Daily supplementation with 5 mg of folic acid in Brazilian patients with hereditary spherocytosis

Clóvis Paniz, Maylla Rodrigues Lucena, Juliano Felix Bertinato, Felipe Rebello Lourenço, Bruna Cipriano A. Barros, Guilherme Wataru Gomes, Maria Stella Figueiredo, Rodolfo Delfini Cançado, Vera Lúcia Nascimento Blaia-D Avila, Christine M. Pfeiffer, Zia Fazili, Ralph Green, Valdemir Melechco Carvalho, Elvira Maria Guerra-Shinohara

Research output: Contribution to journalArticle

Abstract

Patients with hereditary spherocytosis (HS) have increased rates of erythropoiesis and higher folate requirements. In a case-control study of patients with HS, we evaluated the associations between the use of 5 mg folic acid (FA) daily and serum concentrations of folate, unmetabolized folic acid (UMFA), interleukin (IL)-6, IL-8, IL-10, interferon-γ(IFN- 3) and tumor necrosis factor-α (TNF-α); and mRNA expression of dihydrofolate reductase (DHFR), methylene tetrahydrofolate reductase (MTHFR), IL8, IFNG and TNFA genes. Total serum folate and folate forms were measured in 27 patients with HS (21 users [HS-U] and 6 non-users [HS-NU] of supplemental FA) and 54 healthy controls not consuming 5 mg/day supplemental FA. Each patient was matched to two controls based on age, sex and body mass index. The mononuclear leucocyte mRNA expression of relevant genes and their products were determined. Serum folate, UMFA, 5-methyl-tetrahydrofolate (5-methyl-THF) and tetrahydrofolate (THF) concentrations were significantly higher in HS-U compared with matched healthy controls (p<0.001, n=42). HS-NU had lower serum folate concentrations than matched healthy controls (p=0.044, n=12). HS-U and HS-NU presented similar hematological and biochemical markers profiles. No differences were found between HS-U and HS-NU for cytokine serum concentrations and mRNA expression genes. DHFR mRNA expression was higher in HS-U than in HS-NU. The use of high daily doses of FA for treatment of patients with HS may be excessive and is associated with elevated serum UMFA and elevated DHFR mRNA expression. It is not known whether long-term high-dose FA use by patients with HS might have adverse health effects.

Original languageEnglish (US)
JournalJournal of Investigative Medicine
DOIs
StatePublished - Jan 1 2019

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Hereditary Spherocytosis
Folic Acid
Tetrahydrofolate Dehydrogenase
Messenger RNA
Serum
Interleukin-8
Genes
Mononuclear Leukocytes
Gene Expression
Methylenetetrahydrofolate Reductase (NADPH2)
Erythropoiesis

Keywords

  • cytokines
  • folic acid

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Paniz, C., Lucena, M. R., Bertinato, J. F., Lourenço, F. R., Barros, B. C. A., Gomes, G. W., ... Guerra-Shinohara, E. M. (2019). Daily supplementation with 5 mg of folic acid in Brazilian patients with hereditary spherocytosis. Journal of Investigative Medicine. https://doi.org/10.1136/jim-2019-001025

Daily supplementation with 5 mg of folic acid in Brazilian patients with hereditary spherocytosis. / Paniz, Clóvis; Lucena, Maylla Rodrigues; Bertinato, Juliano Felix; Lourenço, Felipe Rebello; Barros, Bruna Cipriano A.; Gomes, Guilherme Wataru; Figueiredo, Maria Stella; Cançado, Rodolfo Delfini; Blaia-D Avila, Vera Lúcia Nascimento; Pfeiffer, Christine M.; Fazili, Zia; Green, Ralph; Carvalho, Valdemir Melechco; Guerra-Shinohara, Elvira Maria.

In: Journal of Investigative Medicine, 01.01.2019.

Research output: Contribution to journalArticle

Paniz, C, Lucena, MR, Bertinato, JF, Lourenço, FR, Barros, BCA, Gomes, GW, Figueiredo, MS, Cançado, RD, Blaia-D Avila, VLN, Pfeiffer, CM, Fazili, Z, Green, R, Carvalho, VM & Guerra-Shinohara, EM 2019, 'Daily supplementation with 5 mg of folic acid in Brazilian patients with hereditary spherocytosis', Journal of Investigative Medicine. https://doi.org/10.1136/jim-2019-001025
Paniz, Clóvis ; Lucena, Maylla Rodrigues ; Bertinato, Juliano Felix ; Lourenço, Felipe Rebello ; Barros, Bruna Cipriano A. ; Gomes, Guilherme Wataru ; Figueiredo, Maria Stella ; Cançado, Rodolfo Delfini ; Blaia-D Avila, Vera Lúcia Nascimento ; Pfeiffer, Christine M. ; Fazili, Zia ; Green, Ralph ; Carvalho, Valdemir Melechco ; Guerra-Shinohara, Elvira Maria. / Daily supplementation with 5 mg of folic acid in Brazilian patients with hereditary spherocytosis. In: Journal of Investigative Medicine. 2019.
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abstract = "Patients with hereditary spherocytosis (HS) have increased rates of erythropoiesis and higher folate requirements. In a case-control study of patients with HS, we evaluated the associations between the use of 5 mg folic acid (FA) daily and serum concentrations of folate, unmetabolized folic acid (UMFA), interleukin (IL)-6, IL-8, IL-10, interferon-γ(IFN- 3) and tumor necrosis factor-α (TNF-α); and mRNA expression of dihydrofolate reductase (DHFR), methylene tetrahydrofolate reductase (MTHFR), IL8, IFNG and TNFA genes. Total serum folate and folate forms were measured in 27 patients with HS (21 users [HS-U] and 6 non-users [HS-NU] of supplemental FA) and 54 healthy controls not consuming 5 mg/day supplemental FA. Each patient was matched to two controls based on age, sex and body mass index. The mononuclear leucocyte mRNA expression of relevant genes and their products were determined. Serum folate, UMFA, 5-methyl-tetrahydrofolate (5-methyl-THF) and tetrahydrofolate (THF) concentrations were significantly higher in HS-U compared with matched healthy controls (p<0.001, n=42). HS-NU had lower serum folate concentrations than matched healthy controls (p=0.044, n=12). HS-U and HS-NU presented similar hematological and biochemical markers profiles. No differences were found between HS-U and HS-NU for cytokine serum concentrations and mRNA expression genes. DHFR mRNA expression was higher in HS-U than in HS-NU. The use of high daily doses of FA for treatment of patients with HS may be excessive and is associated with elevated serum UMFA and elevated DHFR mRNA expression. It is not known whether long-term high-dose FA use by patients with HS might have adverse health effects.",
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AU - Gomes, Guilherme Wataru

AU - Figueiredo, Maria Stella

AU - Cançado, Rodolfo Delfini

AU - Blaia-D Avila, Vera Lúcia Nascimento

AU - Pfeiffer, Christine M.

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