Introduction

Metabolic syndrome (MetS), as a constellation of metabolic disturbances, is a well-established predictor of cardiovascular disease, type 2 diabetes and all-cause mortality.1, 2, 3 Although the prevalence of MetS differs based on the criteria applied in various studies, a marked increasing trend of the syndrome has been reported not only in developed countries but also in developing nations.4, 5, 6, 7 MetS is highly prevalent in Iran, where more than 30% of adults are affected.8

MetS is a complex multifactorial disorder that results from the interactions of genetic, metabolic and environmental factors including diet.9 Although some dietary components including hydrogenated vegetable oil,10 red meat11 and refined grains12 have been reported as contributing to greater odds of this condition, the exact underlying dietary determinants are poorly identified. Earlier investigations have mostly focused on nutrients13, 14, 15 or dietary patterns,16, 17, 18, 19 and comparatively limited emphasis has been laid down on the specific contribution of foods and food groups, particularly fish consumption.

Fish is a rich source of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) and high consumption of these fatty acids has been related to lower blood pressure, serum triglycerides and 2-h glucose and higher high-density lipoprotein cholesterol (HDL-C).20, 21 Protective relations between DHA and EPA intake and MetS have also been found.22 Besides polyunsaturated fats, fish contains vitamin D, calcium and high-quality proteins, which may affect MetS and its features.23, 24, 25, 26

Although the association between fish consumption and several metabolic abnormalities has been widely investigated,27, 28, 29, 30 relatively limited and inconsistent evidence is available regarding the direct relation of fish consumption and MetS. In a population-based cross-sectional study, increased fish intake was associated with reduced risk of MetS.31 Favorable association of fish consumption and MetS has also been found in other investigations; however, these significant inverse associations were found only among men, but not in women.32, 33 In addition, protective relations between fish intake and MetS were not observed by others.34, 35 Furthermore, most information regarding the beneficial health effects of fish has predominantly been derived from investigations performed in developed countries and limited data are available in developing ones, particularly from the Middle East region, where the dietary intakes are different from those in western countries.36, 37 Fish intake in this region is much lower than that in other parts of the world38 and whether such lower amounts of fish consumption can protect against MetS is unknown. This study was, therefore, conducted to examine the association between fish consumption and MetS among a group of adult females in Isfahan, Iran.

Subjects and methods

Subjects

This cross-sectional study was conducted in 2012 among a representative sample of Isfahani female nurses aged >30 years who were selected by a multistage cluster random sampling method. A total of seven hospitals, considering the number of public and private hospitals, were randomly selected. From female nurses working in these hospitals, 510 randomly selected nurses were invited to participate in this study and 420 women agreed to do so. The current analysis was carried out on these 420 nurses. The Regional Bioethics Committee of Isfahan University of Medical Sciences approved the study protocol, and written informed consent was obtained from each participant.

Assessment of dietary intakes

Usual dietary intakes were assessed, using a 106-item dish-based semiquantitative food frequency questionnaire (DS-FFQ), through a self-administered method.39 The DS-FFQ contained information on frequency of consumption of different foods or dishes over the last year, along with common portion sizes used in Iran. Foods and dishes were classified into five main domains such as: (1) mixed dishes, (2) grains, (3) dairy products, (4) fruits and vegetables and (5) miscellaneous food items and beverages. Participants were asked to mention their frequency of consumption of a specified portion of each food or dish item during the previous year. The frequency response section consists of multiple choices ranging from ‘never or less than once a month’ to ‘12 or more times per day’. The number of frequency response categories was not similar for all foods, they differed from 6 to 9 choices. For instance, the frequency response for less consumed items like tuna were six categories as follows: never or less than once per month, 1–3 times per month, 1 times per week, 2–4 times per week, 5–6 times per week, 1–2 times per day; and for highly consumed items like tea, the frequency response were nine categories as follows: never or <1 cup per month, 1–3 cup per month, 1–3 cup per week, 4–6 cup per week, 1 cup/day, 2–4 cup per day, 5–7 cup per day, 8–11 cup per day, ⩾12 cup per day. To assess food composition of mixed dishes, we applied recipes commonly used in Iran. Food composition, specified portion sizes and the average of reported frequency were used to estimate mean daily intake of each item, and then portion sizes of each items were used to calculate grams per day of each food items considering household measures.40 By summing up the energy intakes of all foods, total energy intake was obtained. Fish consumption was calculated as the summation of fish and tuna intake.

