boston-Area Vegetarians and Vegans. The Journal of Clinical Endocrinology & Metabolism. 2011;96(8):E1303-E1307. doi:10.1210/jc.2011-0256
5. Healy WB, Crouchley G, Gillett RL, Rankin Pc, Watts HM. Ingested soil and iodine deficiency in lambs. New Zealand Journal of Agricultural Research. 1972/11/01 1972;15(4):778-782. doi:10.1080/00288233.1972.10421631
6. Niwattisaiwong S, Burman KD, Li-Ng M. Iodine deficiency: Clinical implications. Cleve Clin J Med. Mar 2017;84(3):236-244. doi:10.3949/ccjm.84a.15053
7. Redman K, Ruffman T, Fitzgerald P, Skeaff S. Iodine Deficiency and the Brain: Effects and Mechanisms. Crit Rev Food Sci Nutr. Dec 9 2016;56(16):2695-713. doi:10.1080/10408398.2014.922042
8. Hetzel BS. Iodine deficiency disorders (IDD) and their eradication. Lancet. Nov 12 1983;2(8359):1126-9. doi:10.1016/s0140-6736(83)90636-0
9. Pearce EN. National trends in iodine nutrition: is everyone getting enough? Thyroid. Sep 2007;17(9):823-7. doi:10.1089/thy.2007.0102
10. Li W-h, Dong B-s, Li P, Li Y-f. Benefits and risks from the national strategy for improvement of iodine nutrition: A community-based epidemiologic survey in Chinese schoolchildren. Nutrition. 2012/11/01/ 2012;28(11):1142-1145. doi:https://doi.org/10.1016/j.nut.2012.04.014
11. Koukkou EG, Roupas ND, Markou KB. Effect of excess iodine intake on thyroid on human health. Minerva medica. Apr 2017;108(2):136-146. doi:10.23736/s0026-4806.17.04923-0

Shilajit is a resinous substance that is found that is forced out from between rock layers in the Himalayas during the heat of the summer months. It contains a mixture of herbs and minerals from decomposition of the plant matter in the rocks centuries earlier.¹ The actual composition changes depending on the geographical region, environmental factors such as humidity and temperature, as well as the presence of plants, molds and bacteria.² Shilajit is well-known to occur in the Himalayas but is also found in Afghanistan, the Caucasus and Ural ranges, as well as in the Northern Pollock ranges in Australia³ and in the Chilean Andes.⁴

Shilajit has been used for over 3000 years in traditional Hindu Ayurvedic, Siddha and Unani medicine in Tibet and India. It is described as a “Rasayana,” a rejuvenator³ supporting a youthful long lifespan.¹ Its Sanskrit meaning is “conqueror of mountains and destroyer of weakness.”

Shilajit was also used secretly in the former USSR to enhance the mental and physical performance of Olympic athletes and special military forces.²

Constituents & Mechanisms of action

Humic substances make up 80-85% of Shilajit.⁵ These are organic compounds that occur in humus that makes up soil. Of these, Fulvic acid is the most well-known.⁴ Trace minerals including Phosphate, Silicon, Sulphur, Chlorine, Potassium, Calcium and Iron make up the rest of the compound.⁵

Early studies indicated that Shilajit has anti-inflammatory, anti-oxidant, analgesic, immunomodulator, anti-diabetic, lipid modulating, nootropic, anxiolytic, anti-viral and anti-fungal activity. It also stops the release of histamine.³ Shilajit seems to increase the production of ATP (energy) in cells, as well as increase Acetylcholine, necessary for cognitive functioning.²

Few human intervention studies have been undertaken. However, Shilajit shows promise in supporting ovulation and sperm production,¹ and has been used as a potent aphrodisiac and memory enhancer.⁶ It is also an adaptogenic agent, improving the body’s response to stress.⁷ Indeed this was apparently extensively studies behind the iron curtain, although these studies have not been published.² Interestingly, Shilajit has been shown to hasten healing of fractures.⁸

Safety

Initial animal studies have indicated that Shilajit is well tolerated with no adverse effects.^2,9

References

1. Chaudhary, S., Singh, A.K. & Dwivedi, K. MEDICINAL PROPERTIES OF SHILAJIT A REVIEW. 2(2016).
2. Stohs, S.J. Safety and efficacy of shilajit (mumie, moomiyo). Phytother Res 28, 475-479 (2014).
3. Khokra, S. Therapeutic Potentials of “Shilajit Rasayana”-A Review. 1(2009).
4. Carrasco-Gallardo, C., Guzmán, L. & Maccioni, R.B. Shilajit: a natural phytocomplex with potential procognitive activity. Int J Alzheimers Dis 2012, 674142 (2012).
5. Al-Salman, F., Ali Redha, A. & Al-Zaimoor, Z. Inorganic Analysis and Antioxidant Activity of Shilajit. (2020).
6. Azhar, M., Quddusi, N., Akram, U., Anjum, A. & Hannan. Pharmacologial Activities Of Salajit (Asphaltum)-A Unani Drug a* a b b c d. (2011).
7. Agarwal, S., Khanna, R., Karmarkar, R., Anwer, M.K. & Khar, R. Shilajit: A review. Phytother Res 21, 401-405 (2007).
8. Sadeghi, S.M.H., et al. Efficacy of Momiai in Tibia Fracture Repair: A Randomized Double-Blinded Placebo-Controlled Clinical Trial. J Altern Complement Med 26, 521-528 (2020).
9. Kumar, S. SHILAJIT GOLD ARTICLE. (2020).

Iron is abundant on earth and is essential to all living organisms.¹

The only way to obtain iron is through the diet and a constant supply is necessary. This is particularly important in women of child-bearing age, which is why Omic has included it in its Femme formula. Iron deficiency is the most common micronutrient deficiency worldwide.²

Population groups such as menstruating women lose iron regularly, as do those you donate blood on a regular basis. Endurance athletes are also known to have increased iron requirements as their loss through the gut is much higher.¹

Iron in the Diet

Iron is found in the heme form in meat. Good sources include liver, muscle meat, poultry, and shell-fish. Non-heme iron is found in plants such as nuts, legumes, beetroot and grains.³ However the iron in plants is much less bio-available as the phytates and phenols in plants inhibits its absorption.¹ Furthermore, adequate stomach acid is necessary for the absorption of iron and calcium may inhibit iron uptake from any source.¹

Iron is absorbed from the intestines, transported in the blood (attached to transferrin) and then stored in the liver. Most iron is used by the bone marrow to make red blood cells. When the red blood cells break down, they are taken up by the Reticuloendothelial System where the iron is recycled back into the circulation. However, some iron is inevitably lost in the bowel, through sloughing of skin, in bile and of course in any bleeding.¹

Actions & Functions

Iron is essential for normal cellular function.¹ The reason iron is so central to human health is in its chemistry, being able to transfer electrons and bind oxygen (redox reactions).⁴

Iron is known largely as part of heme, a structure that is required by the cells to make certain proteins, including Hemoglobulin. If your Hemoglobulin is low, you are anemic. Iron deficiency is only one cause of anemia however and iron deficiency can cause many other problems besides anemia.⁴

Besides Hemoglobulin, iron is also required for other heme containing proteins, as well as non-heme iron-containing enzymes and iron-sulfur clusters.

All these proteins, enzymes and redox reactions help to make your cells go round.

Redox Reactions

Redox reactions are the processes in the cell that make free radicals and that squash free radicals. Free radicals (or oxidants) are “unbalanced” molecules. These free radicals, try and get rebalanced by taking an electron from another molecule. Some molecules, such as Vitamin E, can neutralize the free radical by giving them an electron. If there are more free radicals than neutralizers (anti-oxidants), the cell can be in a state of Oxidative Stress. This is not necessarily bad. Oxidative stress is very important for functions such as killing viruses and bacteria, as well as acting as signaling messengers, directing cells to change according to environmental stimuli.^{5 6}

Iron can catalyze the formation of potent free radicals within cells.⁷ As you can see below, however, Iron is also important for incorporation into anti-oxidant molecules.

Excess iron, however, can be problematic as there is a risk of free radical damage to DNA or cell membranes.⁴ The cell therefore maintains tight control on the availability of iron. It does this by controlling absorption, binding iron into storage proteins such as Ferritin and only releasing iron when this is necessary for one of its many functions.⁸

Heme Proteins

Hemoglobulin

Hemoglobulin in red blood cells, is of course, the way Oxygen is transported around the body. Low Hemoglobulin, known as anemia, has a number of different causes, but the most common is insufficient iron. Each and every cell needs oxygen where it is critical for optimal energy (ATP) production.

Iron is incorporated into heme and heme is incorporated into hemoglobulin. 70% of iron in the adult human body is found in Hemoglobulin.⁴ The body recycles used hemoglobulin, reusing the iron to fulfill the constant oxygen requirements of all tissues.⁹

Myoglobulin

Myoglobulin is found in muscle where it binds and stores Oxygen, releasing it as required for muscular contractions. Myoglobulin is the reason most muscle is red. Myoglobulin also has a role in neutralizing free radicals.¹⁰

Catalase

Catalase is essential in neutralizing free radicals in the cells. At its core, Catalase contains a heme molecule with its iron centre.¹¹

Peroxidases

These enzymes protect the cell from oxidative stress, basically acting as an anti-oxidant. One class of these enzymes (Myeloperoxidase) also performs oxidant activities, killing invading micro-organisms.¹²

Thyroid peroxidases is essential for the synthesis and secretion of thyroid hormones.⁴

Cytochromes

Cytochrome C is needed in the electron transport chain. This is the part of the mitochondria where most of the ATP (energy molecules) are made.

Cytochrome P450 is how your liver detoxifies (breaks down) compounds such as hormones and medications.

