Discussion
To our knowledge, the efficacy of soy protein and soy products has not been distinctly established for adipocytokines concentration; therefore, this systematic review and meta-analysis provided insight into the potential advantages conferred by such supplementation to allow healthy and unhealthy people to make informed decisions on their usage. This meta analysis suggests that soy protein supplementation have a meaningful effect on plasma levels of adiponectin; however, pooled effect size were not significant for leptin concentration.
The soy protein beneficial effects on traditional CVD risk factors, blood pressure and primarily lipids, has been demonstrated previously40,41. The evidence for a dietary protein intake association on novel CVD risk factors is less conclusive. A high adiponectin concentration is related to insulin sensitivity and decreased risk for CVDs. Adiponectin is also an independent marker of risk for metabolic syndrome in patients with type 2 diabetes 42. Generally, serum adiponectin concentration are decreased in diabetes type-2 and obesity and this is considered to be of etiological importance in causing insulin resistance5. Therefore, any measure that increases adiponectin concentration would be predicted to improve insulin resistance. Contrary to adiponectin, reduced plasma leptin levels are positively correlated with parameters of overall obesity and CVDs 43. Leptin is secreted exclusively by adipocytes, and this secretion is regulated by the size of fat stores both in pathophysiological and in physiological states44. This protein provides the brain with information about the body’s fat deposits. This acts as a feedback mechanism that can function as a lipostat45 via control of satiety, energy expenditure, and other neuroendocrine functions46. Because of all of these pathological conditions, it is important to design strategies to reduce leptin levels.
Despite the heterogeneity of the data, our meta analysis showed that serum adiponectin concentration increased in participant taking isoflavones compared to placebo. However, performed subgroup analysis based on sex, baseline BMI, dose, duration, type of supplementation and study design were did not showed any significant effect of soy and soy product supplementation on adiponectin serum level. We found that soy protein supplementation resulted in no significant reduction in leptin concentration, but we observed a significant increase in leptin concentration in studies that used more than 20 g/day soy protein compared with control group. The observed increase in plasma leptin was not documented in any of studies, but in two studies,26,27intervention of soy protein supplement resulted in lower leptin reduction compared with control group. Deibert et al.26 have used lifestyle change group as control group that attended 6 weekly teaching sessions about nutrition and physical exercise. Also, Llanos et al,27 have designed interventions included 10 weeks of consumption of a tomato-based diet and 10 weeks of consumption of a soy-based diet. Although these two studies have used more than 20 g/day soy protein, but may distorted the results, because control group of these studies resulted more reduction of leptin concentration compared with soy-based diet. As well as, studies that used less than 20 g/day soy protein had a trend toward decreased circulating leptin with the soy supplement compared to placebo (p = 0.056). Due to standard method and strategy of supplementation in these studies, this result is more reliable.
To our knowledge, interactions between adiponectin and estrogens have not yet been fully characterized. Higher concentrations of adiponectin in women than in men of comparable BMI and age suggest that estrogens might have a stimulatory effect on adipocytes production adiponectin47,48. The use of soy products clearly appears to be beneficial from a viewpoint of cardiovascular disease, leastways in part, because of the actions of isoflavones which resemble estrogen effect49. Because of these effects, 7 studies that included in this meta analysis conducted trial on postmenopausal women and hypothesized that adipocytokines concentration in postmenopausal women using soy protein could be higher than in women without soy protein using15,16,20,25,27,36,37. Wide array of both in vivo and in vitro studies done by investigators showing an effect of estrogens on adipocyte for adipocytokines production. They concluded that adiponectin concentrations in postmenopausal women using estrogens could be higher than in women without hormone replacement therapy50,51. Also, Casabiell et al. found what appeared to be a direct estradiol effect to stimulate leptin production in a tissue organ culture52. In fact, isoflavones of soy are relatively potent agonists of the β-of estrogen receptor isoform, and its effects on adipocyte function and differentiation have been reported53, and we conclude soy protein effects on adipocytokines is due to estrogen-like probable actions of isoflavones.
Many studies have showed that soy isoflavones have multiple biological functions and may help to restore adiponectin expression. Soy isoflavones (Both genistein and daidzein) significantly inhibited the TNF-ɑ mediated downregulation of adiponectin expression in adipocytes. Some possible molecular mechanisms are that these active components (I) inhibit the TNF- ɑ mediated JNK signaling pathway involved in adiponectin expression, or (II) inhibit the TNF- ɑ mediated downregulation of FoxO1, which is involved in adiponectin expression, (III) function as PPARγ agonists and increase the transcriptional activity of PPARγ, which ultimately leads to the inhibition of the TNF- ɑ mediated downregulation of adiponectin expression54. Also, high dosage of soy isoflavones may enhance circulating leptin level in insulin resistant rats by elevating the efficiency of translating leptin mRNA into leptin protein 55.
The strengths of our study is that we considered all published clinical trials conducted on the effect of soy protein supplementation on adipocytokines. In addition, we considered all RCTs which were done on individuals with different health conditions. Also different study designs and the lack of controlling for baseline measures in some studies should be taken into account. Moreover, many factors can affect the high heterogeneity and the inconclusive findings stated different manufacturers of soy protein and variations in soy protein classifications between countries may contribute to the inconsistencies in results.