Iron Deficiency

What Is Iron?

Iron is an essential mineral that is required for normal body function.

Almost two-thirds of iron in the body is found in hemoglobin, the protein in red blood cells that carries oxygen to tissues. Smaller amounts of iron are found in myoglobin, a protein that helps supply oxygen to muscle, and in enzymes that assist biochemical reactions.

Iron is also found in proteins that store iron for future needs and that transport iron in blood.

Q: How are iron stores regulated?

A:Iron stores are regulated by intestinal iron absorption.1That is, whenever iron is needed, more iron is absorbed than when iron is sufficient. This mechanism prevents excess iron in the body which is harmful.

In the brain, iron is necessary to ensure oxygenation and to produce energy in the cerebral parenchyma (via cytochrome oxid. ase), and for the synthesis of neurotransmitters and myelin.

Iron concentrations in the umbilical artery are critical during the development of the fetus, and in relation with the IQ in the child.2

What Is Iron Deficiency In Celiac Disease and/or Gluten Sensitivity?

• Iron 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.
• Deficiency is characterized by impaired: red blood cell formation, free-radical disposal, oxygenation of cells, immune response to infection, enzyme activity, cognitive performance, digestion, nail structure, and fetal health.3
• Celiac disease induces malabsorption and deficiency of iron essential for fetal organogenesis (organ formation and development in a fetus).4
• Iron deficiency has been implicated in elevated prolactin hormone characterized by altered estrogen production in women and androgen production in men.5
• A study investigating life-long gluten-free diet in celiac disease patients shows that inadequate intake of iron 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.”6

How Prevalent Is Iron Deficiency In Celiac Disease and/or Gluten Sensitivity?

• Iron deficiency is common in patients with untreated celiac disease.7
• Of the general population, it is the most common nutritional deficiency in the world,8 but it does not respond to treatment in persons with untreated celiac disease.
• Research showed that 69% of 49 patients had iron deficiency at initial presentation of celiac disease.9
• A prospective Dutch study in 80 newly diagnosed adult patients with celiac disease found 46% had decreased iron storage.10
• A study analyzing the charts of 405 patients at diagnosis of celiac disease, showed that iron deficiency was common, occurring in 33% of men and 19% of women. Anemia was present in approximately 20% of the cohort. Among the anemic patients, ferritin was less than the 10th percentile in 45%, between the 10th and 50th percentile in 39% and greater than the 50th percentile in 13%.11
• A prospective study investigating the association of cervical esophageal web (Plummer-Vinson syndrome) with celiac disease found that all patients with Plummer-Vinson syndrome and celiac disease had evidence of iron deficiency.12

What Are The Symptoms Of Iron Deficiency?

Iron deficiency is marked by this wide variety of symptoms showing the essential need for adequate supplies:

• Pallor (pale skin color).
• Fatigue.
• Headache.
• Lightheadedness.
• Shortness of breath.
• Rapid heartbeat.
• Blurry vision.
• Angina.
• Increased susceptibility to bacterial infection.
• Reduced learning.
• Inattention.
• Reduced memory.
• Sensorimotor incompetence.
• Anorexia (loss of appetite).
• Dysphagia (difficult swallowing).
• Pale, smooth, and sore tongue.
• Koilonychia.
• Loss of vitality.
• Infertility.
• Alopecia (hair loss/thin hair).
• Restless leg syndrome.
• Defects in fetal development.

How Does The Body Get Iron?

Iron must be obtained from the diet since the body cannot make it. Iron absorption depends on the ionization (gaining a positive electrical charge) in the acidic environment of stomach juice. Ionized iron is absorbed in the duodenum, the first part of the small intestine.

Heme iron, obtained from animal food, is absorbed across the brush border of the intestinal lining then by active transport into the blood. Nonheme iron, obtained from plants, binds with apoprotein after entering the enterocyte (surface mucosa cell) to be ferried to the basolateral membrane (beneath the enterocytes) and exited by active transport into the bloodstream. Vitamin C and intestinal acidity in the duodenum are needed for absorption.3

Healthy adults absorb about 10% to 15% of dietary iron, but individual absorption varies.1

What Does Iron Do In The Body?

