Also Known As
ZPP
ZP
Free Erythrocyte Protoporphyrin
FEP
ZPP/Heme Ratio
This article was last reviewed on
This article waslast modified on November 15, 2019.
At a Glance
Why Get Tested?

To screen for and monitor chronic exposure to lead in adults; to detect iron deficiency in children

When To Get Tested?

When you have been chronically exposed to lead, as part of a program to monitor industrial lead exposure, and/or when your healthcare provider suspects lead poisoning; as part of screening and diagnosing iron deficiency in children and adolescents

Sample Required?

A blood sample drawn from a vein or from a fingerstick

Test Preparation Needed?

None

You may be able to find your test results on your laboratory's website or patient portal. However, you are currently at Lab Tests Online. You may have been directed here by your lab's website in order to provide you with background information about the test(s) you had performed. You will need to return to your lab's website or portal, or contact your healthcare practitioner in order to obtain your test results.

Lab Tests Online is an award-winning patient education website offering information on laboratory tests. The content on the site, which has been reviewed by laboratory scientists and other medical professionals, provides general explanations of what results might mean for each test listed on the site, such as what a high or low value might suggest to your healthcare practitioner about your health or medical condition.

The reference ranges for your tests can be found on your laboratory report. They are typically found to the right of your results.

If you do not have your lab report, consult your healthcare provider or the laboratory that performed the test(s) to obtain the reference range.

Laboratory test results are not meaningful by themselves. Their meaning comes from comparison to reference ranges. Reference ranges are the values expected for a healthy person. They are sometimes called "normal" values. By comparing your test results with reference values, you and your healthcare provider can see if any of your test results fall outside the range of expected values. Values that are outside expected ranges can provide clues to help identify possible conditions or diseases.

While accuracy of laboratory testing has significantly evolved over the past few decades, some lab-to-lab variability can occur due to differences in testing equipment, chemical reagents, and techniques. This is a reason why so few reference ranges are provided on this site. It is important to know that you must use the range supplied by the laboratory that performed your test to evaluate whether your results are "within normal limits."

For more information, please read the article Reference Ranges and What They Mean.

What is being tested?

Zinc protoporphyrin (ZPP) is normally present in red blood cells in small amounts, but the level may increase in people with lead poisoning and iron deficiency. This test measures the level of ZPP in the blood.

To understand how lead poisoning and iron deficiency affect the ZPP level, it is necessary to know about heme. Heme is an essential component of hemoglobin, the protein in red blood cells that carries oxygen from the lungs to the body's tissues and cells.

Heme formation occurs in a series of steps that concludes with the insertion of an iron atom into the center of a molecule called protoporphyrin. When there is not enough iron available, as in iron deficiency, or when the insertion of iron is inhibited, as in lead poisoning, then protoporphyrin combines with zinc instead of iron to form zinc protoporphyrin. ZPP serves no useful purpose in red blood cells since it cannot bind to oxygen.

Erythrocyte protoporphyrin (EP) accumulates in red blood cells when there is insufficient iron present for proper heme synthesis. A small percentage of EP may be unbound and can be measured as free erythrocyte protoporphyrin (FEP), with the remainder EP (about 90%) measured as zinc protoporphyrin (ZPP).

See More
See Less
Common Questions
  • How is it used?

    Zinc protoporphyrin (ZPP) is used to monitor chronic exposure to lead in adults. It is also elevated in iron deficiency and maybe ordered to help detect this deficiency in children. A ZPP level can be compared with the hemoglobin level to form a ZPP/heme ratio that is sensitive to diagnosing iron deficiency.

    Lead exposure in adults

    ZPP testing may be ordered along with a lead level to test for chronic lead exposure. Hobbyists who work with products containing lead and people, especially children who live in older houses built prior to 1960, may have been exposed to lead-based paint products and can be at increased risk for lead poisoning. Inhaling or ingesting lead dust particles from lead batteries, lead pipe-contaminated water, certain leaded fuels, and foods that have been transported in lead-soldered containers, can may also cause elevated lead levels.