The FFQ was validated among a subsample of 200 randomly selected participants. The reliability of the FFQ was assessed by comparing dietary intakes estimated by responses to the FFQ on two different occasions. The validity of FFQ was assessed using the three 24-h dietary recalls as gold. Overall, these data indicated that the FFQ provides reasonably valid and reliable measures of the average long-term dietary intakes.39

Assessment of anthropometric measures

Weight was measured by a trained dietitian using digital scales while participants were wearing light cloths and were without shoes and recorded to the nearest 0.1 kg. Height measurement was made while subjects were standing in a normal position without shoes by means of a tape measure. Body mass index (BMI) was calculated as weight (kg) divided by height squared (m2). Waist circumference was measured at the narrowest level over light clothing using an unstretched tape and recorded to the nearest 0.1 cm.

Assessment of biomarkers

Fasting blood samples were drawn after a 12 h overnight fast to measure plasma glucose and serum lipid concentrations. Fasting plasma glucose was measured on the day of blood collection with an enzymatic colorimetric method using glucose oxidase. Serum triglyceride concentrations were assayed with the use of triacylglycerol kits by enzymatic colorimetric tests with glycerol phosphate oxidase. HDL-C was measured after precipitation of the apolipoprotein B-containing lipoproteins with phosphotungstic acid.

Assessment of blood pressure

To measure blood pressure, participants were asked to rest for 10 min. A trained nurse recorded blood pressure in a seated position, using a standard mercury sphygmomanometer. Measurement repeated after 5 min interval and the average of the two readings was considered as the subject’s blood pressure. The systolic blood pressure was defined as the appearance of the first sound (Korotkoff phase 1) and the diastolic blood pressure was defined as the disappearance of the sound (Korotkoff phase 5) during deflation of the cuff at a 2–3 mm/s decrement rate of the mercury column.

Assessment of other variables

A self-reported questionnaire that included information about age, smoking habits, menopausal and marital status, medical history, current use of supplements and medications was administered. Physical activity was assessed by administering the short form of International Physical Activity Questionnaire. Data on physical activity were expressed as metabolic equivalent-hours per week (MET-h per day) using standard guidelines.41

Definition of MetS

The syndrome was defined based on the presence of at least three of the following risk factors, according to the guidelines of National Cholesterol Education Program Adult Treatment Panel III (ATP III):42 (1) abdominal obesity (waist circumference >88 cm); (2) hypertriglyceridemia (serum triglyceride levels ⩾150 mg/dl); (3) low HDL-C (<50 mg/dl); (4) elevated blood pressure (systolic blood pressure ⩾130 mm Hg or diastolic blood pressure ⩾85 mm Hg or antihypertensive medication use); (5) abnormal glucose homeostasis(fasting plasma glucose ⩾100 mg/dl).

Statistical methods

Energy-adjusted intakes of fish were estimated by using residual method. Then, participants were categorized based on tertile cut-points of energy-adjusted intake of fish. To compare age-adjusted general characteristics of study participants, we applied analysis of covariance. χ2-test was used to examine significant differences in the distribution of subjects with regard to categorical variables. Age- and energy-adjusted means for dietary variables across tertiles of fish intake were assessed by using analysis of covariance. The prevalence of MetS as well as its features across tertiles of fish intake was computed through cross-tabulation with the use of χ2-test. To identify the association between fish consumption and MetS, we used logistic regression in different models. First we adjusted for age (continuous) and total energy intake (kcal per day). Then, we additionally controlled for physical activity (MET-h per day, continuous), medication use (yes/no), menopausal (yes/no), marital (single/married/divorced) and socioeconomic status (low/moderate/high). Further adjustments were made for dietary intakes, including red meats, vegetables, fruits, dairy products, grains, legume and nuts, oils and fiber (all as continuous), in the third model. Finally, we controlled for BMI (continuous) to determine whether these associations are independent of obesity. To detect the relationship between fish consumption and features of MetS, logistic regression was applied either before or after controlling for age (continuous), total energy intake (kcal per day), physical activity (continuous), medication use (yes/no), menopausal (yes/no), marital (single/married/divorced) and socioeconomic status (low/moderate/high) and dietary intakes of red meats, vegetables, fruits, dairy products, grains, legume and nuts, oils and fiber (all as continuous). In all regression models, the first tertile of fish consumption was considered as reference. To examine the trend of odds ratios across tertile categories of fish intake, we assigned the median value of fish intake in each tertile as a continuous variable and then used this variable in the analysis. All statistical analyses were carried out using the Statistical Package for Social Sciences (version 16.0; SPSS Inc., Chicago, IL, USA). P-values <0.05 (two-sided) were considered statistically significant.