Nitric Oxide synthase

Nitric oxide is essential in healthy blood vessel and to defending against micro-organisms.¹³

Iron-sulfur clusters

These molecules are essential for DNA synthesis and repair and the healthy life-cycle of a cell.⁴ While universally important when not functioning optimally, this can be apparent in tissues with a high cell turnover leading to hair loss and brittles nails. Activation of immune cells is part of cell cycling and division.⁴

Iron containing enzymes

Enzymes make our body’s work like clockwork. Enzymes are molecules that help all biological processes to function efficiently. Iron metalloenzymes are enzymes that need to iron to make them work. These enzymes are critical for physiological processes including:

• Synthesizing neurotransmitters such as Dopamine and Serotonin (monoxygenases), as well as GABA. If your iron is low, even if your hemoglobulin is still normal, you may be feeling sad due to low neurotransmitters.^{1, 4}
• Synthesizing pro-inflammatory chemicals (lipogenases). Inflammation is a very important part of human health, without which we would not exist.¹
• Energy production (aconitase and dehydrogenases). These iron containing enzymes is critical for the citric acid cycle and the electron transport chain to work. The citric acid cycle is an interim step in making ATP, the energy molecule. The electron transport chain then takes over to produce ATP. Anemia is not the only reason a low iron can make you feel tired. Low ATP (energy) will make everything in your body work much more slowly.⁴

The End Points

Iron is involved in

• Carrying Oxygen to cells
• Making energy
• Supporting heart function
• Detoxification
• Tissue turnover such as in hair and nail growth
• Mounting a healthy immune response
• Healthy mood
• Cognitive function and normal brain development
• Preventing restless leg syndrome
• Healthy thyroid function

Safety

Accidental iron overdose especially by children is a medical emergency. Iron supplements can also cause gastric upset and constipation. Iron supplementation can also decrease zinc uptake if both are taken at the same time. Those with a genetic disorder, Hemochromatosis, should not take iron supplements.¹⁴

References

1. Wood RJ, Ronnenber, A.G. Iron. In: Shils M, ed. Modern Nutrition in Health and Disease. 10th ed. Lippincott Williams & Wilkins; 2006.
2. Percy L, Mansour D, Fraser I. Iron deficiency and iron deficiency anaemia in women. Best practice & research Clinical obstetrics & gynaecology. Apr 2017;40:55-67. doi:10.1016/j.bpobgyn.2016.09.007
3. Braun L, Cohen M. Herbs & Natural Supplements; An evidence-based guide. 3rd ed. Churchill Livingston; 2010.
4. Musallam KM, Taher AT. Iron deficiency beyond erythropoiesis: should we be concerned? Curr Med Res Opin. Jan 2018;34(1):81-93. doi:10.1080/03007995.2017.1394833
5. Sivanandham V. FREE RADICALS IN HEALTH AND DISEASES ─ A MINI REVIEW. Pharmacologyonline. 01/01 2011;1:1062.
6. Finley JW, Kong AN, Hintze KJ, Jeffery EH, Ji LL, Lei XG. Antioxidants in foods: state of the science important to the food industry. J Agric Food Chem. Jul 13 2011;59(13):6837-46. doi:10.1021/jf2013875
7. Kehrer JP. The Haber-Weiss reaction and mechanisms of toxicity. Toxicology. Aug 14 2000;149(1):43-50. doi:10.1016/s0300-483x(00)00231-6
8. Waldvogel-Abramowski S, Waeber G, Gassner C, et al. Physiology of iron metabolism. Transfus Med Hemother. Jun 2014;41(3):213-21. doi:10.1159/000362888
9. Silva B, Faustino P. An overview of molecular basis of iron metabolism regulation and the associated pathologies. Biochim Biophys Acta. Jul 2015;1852(7):1347-59. doi:10.1016/j.bbadis.2015.03.011
10. Vanek T, Kohli A. Biochemistry, Myoglobin. StatPearls. StatPearls Publishing Copyright © 2020, StatPearls Publishing LLC.; 2020.
11. Sepasi Tehrani H, Moosavi-Movahedi AA. Catalase and its mysteries. Progress in biophysics and molecular biology. Dec 2018;140:5-12. doi:10.1016/j.pbiomolbio.2018.03.001
12. Wojtunik-Kulesza K, Oniszczuk A, Oniszczuk T, Waksmundzka-Hajnos M. The influence of common free radicals and antioxidants on development of Alzheimer’s Disease. Biomedicine & Pharmacotherapy. 03/01 2016;78:39-49. doi:10.1016/j.biopha.2015.12.024
13. Maher A, Abdel Rahman MF, Gad MZ. The Role of Nitric Oxide from Neurological Disease to Cancer. Adv Exp Med Biol. 2017;1007:71-88. doi:10.1007/978-3-319-60733-7_5
14. Iron. National Institutes of Health Office of Dietary Supplements. Updated 2020, February 283. Accessed 2021, Jan 4, 2021. https://ods.od.nih.gov/factsheets/Iron-HealthProfessional/

Copper has been used throughout human history with the earliest recorded medicinal use of copper being traced to ancient Egypt. Copper was used to sterilize chest wounds and drinking water.¹ Even in our learned modern world, Copper objects in ICU were shown to decrease infections.²

Copper became biologically available in the atmosphere about 2-3 billion years ago and became an essential element for all organisms that use oxygen as part of their metabolism.³ The first known use of Copper in tools has been traced to the Anatolian region, dating around 9000 BC.⁴

Copper is relatively abundant in food and water.⁵ Good food sources of Copper are liver, shellfish and nuts, including cocoa. Potatoes, whole grains, seeds, mushrooms, and meat also contain moderate amounts. The amount of Copper in drinking water depends on the Copper in the soil. Copper pipes, cookware and utensils also contribute to the amount of Copper ingested.

Actions & Functions

Copper is essential to life. The adult body contains 100-200mg of Copper, with the highest levels in the brain, liver and kidneys.⁵

Copper, like most other essential nutrients in the body, can also be toxic.³ This is what is known as a U-shaped curve. Amongst other effects, Copper can act as a pro-oxidant damaging the cell and as an anti-oxidant, protecting the cell.³ Too little is bad, too much is bad. Copper imbalance is associated with neurological (including mental health) disease, gastro-intestinal, disease, liver disease and cancer.^{6, 7}

When obtaining sufficient minerals, such as Copper, the body these keeps the availability of these minerals under tight control by binding them to proteins so that they cannot cause any damage to delicate cellular structures.⁸

Copper deficiency in humans is relatively rare. However, Copper is particularly important in fetal development.⁹ This is why it has been included in Omic Femme, aimed at those women of child-bearing age. The body increases the amount of available Copper in pregnancy, supporting normal fetal growth.¹⁰ Copper deficiency can also be caused by supplementing with large amounts of Zinc.¹⁰

Copper is involved in many physiological pathways via a number of actions.^{3, 7, 10, 11}

Safety

As previously stated, too much Copper can be a bad thing. Copper contamination of food and beverages (usually from copper drinking vessels) can cause gastro-intestinal upset.⁴ Women on the Contraceptive pill may have elevated levels of Copper due to the effect of Estrogen in increasing Copper availability.¹² In essence, when on the Pill, the body is in a metabolic pregnancy state.

Ongoing high Copper intake can be associated with liver damage, gastro-intestinal upset, neurological and mental health disorders and possibly cancer.^{7, 13} There are also certain genetic disorders that lead to the abnormal accumulation of Copper in the liver and brain, with low levels in the rest of the body.¹⁰

The Upper Intake Level, set by the National Institutes of Health is based on Copper obtained from food and supplements and is set at around 10mg.¹³ As it is very difficult to actually know how much Copper you are obtaining from food, it is best to stick with a low-dose supplement, in a multivitamin such as Balance Femme.

References

1. Hodgkinson V, Petris MJ. Copper homeostasis at the host-pathogen interface. The Journal of biological chemistry. Apr 20 2012;287(17):13549-55. doi:10.1074/jbc.R111.316406
2. Salgado CD, Sepkowitz KA, John JF, et al. Copper surfaces reduce the rate of healthcare-acquired infections in the intensive care unit. Infect Control Hosp Epidemiol. May 2013;34(5):479-86. doi:10.1086/670207
3. Scheiber I, Dringen R, Mercer JF. Copper: effects of deficiency and overload. Met Ions Life Sci. 2013;13:359-87. doi:10.1007/978-94-007-7500-8_11
4. Barceloux DG. Copper. J Toxicol Clin Toxicol. 1999;37(2):217-30. doi:10.1081/clt-100102421
5. Altarelli M, Ben-Hamouda N, Schneider A, Berger MM. Copper Deficiency: Causes, Manifestations, and Treatment. Nutr Clin Pract. Aug 2019;34(4):504-513. doi:10.1002/ncp.10328
6. Bartnicka JJ, Blower PJ. Insights into Trace Metal Metabolism in Health and Disease from PET: “PET Metallomics”. J Nucl Med. Sep 2018;59(9):1355-1359. doi:10.2967/jnumed.118.212803
7. Krzywoszyńska K, Witkowska D, Swiatek-Kozlowska J, Szebesczyk A, Kozłowski H. General Aspects of Metal Ions as Signaling Agents in Health and Disease. Biomolecules. Oct 7 2020;10(10)doi:10.3390/biom10101417
8. Calvo J, Jung H, Meloni G. Copper metallothioneins. IUBMB Life. Apr 2017;69(4):236-245. doi:10.1002/iub.1618
9. Gambling L, Kennedy C, McArdle HJ. Iron and copper in fetal development. Semin Cell Dev Biol. Aug 2011;22(6):637-44. doi:10.1016/j.semcdb.2011.08.011
10. Turnland JR. Copper. In: Shils M, ed. Modern Nutrition in Health and Disease. 10th ed. Lippincott Williams & Wilkins; 2006.
11. Ogórek M, Gąsior Ł, Pierzchała O, Daszkiewicz R, Lenartowicz M. Role of copper in the process of spermatogenesis. Postepy higieny i medycyny doswiadczalnej (Online). Aug 9 2017;71(0):663-683. doi:10.5604/01.3001.0010.3846
12. Mehta SW, Eikum R. Effect of estrogen on serum and tissue levels of copper and zinc. Adv Exp Med Biol. 1989;258:155-62. doi:10.1007/978-1-4613-0537-8_13
13. Copper. National Institutes of Health Office of Dietary Supplements. Updated 2020, June 3. Accessed 2021, Jan 3, 2021. https://ods.od.nih.gov/factsheets/Copper-HealthProfessional/

Bacopa, a native of India and Australia, also known as Brahmi, has been used in Ayurvedic medicine for centauries as a medical plant that rejuvenates intellect and memory.¹ Recent research indicates that Bacopa may improve brain function involved in processing environmental inputs and enhancing learning and memory.²

Constituents & Mechanisms of Action

The main nootropic constituents of Bacopa are thought to be saponins known as bacosides.³ Other compounds include alkaloids, D-mannitol and apigenin.⁴

Bacopa exhibits multiple mechanisms by which it nourishes neurons, enhancing cognitive function.

