Iron supplementation;

In my patient with iron deficiency anemia (IDA), should I prescribe daily or every other day oral iron supplementation?    

FA Manian MD, MPH, , , , , , , , Leave a comment

Oral iron supplementation dosed every 48 hours is preferred over a daily regimen for at least 2 reasons: higher absorption and better tolerability. Improved absorption is due to an increase in hepcidin after oral intake of iron that lasts up to 48 hours which, paradoxically, also results in blocking further iron absorption during that period. In fact, a study comparing consecutive-day versus alternate-day dosing of oral iron supplementation found the fractional iron absorption to be 40-50% higher in alternate-day dosing.1

As for tolerability, the most frequent side effect of oral iron is gastrointestinal in nature, including nausea, vomiting, diarrhea, and constipation which are related to: 1. Excess amounts of unabsorbed iron leading to inflammation in the gut; and 2. An increase in the production of free radicals and peroxidation in the gut.2 Not surprisingly, alternate-day dosing has been shown to result in less side effects due to higher fractional iron absorption – leading to reduced levels of unabsorbed iron in the gut.3

Understanding the importance of optimal dosing regimen for oral iron supplementation is more than an academic exercise. Iron deficiency is the number one nutritional deficiency globally, affecting 30% of the world’s population.4 The most common causes are gastrointestinal blood loss and menstrual cycle blood loss, followed by a decrease in dietary fiber intake and decreased iron absorption. Undoubtedly, many providers will encounter patients with iron deficiency in need of oral supplementation. To increase both efficacy and compliance of oral iron supplementation, providers should consider every other day (every 48 h) dosing of oral iron in preference to daily dosing. 

Bonus Pearl:  Did you know that heme sources of iron from animals (eg, red meat, liver or kidney) are usually more bioavailable than their non-heme counterparts (eg, from green leafy vegetables) except for blackstrap molasses which has high iron content as well as exceptionally high bioavailability?5,6 

Contributed by Morgan Walters, DO, Internal Medicine Resident, Mercy Hospital-St. Louis, St. Louis, Missouri 

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References: 

  1. Stoffel N, Zeder C, Brittenham G, et al. Iron absorption from supplements is greater with alternate day than with consecutive day dosing in iron-deficient anemic women. Haematologica. 2020 May;105(5):1232-1239. doi: 10.3324/haematol.2019.220830.  Epub 2019 Aug 14. https://pubmed.ncbi.nlm.nih.gov/32650997/
  2. DeLoughery T, Jackson C, Ko C, et al. AGA Clinical Practice Update on management of Iron Deficiency Anemia: Expert Review. Clinical Gastroenterology and Hepatology 2024;22:1575–1583. Doi:0.1016/j.cgh.2024.03.046.  https://pubmed.ncbi.nlm.nih.gov/38864796/
  3. Stoffel N, Zeder C, Brittenham G, et al. Iron absorption from supplements is greater with alternate day than with consecutive day dosing in iron-deficient anemic women Haematologica. 2020 May;105(5):1232-1239. doi: 10.3324/haematol.2019.220830.  Epub 2019 Aug 14. https://pubmed.ncbi.nlm.nih.gov/32650997/
  4. Kumar A, Sharma E, Marley A, et al. Iron deficiency anaemia: pathophysiology, assessment, practical management. BMJ Open Gastro 2022;9:e000759. doi:10.1136/bmjgast-2021-000759. https://pubmed.ncbi.nlm.nih.gov/34996762/
  5. Brittany Lubeck, MS. “Is Molasses Healthy? What to Know about This Sweetener.” Verywell Health, May 10, 2024. https://www.verywellhealth.com/molasses-8640108.
  6. Hamlett, C. (2024, March 22). Meet Blackstrap Molasses: The “best source” of plant-based Iron. Plant Based News. https://plantbasednews.org/lifestyle/health/blackstrap-molasses-is-an-iron-rich-nutritional-powerhouse/ 

 

Disclosures/Disclaimers: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

In my patient with iron deficiency anemia (IDA), should I prescribe daily or every other day oral iron supplementation?    

200 pearls and counting! Take the Pearls4Peers quiz #2!

FA Manian MD, MPH, , , , , , , , , , , , , , , Leave a comment
Multiple choice (choose 1 answer)
1. Which of the following classes of antibiotics is associated with peripheral neuropathy?
a. Penicillins
b. Cephalosporins
c. Macrolides
d. Quinolones

 

 

2. The best time to test for inherited thrombophilia in a patient with acute deep venous thrombosis is…
a. At least 1 week after stopping anticoagulants and a minimum of 3 months of anticoagulation
b. Just before initiating anticoagulants
c. Once anticoagulation takes full effect
d. Any time, if suspected

 

 

3. All the following is true regarding brain MRI abnormalities following a seizure, except…
a. They are observed following status epilepticus only
b. They are often unilateral
c. They may occasionally be associated with leptomeningeal contrast enhancement
d. Abnormalities may persist for weeks or months

 

 

4. Which of the following is included in the quick SOFA criteria for sepsis?
a. Heart rate
b. Serum lactate
c. Temperature
d. Confusion

 

 

5. All of the following regarding iron replacement and infection is true, except…
a. Many common pathogens such as E.coli and Staphylococcus sp. depend on iron for their growth
b. Association of IV iron replacement and increased risk of infection has not been consistently demonstrated
c. A single randomized-controlled trial of IV iron in patients with active infection failed to show increased infectious complications or mortality with replacement
d. All of the above is true

 

True or false

1. Constipation may precede typical manifestations of Parkinson’s disease by 10 years or more
2. Urine Legionella antigen testing is >90% sensitive in legionnaire’s disease
3. Spontaneous coronary artery dissection should be particularly suspected in males over 50 years of age presenting with acute chest pain
4. Urine dipstick for detection of blood is >90% sensitive in identifying patients with rhabdomyolysis and CK >10,000 U/L
5. Diabetes is an independent risk factor for venous thrombophlebitis

 

 

 

Answer key
Multiple choice questions:1=d; 2=a;3=a;4=d;5=c
True or false questions:1=True; 2,3,4,5=False

 

200 pearls and counting! Take the Pearls4Peers quiz #2!