Results

MetS was identified in 8.2%. The prevalence of abnormal glucose homeostasis, abdominal obesity and hypertriglyceridemia was 6.4%, 23.8% and 6.4%, respectively. Low HDL-C and elevated blood pressure was prevalent among 46.9% and 31.2% of population, respectively. Mean energy-adjusted fish intake in the study population was 14.4 g per day. Age-adjusted characteristics of study participants across tertiles of energy-adjusted fish consumption are shown in Table 1. Compared with participants in the lowest tertile, those in the highest tertile of fish intake were younger. The prevalence of obesity (BMI ⩾30 kg/m2) among subjects in the second tertile of fish intake was 31%, whereas the corresponding figures among subjects in the first and third tertile were 45% and 41% (P=0.04), respectively. No significant differences were detected between tertiles of fish consumption in terms of weight, BMI, physical activity and socioeconomic status. The distribution of married and postmenopausal female subjects was not statistically different between tertiles of fish consumption, as well. No significant differences were also observed regarding the distribution of current oral contraceptive pill users or corticosteroid users between different tertiles of fish intake.

Table 1 Age-adjusted characteristics of study participants across tertiles of fish intake
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Prevalence of MetS across tertiles of energy-adjusted fish intake is shown in Figure 1. Individuals in the highest tertile of fish intake were less likely to have MetS compared with their counterparts in the lowest tertile (P=0.03).

Figure 1
figure 1

Numbers of participants with MetS across tertiles of energy-adjusted fish intake.

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Age- and energy-adjusted means of dietary intakes across tertiles of energy-adjusted fish consumption are presented in Table 2. High consumption of fish was associated with increased intake of total energy, carbohydrates and refined grains. The mean daily intakes of other dietary variables and food groups were not different across tertiles of fish intake.

Table 2 Dietary intakes of participants across tertiles of fish intakea
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Multivariable-adjusted odds ratios for MetS across different tertiles of energy-adjusted fish intake are provided in Table 3. In crude model, subjects in the upper category of fish consumption were 65% less likely to have MetS compared with those in the lowest tertile (odds ratio: 0.35; 95% confidence interval (CI): 0.14–0.88). Adjustment for potential confounders including sociodemographic and dietary variables strengthened this association. Even when BMI was taken into account, individuals with the highest category of fish intake were 96% less likely to have MetS compared with the lowest (odds ratio: 0.04; 95% CI: 0.004–0.61).

Table 3 Multivariable-adjusted odds ratios for metabolic syndrome across tertiles of fish intakea
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When the data were analyzed for features of MetS, we found that participants in the highest tertile of energy-adjusted fish consumption were 49% less likely to have abnormal glucose homeostasis compared with those in the lowest tertile (odds ratio: 0.51; 95% CI: 0.17–0.89) (Table 4). However, after controlling for potential cofounders, this association disappeared. High fish intake was inversely associated with lower odds of hypertriglyceridemia, low HDL-C and elevated blood pressure after taking potential confounders into account. Compared with those in the lowest tertile, individuals in the top tertile of fish consumption were 89%, 43% and 77% less likely to have hypertriglyceridemia (odds ratio: 0.11; 95% CI: 0.85–1.01), low HDL-C (odds ratio: 0.57; 95% CI: 0.19–0.89) and elevated blood pressure (odds ratio: 0.23; 95% CI: 0.14–0.89), respectively. No significant association was found between fish consumption and enlarged waist circumference either before or after adjustment for potential confounders including dietary variables. When the analysis for enlarged waist circumference and the whole MetS was repeated using nationally suggested cutoff values for waist circumference in Iranian adults,43 we reached the same findings.

Table 4 Multivariable-adjusted odds ratios for features of the metabolic syndrome across tertiles of fish intakea
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Discussion

The current cross-sectional study, conducted in a group of Iranian adults, showed that higher fish consumption was inversely associated with MetS and some of its features including low HDL-C, hypertriglyceridemia and high blood pressure. Controlling for potential confounders and dietary variables strengthened these associations. Thus, the relations we found are not likely to be confounded by other lifestyle factors associated with fish consumption. To our knowledge, this is the first study in the Middle-East reporting the relationship between fish consumption and MetS.

