The 2020 Practitioner's Guide to Zinc and Zinc Supplements - Metabolics

The 2020 Practitioner's Guide to Zinc and Zinc Supplements

Apr 29, 2020Emily

Zinc is one of the most abundant minerals in the body (after Iron) and is present in every cell. Approximately 20-40% of consumed zinc is absorbed by the body, depending on the bioavailability in the actual food source (bioavailability of zinc from grains and plant foods is lower than that from animal foods). The groups of foods providing the most bioavailable Zinc tend to be supplied by red meat & poultry, with oysters containing more zinc per serving than any other food. Other food sources include beans, nuts, certain types of seafood (such as crab and lobster), whole grains, fortified breakfast cereals, and dairy products.

An average-sized adult has 1.4 to 2.3 g of zinc and requires a mean consumption of zinc of about 10-15 mg daily. Because the body doesn’t naturally produce or store zinc, it is considered an essential nutrient and you must obtain it through food or supplements.

Zinc plays important roles in growth and development, immune function, neurotransmission, vision, reproduction, and intestinal ion transport. In fact, numerous aspects of cellular metabolism are zinc-dependent and, for zinc to perform these roles, it requires a number of specific systems to transport zinc across the cell membrane. Zinc transporter proteins carry out this role and are therefore indispensable in the physiology of zinc.

Functions Of Zinc

 At the cellular level, the function of zinc can be divided into three categories:

1) Catalytic

Over 100 different enzymes depend on zinc for their ability to catalyse vital chemical reactions

2) Structural

Zinc plays an essential role in the folding and structure of some proteins. Proteins are built as loose chains that fold on themselves to form more stable, compact structures. Zinc can often help this process by forming finger-like structures, known as a ‘zinc finger proteins’. These are one of the most abundant groups of proteins and are involved in numerous cellular processes, such as playing an essential role in the development of blood cells,  as described in the article, Zinc-finger proteins in health and disease.

Other examples of zinc finger proteins include nuclear receptors that bind and respond to steroids and other molecules, such as Vitamin D, Vitamin A, estrogen, and thyroid hormones.

Metallothioneins are also examples of proteins with a zinc-binding motif. They are small metal-binding cysteine-rich proteins with a high affinity for zinc. They work together with zinc transporters, regulating free zinc concentrations in the cytosol, as described in THE PHYSIOLOGICAL, BIOCHEMICAL, AND MOLECULAR ROLES OF ZINC TRANSPORTERS IN ZINC HOMEOSTASIS AND METABOLISM.

Metallothioneins are also involved in the regulation of metal ion homeostasis, the detoxification of heavy metals, and the defence against oxidative stress at a cellular level.

Removal of zinc from zinc-containing proteins results in protein misfolding and loss of function.

3) Regulatory

By acting as transcription factors and binding to DNA, zinc finger proteins can regulate gene expression.

Zinc has also been found to have a role in ‘apoptosis’ (cell death), modulating the activity of cell signalling enzymes, influencing hormone release and nerve impulse transmission, which is discussed in the paper, Zinc in Cellular Regulation: The Nature and Significance of “Zinc Signals”.

The passage of zinc into the body

Studies involving a direct comparison of the bioavailability of different forms of zinc in humans are few. The important fact is that the form of zinc needs to become dissociated into zinc ions, which then bind to ligands (proteins) that transport the zinc into the cells of the small intestine. There are specific transport proteins that carry zinc across the cell membrane into the portal circulation where it is transported directly to the liver before being released into the circulation for delivery to all tissues. Zinc homeostasis is tightly controlled at the whole body, tissue, cellular, and subcellular levels by a number of proteins, with zinc transporters being particularly important.

Approximately 70% of circulating zinc is bound to serum albumin (a plasma protein) and factors or conditions affecting this serum albumin concentration can, in turn, affect serum zinc levels. Serum zinc has a rapid turnover to meet tissue demands.

