Skip to main content
SpringerLink
Log in

Serum Folate Levels in Patients with Chronic Hemolytic Anemia on Regular Folic Acid Supplementation Before and After Dose Modification

  • Research Paper
  • Published:
Indian Pediatrics Aims and scope Submit manuscript

Abstract

Objective

In light of the recommendation of folic acid supplementation in chronic hemolytic anemia, with possible supratherapeutic dosing and associated side effects, we performed this study to investigate serum folate levels in children with chronic hemolytic anemia.

Methods

Phase 1 was a cross-sectional study of 134 patients in the Pediatric Hematology service, documenting daily dosage and performing serum folate levels. In phase 2, we reduced the dose to 1 mg for 148 patients and repeated the testing after six months.

Results

We found very high serum folate levels with Phase 1, with 93.2% above the upper level of normal. In Phase 2, values remained high with 42.5% above the acceptable upper limit.

Conclusions

Doses of folic acid given to sickle cell and thalassemia patients exceed their actual needs. This should be re-evaluated to strike a balance between benefit and harm, with close monitoring of serum folate levels.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Hazra A, Tripathi SK. Folic acid revisited. Indian J Pharmacol. 2001;33:322–42.

    CAS  Google Scholar 

  2. Kennedy TS, Fung EB, Kawchak DA, Zemel BS, Ohene-Frempong K, Stallings VA. Red blood cell folate and serum vitamin B12 status in children with sickle cell disease. J Pediatr Hematol Oncol. 2001;23:165–9.

    Article  CAS  Google Scholar 

  3. Liu YK. Folic acid deficiency in sickle cell anaemia. Scand J Haematol. 1975;14:71–9.

    Article  CAS  Google Scholar 

  4. van der Dijs FP, Schnog JJ, Brouwer DA, Velvis HJ, van den Berg GA, Bakker AJ, et al. Elevated homocysteine levels indicate suboptimal folate status in pediatric sickle cell patients. Am J Hematol. 1998;59:192–8.

    Article  CAS  Google Scholar 

  5. Dixit R, Nettem S, Madan SS, Soe HHK, Abas AB, Vance LD, et al. Folate supplementation in people with sickle cell disease. Cochrane Database Syst Rev. 2018;3:CD011130.

    PubMed  Google Scholar 

  6. Fischbach F, Dunning MB. Manual of Laboratory and Diagnostic Tests. 8th ed. Philadelphia: Lippincott Williams & Wilkins; 2008.

    Google Scholar 

  7. Gall S, Seal J, Taylor R, Dwyer T, Venn A. Folate status and socio-demographic predictors of folate status, among a national cohort of women aged 26–36 in Australia, 2004–2006. Aust N Z J Public Health. 2012;36:421–6.

    Article  Google Scholar 

  8. Matsuzaki M, Haruna M, Ota E, Sasaki S, Nagai Y, Murashima S. Dietary folate intake, use of folate supplements, lifestyle factors, and serum folate levels among pregnant women in Tokyo, Japan. J Obstet Gynaecol Res. 2008;34:971–9.

    PubMed  Google Scholar 

  9. Dhar M, Bellevue R, Carmel R. Pernicious anemia with neuropsychiatric dysfunction in a patient with sickle cell anemia treated with folate supplementation. N Engl J Med. 2003;348:2204–7.

    Article  Google Scholar 

  10. Smith AD, Kim Y, Refsum Y. Is folic acid good for everyone? Am J Clin Nutr. 2008;87:517–33.

    Article  CAS  Google Scholar 

  11. Conley CL, Krevans JR. Development of neurologic manifestations of pernicious anemia during multivitamin therapy. N Engl J Med 1951;245:529–31.

    Article  CAS  Google Scholar 

  12. Rosenberg IH. Science-based micronutrient fortification: which nutrients, how much, and how to know? Am J Clin Nutr. 2005;82:279–80.

    Article  CAS  Google Scholar 

  13. Claster S, Wood JC, Noetzli L, Carson SM, Hofstra TC, Khanna R, et al. Nutritional deficiencies in iron overloaded patients with hemoglobinopathies. Am J Hematol. 2009;84:344–8.

    Article  CAS  Google Scholar 

  14. Kim YI. Does a high folate intake increase the risk of breast cancer? Nutr Rev. 2006;64:468–75.

    Article  Google Scholar 

  15. Kim SJ, Zuchniak A, Sohn KJ, Lubinski J, Demsky R, Eisen A, et al. Plasma folate, vitamin B-6, and vitamin B-12 and breast cancer risk in BRCA1- and BRCA2-mutation carriers: A prospective study. Am J Clin Nutr. 2016;104:671–7.

    Article  CAS  Google Scholar 

  16. Tomaszewski JJ, Cummings JL, Parwani AV, Dhir R, Mason JB, Nelson JB, et al. Increased cancer cell proliferation in prostate cancer patients with high levels of serum folate. Prostate. 2011;71:1287–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Castillo-L C, Tur JA, Uauy R. Folate and breast cancer risk: A systematic review. Rev Med Chil. 2012;140:251–60.

    Article  Google Scholar 

  18. Venn BJ, Mann JI, Williams SM, Riddell LJ, Chisholm A, Harper MJ, et al. Assessment of three levels of folic acid on serum folate and plasma homocysteine: A randomised placebo-controlled double-blind dietary intervention trial. Eur J Clin Nutr. 2002;56:748–54.

    Article  CAS  Google Scholar 

  19. Pena AS, Maftei O, Dowling K, Gent R, Wiltshire E, MacKenzie K, et al. Folate fortification and supplementation do not provide vascular health benefits in type 1 diabetes. J Pediatr. 2013;163:255–60.

    Article  CAS  Google Scholar 

  20. Nguyen GT, Lewis A, Goldener C, Reed B, Dulman RY, Yang E. Discontinuation of folic acid supplementation in young patients with sickle cell anemia. J Pediatr Hematol Oncol. 2017;39:470–2.

    Article  CAS  Google Scholar 

Download references

Funding

Funding: None; Competing Interest: None stated.

Author information

Authors and Affiliations

  1. Pediatric Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt

    Mona Azzam

  2. Medical laboratory Department, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia

    Samy Attalla

Authors
  1. Mona Azzam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Samy Attalla
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Contributors: MA: designed the study, participated in collection and interpretation of data, and drafted and finalized the manuscript; SA: assisted in study design, conducted the laboratory tests for both phases, reviewed statistical analysis of the data, and drafted part of the manuscript. Both authors approved final version of the study.

Corresponding author

Correspondence to Mona Azzam.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Azzam, M., Attalla, S. Serum Folate Levels in Patients with Chronic Hemolytic Anemia on Regular Folic Acid Supplementation Before and After Dose Modification. Indian Pediatr 56, 845–848 (2019). https://doi.org/10.1007/s13312-019-1611-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13312-019-1611-6

Keywords

Search

Navigation