One of the more interesting mechanisms is via increasing the number of connections between dendritic neurons in the brain.¹ Dendritic neurons have a major role in integrating and processing incoming information,¹ basically helping your brain to work better.

Bacopa also works to protect neurons via

• anti-oxidant effects^5,6
• supporting the production of Aceytlcholine⁶ and preventing its breakdown;⁷ Acetylcholine is pivotal to focus, learning and memory
• elevating levels of serotonin and dopamine⁶
• protecting against neurotoxins such as methylmercury,⁸ paraquat,⁹ acrylamide¹⁰
• increasing ATP (energy) in the brain¹¹
• improving blood flow to the brain¹²

In animal studies, Bacopa has been shown to improve:

• spatial learning performance¹
• learning and Memory retention^1,13
• mood¹⁴
• the response to stress¹⁵

Bacopa also displays longevity potential.⁶

Efficacy

Early human trials in healthy volunteers have indicated that Bacopa may decrease anxiety² and improve:

• speed of visual information processing²
• rate of learning²
• memory consolidation^2,16 and recall^17,18
• decreases anxiety²
• working memory⁷
• attention and cognitive processing⁷

Safety

Side effects to Bacopa are rare.⁴ While long term studies are needed, the most common side effect of Bacopa is mild gastrointestinal upset.²

References

1. Vollala, V.R., Upadhya, S. & Nayak, S. Enhancement of basolateral amygdaloid neuronal dendritic arborization following Bacopa monniera extract treatment in adult rats. Clinics (Sao Paulo) 66, 663-671 (2011).
2. Stough, C., et al. The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects. Psychopharmacology (Berl) 156, 481-484 (2001).
3. Sivaramakrishna, C., Rao, C.V., Trimurtulu, G., Vanisree, M. & Subbaraju, G.V. Triterpenoid glycosides from Bacopa monnieri. Phytochemistry 66, 2719-2728 (2005).
4. Aguiar, S. & Borowski, T. Neuropharmacological review of the nootropic herb Bacopa monnieri. Rejuvenation Res 16, 313-326 (2013).
5. Anbarasi, K., Vani, G., Balakrishna, K. & Devi, C.S. Effect of bacoside A on brain antioxidant status in cigarette smoke exposed rats. Life Sci 78, 1378-1384 (2006).
6. Rastogi, M., et al. Prevention of age-associated neurodegeneration and promotion of healthy brain ageing in female Wistar rats by long term use of bacosides. Biogerontology 13, 183-195 (2012).
7. Peth-Nui, T., et al. Effects of 12-Week Bacopa monnieri Consumption on Attention, Cognitive Processing, Working Memory, and Functions of Both Cholinergic and Monoaminergic Systems in Healthy Elderly Volunteers. Evid Based Complement Alternat Med 2012, 606424 (2012).
8. Sumathi, T., Shobana, C., Christinal, J. & Anusha, C. Protective effect of Bacopa monniera on methyl mercury-induced oxidative stress in cerebellum of rats. Cell Mol Neurobiol 32, 979-987 (2012).
9. Singh, M., Murthy, V. & Ramassamy, C. Standardized extracts of Bacopa monniera protect against MPP+- and paraquat-induced toxicity by modulating mitochondrial activities, proteasomal functions, and redox pathways. Toxicol Sci 125, 219-232 (2012).
10. Shinomol, G.K., Raghunath, N., Bharath, M.M. & Muralidhara. Prophylaxis with Bacopa monnieri attenuates acrylamide induced neurotoxicity and oxidative damage via elevated antioxidant function. Cent Nerv Syst Agents Med Chem 13, 3-12 (2013).
11. Liu, X., et al. Neuroprotective effects of bacopaside I in ischemic brain injury. Restor Neurol Neurosci 31, 109-123 (2013).
12. Kamkaew, N., Norman Scholfield, C., Ingkaninan, K., Taepavarapruk, N. & Chootip, K. Bacopa monnieri increases cerebral blood flow in rat independent of blood pressure. Phytother Res 27, 135-138 (2013).
13. Singh, H.K. & Dhawan, B.N. Effect of Bacopa monniera Linn. (brahmi) extract on avoidance responses in rat. J Ethnopharmacol 5, 205-214 (1982).
14. Sairam, K., Dorababu, M., Goel, R.K. & Bhattacharya, S.K. Antidepressant activity of standardized extract of Bacopa monniera in experimental models of depression in rats. Phytomedicine : international journal of phytotherapy and phytopharmacology 9, 207-211 (2002).
15. Sheikh, N., et al. Effect of Bacopa monniera on stress induced changes in plasma corticosterone and brain monoamines in rats. J Ethnopharmacol 111, 671-676 (2007).
16. Morgan, A. & Stevens, J. Does Bacopa monnieri improve memory performance in older persons? Results of a randomized, placebo-controlled, double-blind trial. J Altern Complement Med 16, 753-759 (2010).
17. Pase, M.P., et al. The cognitive-enhancing effects of Bacopa monnieri: a systematic review of randomized, controlled human clinical trials. J Altern Complement Med 18, 647-652 (2012).
18. Neale, C., Camfield, D., Reay, J., Stough, C. & Scholey, A. Cognitive effects of two nutraceuticals Ginseng and Bacopa benchmarked against modafinil: a review and comparison of effect sizes. Br J Clin Pharmacol 75, 728-737 (2013).

Cannabis is one of the most ancient non-food crops cultivated by humans. It has been used in the Traditional Medicines of South Africa, South America, Turkey, Egypt and many regions of Asia.¹ Only two to three generations ago, Cannabis was routinely used in Europe and the USA to treat a variety of conditions, from migraine to nausea to Parkinson’s disease.²

Constituents & Mechanism of Actions

The Cannabis sativa plant contains over 500 known compounds. ³ The most well-known group of these compounds are the phytocannabinoids, of which there are over 100 different types. These phytocannabinoidss can broadly divided into:

• Psychoactive compounds such as Tetrahydrocannabinol (THC)
• Non-psychoactive compounds including Cannabidiol (CBD), Cannabigerol (CBG) and other plant chemicals such as Cannabis terpenes.⁴

The phytocannabinoids all have an effect on the body’s own cannabinoid system, binding to the Endocannabinoid receptors found throughout the body.⁵

Omic Focus uses the THC-free Cannabinoids, CBD (Cannabidiol) and CBG (Cannabigerol), as well as Cannabis Terpenes in a synergistic mix.

The actions of CBD and CBG include:¹

• Neuroprotection (protecting nerves against damage) via anti-oxidant, anti-inflammatory, and immune mechanisms^1,6 as well as increasing glucose uptake by the neurons.⁷
• Pain-relief
• Anti-nausea
• Anti-psychotic
• Immune support
• Reduction of the effects of stress⁸
• Anti-anxiety effects⁹
• Anti-inflammatory⁴
• Sleep induction¹⁰

Plant terpenes have diverse effects¹¹ including:

• Anti-anxiety
• Immune enhancing
• Inhibition of the breakdown of Acetylcholine – pivotal to focus, learning and memory

The Cannabinoids and other plant compounds such as the Terpenes work synergistically together in the plant and when consumed by humans.⁴

Efficacy

CBD shows promise in treating anxiety, depression and psychosis.¹² CBD may potentially also treat disorders of the central nervous system such as Alzheimer’s disease, Parkinson’s disease, Multiple Sclerosis and Epilepsy.¹

Research on CBD, CBG and Cannabis Terpenes as nootropics are yet to be done. However, these cannabinoids are likely to improve brain health by

• Decreasing anxiety
• Protecting neurons
• Regulating mood
• Supporting a healthy stress response

