Eagle

Zinc for Optimal Health Outcomes

Zinc is an essential mineral, critical for human health and required for proper growth, enzymatic and immune functions, hormone production and gene expression. It is estimated that 25 per cent of the global population is zinc deficient,1 equating
to approximately 1.7 billion people.2

In Australia, the major agricultural growing regions have widespread deficiency in soil zinc levels.3 Zinc is an essential nutrient for the proper growth of grains, fruit and vegetables.3 Zinc soil deficiency results in significantly reduced crop yields of approximately 40 per cent, as well as abnormal physical growth.3 With low zinc levels in food crops, the zinc status in animals and humans are subsequently affected as part of the food chain.3 Fertilisers containing zinc sulfate are employed to improve soil zinc levels.3 There are several groups of people at an increased risk of having an inadequate dietary zinc intake or an increased physiological requirement for the mineral. Vegetarians and vegans, particularly females, have a decreased dietary intake of zinc. Compared to omnivorous women, 44 per cent of vegetarians had a daily zinc intake below 6 mg versus only 13 per cent of female omnivores.4 Plants contain considerably less zinc than animal foods. In addition, phytates impair the absorption of zinc, and vegetarians may have a 50 per cent increased dietary zinc requirement due to this factor.5 The elderly and adolescents were also found to have inadequate dietary intakes of zinc.6 Female adolescents are particularly likely to have insufficient zinc levels due to menarche, excessive exercise, poor food selections and reduced total caloric intake.7 This is compounded by a high physiological demand for zinc needed for

the growth of body tissues and increased erythrocyte mass.7 The demand for zinc is increased during times of growth especially during pregnancy, infancy and childhood.5 Chronic diseases may be associated with a greater risk of zinc deficiency, including inflammatory bowel diseases, coeliac disease, alcoholic liver disease and sickle cell anaemia.8 People are at a greater risk of zinc depletion when using the oral contraceptive pill, ACE inhibitors, excessive alcohol and intense exercise.

Biological Roles of Zinc

A metallic chemical element, zinc is an essential component of numerous enzymes responsible for regulating gene expression and the integrity of body proteins.5 Zinc function falls into three categories on a biological cellular level catalytic, structural and regulatory.8 There are over 100 enzymes dependent on zinc for their function or as a cofactor. Zinc metalloenzymes are involved in digestion (carboxypeptidases), insulin packaging, cellular signal transmission (protein kinase C), antioxidant function (cytoplasmic superoxide dismutase) and immune system function (component nine of the complement system and zinc-bound thymulin from the thymus gland).9

Symptoms of Zinc Deficiency5,8

Level Signs and Symptoms Subclinical Mild Poor neuropsychological functioning Decreased immune system integrity Suboptimal pregnancy outcomes Impaired immune responses Impaired growth velocity Growth impairment Delayed sexual development Impotency Eye and skin lesions Alopecia Chronic and severe diarrhoea Impaired appetite and taste Corneal changes

Biological Functions of Zinc Metalloenzymes8,9

Enzyme Biological Function Carbonic anhydrase Interconversion of CO2 and bicarbonate, catalyses formation of carbonic acid in erythrocytes Proteolysis of dietary proteins Hydrolysis of phosphate groups Hydrolysis of alcohols to acetyladehyde, retinal to retinol Removal of toxic oxygen species Internal cellular signal transmission

Carboxypeptidase A Alkaline phosphatase Alcohol dehydrogenase

Severe

Cytosolic superoxide dismutase Protein kinase C

Practitioner Technical Information

Zinc Fingers
Numerous DNA-binding proteins (transcription factors) and enzymes involved in DNA metabolism are composed of a sequence of approximately 30 amino acids tightly bound to a zinc atom.9 These zinc and amino acid sequences are found in a coiled formation, resembling a finger.9 Zinc fingers are essential components involved in gene expression, including particular genes that regulate hormonal transcription.9 It is proposed that reproductive defects result from zinc deficiency causing inadequate binding via this mechanism.9

Zinc supplementation in combination with vitamins E and C, resulted in reduced oxidative stress and faster wound healing in children hospitalised with burns.17 Topical applications of zinc have also been found to accelerate wound healing and reduce infections.18 A common side-effect of radiation is the development of mucositis and oral ulceration. A clinical trial involving patients receiving radiation treatment for head and neck cancers found that oral zinc supplementation significantly reduced the severity and incidence of radiation induced ulceration and oral discomfort versus placebo.19 Zinc has been found to increase alkaline phosphatase activity and serum zinc levels in patients with bone fractures.20 Bone x-ray examination has also shown improved callus formation in patients receiving zinc versus controls.20 Therefore zinc supplementation may be beneficial in the treatment of patients with bone fractures or breaks.

