Zinc

Zinc, a trace mineral essential for human health, is required for many biological processes. It is a vital component in over 300 enzymes that aid in metabolism, digestion, nerve function, antioxidant functions, and many other processes. 

Zinc is also crucial for the development and function of immune cells, making it a key player in maintaining a healthy immune system.  Its role in supporting the activity of antioxidant enzymes such as superoxide dismutase also has implications for immune function as well as overall health.

This article explores Zinc's importance as a dietary necessity as well as its role as a biomarker, shedding light on its essential roles in the human body in health and disease.

Understanding Zinc: Definition and Function

What is Zinc?  [2., 7., 21.]

Zinc is a trace mineral, meaning that it is present in the human body in small amounts, yet it is essential for a multitude of physiological functions.  As a trace element, it is secondary only to iron regarding its concentration in the human body.  

Zinc is vital for various bodily functions including immune system regulation, cell growth, wound healing, and carbohydrate metabolism.  It is found in adult humans in concentrations of 2 to 3 grams. 

Dietary zinc is absorbed in the small intestine ,primarily in the jejunum and enters portal circulation bound to albumin.  The majority of zinc in the body is stored in skeletal muscle and bone, with plasma concentrations of zinc representing about 0.1% of total zinc concentration.  Plasma zinc levels are tightly regulated to maintain a plasma zinc status of 10-15 micromols/L.  [4.]

Research has identified numerous catalytically active zinc metalloproteins and transcription factors crucial for gene expression. 

Zinc exhibits its therapeutic effects through various mechanisms: it inhibits intestinal ion secretion pathways, including cyclic adenosine monophosphate (cAMP), calcium, and nitric oxide, thus treating acute and chronic diarrhea. 

Although the exact mechanism of zinc's action in treating the common cold remains unclear, it's hypothesized to competitively inhibit ICAM-1, a receptor involved in rhinovirus infection. 

Additionally, zinc facilitates wound repair by enhancing auto-debridement and keratinocyte migration through its involvement as a cofactor in transcription factors and enzyme systems. 

Furthermore, zinc's antioxidant properties, mediated by cysteine-rich metallothioneins, protect against reactive oxygen species and bacterial toxins. 

Lastly, zinc regulates copper concentration by inducing the synthesis of a copper-binding ligand, sequestering copper in mucosal cells and preventing its transfer in the gastrointestinal tract.

Major enzyme types that require zinc to function properly include:

Metalloproteinases: Metalloproteinases are involved in the breakdown of extracellular matrix proteins and play crucial roles in tissue remodeling, wound healing, and various physiological processes.

Superoxide Dismutase (SOD): Superoxide dismutase is an antioxidant enzyme that catalyzes the dismutation of superoxide radicals into oxygen and hydrogen peroxide, protecting cells from oxidative stress and damage.

Carbonic Anhydrase: Carbonic anhydrase is essential for maintaining acid-base balance by catalyzing the reversible hydration of carbon dioxide to bicarbonate ions, crucial for various physiological processes including respiration and acid-base balance regulation.

DNA Polymerases: DNA polymerases are enzymes responsible for synthesizing new DNA strands during DNA replication, repair, and recombination processes, and zinc ions stabilize their structure and enhance their activity.

Alcohol Dehydrogenase: Alcohol dehydrogenase is involved in the metabolism of ethanol and other alcohols by catalyzing their oxidation to aldehydes or ketones, playing a crucial role in alcohol metabolism and detoxification.

RNA Polymerases: RNA polymerases are enzymes responsible for synthesizing RNA molecules from DNA templates during transcription, and zinc ions play a structural role in stabilizing their active sites.

Alkaline Phosphatase: Alkaline phosphatase is involved in the dephosphorylation of various molecules, playing crucial roles in bone mineralization, nutrient absorption, and cellular signaling processes.

Carboxypeptidases: Carboxypeptidases are enzymes involved in the breakdown of proteins by cleaving peptide bonds, with zinc ions serving as essential cofactors for their catalytic activity.

Functions of Zinc: What Does Zinc Do For the Body?

The functions of Zinc in the human body are diverse and vital. It is a key component in the activity of over 300 enzymes that are essential in metabolism, digestion, and nerve function. 

Zinc in the Immune System  [18., 19.]

Zinc influences the development and function of innate immune cells like neutrophils, natural killer (NK) cells, and macrophages. It affects crucial immune processes such as phagocytosis, intracellular killing, and cytokine production. 

Zinc deficiency adversely impacts the growth and function of T and B cells. 

Furthermore, zinc acts as an antioxidant, stabilizing membranes and preventing free radical-induced injury during inflammatory processes. 

