Zinc Deficiency

What Is Zinc?

[dropcap]Z[/dropcap]inc is an essential trace mineral that is involved in numerous aspects of cellular metabolism, being essential for activation of almost 200 enzymes that have vital roles in the body.

Q: What happens when enzymes do not get activated?

A: When enzymes do not get activated, they cannot perform their necessary functions which, in turn, damages health.

Zinc promotes healthy skin, hair, immunity, fertility, and growth.

A daily intake of zinc is required to maintain a steady state because the body has no specialized zinc storage system.¹ Functions are more fully described below.

What Is Zinc Deficiency in Celiac Disease?

• Relationship between zinc deficiency and celiac disease: Zinc deficiency is a classic symptom of celiac disease that results when the level within cells is too low to meet metabolic needs of the body for this mineral.
• Relationship between zinc deficiency and inflammation. Inflammation caused by gluten increases the demand for zinc. In the reverse, pro-inflammatory chemicals (cytokines) decrease in direct response to increasing zinc levels.
• Relationship between zinc deficiency and features: It is characterized by disturbances in energy metabolism, growth, hemoglobin, carbon dioxide transport, hormone activity, insulin storage, many enzyme activities, prostaglandin function, synthesis of collagen, immune response to infection, male fertility, protein synthesis, and vitamin A metabolism.
• Relationship between zinc deficiency and vitamin A: Disturbed zinc metabolism results in vitamin A deficiency.²
• Relationship between zinc deficiency and sexual hormones: Zinc deficiency has been implicated in elevated prolactin hormone, characterized by altered estrogen production in women and androgen production in men.³
• Relationship between zinc deficiency and children undergoing evaluation: Serum zinc concentration is decreased in untreated celiac children with enteropathy (damage to small intestine) and normalizes on gluten-free diet. A low serum zinc value in a child being investigated for possible celiac disease on clinical grounds can thus be used as a complementary marker for enteropathy indicating further investigation with small bowel biopsy. The mean serum concentration of zinc was significantly lower in 11 children with untreated celiac disease compared to 16 non-celiac children without enteropathy, 14 celiac children on a gluten-free diet without enteropathy, 12 celiac children on gluten challenge with enteropathy, and 6 celiac children on gluten challenge without enteropathy.⁴

How Prevalent Is Zinc Deficiency?

• Zinc deficiency was found to be common in study patients with untreated celiac disease.⁵
• A Dutch study in 80 newly diagnosed adult patients with celiac disease found the prevalence for zinc was 67%.⁶
• In a study of 109 children at diagnosis, zinc deficiency was found in 64.1%.⁷
• Zinc concentrations in patients diagnosed with celiac disease were significantly lower than healthy subjects (75.97±12 compared with 92.83±18).⁸

How Does The Body Get Zinc?

• Zinc is absorbed throughout the small intestine, including the ileum. A carrier absorption mechanism that binds zinc to amino acids operates at low zinc concentrations within the small intestine and a passive mechanism involving movement into and through the enterocytes (cells that form the villi) at high intake.
• Exit step out of the cell is by active transport via a protein carrier (metallothionein) into the blood.
• Protein and vitamin D increase zinc absorption.
• Copper, iron, calcium, and folic acid decrease zinc absorption.
• Both copper and cadmium compete for the same protein carrier (metallothionein), so they reduce zinc absorption.⁹

What Are The Symptoms Of Zinc Deficiency?

Zinc deficiency is marked by these symptoms:

• Apathy.
• Anemia, macrocytic (meaning overly large cells without sufficient hemoglobin).
• Brittle nails.
• Depression.
• Fatigue/Low energy.
• Frequent infections.
• Hair loss.
• Impaired taste, especially for bitter so you consume more bitter foods like coffee and tea to satisfy.
• Infertility in females (low estrogen) and males (low testosterone and sperm production).
• Loss of appetite.
• Mental lethargy.
• Nervousness.
• Nightblindness (seeing poorly in twilight or darkness).
• Poor adaption to slow wound healing.
• Skeletal abnormalities.
• Sore Tongue.
• White spots on fingernails.
• Worsened skin disorders (rough skin, acne, eczema, psoriasis).
• In children and youths: delayed growth, hypogonadism and delayed sexual maturation occur.
• In pregnancy: zinc-deficiency syndrome includes abnormally short or prolonged gestations, inefficient labor, bleeding and increased risks to fetus such as malformations, growth retardation, prematurity and perinatal death.¹⁰
• Diarrhea has been isolated in infants with celiac disease and zinc deficiency.¹¹

What Does Zinc Do In The Body?