The availability of serum zinc is sensitive to the amounts of zinc absorbed from your diet and a reasonably constant dietary supply is thought to be necessary to satisfy the normal requirements of zinc for maintenance and growth.

Zinc is lost through the skin and kidneys (combined loss of 0.5-0.8mg/day), more zinc being lost when the body sweats more, as in hot climates and during strenuous exercise. Approximately half of all zinc eliminated from the body is lost through the shedding of epithelial cells in the gastro intestinal tract (0.5- 3mg/day) and, although a considerable amount is secreted through both biliary and intestinal secretions, most of the secretions are reabsorbed regulating the zinc balance. Starvation and muscle breakdown also increase zinc loss through the urine.

Protein enhances the absorption of zinc however a phytate rich diet (such as found in cereals, grains, corn and rice) can inhibit the absorption of zinc.

There is a very fine balance between zinc and copper during intestinal absorption. Zinc reduces the amount of copper your body absorbs because copper competes with zinc to bind with metallothionein, the binding protein that brings zinc into the intestinal cells. The ratio of zinc: copper is arguably more important than the concentration of either copper or zinc, and a common problem is excessive copper in water from copper pipes or copper cookware.

Zinc also competes with iron during intestinal absorption, with studies showing a link with whole body zinc status and iron homeostasis, illustrating the importance of a balance of these minerals.

Dietary factors influencing zinc absorption

It is important to have an understanding of zinc absorption and dietary influences when thinking about the best way to address your zinc nutritional status.

Marginal zinc deficiency and low zinc status have been recognized, as reported in zinc deficiency studies, in many groups of the population in not only less developed countries but industrialized ones as well.

Whilst the cause in some cases may be inadequate dietary intake of zinc, inhibitors of zinc absorption also have an impact. Phytate, which is present in staple foods like cereals, corn and rice, has shown in some zinc studies and reports to have a strong negative effect on zinc absorption following consumption.

Iron also affects zinc absorption, as can Cadmium (increasingly prevalent in our environment). Whilst the amount of protein in our meals can enhance zinc absorption, individuals proteins can have an inhibitory effect, as shown in this article on the dietary factors that influence zinc absorption.

Zinc Contributes to:

The normal function of the immune system

Zinc plays a central role in the immune system and immune system support affecting cellular and humoral immunity. It plays a role in cell mediated and antibody mediated responses. Zinc deficiency appears to induce apoptosis, resulting in a loss of B-cell and T-cell precursors within the bone marrow. The zinc dependent enzyme, Thymulin, stimulates the development of T cells within the thymus and the production of cytokines by mononuclear cells is also reduced by zinc deficiency. Adequate zinc status is necessary for natural killer cell function and zinc ions also exhibit direct anti-microbial activity, as highlighted in the scientific paper, Roles of Zinc Signaling in the Immune System.

DNA synthesis and cell division

The body needs zinc to make proteins and DNA, the genetic material in all cells.

Zinc is essential for cell proliferation and differentiation, especially for the regulation of DNA synthesis and mitosis. Zinc is a structural component of a number of proteins, including enzymes of cellular signalling pathways and transcription factors.

Zinc is essential for Insulin-like growth factor (IGF) which induces cell proliferation, and reduced zinc availability appears to affect membrane signalling and secondary messengers that coordinate cell proliferation.

Protection of DNA, proteins and lipids from oxidative damage

Zinc takes part in antioxidant activities in the body. By binding to thiol groups in proteins, it renders them less susceptible to oxidation. Zinc also supports in the scavenging of reactive oxygen species by inducing the expression of metallothionein and increasing catalase activity and functions as an antioxidant through the catalytic action of copper/zinc-superoxide dismutase.

Contribution to normal protein synthesis

Zinc contributes to normal protein synthesis including keratin and collagen synthesis. One of the important zinc dependent proteins is Gustin, which is involved in taste and smell. Poor or absent gustin levels results in impaired taste and smell, as shown in this zinc research on protein synthesis.

