Zinc deficiency is more common than you might think! Zinc deficiencies are characterized by delayed growth, loss of appetite, and many other potentially serious symptoms. Read on to learn all about zinc side effects, dosage, and more.
Sources of Zinc
In the United States, pulses and cereals provide about 30%, meat about 50%, and dairy products about 20% of dietary zinc .
Although whole-grain breads, cereals, and legumes contain phytates that decrease zinc absorption, they are still good sources of zinc .
Zinc should be supplemented in:
- proven zinc deficiency and zinc-losing conditions
- acrodermatitis enteropathica and Wilson’s disease [8, 9]
- acute diarrhea in children in developing countries 
- pneumonia and perhaps malaria 
The Recommended Dietary Allowance (RDA) for zinc dosage (according to the Food and Nutrition Board (FNB) at the Institute of Medicine of the National Academies):
|0–6 months||2 mg*||2 mg*|
|7–12 months||3 mg||3 mg|
|1–3 years||3 mg||3 mg|
|4–8 years||5 mg||5 mg|
|9–13 years||8 mg||8 mg|
|14–18 years||11 mg||9 mg||12 mg||13 mg|
|19+ years||11 mg||8 mg||11 mg||12 mg|
However, optimal Zinc dosages may vary based on the individual. I recommend taking 15mg a day as a preventative. I recommend 30mg if you suspect a zinc deficiency.
The Tolerable Upper Intake Level (UL), the highest level of daily nutrient intake that is likely to pose no risk of adverse health effects for almost all individuals, for adults is 40 mg/day.
Around 10% of persons in the United States have a dietary intake of less than half the RDA of zinc while over 50% of persons in the third world countries are zinc deficient .
1.4% of deaths worldwide are associated with severe zinc deficiency in childhood .
In more severe cases, zinc deficiency causes hair loss, diarrhea, impaired taste acuity, weight loss, delayed sexual maturation, impotence, testosterone deficiency (hypogonadism) in males, and eye and skin lesions [15, 16, 17].
Causes of Zinc Deficiency
1) Inadequate Zinc Intake
Vegetarians have an increased risk of zinc deficiency because they do not eat meat (high in zinc and may enhance zinc absorption). In addition, their diet is typically rich in legumes and whole which contain phytates that bind zinc and inhibit its absorption [19, 20].
2) Inadequate Zinc Absorption
Several diseases of the digestive system could cause inadequate zinc absorption, including:
- acrodermatitis enteropathica [21, 22]
- sprue 
- cystic fibrosis [24, 25]
- inflammatory bowel diseases (Crohn’s disease) [26, 27, 28]
- short bowel syndrome 
Another cause of low iron absorption in the gut is a high intake of food substances that inhibit zinc absorption, such as:
3) Increased zinc loss
- prolonged diarrhea [14, 18]
- kidney diseases 
- liver cirrhosis [33, 34, 35]
- alcoholism [36, 37]
- prolonged bleeding (intestinal parasites and heavy menstrual bleeding) 
- chronic inflammatory diseases that increase IL-1 [39, 40]
- hemolytic anemias such as sickle cell disease and thalassemia [41, 42]
- excessive sweating and exercise [43, 44]
- type I and type II diabetics [45, 46, 47]
Zinc overload is uncommon but it can occur due to an overdose or toxic overexposure to zinc .
Consumption of food or beverages contaminated with zinc released from galvanized containers may also lead to zinc toxicity .
“Zinc shakes”, also known as “zinc chills” or “metal fume fever”, are caused by intense inhalation of fresh industrial fumes containing zinc oxide, and presented as fever, chills, cough, chest pain, and abdominal discomfort [52, 53].
It may also lead to an increase in low-density lipoprotein (LDL) cholesterol and a decline in high-density lipoprotein (HDL) cholesterol, altered heart function, and impaired pancreatic enzymes .
Long-term supplementation with doses over 100 mg/day of zinc increased the relative risk of prostate cancer almost 3 fold due to the immunosuppressive effect of zinc .
Zinc Interactions with Medications
Zinc can reduce the absorption and effectiveness of penicillamine, a drug used to treat rheumatoid arthritis and Wilson’s disease. Zinc and penicillamine should be taken at least 2 hours apart .
Both quinolones (Cipro®, Levaquin®) and tetracyclines (Achromycin®, Minocin®) decrease the absorption of zinc in the gut, and vice versa .
Taking the antibiotic at least 2 hours before or 4 – 6 hours after taking a zinc supplement minimizes this interaction.
