Zinc Imbalance Signs & Symptoms

Updated: Jan 16


An Introduction to Zinc and its Role in the Human Body


Zinc is ubiquitous in its involvement in the human body, and a zinc depletion can have varied signs and symptoms affecting many different body systems (Gropper & Smith, 2013). Understanding zinc’s various roles within the body can aid the clinician in ruling in and ruling out a zinc imbalance. As such, one symptom of zinc deficiency should occur with another symptom of a different body symptom such as seen with concurrent eczematous dermatitis AND night blindness (Yansdown et al., 2007).





Zinc is absorbed within the proximal small intestine (duodenum and jejunum), and absorption takes place via two mechanisms; the carrier-mediated transport system to cross the brush border and paracellular diffusion when zinc intake is more than 20mg/day (Gropper & Smith, 2013). The main function of zinc within the body is as a structural component of many enzymes as well as a functional role at catalyst sites of enzymes (Gropper & Smith, 2013).


There are 300 different types of enzymes in the human body that contain zinc, so the nutrient status of zinc effects many different body systems (Gropper & Smith, 2013). Some of the many roles of zinc are as follows. Metalloenzymes & zinc-dependent processes include carboxypeptidases A & B which is used in protein digestion and as part of pancreas secretions (Gropper & Smith, 2013). Carbonic acid requires zinc within renal tubules and aids the acid-base balance/buffering (Gropper & Smith, 2013). Additionally, zinc has a relationship with vitamin A and helps convert vitamin A to retinol and retinal which promotes the vision cycle and night vision (Gropper & Smith, 2013). Delta-aminolevulinic acid dehydrogenase requires zinc for heme synthesis and boosts optimal health of red blood cells (Gropper & Smith, 2013). Zinc also plays a role in phospholipid metabolism which helps phospholipase C in hydrolyzing a bond in phospholipids (Gropper & Smith, 2013). In this way, zinc impacts every cell membrane in the human body! Zinc helps glutamate-bound folate to breakdown in the intestinal tract so it can be absorbed (Gropper & Smith, 2013). And zinc also is carcinopreventive as it aids in nucleic acid synthesis and cell replication and growth (Gropper & Smith, 2013). Zinc has an important role in wound repair, wound debridement, and the epithelization of new skin promoting optimal skin health and wound healing (Gropper & Smith, 2013).



Zinc Deficiency - an explanation of pathology

With the many roles of zinc within the body, signs and symptoms of a zinc deficiency can affect nearly every body system. Zinc deficiency can cause an increase in proinflammatory cytokine production and oxidative stress which can increase likelihood of or exacerbate existing chronic diseases (Mohommad et al., 2012). It can also depress the immune system increasing susceptibility to infections and delay wound healing (Yanagisawa, 2007). Chronic zinc deficiency is carcinogenic by impairing protein synthesis (Prasad et al., 1983; Ames, 2006). In children with chronic zinc deficiency, growth retardation (caused by inadequate cell division), skeletal abnormalities (impaired development of epiphyseal cartilage or defective collagen synthesis or cross-linking), poor wound healing, diarrhea, skin rash/lesions/dermatitis (especially around body orifices), and delayed sexual maturation have all been noted to occur (Gropper & Smith, 2013). In adults with zinc deficiency, anorexia, diarrhea, lethargy, depression, skin rash/lesions/dermatitis, hypogeusia (blunting of sense of taste), alopecia, impaired immune function, and impaired wound healing have been noted to occur (Gropper & Smith, 2013).