Safety

CBD (without THC) is considered safe and well tolerated.¹³

References

1. Giacoppo, S., Mandolino, G., Galuppo, M., Bramanti, P. & Mazzon, E. Cannabinoids: new promising agents in the treatment of neurological diseases. Molecules 19, 18781-18816 (2014).
2. Russo, E.B. History of cannabis and its preparations in saga, science, and sobriquet. Chem Biodivers 4, 1614-1648 (2007).
3. Solymosi, K. & Köfalvi, A. Cannabis: A Treasure Trove or Pandora’s Box? Mini Rev Med Chem 17, 1223-1291 (2017).
4. Russo, E. Taming THC: Potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. British journal of pharmacology 163, 1344-1364 (2011).
5. Russo, E. & Guy, G.W. A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. Med Hypotheses 66, 234-246 (2006).
6. Gugliandolo, A., Pollastro, F., Grassi, G., Bramanti, P. & Mazzon, E. In Vitro Model of Neuroinflammation: Efficacy of Cannabigerol, a Non-Psychoactive Cannabinoid. Int J Mol Sci 19(2018).
7. Köfalvi, A., et al. Stimulation of brain glucose uptake by cannabinoid CB2 receptors and its therapeutic potential in Alzheimer’s disease. Neuropharmacology 110, 519-529 (2016).
8. Akirav, I. Cannabinoids and glucocorticoids modulate emotional memory after stress. Neuroscience and biobehavioral reviews 37, 2554-2563 (2013).
9. Campos, A.C. & Guimarães, F.S. Involvement of 5HT1A receptors in the anxiolytic-like effects of cannabidiol injected into the dorsolateral periaqueductal gray of rats. Psychopharmacology (Berl) 199, 223-230 (2008).
10. Babson, K.A., Sottile, J. & Morabito, D. Cannabis, Cannabinoids, and Sleep: a Review of the Literature. Curr Psychiatry Rep 19, 23 (2017).
11. Andre, C.M., Hausman, J.F. & Guerriero, G. Cannabis sativa: The Plant of the Thousand and One Molecules. Front Plant Sci 7, 19 (2016).
12. Campos, A.C., Moreira, F.A., Gomes, F.V., Del Bel, E.A. & Guimarães, F.S. Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders. Philos Trans R Soc Lond B Biol Sci 367, 3364-3378 (2012).
13. Iseger, T.A. & Bossong, M.G. A systematic review of the antipsychotic properties of cannabidiol in humans. Schizophrenia research 162, 153-161 (2015).

Cordyceps is a type of fungus that parasitizes insects. It is found throughout the world and is especially abundant in tropical forests and humid regions.¹

Cordyceps has been used for centuries in Traditional Chinese Medicine for the treatment of fatigue, low libido, as a recovery aid after illness, and to enhance physical strength and endurance.² While there are many species of Cordyceps, C. sinesis and C. militaris have been the most used and the most studied with C. militaris being considered a suitable substitute for the more extensively studied C. sinesis.³

Constituents & Mechanism of Actions

Cordyceps species contain a wide variety of compounds including polysaccharides, sterols, and amino acids. However, it is thought that nucleosides including cordycepsin (3’-deoxyadenosine), adenine and inosine acting on the purinergic receptors are responsible for most of the effects in the human body.³

The compounds in Cordyceps have, amongst other actions been shown to be:^1,3

• Anti-inflammatory, Anti-oxidant, Immune enhancing
• Anti-tumor
• Anti-diabetic
• Anti-aging⁴
• Energy enhancing⁵

In the laboratory, (in vitro) Cordyceps has also been shown to:

• Inhibit the breakdown of Acetylcholine⁶ – critical for focus, learning and memory
• Increase BDNF, promoting the survival of nerve cells⁷

While the exact mechanism are still being worked out, it is likely that all of these actions contribute to Cordyceps’ effects as a nootropic.⁸

Efficacy

Cordyceps has a long traditional use as a “powerhouse of energy.”⁹ However, modern clinical trials are only just starting to be done and indicate that in humans, Cordyceps increases aerobic capacity^10,11

In animal studies, Cordyceps has been shown to:

• Improve cognitive function^12,13
• Improve learning and memory¹⁴
• Improve the response to stress¹⁵

Safety

Cordyceps is generally well tolerated. Mild side-effects such as nausea and diarrhoea have been described.¹⁶

References

1. Liu, Y., et al. The Chemical Constituents and Pharmacological Actions of Cordyceps sinensis. Evid Based Complement Alternat Med 2015, 575063 (2015).
2. Lin B, L.S. Cordyceps as an Herbal Drug. in Herbal Medicine: Biomolecular and Clnical Aspects (ed. Benzie IFF, W.-G.S.) (CRC Press/Taylor & Francis, Boca Raton (Fl), 2011).
3. Olatunji, O.J., et al. The genus Cordyceps: An extensive review of its traditional uses, phytochemistry and pharmacology. Fitoterapia 129, 293-316 (2018).
4. Ji, D.B., et al. Antiaging effect of Cordyceps sinensis extract. Phytother Res 23, 116-122 (2009).
5. Dai, G., Bao, T., Xu, C., Cooper, R. & Zhu, J.S. CordyMax Cs-4 improves steady-state bioenergy status in mouse liver. J Altern Complement Med 7, 231-240 (2001).
6. Tsai, C.H., Yen, Y.H. & Yang, J.P. Finding of polysaccharide-peptide complexes in Cordyceps militaris and evaluation of its acetylcholinesterase inhibition activity. J Food Drug Anal 23, 63-70 (2015).
7. Lee, S.H., et al. Aqueous extract of Cordyceps alleviates cerebral ischemia-induced short-term memory impairment in gerbils. J Exerc Rehabil 12, 69-78 (2016).
8. Shashidhar, M.G., Giridhar, P., Udaya Sankar, K. & Manohar, B. Bioactive principles from Cordyceps sinensis: A potent food supplement – A review. J Funct Foods 5, 1013-1030 (2013).
9. Ashraf, S.A., et al. Cordycepin for Health and Wellbeing: A Potent Bioactive Metabolite of an Entomopathogenic Cordyceps Medicinal Fungus and Its Nutraceutical and Therapeutic Potential. Molecules 25(2020).
10. Steinkraus, D.C. & Whitfield, J.B. Chinese Caterpillar Fungus and World Record Runners. American Entomologist 40, 235-239 (1994).
11. Xiao, Y., et al. Increased aerobic capacity in healthy elderly humans given a fermentation product of Cordyceps CS-4. Medicine and Science in Sports and Exercise – MED SCI SPORT EXERCISE 31(1999).
12. He, M.T., et al. Protective role of Cordyceps militaris in Aβ(1-42)-induced Alzheimer’s disease in vivo. Food Sci Biotechnol 28, 865-872 (2019).
13. Cai, Z.L., et al. Effects of cordycepin on Y-maze learning task in mice. European journal of pharmacology 714, 249-253 (2013).
14. Gong, M.F., Xu, J.P., Chu, Z.Y. & Luan, J. [Effect of Cordyceps sinensis sporocarp on learning-memory in mice]. Zhong Yao Cai 34, 1403-1405 (2011).
15. Koh, J.H., Kim, K.M., Kim, J.M., Song, J.C. & Suh, H.J. Antifatigue and antistress effect of the hot-water fraction from mycelia of Cordyceps sinensis. Biol Pharm Bull 26, 691-694 (2003).
16. Hu, R., et al. Comparison of drug safety data obtained from the monitoring system, literature, and social media: An empirical proof from a Chinese patent medicine. PloS one 14, e0222077 (2019).

Gamma-aminobutyric acid (GABA) is a naturally occurring compound made in our bodies and found in foods such as tea and mushrooms. GABA can also be taken as a supplement.

GABA in the Body

Gamma-aminobutyric acid (GABA) is a naturally occurring amino acid that is made in the body. GABA is mostly known as the main inhibitory neurotransmitter in the brain while glutamate is the main excitatory neurotransmitter. Neurotransmitters are compounds that are found in neurons (brain cells). They act as chemical messengers, relying information from one neuron to the next resulting in an action. Neurotransmitters will either “fire up” a target cell (another neuron, muscle cell or hormone producing cell) or will dampen it down. The balance of the firing up (excitation) and the dampening down (inhibition) is of paramount importance in general and mental health. Too much firing up (excitation) can lead to agitation, distraction and to significant psychiatric disorders, while too much dampening down (inhibition) can lead to low mood and lethargy. Conversely too little inhibition leads to anxiety and insomnia.¹ Furthermore, neurotransmitters affect each other. Scientists are still investigating the complex neurotransmitter system and how this affects behavior.² GABA, the main inhibitory neurotransmitter is thought to support the “ability to stay focused on selected features of objects with suppression of behavioral reactivity to other features” as well as the “speed of integration of an action in physical manipulations with objects with well-defined scripts of actions.”² GABA is made in the neuron from glutamate with the help of Vitamin B6.³ It then sits in little vesicles (membrane sacs) waiting for a signal. Once the signal is received, GABA is released from the cell into the space between two cells (synapse). It then attaches to a receptor on the receiving cell where it inhibits firing. Although the brain is much more complex that a simple balance between neurotransmitters, in general the balance between excitation (glutamate) and inhibition (GABA) swings towards excitation, we may suffer anxiety,⁴ have difficulty sleeping and even difficulty concentrating.¹ Activating GABA receptors has long been used in pharmacology and plant medicine to help with sleep.^1,5 GABA is not only made in the brain but is also made in the gut but “good” gut bacteria in the gut microbiome.⁶ GABA seems send message from the gut to the brain via the vagus nerve.⁷

GABA in Food & Drink

GABA is found in tea, especially in white tea, cruciferous vegetables, spinach, tomato, mushroom and sprouted beans and grains.⁸

GABA as a Supplement

Taking GABA has been shown to have a positive effect on sleep.⁹ It also helps to decrease the stress that is induced by mental tasks,¹⁰ as well as supporting the nervous system, inducing relaxation. Supplementing GABA may “help to distribute limited attentional resources more efficiently.”¹¹

References

1. Savage, K., Firth, J., Stough, C. & Sarris, J. GABA-modulating phytomedicines for anxiety: A systematic review of preclinical and clinical evidence. Phytother Res 32, 3-18 (2018).
2. Trofimova, I. & Robbins, T.W. Temperament and arousal systems: A new synthesis of differential psychology and functional neurochemistry. Neuroscience and biobehavioral reviews 64, 382-402 (2016).
3. Jewett BE, S.S. Physiology, GABA, (Treasure Island (FL): StatPearls Publishing, 2020).
4. Wong, C.G., Bottiglieri, T. & Snead, O.C., 3rd. GABA, gamma-hydroxybutyric acid, and neurological disease. Ann Neurol 54 Suppl 6, S3-12 (2003).
5. Gottesmann, C. GABA mechanisms and sleep. Neuroscience 111, 231-239 (2002).
6. Yunes, R.A., et al. GABA production and structure of gadB/gadC genes in Lactobacillus and Bifidobacterium strains from human microbiota. Anaerobe 42, 197-204 (2016).
7. Bravo, J.A., et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A 108, 16050-16055 (2011).
8. Briguglio, M., et al. Dietary Neurotransmitters: A Narrative Review on Current Knowledge. Nutrients 10(2018).
9. Yamatsu, A., et al. The Improvement of Sleep by Oral Intake of GABA and Apocynum venetum Leaf Extract. J Nutr Sci Vitaminol (Tokyo) 61, 182-187 (2015).
10. Yoto, A., et al. Oral intake of γ-aminobutyric acid affects mood and activities of central nervous system during stressed condition induced by mental tasks. Amino Acids 43, 1331-1337 (2012).