1. Role in cell regulation;
2. Required in immune function to fight off invading bacteria and viruses;
3. Role in maintaining proper acid/base balance;
4. Role in production of DNA and RNA (genetic material in all cells);
5. Role in production of proteins;
6. Required for lipid metabolism;
7. Required for production of eicosanoids (signaling chemical);
8. Essential for male and female fertility;
9. Required in vitamin A metabolism (getting out of liver storage and transporting);
10. Supports normal development during gestation, childhood and adolescence;
11. Required for normal pregnancy and labor;
12. Component of insulin (energy metabolism);
13. Component of thymic hormones (immune function); and
14. Component of gustin for sense of smell and taste (taste acuity).

How Does Deficiency Develop In Celiac Disease and/or Gluten Sensitivity?

• Zinc deficiency in celiac disease results from malabsorption due to gluten enteropathy, and
• Insufficient proteins to carry zinc across the absorbing cells into the blood due to malabsorption and also for transport of zinc in the bloodstream.
• Albumin is the main transport protein for zinc in blood.

Does Zinc Deficiency Respond To Gluten-Free Diet?

Yes. Celiac disease-related zinc deficiency responds to zinc-containing gluten free diet. Supplementation in some patients on gluten free diet may be required.¹²

Serum zinc concentration is decreased in untreated celiac children with enteropathy and normalizes on gluten-free diet.⁴

A study investigating life-long gluten-free diet in celiac disease patients shows that inadequate intake of zinc is common (more than 10% of patients) and may relate to habitual poor food choices in addition to inherent deficiencies in the gluten free diet. “Dietary education should also address the achievement of adequate micronutrient intake.”¹³

6 Steps To Correct Zinc Deficiency:

• [dropcap]1[/dropcap]Meet, or Exceed the RDA (Recommended Dietary Allowances) for Zinc in milligrams (mg) per day:

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2 mg for infants birth-6 months; 3 mg for infants 7-12 months;

3 mg for children 1-3 years; 5 mg for children 4-8 years;

8 mg for children 9-12 years;

11 mg for teen boys 13-18 years and adult men;

9 mg for teen girls 13-18 years;

8 mg for adult women;

13 mg for pregnancy; 14 mg for breastfeeding women.¹⁴[/box]

• [dropcap]2[/dropcap]Diet – Include Food Sources Richest in Zinc:

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Plant sources:

Highest plant sources are tree nuts.

Good plant choices include:

• Soybeans.
• Pumpkin seeds.
• Dry peas.
• Dry beans.
• Brown rice.
• Sunflower seeds.¹⁵

Animal sources: Compounds found in meats enhance absorption of zinc from plant sources.

• Highest animal source of zinc is oyster.
• Canned salmon.
• Beef.
• Liver.
• Dark turkey.
• Shellfish.
• Poultry.
• Fish.¹⁵[/box]

• [dropcap]3[/dropcap] Diet – Avoid, Limit, or Eat at Different Times These Foods That Deplete or Interfere With Absorption:

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• High fiber consumption.
• Whole grains and seeds because phytate contained in the bran decreases absorption by binding zinc.
• Citrus foods (contain vitamin C).
• Milk products decrease ionization of zinc (getting a positive electrical charge) in the stomach. Calcium in milk competes with zinc for absorption in the small intestine.

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• [dropcap]4[/dropcap]Monitor Medications That Deplete or Interfere With Absorption:

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Here are common medications that deplete zinc. Ask your doctor or pharmacist about this possible adverse effect if you are taking any of the drugs listed below. Do not stop prescribed medications without supervision.

This is not a complete listing.

