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

Author(s):Show less -

Paniz, Clovis ^[1] ; Lucena, Maylla Rodrigues ^[2] ; Bertinato, Juliano Felix ^[1] ; Lourenco, Felipe Rebello ^[3] ; Barros, Bruna Cipriano A. ^[2] ; Gomes, Guilherme Wataru ^[1] ; Figueiredo, Maria Stella ^[2] ; Cancado, Rodolfo Delfini ^[4] ; Nascimento Blaia-D Avila, Vera Lucia ^[5] ; Pfeiffer, Christine M. ^[6] ; Fazili, Zia ^[6] ; Green, Ralph ^[7] ; Carvalho, Valdemir Melechco ^[8] ; Guerra-Shinohara, Elvira Maria ^{[2, 1]}

Affiliation

^[1] Univ Sao Paulo, Anal Clin & Toxicol, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Fed Sao Paulo, Disciplina Hematol & Hemoterapia, Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Farm, Sao Paulo, SP - Brazil

^[4] Fac Med Santa Casa Sao Paulo, Secao Hematol & Oncol, Sao Paulo, SP - Brazil

^[5] Pontificia Univ Catolica Sao Paulo, Div Hematol, Sorocaba - Brazil

^[6] CDC, Natl Ctr Environm Hlth, Atlanta, GA 30333 - USA

^[7] Univ Calif Davis, Sch Med, Pathol & Lab Med, Sacramento, CA - USA

^[8] Grp Fleury, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF INVESTIGATIVE MEDICINE; v. 67, n. 8, p. 1110-1117, DEC 2019.
• Web of Science Citations: 0

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-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha); 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. (AU)

• FAPESP's process: 12/12912-1 - Effects of unmetabolized folic acid on global DNA methylation, mRNA expression and NK cells cytotoxicity in individuals exposed to mandatory fortification with folic acid and / or therapeutic use of this vitamin
• Grantee: Elvira Maria Guerra Shinohara
• Support Opportunities: Regular Research Grants