Association between Ultra-Processed Food Consumption and Metabolic Syndrome among Adults in China—Results from the China Health and Nutrition Survey

The prevalence of metabolic syndrome (MetS) is increasing and the relationship between ultra-processed food (UPF) consumption and MetS remains uncertain in Chinese adults. This study aimed to examine the longitudinal association of UPF consumption with the risk of MetS and its components in Chinese adults. Adults aged 18 years and above who participated in at least two waves of the China Health and Nutrition Survey (CHNS) in 2009, 2015, and 2018 were included in this analysis. Dietary intake data were collected by three consecutive 24 h dietary recalls and weighing household foods and condiments. Depending on the purpose and extent of food processing, UPFs were classified using the NOVA food classification system. A multivariate Cox proportional risk model was used to explore the association between UPF consumption (grouped by quartile: quartile 1 (Q1), quartile 2 (Q2), quartile 3 (Q3), and quartile 4 (Q4)) and risk of MetS and its components. A total of 5147 adults were included. During a median (IQR) 6.0 (3.0, 9.0) year follow-up with 31,878 person-years, 1712 MetS cases were identified, with an incidence of 33.26%. After multivariable adjustment, the risk of MetS was increased by 17% in the highest quartile with UPF consumption (HR: 1.17, 95% CI: 1.01–1.35, p trend: 0.047), with the lowest quartile as a reference. For the components of MetS, the risk of central obesity, raised triglycerides (TG), reduced high-density lipoprotein cholesterol (HDL-C), and raised blood pressure (BP) was increased by 33% (HR: 1.33, 95% CI: 1.18–1.51, p trend: <0.001), 26% (HR: 1.26, 95% CI: 1.08–1.48, p trend: 0.003), 25% (HR: 1.25, 95% CI: 1.07–1.46, p trend: 0.007), and 16% (HR: 1.16, 95% CI: 1.03–1.32, p trend: 0.018) in the highest quartile with UPF consumption, respectively. Adults aged 45–59 years and living in urban areas with higher UPF consumption had higher odds of MetS. These results indicate that higher long-term UPF consumption was associated with an increased risk of MetS in Chinese adults. Further studies such as intervention trials are needed to confirm the mechanism of correlation between UPF consumption and health-related outcomes. Nutritional education actions are warranted to promote a balanced diet and improve the overall dietary quality of residents to reduce the risk of MetS effectively.


Introduction
Metabolic syndrome (MetS) is defined as a cluster of cardiovascular risk factors characterized by abdominal obesity, dyslipidemia, hypertension, and high fasting blood glucose [1]. MetS has received increased attention over the past decade and has become a major public health challenge worldwide. MetS is considered to be a risk factor for multiple noncommunicable diseases (NCDs), including cardiovascular disease (CVD), stroke, coronary heart disease, type 2 diabetes (T2D), and all-cause mortality [2]. A nationally representative cross-sectional survey among Chinese adults in 2000-2001 indicated that the community conditions, diet, and health in 15 provinces. The detailed design and procedures have been described elsewhere [31,32]. During the three waves of investigation in 2009, 2015, and 2018, blood samples were added at the same time, so the data from these three waves were used for analysis in this study. We excluded 4713 participants with deficiency of dietary, anthropometric data, and blood samples data; 30 pregnant or lactating women; 204 participants with implausible energy intakes (men: <800 kcal/day or >6000 kcal/day; women: <600 kcal/day or >4000 kcal/day); 7385 participants with only one wave; 5917 participants with MetS at baseline. Finally, a total of 5147 adults aged 18 years and above were included in this study ( Figure 1).

Dietary Assessment and UPF Consumption
Dietary data were collected using consecutive three-day 24 h dietary recalls (two weekdays and one weekend) for individuals in each wave of the CHNS. Meanwhile, a trained investigator weighed food items and seasonings such as oil and salt in the household inventory. Food consumption at the household level was calculated by the times of eating at home and the ratio of the energy intake of all members. Total energy and nutrients such as protein, fat, carbohydrate, and dietary sodium intake per day were calculated using the Chinese Food Composition Table [33,34].
According to the definition of NOVA classifications, food items were categorized into four groups [11]. UPF mainly includes the following food items, sugar-sweetened beverages (SSBs), packaged snacks, sweet, ice cream, chocolate, mass-produced packaged breads, cakes, desserts, biscuits, pastries, pre-prepared pies, pizza dishes, hot dogs, and

