IJCS | Volume 32, Nº2, May/June 2019

280 Silva et al. Nuts and cardiovascular diseases Int J Cardiovasc Sci. 2019;32(3)274-282 Review Article not reduce significantly. Plasma selenium significantly increased after the ingestion of 5, 20 and 50 g of nuts, but its concentrations were not significantly different between the different levels of ingestion. The levels of inflammatory biomarkers IL-1, IL-6, tumor necrosis factor- alpha (TNF- α ) and interferon gamma (IFN- γ ) significantly decrease and the levels of IL-10 significantly increased after the ingestion of 20 or 50 g of nuts. Other inflammatory and oxidative stress biomarkers, such as C-reactive protein, erythrocyte glutathione peroxidase activity, DNAdamage and δ -aminolevulinate dehydratase activity, did not show significantly results. 23,28 Obese female adolescents were also evaluated after consumption of 15 to 25 gBrazil nuts dailyduring 16weeks and compared with a placebo group (PG). The authors showed a significant reduction of TC, LDL-c and TG in the Brazil nuts group (BNG). Concerning the antioxidant capacity biomarkers, the oxidized LDL (LDL-ox) levels significantly decrease in BNG compared to PG after the supplementation. Plasma selenium and red blood cell velocity (RBCV), a marker of microvascular function, showed a significant increase after the supplementation, demonstrating the positive effect of Brazil nuts on lipid profile and microvascular function in this population. 29 Similar results were described in a study with obese women; the consumption of one Brazil nut per day for 8 weeks, significantly increased HDL-c and decreased AR index, calculated through Castelli I and II indexes. Besides, a significant increase by 138% in plasma selenium status, and 46% in GPx activity were found after the consumption of Brazil nuts. 30 In studies with hemodialysis patients, after 3 months of supplementation with one Brazil nut/day, there was a significant decrease in LDL-c and AR index, Castelli I and Castelli II, as well as an expressive increase in HDL-c. However, no significant changes were found in total cholesterol and TG levels. There was also a significant increase in plasma selenium and GPx activity. Regarding the oxidative DNA damage and lipid peroxidation, 8-hydroxy-2-deoxyguanosine (8- OHdG), malonilaldehyde (MDA) and 8-isoprostane showed a significant decrease, as well the inflammatory markers, IL-6, TNF α , CRP, and factor nuclear kappa B (Nf- κ B) an important regulator of the transcription factor. Subsequently the authors evaluated the nuclear factor erythroid 2-related factor 2 (Nfr2), which plays an important role in the activation of several pathways against cellular oxidative stress and NAD(P)H:quinone oxide reductase 1 (NQO1), and phase II detoxifying enzymes, which also decreased significantly after the supplementation. 31-34 It’s important to highlight, in this case, that most patients had selenium deficiency before the supplementation, which was reversed after the consumption of one Brazil nut per day. Hypertensive and dyslipidemic patients were also studied after the supplementation of 13 g/day of granulated Brazil nut for three months. The results showed a significant increase in selenium plasma, GPx activity and decrease in LDL-ox. 35 The microvascular endothelial function was also assessed, showing a significant increase in nitric oxide, with no change in systemic microvascular reactivity or density. 36 Concerning the lipid profile, total cholesterol and apolipoprotein A1 (Apo A1) significantly decrease compared with pre-supplementation. 37 Other studies evaluating Brazil nut supplementation were described in the review from Cardoso et al. 38 A study conducted with children that received 15 to 30 g (3 to 6 units) of Brazil nuts three days per week showed a significant excess of selenium intake, combined with high levels of selenium in plasma, erythrocytes, urine, hair and nails, with no signs of selenosis, though. 39 Another study involved older patients with mild cognitive impairment, and after the supplementation of one Brazil nut during six months, it was observed an improvement in selenium status, with a significant increase in plasma, erythrocyte and GPx activity, as well as an improvement in performance in cognitive tests. 40 The potential effect of Brazil nut regarding the development of colorectal cancer was also investigated, and after the supplementation of six nuts for six weeks, the selenium levels increased in plasmawith upregulated expression of genes associated with selenoproteins (SePP) and decreased rectal gene expression of β -catenin, biomarkers related to colorectal oncogenesis. 41 As previously discussed, Brazil nut consumption is effective in improving lipid profile, and inflammatory and oxidative stress biomarkers in different populations, including healthy subjects, obese women, and hemodialysis patients. This review showed the vast benefits of the consumption of nuts on cardiovascular risk factors and drew attention to the lack of studies showing the effects of Brazil nuts in this regard. Conclusion The nutritional composition of nuts, abundant in unsaturated fatty acids, antioxidant minerals and