Lion’s mane (Hericium erinaceus) is a fungus that grows on old or dead broadleaf trees. It is used as food and medicine in Asia and has a long history of use in traditional Chinese and Japanese Medicine as a restorative, promoting vigour and strength.¹

Constituents & Mechanism of Actions

Lion’s Mane contains a large amount of different bioactive compounds² including polysaccharides (e.g. β-glucan), terpenoids (e.g. hericenones, erinacines) and sterols.¹

The actions of these compounds include:

• Protection of nerves cells and stimulation of nerve growth³
• Anti-oxidation¹
• Anti-inflammatory²
• Anti-cancer effects⁴
• Anti-biotic properties²
• Anti-aging⁵
• Beneficial effects on glucose and fat metabolism²

While the exact mechanisms are still unknown, ut is likely that the neuroprotective, anti-inflammatory and anti-oxidation effects of Lions’ Mane contribute to its actions in the brain.⁶

Efficacy

While further clinical studies are needed to confirm the actions in the body of Lion’s Mane, Animal studies have shown that Lion’s Mane can

• Increase physical performance⁷
• Improve the functioning of the hippocampus, a region of the brain responsible for processing memories and emotional responses^8,9

Early studies in humans, indicate that Lion’s Mane can

• Reduce anxiety and depression⁶
• Improve cognitive function in those with mild cognitive impairment¹⁰

Safety

Lion’s mane is well tolerated and no adverse events have been reported, although those with mushroom allergy may need to avoid this.¹

References

1. Spelman, K., Sutherland, E. & Bagade, A. Neurological Activity of Lion’s Mane ( Hericium erinaceus ). Journal of Restorative Medicine 6, 19-26 (2017).
2. Friedman, M. Chemistry, Nutrition, and Health-Promoting Properties of Hericium erinaceus (Lion’s Mane) Mushroom Fruiting Bodies and Mycelia and Their Bioactive Compounds. J Agric Food Chem 63, 7108-7123 (2015).
3. Lee, K.F., et al. Protective effects of Hericium erinaceus mycelium and its isolated erinacine A against ischemia-injury-induced neuronal cell death via the inhibition of iNOS/p38 MAPK and nitrotyrosine. Int J Mol Sci 15, 15073-15089 (2014).
4. Zan, X., et al. Hericium erinaceus polysaccharide-protein HEG-5 inhibits SGC-7901 cell growth via cell cycle arrest and apoptosis. Int J Biol Macromol 76, 242-253 (2015).
5. Noh, H.J., et al. Chemical constituents of Hericium erinaceum associated with the inhibitory activity against cellular senescence in human umbilical vascular endothelial cells. J Enzyme Inhib Med Chem 30, 934-940 (2015).
6. Nagano, M., et al. Reduction of depression and anxiety by 4 weeks Hericium erinaceus intake. Biomed Res 31, 231-237 (2010).
7. Liu, J., Du, C., Wang, Y. & Yu, Z. Anti-fatigue activities of polysaccharides extracted from Hericium erinaceus. Exp Ther Med 9, 483-487 (2015).
8. Brandalise, F., et al. Dietary Supplementation of Hericium erinaceus Increases Mossy Fiber-CA3 Hippocampal Neurotransmission and Recognition Memory in Wild-Type Mice. Evid Based Complement Alternat Med 2017, 3864340 (2017).
9. Ryu, S., Kim, H.G., Kim, J.Y., Kim, S.Y. & Cho, K.O. Hericium erinaceus Extract Reduces Anxiety and Depressive Behaviors by Promoting Hippocampal Neurogenesis in the Adult Mouse Brain. Journal of medicinal food 21, 174-180 (2018).
10. Mori, K., Obara, Y., Moriya, T., Inatomi, S. & Nakahata, N. Effects of Hericium erinaceus on amyloid β(25-35) peptide-induced learning and memory deficits in mice. Biomed Res 32, 67-72 (2011).

Shilajit is a resinous substance that is found that is forced out from between rock layers in the Himalayas during the heat of the summer months. It contains a mixture of herbs and minerals from decomposition of the plant matter in the rocks centuries earlier.¹ The actual composition changes depending on the geographical region, environmental factors such as humidity and temperature, as well as the presence of plants, molds and bacteria.² Shilajit is well-known to occur in the Himalayas but is also found in Afghanistan, the Caucasus and Ural ranges, as well as in the Northern Pollock ranges in Australia³ and in the Chilean Andes.⁴

Shilajit has been used for over 3000 years in traditional Hindu Ayurvedic, Siddha and Unani medicine in Tibet and India. It is described as a “Rasayana,” a rejuvenator³ supporting a youthful long lifespan.¹ Its Sanskrit meaning is “conqueror of mountains and destroyer of weakness.”

Shilajit was also used secretly in the former USSR to enhance the mental and physical performance of Olympic athletes and special military forces.²

Constituents & Mechanisms of action

Humic substances make up 80-85% of Shilajit.⁵ These are organic compounds that occur in humus that makes up soil. Of these, Fulvic acid is the most well-known.⁴ Trace minerals including Phosphate, Silicon, Sulphur, Chlorine, Potassium, Calcium and Iron make up the rest of the compound.⁵

Early studies indicated that Shilajit has anti-inflammatory, anti-oxidant, analgesic, immunomodulator, anti-diabetic, lipid modulating, nootropic, anxiolytic, anti-viral and anti-fungal activity. It also stops the release of histamine.³ Shilajit seems to increase the production of ATP (energy) in cells, as well as increase Acetylcholine, necessary for cognitive functioning.²

Few human intervention studies have been undertaken. However, Shilajit shows promise in supporting ovulation and sperm production,¹ and has been used as a potent aphrodisiac and memory enhancer.⁶ It is also an adaptogenic agent, improving the body’s response to stress.⁷ Indeed this was apparently extensively studies behind the iron curtain, although these studies have not been published.² Interestingly, Shilajit has been shown to hasten healing of fractures.⁸

Safety

Initial animal studies have indicated that Shilajit is well tolerated with no adverse effects.^2,9

References

1. Chaudhary, S., Singh, A.K. & Dwivedi, K. MEDICINAL PROPERTIES OF SHILAJIT A REVIEW. 2(2016).
2. Stohs, S.J. Safety and efficacy of shilajit (mumie, moomiyo). Phytother Res 28, 475-479 (2014).
3. Khokra, S. Therapeutic Potentials of “Shilajit Rasayana”-A Review. 1(2009).
4. Carrasco-Gallardo, C., Guzmán, L. & Maccioni, R.B. Shilajit: a natural phytocomplex with potential procognitive activity. Int J Alzheimers Dis 2012, 674142 (2012).
5. Al-Salman, F., Ali Redha, A. & Al-Zaimoor, Z. Inorganic Analysis and Antioxidant Activity of Shilajit. (2020).
6. Azhar, M., Quddusi, N., Akram, U., Anjum, A. & Hannan. Pharmacologial Activities Of Salajit (Asphaltum)-A Unani Drug a* a b b c d. (2011).
7. Agarwal, S., Khanna, R., Karmarkar, R., Anwer, M.K. & Khar, R. Shilajit: A review. Phytother Res 21, 401-405 (2007).
8. Sadeghi, S.M.H., et al. Efficacy of Momiai in Tibia Fracture Repair: A Randomized Double-Blinded Placebo-Controlled Clinical Trial. J Altern Complement Med 26, 521-528 (2020).
9. Kumar, S. SHILAJIT GOLD ARTICLE. (2020).

