Zinc Functions

Zinc is an essential trace element required by almost every biological process in the human body including growth and development, immune function, wound healing, protein and DNA synthesis, and cell division. It is used in over 300 enzymatic reactions, serves as an anti-inflammatory and an antioxidant, and is important for sight, hearing, and taste.

The system-wide ubiquity of zinc increases the clinical importance of detecting and supporting a deficiency when present. Unfortunately, it is frequently underutilized in clinical practice. Gaining a deeper understanding of the many roles zinc plays in human health, learning the appropriate methods for assessing deficiency, reviewing which conditions may benefit from supplementation with zinc, along with supplementation guidelines and recommendations will increase the clinician’s confidence in the appropriate use of zinc with patients.

Zinc Select

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Causes of Zinc Deficiency

The most common reasons for a zinc deficiency are increased losses of zinc, increased requirements for zinc, inadequate dietary intake, or reduced bioavailability/absorption of zinc. Increased losses can come from gastrointestinal diseases, surgery, trauma, oral contraceptives, and zinc lost in ejaculate with excessive sex. The requirement for zinc increases during periods of rapid growth, pregnancy, and lactation. Common examples of inadequate dietary intake include teenagers and college students as well as individuals following plant-based diets. Diets high in fiber are also rich in phytates which inhibit absorption.

Dietary factors, such as the consumption of alcohol or following a vegetarian/vegan diet, can impair zinc absorption. Decreased absorption increases the risk for deficiency. Plant-based diets and diets high in seeds, legumes, and unprocessed whole grains contain phytates that bind with zinc, inhibiting its absorption. Soaking, sprouting, and/or fermenting can reduce the phytic acid content of these foods, increasing the bioavailability of zinc. It has been shown that the process of sour leavening to make sourdough bread reduced the phytate content by ~ 25% and increased the rate of zinc absorption by 30-50%.

Other dietary factors that reduce the absorption rate include coffee, calcium in dairy products, increased fiber intake from fruits and vegetables, and a high fat diet (> 100g/day) in those with fat malabsorption issues. Deficiency can also be present in those with gastrointestinal issues that impair absorption such as Celiac disease, Crohn’s disease, or bypass surgery, and in those with hypochlorhydria (commonly seen with aging).

Assessment of Zinc Status
Laboratory Assessment

A zinc deficiency is not always easy to recognize. It can manifest as a variety of symptoms and routine laboratory testing does not provide a reliable indicator of zinc status. Low plasma stores of zinc (~0.1%) cause the standard blood test for plasma zinc concentrations to lack sensitivity and specificity, making it unreliable as a marker of deficiency. Therefore, an assessment of zinc status and a diagnosis of deficiency is largely based on clinical findings.

Clinical Zinc Assessment

Zinc homeostasis is primarily regulated by the amount of zinc in the diet. Clinical evaluation should include a detailed review of the patient’s dietary eating patterns to determine if a deficiency is likely. The physical examination may reveal white spots on their fingernails and/or patches of dry skin. The patient history should be reviewed for associated conditions or medications known to cause impaired zinc absorption and a therapeutic trial of zinc may be recommended in those instances.

A Zinc Taste Test provides a quick and inexpensive evaluation of zinc levels that can be conducted during the office visit. This test is not completely reliable due to the dependence on individual variances in self-reporting for the evaluation of taste. The taste test can provide a general guideline, combined with clinical observation, to help in the assessment of zinc status.

Clinical Applications/Research
Zinc and the Thyroid

Normal thyroid function is dependent on adequate levels of zinc. Zinc is necessary for the synthesis of thyrotropin releasing hormone (TRH), thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), and is used by the deiodinase enzymes in the conversion of T4 to T3. Zinc status has also been linked to Hashimoto’s disease and high thyroglobulin and/or thyroid peroxidase antibodies.