Signs and symptoms of zinc deficiency can be evaluated during a nutrition assessment. For biochemical measurements, impaired glucose tolerance resulting in hyperglycemia as well as anemia may occur (Lansdown et al., 2007). Moderate zinc deficiency can manifest as a decreased sense of taste and smell (Mohommad et al., 2012; Yanagisawa, 2007). Concurring, atrophy of the tongue's lingual papillae and mouth ulcers may also be seen in acute, severe zinc deficiency (Adams & Murray, 1987; Lansdown et al., 2007). Chronic zinc deficiency can affect eye health and vision and most notably contributes to night blindness (Yanagisawa, 2007; Prasad et al., 1983; Myung et al., 1998). Neurological symptoms associated with zinc deficiency are altered mental status, depression, and ataxia in severe zinc deficiency (Lansdown et al., 2007). Of the skin and nails, moderate zinc deficiency can cause eczematous dermatitis and white-spotting leukonychia, and severe zinc deficiency can cause necrolytic acral erythema and acrodermatitis enteropathica (Kight, 1987; Myung et al., 1998; Lansdown et al., 2007).


Stages of Nutritional Injury in Zinc Deficiency

Deficiency can happen quickly within five days but can also be repleted within the same timeframe (King, 2011). For severe, acute signs and symptoms to manifest can take between 20-40 days (King, 2011). Mild zinc deficiency can have ambiguous and variable signs and symptoms that may be difficult to differentiate from other etiologies (King, 2011). Signs and symptoms of moderate zinc deficiency, stages four and five of the nutriodynamic model, manifest in children and adults differently. For children, zinc plays a major role in growth (Gropper & Smith, 2013). A zinc deficiency will stunt a child’s growth as well as delay puberty or, if the deficiency is severe, prevents the onset of puberty altogether (Gropper & Smith, 2013). Effecting both children and adults is poor wound healing, diarrhea, alopecia, impaired immune function, and impaired protein synthesis (Gropper & Smith, 2013). Other signs and symptoms seen in stages four and five are hypogeusia (loss of taste), hyposmia (loss of smell), alopecia (thin, sparse hair), white-spotting leukonychia, susceptibility to infections, altered mental status, and night blindness (Gropper & Smith, 2013; Prasad et al., 1983; McCall et al., 2000). Long-term TPN without zinc and in liver disease case studies have been useful for studying the clinical manifestations of zinc deficiency. Specifically, acrodermatitis enteropathica, tense bullous lesions at the finger knuckles, and necrolytic acral erythema (Myung, 1998; Litchford, 2015; Tabibian, et al, 2010). Signs and symptoms of zinc deficiency, stages five and six are the later stages and are seen with severe and chronic Zn deficiency mostly seen in third world countries. Since zinc has a significant role in growth, children will experience growth retardation and puberty will be delayed for as long as the zinc deficiency exists. In a case study of a 24 yr old with long-standing zinc deficiency, puberty onset had been delayed. Presenting in the same case study participant were also signs of dermatitis and hyperpigmentation of the face (Prasad et al., 1983).


Zinc in Excess

The main concern with of excessive zinc intake with an upper limit of 40mg/day is due to the increasing risk of copper deficiency (Gropper & Smith, 2013). Metallothionein is the main storage and transporter protein for zinc, as it is also for copper (Gropper & Smith, 2013). Therefore, if zinc is supplemented at too high a dose and for too long (chronic intake), then copper deficiency can manifest (Gropper & Smith, 2013). Manifestations of a copper deficiency begin as numbness and weakness and progresses to a spastic gait and ataxia with increasing severity of the deficiency (Gropper & Smith, 2013). Aside from secondary deficiencies caused by zinc supplementation, zinc toxicity may result in clinical signs and symptoms when zinc is supplemented at 100-300 mg/day (Jensen & Brinkley, 2002). Symptoms of a zinc toxicity begin with headache, nausea, vomiting, abdominal discomfort, and a metallic taste (Gropper & Smith, 2013). Signs include bloody diarrhea and alterations in copper and iron biochemical measures including anemia (Litchford, 2015). And acute zinc toxicity causes nausea and dizziness (Jensen & Brinkley, 2002).