Turmeric is an ancient spice native to India. It has been used for at least 600 years in traditional medicine and religious ceremonies.¹ Turmeric is commonly used not just as a flavoring agent in cooking, but also as a paste applied to the skin or added to a bath. Turmeric is a sign of auspiciousness and prosperity. It was brought to Europe by Arab traders.²

In Traditional Medicine, Turmeric is used for a wide range of effects including as a general tonic, for the treatment respiratory infections and peptic ulcers, as well as for arthritis and would healing.³

Constituents & Mechanisms of Action

Over 400 different compounds have been isolated from Turmeric.⁴

The polyphenols called Curcuminoids are the most active constituents of Turmeric and give it the yellow color that is so familiar in spice blends and curries. Turmeric also contains a number of essential oils,⁵ flavonoids, tannins, anthocyanin⁴ and polypeptides that display biological activity.⁶

Curcumin is the most prominent and well-studied of these bioactive compounds.⁷ It has a broad range of effects via multiple signaling pathways.¹

Curcumin has been shown to exhibit antioxidant, anti-inflammatory, immunomodulatory, anti-carcinogenic, hypoglycemic, anti-rhematic and hepato-protective⁸ and neuro-protective properties.⁴

It is perhaps best known for its anti-inflammatory effects.⁹ However, the anti-oxidant effects of curcumin may be associated with its cognitive enhancing effects by increasing glutathione (the master anti-oxidant), stimulating the growth of neurons and increasing Acetylcholine.¹⁰

Efficacy

Human clinical trials are limited. However, Turmeric / curcumin have been shown to be effective in

• Inflammatory conditions such as Ulcerative colitis¹¹
• Depression¹²
• Cognitive improvements such as memory and attention¹³
• Improving inflammatory markers and energy¹⁴

Safety

Turmeric and curcumin are generally recognized as safe. Mild stomach upset may occur.¹⁵

References

1. Gopinath, H. & Karthikeyan, K. Turmeric: A condiment, cosmetic and cure. Indian J Dermatol Venereol Leprol 84, 16-21 (2018).
2. Rajagopalan, R. & Suvarna, Y. TURMERIC: THE SPICE KING OF HEALTH. (2015).
3. Krishnaswamy, K. Traditional Indian spices and their health significance. Asia Pac J Clin Nutr 17 Suppl 1, 265-268 (2008).
4. Ayati, Z., et al. Ethnobotany, Phytochemistry and Traditional Uses of Curcuma spp. and Pharmacological Profile of Two Important Species (C. longa and C. zedoaria): A Review. Curr Pharm Des 25, 871-935 (2019).
5. Hwang, K.-W., et al. Levels of curcuminoid and essential oil compositions in turmerics (Curcuma longa L.) grown in Korea. Applied Biological Chemistry 59, 209-215 (2016).
6. Ramírez-Tortosa, M.C., et al. Oral administration of a turmeric extract inhibits LDL oxidation and has hypocholesterolemic effects in rabbits with experimental atherosclerosis. Atherosclerosis 147, 371-378 (1999).
7. Thomas-Eapen, N.E. Turmeric: the intriguing yellow spice with medicinal properties. Explore (NY) 5, 114-115 (2009).
8. Mirzaei, H., et al. Phytosomal curcumin: A review of pharmacokinetic, experimental and clinical studies. Biomed Pharmacother 85, 102-112 (2017).
9. Zdrojewicz, Z., Szyca, M., Popowicz, E., Michalik, T. & Śmieszniak, B. [Turmeric – not only spice]. Pol Merkur Lekarski 42, 227-230 (2017).
10. Howes, M.R., Perry, N.S.L., Vásquez-Londoño, C. & Perry, E.K. Role of phytochemicals as nutraceuticals for cognitive functions affected in ageing. British journal of pharmacology 177, 1294-1315 (2020).
11. Hanai, H., et al. Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial. Clin Gastroenterol Hepatol 4, 1502-1506 (2006).
12. Sanmukhani, J., et al. Efficacy and safety of curcumin in major depressive disorder: a randomized controlled trial. Phytother Res 28, 579-585 (2014).
13. Small, G.W., et al. Memory and Brain Amyloid and Tau Effects of a Bioavailable Form of Curcumin in Non-Demented Adults: A Double-Blind, Placebo-Controlled 18-Month Trial. Am J Geriatr Psychiatry 26, 266-277 (2018).
14. Kawasaki, K. & et al. Effect of a Combination of Hot Water Extract of Curcuma longa and Curcumin on Serum Liver Enzymes, Inflammatory Markers, and Emotional States in Healthy Participants with Moderately High Body Mass Index ―A Randomized, Double—blind, Placebo—controlled Clinical Trial―. 薬理と治療 45, 243-252 (2017).
15. Soleimani, V., Sahebkar, A. & Hosseinzadeh, H. Turmeric (Curcuma longa) and its major constituent (curcumin) as nontoxic and safe substances: Review. Phytother Res 32, 985-995 (2018).

Valerian is a medicinal herb native to North America, Asia and Europe. The root of Valerian has been used since the late sixteenth century.¹ It is used in Traditional Western Herbal Medicine, mainly to treat insomnia especially where this is associated with “nervous conditions.” Valerian is also used for anxiety, generalized pain, headache, and irritable bowel syndrome. It is listed as an approved herb in the German Commission E monographs.

Constituents & Mechanisms of Action

Valerian contains a number of plant chemicals, including:²

• Valeric acid, a terpene of the volatile oil
• Iridoids
• Alkaloids
• Lignans
• Free amino acids including:
  • GABA
  • Tyrosine
  • Arginine
  • Glutamine

It is thought that the terpenes are responsible for the effects of Valerian. However, it is more likely that the active constituents work together to produce the anxiolytic and hypnotic effects of Valerian. While the full mechanisms are still being worked out, Valerian seems to increase the concentration of GABA in the brain³ and by modulating the GABA-A receptors in the brain producing a sense of calm and improving sleep.⁴

Efficacy

Valerian root has been shown to be effective in improving:

• Sleep⁵
• Hot flushes in menopausal women⁶
• Anxiety⁷
• Response to stress⁸

Safety

According to researchers, Valerian is safer than pharmaceutical hypnotics, such as Diazepam, while improving sleep quality.⁹

References

1. Plushner, S.L. Valerian: Valeriana officinalis. Am J Health Syst Pharm 57, 328, 333, 335 (2000).
2. Hadley, S. & Petry, J.J. Valerian. Am Fam Physician 67, 1755-1758 (2003).
3. Kim, J., et al. Natural Products from Single Plants as Sleep Aids: A Systematic Review. Journal of medicinal food 21, 433-444 (2018).
4. Savage, K., Firth, J., Stough, C. & Sarris, J. GABA-modulating phytomedicines for anxiety: A systematic review of preclinical and clinical evidence. Phytother Res 32, 3-18 (2018).
5. Bent, S., Padula, A., Moore, D., Patterson, M. & Mehling, W. Valerian for sleep: a systematic review and meta-analysis. Am J Med 119, 1005-1012 (2006).
6. Jenabi, E., Shobeiri, F., Hazavehei, S.M.M. & Roshanaei, G. The effect of Valerian on the severity and frequency of hot flashes: A triple-blind randomized clinical trial. Women & health 58, 297-304 (2018).
7. Kohnen, R. & Oswald, W.D. The effects of valerian, propranolol, and their combination on activation, performance, and mood of healthy volunteers under social stress conditions. Pharmacopsychiatry 21, 447-448 (1988).
8. Cropley, M., Cave, Z., Ellis, J. & Middleton, R.W. Effect of kava and valerian on human physiological and psychological responses to mental stress assessed under laboratory conditions. Phytother Res 16, 23-27 (2002).
9. Kelber, O., Nieber, K. & Kraft, K. Valerian: no evidence for clinically relevant interactions. Evid Based Complement Alternat Med 2014, 879396 (2014).

Known as Lingzhi in China and Reishi in Japan, Ganoderma lucidum has a history in Asian Medicine for promoting general health and longevity for over 2000 years.¹ “The name Lingzhi represents a combination of spiritual potency and essence of immortality and is regarded as the “herb of spiritual potency,” symbolizing success, well-being, divine power, and longevity”.²

Constituents & Mechanisms of Action

While Reishi has been used traditionally for centuries, it is only recently that researchers have started to elucidate the bioactives and their mechanisms of action in the body. The bioactive constituents include terpenes, fatty acids and sterols. Reishi displays immune and cognitive enhancing effects as well as cardioprotective, anti-cancer, and anti-depressant actions, among other effects.¹ The mechanism for its action in sleep is not fully known but is thought to involve TNF-α³ as well as the GABA system.⁴

Efficacy

Most research has been done on human cells or animals,⁵ but controlled studies in humans are being undertaken. Preclinical and/or early clinical studies indicate that Reishi has been shown to support:

• Healthy glucose metabolism^6,7
• Healthy liver function⁸
• Sleep³

Safety

In most studies, Reishi is well tolerated by participants. This was born out in research that analyzed the experience of volunteers, as well as their biochemistry.⁹

References

1. Ahmad, M.F. Ganoderma lucidum: Persuasive biologically active constituents and their health endorsement. Biomed Pharmacother 107, 507-519 (2018).
2. Wachtel-Galor, S., Yuen, J., Buswell, J.A. & Benzie, I.F.F. Ganoderma lucidum (Lingzhi or Reishi): A Medicinal Mushroom. in Herbal Medicine: Biomolecular and Clinical Aspects (eds. Benzie, I.F.F. & Wachtel-Galor, S.) (CRC Press/Taylor & Francis Copyright © 2011 by Taylor and Francis Group, LLC., Boca Raton (FL), 2011).
3. Cui, X.Y., et al. Extract of Ganoderma lucidum prolongs sleep time in rats. J Ethnopharmacol 139, 796-800 (2012).
4. Chu, Q.P., et al. Extract of Ganoderma lucidum potentiates pentobarbital-induced sleep via a GABAergic mechanism. Pharmacol Biochem Behav 86, 693-698 (2007).
5. Frost, M. Three Popular Medicinal Mushroom Supplements: A Review of Human Clinical Trials. BYU Faculty Publications 1609(2016).
6. Chu, T.T., et al. Study of potential cardioprotective effects of Ganoderma lucidum (Lingzhi): results of a controlled human intervention trial. Br J Nutr 107, 1017-1027 (2012).
7. Gao, Y., Lan, J., Dai, X., Ye, J. & Zhou, S. A Phase I/II Study of Ling Zhi Mushroom Ganoderma lucidum (W.Curt.:Fr.)Lloyd (Aphyllophoromycetideae) Extract in Patients with Type II
   Diabetes Mellitus. International Journal of Medicinal Mushrooms – INT J MED MUSHROOMS 6, 33-40 (2004).
8. Gao, Y., et al. Protective Effect of Ganoderma (a Mushroom with Medicinal Properties) Against Various Liver Injuries. Food Reviews International 21, 27-52 (2005).
9. Wicks, S.M., et al. Safety and tolerability of Ganoderma lucidum in healthy subjects: a double-blind randomized placebo-controlled trial. Am J Chin Med 35, 407-414 (2007).

