Association of meal frequency with metabolic syndrome in Korean adults: from the Korea National Health and Nutrition Examination Survey (KNHANES)

Metabolic syndrome (MetS) is a cluster of factors associated with an increased risk of developing cardiovascular disease (CVD) and type 2 diabetes [1]. MetS is known to be a complex interaction among genetic, metabolic, and environmental factors such as physical activity and diet [2]. Over the last several decades, the prevalence of MetS has increased, and it has become a major public health concern worldwide, including in Korea [3]. Identifying ways to reduce the risk of MetS is very important to public health. Among modifiable environmental factors, dietary habits are of central importance in the prevention and treatment of MetS.

Although the modern Westernized lifestyle is characterized by irregular meal pattern such as skipped meals, consumption of 3 meals/day is the most common pattern of eating. Also, there is a long-held belief that three regular meals consumption per day are beneficial to metabolic health and therefore is recommended to the general population, although there is limited scientific evidence to support this recommendation. In addition, research about relationship between dietary pattern and MetS is limited [4‐6].

Several epidemiologic and clinical data suggest that regular meal patterns appear beneficial to metabolic profiles. Sierra-Johnson et al. reported that, in a population-based study of 3607 individuals, aged 60 years, eating regular meals was associated with a lower risk of MetS and insulin resistance compared to that in irregular eaters who eat 1 or 2 meals/day [7]. A study of Finnish adolescents found that 5 meals/day had a reduced risk of being overweight/obese in both genders and reduced abdominal obesity in boys compared to 4 or fewer meals/day [8]. Carlson et al. reported that consuming 1 meal/day without calorie restriction during a 2-month period exhibited elevated fasting plasma glucose and impaired glucose tolerance associated with a delayed insulin response compared to those consuming 3 meals/day [9].

On the other hand, other studies suggest that subjects who have reported reduced meal frequency appear beneficial health outcomes [10]. Intermittent fasting has attracted much attention worldwide because it can increase longevity in animals and also has beneficial effects on risk factors for CVD and several other diseases including cancer, diabetes, and neurologic disorders [11‐13]. Several studies related to Ramadan fasting as a unique natural model of intermittent fasting, showed improvements in risk profiles of CVD [14]. As a result, reduced meal frequency by intermittent fasting supported an association between lower meal frequency and reduced risk of MetS. Although the question of whether the effects of reduced meal frequency are the result of caloric restriction or fasting itself is not resolved, at least some of the beneficial effects of intermittent fasting are suggested to be independent of calorie intake [15].

Caloric intake has been established as the most fundamental factor for longevity and health outcome. Thus, research exploring the effects of meal frequency should consider caloric intake at the same time because the effect of meal frequency on MetS would be difficult to isolate from any effect induced by calorie restriction. Therefore, we evaluated the association between meal frequency adjusted by caloric intake and MetS using a large nationally representative dataset. We hypothesized that, in the general population, eating 3 meals/day would be associated with a different risk of MetS than eating 2 or fewer less meals/day after adjusting for confounding factors including caloric intake.

In this study, we found that lower meal frequency was associated with increased MetS in Korean men, after adjusting for confounding factors including total calorie intake per day and physical activity. Most of the participants in KNHANES (84.2%) had 3 meals/day, indicating that, though diet patterns in Korea are rapidly changing, eating 3 ‘meals’/day still is the typical major eating habits in Koreans.

Previous studies established that calorie restriction extends the lifespan of laboratory animals and might have beneficial effects on chronic diseases such as cardiovascular disease, cancer, and neurodegenerative disorders in humans [12]. Recently, intermittent fasting has received much public attention. Experimental intermittent fasting resulted in overall reductions in calorie intake of up to 30%. However, in some studies, although the small amount of calorie restriction (5–10%) was performed, beneficial physiologic events were observed. This suggests that an extended fasting period itself may contribute to these benefits [15]. Stote et al. conducted to establish the effects of a reduced-meal frequency diet on health indicators in 15 healthy, normal-weight adults aged 40–50 years [19]. During the two 8-week treatment periods, subjects consumed all the calories needed for weight maintenance in either 3 meals/day or once meal day. Their study suggests that without a reduction in calorie intake, reduced frequency of meals does not afford major health benefits in humans.

Previous epidemiological studies have reported an inverse relationship between meal frequency and body weight and adiposity. Some studies showed higher meal frequency is related to lower body weight or obesity, while other studies didn’t show any association between meal frequency and markers of adiposity [20]. These inconsistent findings could be the result of the influence of additional confounding factors, such as total energy intake and physical activity [21]. MetS and dietary intake are closely related, and excessive energy intake causes obesity and results in increasing incidence of MetS. Therefore, a study evaluating the relationship between MetS and diet must account for total calorie intake. In this study, we checked whether there is an interaction between total calorie intake and meal frequency to examine whether we should adjust calorie intake as a confounding factor or analyze by range of calorie intake. We found that there was no significant interaction between calorie intake and meal frequency. Therefore, we adjusted for calorie intake as a confounding factor instead of analyzing data by range of calorie intake.

