CLINICALLY PROVEN;

• Supports immunological function, including the development, function and mediation of immune cells

• Supports 300 different enzymes in their ability to catalyse vital chemical reactions in the body

• Increases antibody production 

• Reduces the Severity of Cold and Flu Symptoms

• Supports cognitive health via intercellular neuronal signalling

• Supports early childhood brain development

• Improves skin integrity, tissue repair and wound healing

• Acne Management

• Supports Testosterone production and sperm health

• Antioxidant and Anti-Inflammatory Support

• High bioavailability

ABOUT ZINC

Over 300 different enzymes are dependent on zinc for their ability to catalyse vital chemical reactions in the body. As a component of finger-like structures known as zinc finger proteins, zinc plays an important structural role in proteins and cell membranes. In its regulatory role, zinc helps to regulate gene expression. By binding to DNA, zinc plays a role in cell signalling, and has been found to influence hormone release and nerve impulse transmission.[1],[2]

Unlike other micronutrients, there is no storage form of zinc in the body that can be readily mobilised when dietary intakes are inadequate. This emphasises the need for a regular dietary supply.[3] Rich sources of dietary zinc include meat, fish, shellfish, nuts, seeds, legumes and wholegrain cereals.[4]

Zinc homeostasis is maintained during reductions in zinc intake through the up-regulation of absorption and conservation of zinc losses in the gastrointestinal tract and kidneys. When these homeostatic mechanisms fail to ensure that the body’s requirements are met, clinical symptoms of zinc deficiency ensue.[5] Numerous research studies have found that sub-optimal levels of zinc are very common at all ages, especially in adolescents, vegetarians and the elderly.[6],[7],[8],[9] 

The 2012 Australian National Health Survey found that approximately 9% of females and 37% of males had inadequate zinc intakes,[10] strongly suggesting that zinc deficiency is widespread. Typically, adult Western diets contain approximately 10 mg of zinc per day,[11] whilst the ideal zinc supplemental intake for acute dosing is 50 mg per day.[12]

Aside from dietary choices and reduced zinc intake, several other factors can contribute to zinc deficiency including malabsorption syndromes such as cystic fibrosis, coeliac disease and Crohn’s disease, hypochlorhydria, alcoholism, diabetes, diarrhoea, excessive vomiting and some genetic diseases.[13]

Typically, adult Western diets contain approximately 10 mg of zinc per day, whilst the ideal zinc supplemental intake for acute dosing is 50 mg per day.

IMMUNE SUPPORT

Zinc

Zinc is involved in several aspects of immunological function, including the development, function and mediation of immune cells, such as neutrophils, monocytes and natural killer cells. Zinc also affects the development of acquired immunity and T lymphocyte function.[20] 

Zinc deficiency adversely affects a number of immune functions. This results in decreased production of certain cytokines, reduced activation of zinc-dependent enzymes and transcription factors, and decreased activity of thymulin, a zinc-dependent thymic hormone important for T cell function.[21],[22] Consequently, individuals with zinc deficiency experience increased susceptibility to a variety of infectious agents.[23],[24]

Vitamin C

Vitamin C is required for cell-mediated immune responses, antimicrobial activity, interferon synthesis and antihistamine properties. Vitamin C and zinc hold central positions amongst the micronutrients required to ensure proper immune function. They achieve this by supporting components of innate and adaptive immunity, such as epithelial barriers, cellular proliferation and antibody production, and by providing antioxidant protection. Deficiencies of vitamin C and zinc both severely suppress immune responses.[25]

Vitamin B6

Vitamin B6 is required for nucleic acid and protein synthesis, and therefore for cellular multiplication. Cellular multiplication is important for the normal function of immune cells and tissues. Isolated deficiencies of this nutrient appear to consistently inhibit cell-mediated immune function, as well as humoral responsiveness to a variety of test antigens. Immune function changes in the presence of vitamin B6 deficiency include decreased lymphocyte response, impaired antibody response, atrophy of lymphoid tissue and diminished neutrophil and inflammatory responses.[26]

Vitamin D

Vitamin D appears to influence bodily defence systems via multiple mechanisms. Adequate levels of vitamin D are required for barrier integrity, the production of antimicrobial peptides including cathelicidin, chemotaxis of other immune cells and the regulation of inflammation in the innate and adaptive immune system.[27],[28],[29],[30]The Australian Bureau of Statistics’ National Health Measures survey recently found that 23% of Australian adults have a vitamin D deficiency, with levels of <50 nmol/L serum 25-hydroxyvitamin D (25-OHD).[31]

23% of Australian adults have a vitamin D deficiency

COLDS AND FLU

Vitamin C and zinc have been shown to reduce the severity and duration of common cold symptoms, according to a recent systematic review and meta-analysis.[75] In a double-blind randomised controlled trial, school children were given 15 mg/day zinc bisglycinate for three months. The researchers found that the number of days that the children suffered from cough, rhinorrhoea and the likelihood of having two or more symptoms of the common cold was decreased.[76]

In other studies, a pooled analysis showed that participants diagnosed with the common cold with clear rhinorrhoea, experienced a definite rate of relief of symptoms when supplemented with vitamin C and zinc as compared to the placebo group (Figure 4).[79]

