Adiponectin, visfatin, resistin, and bone-ALP blood levels through the study. *P < 0.05 versus basal; § P < 0.05 versus placebo.
The intra-group analysis revealed that only HDL-C and adiponectin were not affected by NRT treatment at the end of the 6 months, while all the other studied variables were significantly changed from basal values ( and Figures and ). In the placebo group after 6 months a significant difference from basal values was observed for triglycerides and adiponectin, probably due to diet, despite no changes in BMI were noted in the enrolled subjects ( and Figures and ).
4. Discussion
The results of this study demonstrate a protective effect on cardiovascular markers following 6 months administration of a combination of myo-inositol, soy isoflavones, and cocoa polyphenols, in postmenopausal women with metabolic syndrome.
A limit of this study is the number of women enrolled, which reduced the statistical significance of the outcomes; in spite of all that, some interesting results have been obtained. One of these was the persistence, in the six months follow-up period, of the positive results achieved during the six-month treatment period; this data concerns all the markers studied. No differences were highlighted in BMI and waist circumference between and within groups, but this may be due to the short treatment period and somewhat to the low adherence to diet. In the treated group, serum glucose and triglycerides values significantly decreased after six months, maintaining in the subsequent 6 months a significant difference from basal levels. These results are in accordance with other studies, in which each component of the supplement of this trial was used [10, 14, 16][10][14][15]. No difference in HDL-C was shown either between groups or from 6-month to basal values; this data is confirmed by some studies in which only cocoa polyphenols were used [5[5][16], 17], but not by others [10[10][14][15], 14, 16], in which a significant difference compared to control group was shown, when each single component of the supplement studied was used. Blood pressure didn't significantly change through the study period, although significant differences were highlighted in other studies in which either myo-inositol or cocoa polyphenols were used [6, 10][6][10]; probably the limited number of women studied has negatively influenced this outcome. More interesting were the data about biomarkers which usually depend on insulin resistance. In particular, serum adiponectin levels were significantly increased, after 12 months, in the treated group compared to the control group and also increased at 12 months from basal values in the same group. This result is in accordance with a recent study of our group where genistein aglycone was used [14]. Adiponectin is an adipocyte-specific, secreted protein that sensitizes the liver and muscle to the action of insulin [18][17]. It is the only adipocyte-derived hormone to be downregulated in the insulin-resistant state, so the levels of adiponectin strongly correlate with basal insulin levels and insulin sensitivity [19][18]. This explains why low concentrations of adiponectin are associated with increased prevalence of metabolic syndrome, especially in postmenopausal women [20][19]. If an improvement of insulin resistance is expeceted using isoflavones, because they act through estrogen receptors; or myo-inositol, because of its insulin-like effect [10, 11][10][11]; an insulin sensitizing effect is not yet clear for cocoa polyphenols. According to Grassi and coworkers [21][20], a possible explanation might be found in the positive effect that cocoa extracts have on endothelium-dependent relaxation; in fact, since insulin sensitivity may be in part considered dependent on NO availability, cocoa polyphenols may improve NO production and insulin sensitivity as a consequence [22][21]. For resistin and visfatin a significant difference occurred only in the treated group, in which both markers were significantly reduced after 6 months of supplement assumption, reaching a plateau until the 12th month. Resistin, is a peptide hormone produced by adipocytes that is more highly expressed in omental and abdominal subcutaneous white fat [23][22]. In postmenopausal, and in obese women, resistin levels nearly double, representing the hormone that links obesity to diabetes [24][23]; in addition, a close association of resistin to metabolic syndrome has been recently established [25][24]. Visfatin role is controversial, but recent evidences have shown increased serum levels in overweight/obese, type-2 diabetics, metabolic syndrome, and CVD patients [26][25]. Kim and coworkers [27][26] have suggested that visfatin may act as the underlying pathophysiological trigger for metabolic syndrome in postmenopausal women and as a marker of abdominal fat deposition and tissue inflammation. The here reported significant reduction in visfatin values, is in agreement with our recent findings in postmenopausal women with metabolic syndrome taking the isoflavone genistein for 12 months [14]. Among the biomarkers evaluated, bone-ALP was also included. This molecule is synthesized by the osteoblasts and it is considered a specific marker of bone formation [28][27]. In this study, the group receiving the combination formula showed increased levels of bone-ALP over time, with significant differences compared to the placebo group after 12 months and a significant difference with respect to basal values. This result is in accordance with a previous study [29][28], showing that 54 mg of genistein improved bone turnover, prevented osteoporosis, and increased bone mass density in postmenopausal osteopenic women. Thus, we may hypothesize that probably isoflavones have determined an improvement in bone turnover; however, an experimental study [30][29] has shown that also myo-inositol is essential for osteogenesis and bone formation.
In conclusion, the supplement used in this study has shown to improve most of the biomarkers linked to metabolic syndrome, suggesting a possible reduction of CVD risk. Furthermore, this study has shown that the positive effects of the supplement may last in the subsequent six months, together with an increase in bone formation. Further studies are warranted to reproduce the present data in a larger cohort of postmenopausal women with metabolic syndrome.
Acknowledgments
This work has been supported by departmental funding.
Conflict of Interests
The authors declare that there is no conflict of interests regarding the publication of this paper.
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