• Cipro® and Tetracycline® antibiotic interact with zinc so neither is absorbed.
• Corticosteroids (Prednisone, Medrol®, Aristocort®, Decadron®).
• Ulcer Medications (Pepcid®, Tagamet®, Zantac®).
• Magnesium and Aluminum Antacid preparations (Gaviscon®, Maalox®, Mylanta®).
• Anticonvulsants (Phenobarbital and Barbituates; and Dilantin®, Tegretol®, Mysoline®, Depakane/Depacon®).
• Thiazide Diuretics (Hydrochlorothiazide, Enduron®, Diuril®, Lozol®, Zaroxolyn®, Hygroton® and others.)
• Loop Diuretics (Lasix®, Bume®x, Edecrin®).
• Potassium Sparing Diuretics (Midamor®, Aldactone®, Dyrenium® and others).
• Anti-viral (Zidovudine (Retrovir®, AZT and other related drugs).
• Oral Estrogen/Hormone Replacement (Evista®, Prempro®, Premarin®, Estratab® and others).
• Antihypertensives (Catapres®, Aldomet). ACE Inhibitors (Capoten, Vasotec®, Monopril® and others).
• Female oral contraceptives (Norinyl®, Ortho-Novum®, Triphasil®, and others). Correlation analysis shows significant association between some trace elements and the duration of contraception and body mass index of the study participants.¹⁶[/box]

• [dropcap]5[/dropcap]Manage Nutritional Supplements to Obtain Zinc: 

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• A blood level concentration should be obtained to determine status before supplementing.
• Zinc is available in tablet and lozenge form alone or combined with other ingredients in dietary supplements, and is present in almost all multivitamin/mineral dietary supplements.
•  Significant differences in tolerability between inorganic zinc salts and organic zinc chelates exist with organic chelates recommended for supplementation.
• Protein increases zinc absorption from the gut.
• In general, daily doses up to 50 mg of elemental zinc appear safe. ((Kathleen Mahan and Sylvia Escott-Stump, ed. Krause’s Food, Nutrition & Diet Therapy, 10th Edition. Philadelphia, PA. USA: W.B. Saunders Company, 2000.))

Caution: Signs of too much zinc (nausea, vomiting, loss of appetite, stomach cramps, diarrhea, fever, muscle pain, and headaches) may occur after intake of 1,000-2,000 mg of zinc. Chronic intakes of 150 mg of zinc for several months may impair certain immune responses, decrease high-density lipoprotein levels (good cholesterol) or impair copper status (possibly leading to anemia). [/box]

• [dropcap]6[/dropcap]Other Supplements That Deplete or Interfere With Absorption:

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• Calcium supplements used for osteoporosis compete with zinc for absorption.
• Copper, iron, vitamin C, and folic acid compete with zinc for absorption.
• Phosphorus interferes with the balance of zinc in the body.
• High dose zinc impairs absorption of iron in the form of ferrous sulfate supplement but not ferrous fumarate.[/box]

What Do Medical Research Studies Tell About Zinc Deficiency in Celiac Disease?

RESEARCH STUDY SUMMARIES

“Vitamin and mineral deficiencies are highly prevalent in newly diagnosed celiac disease patients.” This study aiming to assess the nutritional and vitamin/mineral status of current “early diagnosed” untreated adult celiac disease (CD)-patients in the Netherlands found that vitamin/mineral deficiencies are still common in these patients. Specifically, zinc deficiency was found in 67% of the CD-patients.

Eighty newly diagnosed adult CD-patients were included and a comparable sample of 24 healthy Dutch subjects was added to compare vitamin concentrations. Nutritional status and serum concentrations of folic acid, vitamin A, vitamin B6, vitamin B12, and (25-hydroxy) vitamin D, zinc, haemoglobin (Hb) and ferritin were determined before prescribing gluten free diet. Almost all CD-patients (87%) had at least one value below the lower limit of reference.