    In an industrial setting, the Occupational Safety & Health Administration (OSHA) mandates the use of the ZPP test and strongly recommends that a ZPP test is ordered every time a lead level is ordered in order to monitor an employee's exposure. Both are necessary because ZPP will not reflect recent or acute lead exposure because it does not change quickly when a person's source of lead exposure is removed. ZPP is best at detecting a person's average exposure to lead over the last 3-4 months.

    ZPP is not sensitive enough for use as a lead screening test in children, as values do not rise until lead concentrations exceed the acceptable range. The maximum lead concentration considered safe in children has been set at a very low level by the Centers for Disease Control and Prevention (CDC). In this age group, tests that directly measure the blood lead concentration are done to detect exposure to lead.

    Iron deficiency anemia in children

    In children, the ZPP/heme ratio is sometimes ordered as an early indicator of iron deficiency. An increase in the ZPP/heme ratio is one of the first signs of insufficient iron stores and will be elevated in most young people before signs or symptoms of anemia are present. More specific tests of iron status are required to confirm iron deficiency.

  • When is it ordered?

    ZPP may be ordered along with a lead test when chronic exposure to lead is known or suspected in adults. Signs and symptoms of lead poisoning include:

    • High blood pressure
    • Numbness and/or tingling in the hands and feet
    • Memory loss, mood disorders
    • Weakness
    • Abdominal pain
    • Headache


    The test may be ordered when an employee is a participant in an occupational lead monitoring program or when someone has a hobby, such as working with stained glass, that brings the person into frequent contact with lead.

    The ZPP/heme ratio may be ordered as a screening test for iron deficiency in children and adolescents or when iron deficiency is suspected. Some symptoms of iron deficiency include:

    • Chronic fatigue, tiredness
    • Dizziness
    • Weakness
    • Headaches


    If the iron-deficiency anemia is severe, shortness of breath, dizziness, chest pain, headaches, and leg pains may occur. Children may develop learning (cognitive) disabilities. Besides the general symptoms of anemia, there are certain symptoms that are characteristic of iron deficiency. These include pica (cravings for specific substances, such as licorice, chalk, dirt, or clay), a burning sensation in the tongue or a smooth tongue, sores at the corners of the mouth, and spoon-shaped fingernails and toenails.

  • What does the test result mean?

    The ZPP concentration in blood is usually very low. An increase in ZPP indicates a disruption of normal heme production but is not specific as to its cause. The main reasons for increases in ZPP are iron deficiency and lead poisoning.

    It is important that ZPP levels be evaluated in the context of a person's history, clinical findings, and the results of other tests such as ferritin, lead, and a complete blood count (CBC). It is possible that the person may have both iron deficiency and lead poisoning.

    In cases of chronic lead exposure, ZPP reflects the average lead level over the previous 3-4 months. However, the amount of lead currently present in the blood and the amount in the organs and bones cannot be determined with a ZPP test. Values for ZPP rise more slowly than blood lead concentrations following exposure and take longer to drop after exposure to lead has ceased.

    An increase in the ZPP/heme ratio in a child is most often due to iron deficiency. A decreasing ZPP/heme ratio over time following iron supplementation likely indicates successful treatment.

  • Is there anything else I should know?

    ZPP may be elevated in inflammatory conditions, infections, and in people with anemia of chronic disease, but it is not generally used to monitor or diagnose these conditions. A very high ZPP level may be seen in two hereditary diseases: protoporphyria and congenital erythropoietic porphyria (see Porphyria). Both of these disorders are very rare and present with symptoms related to the skin (extreme sensitivity to sunlight). 

    Depending on the method used to test ZPP, high levels of other substances in the blood, such as bilirubin and riboflavin, can produce false-positive results. Falsely low values may occur if the sample is not protected from light before testing.

  • Besides ZPP and lead levels, what other tests might my doctor order to monitor exposure to lead?

    If you are in an occupational setting where you are frequently exposed to lead, your healthcare practitioner may order the following tests to evaluate your kidneys and red blood cell production:

  • If I have a hobby such as stained glass working but no symptoms, do I need to have a ZPP test done?