• Required for hemoglobin production.
• Required for myoglobin activity.
• Required for production of numerous heme and nonheme enzymes.
• Required for the respiratory transport of O2 and CO2 because of its redox properties (giving and taking of oxygen molecules).
• Required as an active component of cytochromes involved in cellular respiration.
• Required in antibody production and cellular immunity for adequate concentrations of circulating T lymphocytes, mitogenic response, natural killer cell activity, and production of interleukin 1 and 2.
• Involved in the function and production of neurotransmitters and, possibly, myelin.

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

Iron deficiency results from these mechanisms in celiac disease:

• Deficiency results primarily from malabsorption of this mineral due to inflammation of intestinal lining.
• Malabsorption can occur as a consequence of low stomach acid. Sufficient acid is required to ionize iron (receives a positive charge) which is required for absorption later in the small intestine.
• Malabsorption can occur as a consequence of insufficient carrier proteins needed to transport ionized into the bloodstream from the absorbing cells of the small intestine.
• Deficiency of necessary vitamin C impairs absorption.
• However, nutritional deficiencies alone do not explain iron deficiency anemia in all cases; inflammation appears to contribute.13

Does Iron Deficiency Respond To Gluten Free Diet?

Yes. Celiac disease-related iron deficiency responds to gluten free diet; iron supplementation is required if iron deficiency anemia results from celiac disease.1 A gluten-free diet resulted in increased serum ferritin in iron-deficient patients, and decreased ferritin levels in those with high ferritin.13

6 Steps To Correct Iron Deficiency In Celiac Disease and/or Gluten Sensitivity:

• 1Meet, or Exceed the RDA (Recommended Dietary Allowances) for Iron in milligrams (mg) per day:

• 2Diet – Include Food Sources Richest in Iron:

• 3 Diet – Avoid, Limit, or Eat Separately These Foods That Deplete or Interfere With Iron Absorption:

• 4Monitor Medications That Deplete or Interfere With Iron Absorption:

• 5Manage Nutritional Supplements to Obtain Iron:

• 6Other Supplements That Deplete or Interfere With Absorption:

Medical Research Findings On Iron Deficiency In Celiac Disease and/or Gluten Sensitivity:

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 newly “early diagnosed” CD-patients, even though the prevalence of obesity at initial diagnosis is rising. 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, hemoglobin (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. Specifically, 46% had decreased iron storage and 32% had anemia.

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.10

“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 iron 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.”6

“Cervical esophageal web and celiac disease.” This prospective study investigating the association of cervical esophageal web (Plummer-Vinson syndrome) with celiac disease found that all patients with Plummer-Vinson syndrome and celiac disease had evidence of iron deficiency. None of these patients gave a history of chronic diarrhea. Researchers suggest that all adult patients with cervical esophageal web and iron deficiency need screening for celiac disease even in the absence of chronic diarrhea.

Subjects included were consecutive patients with symptomatic cervical esophageal web diagnosed over a period of 4.5 years. Tissue transglutaminase antibody was measured in serum of each patient. Patients with elevated tissue transglutaminase antibody titer were subjected to esophagogastroduodenoscopy and biopsies were obtained from the descending duodenum to look for histological changes of celiac disease. Celiac disease was diagnosed on the basis of elevated tissue transglutaminase antibody and suggestive duodenal histology.