Vitamin/mineral deficiencies were counter-intuitively not associated with a (higher) grade of histological intestinal damage or (impaired) nutritional status. Extensive nutritional assessments seem warranted to guide nutritional advices and follow-up in CD treatment.⁶

“Nutritional inadequacies of the gluten-free diet in both recently-diagnosed and long-term patients with celiac disease.” This study investigating life-long gluten-free diet (GFD) in celiac disease patients aimed to determine the nutritional adequacy of the ‘no detectable gluten’ diet. Results show that inadequate intake of zinc is common (more than 10%) and may relate to habitual poor food choices in addition to inherent deficiencies in the GFD. “Dietary education should also address the achievement of adequate micronutrient intake.”

A seven-day prospective food intake was assessed in 55 patients who were adherent to a GFD for more than 2 years and in 50 newly-diagnosed age- and sex-matched patients (18-71 years, 24% male) studied prospectively over 12 months on GFD. Historical pre-celiac intake was also assessed in the latter group. Intake was compared with Australian Nutritional Recommendations and the Australian population data.

RESULTS: Nutritional intake was similar between groups. Of macronutrients, only starch intake fell over 12 months (26% to 23%). Fibre intake was inadequate for all except in diet-experienced men. More than one in 10 of both newly-diagnosed and experienced women had inadequate thiamin, folate, vitamin A, magnesium, calcium and iron intakes. More than one in 10 newly-diagnosed men had inadequate thiamin, folate, magnesium, calcium and zinc intakes. Inadequate intake did not relate to nutrient density of the GFD. Inadequacies of folate, calcium, iron and zinc occurred more frequently than in the Australian population. The frequency of inadequacies was similar pre- and post-diagnosis, except for thiamin and vitamin A, where inadequacies were more common after GFD implementation.  Because dietary intake patterns at 12 months on a GFD are similar to longer-term intake, researchers stress that fortification of GF foods also need to be considered.”¹³

“The concentration of serum zinc in celiac patients compared to healthy subjects in Tehran.” This study investigating serum levels of zinc in patient with celiac disease compared to healthy subjects demonstrated that serum zinc concentration is decreased in celiac patients compare to healthy controls.

Sera of 30 celiac cases and 30 healthy normal cohorts as control group were obtained. Atomic absorption spectrophotometer was employed for estimating serum zinc level. Zinc concentrations in patients diagnosed with celiac disease were significantly lower than healthy subjects (75.97±12 compared with 92.83±18, P-value < 0.0001).⁸

“Celiac Disease: Presentation of 109 Children.” This retrospective study investigating clinical and laboratory features of 109 patients with celiac disease to determine presentation and manifestations found zinc deficiency in 64.1%.

Of 109 patients with celiac disease, 66 (60.6%) were classical type, 41 (37.6%) were atypical type and 2 (1.8%) were silent type. The mean age was 8.81 ± 4.63 years and the most common symptom was diarrhea (53.2%) followed by failure to thrive, short stature, and abdominal pain. Paleness (40.4%), underweight (34.8%), and short stature (31.2%) were the most common findings.

Iron deficiency anemia (81.6%), prolonged prothrombin time (35.8%), and elevated transaminase levels (24.7%) were the most common laboratory findings. Eight percent of patients had at least 1 autoantibody, and 28 of 52 patients had low BMD. Abdominal distention, iron deficiency, prolonged prothrombin time, hypoalbuminemia, and elevated transaminase levels were more significantly frequent in the classical type than atypical type.⁷

“Serum zinc in small children with celiac disease.” This study investigated the relationship between the serum concentration of zinc to the morphology of the small bowel mucosa in 58 children, all under 4 years of age and under investigation for celiac disease.  It showed that serum zinc concentration is decreased in untreated celiac children with enteropathy and normalizes on gluten-free diet. A low serum zinc value in a child being investigated for possible celiac disease on clinical grounds can thus be used as a complementary marker for enteropathy indicating further investigation with small bowel biopsy.