Other important zinc containing enzymes are carboxopeptidase, which helps break down protein. Zinc deficiency also impairs the synthesis of the protein Opsin, the precursor of Rhodopsin, which, if decreased, results in abnormal dark adaptation of the eye. Zinc is also required for the enzyme alcohol dehydrogenase, responsible for converting retinol to retinal, essential for eye function. Zinc is important for haemoglobin synthesis, a protein responsible for transporting oxygen in the blood.

Maintenance of bone

Zinc promotes the formation of bone-building cells and prevents the excessive breakdown of bone.

It is an essential cofactor in enzymes involved in synthesising various bone matrix cells and plays a role in bone deposition and resorption. In addition to this, it plays a structural role in the bone matrix itself. The hydroxyapatite crystals, making up the bone mineral, contain a zinc-fluoride complex and zinc is needed for osteoblastic (bone formation) activity. Zinc deficiency decreases the activity of matrix proteins, type 1 collagen and alkaline phosphatase decreasing calcium and phosphorus accumulation. Therefore, zinc deficiency may become a risk factor for poor extra cellular matrix calcification.

Zinc has also been shown in an observational study to be associated with an increased incidence of fracture.

Some studies indicate a reduction in serum zinc levels or excretion of zinc in bone disease cases such as osteoporosis.  

Maintenance of normal serum testosterone concentrations

Low dietary zinc status has been associated with low circulating concentrations of several hormones including testosterone, in some zinc research papers.

Serum testosterone appears to increase with oral zinc intake. In one zinc supplementation study, supplementing with 250 mg per day zinc sulphate for 6 weeks was shown to increase serum testosterone levels in people on haemodialysis.

Free Testosterone is converted to DHT (dehydrotestosterone) by the enzyme 5alpha-reductase) primarily in the prostate gland, testes, adrenal glands and hair follicles. DHT is increased in infertile men and, as it has an affinity for the hair follicles, can result in male pattern baldness. Zinc has been shown, as reported in this zinc study,to inhibit (up to 98%) the enzyme 5 alpha reductase.

The class of zinc finger transcription factors called the steroid/thyroid receptor superfamily, are responsible for mediating the biological response to a wide range of hormonal and metabolic signals.

Maintenance of normal hair, nails and skin

Zinc supports healthy hair skin and nails in a number of ways. Patchy loss of hair is a feature of zinc deficiency. This may be related to zinc’s role in the Hedgehog signalling pathway, a critical component in the pathways that govern hair follicle morphogenesis, according to this research on the hedgehog signalling pathway.

Akrodermatitis enteropathica, an autosomal recessive disorder caused by a defect in zinc absorption, is characterised by extensive dermatitis, growth retardation, diarrhoea, hair loss and paronchya.

Nail dystrophy has also been reported as a symptom of zinc deficiency, as shown in this report on the link between nutrition and nail disease.

Collagen in skin is produced by zinc dependent enzymes, the collagenases. Type 1 collagen is produced in the skin and is a structural long-lived protein produced by fibroblasts. Collagen constitutes 70% dry skin mass and gives the skin its structure and resistance to traction and strains. Total collagen in the body decreases 1% a year as a natural part of ageing, resulting in decreased elasticity and ageing skin. Zinc is essential not only for the enzymes producing collagen but also the cross linking that gives collagen its stability. Collagen and zinc studies have suggested that the rate of breakdown of collagen can be decreased by the administration of Zinc.

Cells express many zinc transporters, which contribute to homeostatic control of cells and tissues. Recent studies on zinc and the skin show links to the function of zinc and zinc transporters in various types of skin cells, with one scientific view stating that

  ‘One of the clinical manifestations of severe zinc deficiency in humans is akrodermatitis, characterised by erythematous, vesiculobullous and pustular rashes primarily around the body orifices and at the extremities.’ As detailed in this report on related to zinc and maintenance of normal skin.