Zinc and Immune System

Adequate zinc levels are essential for proper adaptive and innate immune system functioning. Proper zinc homeostasis creates a balance between immune cell numbers and their functions as well as between tolerance and defense mechanisms. A deficiency in zinc contributes to an overproduction of pro-inflammatory cytokines such as IL-1β. TNF-α, IL-6, NFкB, and STAT3. Zinc is important for Th1 activation which drives cell mediated immunity and antiviral defense mechanisms. In a deficiency state, an increase in Th2 driven allergic responses, due to an imbalance in the Th1/Th2 ratio, has been observed.

Optimum concentrations of zinc decrease autoimmune reactions by increasing immune system tolerance with an increase in Treg cell development. Increases in tolerance result in less development of Th17 cells. An optimal zinc state also decreases autoimmune reactions by inhibiting the STAT3 signaling cascade which contributes to a decrease in the expression of Th17 cells. A systemic review and meta-analysis conducted in 2018 found a direct correlation between zinc status and Th17 driven autoimmunity. The authors reported that zinc levels were significantly lower in those with autoimmune disease/s compared to controls. These findings make it clinically important to include assessment of zinc status in patients that have autoimmune issues.

Zinc has shown a synergistic effect when used in combination with vitamins C, D, E, and A as immune system support. Zinc has also displayed efficacy in use as a treatment option against many viruses commonly seen in clinical practice including coronavirus, hepatitis C, herpes simplex virus, respiratory syncytial virus, etc. A 2021 study specifically addressed the benefits of using zinc as a treatment option for SARS-CoV-2.

Zinc and the Adrenals

Zinc has demonstrated a suppressive effect (four hours duration) on excess cortisol levels. Clinically, this may be useful in patients that have insomnia due to excessive cortisol levels. These individuals will often have trouble falling asleep and will often report that they are light sleepers. Zinc, along with adrenal adaptogens, may also help reduce the cortisol spikes common during periods of increased stress.

Zinc and Small Intestinal Bacterial Overgrowth (SIBO)

Lee et al (2019) studied a large cohort of patients with chronic pancreatitis to establish predictive markers for determining the presence of SIBO in this population. They state that clinical symptoms are not predictive of SIBO in chronic pancreatitis. Their study identified 5 variables, of the 46 studied, that were predictive of SIBO in those with chronic pancreatitis: low zinc levels, diabetes mellitus (DM), total Mayo score > 4 (0-16), low albumin levels, and opiate use. The multivariable analysis conducted indicated that zinc levels were an independent negative predictor for SIBO. The combination of DM and opiate use also demonstrated a positive predictive value of 72.5% for SIBO.

Associated Conditions and Consequences of Zinc Deficiency

These conditions have research to support the use of zinc supplementation. A therapeutic trial offering low levels of zinc can be administered in these conditions, along with copper and a good diet.

• Acne
  
• Acrodermatitis enteropathica
  
• ADHD
  
• AIDS
  
• Altered taste and smell
  
• Anemia
  
• Anorexia
  
• Aphthous ulcers
  
• Behcet’s disease
  
• Beta-thalassemia
  
• Blepharitis
  
• Body order
  
• BPH
  
• Brittle nails
  
• Burns
  
• Cancer
  
• Cholera
  
• Cirrhosis
  
• Colds
  
• Depression
  
• Dermatitis
  
• Diarrhea
  
• Down syndrome
  
• Eczema
  
• Ehlers-Danlos Syndrome
  
• Erectile dysfunction
  
• Excessive cortisol levels
  
• Furuncles
  
• Gastroenteritis
  
• Growth retardation
  
• Hearing loss
  
• Heavy metal toxicity
  
• Hepatitis
  
• Herpes simplex
  
• Hidradenitis suppurativa
  
• Hypogonadism
  
• Hypothyroidism
  
• Impaired concentration
  
• Impaired ovarian and testicular function (low testosterone)
  