    Talk to your healthcare provider about this. If the hobby is a frequent activity, then it may be recommended that you have a ZPP test and a lead test to evaluate your lead exposure. You can have an increased ZPP level with few to no symptoms or you may have symptoms that have not yet been linked to lead exposure.

  • Should everyone have a ZPP test?

    No. This test will only be done for adults with suspected chronic exposure to lead, as a screening test to detect iron deficiency in children, or occasionally to test for a porphyria that affects the skin. 

See More Common Questions See Less Common Questions
Related Content

On This Site

Tests
Iron
Iron Tests
Lead
Complete Blood Count (CBC)
Hemoglobin
Hematocrit
Porphyrin Tests
Conditions
Lead Poisoning
Anemia

Elsewhere On The Web

Centers for Disease Control and Prevention: Lead
Occupational Safety & Health Administration: Lead
MedlinePlus Medical Encyclopedia: Lead poisoning
KidsHealth.org: Iron-Deficiency Anemia
National Heart, Lung, and Blood Institute: Iron-Deficiency Anemia
View Sources

Sources Used in Current Review

Kaneshiro, N, et. al. (2018 February 19, Reviewed). Anemia caused by low iron - infants and toddlers. MedlinePlus Medical Encyclopedia. Available online at https://medlineplus.gov/ency/article/007618.htm. Accessed on 3/16/19.

Kanuri, G. et. al. (2018 December). Optimizing diagnostic biomarkers of iron deficiency anemia in community-dwelling Indian women and preschool children. Haematologica. 2018 Dec; 103(12): 1991–1996. Available online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269316/. Accessed on 3/16/19.

Teshome, E. et. al. (2017 July 27). Diagnostic utility of zinc protoporphyrin to detect iron deficiency in Kenyan preschool children: a community-based survey. BMC Hematol. 2017; 17: 11. Available online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5532779/. Accessed on 3/16/19.

(2015 September).Iron Deficiency Anemia in Young Children: Screening. US Preventive Services Task Force. Available online at https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/iron-deficiency-anemia-in-young-children-screening#consider. Accessed on 3/16/19.

(© 1995-2019). Zinc Protoporphyrin, Blood. Mayo Clinic Laboratories. Available online at https://www.mayocliniclabs.com/test-catalog/Clinical+and+Interpretive/89375. Accessed on 3/16/19.

O’Malley, G. and O’Malley, R. (2018 January, Reviewed). Lead Poisoning. Merck Manual Professional Version. Available online at https://www.merckmanuals.com/professional/injuries-poisoning/poisoning/lead-poisoning?query=zinc%20protoporphyrin. Accessed on 3/16/19.

(2017 June 12). Lead Toxicity Clinical Assessment - Diagnostic Tests and Imaging. Agency for Toxic Substances & Disease Registry CE. Available online at https://www.atsdr.cdc.gov/csem/csem.asp?csem=34&po=13. Accessed on 3/16/19.

Mei, Z. et. al. (2017 May 31). Is Erythrocyte Protoporphyrin a Better Single Screening Test for Iron Deficiency Compared to Hemoglobin or Mean Cell Volume in Children and Women? Nutrients. 2017 May 31;9(6). Available online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5490536/pdf/nutrients-09-00557.pdf. Accessed on 3/16/19.

Hennig, G. et. al. (2016 February 17). Non-invasive detection of iron deficiency by fluorescence measurement of erythrocyte zinc protoporphyrin in the lip. Nature Communications volume 7, Article number: 10776 (2016). Available online at https://www.nature.com/articles/ncomms10776. Accessed on 3/16/19.

Magge H, et al., Zinc protoporphyrin and iron deficiency screening: trends and therapeutic response in an urban pediatric center. JAMA Pediatr. 2013 Apr;167(4):361-7. doi: 10.1001/jamapediatrics.2013.751 Available on line at file:///C:/Users/Tony/Downloads/poa120081_361_367%20(3).pdf. Accessed 4/14/2019.

Sources Used in Previous Reviews

Thomas, Clayton L., Editor (1997). Taber's Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition].

Pagana, Kathleen D. & Pagana, Timothy J. (2001). Mosby's Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO.

