1. Introduction
Metabolic syndrome (MetS) is a condition characterized by clustering of abdominal obesity, insulin resistance, high blood pressure, dyslipidemia, and high blood glucose levels, often accompanied by a proinflammatory and prothrombotic state [
1,
2]. MetS has become a public health concern not only in developed, but also developing countries because of its high frequency of occurrence [
3]. According to the National Nutritional and Health Survey of 2016, the prevalence of MetS in Japan was estimated at 27.0% for men and 10.0% for women aged 20 years or older [
4]. Prospective studies have shown that persons who have MetS are at increased risk of developing type 2 diabetes [
5,
6] and atherosclerotic cardiovascular diseases [
5,
7]. Therefore, primary prevention of MetS is important to prevent more severe health consequences. Although excessive energy intake and physical inactivity are major risk factors, diet quality may also contribute to MetS development [
1].
There are several approaches to investigate the associations of diet with chronic diseases in epidemiologic studies. Dietary pattern analysis has been frequently used because foods and nutrients are consumed as an aggregate, and amounts of foods and nutrients are often highly correlated with each other, making it difficult to investigate the contribution of an individual food or nutrient separately [
8,
9]. A priori approach evaluates the degree of adherence to specific dietary patterns such as the Alternate Healthy Eating Index [
10], Dietary Approach to Stop Hypertension (DASH) diet [
11], and Mediterranean diet [
12]. The latter two diets [
13,
14] were inversely associated with MetS. On the other hand, a posteriori approach extracts dietary patterns from data at hand. The most frequently used are principal component or factor analysis. A recent meta-analysis showed that a prudent/healthy pattern was inversely associated, while a Western/unhealthy pattern was positively associated, with MetS in cross-sectional studies, but not in cohort studies [
15]. Nutrient pattern analysis extracts patterns from nutrient intake data instead of food intake. Recently, this approach has been applied to examine nutritional factors associated with MetS and fasting blood glucose levels in several studies [
16,
17,
18,
19].
In the present study, we investigated the associations of nutrient patterns with the prevalence of MetS in individuals who had participated in the baseline survey of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study.
3. Results
Table 1 shows the characteristics of the study subjects according to the presence of MetS. The prevalence of MetS was 22.6% for men and 10.6% for women. Subjects who had MetS were older, more likely to be men, current or past-smokers, current drinkers, and consumed more total energy. There was no significant difference in the physical activity level in leisure time among subjects who had MetS and those who did not.
Table 1 also shows the median intake of total fat and 21 nutrients used for factor analysis according to the presence of MetS.
In factor analysis, three nutrient patterns were extracted (
Table 2). In this analysis, factors with eigenvalues >1.5 were retained because this cut-off yielded more interpretable nutrient patterns. The first factor (Factor 1) explained by far the largest proportion of total variance in nutritional intake (45%), followed by the second (Factor 2, 12%) and third (Factor 3, 9%). Factor 1 was named the “fiber, potassium and vitamins pattern” because of the high factor loadings for folate, insoluble dietary fiber, carotene, soluble dietary fiber, iron, vitamin C, and potassium. Factor 2 was labeled the “fats and fat-soluble vitamins pattern” because it was positively correlated with monounsaturated fatty acid,
n-3 fatty acids,
n-6 fatty acids, and vitamin E. Factor 3 was named the “saturated fatty acids, calcium and vitamin B
2 pattern” because of a positive correlation with saturated fatty acids, calcium, vitamin B
2, and protein, and a negative correlation with carbohydrate. When factor analysis was performed for sex separately, the extracted nutrient patterns were similar (
Table S1). Therefore, we adopted combined analysis of men and women.
Table 1 presents the mean factor scores among subjects who had MetS and those who did not.
