Role of soy in metabolic syndrome

The metabolic syndrome is a clustering of metabolic abnormalities including central obesity, insulin resistance and hyperglycemia, dyslipidemia and hypertension (1, 2). Existing data suggest that the incidence of the metabolic syndrome is rising at an alarming rate both in developing and developed countries (3-6). The etiology of this syndrome is largely unknown; genetic, metabolic and environmental factors, including diet, are thought to play a major role (7). Consumption of unsaturated fatty acids (8), omega-3 fatty acids (9), dairy products (10), and whole grains (11) appeared to influence the prevalence of this syndrome, either positively or negatively. Diets with high amounts of vegetables, fruits, legumes, whole grains, low-fat dairy foods, and low amounts of saturated fat and salt had also therapeutic effects in this syndrome (12-15). Foods that improve insulin sensitivity might also modulate the metabolic abnormalities linked with insulin resistance (16). 

Role of soy in Diabetes

Diabetes is one of the major causes of morbidity and mortality in both developed and developing world. Individuals with diabetes are at increased risk of developing heart disease, hypertension, nervous system disorders, blindness and kidney dysfunction (17). Prevalence of diabetes among adults aged 20 to 74 y increased from 5.08% in 1976-1980 to 8.83% in 1999-2004 worldwide (18). Genetic, metabolic and environmental factors, including diet, are thought to play a key role in the etiology of this disease (19-20). Numerous studies have assessed the effects of dietary intakes on glycemic control and insulin resistance in type 2 diabetes (21-24). Soy, as a component of the diet, has received considerable attention in this regard. Several studies have reported the beneficial effects of soy consumption on insulin resistance and glycemic control (18,25-27); however, the exact mechanism remains unknown. Possible suggested mechanisms include a tyrosine kinase inhibitory action, changes in insulin receptor numbers and affinity, intracellular phosphorylation and alterations in glucose transport (28). 

Studies in diabetic rats showed that soy intake could reduce plasma glucose levels, increase first-phase insulin, reduce glucagons (29-31) and improve intra-arterial glucose tolerance test (32). It is also demonstrated that soy protein consumption reduces hyperinsulinemia by stimulating insulin secretion to a lower extent. Furthermore, lower insulin levels and pancreatic islet area were found in soy protein fed rats as compared to rats fed the casein diet (33).

Published clinical trials have indicated that soy protein consumption favorably alters insulin resistance, glycemic control, and serum lipoproteins in postmenopausal women with type 2 diabetes (16).

Recently, our group performed a 4-year randomized controlled clinical trial among 41 type 2 diabetic patients with nephropathy who were free of any uncontrolled condition or other renal diseases. Patients in the control group followed a usual nephropathy diet (0.8 g protein/kg body weight as 70% animal and 30% vegetable proteins) and those in the soy protein group consumed a similar diet containing 35% soy protein, 35% animal protein and 30% vegetable protein. The results showed a significant improvement in glycemic control in the soy protein group (Ptime=0.03, Pgroup=0.01, Ptime*group=0.02) (Data not published yet).

Findings from our clinical trial in postmenopausal women with the metabolic syndrome (related to insulin resistance):

We demonstrated a significant decrease in the homeostasis model assessment-insulin resistance (HOMA-IR) score after soynut consumption as compared to soy protein (difference in percent change: -7.4±0.8; P<0.01) or control diets (difference in percent change: -12.9±0.9; P<0.01) in a randomized cross-over clinical trial among 42 postmenopausal women with the metabolic syndrome.

Three kinds of diets were administered in the study: 1) the control diet was a DASH diet (Dietary Approach to Stop Hypertension). The general recommendation for macronutrient composition of the DASH diet was: carbohydrates 50-60%; protein 15-20% and total fat <30% of total energy intake. This diet had one serving of red meat and was rich in fruits, vegetables, whole grains, low-fat dairy products, and low in saturated fat, total fat, cholesterol, refined grains and sweets. The amount of Na intake was 2400 mg per day. We prescribed little added salt during cooking (only 1 teaspoon) and no table salt; 2) diet with soynut: This diet was the same as the control diet but we replaced red meat by soynut. Every 30 grams of soynut was considered as 1 serving of red meat; 3) diet with soy protein: This diet was the same as the control diet but we replaced red meat by soy protein. Every 30 grams of soy protein was considered as 1 serving of red meat.

In Table 1 we have provided the means of fasting plasma glucose, HOMA-IR, fasting serum insulin and C-peptide levels at baseline and after each period of this cross-over trial.