• Impaired wound healing
  
• Increased infections
  
• Infertility
  
• Insect repellent exposure
  
• Insulin resistance
  
• Intention tremors
  
• Jitteriness
  
• Leprosy
  
• Low sperm count
  
• Macular degeneration
  
• Malaria
  
• Nephrotic syndrome
  
• Night blindness
  
• Olfactory dysfunction
  
• Peptic ulcer
  
• Photophobia
  
• Pica
  
• Prostatitis
  
• Psoriatic arthritis
  
• Rash
  
• Rheumatoid arthritis
  
• Sepsis & systemic inflammation
  
• Sickle cell disease
  
• Taste disorders
  
• Teratogenesis
  
• Thinning hair/hair loss
  
• Tinnitus
  
• Thymus gland atrophy
  
• Tuberculosis
  
• Uremic pruritus
  
• Vaginitis due to trichomoniasis
  
• Warts
  
• White spots on fingernails
  
• Wilson’s disease
  
• Xerostomia
  

Physical Evaluation of Zinc Status

Nail abnormalities:

• White spots on fingernails (may also indicate protein deficiency)
  
• Muehrcke’s lines (transverse white lines across the nail bed)
  
• Leukonychia (white discoloration of the nail plate)
  
• Beau lines (horizontal grooves on the nail plate)
  
• Onychorrhexis (superficial white distribution located on nail surface)
  

-Patches of dry skin (early indicators)
-Evidence of malabsorption
-Inflammatory processes
-Medications
-Improvements with zinc supplementations
-Crohn’s Disease

Dietary Evaluation of Zinc Status

Top Food Sources:

• Egg yolk
  
• Dairy
  
• Legumes
  
• Liver
  
• Meat—especially red meat
  
• Nuts
  
• Seafood—oysters
  
• Seeds
  
• Wheat bran
  
• Wheat germ
  
• Whole grains
  

-Increase zinc:phytate ratio to improve zinc status
-12 mg/day from diet is sufficient. 18 mg/day for plant-based diets

Zinc Taste Test

Testing agent—Moss Nutrition ZincEval Select—(answer 1, 2, or 3)

1. Immediate, very noticeably bitter, unpleasant, or metallic taste
-Indicates optimal levels of zinc are present. Suggests no need for zinc supplementation.
2. Slight bitter or metallic taste
-Indicates suboptimal zinc levels. Suggests need for zinc supplementation.
3. Absence of taste, sweet or “water-like” taste
-Indicates low zinc levels. Suggests definite need for zinc supplementation.

Zinc Lab Testing

• Non-fasting blood labs will show a postprandial decrease of zinc levels.
  
• Presence of a normal zinc level does not rule out a deficiency.
  
• Presence of a low zinc level does not rule out deficiency
  
• Low albumin may be an indicator of zinc deficiency. Plasma zinc is almost entirely protein bound. Changes in serum protein levels will influence zinc levels.
  
• Low alkaline phosphatase is not a reliable indicator of zinc deficiency.
  
• Elevated zinc protoporphyrin test can help confirm a deficiency. Test can be ordered from LabCorp.
  
• A high C-reactive protein is often indicative of increased inflammatory cytokine IL-6.
  

Treatment and Dosage Recommendations
Zinc Insufficiency

Moss Nutrition Zinc Select:

• 30 mg, 1-3 times/day with meals for 2-3 months in true deficiency.
  
• 10-20 mg/day prevents deficiency if diet is low in zinc.
  
• Empty stomach dosing is ideal, but many people experience nausea.
  
• Contains zinc bis-glycinate chelate and zinc arginate chelate, copper, ginger, artichoke, and betaine HCL.
  

Pancreatic Insufficiency

It is also important to use pancreatic enzyme support along with zinc supplementation when a zinc deficiency is present.

Moss Nutrition Pancreatin Select:

• Take 1-3 per meal
  
• Contains pancreatic digestive enzymes, betaine HCL, ox bile, artichoke, and gentian root.
  