Table 3,
Table 4 and
Table 5 show the associations of three nutrient pattern scores with the prevalence of MetS and its components. After adjustment for sex, age, study site, physical activity, total energy intake, smoking and drinking habits, and school career (Model 2), Factor 1 scores were inversely and significantly associated with the prevalence of MetS (Q1 versus Q4, OR = 0.69, 95% CI 0.63–0.77,
p for trend <0.001) and all five components (
Table 3). On the other hand, Factor 2 scores were significantly associated with increased OR of MetS (Q1 versus Q4, OR = 1.27, 95% CI 1.17–1.39,
p for trend <0.001), obesity, and high blood pressure in Model 2 (
Table 4). To examine whether the associations of Factor 2 scores with four components of MetS (except for obesity) were mediated by obesity, BMI was further adjusted in Model 3. The OR for high blood pressure became somewhat lower, but remained statistically higher than 1.00. Factor 3 scores were associated with significantly reduced OR of MetS (Q1 versus Q4, OR = 0.87, 95% CI 0.79–0.95,
p for trend <0.001), high blood pressure, high serum triglycerides, and low serum HDL cholesterol levels (
Table 5). After adjusting for BMI, there were essentially no changes in the OR of each component.
When logistic regression analysis was performed using nutrient pattern scores as continuous variables, the
p-values did not differ greatly from the
p for trend shown in
Table 3,
Table 4 and
Table 5 (
Tables S2–S4). In a subgroup with BMI < 25 kg/m
2 (total No. = 22,748, No. of MetS = 1194), only Factor 1 scores were significantly associated with reduced OR of MetS. In a subgroup with BMI ≥25 kg/m
2 (total No. = 7360, No. of MetS = 3782), Factor 1 and 3 scores were inversely associated, while Factor 2 scores were positively associated with the prevalence of MetS (
Table 6). When stratified by sex, the associations of Factor 1, 2, and 3 scores and MetS were similar for men and women.
4. Discussion
In the present study, Factor 1 scores, which were positively correlated with intake of folate, insoluble and soluble dietary fiber, carotene, iron, vitamin C and potassium, showed significant inverse associations with MetS and all its components. These seven nutrients are abundantly contained in vegetables and fruits. Therefore, the present results are consistent with observations that the prudent/healthy diet pattern, characterized by high intake of vegetables, fruits, legumes and cereals, was inversely associated with MetS in cross-sectional [
15,
25,
26,
27,
28] and cohort studies [
29,
30]. A vitamins and trace elements pattern, extracted from 24-h dietary recall, was also reported to be inversely associated with the prevalence of MetS in the National Health and Nutrition Examination Survey [
19]. Among the seven nutrients, insoluble dietary fiber and potassium were the most strongly associated with reduced OR of MetS (
Table S5). Insoluble dietary fiber is known to prolong the intestinal transit time and increase post-meal satiety [
31], as well as reducing insulin resistance [
32]. After adjustment for BMI, insoluble dietary fiber remained inversely associated with low serum HDL cholesterol levels (
Table S5), but we could not find plausible biological mechanisms. A recent meta-analysis showed that high dietary potassium intake was associated with lower prevalence of MetS [
33]. A cross-sectional study conducted in China also reported an inverse association between serum potassium concentration and the prevalence of MetS [
34]. Regarding this MetS component, it is established that increased potassium intake reduces blood pressure by counteracting the effects of sodium [
35]. The other nutrients positively correlated with Factor 1 may have also contributed to the inverse association with MetS, through mechanisms such as the gel-forming effects of soluble dietary fiber to reduce postprandial blood glucose [
31], and the anti-oxidative effects of vitamin C.
Factor 2 scores, which were positively correlated with monounsaturated fatty acid, n-3 and n-6 polyunsaturated fatty acids, and vitamin E, were positively associated with the prevalence of MetS, obesity, and high blood pressure. We think that Factor 2 reflects the overall consumption of a high fat diet because this pattern was positively correlated with deep fried foods, stir fried foods, mayonnaise, beef/pork, ham/sausage/salami/bacon, and fish. A high fat diet has high energy density, so it may lead to excessive energy intake over the long term. When BMI was additionally adjusted, the association of Factor 2 scores with high blood pressure was attenuated, but was still significantly increased for Q3 and Q4. This suggested that the association between Factor 2 scores and high blood pressure was partially mediated by obesity. In diet pattern analysis, the Western/unhealthy pattern, characterized by high intake of refined grains, red meat, processed meat, and fried foods, has been reported to be positively associated with MetS [
15,
25,
36]. Factor 2 extracted in our study resembled the Western/unhealthy diet pattern, but was somewhat different in terms of the positive correlation with n-3 polyunsaturated fatty acids and fish intake, and a low correlation with saturated fatty acids. The association between Factor 2 and refined grains was unknown, since the distinction between whole/refined grains was not taken into account in our FFQ.