Ziziphus (also known as Jujube, red date and Chinese date) has a long history of use in Traditional Chinese Medicine to calm the mind and reduce insomnia.¹ It is native to Asia and southern Europe. Ziziphus fruit has been used as a food and medicine for thousands of years in China,² where it is known as the “fruits of life.”³ Technically Ziziphus jujuba refers to the fruit of the plant and Ziziphus spinosa refers to the seeds found in the single hard kernel of the fruit. In Traditional Chinese Medicine, the seeds are most commonly used for sleep.¹

Constituents & Mechanisms of Action

Ziziphus seeds contains many bioactive compounds including:

• Alkaloids e.g. fragufoline, sanjoinin A
• Saponins e.g. jububosides
• Flavonoids e.g. spinosyn, epigallocatechin
• Alkaloids e.g. sanjoinine, zizyphusine
• Unsaturated fatty acids e.g. lauric acid, oleic acid, linoleic acid
• Amino acids e.g. proline, alanine, valine, glutamic acid

The bioactives in Ziziphus exert their effect partially via the GABA system in the brain. GABA is the main calming neurotransmitter and Ziziphus partially binds to the GABA-A receptors. The resultant chemical cascade in the brain promotes mild sleep induction while limiting receptor desensitization and thus the addictive effects often seen with pharmaceuticals such as Diazepam. Ziziphus also acts on the Serotonin system and may exert neuroprotection by inhibition of NMDA-induced cell death by inhibiting free radical generation³ it’s effect are likely to be greater than the sum of its parts.

Efficacy

Ziziphus improves sleeps, calming and protects neurons. When compared with Diazepam, Ziziphus is slower acting but lasts longer with less impairment of learning and memory and less addictive effects.¹ In fact, Ziziphus may improve memory.³ Ziziphus may also lower cholesterol and improve menopausal symptoms.³

Safety

While research is continuing, a low dose of Ziziphus may be effective and safe as an ongoing support for sleep,¹ with adverse effects similar to placebo.⁴

References

1. Shergis, J.L., et al. Ziziphus spinosa seeds for insomnia: A review of chemistry and psychopharmacology. Phytomedicine : international journal of phytotherapy and phytopharmacology 34, 38-43 (2017).
2. Ji, X., et al. Isolation, structures and bioactivities of the polysaccharides from jujube fruit (Ziziphus jujuba Mill.): A review. Food Chem 227, 349-357 (2017).
3. Rodríguez Villanueva, J. & Rodríguez Villanueva, L. Experimental and Clinical Pharmacology of Ziziphus jujuba Mills. Phytother Res 31, 347-365 (2017).
4. Yeung, W.F., et al. Chinese herbal medicine for insomnia: a systematic review of randomized controlled trials. Sleep Med Rev 16, 497-507 (2012).

Kava’s use as a ceremonial and medicinal¹ beverage in the South Pacific islands predates written history. J Pepping described this beautifully in his 1999 monograph published in the American Journal of Health-System Pharmacy: “Drinking a kava beverage has been described as inducing a “warm, pleasant and cheerful, but lazy feeling,” making people “sociable, though not hilarious or loquacious,” and not interfering with reasoning.”² Today Kava is used either socially by drinking a water-based extract or medicinally in capsule or tablet forms. When consumed socially, this is usually done in a semi-traditional manner as a water-extract served from a large communal bowl.³ Generally much higher doses are consumed when using Kava socially than when using Kava as a medicine. When used medicinally the dose of active constituents is usually standardized and have been extracted with alcohol, acetone or water.⁴ Kava is listed as an approved herb in the German Commission E monographs for the treatment of nervous anxiety, stress and restlessness.

Constituents & Mechanisms of Action

The bioactive compounds in Kava are known as kavalactones. At least 18 different kavalactones have been identified and are thought to be the main active compounds. However, Kava also contains other bioactive constituents, such as cinnamic acid, phenolics, flavones and fatty acids that may be important in its clinical effect.¹ Different preparation of Kava may contain different ratios of these compounds. The constituents in Kava are thought to act by enhancing the GABA system in the brain.

Efficacy

Kava extract may be effective in supporting:

• Calm mood in those suffering with anxiety⁶
• Female sexual performance and enjoyment⁷
• Sleep⁵
• Menopausal symptoms⁸

Safety

Long term Kava use has been associated with:

• Skin conditions such as dermatitis
• Depression
• Liver damage

However, studies and reports are inconsistent and may reflect the type of extraction, specific cultivar consumed, as well as traditional vs recreational use. It has been suggested that poor quality material could be responsible for liver toxicity.⁹ However, Kava can inhibit detoxification enzymes. So when Kava is taken with alcohol, medications or other substances, the result may be heightened toxicity of those substances.¹⁰

It is best not to use Kava in those with Parkinson’s disease or taking L-Dopa or drugs used to treat Parkinson’s. Kava, when used as a medicine, does not appear to have addictive effects.⁷

References

1. Showman, A.F., et al. Contemporary Pacific and Western perspectives on `awa (Piper methysticum) toxicology. Fitoterapia 100, 56-67 (2015).
2. Pepping, J. Kava: Piper methysticum. Am J Health Syst Pharm 56, 957-958, 960 (1999).
3. Baker, J.D. Pills, Potions, Products: Kava's Transformations in New and Nontraditional Contexts. The Contemporary Pacific 24, 233-265 (2012).
4. Côté, C.S., Kor, C., Cohen, J. & Auclair, K. Composition and biological activity of traditional and commercial kava extracts. Biochemical and Biophysical Research Communications 322, 147-152 (2004).
5. Sarris, J., Panossian, A., Schweitzer, I., Stough, C. & Scholey, A. Herbal medicine for depression, anxiety and insomnia: a review of psychopharmacology and clinical evidence.
   Eur Neuropsychopharmacol 21, 841-860 (2011).
6. Sarris, J., et al. Kava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled study. J Clin Psychopharmacol 33, 643-648 (2013).
7. Sarris, J., et al. Kava for the Treatment of Generalized Anxiety Disorder RCT: Analysis of Adverse Reactions, Liver Function, Addiction, and Sexual Effects. Phytotherapy Research 27, 1723-1728 (2013).
8. Huntley, A.L. & Ernst, E. A systematic review of herbal medicinal products for the treatment of menopausal symptoms. Menopause 10, 465-476 (2003).
9. Teschke, R. & Lebot, V. Proposal for a Kava Quality Standardization Code. Food and Chemical Toxicology 49, 2503-2516 (2011).
10. Toohey, T.P., Lu, B.Y. & Wada, C. Toxic effects of psychotropics related to possible p450 enzyme inhibition by kava: report of 2 cases. Prim Care Companion CNS Disord 15(2013).

Magnolia bark has been used for thousands of years in Traditional Chinese and Japanese medicines to treat a variety of disorders including anxiety, insomnia, depression and stomach upsets.¹

Constituents & Mechanisms of Action

Over 250 compounds have been isolated from the Magnolia plant including a variety of terpenes, flavonoids, alkaloids and lignans. The main bioactive compound appears to be the lignans, magnolol and honokiol.¹ The constituents of Magnolia bark have anti-inflammatory, anti-microbial, anti-oxidant actions, as well as being supporting brain health, heart health and metabolic health.² Magnolia appears to have a GABA like effect in the brain³, promoting calmness. It also actives the receptors of the human endocannabinoid system. Although this does need to be further investigated.⁴

Efficacy

Most controlled studies have been done in test tubes or in animals. Early research suggests that Magnolia may improve:

• Anxiety⁵
• Sleep⁶
• Cognition⁷
• Metabolism⁸

Safety

Magnolia has been found to be safe in animal studies, even at high doses.⁹

References

1. Poivre, M. & Duez, P. Biological activity and toxicity of the Chinese herb Magnolia officinalis Rehder & E. Wilson (Houpo) and its constituents. J Zhejiang Univ Sci B 18, 194-214 (2017).
2. Zhang, J., et al. Insights on the Multifunctional Activities of Magnolol. Biomed Res Int 2019, 1847130 (2019).
3. Han, H., et al. Anxiolytic-like effects of 4-O-methylhonokiol isolated from Magnolia officinalis through enhancement of GABAergic transmission and chloride influx. Journal of medicinal food 14, 724-731 (2011).
4. Rempel, V., et al. Magnolia Extract, Magnolol, and Metabolites: Activation of Cannabinoid CB2 Receptors and Blockade of the Related GPR55. ACS Med Chem Lett 4, 41-45 (2013).
5. KURIBARA, H., KISHI, E., HATTORI, N., OKADA, M. & MARUYAMA, Y. The Anxiolytic Effect of Two Oriental Herbal Drugs in Japan Attributed to Honokiol from Magnolia Bark. Journal of Pharmacy and Pharmacology 52, 1425-1429 (2000).
6. Chen, C.R., et al. Magnolol, a major bioactive constituent of the bark of Magnolia officinalis, induces sleep via the benzodiazepine site of GABA(A) receptor in mice. Neuropharmacology 63, 1191-1199 (2012).
7. Lee, Y.K., et al. Protective effect of the ethanol extract of Magnolia officinalis and 4-O-methylhonokiol on scopolamine-induced memory impairment and the inhibition of acetylcholinesterase activity. J Nat Med 63, 274-282 (2009).
8. Zhang, Z., et al. The magnolia bioactive constituent 4-O-methylhonokiol protects against high-fat diet-induced obesity and systemic insulin resistance in mice. Oxidative medicine and cellular longevity 2014, 965954 (2014).
9. Liu, Z., et al. Evaluation of short-term and subchronic toxicity of magnolia bark extract in rats. Regul Toxicol Pharmacol 49, 160-171 (2007).