Agent, Host, and Environmental Factors of Zinc Deficiency and Toxicity

Zinc deficiency tends to exist under certain circumstances. Agent factors include zinc supplements which can promote adequate intake but can also contribute to toxicity of zinc or deficiency of other relevant nutrients such as iron and especially copper. Alimentation of ligands can bind to zinc and increase its solubility (Gropper & Smith, 2013). Inhibitors of zinc are molecules that bind zinc preventing its absorption such as high dietary intake of phytic acid, oxalates, and calcium supplements. Geophagia and vegetarian diets are also at risk for zinc deficiency. Geophagia appears to be the biggest causal factor for zinc deficiency but is limited to unindustrialized countries where clay intake is a cultural norm (Pasad et al., 1983).


Medications appear to be one of the biggest causal factors for zinc deficiency in the Western world. Thiazide diuretics decreases zinc stores, hydralazines and nitrates such as Apresoline, Nitrobid, Imdur, and Isordil which are known to decrease blood levels of zinc and increase urine output of zinc (Jensen & Binkley, 2002; Pronsky, Elbe, & Ayoob, 2015). Lisinopril depletes zinc but to what extent - the evidence is lacking (Pronsky et al., 2015). Combine these drugs with a diet of minimal meat intake increases risk for zinc deficiency. The acidic environment of the stomach can help zinc digestion and host factors include compromised gastric acid production related to gastric bypass or proton pump inhibitors. The environment can also increase zinc deficiency risk such as in the neglected and undernourished individual (Prasad et al., 1983). Deficiency is also influenced by hotter climates that cause excessive sweating and lead to zinc loss in the sweat (Prasad et al., 1983). Third world countries including Turkey, Iran, and Egypt have higher rates of geophagia, a social norm, which increases zinc deficiency with the consumption of clay. The clay binds to zinc, inhibiting its absorption, and with this has the potential of causing severe and chronic zinc deficiency (Prasad, 1983). Populations reliant on cereal proteins (i.e. phytic acids) and inadequate zinc intake (i.e. meat) are at higher risk of deficiency (Prasad, 1983). Lastly, the growing child and the pregnant have a higher need for zinc and are therefore at higher risk of deficiency (Prasad, 1983).



Summary & Conclusion


Implications for Medical and Nutritional Practice

Zinc nutrient status can be thought of within the Triage Theory whereas the body favors short term survival at the expense of long term survival (Ames, 2006). In this way, a mild zinc deficiency may be difficult to detect as the body will use the zinc stores that are available but long term consequences of mild deficiency may be carcinogenic (Ames, 2006). Signs and symptoms of deficiency vary widely as zinc status impacts multiple organ systems, thus, looking for concurrent signs and symptoms of different body systems is important when ruling in a zinc deficiency diagnosis.


The most immediate concern of zinc excess is its ability to induce copper deficiency which is why the upper limit of zinc is set at 40mg/d (Gropper & Smith, 2013). Zinc toxicity, though, is induced at 100-300 mg/d supplementation (Jensen & Brinkley, 2002) and is associated with signs and symptoms. A dose of 30g/day is considered safe and will not induce copper deficiency (Gropper & Smith, 2013). In developed countries, zinc deficiency is at increased risk in certain population groups such as in the elderly, growing children, pregnancy, and those taking zinc-depleting or zinc-interfering medications.



References


Adams, R. & Murray, F. (1978). Improving Your Health with Zinc. New York: Larchmont Books.


Ames, B. (2006). Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage. PNAS. 103 (47) 17589-17594. https://doi.org/10.1073/pnas.0608757103


Baer, M., King, J., Tamura, T., & Margen, S. (1978). Acne in zinc deficiency. Arch Dermatol, 144, 1093


Dorland's pocket medical dictionary. (2013). (29th ed., p. 579). Philadelphia, Pa.


Gropper, S. & Smith, J. (2013). Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth.


Jelliffe, D. (1966). The assessment of the nutritional status of the community. WHO Monographs Series, No 53, Part 2, 53, part 2, 24–96.


