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.