Contribution to macronutrient metabolism

Zinc has essential structural, regulatory or catalytic roles in many enzymes. Many of the enzymes of the intermediate metabolism contain zinc and the deficiency of zinc affects the metabolism of all macronutrients. Protein synthesis, DNA synthesis and RNA synthesis all require zinc and lipid metabolism is also affected, with zinc deficiency being associated with reductions in circulating high-density lipoprotein. remove

Zinc is necessary to maintain normal concentrations of vitamin A in the plasma, being essential for normal mobilization of Vitamin A from the liver. Zinc deficiency decreases the synthesis of Retinol Binding protein (RBP) in the liver leading to lower levels of RBP in the plasma. It influences the absorption, transport and utilisation of Vitamin A. Zinc is also required for the enzyme Alcohol dehydrogenase, responsible for converting retinol to retinal, essential for eye function.

Contribution to normal carbohydrate metabolism

Zinc is an essential component of a large number of enzymes that participate in the synthesis and degradation of carbohydrates, lipids, proteins and nucleic acids, as described in this medical article on the role of zinc. There are also medical studies showing links with Zinc homeostasis and its role in diabetes and metabolic diseases.

Contributes to normal cognitive function

Zinc is highly concentrated in the cerebral cortex, pineal gland and hippocampus and zinc deficiency is associated with impaired memory formation and mood disorders. It is thought, as described by Science Daily, that zinc may influence the release of messenger molecules (neurotransmitters), which could be important for the formation and storage of memories.

In the hippocampus, zinc can reach concentrations of 8% of the total zinc in the brain. Zinc inhibits the NMDA (N-methyl-D –aspartate) receptor via its binding site located on one of its subunits, acting as an antagonist, which is reported in this scientific article to be associated with the potential antidepressant properties of zinc.

brain walnut representation

Contributes to normal fertility and reproduction

Zinc plays a role in fertility and conception support. It is one of the most important compounds of seminal fluid contributed by the prostate gland. Zinc plays an important role in normal testicular development, spermatogenesis, and sperm motility, as is illustrated in this article on zinc levels in seminal fluid. The zinc finger transcription factors in the steroid/thyroid receptor super family are responsible for bringing about the biological response to a wide range of hormonal and metabolic signals. Low dietary zinc status has been associated with low circulating concentrations of several hormones, including testosterone.

Zinc contributes to normal metabolism of fatty acids

As described in this article on the interactions between zinc and fatty acids, zinc is shown to be necessary for the conversion of linoleic acid to gamma-linolenic acid (GLA) and the mobilization of dihomo gamma linolenic acid for the synthesis of prostaglandins series-1 (anti-inflammatory prostaglandins) showing that it’s important for the metabolism of fatty acids.

Zinc contributes to normal acid-base metabolism

The pH of blood and extracellular fluid is tightly regulated by the presence of buffer systems, which bring about changes as a consequence of acid production from cellular metabolism or the ingestion of acids in the diet. Acid/Base metabolism is the balance between acid and alkaline to keep body fluids as close to a neutral pH (pH7) as possible. Any changes from this can result in reduced oxygen delivery to tissues, disturbances to electrolyte levels and changes to heart muscle contractility.

In blood, the major product of oxidative metabolism, CO2, reacts with water in the presence of carbonic anhydrase to form carbonic acid (H2CO3), which is relatively unstable and tends to dissociate and generate H+ and HCO3. The enzyme responsible for this is a zinc dependent enzyme is known as Carbonic Anhydrase and studies have shown that dietary deficiency of zinc reduces red blood cell carbonic anhydrase activity.

Zinc contributes to normal metabolism of vitamin A

Zinc participates in the absorption, transport and utilisation of Vitamin A. Zinc is necessary to maintain normal concentrations of vitamin A in the plasma, which makes it essential for the normal mobilisation of Vitamin A from the liver. Because zinc is required for the synthesis of retinol binding protein (RBP), zinc deficiency influences the mobilisation of vitamin A from the liver and its transport into the circulation.

