SEPP1 polymorphisms modulate serum glucose and lipid response to Brazil nut supplementation

  • Janaina L. S. Donadio
  • Marcelo M. Rogero
  • Elvira M. Guerra-Shinohara
  • Charles Desmarchelier
  • Patrick Borel
  • Silvia M. F. Cozzolino
Original Contribution



The consumption of Brazil nuts has been associated with benefits to lipid metabolism and reductions in total cholesterol and LDL concentrations. They are the richest natural source of selenium which has essential functions in human physiology. Genetic polymorphisms in Selenoprotein P could impair lipid and glucose metabolisms. The aim of this work was to verify the influence of polymorphisms in genes for selenoproteins on blood lipid levels after dietary supplementation with Brazil nuts in healthy adults.


The study included 130 healthy volunteers selected at the University of São Paulo, Brazil. They were supplemented with one nut a day for 8 weeks, followed by 8 weeks without intervention. The following analyses were performed: anthropometric measurements, serum fasting glucose, lipid profile, C-reactive protein and plasma MDA levels. The volunteers were genotyped for SNPs rs1050450, rs3811699, rs1800699, rs713041, rs3877899, rs7579, rs34713741, and rs5845 in genes for selenoproteins.


The concentrations of total cholesterol and fasting glucose levels decreased after 8 weeks of supplementation (p < 0.05). Glucose levels were modulated by rs3877899 in SEPP1, with significantly lower levels observed for individuals with the GA + AA genotype (p = 0.025). In addition, rs7579 was associated with cholesterol concentrations, which were significantly lower for individuals with the GG genotype (p = 0.053).


Supplementation with one Brazil nut a day for 8 weeks reduced total cholesterol and glucose levels. Furthermore, our results suggest that rs3877899 might be associated with glucose concentrations and rs7579 with cholesterol concentrations. Therefore, the effect of genetic variations should be considered in future nutritional interventions evaluating the response to Brazil nut supplementation.


Brazil nuts Lipid profile Polymorphisms Nutrigenetics 



The authors are grateful to the Sao Paulo Research Foundation (FAPESP process: 2011/17720-0) for the scholarship and the financial support provided for this study. The authors are also very grateful to all volunteers who took part in this study. J.L.S.D., M.M.R. and S.M.F.C. conceived and designed the study; J.L.S.D. was responsible for generation, collection, assembly, analysis and interpretation of data; J.L.S.D, C.D. and E.M.G.S. performed the statistical analysis. J.L.S.D. wrote the manuscript, and P.B., S.M.F.C and M.M.R. revised the manuscript. All the authors approved the final version of the manuscript before submission.

Compliance with ethical standards

Conflict of interest

There are no actual or potential conflicts of interest that might influence judgment on the part of any author.