Moss Nutrition Digest Select:

• Take 1-3 per meal
  
• Plant-based digestive enzyme complex
  

Forms of Zinc Supplements

• Zinc oxide has low bioavailability
  
• Zinc bis-glycinate chelate, arginate chelate, acetate, gluconate, methionine, aspartate, and picolinate are all excellent sources.
  
• Zinc gluconate and acetate are preferred in lozenges due to the best release of zinc ions in the oral cavity.
  

Signs and Symptoms of Zinc Toxicity

• Impaired immune system function
  
• Nausea
  
• Vomiting
  
• Abdominal cramps
  
• Loss of appetite
  
• Diarrhea
  
• Headache
  
• Lowers HDL levels
  
• Metallic taste in the mouth
  

Drug Interactions

• Proton pump inhibitors = zinc deficiency
  
• ACE inhibitors increase zinc excretion
  
• Zinc inhibits the absorption of Tetracycline and Fluoroquinolone antibiotics
  
• Glucocorticoids = zinc deficiency
  
• Aspirin increases excretion and lowers plasma levels
  
• Oral contraceptives deplete zinc
  
• Diuretics increase zinc excretion
  
• Penicillamine increases urinary excretion of zinc
  

Nutrient Interactions

Zinc and Copper

• There is a delicate physiologic balance between zinc and copper. Taking 18.5mg of zinc a day can increase fecal copper excretion and reduce copper retention which may result in a copper deficiency. For this reason, supplementation with small amounts of copper is recommended concurrently with zinc supplementation.
  1-2 mg/day of copper for 15-30 mg/day of zinc
  2-3 mg/day of copper for 30-60 mg/day of zinc
  3-4 mg/day of copper for >60 mg/day of zinc
  
• Copper and zinc can be taken together.
  

  Zinc and Magnesium

  
  
• High doses of zinc (~150 mg/day) reduce magnesium absorption and magnesium balance.
  

  Zinc and Calcium

  
  
• Calcium impairs zinc absorption and zinc impairs calcium absorption but only when dietary calcium intake is low.
  

  Zinc and Iron

  
  
• Iron impairs zinc and vice versa. Zinc is beneficial in iron overload, however. Use less than 2:1 iron to zinc ratio daily or limit total dose to 25 mg or less for individual doses throughout the day.
  

  Zinc and Folate

  
  
• Zinc and folate dissociate in the duodenum at a pH of 6.0 so pancreatic insufficiency resulting in a lower pH may prevent dissociation.
  
• Patients with pancreatic insufficiency may need to avoid zinc and folate supplementation which can inhibit food-derived sources of these nutrients.
  

Zinc and Vitamin A

• Zinc is important for vitamin A transport. Zinc deficiency decreases circulating and liver stores of vitamin A.
  
• Zinc supplementation improves vitamin A status compared to vitamin A supplementation alone.
  

Miscellaneous

• Zinc participates in the conversion of linoleic acid to gamma linoleic acid thus Evening Primrose oil can be helpful in zinc deficiency.
  
• Zinc deficiency amplifies signs of EFA deficiency.
  
• B6 may increase requirement of zinc.
  
• N-Acetylcysteine (NAC) increases urinary excretion of zinc by forming a complex, but NAC increases the intestinal absorption of zinc. Watch patients closely if taking high doses of NAC for long periods.
  
• 500 mg/day of vitamin C improves zinc balance.
  
• Vitamin E may minimize the negative effects of zinc deficiency.
  