Immune System
The immune system is impacted in various ways by zinc status. Zinc is necessary for the proper development and functioning of the cells involved in innate immune responses, including natural killer (NK) cells, macrophages and neutrophils. Deficiency causes decreased interleukin-2 (IL-2) gene expression and nuclear factor-B (NF-B) activation in T-helper cells.10 Zinc supplementation of 25 mg daily for a three month period in adults over the age of 65 resulted in increased levels of circulating lymphocytes.11 Thymulin, a thymus-specific hormone binding to receptors located on T cells, is dependent on zinc for its function. This hormone stimulates T-lymphocyte production in the thymus and promotes T cell function (including IL-2 production, cytotoxicity and suppressor functions).10 Zinc deficiency is known to lead to thymic atrophy and reduced lymphopoiesis.10 Zinc supplementation is recommended by the World Health Organisation for the treatment of infectious diarrhoeal diseases in children around the globe.12 In a meta-analysis zinc has been shown to reduce the severity, duration, risk of hospitalisation, all-cause mortality and direct mortality from diarrhoeal diseases in children, with a reduction in diarrhoeal mortality by 23 per cent.13 The elderly are at an increased risk of developing pneumonia. It was found that elderly people with a normal serum level of zinc (>70 mcg/dL) had a lower incidence and duration of pneumonia, a 50 per cent reduction in antibiotic prescription and duration of use, as well as a reduction in all-cause mortality, when compared to those with low serum zinc levels (<70 mcg/dL).14 Atopic conditions such as allergic asthma and eczema involve the release of histamine from mast cells and basophils with subsequent inflammation and associated symptoms. Zinc has been shown to inhibit the release of histamine in vitro and may be useful in the treatment of allergies.15

Reproductive System
Zinc plays many essential roles in reproductive health of both males and females. In males, low serum zinc levels are associated with low libido, altered sperm morphology, reduced sperm count and motility. Fertile men have been shown to have significantly higher seminal levels of zinc than their infertile counterparts.21 Supplementation with folic acid and 66 mg of zinc sulfate daily for 26 weeks in subfertile men increased normal sperm counts by up to 74 per cent and also increased sperm counts in fertile men.22 Testosterone production and the prostate are also influenced by zinc status in males.23-4 Zinc deficiency is associated with reduced testosterone levels in men. A study has shown supplementation with zinc for 6 months increased testosterone levels by 93 per cent, from 8.3 nmol/L at baseline to 16 nmol/L at study completion.25 A clinical trial with male athletes also found that oral zinc supplementation at a dose of 3 mg/kg per day for four weeks inhibited the reduction in both thyroid hormones and testosterone after exhaustive exercise compared to non-treatment.26 Therefore zinc supplementation may also improve performance in athletes. A 2007 Cochrane review involving over 9,000 women found that zinc supplementation resulted in a significant 14 per cent reduction in preterm births.27 Increased perinatal mortality, neurological and physiological difficulties are associated with preterm births. Therefore supplementation with zinc during pregnancy is beneficial to positively influence pregnancy outcomes.

Nervous System
Zinc is an essential component for neurobiological function and health. It is a crucial signalling ion of the inter- and intracellular central nervous system.28 Low serum zinc levels have been linked to a higher incidence of depression and zinc supplementation has shown antidepressant effects.29 Treatment with 25 mg of zinc daily also increases the efficacy of antidepressant medications such as imipramine when compared to placebo.30

Tissue Integrity
Numerous clinical trials have found an inverse correlation between serum zinc levels and the incidence and severity of acne. One trial involving supplementation with 30 mg of zinc daily for two months, found a significant reduction in inflammatory acne lesions in those with and without the presence of Propionibacterium acnes.16