3) Diuretics (Water Pills)
Prolonged use of thiazide diuretics (Hygroton®, Esidrix®, and HydroDIURIL®) could deplete zinc levels by increasing zinc removal in the urine by as much as 60% .
Amiloride (Midamor®) can increase the amount of zinc in the body .
4) Blood Pressure Medication
Cisplatin, used to treat some types of cancers, increases urinary zinc excretion thus decreasing blood levels of zinc in patients treated with cisplatin .
Interactions with nutrients
High doses of zinc can interfere with the absorption of iron .
Iron supplements, taken together with zinc supplements on an empty stomach, may inhibit the absorption of zinc.
Zinc supplementation can interfere with the absorption of copper, and cause a copper deficiency which has been reported in humans using up to 600 mg elemental zinc daily or excessive usage of zinc-based dental adhesives [69, 70, 71].
Alcohol decreases the absorption of zinc and increases urinary zinc excretion .
Excessive dietary calcium decreases zinc absorption .
Protein enhances zinc absorption .
6) Phytates and Fiber
7) Chlorogenic Acid
8) Vitamin A
9) Vitamin B6 and Magnesium
Zinc Side Effects
Short term effects of zinc toxicity include nausea, vomiting, diarrhea, headaches, stomach cramps, loss of appetite, and irritability .
Tests to Assess Zinc Status in Humans
The assessment of zinc status is difficult and challenging because there are no sensitive and specific biomarkers to detect zinc deficiency in humans.
Dietary and medical history and physical examination may all lead to a proper diagnosis.
Laboratory assays for measurement of zinc status:
1) Blood Zinc
Plasma/serum Zinc Concentrations
Normal values for plasma/serum zinc range from 10.7 to 23.0 µmol/L .
Blood zinc is a useful indicator of the size of the exchangeable zinc pool located in the bone, liver, and blood .
Reductions in dietary zinc beyond the capacity to maintain balance lead to utilization of zinc from this pool which leads to the rapid onset of both metabolic and clinical signs of zinc deficiency .
White Blood Cell Zinc Concentration
Zinc in the red cells may also be used for assessment of body zinc but the zinc levels do not reflect recent changes with respect to body zinc stores .
Oral Zinc Tolerance Test
Oral zinc tolerance test measures the increase in blood zinc caused by oral ingestion of 25 or 50 mg zinc acetate. The test is quite variable among subjects .
This test has also been used to assess the effects of different foods, meals, vitamin and mineral supplements, diseases and medications on zinc absorption .
Metallothionein is a protein found in most tissues, particularly in the liver, pancreas, and kidney, and binds zinc and copper .
Metallothionein can also be detected in the plasma and red blood cells, and both clearly indicate whether an individual is zinc-deficient because they reflect recent changes in dietary zinc .
Possibly, metallothionein concentrations will also prove to be a useful indicator of changes in dietary zinc .
2) Urinary Zinc
Levels of zinc in the urine usually range from 0.3 to 0.6 mg/day .
The measurement of zinc in 24-hr urine sample is helpful for diagnosing zinc deficiency in healthy individuals. Urinary excretion of zinc is decreased as a result of zinc deficiency .
Many diseases such as cirrhosis of the liver, sickle cell disease, chronic kidney disease, burns, and starvation, are characterized by excessive urinary zinc excretion, thus these conditions should be eliminated [88, 90].
3) Hair Zinc
Hair zinc levels of less than 1.07 µmol/g probably reflect a chronic suboptimal zinc status in children. The validity of hair zinc level as an indicator of chronic suboptimal zinc status in adults remains uncertain [78, 91].
Hair zinc analysis cannot be used in cases of severe zinc deficiency or malnutrition because the rate of hair growth is decreased in malnourished patients. In such cases, hair zinc concentrations may be normal or even high [92, 88].
Hair zinc concentrations vary with hair color, season, sex, age, anatomical site of sampling and rate of hair growth. These factors must be considered when interpreting hair zinc concentrations .
4) Taste Acuity
Diminished taste acuity (hypogeusia) is a symptom of zinc deficiency, and it has been used as a functional test of zinc status (93).
In a taste acuity test, solutions of varying concentrations of the four different taste qualities (salt, sweet, bitter, and sour) are used. The test is based on the detection and recognition thresholds for each taste quality .
Zinc taste tests should be performed midmorning, at least 2 h after a meal, and by the same person on each occasion .