BRAIN AND COGNITIVE HEALTH

Zinc is a key modulator of intracellular and intercellular neuronal signalling. It is found in high levels in the brain, particularly the hippocampus, considered as the area involved in learning and memory, and in the amygdala, striatum and neocortex.[32] In the brain, most zinc is tightly bound to proteins, whilst free zinc is present in synaptic vesicles and plays a role in neurotransmission mediated by glutamate and gamma aminobutyric acid (GABA).[33]

CHILDHOOD BRAIN DEVELOPMENT 

During early development, cellular activity may be particularly sensitive to zinc deficiency, which has been shown to compromise cognitive function.[80] Experimentally induced zinc deficiency in humans has been shown to impair measures of mental and neurologic function, especially during critical periods of cognitive development. For instance, zinc deficiency during foetal brain development can cause congenital malformations, and zinc deficiency during later stages of brain development has been associated with deficits in attention, learning, memory, and neuropsychological behaviour.[81]

Furthermore, studies indicate that zinc supplementation may assist in infant and childhood development. A randomised controlled trial found that children who were administered 10 mg/day of zinc and also received a weekly psychosocial stimulation program (home visits during which play was demonstrated and maternal-child interactions were encouraged), showed benefits in overall development compared to zinc alone, stimulation alone, or no intervention. In addition, both groups receiving zinc demonstrated improvements in hand-eye coordination compared to groups not receiving zinc.[82] Similar results were reported in another study on children, who received five mg/day of zinc for one year, and demonstrated better motor skills than a control group of children.[83]

A recent meta-analysis and systematic review examined the relationship between zinc levels in autistic patients and the development of pathogenesis. In comparison with healthy individuals, autistic patients have different levels of trace elements such as copper, magnesium and zinc. Trace elements have been proven to influence the brain neurotransmitter metabolism significantly. Zinc itself is one of the important elements involved in GABA and glutamate regulation, cell signalling and cellular repair. The review found a significant difference in plasma zinc concentration between autistic patients and healthy controls. It concluded that while no significant relationship between zinc levels and autism has been found, zinc supplements can be used for nutritional therapy for autistic patients.[84]

SKIN INTEGRITY AND WOUND HEALING

Zinc

Tissue repair and wound healing are complex processes that involve a series of biochemical and cellular reactions, beginning with inflammation and followed by the repair and remodelling of the injured tissue.[34]  Zinc is intimately involved in connective tissue repair and wound healing. A deficiency of zinc retards both fibroplasia and epithelialisation and results in delayed wound healing, in spite of maintained skin stores of zinc.[35],[36]

Surgical trauma and infection are associated with an acute phase response most likely due to the induction of metallothioneins (MTs). MTs are proteins which serve as a storage form for zinc. They may also regulate the distribution and transfer of zinc and help to control free radical concentrations. This response involves a reduction of serum zinc, along with concurrent redistribution of zinc from the circulation to the liver, and possibly other tissues.[37],[38]

The results of several clinical studies suggest a beneficial role for orally supplemented zinc in surgical wound repair.[39] This was demonstrated in a study of 80 individuals who underwent a total hip replacement. The findings suggest that low serum zinc levels were significantly related to increased rates of infection and dehiscence (wound ruptures along a surgical incision).[40]

Similarly, an intervention study of pre- and postoperative zinc infusion of 30 mg/day in patients undergoing major vascular reproductive surgery attenuated the anticipated decline in serum zinc and produced significantly fewer wound healing complications than placebo. This suggests a role for the use of zinc in pre-operative care for the healing of wounds and maintenance of healthy skin.[41],[42] Another study indicated that zinc supplementation during the immediate post-injury period is associated with improved rates of neurologic recovery and visceral protein concentrations for patients with severe closed head injury.[43]

Vitamin C

Vitamin C is involved in all phases of wound healing. In the inflammatory phase it is required for neutrophil apoptosis and clearance. During the proliferative phase (tissue growth), it contributes towards collagen synthesis, maturation (tissue remodelling), secretion and degradation. Deficiencies affect the maturation phase by adversely altering collagen production and scar formation. Following tissue injury, plasma and tissue levels of vitamin C diminish, and as a consequence the wound healing process may be hindered. Vitamin C supplements may be useful to aid the healing process. In individuals with adequate vitamin C levels and tissue injury, studies have shown that vitamin C supplementation may also be beneficial because it helps to speed up wound healing.[44]

Vitamin D

Vitamin D regulates the expression of an antimicrobial protein, cathelicidin LL-37/hCAP18n. Cathelicidin LL-37/hCAP18n appears to mediate innate immunity in the skin by promoting wound healing and tissue repair. Studies have shown that it modulates inflammation in skin, induces angiogenesis, and improves re-epithelialisation (the process of restoring the epidermal barrier to re-establish a functional barrier that protects underlying cells from environmental exposures). Vitamin D therefore helps to maintain skin integrity and promote wound healing.[45],[46]