  1. 1.
    Sabaté J, Ang Y (2009) Nuts and health outcomes: new epidemiologic evidence. Am J Clin Nutr 89:1643S–1648S. doi: 10.3945/ajcn.2009.26736Q.Am CrossRefGoogle Scholar
  2. 2.
    Jiang R, Jacobs DR, Mayer-Davis E et al (2006) Nut and seed consumption and inflammatory markers in the Multi-Ethnic Study of Atherosclerosis. Am J Epidemiol 163:222–231. doi: 10.1093/aje/kwj033 CrossRefGoogle Scholar
  3. 3.
    O’Neil CE, Fulgoni VL, Nicklas TA (2015) Tree nut consumption is associated with better adiposity measures and cardiovascular and metabolic syndrome health risk factors in US adults: NHANES 2005–2010. Nutr J 14:64–71. doi: 10.1080/07315724.2011.10719996 CrossRefGoogle Scholar
  4. 4.
    Mukuddem-Petersen J, Oosthuizen W, Jerling JC (2005) A systematic review of the effects of nuts on blood lipid profiles in humans. J Nutr 135:2082–2089Google Scholar
  5. 5.
    Welna M, Klimpel M, Zyrnicki W (2008) Investigation of major and trace elements and their distributions between lipid and non-lipid fractions in Brazil nuts by inductively coupled plasma atomic optical spectrometry. Food Chem 111:1012–1015. doi: 10.1016/j.foodchem.2008.04.067 CrossRefGoogle Scholar
  6. 6.
    Segura R, Javierre C, Lizarraga MA, Ros E (2006) Other relevant components of nuts: phytosterols, folate and minerals. Br J Nutr 96(Suppl 2):S36–S44. doi: 10.1017/BJN20061862 CrossRefGoogle Scholar
  7. 7.
    Bao Y, Han J, Hu FB et al (2013) Association of nut consumption with total and cause-specific mortality. N Engl J Med 369:2001–2011. doi: 10.1056/NEJMoa1307352 CrossRefGoogle Scholar
  8. 8.
    Cominetti C, de Bortoli MC, Garrido AB, Cozzolino SMF (2012) Brazilian nut consumption improves selenium status and glutathione peroxidase activity and reduces atherogenic risk in obese women. Nutr Res 32:403–407. doi: 10.1016/j.nutres.2012.05.005 CrossRefGoogle Scholar
  9. 9.
    Colpo E, Vilanova CDDA, Brenner Reetz LG et al (2013) A single consumption of high amounts of the Brazil nuts improves lipid profile of healthy volunteers. J Nutr Metab. doi: 10.1155/2013/653185 Google Scholar
  10. 10.
    Maranhão PA, Kraemer-Aguiar LG, de Oliveira CL et al (2011) Brazil nuts intake improves lipid profile, oxidative stress and microvascular function in obese adolescents: a randomized controlled trial. Nutr Metab (Lond) 8:32. doi: 10.1186/1743-7075-8-32 CrossRefGoogle Scholar
  11. 11.
    Strunz CC, Oliveira TV, Vinagre JCM et al (2008) Brazil nut ingestion increased plasma selenium but had minimal effects on lipids, apolipoproteins, and high-density lipoprotein function in human subjects. Nutr Res 28:151–155. doi: 10.1016/j.nutres.2008.01.004 CrossRefGoogle Scholar
  12. 12.
    Thomson CD, Chisholm A, Mclachlan SK, Campbell JM (2008) Brazil nuts: an effective way to improve selenium status. Am J Clin Nutr 87:379–384Google Scholar
  13. 13.
    Rayman MP (2012) Selenium and human health. Lancet 379:1256–1268. doi: 10.1016/S0140-6736(11)61452-9 CrossRefGoogle Scholar
  14. 14.
    Hatfield DL, Gladyshev VN (2002) How selenium has altered our understanding of the genetic code. Mol Cell Biol 22:3565–3576. doi: 10.1128/MCB.22.11.3565 CrossRefGoogle Scholar
  15. 15.
    Burk RF, Hill KE (2005) Selenoprotein P: an extracellular protein with unique physical characteristics and a role in selenium homeostasis. Annu Rev Nutr 25:215–235. doi: 10.1146/annurev.nutr.24.012003.132120 CrossRefGoogle Scholar
  16. 16.
    Yang SJ, Hwang SY, Choi HY et al (2011) Serum selenoprotein P levels in patients with type 2 diabetes and prediabetes: implications for insulin resistance, inflammation, and atherosclerosis. J Clin Endocrinol Metab 96:1325–1329. doi: 10.1210/jc.2011-0620 CrossRefGoogle Scholar
  17. 17.
    Misu H, Takamura T, Takayama H et al (2010) A liver-derived secretory protein, selenoprotein P, causes insulin resistance. Cell Metab 12:483–495. doi: 10.1016/j.cmet.2010.09.015 CrossRefGoogle Scholar
  18. 18.
    Steinbrenner H (2013) Interference of selenium and selenoproteins with the insulin-regulated carbohydrate and lipid metabolism. Free Radic Biol Med 65:1538–1547. doi: 10.1016/j.freeradbiomed.2013.07.016 CrossRefGoogle Scholar
  19. 19.
    Kryukov GV, Castellano S, Novoselov SV et al (2003) Characterization of mammalian selenoproteomes. Science 300:1439–1443. doi: 10.1126/science.1083516 CrossRefGoogle Scholar