Porphyrins, Blood and Serum. ARUP's Guide to Clinical Laboratory Testing [On-line information]. Available online at http://www.arup-lab.com/guides/clt/tests/clt_143b.jsp#1145040.

(2000 May 19, Revised). The Interaction of Iron and Erythropoietin. Information Center for Sickle Cell and Thalassemic Disorders [On-line information]. Available online at http://sickle.bwh.harvard.edu/iron_epo.html.

Iron Metabolism Disorders. ZPP Hematofluorometer. AVIV Biomedical [On-line information]. Available online at http://www.avivbiomedical.com/Pages/IRON%20METAB.html.

Staudinger, K. and Roth, V. (1998 February 15). Occupational Lead Poisoning. American Family Physician [On-line journal]. Available online at http://www.aafp.org/afp/980215ap/stauding.html.

Labbe, R., et. al. (1987). Zinc protoporphyrin. Past, present, and future. Annals of the New York Academy of Sciences, vol 514 (1) [Abstract]. Available online at http://www.annalsnyas.org/cgi/content/abstract/514/1/7.

Mei, Z., et. al. (2003). Erythrocyte protoporphyrin or hemoglobin: which is a better screening test for iron deficiency in children and women? American Society for Clinical Nutrition, AM J Clin Nutr 2003;77:1229-33.

Roh, Y., et. al. (2000). Zinc Protoporphyrin IX Concentrations between Normal Adults and the Lead-Exposed Workers Measured by HPLC, Spectrofluorometer, and Hematofluorometer. Industrial Health 2000, 38, 372-379. [On-line journal]. PDF available for download at http://www.niih.go.jp/en/indu_hel/2000/pdf/IH38_48.pdf.

The Heme Biosynthetic Pathway. The Merck Manual of Diagnosis and Therapy. [On-line information]. Available online at http://www.merck.com/mrkshared/mmanual/section2/chapter14/14a.jsp.

Lead Poisoning. The Merck Manual of Diagnosis and Therapy [On-line information]. Available online at http://www.merck.com/mrkshared/mmanual/section19/chapter263/263b.jsp.

DiGuiseppi, C. (1996). Guide to Clinical Preventive Services, Second Edition Metabolic, Nutritional, and Environmental Disorders Screening for Elevated Lead Levels in Childhood and Pregnancy, Recommendation. U.S. Preventive Services Task Force. Guide to Clinical Preventive Services, 2nd Edition. Washington, DC: U.S. Department of Health and Human Services, Office of Disease Prevention and Health Promotion, 1996. [On-line information]. Available online at http://cpmcnet.columbia.edu/texts/gcps/gcps0033.html.

(60 FR 52856, Oct. 11, 1995; 63 FR 1152, Jan. 8, 1998) Regulations (Standards - 29 CFR), Employee standard summary - 1910.1025 App B. U.S. Department of Labor, Occupational Safety & Health Administration (OSHA) [Current on-line Regulation Standard for Lead Exposure]. Available online through http://www.osha.gov.

(57 FR 26627, May 4, 1993, as amended at 58 FR 34218, June 24, 1993). Regulations (Standards - 29 CFR), Medical Surveillance Guidelines - 1926.62 App C. U.S. Department of Labor, Occupational Safety & Health Administration (OSHA) [Current on-line Regulation Standard for Lead Exposure]. Available online through http://www.osha.gov.

 Labbe, R., et. al. (1999). Observations on the Zinc Protoporphyrin/Heme Ratio in Whole Blood. Clinical Chemistry, Technical Briefs 45:146-148 [On-line journal]. Available online at http://www.clinchem.org/cgi/content/full/45/1/146.

Labbe, R., et. al. (1999). Zinc Protoporphyrin: A Metabolite with a Mission. Clinical Chemistry 45:2060-2072 [On-line journal]. Available online at http://www.clinchem.org/cgi/content/full/45/12/2060.

CDC. Preventing Lead Poisoning in Young Children. Available online at http://www.cdc.gov/nceh/lead/publications/books/plpyc/chapter3.htm#Lead-Based%20Paint.