Studies also suggest that zinc deficiency may lead to immune dysfunctions, as observed in zinc-deficient individuals, contributing to increased susceptibility to infections. 

Additionally, zinc activates NF-κB, a key transcription factor involved in immune responses, and enhances the expression of interleukin-2 (IL-2) and IL-2 receptors, promoting T-cell activation and proliferation. 

Zinc also decreases oxidative stress and inflammatory cytokines, highlighting its potential therapeutic role in various chronic diseases where oxidative stress plays a significant role. 

Moreover, zinc supplementation has shown promise in reducing the incidence and duration of infectious diseases in clinical trials, indicating its therapeutic potential in bolstering immune function.

Zinc in Cellular Growth, Protein, DNA and RNA Synthesis  [12.]

Zinc plays a crucial role in cell growth and proliferation, as well as protein, DNA, and RNA synthesis. 

Zinc deficiency leads to growth inhibition and decreased food intake in animals, with reduced thymidine incorporation into DNA observed early in various tissues. Zinc is essential for maintaining the structure of DNA, RNA, and ribosomes and regulates the transcription of enzymes involved in DNA and RNA synthesis. 

Additionally, zinc influences hormone-directed cell division, particularly through its impact on growth hormone (GH) and insulin-like growth factor-I (IGF-I). While zinc deficiency decreases circulating GH and IGF-I levels, exogenous administration of these hormones fails to stimulate growth in zinc-depleted animals. 

Zinc also regulates DNA synthesis in cultured cells by mediating the entry of cells into S phase and affecting IGF-I regulation of the G1-to-S phase transition. 

Moreover, zinc deficiency alters the expression of IGF binding proteins, which may sequester IGF-I and inhibit its binding to cell surface receptors, consequently impairing DNA synthesis. 

Overall, zinc deficiency disrupts multiple pathways involved in cell growth and proliferation, highlighting its essential role in these processes beyond its effects on GH and IGF-I.

Zinc in Wound Healing  [9.]

Zinc influences various phases of wound healing including haemostasis, inflammation, and immune defense, inflammatory resolution, tissue proliferation, and matrix remodeling. 

In the initial stages, zinc enhances platelet activity and aggregation, crucial for clot formation. It also induces alpha-granule release from platelets, aiding in the recruitment and activation of immune cells to the wound site. 

In the inflammatory phase, zinc modulates cytokine production and oxidative stress, reducing inflammation markers. Zinc deficiency impairs neutrophil chemotaxis and phagocytosis, hindering pathogen clearance, while supplementation enhances these functions. 

Additionally, zinc regulates macrophage differentiation and function, influencing the balance between pro-inflammatory M1 and anti-inflammatory M2 phenotypes. Macrophages employ nutritional immunity by manipulating zinc levels within phagosomes to combat intracellular pathogens. 

Zinc also affects TLR/NF-κB signaling, impacting inflammatory responses. Furthermore, zinc influences lymphocyte function, affecting antibody production and wound clearance.

Zinc deficiency impacts T lymphocyte populations, while supplementation increases regulatory T lymphocytes (Tregs), aiding in inflammation resolution and promoting re-epithelization. 

Fibroblasts, crucial for tissue proliferation, initiate collagen deposition with zinc's involvement in TGFβ/SMAD signaling, supporting granulation tissue formation. Zinc facilitates epithelial cell migration and wound closure, enhances keratinocyte migration, and promotes angiogenesis, supplying essential nutrients for tissue growth. 

However, zinc's effects on angiogenesis remain contradictory. In matrix remodeling, zinc-dependent matrix metalloproteinases (MMPs) modulate growth factor activation, ECM composition, and cell-matrix signaling, essential for wound repair. 

Zinc's role in MMPs activation and regulation is vital for ECM degradation, cell migration, and tissue integrity restoration, although further research is needed to fully elucidate its mechanisms in vivo.

Zinc for Healthy Skin, Eyes and Heart  [18., 19.]

Zinc demonstrates potent anti-inflammatory effects crucial for eye, heart, and skin health. Studies on human promyelocytic and monocytic leukemia cell lines, as well as aortic endothelial cells, reveal that zinc sufficiency significantly reduces the generation of inflammatory cytokines and oxidative stress markers compared to zinc-deficient conditions. 

Zinc supplementation increases the expression of key regulators of inflammation, while inhibiting NF-κB activation, a major immune response transcription factor. 

By downregulating NF-κB activation via A20-PPAR-α signaling pathways, zinc diminishes the production of inflammatory cytokines and adhesion molecules, thereby protecting endothelial cells from atherosclerosis. Furthermore, zinc acts as an antioxidant by competing with redox-active metals, enhancing antioxidant enzyme activity, and upregulating the Nrf2 pathway, which regulates antioxidant gene expression. 