Jensen, G. & Binkley, J. (2002). Clinical manifestations of nutrient deficiency. JPEN. 26(5). Pp. 29


Kalantar-Zadeh, K. & Kopple, J. (2003). Trace elements and vitamins in maintenance dialysis patients. Advances in Renal Replacement Therapy. 10(3):170-182. doi:10.1053/j.arrt.2003.09.002.


Kight, M. (1987). The Nutrition Physical Examination. CRN Quarterly, 11(3), 9–12.

King, J. C. (2011). Zinc: an essential but elusive nutrient. American Journal of Clinical Nutrition. (94) 679-684. Doi: 10.3945/ajcn.110.005744.2


Lansdown, Mirastschijski, Stubbs, Scanlon, & Agren. (2007). Zinc in wound healing: Theoretical, experimental, and clinical aspects. Wound Repair and Regeneration. 15:2-16. doi:10.1111/j.1524-475X.2006.00179.x.


Litchford, M. (2015). Nutrition Focused Physical Assessment: Making Clinical Connections. Greensboro, NC: Case Software & Books.


Litchford, M. (2017). Laboratory assessment of nutritional status. Greensboro, NC: Case software & books.


Mohommad, Zhou, Cave, Barve, & McClain. (2012). Zinc and liver disease. Nutrition in Clinical Practice. 27(1).


McCall, K., Huang, C., & Fierke, C. (2000). Function and mechanism of zinc metalloenzymes. J Nutr. 130(5S Suppl):1437S- 1446S.


Myung, S., Yang, S., & Jung, H. (1998). Zinc deficiency manifested by dermatitis and visual dysfunction in a patient with Crohns disease. Journal of Gastroenterology. 33(6):876-879. doi:10.1007/s005350050192.


Prasad, A., Cavdar, H., Brewer, G., & Aggett, P. (1983). Zinc Deficiency in Human Subjects: Proceedings of an International Symposium Held in Ankara, Turkey, April 29-30, 1982. New York: A.R. Liss


Pronsky, Elbe, & Ayoob. (2015). Food Medication Interactions (18th ed.). Birchrunville, PA: Food-Medication Interactions.


Rousseau, A., Losser, M., Ichai, C., & Berger, M. (2013). ESPEN endorsed recommendations: Nutritional therapy in major burns. Clinical Nutrition. 32(4):497-502. doi:10.1016/j.clnu.2013.02.012.


Sandstead, H., Carter, J., & Darby, W. (1969). How to diagnose nutritional disorders in daily practice. Nutrition Today, Summer, 20–27.


Sauberlich, H. (1999). Laboratory tests for the assessment of nutritional status. 2nd ed. Boca Raton: CRC Press.


Sturniolo, Molokhia, Shields, & Turnberg. (1980). Zinc absorption in crohn’s disease. Gut. 21:387-391


Tabibian, J., Gerstenblith, M., Tedford, R., Junkins-Hopkins, J., & Abuav, R. (2010). Necrolytic acral erythema as a cutaneous marker of hepatitis C: Report of two cases and review. Digestive Diseases and Sciences. 55(10):2735-2743. doi:10.1007/s10620-010-1273-7.


Tasman-Jones. (1998). Zinc deficiency states. Year Book Medical Publishers.


Truong-Tran, A., Ho, L., Chai, F., & Zalewski, P. (2000). Cellular zinc fluxes and the regulation of apoptosis/gene-directed cell

death. J Nutr. 130(5S Suppl):1459S-1466S.


Yanagisawa, H. (2007). Zinc Deficiency and Clinical Practice - Validity of Zinc Preparations. The Pharmaceutical Society of Japan. 128(3):333-339.

Zinc. (2018). Linus Pauling Institute. http://lpi.oregonstate.edu/mic/minerals/zinc. Published January 1, 2018. Accessed April 29, 2018.

0 comments

Recent Posts

See All

The signs and symptoms of gluten ataxia are [. . .] Gluten Ataxia is diagnosed [. . .]