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References

1. Sharma P, Reddy PK, Kumar B. Trace Element Zinc, a Nature’s Gift to Fight Unprecedented Global Pandemic COVID-19. Biol Trace Elem Res. 2021;199(9):3213-3221. doi:10.1007/s12011-020-02462-8
   
2. Livingstone C. Zinc: physiology, deficiency, and parenteral nutrition. Nutr Clin Pract. 2015;30(3):371-382. doi:10.1177/0884533615570376
   
3. Nriagu J. Zinc Deficiency in Human Health. In: Nriagu JO, ed. Encyclopedia of Environmental Health. Elsevier; 2011:789-800. doi:10.1016/B978-0-444-52272-6.00674-7
   
4. Zinc Availability in Leavened and Unleavened Bread. Nutrition Reviews. 1975;33(1):18-19. doi:10.1111/j.1753-4887.1975.tb07080.x
   
5. Pécoud A, Donzel P, Schelling JL. Effect of foodstuffs on the absorption of zinc sulfate. Clin Pharmacol Ther. 1975;17(4):469-474. doi:10.1002/cpt1975174469
   
6. Hessov I, Andersson H, Isaksson B. Effects of a low-fat diet on mineral absorption in small-bowel disease. Scand J Gastroenterol. 1983;18(4):551-554. doi:10.3109/00365528309181636
   
7. Severo JS, Morais JBS, de Freitas TEC, et al. The Role of Zinc in Thyroid Hormones Metabolism. Int J Vitam Nutr Res. 2019;89(1-2):80-88. doi:10.1024/0300-9831/a000262
   
8. Ertek S, Cicero AF, Caglar O, Erdogan G. Relationship between serum zinc levels, thyroid hormones and thyroid volume following successful iodine supplementation. Hormones (Athens). 2010;9(3):263-268. doi:10.14310/horm.2002.1276
   
9. Murni IK, Prawirohartono EP, Triasih R. Potential Role of Vitamins and Zinc on Acute Respiratory Infections Including Covid-19. Glob Pediatr Health. 2021;8:2333794X211021739. doi:10.1177/2333794X211021739
   
10. Wessels I, Maywald M, Rink L. Zinc as a Gatekeeper of Immune Function. Nutrients. 2017;9(12):E1286. doi:10.3390/nu9121286
    
11. Prasad AS. Effects of Zinc Deficiency on Th1 and Th2 Cytokine Shifts. The Journal of Infectious Diseases. 2000;182(Supplement_1):S62-S68. doi:10.1086/315916
    
12. Kitabayashi C, Fukada T, Kanamoto M, et al. Zinc suppresses Th17 development via inhibition of STAT3 activation. Int Immunol. 2010;22(5):375-386. doi:10.1093/intimm/dxq017
    
13. Sanna A, Firinu D, Zavattari P, Valera P. Zinc Status and Autoimmunity: A Systematic Review and Meta-Analysis. Nutrients. 2018;10(1):E68. doi:10.3390/nu10010068
    
14. Read SA, Obeid S, Ahlenstiel C, Ahlenstiel G. The Role of Zinc in Antiviral Immunity. Adv Nutr. 2019;10(4):696-710. doi:10.1093/advances/nmz013
    
15. Asl SH, Nikfarjam S, Majidi Zolbanin N, Nassiri R, Jafari R. Immunopharmacological perspective on zinc in SARS-CoV-2 infection. Int Immunopharmacol. 2021;96:107630. doi:10.1016/j.intimp.2021.107630
    
16. Brandão-Neto J, de Mendonça BB, Shuhama T, Marchini JS, Pimenta WP, Tornero MT. Zinc acutely and temporarily inhibits adrenal cortisol secretion in humans. A preliminary report. Biol Trace Elem Res. 1990;24(1):83-89. doi:10.1007/BF02789143
    
17. Lee AA, Baker JR, Wamsteker EJ, Saad R, DiMagno MJ. Small Intestinal Bacterial Overgrowth Is Common in Chronic Pancreatitis and Associates With Diabetes, Chronic Pancreatitis Severity, Low Zinc Levels, and Opiate Use. Am J Gastroenterol. 2019;114(7):1163-1171. doi:10.14309/ajg.0000000000000200