Zinc contributes to maintenance of normal vision

The conversion of retinol to retinaldeyde (retinal) is regulated by zinc via the zinc-dependent enzyme, retinol dehydrogenase, making it very important for eye health. The conversion of retinol to retinal is a critical step in the visual cycle in the retina of the eye. Zinc is believed, according to this article on zinc and the eye, to affect photoreceptor plasma membranes, regulate the light-rhodopsin reaction, modulate synaptic transmission, and act as an antioxidant.

Note: These EU health claims apply where a food is at least a source of zinc as per Annex to Regulation (EC) No 1924/2006. Such amounts can be easily consumed as part of a balanced diet. The target population is the general population.  

Zinc and Gut Health

Food is broken down in the digestive tract and nutrients then get absorbed into the bloodstream. The walls of the intestines effectively act as a barrier allowing certain nutrients to pass through whilst blocking the passage of harmful substances. Small gaps withing the intestinal wall allow nutrients and water to pass through and these are known as tight junctions. In some cases, these tight junctions can become loose allowing more harmful substances such as bacteria and other toxins to pass through into the bloodstream. This is known as ‘Leaky Gut’ and is thought to cause widespread inflammation and often triggers an immune response.

Zinc is reported to support the immune system and important in many metabolic processes.

It was reported in a 2001 study on zinc and leaky gut, that, when given to patients with Crohn’s disease, zinc can have a positive effect on gut lining.

Recent research on intestinal permeability suggested that zinc was able to limit gut permeability by modifying the tight junctions.

This reported effect of zinc on the barrier function of the intestinal walls has led to the consideration of what effect zinc deficiency and supplementation may have with regard to various gastrointestinal issues and gut health, as discussed in this review on zinc and gastrointestinal conditions.

What happens if you are deficient in Zinc?

With Zinc being such an essential nutrient and extensively involved in so many vital roles in the body, deficiencies of zinc can manifest and present with various conditions. Zinc deficiency most commonly results from inadequate dietary intake but can also result from inadequate absorption (as seen in small bowel disease) and increased loss (such as seen with diuretics, hepatic insufficiency).

In fact, those at risk of a zinc deficiency may include:

  • Strict vegetarians and vegans
  • People with digestive problems like Crohn’s disease
  • Pregnant and breastfeeding women
  • People with chronic kidney disease
  • People who abuse alcohol

Symptoms of mild zinc deficiencies include:

  • Decreased immunity
  • Loss of appetite
  • Weight loss
  • Diminished taste or smell
  • Skin problems, acne, psoriasis atopic dermatitis
  • Poor vision, night blindness
  • White spots on fingernails
  • Depression, apathy

Symptoms of severe zinc deficiencies include:

  • Increased susceptibility to infections
  • Hair loss
  • Diarrhoea
  • Delayed sexual maturation
  • Impotence
  • Hypogonadism in males
  • Skin and eye lesions
  • Poor wound healing
  • Behavioural changes

Why should I take a zinc supplement?

As discussed, zinc is an essential micronutrient that is crucial to almost every aspect of your health. Many animal and plant foods are naturally rich in zinc but, in cases where you want to make sure you get sufficient of this essential nutrient to help support your nutritional requirements, taking a supplemental form is a suitable alternative. Estimates now indicate that approximately 2 billion people worldwide are deficient in zinc due to inadequate dietary intake.

Because zinc supports a wide range of the body’s physiological processes ensuring adequate intake is crucial.

One such physiological process is the support of immune cell function, helping stimulate particular immune cells. One study on zinc lozenges and their effect on the common cold showed that taking zinc every day may reduce the length of time you have a common cold. Zinc has also been shown to promote the immune response in the elderly, with one study looking at the elderly and zinc, suggesting that a daily dose of 45 mg may reduce infection rates in the elderly by as much as 66%.

