1. Introduction
Metabolic syndrome (MetS) characterized by hypertension, central obesity, dyslipidemia, and glucose metabolism disturbances, describes a combination of interrelated genetic, metabolic, and environmental factors [
1] and can cause a 2-fold increase in the risk of developing cardiovascular disease (CVD) [
2], a 2.5-fold increase in risk of renal disease [
3], and a 5-fold increase in risk of type 2 diabetes mellitus (T2DM) [
4]. Of note, 20–30% of the adult population worldwide can be defined as having MetS [
5]; in Iran, the prevalence is 33.8% [
6]. It is predicated that the prevalence of MetS will rise mainly due to a parallel increase in obesity [
5], making it essential to address this situation, through dietary intake, which is a modifiable risk factor among other contributing factors (genetic, physical activity, smoking, and education level) associated with MetS [
1,
7,
8]. Among dietary determinants, nuts contain an abundance of healthy fats, fiber, antioxidants, phytochemicals, phytosterols and minerals [
9] that can beneficially affect insulin resistance, blood pressure, and dyslipidemia, contributing to their reduction theses inflammatory markers, which are all well-known risk factors for MetS [
10,
11].
Evidence has emerged from controlled clinical trials showing the beneficial effects of the consumption of nuts (either alone or as part of a Mediterranean diet) on metabolic features among people with MetS [
11,
12]. To date, there are limited epidemiological studies investigating the association between nut consumption and MetS, and they document conflicting results [
10,
13,
14,
15,
16,
17,
18]. Although cross-sectional [
13,
14,
15] studies have shown that nut consumption is inversely associated with obesity and MetS, limited prospective studies investigated the association between nut consumption and MetS; most of them investigate the association between the prudent dietary pattern or a Mediterranean diet enriched with nuts and MetS with conflicting results [
10,
16]. However, considering other healthy components, besides nuts in prudent dietary patterns, the synergic effects of nuts in the risk of MetS should be taken into account. Only one prospective study reports a reduced risk of MetS with consumption of over two servings/week of nuts over six years of follow-up [
10].
Each type of nut has its own particular characteristics [
9,
19]. To the best of our knowledge, regarding the unique nutrient profiles of nuts and their effects on metabolic status, no previous studies have elucidated the direct association of different types of nuts such as almonds, walnuts, hazelnuts, peanuts and pistachio with MetS risk. Moreover, most of the aforementioned studies were conducted among Mediterranean populations in developed countries [
10,
11,
12], and the long-term potential effects of consumption of different types of nuts on MetS risk among non-Mediterranean populations are not well documented. Thus, this prospective population-based study aimed to investigate the association between the consumption of nuts (total) and its various types including walnuts, almonds, hazelnuts, peanuts and pistachios (each per se) and risk of MetS in a 6.2 ± 0.7-year follow-up study conducted among adults in Tehran, Iran.
3. Results
Over the median 6.2 ± 0.7 years of follow-up, 276 new cases of MetS developed among the 1265 study participants. At baseline, the means ± SD of age and BMI were 37.2 ± 11.9 years and 26.4 ± 4.6 kg/m2, respectively; 9.5% were smokers, 45.8% were overweight and obese, and 39.2% had academic degrees. Median ± interquartile range (IQR) for consumption of nuts among the study population was 2.08 (0.88–5.68) servings/week. Median ± IQR of nuts were 1.0 (0.4–2.0) for the first, 4.2 (2.6–6.3) for the second and 24.7 (12.1–28.1) grams/week for the third categories of nut consumption, respectively.
Table 1 illustrates the characteristics of participants by tertiles of nut consumption. Participants with higher intakes of nuts were older and were more likely to be smokers. At baseline examination in phase III, fasting serum glucose and serum HDL-C were significantly associated with nut consumption; however, after 6.2 years of follow-up, systolic blood pressure, fasting serum glucose, serum TG, and WC were significantly and inversely associated with nut consumption. No statistically significant associations were observed for gender, physical activity, family history of diabetes, BMI, education levels, occupational status, and use of anti-hyperglycemia, anti-hypertensive and hypolipidemic drugs across tertiles of nut consumption.
No difference in baseline characteristics including age, gender, physical activity, family history of diabetes, BMI, education levels, occupational status, and use of anti-hyperglycemic and anti-hypertensive and hypolipidemic drugs was shown between total nut consumption and its various per se, except for smoking status (
Supplementary Materials Tables S1–S5).
Table 2 illustrates the dietary intakes of participants by tertiles of nut consumption. Participants who consumed more nuts had significantly higher intakes of total energy, carbohydrates, protein, fat, polyunsaturated fat (PUFA), total fiber, and fruit. Similarly, with an increasing intake of nuts, intakes of all types of nuts including almonds, peanuts, pistachios, hazelnuts and walnuts increased. Consumption of saturated- and mono-saturated fatty acids, vegetables, cholesterol, meat, poultry, fish, whole grain, legumes, and dairy products did not differ by tertiles of nuts.