Eagle

Children with attention deficit hyperactivity disorder (ADHD) or autism have been found to have 50 and 90 per cent lower levels of serum zinc respectively than healthy children.31-2 Treatment of ADHD children with 15 mg of zinc daily resulted in significantly improved reported behaviours as measured by the Conners Rating Scales by teachers and parents versus placebo controls.33

acid is regarded as the most highly absorbable form of vitamin C. Recent studies have found that ascorbic acid has antiproliferative and anti-angiogenic effects, possibly due to suppression of nitric oxide generation and the gene expression influencing cell cycle progression.40-1 Vitamin C has many influences on immune system function. Clinical trials have demonstrated the ability of vitamin C to increase the number of circulating immunoglobulins, including IgA, IgG and IgM.42 Supplementation with vitamin C increases the activity of neutrophils, which act to identify and destroy both bacterial and viral pathogens and increase their vitamin C concentrations.43 In the presence of pathogens, leukocytes release non-specific toxic substances including reactive oxygen species with the ability to destroy pathogens.44 The accumulation of vitamin C within neutrophils, lymphocytes and mononuclear phagocytes, protects against oxidative damage during the process of pathogen destruction.45

Diabetes and Blood Glucose Metabolism

Zinc is required in the pancreas for hormone production by the islet cells and as a component of the exocrine pancreatic juices of digestion. Zinc is found as part of the ZnT8 transporter in pancreatic beta cells, which responds to increased glucose levels by increasing insulin production.34 This transporter has also been found located in the cells of the thyroid and adrenal glands, indicating a possible role in the production of these related hormones.34 Type 1 and 2 diabetics have lower zinc levels than healthy subjects.35 A 2009 review found that zinc supplementation improved glycaemic control in both type 1 and 2 diabetics.35 The underlying mechanisms are proposed to involve improved signal transduction of insulin, reduction of inflammatory cytokine production and modulation of gene expression.35

Vitamin B6
Similarly to zinc and magnesium, vitamin B6 is also required for proper functioning of a number of enzymes within the body. These enzymes are involved in many processes including amino acid catabolism, catecholamine biosynthesis, histamine production, neurotransmitter synthesis and glucose metabolism.9 In critically ill hospitalised patients, administration of 50 or 100 mg of vitamin B6 daily resulted in improved immune system function.46 This was demonstrated by increased numbers of T-lymphocytes, T-helper and T-suppressor cells.46

Magnesium
A mineral involved in over 300 enzymatic reactions in the body, magnesium has a myriad of biological functions. Magnesium is essential for neuromuscular function, protein and lipid synthesis and the production of cellular energy.36 In the treatment of mild to moderate asthma, supplementation with magnesium resulted in improved peak expiratory flow rate, reduced bronchial reactivity to methacholine and significantly improved subjective Asthma Quality of Life Questionnaire responses compared to placebo.37 Magnesium also exerts anti-inflammatory activity, although its mechanisms are still being researched. Magnesium is a natural agonist to calcium and anti-inflammatory activity may occur via modulation of intracellular calcium concentrations.38 Potential mechanisms include opening of the calcium channel and N-methyl-d-aspartate receptor activation, priming of phagocytes, and activation of NF-kB.38 The role of magnesium deficiency in inducing a systemic stress response may also have adverse effects on nervous, endocrine, muscular and immune system health.38 Magnesium is required for the activation of the majority of ATPases. With inadequate levels the transportation of vital nutrients may be impaired, resulting in suboptimal mitochondrial function.39 Zinc and magnesium have a synergistic biochemical relationship. Inadequate zinc levels cause impaired enzymatic activity including RNA polymerases. As a result impaired protein and DNA synthesis can lead to inadequate production of serotonin and/or parathyroid hormone and subsequent poor absorption of magnesium.39

Manganese
The biological role of manganese involves acting as an enzymatic cofactor in carbohydrate, protein and lipid metabolism, collagen formation, prothombin synthesis, energy production and the functioning of superoxide dismutase.9 Deficiency of manganese manifests as a scaly red rash on the torso in humans.9 An in vivo trial investigating manganese and magnesium for immunomodulatory activity found that after 12 weeks of treatment, both groups demonstrated decreased reactive oxygen species present in macrophages and reduced nitric oxide production.47 Additionally, tumouricidal activities of peritoneal macrophages and splenic NK cells were increased.47 Mineral supplementation for immune system support is therefore considered prudent. Manganese complements many functions of zinc and has biological roles in glycolysis, protein metabolism and immune system function.