Zinc supports healthy skin and has shown benefit in treating multiple dermatological conditions, through various mechanisms.  [6.] 

Zinc plays a crucial role in maintaining eye health, particularly in age-related macular degeneration (AMD), which affects a significant portion of the aging population. Studies have shown that zinc deficiency may contribute to oxidative stress and retinal damage. 

Clinical trials have demonstrated that zinc supplementation, either alone or in combination with antioxidants, significantly reduces the risk of advanced AMD and vision loss, with no significant side effects noted. 

Additionally, zinc supplementation has been associated with increased longevity and reduced mortality, particularly from cardiovascular diseases, highlighting its potential beneficial effects beyond eye health.

Zinc in Pregnancy, Infancy, and Childhood

Because of zinc’s essential roles in growth and development, it is reasonable to consider that zinc is an important nutrient for healthy pregnancy and infant development.  Studies on zinc supplementation in pregnancy are inconclusive; however, the risks of zinc deficiency in affected infants have been demonstrated.  [23.] 

Other Functions of Zinc

Zinc is also required for taste and smell.  [15., 20.]  It is also an essential element for proper carbohydrate, lipid and protein metabolism.  [3.]

Finally, zinc may benefit a healthy mood; zinc deficiency has been correlated with major depression.  [22.]

The Copper/Zinc Relationship  [16.]

The relationship between copper and zinc is intricately intertwined, as both minerals play essential roles in various biological processes. 

Copper and zinc often compete for absorption in the gastrointestinal tract due to their similar chemical properties, and an imbalance in their levels can have significant physiological consequences. 

While zinc is crucial for immune function, DNA synthesis, and wound healing, copper is involved in the formation of connective tissue, neurotransmitter synthesis, and antioxidant defense mechanisms. 

However, excessive zinc intake can interfere with copper absorption and metabolism, leading to copper deficiency and subsequent health issues such as anemia, neurological disorders, and impaired immune function. 

Conversely, copper overload can inhibit zinc absorption and utilization, potentially disrupting zinc-dependent enzymatic reactions and contributing to oxidative stress. 

Maintaining a balanced ratio of copper to zinc is essential for optimal health and physiological function.

Dietary Sources of Zinc: What Foods Have Zinc? 

Animal-Based Sources of Zinc:

• Seafood: Oysters, crabs, lobsters
• Meats: Beef, lamb

Plant-Based Sources of Zinc:

• Legumes: Lentils, chickpeas, beans
• Seeds and nuts
• Whole grains
• Dairy products (not plant-based)

It's essential to note that while plant-based sources offer alternatives for those on vegetarian or vegan diets, the bioavailability of zinc from these sources may be lower due to the presence of phytates, which can hinder absorption.  [7.]

Therefore, individuals relying on plant-based diets should ensure a diverse intake of zinc-rich foods to meet their nutritional requirements effectively.  Supplementation may be considered, and should be monitored by a medical professional. 

Zinc Deficiency

While severe zinc deficiency is uncommon in developed nations, milder forms may be prevalent, especially in the developing world, where it ranks as the fifth leading cause of healthy life years lost. Zinc supplementation, proposed to be added to oral rehydration therapy (ORT), has shown promise in reducing child mortality rates globally. 

Zinc deficiency can lead to adverse health effects, such as compromised immune responses, skin manifestations, and delayed wound healing, while regular zinc intake may mitigate risks of common colds and improve metabolic parameters like blood pressure and cholesterol levels. Moreover, zinc's role in diseases like cancer, depression, and sepsis warrants further investigation to explore its potential therapeutic benefits.

Recommended Dietary Allowance and Supplementation

Recommended Dietary Allowance of Zinc: How Much Zinc Should I Have Per Day?  [7.]

The Recommended Dietary Allowance (RDA) for adults is 8 mg/ day for women and 11 mg/day for men.  In pregnancy, the RDA is 11 mg/day and in lactation it is 12 mg/day.  

Indications for Zinc Supplementation: What is Zinc Good For?

While dietary sources are the preferred method for obtaining zinc, supplementation can be beneficial in certain circumstances.  

However, it's important to approach Zinc supplementation with caution. Excessive intake can lead to adverse effects, and supplements can interact with certain medications and medical conditions.

Zinc Deficiency

Supplementation is crucial for individuals with diagnosed zinc deficiency, characterized by symptoms such as impaired growth, weakened immune function, delayed wound healing, and skin problems.

Wound Healing

Zinc supplementation can aid in wound healing by promoting tissue repair, reducing inflammation, and supporting immune function.

Acne Treatment  [6.]