Gamma-aminobutyric acid (GABA) is a naturally occurring compound made in our bodies and found in foods such as tea and mushrooms. GABA can also be taken as a supplement.

GABA in the Body

Gamma-aminobutyric acid (GABA) is a naturally occurring amino acid that is made in the body. GABA is mostly known as the main inhibitory neurotransmitter in the brain while glutamate is the main excitatory neurotransmitter. Neurotransmitters are compounds that are found in neurons (brain cells). They act as chemical messengers, relying information from one neuron to the next resulting in an action. Neurotransmitters will either “fire up” a target cell (another neuron, muscle cell or hormone producing cell) or will dampen it down. The balance of the firing up (excitation) and the dampening down (inhibition) is of paramount importance in general and mental health. Too much firing up (excitation) can lead to agitation, distraction and to significant psychiatric disorders, while too much dampening down (inhibition) can lead to low mood and lethargy. Conversely too little inhibition leads to anxiety and insomnia.¹ Furthermore, neurotransmitters affect each other. Scientists are still investigating the complex neurotransmitter system and how this affects behavior.² GABA, the main inhibitory neurotransmitter is thought to support the “ability to stay focused on selected features of objects with suppression of behavioral reactivity to other features” as well as the “speed of integration of an action in physical manipulations with objects with well-defined scripts of actions.”² GABA is made in the neuron from glutamate with the help of Vitamin B6.³ It then sits in little vesicles (membrane sacs) waiting for a signal. Once the signal is received, GABA is released from the cell into the space between two cells (synapse). It then attaches to a receptor on the receiving cell where it inhibits firing. Although the brain is much more complex that a simple balance between neurotransmitters, in general the balance between excitation (glutamate) and inhibition (GABA) swings towards excitation, we may suffer anxiety,⁴ have difficulty sleeping and even difficulty concentrating.¹ Activating GABA receptors has long been used in pharmacology and plant medicine to help with sleep.^1,5 GABA is not only made in the brain but is also made in the gut but “good” gut bacteria in the gut microbiome.⁶ GABA seems send message from the gut to the brain via the vagus nerve.⁷

GABA in Food & Drink

GABA is found in tea, especially in white tea, cruciferous vegetables, spinach, tomato, mushroom and sprouted beans and grains.⁸

GABA as a Supplement

Taking GABA has been shown to have a positive effect on sleep.⁹ It also helps to decrease the stress that is induced by mental tasks,¹⁰ as well as supporting the nervous system, inducing relaxation. Supplementing GABA may “help to distribute limited attentional resources more efficiently.”¹¹

References

1. Savage, K., Firth, J., Stough, C. & Sarris, J. GABA-modulating phytomedicines for anxiety: A systematic review of preclinical and clinical evidence. Phytother Res 32, 3-18 (2018).
2. Trofimova, I. & Robbins, T.W. Temperament and arousal systems: A new synthesis of differential psychology and functional neurochemistry. Neuroscience and biobehavioral reviews 64, 382-402 (2016).
3. Jewett BE, S.S. Physiology, GABA, (Treasure Island (FL): StatPearls Publishing, 2020).
4. Wong, C.G., Bottiglieri, T. & Snead, O.C., 3rd. GABA, gamma-hydroxybutyric acid, and neurological disease. Ann Neurol 54 Suppl 6, S3-12 (2003).
5. Gottesmann, C. GABA mechanisms and sleep. Neuroscience 111, 231-239 (2002).
6. Yunes, R.A., et al. GABA production and structure of gadB/gadC genes in Lactobacillus and Bifidobacterium strains from human microbiota. Anaerobe 42, 197-204 (2016).
7. Bravo, J.A., et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A 108, 16050-16055 (2011).
8. Briguglio, M., et al. Dietary Neurotransmitters: A Narrative Review on Current Knowledge. Nutrients 10(2018).
9. Yamatsu, A., et al. The Improvement of Sleep by Oral Intake of GABA and Apocynum venetum Leaf Extract. J Nutr Sci Vitaminol (Tokyo) 61, 182-187 (2015).
10. Yoto, A., et al. Oral intake of γ-aminobutyric acid affects mood and activities of central nervous system during stressed condition induced by mental tasks. Amino Acids 43, 1331-1337 (2012).

Magnesium is necessary for every major biological process and is especially important in the activation of vitamins which go on to perform many important functions that support your cells and your life. Magnesium is found in beans, nuts, grains and green leafy vegetables as well as red meat and fish, with small amounts in water. However, Magnesium absorption is generally from plant food sources due to the phytates and oxalates found in plant foods especially when insufficiently prepared. The stressors of modern life and lower levels of magnesium in our food¹ due to poor soils and processing, make us especially vulnerable to magnesium insufficiency. We need to consume magnesium regularly to keep magnesium sufficient.² Magnesium plays a key role in the regulation of sleep, improving all aspects of sleep. This is thought to be by both enhancing GABA (calming brain chemical) and inhibiting NMDA. Magnesium citrate is also described as mildly sedating.

Magnesium Actions

Magnesium is involved in more than 300 essential reactions including:

• Activation of enzymes without which there would be no life.² These enzymes go on to perform functions such as:
  •  Making ATP, the energy molecules that allow the body to function (Mitochondrial ATP synthase).
  • Creating a beneficial charge across cell walls. Amongst other actions, this allows the transport of compounds such as glucose and other nutrients into the cell and supports nerve cells to fire correctly (Na + /K + -ATPase)
  • Utilizing food for energy (Hexokinase, Phosphofructokinase, Tyrosine Kinase on the insulin receptor)
  • Generating phosphocreatine for energy use and recycling of ATP (Creatine kinase)
  • Translating signals outside the cell into responsive actions inside the cells (Adenylate cyclase)
• Energy production
  • The breakdown and utilization of carbohydrates, protein, and fats to make ATP both in the aerobic pathway (oxidative phosphorylation) and anaerobic pathway (glycolysis)
  • ATP mainly exists as a complex with magnesium
• Synthesis of glutathione, the most important anti-oxidant in cells
• Antagonises calcium to support:
  • Blood vessel tone
  • Muscular contraction and relaxation
  • Release of neurotransmitters and “firing” of neurons (brain cells)
• Heart health
  • Protects heart cells from stress
  • Regulates potassium in heart cells
  • Reduces clumping of blood cells
• Cell health
  • Regulates cell movements
• Structural: Magnesium is an important structural element of:
  • Bones
  • Protein tissue such as muscle
  • DNA
  • Mitochondria (energy factories of the cells)
• Activation of other nutrients:
  • Vitamin D (Vitamin D also increases Magnesium absorption)
  • B-vitamins

Magnesium in the Body

Magnesium is the fourth most abundant mineral in the body,³ with 50% found in bone. 49% is found inside tissues and organs where it is bound to protein and to ATP, with only 1% being found in blood. Magnesium is lost from the body through mainly through urine but also through feces and sweat. The kidneys play a critical role in controlling the amount of magnesium in the body by controlling how much magnesium is lost in the urine. An average 70kg adult will have around 24 grams of magnesium in their body.  Research shows that nearly two-thirds of the people in the Western World, do not achieve the recommended daily allowance for magnesium.⁴ Stress, whether physical or emotional increases the need for magnesium.⁵ Furthermore, many medications cause loss of magnesium in the urine,² leaving many with a triple whammy. Ongoing magnesium deficiency is associated with many chronic and metabolic diseases including high blood pressure, heart disease, stroke, imbalanced cholesterol, insulin resistance, osteoporosis, depression, and insomnia. Furthermore, magnesium deficiency may help link inflammation, oxidative stress and aging. Sufficient magnesium is critical to overall health and neurological health, supporting sleep.

Magnesium in the World

Magnesium is the 8th most common element in the earth’s crust where it is most often found as magnesium carbonate or dolomite. However, most biologically available magnesium in the sea and the rivers. Due to the electromagnetic activity of magnesium, it naturally occurs in combination with other compounds

Magnesium Citrate

This form of magnesium has been chosen by Omic as it better absorbed and is more soluble than some other types of magnesium.⁶

References

1. Guo, W., Nazim, H., Liang, Z. & Yang, D. Magnesium deficiency in plants: An urgent problem. The Crop Journal 4, 83-91 (2016).
2. Gröber, U., Schmidt, J. & Kisters, K. Magnesium in Prevention and Therapy. Nutrients 7, 8199-8226 (2015).
3. Boomsma, D. The magic of magnesium. International journal of pharmaceutical compounding 12, 306-309 (2008).
4. Schwalfenberg, G.K. & Genuis, S.J. The Importance of Magnesium in Clinical Healthcare. Scientifica (Cairo) 2017, 4179326 (2017).
5.  Seelig, M.S. Consequences of magnesium deficiency on the enhancement of stress reactions; preventive and therapeutic implications (a review). Journal of the American College of Nutrition 13, 429-446 (1994).
6. Walker, A.F., Marakis, G., Christie, S. & Byng, M. Mg citrate found more bioavailable than other Mg preparations in a randomised, double-blind study. Magnes Res 16, 183-191 (2003).