Is iron therapy contraindicated in my patient with active infection?

FA Manian MD, MPH, , , , , , 1 Comment

In the absence of randomized-controlled trials of iron therapy in patients with active infection, the harmful effects of iron therapy (IT) in this setting remains more theoretical than proven. 1,2

Although many pathogens (eg, E. coli, Klebsiella, Salmonella, Yersinia, and Staphylococcus species) depend on iron for their growth2,3, and iron overload states (eg, hemochromatosis) predispose to a variety of infections, studies evaluating the risk of infection with iron therapy have reported conflicting results.1-4 A 2015 systematic review and meta-analysis of 103 trials comparing IV iron therapy  with several other approaches, including oral iron therapy or placebo, found no increased risk of infections with IV iron.5 In contrast, an earlier systematic review and meta-analysis involving fewer number of trials found an increased risk of infections with IV iron. 6

These varied results are perhaps not surprising since the effects of iron therapy on the risk of infection is likely to be context-specific, depending on the patient’s preexisting iron status, exposure to potential infections and co-infection and genetic background. 4 Of interest, mice with sepsis have worse outcomes when treated with IV iron.7

Perhaps the most prudent approach is to hold off on iron therapy until the active infection is controlled, unless the benefits of urgent iron therapy is thought to outweigh its theoretical harmful effects.

 

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References

  1. Daoud E, Nakhla E, Sharma R. Is iron therapy for anemia harmful in the setting of infection? Clev Clin J Med 2011;78:168-70. http://www.mdedge.com/ccjm/article/95480/hematology/iron-therapy-anemia-harmful-setting-infection
  2. Hain D, Braun M. IV iron: to give or to hold in the presence of infection in adults undergoing hemodialysis. Nephrology Nursing Journal 2015;42:279-83. https://www.ncbi.nlm.nih.gov/pubmed/26207288
  3. Jonker FAM, van Hensbroek MB. Anaemia, iron deficiency and susceptibility of infections. J Infect 204;69:523-27. https://www.ncbi.nlm.nih.gov/pubmed/28397964
  4. Drakesmith H, Prentice AM. Hepcidin and the iron-infection axis. Science 2012;338:768-72. https://www.ncbi.nlm.nih.gov/pubmed/23139325  
  5. Avni T, Bieber A, Grossman A, et al. The safety of intravenous iron preparations: systematic review and meta-analysis. Mayo Clin Proc 2015;90:12-23. http://www.mayoclinicproceedings.org/article/S0025-6196(14)00883-0/pdf
  6. Litton E, Xiao J, Ho KM. Safety and efficacy of intravenous iron therapy in reducing requirement for allogeneic blood transfusion: systematic review and meta-analysis of randomized clinical trials. BMJ 2013;347:f4822. https://www.ncbi.nlm.nih.gov/pubmed/23950195
  7. Javadi P, Buchman TG, Stromberg PE, et al. High dose exogenous iron following cecal ligation and puncture increases mortality rate in mice and is associated with an increase in gut epithelial and splenic apoptosis. Crit Care Med 2004;32:1178-1185. https://www.ncbi.nlm.nih.gov/pubmed/15190970
Is iron therapy contraindicated in my patient with active infection?

Does oral iron cause false-positive stool guaiac test?

FA Manian MD, MPH, , , Leave a comment

The general agreement in the literature is that oral iron supplementation does not cause a false-positive guaiac-based fecal occult blood test (GFOBT).

GFOBT is based on rapid oxidization of α-guaiaconic acid to “guaiacum blue”, with hemoglobin serving as a catalyst through a non-enzymatic or “pseudoperoxidase” action. Although in vitro Fe3+ may serve as an oxidizing agent, this reaction is possible only under acidic conditions not found in the stool (pH ≥ 6-7)1.  Also, in the absence of a catalyst, Fe3+ alone would not be expected to cause rapid (within 30 seconds) conversion of α-guaiaconic acid to guaiacum blue1. 

Although a number of earlier clinical studies reported false-positive GBFOBT because of oral iron supplementation, subsequent investigations have uniformly failed to confirm these findings2. Potential reasons for earlier false-positive GBFOBT results include false interpretation of the color change—eg, green instead of blue— particularly when the discoloration is weakly positive, and non-standardized method of stool collection with the possibility of stool sample contamination by toilet water.

Other fascinating facts: Did you know that guaiac plant extract was used for centuries for treatment of syphilis and that the earliest application of guaiac testing was in forensic medicine in 1800s?

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References

  1. McDonnell WM, Ryan JA, Seeger DM, Elta GH. Effect of iron on the guaiac reaction. Gastroenterology. 1989 Jan;96(1):74-8. https://www.ncbi.nlm.nih.gov/pubmed/2909440
  2. Anderson GD, Yellig TR, Krone RE. An investigation into the effects of oral iron supplementation on in vivo hemoccult stool testing. Am J Gastroenterol 1990;85:558-561. https://www.ncbi.nlm.nih.gov/pubmed/218661

Contributed by Brian Li, Medical Student, Harvard Medical School

Does oral iron cause false-positive stool guaiac test?