The relationship between fish consumption and MetS is equivocal. In the current study, we found that higher intakes of fish were related to the lower prevalence of MetS. This finding was in accordance with a population-based cross-sectional study among French middle-aged men, which reported an inverse association between consumption of fish, grain and dairy products with insulin resistance syndrome separately and in combination with each other.31 That study showed that fish had greater protective effects against insulin resistance syndrome than that of grains and dairy products. Baik et al.32 found that increased fish consumption was inversely associated with future development of MetS among Korean men, but not among women. The investigators of that study attributed the lack of association among women to the consumption levels that failed to produce a therapeutic effect. However, the consumption level in our study was much lower than that in the study of Baik et al.,32 indicating that even lower intakes of fish might protect against MetS. Other investigators have also reported the inverse association between fish consumption and risk of MetS only among men.33 Therefore, it seems that the current study is the first reporting a protective association between fish consumption and MetS among women. The different findings for women between our study and others might be explained by several reasons. It may be noted that in the study of Baik et al.,32 total fat intake was adjusted for as a confounding variable, while we did not control for total fat intake in our analysis. As beneficial effects of fish consumption might be mediated through its fat content, controlling for total fat intake seems an overadjustment. To exclude the effect of fat intake, we adjusted for consumption of dietary oils in the present study rather than total fat intake. Furthermore, in the current study participants were classified based on tertile cut-points of energy-adjusted intake of fish, whereas Baik et al.32 categorized participants according to average fish consumption frequency per week, which might result in great degrees of misclassification. Lack of association between fish intake and MetS among Finnish women in the study of Kouki et al.33 may also be explained by the lack of controlling for potential confounders including intakes of other food groups. Therefore, we believe that further studies are warranted to identify if gender differences exist in the fish–MetS relationship. In contrast to our findings, some studies have failed to reach a significant association between fish consumption and MetS.34, 35 The use of different definitions of the MetS as well as different dietary assessment tools, lack of controlling for potential confounders including intakes of other food groups in some studies and looking at fish–MetS relation as an accessory objective, instead of the main aim, may help explain the different findings.

Besides MetS, fish consumption was also inversely associated with some features of this syndrome. We found a significant inverse association between fish intake and low HDL-C, high blood pressure and high triglyceride levels. In line with ours, a prior observational investigation31 has also suggested that high intakes of fish-based dietary pattern were inversely associated with elevated blood pressure, high triglyceride and low HDL-C concentrations. The same findings were also reported by Baik et al.32 among men. These findings suggest that the inverse relation of fish intake and MetS is mainly mediated through its effect on blood pressure, triglyceride and HDL-C concentrations.

The exact underlying mechanisms of the protective relations between fish intake and risk of MetS have not been thoroughly understood. The favorable effects of fish might be explained by its high content of EPA and DHA. These fatty acids may reduce triglyceride concentrations through different ways including suppression of hepatic lipogenesis and VLDL secretion, elevation of fatty acids β-oxidation and increment of apolipoprotein B-100 degradation.44, 45 It has also been shown that EPA and DHA intake are inversely associated with gene expression of sterol regulatory element-binding protein 1, a transcription factor that increases the synthesis of lipogenic enzymes including fatty acid synthase and acetyl-CoA carboxylase-1.46, 47 EPA and DHA can activate lipoprotein lipase, which is partially mediated by stimulation of peroxisome proliferator-activated receptor-γ, which consequently leads to increased clearance of VLDL.48, 49 The effect of EPA and DHA on blood pressure might be mediated through influence on vascular and endothelial function, elevation of arterial compliance and endogenous production and release of nitric oxide.50, 51, 52 Furthermore, DHA has been linked to the inhibition of vascular wall fibrosis and subsequent development of hypertension.53, 54

While interpreting, some limitations of our findings should be considered. Owing to the cross-sectional nature of the study, causal relationships cannot be inferred. Prospective cohort studies are required to determine the exact causal association between fish intake and MetS. As self-administered DS-FFQ was applied to collect dietary information, misclassification of participants is inevitable, as is in all epidemiological investigations. Adherence to high fish diets was related to healthier lifestyle behaviors that may not have been precisely evaluated and controlled in our analysis. Therefore, residual confounding cannot be excluded. As the current study was confined to educated female nurses, our findings cannot be extrapolated to all Iranian female subjects. However, participants in the current study were recruited from different parts of the city with discrepant sociodemographic status. Furthermore, the study population was relatively young with a low prevalence of MetS, which could further limit the generalizability of our findings. It has been shown that various species of fish could differentially affect cardiovascular disease, atherosclerosis progression and diabetes;28, 29 however, we could not assess the associations by the different kinds of fish and various methods of cooking. Assessment of these factors might provide additional information into the fish–MetS relations. Furthermore, we were not able to consider halogenated hydrocarbons or mercury contents of fish in the current study.

In conclusion, the current study suggested that greater fish consumption was associated with reduced risk of MetS and its features among a group of Iranian adult females. This evidence supports current dietary recommendations regarding regular fish consumption to prevent cardiovascular disease.