Wu, A. (2006). Tietz Clinical Guide to Laboratory Tests, Fourth Edition. Saunders Elsevier, St. Louis, Missouri. Pp 1154-1156.

(1993 June 24, Amended). Regulations (Standards - 29 CFR) Medical Surveillance Guidelines - 1926.62 App C. OSHA (Occupational Safety & Health Administration Medical Surveillance Guidelines [On-line information]. Available online at http://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=STANDARDS&p_id=10644. Accessed on 8/16/07.

(2006 July). Comparative Effectiveness of Zinc Protoporphyrin and Hemoglobin Concentrations in Identifying Iron Deficiency in a Group of Low-Income, Preschool-Aged Children: Practical Implications of Recent Illness. Pediatrics v118(1) [On-line information]. Available online at http://pediatrics.aappublications.org/cgi/content/abstract/118/1/224. Accessed on 8/18/07.

Rettmer, R. et. al., (1999 September 3). Zinc Protoporphyrin/Heme Ratio for Diagnosis of Preanemic Iron Deficiency. Pediatrics v104 (3) [On-line information]. Available online at http://pediatrics.aappublications.org/cgi/content/full/104/3/e37. Accessed on 8/16/07.

(© 2007). Zinc Protoporphyrin (ZPP), Whole Blood. ARUP's Laboratory Test Directory [On-line information]. Available online at http://www.aruplab.com/guides/ug/tests/0020605.jsp. Accessed on 8/18/07.

(© 2007). Protoporphyrin, Free Erythrocyte, and Zinc Protoporphyrin. LabCorp Test Information [On-line information]. Available online at http://www.labcorp.com/datasets/labcorp/html/chapter/mono/bm007100.htm. Accessed on 8/18/07.

Dombeck TA and Satonik RC. The Porphyrias. Emergency Medicine Clinics of North America. Volume 23, Issue 3, Pp 885-899.

Arup Laboratories. Test Directory: Zinc Protoporphyrin (Online information). Available online at http://www.aruplab.com/guides/ug/tests/0020605.jsp. Accessed October 2007.

Quest Diagnostics. Test Menus: Zinc Protoporphyrin (Online information). Available online through http://cas2.questdiagnostics.com. Accessed October 2007.

(March 12, 2011) Mayo Clinic. Symptoms of Lead Poisoning. Available online at http://www.mayoclinic.com/health/lead-poisoning/FL00068/DSECTION=symptoms. Accessed April 2011.

(August 6, 2010) Barclay B. Iron-Deficiency Anemia Linked to Memory Deficits in Children. Medscape Medical News. Available online at http://www.medscape.com/viewarticle/726423. Accessed April 2011.

Mayo Medical Laboratories. Zinc Protoporphyrin, Blood. Available online at http://www.mayomedicallaboratories.com/test-catalog/Overview/300009. Accessed April 2011.

(July 26, 2010) Agency for Toxic Substances and Disease Registry. Case Studies in Environmental Medicine, Lead Toxicity: What Tests Can Assist with Diagnosis of Lead Toxicity? Available online at http://www.atsdr.cdc.gov/csem/lead/pbtests_diagnosis2.html. Accessed April 2011.

OSHA: Regulations (Standards - 29 CFR). Medical Surveillance Guidelines - 1926.62 App C, June 24 1993. Available online at http://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=STANDARDS&p_id=10644. Accessed April 2011.

Baumann-Blackmore NL, et.al. Cord blood zinc protoporphyrin/heme ratio in minority neonates at risk for iron deficiency. J Pediatr. 2008 Jul;153(1):133-6. Available online at http://www.ncbi.nlm.nih.gov/pubmed/18571551. Accessed April 2011.

Zimmerman M, et al. Serum transferrin receptor and zinc protoporphyrin as indicators of iron status in African children. American Journal of Clinical Nutrition, Vol. 81, No. 3, 615-623, March 2005. Available online at http://www.ajcn.org/content/81/3/615.full. Accessed April 2011.