ACNE MANAGEMENT

Zinc deficiency and acne development are also linked through another mechanism involving retinol binding protein (RBP). RBP enables the transport of vitamin A to the tissues and its serum level reflects the levels of vitamin A in target organs. Zinc is essential for RBP synthesis and its secretion by the liver. Zinc is also thought to influence vitamin A transport and utilisation, directly or indirectly through certain enzymes, and to prevent keratinisation and follicular obstruction.[69]

Numerous clinical trials have proved the efficacy of zinc supplementation in acne. In a multicentre randomised controlled trial, patients took 30 mg/day of elemental zinc or a broad-spectrum antibiotic, minocycline, for three months. The clinical success rate was 31.2% for zinc in terms of achieving more than a two-third decrease in inflammatory lesions, i.e. papules and pustules.[70]

Another study investigated the effect of zinc on the number of facial superficial lesions (i.e. papules and pustules). Subjects received 30 mg/day of elemental zinc orally for two months. The results demonstrated a statistically significant reduction from day 30 and a further reduction at day 60, confirming the efficacy of zinc in the reduction of inflammatory lesions in acne.[71]

ANDROGEN METABOLISM

Zinc is needed to manufacture testosterone, and therefore may play a role in the hormonal functions of various endocrine organs and sperm health. Low zinc levels prevent the pituitary gland from releasing hormones required to stimulate testosterone production.[47]

Angiotensin converting enzyme (ACE) is closely associated with testicular and sperm development. Zinc deficiency impairs ACE activity, which in turn leads to depletion of testosterone and inhibition of spermatogenesis.[48],[49]

Adequate zinc status is important for optimising male reproductive health.

SPERM HEALTH

Zinc is important for male reproductive and sperm health. Zinc deficiency in men leads to several clinical signs, such as decreased spermatogenesis, altered sperm morphology and impaired male fertility. Given the pivotal role zinc plays as a cofactor in DNA transcription and protein synthesis, this is not surprising. DNA transcription is a major part of germ cell development, thus zinc is considered important for reproductive health.[72]

Sperm are protected against oxidative stress through the antioxidant properties of zinc, vitamin C and betacarotene. Oxidative stress causes extensive structural damage to sperm DNA, reduced sperm motility and defective sperm membrane integrity as a result of lipid peroxidation. Reactive oxygen species (ROS) include hydroxyl radicals, superoxide anions and hydrogen peroxide, the principle source of which are leukocytes and sperm cytoplasm.[73]

A recent systematic review compared a number of studies to assess the effect of antioxidants on male fertility. This included the effect of zinc on semen variables and pregnancy rate, both as a sole antioxidant and in conjunction with other antioxidants including vitamin C. Although the results were mixed, this review concludes that oral antioxidant supplementation with zinc (with or without vitamin C and other antioxidants) may ameliorate male infertility. This was due to improvement in certain sperm parameters, notably sperm motility, concentration and DNA fragmentation; and the likelihood of pregnancy. High ROS levels and oxidative stress have been implicated in the pathophysiology of male infertility and correlated with sperm DNA damage, impaired fertilisation and embryo development, low rates of implantation and occurrence of miscarriage.  This highlights the importance of an adequate zinc status for optimising male reproductive health and pregnancy outcomes.[74]

ANTIOXIDANT AND ANTI-INFLAMMATORY SUPPORT

Zinc is a key component of superoxide dismutase (SOD), an important enzyme, which functions as a scavenger of free radicals and protects the body against oxidative damage.[50],[51],[52]SOD is one of the most effective intracellular enzymatic antioxidants. It neutralises superoxide ions by catalysing the conversion of superoxide anions to dioxygen and hydrogen peroxide. Superoxide radicals, along with other free radicals, can cause peroxidative damage to the phospholipid component of cell membranes, especially disrupting unsaturated double bonds in fatty acids, as well as damaging other cellular components.

BIOAVAILABILITY

A number of factors may negatively impact zinc absorption and lead to zinc deficiency. These include diets containing high phytates and tannins,[54] certain forms of protein, such as casein,[55] supplemental iron and dietary cadmium consumption.[56],[57] Many women taking birth control pills may develop zinc deficiency due to the antagonistic effect upon zinc in the body.[58] Conditions such as alcoholism, malabsorption, sickle cell anaemia, renal disease, and many other chronic diseases are also linked with zinc deficiency.[59]

Zinc is ionised in the gut prior to absorption. The many factors affecting zinc bioavailability therefore act on the ionised (cationic) form of zinc.  Zinc bisglycinate is a totally reacted, nutritionally functional zinc amino acid chelate. As such, it is absorbed into enterocytes intact and is not ionised in the same way as zinc salt forms.[60] Not only does this positively impact absorption rates, but it also overcomes the nausea and cramping that can follow ingestion of high dose zinc supplements,[61] allowing for fast replenishment without these unwanted side effects.

Copper deficiency can be a consequence of long-term high dose zinc supplementation. This may be avoided by the use of zinc bisglycinate. A pilot trial on zinc bisglycinate showed that it did not change copper status over a six-week period at a dose of 60 mg/day, as measured by erythrocyte SOD activity, a marker for zinc-induced copper deficiency.[62]