The multivariate adjusted ORs (95% CIs) for MetS across tertiles of energy-adjusted consumption of nut and its various types are shown in
Table 3. There was a statistically significant decrease in MetS risk among the third (≥5 servings/week) versus the lowest (≤1 serving/week) tertiles of nut consumption in the crude model (OR: 0.55, 95% CI: 0.39–0.77,
p for trend: 0.002). In the adjusted model for family history of diabetes, age, gender, smoking, physical activity, fasting serum glucose and HDL cholesterol at baseline, participants in the third tertile had a 42% lower risk of MetS (OR: 0.58; 95% CI: 0.42–0.81,
p for trend: 0.01) compared with those in the reference tertile (first). Further adjustment for dietary intakes attenuated this association (OR: 0.62; 95% CI: 0.45–0.86,
p for trend: 0.01). This association remained significant after additional adjustment for BMI (OR: 0.68; 95% CI: 0.44–0.91).
Investigation of the associations between consumption of varieties of nuts and the risk of MetS revealed that walnut consumption had a significant inverse association with MetS risk (OR: 0.61, 95% CI: 0.44–0.86, p for trend: 0.02). After adjustment for family history of diabetes, age, gender, smoking, physical activity, fasting serum glucose and HDL cholesterol at baseline, a substantial reduction in the risk of MetS was observed (OR: 0.64, 95% CI: 0.47–0.89, p for trend: 0.02). Further adjustment for dietary intakes weakened this association (OR: 0.70 95% CI: 0.49–0.94). This association remained significant after additional adjustment for BMI (OR: 0.75; 95% CI: 0.53–0.98). Almonds, hazelnuts, peanuts and pistachios were not associated with risk of MetS. Moreover, for each additional serving/week of walnuts consumed, the incidence of MetS was reduced by 3%, in fully adjusted model, (OR: 0.97, 95% CI: 0.93–0.99).
The ORs (95% CI) of MetS across tertiles of nut consumption (total) and its various types (each per se) stratified by age, family history of diabetes and BMI are shown in
Table 4; according to family history of diabetes (yes or no), consumption of total nuts and walnuts was inversely associated with risk of MetS in both groups, associations that were more pronounced in participants with family history of diabetes. Stratified analyses according to age (19–45 or ≥45 years) showed that total nut consumption reduced risk of MetS in both groups, being more pronounced in participants aged ≥45 years; whereas walnut consumption reduced the risk of MetS only in participants aged ≥45 years. Stratified analyses by categories of BMI showed that consumption of total nuts, walnuts and almonds was significantly and inversely associated with reduced risk of MetS only in participants with BMI ≥ 25 kg/m
2.
4. Discussion
In this population-based prospective study with over 6.2 years of follow-up, the consumption of nuts lowered the risk of MetS, independently of confounding factors. Compared with participants who consumed less than one serving/week of nuts, those who had over five servings/week had a 32% lower risk of MetS, an association more pronounced in overweight and obese participants. Walnut consumption was also associated with a 25% reduction in the risk of MetS, an association more pronounced in overweight and obese participants, and participants aged ≥45 years. No association was observed between consumption of almonds, peanuts, pistachios or hazelnuts and the risk of MetS, possibly due to the low consumption of these types of nuts; only almond was inversely associated with MetS among overweight and obese participants.
Results of this study are in agreement with those of other prospective studies investigating the relationship between consumption of nuts and MetS. In a five-year follow-up of the National Health and Nutrition Examination Survey (NHANES), consumption of more than ¼ ounce/day of tree nuts (including walnuts, pistachios, almonds and hazelnuts) reduced the risk of MetS components [
15]. A follow-up of the Seguimiento Universidad de Navarra (SUN) study in Spain showed a 34% reduced risk of MetS in women who consumed >2 servings/week of nuts [
10]. Moreover, in the Coronary Artery Risk Development in Young Adults (CARDIA) study with 20 years of follow-up, a prudent dietary pattern (including nuts) was associated with a reduced risk of MetS and hypertension, hyperglycemia and dyslipidemia, compared to a Western dietary pattern [
29]; these findings are supported by those of a randomized clinical trial in which consuming one serving/day of nuts (15 g walnuts, 7.5 g almonds, or 7.5 g hazelnuts) improved insulin sensitivity among participants with MetS [
11]. In addition, previous case-control and cross-sectional studies have shown that frequent consumption of nuts and peanuts is associated with a lower prevalence of risk factors for CVD, T2DM, and MetS [
15], as well as obesity [
13,
14,
30].
Most studies showing an inverse association between nut consumption and risk of MetS were conducted among Mediterranean populations in developed countries [
10,
15,
29]. However, existence of other healthy foods, apart from nuts in the Mediterranean dietary pattern, the synergic effects of nuts and these foods in reducing the risk of MetS must also be taken into account. Therefore, considering the healthy contents of the Mediterranean dietary pattern, the beneficial effects reported in the above studies were attained by consuming two servings/week of nuts [
10]; amounts less than the five servings/week in the present study. The Atherosclerosis Risk in Communities Study in the United States, however, showed no association between a prudent dietary pattern including nuts and the incidence of MetS [
17], a result which may be due to the inclusion of coffee, sweetened beverages, and refined grains in a prudent dietary pattern, which could reduce the net effect of nuts on MetS. In the present study conducted in a Middle Eastern country, the positive effects of consuming over five servings/week of nuts on MetS was confirmed, which may be due to the fact that Iranian dietary patterns are becoming more similar to Western dietary patterns in recent decades [
31].