The mean serum concentration of zinc was significantly lower in 11 children with untreated celiac disease (9.7 +/- 2.0) compared to 16 non-celiac children without enteropathy (15.1 +/- 2.3 years), 14 celiac children on a gluten-free diet without enteropathy (14.2 +/- 1.6 years) 12 celiac children on gluten challenge with enteropathy (14.1 +/- 2.1) and 6 celiac children on gluten challenge without enteropathy (13.8 +/- 1.9).⁴

“Zinc nutrition in celiac disease.” This early study investigating zinc nutritional status in adults with biopsy-proved celiac-disease demonstrated depression of plasma zinc and lowered taste discrimination among the untreated patients. Some patients who were in clinical remission also had impaired zinc nutrition.¹⁷

Sources:

1. http://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/ [↩]
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3. Sher KS, Jayanthi V, Probert CS, Stewart CR, Mayberry JF. Infertility, obstetric and gynecological problems in celiac disease. Digestive Diseases. May-June 1994; 12(3):186-90. [↩]
4. Högberg L1, Danielsson L, Jarleman S, Sundqvist T, Stenhammar L. Serum zinc in small children with coeliac disease. Acta Paediatr. 2009 Feb;98(2):343-5. doi: 10.1111/j.1651-2227.2008.01085.x. [↩] [↩] [↩]
5. Scholmerich J, Wietholtz H, Buchsel R, Kottgen E, Lohle E, Gerok W. Zinc and vitamin A deficiency in gastrointestinal diseases. Leber, Magen, Darm. Nov 1984; 14(6):625-36. [↩]
6. Wierdsma NJ, van Bokhorst-de van der Schueren MA, Berkenpas M, Mulder CJ, van Bodegraven AA. Vitamin and mineral deficiencies are highly prevalent in newly diagnosed celiac disease patients. Nutrients. 2013 Sep 30;5(10):3975-92. doi: 10.3390/nu5103975. [↩] [↩]
7. Kuloğlu Z, Kirsaçlioğlu CT, Kansu A, Ensari A, Girgin N. Celiac Disease: Presentation of 109 Children. Yonsei Med J. 2009 October 31; 50(5): 617–623. [↩] [↩]
8. Fathi F, Ektefa F, Tafazzoli M, Rostami K, Rostami Nejad M, Fathi M, Rezaei-Tavirani M, Oskouie AA, Zali MR. The concentration of serum zinc in celiac patients compared to healthy subjects in Tehran. Gastroenterol Hepatol Bed Bench. 2013 Spring;6(2):92-5. [↩] [↩]
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10. Jameson S. Zinc status in pregnancy: the effect of zinc therapy on perinatal mortality, prematurity, and placental ablation. Annals of New York Academy of Sciences. Mar 1993; 15(678):178-92.
11. Severe deficiency results in immunologic disorders including thymic atrophy, deficient thymic hormone, lymphopenia, and worsening of diarrhea. ((Kathleen Mahan and Sylvia Escott-Stump, ed. Krause’s Food, Nutrition & Diet Therapy, 10th Edition. Philadelphia, PA. USA: W.B. Saunders Company, 2000. [↩]
12. Giorgi PL, Catassi C, Guerrieri A. Zinc and chronic enteropathies. La Pediatria Medica e Chirurgica: Medical and Surgical Pediatrics. Sep-Oct 1984; 6(5):625-36. [↩]
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14. Shepherd SJ1, Gibson PR. Nutritional inadequacies of the gluten-free diet in both recently-diagnosed and long-term patients with coeliac disease. J Hum Nutr Diet. 2013 Aug;26(4):349-58. doi: 10.1111/jhn.12018. [↩] [↩]
15. Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2001. [↩]
16. Kathleen Mahan and Sylvia Escott-Stump, ed. Krause’s Food, Nutrition & Diet Therapy, 10th Edition. Philadelphia, PA. USA: W.B. Saunders Company, 2000. [↩] [↩]
17. Akinloye O1, Adebayo TO, Oguntibeju OO, Oparinde DP, Ogunyemi EO. Effects of contraceptives on serum trace elements, calcium and phosphorus levels. West Indian Med J. 2011 Jun;60(3):308-15. [↩]
18. Solomons NW, Rosenberg IH, Sandstead HH. Zinc nutrition in celiac disease. The American Journal of Clinical Nutrition. Apr 1976; 29(4):371-5 [↩]