There are significant differences in the fasting plasma glucose (P<0.01), fasting serum insulin (P<0.01) and C-peptide levels (P<0.01) for the three periods of the trial. Furthermore, soynut could reduce all the mentioned glycemic indices more than the soy protein diet or control diet. It is not exactly clear which component of soy protein or soynut is responsible for its beneficial effects. The hypothesis that soy isoflavones modulate glycemic control has not been approved yet. We assume that higher levels of isoflavones in combination with polyunsaturated fatty acids, pinitol and protein content of soynut might influence glycemic control together. However, the effects of other components of soy like soluble fiber content and inositol-derived substances should be taken into account; despite the fact that the amount and kind of these components may vary in different soy products (25).

Some reports have found no significant effect of soy protein intake on glycemic control. For instance, a daily supplement of soy protein did not affect insulin secretion in postmenopausal women in a randomized, double-blind, placebo-controlled 3-month trial (34). Others have also reported the same findings (26). It must be kept in mind that participants in different studies are not in the same range of bodyweight. Soy protein consumption seems to influence glycemic control and insulin resistance more efficiently among obese subjects than among normal weight ones. Most available studies have concluded that soy consumption might have a positive role in the control of the hyperglycemia and insulin resistance.   

Role of soy in the metabolic syndrome

Obesity, which is associated with hyperinsulinemia, insulin resistance, and other metabolic abnormalities, is growing rapidly in both developing and developed countries (35). This heterogeneous disease is the result of interaction between genetic and environmental factors, especially the diet (36). Among nutrients, an important role has been postulated for protein intake in the pathogenesis of obesity. Protein intake can induce higher satiating and thermogenic effects as compared to other macronutrients (37). Findings from well-designed clinical trials demonstrated that high protein diets are the most effective ones in weight reduction (38-39). Besides the amount of protein, the source of protein is also important. Consumption of plant-based proteins, such as soy protein, has been suggested to suppress food intake, increase satiety and reduce body fat gain. Different experimental studies have shown the beneficial effects of soy protein in this regard (40-41) but the results of clinical trials are not consistent. This inconsistency might be attributed to differences in design of the studies or the different composition of the diet consumed in trials (42). A clinical trial by Anderson et al (43) showed that soy meal replacement use, as part of a low-energy diet, resulted in slightly, but not significantly, greater loss in weight and waist circumference over a 12-week period than milk meal replacement use (43). In another randomized controlled trial of a low calorie soy-based meal replacement program, 100 obese subjects were randomized to consume either soy meal replacement treatment diet (240 g/day, 1200 kcal/day) or control diet for the duration of 12 weeks. Results showed that the soy-based meal replacement formula group lost more weight and had significantly greater reductions in body fat mass as compared to the control group (44). Others have found that weight reduction is similar comparing soy and casein groups (45). Deibert et al (46) suggested that a diet with high soy protein and low fat content could reduce weight and fat mass in overweight and obese subjects. Finally, a recent study showed that soymilk is as effective as skimmed milk in promoting weight loss (47) so the authors concluded that to optimize the weight loss effects of calcium; one can consume 720 mL of either soymilk or skimmed milk daily (47). However, it should be kept in mind that soy protein contains not only protein but also isoflavones, fatty acids, saponine and phospholipids which might have additional effects on weight loss (48).

The mechanisms of anti-obesity effects of soy have not been clearly known. Previous investigations suggested that soy protein could improve insulin resistance and plasma lipid levels by activating peroxisome-proliferator activated receptors (PPARs), that regulate the expression of genes involved in glucose homeostasis, lipid metabolism, and fatty acid oxidation. Furthermore, soy consumption can stimulate the adiponectin secretion which in turn would enhance the insulin sensitivity and regulate the differentiation and secretory function of adipocytes. The isoflavone content of soy has also been considered as a possible anti-obesity mechanism for soy, as the isoflavones can decrease fat accumulation in the fat depots of obese rats (42, 49).

Findings from our clinical trial in postmenopausal women with the metabolic syndrome:

Our research group has recently evaluated the effects of soy consumption (in the form of either soy protein or unsalted soynuts) on features of the metabolic syndrome, including plasma lipids, lipoproteins, insulin resistance and glycemic control as well as on the inflammatory markers and indices of the oxidative stress in postmenopausal women with the metabolic syndrome (50-52).

The results showed that soynut had beneficial effects on the glycemic control and some markers of inflammation and oxidative stress. When the effects of soynut and soy protein were compared with each other, soynut was more effective in improving glycemic control and inflammatory biomarkers. However, no significant differences were found between these two products in terms of their effect on markers of oxidative stress. Neither soynut, nor soy protein influenced other features of the metabolic syndrome such as weight, waist circumference, blood pressure, and serum triglyceride levels. These data have been shown with greater details in Table 2 and 3.

In summary, soy consumption can decrease fat accumulation in adipose tissue and affect obesity. Furthermore soy consumption might have beneficial effects on features of the metabolic syndrome. Moreover soy consumption might have a positive role in the control of the hyperglycemia and insulin resistance.

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