Rettmer R, et al. Zinc Protoporphyrin/Heme Ratio for Diagnosis of Preanemic Iron Deficiency. Pediatrics, Sep 1999; 104: e37. Available online at http://pediatrics.aappublications.org/cgi/content/full/104/3/e37. Accessed April 2011.

(April 2011) National Heart, Lung, Blood Institute. How is iron-deficiency anemia diagnosed? Available online at http://www.nhlbi.nih.gov/health/dci/Diseases/ida/ida_diagnosis.html. Accessed April 2011.

ARUP Laboratories. Test Directory Catalog, Zinc Protoporphyrin (ZPP), Whole Blood Industrial. Available online at http://www.aruplab.com/guides/ug/tests/0020614.jsp. Accessed May 2011.

Kathuria, P. et. al. (Updated 2014 January 29). Lead Toxicity. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/1174752-overview. Accessed August 2014.

Strathmann, F. (Updated 2014 June). Lead Poisoning. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/LeadPoisoning.html?client_ID=LTD. Accessed August 2014.

(© 1995–2014). Zinc Protoporphyrin, Blood. Mayo Clinic Mayo Medical Laboratories [On-line information]. Available online at http://www.mayomedicallaboratories.com/test-catalog/Overview/300009. Accessed August 2014.

O'Malley, G. and O'Malley, R. (Revised 2013 February). Lead Poisoning. Merck Manual for Healthcare Professionals [On-line information]. Available online through http://www.merckmanuals.com. Accessed August 2014.

Yu, K.H. (2011 February). Effectiveness of zinc protoporphyrin/heme ratio for screening iron deficiency in preschool-aged children. Nutr Res Pract. Feb 2011; 5(1): 40–45. [On-line information]. Available online at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3061269/. Accessed August 2014.

Pagana, K. D. & Pagana, T. J. (© 2011). Mosby's Diagnostic and Laboratory Test Reference 10th Edition: Mosby, Inc., Saint Louis, MO. Pg 1056.

Magge H, et al. Zinc Protoporphyrin and Iron Deficiency ScreeningTrends and Therapeutic Response in an Urban Pediatric Center. JAMA Pediatr. 2013;167(4):361-367. Available online at http://archpedi.jamanetwork.com/article.aspx?articleid=1653081. Accessed August 2014.

See More
See Less

Ask a Laboratory Scientist

This form enables patients to ask specific questions about lab tests. Your questions will be answered by a laboratory scientist as part of a voluntary service provided by one of our partners, American Society for Clinical Laboratory Science. Please allow 2-3 business days for an email response from one of the volunteers on the Consumer Information Response Team.

Disclaimer
Thank you for using the Consumer Information Response Service ("the Service") to inquire about the meaning of your lab test results.  The Service is provided free of charge by the American Society for Clinical Laboratory Science, which is one of many laboratory organizations that supports Lab Tests Online.
Please note that information provided through this free Service is not intended to be medical advice and should not be relied on as such. Although the laboratory provides the largest single source of objective, scientific data on patient status, it is only one part of a complex biological picture of health or disease. As professional clinical laboratory scientists, our goal is to assist you in understanding the purpose of laboratory tests and the general meaning of your laboratory results. It is important that you communicate with your physician so that together you can integrate the pertinent information, such as age, ethnicity, health history, signs and symptoms, laboratory and other procedures (radiology, endoscopy, etc.), to determine your health status. The information provided through this Service is not intended to substitute for such consultations with your physician nor specific medical advice to your health condition.
By submitting your question to this Service, you agree to waive, release, and hold harmless the American Society for Clinical Laboratory Science and its affiliates or their past or present officers, directors, employees, agents, and Service volunteers (collectively referred to as "ASCLS") and the American Association  for Clinical Chemistry and its affiliates or their past or present officers, directors, employees, agents, and Service volunteers (collectively referred to as "AACC") from any legal claims, rights, or causes of action you may have in connection with the responses provided to the questions that you submit to the Service.
AACC, ASCLS and its Service volunteers disclaim any liability arising out of your use of this Service or for any adverse outcome from your use of the information provided by this Service for any reason, including but not limited to any misunderstanding or misinterpretation of the information provided through this Service.
 
See More See Less