Some studies suggest that zinc supplementation may help alleviate symptoms of acne, possibly due to its anti-inflammatory properties and its role in regulating sebum production.

‍Immune Support

Zinc plays a vital role in immune function, and supplementation may help reduce the duration and severity of colds and other respiratory infections.

Eye Health 

Research indicates that zinc supplementation may benefit individuals with age-related macular degeneration (AMD), a leading cause of vision loss in older adults.

Gastrointestinal Disorders  [24.]

Zinc supplementation may be beneficial for individuals with certain gastrointestinal disorders, such as Crohn's disease and ulcerative colitis, as it can help reduce inflammation and support tissue repair.

Hair Loss  [17.]

Some evidence suggests that zinc supplementation may help reduce hair loss in individuals with zinc deficiency or certain hair disorders.

Diabetes Management  [5.]

Zinc plays a role in insulin metabolism, and supplementation may help improve glycemic control in individuals with diabetes.

Neurological Disorders  [8.]

Preliminary research suggests that zinc supplementation may have potential benefits for certain neurological disorders, such as Alzheimer's disease and depression, although further studies are needed to confirm these effects.

Athletic Performance  [14.]

Zinc plays a role in muscle function and recovery, and supplementation may benefit athletes by supporting muscle repair, immune function energy and recovery during intense training periods.  

Skin Health  [6.]

Zinc supplementation may help improve various skin conditions, including eczema, psoriasis, and wound healing, by reducing inflammation and supporting skin barrier function.

Laboratory Testing for Zinc Levels

Methods of Zinc Testing [7.]

Laboratory assessment of zinc status commonly involves measuring plasma or serum zinc concentration, erythrocyte (red blood cell) zinc concentration, zinc concentration in hair, or zinc levels in urine. 

Plasma zinc concentration is preferred due to minimal contamination from erythrocytes, and while it generally reflects zinc status accurately, its sensitivity as a standalone indicator remains debated. 

Erythrocyte zinc concentration decreases with moderate zinc restriction, but its reliability as an indicator is limited, partly due to sample preparation variations. 

Hair zinc concentration has shown associations with growth, with low levels prompting zinc supplementation in some cases, particularly in children with low meat consumption. However, defining clear cut-off values for hair zinc concentration remains challenging, necessitating further research to establish its utility as an indicator for zinc requirements.

Zinc urinary levels may be used, as they reflect recent intake.  [10.]

Testing Procedures

Sample collection for zinc testing typically involves venipuncture to obtain blood samples, which are then processed to separate plasma or serum for analysis. 

Blood spot testing is another method where a small drop of blood is collected from a finger prick onto filter paper. 

Additionally, hair samples can be collected for zinc analysis, typically by cutting a small sample of hair close to the scalp. 

Sample collection for urine zinc testing typically involves collecting a random or timed urine sample, which is then analyzed to assess zinc levels in the body.

Interpreting Zinc Test Results

Normal range values can vary based on the laboratory and the method used. It's important to consider these results in the context of clinical symptoms and dietary intake.

It’s important to analyze results according to the reference ranges provided by the lab used.  As an example, one lab reports the following reference ranges:

Serum or plasma zinc: 44-115 mcg/dL

Urine zinc: contact lab for reference ranges

Hair zinc: contact lab for reference ranges

Clinical Significance of Low Zinc Levels

Low zinc levels have significant clinical implications, impacting various aspects of health. 

Zinc deficiency is associated with impaired growth and development, weakened immune function, and increased susceptibility to infections. Additionally, it can lead to skin lesions, delayed wound healing, and altered taste perception. 

In children, inadequate zinc intake can result in growth retardation and cognitive deficits, while in adults, it may contribute to impaired fertility and increased risk of chronic diseases such as cardiovascular disease and diabetes. 

Furthermore, low zinc levels have been linked to mental health disorders like depression.  [22.]

Given the diverse roles of zinc in physiological processes, addressing zinc deficiency is crucial for maintaining overall health and well-being.

Clinical Significance of Elevated Zinc Levels

Elevated zinc levels can also have clinical significance, leading to zinc toxicity and adverse health effects. 

While zinc toxicity is rare, excessive intake from supplements or contaminated food sources can cause gastrointestinal symptoms such as nausea, vomiting, and diarrhea. 

Chronic zinc overconsumption may result in copper deficiency due to competitive inhibition of copper absorption in the gastrointestinal tract, leading to anemia and neurological symptoms. 

Furthermore, long-term exposure to high levels of zinc can impair immune function and disrupt lipid metabolism, potentially increasing the risk of cardiovascular disease. 

Monitoring zinc levels and adhering to recommended dietary intake guidelines are essential to prevent toxicity and maintain optimal health.

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