Copper
Zinc at doses higher than 50 mg daily has the capacity to increase copper binding by metallothioneins, sequestering the mineral in intestinal cells and reducing systemic copper levels. Therefore supplementation with copper is important.8 Copper is required by erythrocytes, involved in cellular energy production and is an essential part of many antioxidant

Ascorbic Acid
Vitamin C complements the function of zinc as an antioxidant in tissue repair and to support a healthy immune system. Ascorbic

Eagle
Adjunctive Treatment
Condition Immune Support Pregnancy

enzyme systems.36 Biochemically, copper participates in oxidationreduction reactions.9 The copper metalloenzyme lysyl oxidase, is involved in collagen biosynthesis and is therefore essential for proper tissue integrity and repair.9 This enzyme also requires vitamin C for its proper function. A deficiency of copper may manifest with broken blood vessels, bone and joint problems due to impaired collagen integrity.36 Additionally, nervous system function may be diminished and skin pigmentation reduced in those with low copper status.36 Recurrent infections due to reduced antibody responses to infection may be associated with low copper levels.36

Adjunctive Treatment Vitamin C, Cats Claw, Echinacea, Garlic, Andrographis, Vitamin D3, Selenium Natal Multinutritional Support, Omega 3 Fish Oils, Selenium, Vitamins C and D, Magnesium Cinnamon, Gymnema, Alpha-Lipoic Acid, Chromium, Vitamin D, Methylation Support

Metabolic Health

Selenium
This important trace mineral functions predominantly as an antioxidant, participating in redox reactions and thyroid metabolism. Deiodinase is a selenoprotein involved in the removal of iodine atoms from thyroid hormones, catalysing the conversion of thyroxine (T4) to its active metabolite, triiodothyronine (T3).9 Selenium deficiency increases plasma T4 and decreases T3 levels.9 Glutathione peroxidase selenoproteins are found in the cells of the gut, liver and colon and also in plasma.48 It functions as an antioxidant, protecting cells from lipid peroxidation resulting from the by-products of normal metabolism.48 Glutathione peroxidase also shields neutrophils from the oxidative damage ensuing from the process of destroying pathogens.48 Selenium deficiency is associated with impaired immune system function.8 Supplementation with 200 mcg of selenium daily for eight weeks improved immune cell response to pathogenic antigens in both healthy and immunosuppressed individuals.8 Selenium is a necessary part of clinical treatment protocols for the immune system. The major role of zinc as a structural component of zinc fingers is now well established. However, the addition of selenium has been shown to up-regulate zinc finger proteins, resulting in inhibition of cell invasion and stimulation of transforming growth factor beta (TGF-) signalling and DNA repair.49

Tissue Integrity

Vitamin C, Calcium, Glucosamine Sulfate

Cautions
Zinc has an emetic action and can cause nausea and vomiting in some people. It is recommended that zinc supplements be taken with food or just prior to retiring for sleep. The NHMRC recommended upper level of intake for zinc is 40 mg daily for adults, however the lowest observed adverse effect level (LOAEL) based on studies, is set at 60 mg daily.5 Adverse effects from long term excessive zinc intake are often associated with reduced copper status. Anaemia induced by low copper levels, immune system suppression and decreased HDL cholesterol levels can occur with extended supplementation of 150 mg daily.5

Adjunctive Treatment
Zinc can be complemented with a range of supplements dependent on the condition. Zinc is a core component of many clinical protocols including immune system support, male fertility, optimal pregnancy outcomes, allergies, acne, wound repair, impaired glucose metabolism and hormone production. Zinc supplementation provides a great foundation for optimal health outcomes due to its capabilities ranging from addressing a common nutritional deficiency and to supporting a multitude of physiological functions.

References
1. 2. 3.

4. 5.

6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26.