Zinc Mechanisms of Action
- Induced IL-2 and Interferon-γ (IFN-γ) [94, 95]
- Inhibited caspase-3, caspase-6, caspase-9 and increased Bcl-2/Bax ratio [96, 97, 98, 99, 100]
- Inhibited inducible nitric oxide synthase (iNOS) and NADPH oxidase [101, 102]
- Induced metallothionein (MT) 
- Increased glutathione (GSH), glutathione peroxidase, catalase, and Zn/Cu superoxide dismutase (SOD) [101, 102, 104, 105]
- Increased MMP 2 and MMP 8 
- Decreased serum high-sensitivity C-reactive protein (hs-CRP), IL-6, macrophage chemoattractant protein 1 (MCP-1), vascular cell adhesion molecule 1 (VCAM-1), secretory phospholipase A2, malondialdehyde (MDA) and hydroxy alkenals (HAE) 
- Decreased NF-κB activation; increased PPAR-α 
- Inhibited STAT3 activation 
- Activated PI3K/Akt pathway 
- Increased inducible iTreg cells; reduced TH17 cells 
- Suppressed IFN-γ, TNF-α, GM-CSF and IL-5 production in stimulated human T cells and mouse splenocytes 
- Increased Foxp3 
- Blocked Ca2+ uptake in human basophils and lung mast cells 
- Suppressed ERK and NF-κB pathway in airway smooth muscle cells 
- Decreased bronchoalveolar lavage fluid eosinophils 
- Decreased neutrophil infiltration and TNF-α cytokine release into the airways, decreased NF-κB DNA-binding, decreased serum IgE levels 
- Decreased numbers of eosinophils, neutrophils, and monocytes in bronchoalveolar lavage fluid (BALF); suppressed eotaxin and MCP-1 protein secretion; and increased lung IFN-γ mRNA expression 
- Reduced PBMC proliferation of atopic subjects; increased IFN-γ/IL-10 ratios and enhanced tumor necrosis factor-α (TNF-α) release, increased Treg cells, increased mRNA expression of cytotoxic T-lymphocyte antigen-4 
- Blocked NMDA receptors and pre-synaptic K channels (KATP channels), suppressed glutamate release and glutamate-stimulated neuronal firing [120, 121, 122]
- Decreased ApoB/ApoA-I ratio, oxidized low-density lipoprotein (ox-LDL), leptin, malondialdehyde (MDA), LDL-cholesterol and hs-CRP 
- Inhibited GSK-3beta 
- Increased insulin-like growth factor-1 (IGF-I), Insulin-like growth factor-binding protein 3 (IGFBP-3), and growth hormone (GH) [125, 126]
- Increased alkaline phosphatase (ALP) activity 
- Increased BDNF in hippocampus and serum [128, 129]
- Inhibited dopamine transporter (DAT) 
- Enhanced serotonin uptake in the corpus callosum, cingulate cortex, and raphe nucleus
- Increased mucus secretion in the stomach 
- Enhanced GABA release 
- Increased orexin and neuropeptide Y 
- Increased hemoglobin in uremic patients 
- Inhibited manganese uptake (in Streptococcus pneumonia) 
- Increased insulin sensitivity; lowered blood glucose [137, 123]
- Decreased glycated hemoglobin (HbA1c) 
- Increased leptin 
- Increased testosterone, dihydrotestosterone (DHT), and LH [140, 141]
- Inhibited parathyroid hormone and PGE2 [142, 143, 144, 145, 146]
- Increased T3 and T4 and resting metabolic rate 
- Increased succinate dehydrogenase, glutamate dehydrogenase, cytochrome c oxidase, and ATPase activities in mitochondria 
- Inhibited 5-alpha-reductase 
- Zinc’s antioxidant effects are linked to its ability to stabilize cellular membranes, increase free radical scavengers (i.e. metallothioneins), activate other antioxidant systems (e.g., GSH, catalase, and Cu/Zn SOD), and inhibit pro-oxidant enzymes (e.g., iNOS and NADPH oxidase) [101, 102].
- Zinc’s wound healing effects are likely due to its enhancement of metallothioneins, zinc metalloenzymes (e.g., alkaline phosphatase, RNA and DNA polymerases, and MMPs), and growth factors (e.g., IGF-I), all of which help promote tissue repair, collagen synthesis, vascularization, and cell division [150, 151, 152, 153, 154].
- The anticonvulsant effects of zinc (in moderate doses) are likely linked to zinc’s reduction of glutamate (by blocking NMDA receptors), which is involved in initiating and spreading seizure activity in the brain [155, 120, 156].
- The way that zinc stimulates growth may be linked to its ability to increase circulating growth-promoting molecules (i.e., IGF-1, IGFBP-3, and GH), which are essential for growth and low in zinc-deficient individuals [157, 125, 158, 126].
Irregular Zinc Levels?
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