Factor 3 scores were significantly associated with lower OR of MetS and its three components, except for obesity and high blood glucose. Among three nutrients closely correlated with Factor 3 (saturated fatty acid, calcium, and vitamin B
2), calcium was most strongly associated with a reduced OR of MetS (
Table S6). After adjustment for Ca, saturated fatty acid intake and vitamin B
2 were not independently associated with MetS. With regard to food items, milk, yogurt, beef and pork, and eggs were positively correlated with Factor 3 scores (data not shown), which was considered a reason for the high factor loading of saturated fatty acid on Factor 3. Cross-sectional studies showed inverse associations between calcium intake and MetS in U.S. women [
37] and Korean women with low calcium intake (mean = 331 mg/day) [
38]. Calcium density was also significantly associated with a lower MetS incidence rate [
39]. Consumption of dairy products, a major source of calcium, has been reported to be inversely associated with the MetS incidence rate [
36,
39], despite some inconsistencies [
40]. Mechanisms for the beneficial effects of calcium on lipid profiles include formation of soaps with fatty acids and increased fecal fat excretion, as well as its preventive effects on high blood pressure including reduced intracellular calcium concentration and vascular resistance, especially in individuals with low calcium intake [
41]. In the present study, extracted nutrient patterns were different from those reported for Chinese [
16], Iranian [
17], and African populations [
18]. However, two of the three extracted nutrient patterns were closely related to well-known dietary patterns (healthy/prudent and high fat/Western), which were also extracted in our previous study using the same FFQ [
42]. One advantage of using nutrient patterns may be that interpretation of underlying biological mechanisms is more straightforward than dietary patterns.
In a stratified analysis according to BMI, Factor 1 scores were associated with lower OR of MetS among subjects with normal weight. On the other hand, Factor 1 and 3 scores were inversely associated, and Factor 2 scores were positively associated with the prevalence of MetS among overweight/obese subjects. This kind of analysis may be helpful to clarify the modifiable lifestyle factors associated with transition from metabolically healthy to unhealthy status according to boy weight [
43]. The present results were in line with those recently reported for healthy dietary pattern characterized by high intake of vegetables, fruits and fish [
44] and Mediterranean diet [
45] associated with metabolically healthy obese status.
The strengths of the present study include the large number of study subjects, and use of a validated FFQ. On the other hand, there are also several limitations. First, the number of subjects excluded from the study was large (No. = 13,361). We compared the characteristics of those who were excluded and not excluded from the final analysis. The most striking difference was the availability of data for the diagnosis of MetS, especially high fasting blood glucose. It is unknown how the results were affected by the exclusion of a relatively large number of study subjects. Second, in cross-sectional studies, the temporal relationship between nutrient intake and onset of MetS is unclear. Third, since nutrient intake was assessed using an FFQ, some degree of measurement error is inevitable. However, only a small number of nutrients showed low validity in our FFQ [
21], and nutrient patterns 1-3 were not heavily loaded by these nutrients. Fourth, because of a lack of data on waist circumference, BMI was alternatively used for the diagnosis of MetS. Therefore, some subjects with high muscle mass or excess subcutaneous fat may have mistakenly been judged as having abdominal obesity, while subjects with normal BMI but high abdominal circumference may have been overlooked. When the BMI cut-off point of 25 kg/m
2 was used, the sensitivity and specificity of diagnosing high abdominal circumference were 83% and 82% for men (No. = 633), and 45% and 98% for women (No. = 623), respectively, in the sub-sample of the J-MICC Study in Tokushima Prefecture. Fifth, nutrient patterns may be specific to the study population, and interpretation may be subjective, as is the case for the posteriori dietary pattern analysis. This may make it difficult to generalize the results to other ethnic populations.
In conclusion, the fiber, potassium and vitamins pattern, and saturated fatty acids, calcium and vitamin B2 pattern were associated with a reduced OR of MetS, while a fats and fat-soluble vitamins pattern was associated with an increased OR of MetS. Analysis of nutrient patterns may be useful to assess the overall diet and its association with MetS, and to set dietary guidelines for MetS prevention.