RESULTS: Twenty one patients were diagnosed to have cervical esophageal web. Eighteen (85.7%) had evidence of iron deficiency. Five (23.8%) patients with cervical esophageal web fulfilled criteria for diagnosis of celiac disease. All five had evidence of iron deficiency. None of these patients gave a history of chronic diarrhea. All patients were treated with bougie dilatation. Patients with celiac disease were advised of a gluten-free diet. All five celiac disease patients are free of dysphagia without recurrence after a mean follow up of 10 months (range: 3 to 16 months).12

“Anemia in celiac disease is multifactorial in etiology.” This study assessed the characteristics of anemia from a cohort of patients seen at a hospital care center for celiac disease. Hematological parameters measured within 3 months of diagnosis and degree of villous atrophy from 405 patients diagnosed after 1995 was analyzed. Ferritin (iron) levels were compared with population controls (NHANES III). Iron deficiency was common, occurring in 33% of men and 19% of women. Anemia was present in approximately 20% of the cohort. Among the anemic patients, ferritin was less than the 10th percentile in 45%, between the 10th and 50th percentile in 39% and greater than the 50th percentile in 13%. Ferritin greater than 50th percentile was more common in anemic men (24%) than in anemic women.

A gluten-free diet resulted in increased serum ferritin in iron-deficient patients, and decreased ferritin levels in those with high ferritin. Although anemia is still a common presentation of celiac disease, nutritional deficiencies alone do not explain this phenomenon in all cases; inflammation appears to contribute as evidenced by the presence of anemia of chronic disease in some individuals.14

“Do adults with high gliadin antibody concentrations have subclinical gluten intolerance?” This study measuring IgG and IgA isotypes and IgG subclasses demonstrated significantly decreased transferrin saturation, mean corpuscular volume, and mean corpuscular hemoglobin in patients with positive IgA gliadin antibodies.15

1. http://ods.od.nih.gov/factsheets/Iron-HealthProfessional accessed 12/11/12 [↩] [↩] [↩]
2. Bourre JM. Effects of nutrients (in food) on the structure and function of the nervous system: update on dietary requirements for brain. Part 1: micronutrients. J Nutr Health Aging. 2006 Sep-Oct; 10(5):377-85. [↩]
3. Kathleen Mahan and Sylvia Escott-Stump, ed. Krause’s Food, Nutrition & Diet Therapy, 10th Edition. Philadelphia, PA. USA: W.B. Saunders Company, 2000. [↩] [↩]
4. Stazi AV, Mantovani A. A risk factor for female fertility and pregnancy: celiac disease. Gynecological Endocrinology. Dec 2000; -63. [↩]
5. 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. [↩]
6. 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. [↩] [↩]
7. Murray JA, the widening spectrum of celiac disease. American Journal of Clinical Nutrition. Mar 1999;69(3):354-365. [↩]
8. Mark Beers and Robert Berkow. The Merck Manual, 17th Edition. Whitehouse Station, NL. USA: Merck Research Laboratories, 1999 [↩]
9. Harmanci O, Kav T, Sivri B. Red cell distribution width can predict intestinal atrophy in selected patients with celiac disease. J Clin Lab Anal. 2012 Nov; 26(6):497-502. doi: 10.1002/jcla.21553. [↩]
10. 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. [↩] [↩]
11. Harper JW, Holleran SF, Ramakrishnan R, Bhagat G, Green PH. Anemia in celiac disease is multifactorial in etiology. Am J Hematol. 2007 Nov; 82(11):996-1000. [↩]
12. Sinha SK, Nain CK, Udawat HP, Prasad KK, Das R, Nagi B, Singh K. Cervical esophageal web and celiac disease. J Gastroenterol Hepatol. 2008 Jul;23(7 Pt 1):1149-52. doi: 10.1111/j.1440-1746.2008.05452.x. Epub 2008 Jun 28. [↩] [↩]
13. Harper JW, Holleran SF, Ramakrishnan R, Bhagat G, Green PH. Anemia in celiac disease is multifactorial in etiology. Am J Hematol. 2007 Nov;82(11):996-1000. [↩] [↩]
14. Harper JW, Holleran SF, Ramakrishnan R, Bhagat G, Green PH. Anemia in celiac disease is multifactorial in etiology. Am J Hematol. 2007 Nov; 82(11):996-1000. [↩]
15. Arneson JA, Gudjonsson H, Freysdottir J, Valdimarsson H. Do adults with high gliadin antibody concentrations have subclinical gluten intolerance? Gut. Feb 1992; 33(2):194-7 [↩]