In the present study, the MF ≤ 2 group had higher fat intake and a greater prevalence of obesity than the MF3 group in both genders. There is evidence that fat intake is negatively correlated with insulin sensitivity [22]. Moreover, men in the MF ≤ 2 group exhibited a significantly higher risk of MetS compared to men in the MF3 group even after adjusting for various kinds of confounding factors. There are several possible explanations for the association between lower meal frequency and higher risk of MetS. When people eat only 1 or 2 meals/day, they are more likely to eat more calories at each meal. An abrupt increase in postprandial glucose level induces higher insulin response and eventually results in insulin resistance [23]. Furthermore, postprandial hyperglycemia and hyperlipidemia contribute to oxidative stress and chronic inflammation, providing a mechanistic link between these conditions and components of MetS [24, 25].

The present study found that a higher meal frequency was associated with lower prevalence of MetS in men but not in women. Men who ate more frequently were leaner than others, even if they had a higher total energy intake. In contrast, women who ate more frequently had a higher BMI and waist circumference as well as higher total energy intake than those who ate less frequently. In addition, the present results in men are consistent with previous studies that have reported that a higher eating frequency is associated with a better lipid profile. In a national population-based sample of young Australian adults, a higher number of eating occasions was significantly associated with reduced cardiometabolic risk factors (waist circumference, fasting glucose, fasting insulin, triglycerides, total cholesterol and LDL-cholesterol) in men only. They found no significant associations between eating frequency and adiposity in women [26]. Consistent with this result, several cross-sectional studies also reported that a higher eating frequency is associated with leanness in men but not in women [27‐29]. Drummond et al. and Yannakoulia et al. also reported no association between eating frequency and body composition in women [28, 29]. In addition, Duval et al. reported that in a prospective observational study of 85 premenopausal women, the association between adiposity and eating frequency was no longer significant after adjusting for confounding factors, such as physical activity [21, 30]. However, the precise mechanisms responsible for gender-specific associations between meal frequency and MetS risk are not clear. In the present study, there was no difference in physical activity between men in the MF3 group and men in the MF ≤ 2 group. Furthermore, after adjusting for physical activity, lower meal frequency was associated with higher risk of MS in men. Whereas, in women, the increased risk of MetS in the MF3 group was attenuated after adjusting for confounding factors, including caloric intake and physical activity. Difference in dietary quality may contribute for these findings [31]. It is possible that women who ate more often were eating unhealthy snacks and under-reported these items. Several large surveys have shown that the proportion of total energy intake provided by ‘snacks’ in adults is around 15% [32, 33]. In a Korean study by Kim et al., the prevalence of subjects who ate one or fewer snacks per day was 83% (42% ate no snacks, and 41% ate one snack daily) [34]. However, total calorie intake in the KNHANES was calculated by a food intake survey using the individual 24-h diet recall method. Therefore, our study also took into account calories consumed from ‘snack’ foods. Another suggested explanation is the different fat distribution of men and women. Men are more likely to store excess fat centrally, whereas women store it peripherally. Because central obesity has been known as more metabolically harmful than peripheral fat, if subjects with a lower meal frequency are more likely to be obese and store fat, then this may explain why a lower meal frequency was associated with metabolic risk factors in men. Regarding the gender-specific associations between meal frequency and MetS in adults, the available scientific data are still limited. Therefore, further studies are needed to clarify this issue and, to find underlying mechanism that may be responsible for a gender-specific association.

The strengths of the present study are that it involved a large, nation-wide, population-based sample and also involved the collection of extensive data on potential confounders. Nevertheless, this study has several limitations. First, this was a cross-sectional study, and so could not determine causal relationships between meal frequency and MetS. Second, there was a potential recall bias because information was collected via self-reported questionnaires. In addition, although the present study attempted to overcome potential source of bias by excluding subjects reporting variable meal frequency for both 2 days, we cannot entirely eliminate the possibility that these inclusion/exclusion criteria may affect our study results. In fact, we found that there were significant differences of variables between subjects who were enrolled and excluded. We speculate that age of two groups may explain a considerable part of differences of metabolic and lifestyle profiles. Because younger people tend to have irregular meal pattern, they were more likely to be excluded in this study.

In Korean men, lower meal frequency (2 or fewer meals/day) was associated with higher risk of MetS compared to higher meal frequency (3 meals/day). This inverse relationship between meal frequency and MetS remained even after adjusting for potential confounding factors including total calorie intake and physical activity. However, in Korean women, higher meal frequency was associated with increased risk of MetS compared to lower meal frequency. After adjusting for confounding factors, the difference in MetS risk in Korean women between the higher and lower meal frequency groups disappeared. Our study suggests that both caloric intake and meal frequency may be important factors in metabolic disorders, and their relative influence varies according to gender.