  20. 20.
    Méplan C, Crosley LK, Nicol F et al (2007) Genetic polymorphisms in the human selenoprotein P gene determine the response of selenoprotein markers to selenium supplementation in a gender-specific manner (the SELGEN study). FASEB J 21:3063–3074. doi: 10.1096/fj.07-8166com CrossRefGoogle Scholar
  21. 21.
    AOAC Association of Official Analytical Chemists (1990) Official methods of analysis, 15th ed. WashingtonGoogle Scholar
  22. 22.
    Carvalho RF, Huguenin GVB, Luiz RR et al (2015) Intake of partially defatted Brazil nut flour reduces serum cholesterol in hypercholesterolemic patients- a randomized controlled trial. Nutr J 14:59. doi: 10.1186/s12937-015-0036-x CrossRefGoogle Scholar
  23. 23.
    Bleys J, Navas-Acien A, Guallar E (2008) Serum selenium levels and all-cause, cancer, and cardiovascular mortality among US adults. Arch Intern Med 168:404–410. doi: 10.1001/archinternmed.2007.74 CrossRefGoogle Scholar
  24. 24.
    Hatfield DL, Gladyshev VN (2009) The Outcome of Selenium and Vitamin E Cancer Prevention Trial (SELECT) reveals the need for better understanding of selenium biology. Mol Interv 9:18–21. doi: 10.1124/mi.9.1.6 CrossRefGoogle Scholar
  25. 25.
    Ryan E, Galvin K, O’Connor TP et al (2006) Fatty acid profile, tocopherol, squalene and phytosterol content of brazil, pecan, pine, pistachio and cashew nuts. Int J Food Sci Nutr 57:219–228. doi: 10.1080/09637480600768077 CrossRefGoogle Scholar
  26. 26.
    Moosmann B, Behl C (2004) Selenoproteins, cholesterol-lowering drugs, and the consequences: revisiting of the mevalonate pathway. Trends Cardiovasc Med 14:273–281. doi: 10.1016/j.tcm.2004.08.003 CrossRefGoogle Scholar
  27. 27.
    Rayman MP, Stranges S, Griffin BA et al (2011) Effect of supplementation with high-selenium yeast on plasma lipids. Ann Intern Med 154:656–665CrossRefGoogle Scholar
  28. 28.
    Schomburg L, Schweizer U (2009) Hierarchical regulation of selenoprotein expression and sex-specific effects of selenium. Biochim Biophys Acta 1790:1453–1462. doi: 10.1016/j.bbagen.2009.03.015 CrossRefGoogle Scholar
  29. 29.
    Vunta H, Davis F, Palempalli UD et al (2007) The anti-inflammatory effects of selenium are mediated through 15-deoxy-delta 12,14-prostaglandin J2 in macrophages. J Biol Chem 282:17964–17973. doi: 10.1074/jbc.M703075200 CrossRefGoogle Scholar
  30. 30.
    Klopotek A, Hirche F, Eder K (2006) PPAR gamma ligand troglitazone lowers cholesterol synthesis in HepG2 and Caco-2 cells via a reduced concentration of nuclear SREBP-2. Exp Biol Med 231:1365–1372Google Scholar
  31. 31.
    Sengupta A, Carlson BA, Hoffman VJ et al (2008) Loss of housekeeping selenoprotein expression in mouse liver modulates lipoprotein metabolism. Biochem Biophys Res Commun 365:446–452. doi: 10.1038/jid.2014.371 CrossRefGoogle Scholar
  32. 32.
    Viguiliouk E, Kendall CWC, Blanco Mejia S et al (2014) Effect of tree nuts on glycemic control in diabetes: a systematic review and meta-analysis of randomized controlled dietary trials. PLoS One 9:e103376. doi: 10.1371/journal.pone.0103376 CrossRefGoogle Scholar
  33. 33.
    Mao J, Teng W (2013) The relationship between selenoprotein P and glucose metabolism in experimental studies. Nutrients 5:1937–1948. doi: 10.3390/nu5061937 CrossRefGoogle Scholar
  34. 34.
    Burk RF, Hill KE (2009) Selenoprotein P-expression, functions, and roles in mammals. Biochim Biophys Acta Gen Subj 1790:1441–1447. doi: 10.1016/j.bbagen.2009.03.026 CrossRefGoogle Scholar
  35. 35.
    Steinbrenner H, Hotze AL, Speckmann B et al (2013) Localization and regulation of pancreatic selenoprotein P. J Mol Endocrinol 50:31–42. doi: 10.1530/JME-12-0105 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Department of Food and Experimental Nutrition, Faculty of Pharmaceutical SciencesUniversity of São PauloSão PauloBrazil
  2. 2.Department of Nutrition, School of Public HealthUniversity of São PauloSão PauloBrazil
  3. 3.Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical SciencesUniversity of São PauloSão PauloBrazil
  4. 4.NORT, Aix-Marseille Université, INRA (French National Institute for Agricultural Research), INSERM13005France

Personalised recommendations