Maret W, Sandstead HH. J Trace Elem Med Biol 2006; 20(1): 3-18 U.S. Census Bureau. World POPClock Projection. Available from: http://www.census.gov/ipc/www/ popclockworld.html/Accessed 01.06.10 International Zinc Association. Zinc is an Essential Trace Element for Humans, Animals and Plants. Available from: http://www.zinc-crops.org/why_zinc.html/Accessed 01.06.10 Ball MJ, Ackland MC. Br J Nutr 2000; 83: 27-33 NHMRC. Nutrient Reference Values for Australia and New Zealand: Zinc. Commonwealth of Australia. Canberra. 2006. Woods JL et al. J Nutr Health Aging 2009; 13(8): 693-8 Gibson RS et al. Asia Pac J Clin Nutr 2002; 11(3): 543-52 Higdon J. An Evidence-Based Approach to Vitamins and Minerals. New York. Thieme. 2003. Brody T. Nutritional Biochemistry. San Diego. Academic Press. 1999. Prasad AS. Mol Med 2008; 14(5-6): 353-7 Fortes C et al. J Am Geriatr Soc 1998; 46(1):19-26 Aggarwal R et al. Pediatrics 2007; 119(6): 1120-30 Walker CL, Black RE. Int J Epidemiol 2010; 39(1): 63-9 Meydani SN et al. Am J Clin Nutr 2007; 86(4): 1167-73 Marone G et al. Agents Actions 1986; 18(1-2): 103-6 Dreno B et al. Eur J Dermatol 2005; 15(3): 152-5 Barbosa E et al. J Burn Care Res 2009; 30(5): 859-66 Lansdown AB et al. Wound Repair Regen 2007; 15(1): 2-16 Ertekin MV et al. Int J Radiat Oncol Biol Phys 2004; 58(1): 167-74 Sadighi A et al. Saudi Med J 2008; 29(9): 1276-9 Colagar AH et al. Nutr Res 2009; 29(2): 82-8 Wong WY et al. Fertil Steril 2002; 77(3): 491-8 Hunt CD et al. Am J Clin Nutr 1992; 56(1): 148-57 Leissner KH et al. Investigative Urology 1980; 18: 32-5 Prasad AS et al. Nutrition 1996; 12(5): 344-8 Kilic M et al. Neuro Endocrinol Lett 2006; 27(1-2): 247-52

27. 28. 29. 30. 31.

32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48.

49.

Mahomed K et al. Cochrane Database Syst Rev 2007; 18(2): CD000230 Sensi SL et al. Nat Rev Neurosci 2009; 10(11): 780-91 Levenson CW. Nutrition Reviews 2006; 64(1): 39-42 Siwek M et al. J Affect Disord 2009; 118(1): 187-95 Bradstreet J et al. Biological interventions in the treatment of autism and PDD. San Diego. Autism Research Institute. 2001. Bekaroglu M et al. J Child Psychol Psychiatry 1996; 37(2): 225-7 Uckardes Y et al. Acta Paediatr 2009; 98(4): 731-6 Murgia C et al. Nutr Metab Cardiovasc Dis 2009; 19(6): 431-9 Jansen J et al. J Nutr Biochem 2009; 20(6): 399-417 Bland JS et al. Clinical Nutrition: A Functional Approach. Gig Harbor. The Institute for Functional Medicine. 1999. Kazaks AG et al. Asthma 2010; 47(1): 83-92 Mazur A et al. Arch Biochem Biophys 2007; 458(1): 48-56 Johnson S. Med Hypotheses 2001; 56(2): 163-70 Mikirova NA et al. J Transl Med 2008; 12(6): 50 Belin S et al. PLoS One 2009; 4(2): e4409 Tanaka M et al. Jpn J Pharmacol 1994; 66(4): 451-6 Tauler P et al. Free Radic Res 2003; 37(9): 931-8 Alberts B et al. Molecular Biology of the Cell, 3rd edition. New York. Garland Publishing. 1994. Packer L, Fuchs J, eds. Vitamin C in Health and Disease. New York. Macel Dekker. 1997. Cheng C H et al. Eur J Clin Nutr 2006; 60: 1207-13 Son EW et al. Arch Pharm Res 2007; 30(6): 743-9 NHMRC. Nutrient Reference Values for Australia and New Zealand: Selenium. Commonwealth of Australia. Canberra. 2006. El-Bayoumy K, Sinha R. Mutat Res 2005; 591(1-2): 224-36

2010 Eagle

www.eaglenaturalhealth.com.au