Effect of Brazil nut (Bertholetia excelsa H.B.K.) consumption on selenocompouds in chronic use of statins

Author(s)

Ligia Moriguchi Watanabe

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2020-03-13

Examining board members

Anderson Marliere Navarro; Carla Barbosa Nonino; Mariana Kiomy Osako; Lucia Andreia Seale

• Advisor: Anderson Marliere Navarro

Abstract

Background and aims: Although the mechanisms by which statins promote muscle disorders remain unclear, supplementation with dietary antioxidants may mitigate statins\' side effects. In humans, the individual variation in response to selenium (Se) supplementation may indicate the occurrence of gene variants. Several single nucleotide polymorphisms (SNPs) have been recognized as important sources of inter-individual variations in Se metabolism in response to Se supplementation. In particular, SNPs in GPX1 (encoding GPX1) and SELENOP (encoding SELENOP) have been shown to affect blood selenium or selenoprotein levels in response to supplementation. This study aimed to investigate whether the supplementation with Brazil nuts, a source of dietary Se, could modulate the biomarkers of Se status such as blood Se and GPX activity, and mRNA expression of selenoprotein P (SELENOP), selenoprotein N (SELENON), and GPX. We also verified the influence of Brazil nut supplementation on the control of serum creatine kinase (CK) activity, an indirect marker of muscle damage, of patients in regular use of statins. Moreover, we investigated if nucleotide variations in selenoprotein genes could modulate the response to Brazil nuts in the same study population. Methods: The study was performed in the Ribeirão Preto Medical School University Hospital. Thirty-two patients in regular use of statins received one unit of Brazil nut daily for 3 months. Body composition, blood selenium (Se) concentrations, erythrocyte glutathione peroxidase (GPX) activity, oxidative stress parameters, and CK activity were evaluated before and after Brazil nut supplementation. At first, individuals were divided in groups according to CK activity levels (G1: increased or G2: normal). For the analysis of selenoproteins gene variants, participants were previously genotyped and allocated according to SNPs in GPX1 (rs1050450) and SELENOP (rs3877899 and rs7579) genotypes. Results: Supplementation with one Brazil nut daily for 3 months decreased levels of CK activity in serum, with positive changes in plasma and erythrocyte Se concentrations (p<0.0001), while increasing levels of GPX activity. Regarding oxidative stress, we observed reduced levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in both groups after supplementation. We also found a moderately negative association between CK and GPX activity (r=-41; p<0.02). We did not detect changes in the expression of selenoproteins GPX1, SELENOP, and SELENON after Brazil nut supplementation. The presence of variant alleles rs3877899 and rs7579 for SELENOP modulates response to Se supplementation for blood GPX activity and CK levels. Brazil nut supplementation significantly increased GPX1 mRNA expression only in subjects with CC genotype at rs1050450 in the GPX1 gene. SELENOP mRNA expression was significantly lower in subjects with GG genotype of rs7579, both before and after supplementation. Conclusion: Brazil nut consumption improved the control of CK activity, as well as oxidative stress biomarkers in patients using statins but did not modulate the mRNA expression of selenoproteins. Furthermore, our findings indicated that selenoprotein gene variations modulate the response of GPX activity and CK levels to Brazil nut supplementation. We also demonstrated that selenoprotein polymorphisms lead to different responses in mRNA expression of selenoproteins following Se supplementation with Brazil nut. (AU)

• FAPESP's process: 16/05677-7 - Effect of brazil nut (Bertholetia excelsa H.B.K.) consumption on selenocompouds in chronic use of statins
• Grantee: Lígia Moriguchi Watanabe
• Support Opportunities: Scholarships in Brazil - Doctorate