Nut consumption has been recommended by the American Heart Association (AHA) since 2000 [
32]. In agreement with this recommendation, dietary advice to promoting a healthy diet by inclusion of nuts (≥5 servings/week), with special focus on walnuts can increase public health. As a nutrient-dense food, frequent inclusion of nuts in the diet provides high amounts of mono- and polyunsaturated fatty acids, vegetable protein, fiber, antioxidants, vitamins, minerals such as magnesium and potassium, and multiple bioactive compounds like phytosterols and polyphenols. All these components of nuts are known to have beneficial effects on metabolic and cardiovascular outcomes [
33,
34], effects which can be explained by the amelioration of oxidative stress, inflammation and endothelial function, which decreases the risk of hypertension, dyslipidemia, abdominal obesity, insulin resistance and diabetes. In addition, consumption of one serving/day of nuts has been associated with enhanced satiety [
35] and better weight management [
36].
To the best of our knowledge, previous studies have not examined the direct effect of various types of nuts on MetS risk. In the current study, walnut consumption (median intake 5.8 servings/week) showed a 25% reduction in the risk of MetS, independent of confounding factors. In some interventional studies, walnut consumption has inconsistently been found to be associated with lower risk of MetS, diabetes, and CVD [
37,
38,
39]; however, the association between walnuts and MetS or its components has rarely been investigated in epidemiological studies [
40,
41]. Data from a cross-over clinical trial among Korean adults with MetS demonstrated that 45 g/day of walnut consumption for 16 weeks improved MetS components, especially fasting blood glucose [
37]. In another trial, consumption of 15 g/day of walnuts improved lipid profile of women with MetS [
42]. By contrast, a walnut intervention diet used in a South African population showed no significant effect on lipid profiles, inflammatory factors, blood pressure, or serum uric acid concentrations compared with the control diet [
38]. Another trial concluded that including walnuts in the diet for a participant group who received intensive lifestyle counseling (LC) provided no additional benefits to lipid profiles, compared with a less intensive LC group [
39]. The fairly small sample size, short duration of the intervention (clinically significant outcomes for metabolic factors cannot be determined over a short time), and the low total- and low-density lipoprotein cholesterol concentrations at baseline might partly explain the null findings in the two latter trials [
38,
39]. Each type of nut has its own particular characteristics. Unlike most nuts that are high in monounsaturated fatty acids (almonds, hazelnuts, pistachios and peanuts), walnuts are composed largely of polyunsaturated fatty acids such as ellagic acid and alpha-linolenic acid, all of which have antioxidant and anti-inflammatory properties that protect against cardiometabolic risk factors and MetS.
In our study, no associations were observed for consumption of the other types of nuts studied (almonds, peanuts, pistachios and hazelnuts) and risk of MetS. However, previous interventional and epidemiological studies have reported beneficial effects of the consumption of almonds, pistachios, hazelnuts and peanuts on cardiometabolic profiles, adiposity, glycemic control, and lipid profiles of individuals with MetS [
11,
43], pre-diabetes [
44], and T2DM [
40,
45]. The discrepancies between our results and those of the abovementioned studies might be explained by the low consumption of the abovementioned types of nuts among Tehranian adults. In addition, compared with previous study, the sample size of this study is relatively small. For instance, the SUN study, which is a prospective cohort study with Spanish university graduates, identified 567 new cases of MetS among 9887 participants after six years of follow-up [
10]. Therefore, further prospective investigations with large sample size are needed to confirm the association between consumption of other varieties of nuts and risk of MetS, as well as the underlying mechanisms.
Some strengths need to be mentioned in this study. First, this study has a population-based prospective design and was conducted in a Middle Eastern country; second, the over 6.2-year follow-up in the study rules out potential seasonal changes in participants’ diets. Third, using a valid and reliable FFQ [
24] administered by a trained nutritionist minimized any potential measurement errors. Finally, we adjusted for potential confounding factors, especially total energy intake (usually a confounder of associations between diet and disease in epidemiologic studies) and also took nutrient density into account [
28]. Nevertheless, the present study also has a few limitations. First, MetS is heterogeneous; therefore, in addition to dietary factors, factors such as heredity may need to be addressed. Furthermore, despite carefully adjusting for a range of known confounding factors, unknown confounding factors or potential dietary confounders may affect the relationship between nut consumption and MetS. In addition, our findings cannot be inferred to older or younger populations as this study only included adults. Finally, regarding the different types of nuts (other than walnuts) analyzed in this study, the failure to detect any associations between consumption of these types of nuts and MetS may be due to the narrow range of dietary intakes among our participants.