Zinc is required for proper healing and studies have indicated that being deficient in zinc can slow the wound healing process. Acne is associated with low zinc levels, according to this report on innovative uses for zinc in dermatology.

Different Forms Of Zinc Supplements

There are many forms of zinc compounds. The percentages of zinc in the compounds that Metabolics supplies is given below:

Metabolics products state on the label the amount of elemental zinc delivered in one serving.

Metabolics Triple Zinc is a combination of zinc picolinate, Zinc Citrate, Zinc Sulphate offering an elemental zinc dose of 26.5 mg

Metabolics Zinc Formula- a combination balance of zinc bisglycinate and copper citrate

There is not much substantial evidence of greater effectivity of one form of zinc over another as absorption of zinc in the body is subject to so many variables. One study indicated that Zinc Picolinate might be better absorbed in some cases but, as this was a study looking at the results from 15 test subjects, much more research would be needed to reach a conclusive verdict.

It should be noted that there are many variables that affect zinc bioavailability and absorption including previous zinc intake. Other variables that may need to be considered when working out your nutritional strategy may include;

  • Existing zinc status of the individual. The lower the zinc status of the individual, the greater the absorption of zinc.
  • People that sweat a lot are subject to more zinc loss; for example athletes, those in hot climate, menopausal women experiencing night sweats.
  • Dosage of zinc, as zinc intake in dosages is increased, percentage absorption decreases probably due to the saturation of the transport mechanisms.
  • Zinc absorption appears to be decreased in the elderly.
  • Zinc absorption is increased with dietary protein intake.
  • The type of protein in a meal affects zinc bioavailability. Animal protein enhances absorption.
  • Phytates in cereals and soy inhibit absorption of zinc (except zinc bisglycinate found in Metabolics zinc formula, as shown in the study, “Bioavailability_of_zinc_glycinate_in_comparison_with_zinc_sulphate_in_the_presence_of_dietary_phytate_in_an_animal_model_with_Zn-65_labelled_rats”).
  • Caesin in milk and calcium inhibit absorption by binding with zinc ions.
  • Iron inhibits absorption of zinc. Cadmium- toxic levels of cadmium can inhibit zinc absorption
  • Although Copper (in high amounts) inhibits Zinc absorption, studies using 15mg zinc combined with 2mg copper showed no inhibition of zinc absorption was found. Metabolics Zinc Formula only contains 2 mg Copper.

Dosage

Different zinc supplements contain varying amounts of elemental zinc.

The Government Dietary Recommendations 2016 for Zinc intake can be found here.

The NRV (Nutrient reference value) for zinc is 10 mg per day, with less required for babies, children and teenagers and more for pregnant and breastfeeding individuals.

Supplementing with 15–30 mg of elemental zinc daily may improve immunity, eye, skin and other aspects of your health if you are experiencing health issues in these areas and you’re deficient in zinc.

Excess Zinc consumption can cause negative side effects, so it is best not to exceed the upper tolerable limit of 40 mg per day, unless under medical supervision.

If you experience any negative side effects after taking zinc supplements, decrease your dosage and consider consulting your healthcare professional if symptoms persist.

Zinc can also interfere with the absorption of copper and reduce the effectiveness of certain antibiotics.  Always consult with your healthcare professional if concerned.

Conclusion

Zinc is an essential mineral supporting many areas of your health. Metabolics offers a range of Zinc supplements to support your nutritional needs. The types of zinc supplements you take may remain a personal preference, or be based on some of the information provided.

Generally, zinc should not be taken on an empty stomach (as it can result in nausea), should be taken with an animal protein meal, away from cereals and taken in conservative doses to increase absorption.

As long-term zinc intake can cause copper deficiency, it is recommended you take Metabolics Zinc Formula if you have low copper levels as this contains copper and zinc bisglycinate. This form of zinc is the only form whose absorption is less affected by the presence of phytates in the diet and is balanced with a small amount of Copper.

More articles