Influência da suplementação de compostos bioativos na resposta inflamatória em doenças crônicas: revisões sistemáticas e meta-análises de ensaios clínicos randomizados.

Abstract

Currently, there is a growing body of evidence indicating that numerous bioactive compounds, such as omega-3 fatty acids (ω-3 AG) and resveratrol, can directly influence the chronic inflammatory state, commonly observed in several disorders, such as Polycystic Ovary Syndrome (PCOS) and in Alzheimer's Disease (AD), exerting an anti-inflammatory role in these cases. Considering the importance of the dietary pattern in modulating the immune response, it is necessary to compile evidence related to the biological mechanisms of these nutritional compounds in chronic diseases. In addition to the previous hypotheses, the evaluation of the effects of metformin on the levels of hyperandrogenism markers in women with PCOS emerged as a clinical question to be understood during the management of these patients. Therefore, the present study aims to (1) assess whether subclinical inflammation is important in the pathophysiology of PCOS; (2) to investigate the influence of ω-3 AG and resveratrol on markers of inflammation or cognitive score, respectively, in patients with PCOS or AD, and (3) to investigate the influence of metformin use on androgenic markers in PCOS, with the last two items being evaluated through a systematic review of the literature. To this end, four studies were developed – a primary study and three systematic reviews. In relation to the primary study, plasma cytokines were assessed by flow cytometry. On the other hand, systematic reviews were comprised of systematic searches, in databases, by indexed articles, according to the research question of the study. Finally, for the development of the analysis goals, the grouped estimates of the weighted average differences (WMD) and the standardized average differences (SMD) were calculated and the model of random or fixed effects was adopted, to measure the grouped results, according to the primary data obtained. Relative to the primary study, lower levels of tumor necrosis factor (TNF) and decreased ratios of TNF with interleukins (IL) 2, 4 and 6 were observed in PCOS patients compared to the control group (p < 0.05). In the first systematic review, with a goal, a significant change in the analysis of high-sensitivity C-reactive protein (hs-CRP) was evidenced [SMD -0.29 (95% CI -0.56 to -0.02) mg/l] and an increase in adiponectin levels [WMD 1.42 (95% CI 1.09 to 1.76) ng/ml)] in the intervention group ω-3 AG when compared with the placebo group. In the second systematic review, through sensitivity analysis, the Free Androgen Index (FAI) values [SMD: -0.42 (95% CI -0.67 to -0.16) points] and total testosterone levels [SMD: -0.24 (95% CI -0.40 to -0,07) points] were lower in the metformin-treated group when compared to the control group. Finally, in the third systematic review, the findings showed that there are still few studies in humans, but they showed that resveratrol acts by delaying cognitive impairment in AD patients, administered alone or when associated with dextrose and malate. The results suggest an imbalance between pro- and anti-inflammatory cytokines, with production of counterregulatory cytokines in PCOS. Furthermore, that ω-3 AG supplementation could reduce the inflammatory state in women with PCOS, by decreasing hs-CRP and increasing adiponectin levels; and that metformin can be used to improve hyperandrogenism in this group. Finally, resveratrol supplementation appears to influence progressive cognitive and functional decline in AD patients when compared to the placebo group. Furthermore, in relation to systematic reviews, new primary studies with larger samples, longer interventions, standardization of intervention dosage and better methodological quality of clinical trials are suggested to validate the results.