Dietary Assessment and UPF Consumption
Dietary data were collected using consecutive three-day 24 h dietary recalls (two weekdays and one weekend) for individuals in each wave of the CHNS. Meanwhile, a trained investigator weighed food items and seasonings such as oil and salt in the household inventory. Food consumption at the household level was calculated by the times of eating at home and the ratio of the energy intake of all members. Total energy and nutrients such as protein, fat, carbohydrate, and dietary sodium intake per day were calculated using the Chinese Food Composition Table [33,34].
According to the definition of NOVA classifications, food items were categorized into four groups [11]. UPF mainly includes the following food items, sugar-sweetened beverages (SSBs), packaged snacks, sweet, ice cream, chocolate, mass-produced packaged breads, cakes, desserts, biscuits, pastries, pre-prepared pies, pizza dishes, hot dogs, and sausages and other reconstituted meat products. As for uncertain food items, the presence in the list of ingredients of one or more food substances not used in kitchens including hydrolyzed proteins, "mechanically separated meat", fructose, inverted sugar, maltodextrin, interesterified, or hydrogenated oil identified a product as UPF.

Definition of Metabolic Syndrome
MetS is defined using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria in this study. If at least three out of five of the following components were present, the person was determined to have MetS: (1) central obesity: waist circumference (WC) ≥90 cm (men) and ≥80 cm (women); (2) raised triglycerides (TG): ≥150 mg/dL or relevant specific treatment for hyperlipidemia; (3) reduced high-density lipoprotein cholesterol (HDL-C): < 1.0 mmol/L (men) and 1.3 mmol/L (women); (4) raised blood pressure: systolic blood pressure (SBP) ≥ 130 mmHg or diastolic blood pressure (DBP) ≥ 85 mmHg or specific treatment of previously diagnosed hypertension; (5) raised fasting plasma glucose (FPG): ≥6.0 mmol/L or diagnosed type 2 diabetes previously [35].

Covariates and Physical Measurement
Multiple covariates were involved in this study including gender, age, education level, geographical location, income level, smoking history, alcohol drinking status, physical activity (PA), urbanization levels, body mass index (BMI), total energy intake, dietary protein, dietary fat, dietary carbohydrate, and dietary sodium. Age was divided into three groups (18-44 years, 50-59 years, and 60 years and above). Education level was divided into two groups (junior high school or below and senior high school or above). Residence was separated into two groups (urban and rural areas). In view of the differences between the north and the south, regions were divided into the north (Beijing, Liaoning, Heilongjiang, Shandong, Henan, and Shaanxi) and the south (Shanghai, Jiangsu, Zhejiang, Hubei, Hunan, Guangxi, Chongqing, Guizhou, and Yunnan). Annual per capita household income was divided into three groups (low, medium, and high by the tertiles). Smoking history and drinking past year were divided into two groups (yes and no), respectively. Physical activities included occupational, household chores, leisure time, and transportation, and calculated into a metabolic equivalent of task (METs h/week) based on the American College of Sports Medicine Association's recommended standard, and were then divided into three groups (low, medium, and high by the tertiles) [36]. Urbanization levels were calculated based on the economic environment of the community and the cultural and social environment and divided into three groups (low, medium, and high by the tertiles). BMI was calculated as body weight (kg) divided by the square of height (m 2 ) and divided into three groups (<18.5 kg/m 2 , 18.5-23.9 kg/m 2 , and ≥24.0 kg/m 2 ). WC was measured using an inelastic flexible ruler, and weight and height were measured using an electronic weight scale and portable SECA206 stadiometer. Cholesterol oxidase-phenol and amino phenazone methods were used to measure TG and HDL-C. Blood pressure was measured using a standard mercury sphygmomanometer (Korotkoff sound). The participants were in a seated position in a quiet room for at least five minutes of rest and with the bladder emptied. The average value of three consecutive standard measurements was taken as the result for each participant. Fasting plasma glucose was measured using the hexokinase method with a Roche 702 instrument. All measurements were performed by trained professional technicians with strict quality control.

Statistical Analysis
Categorical and continuous variables were described by n, percentage (%) and mean, and standard deviation, respectively. Categorical and continuous variables were compared by the χ 2 test and Kruskal-Wallis test given the skewed distribution of the data. A multivariate Cox proportional risk model was used to estimate the association between UPF consumption (grouped by quartile: quartile 1 (Q1), quartile 2 (Q2), quartile 3 (Q3), quartile 4 (Q4)) and risk of MetS and its components. We performed tests for linear trends by entering the median value of each quartile of UPF consumption as a continuous variable in the models. Meanwhile, stratified analysis was performed by covariates and interaction analysis was performed to evaluate the effect of stratification factors on the relationship between UPF consumption and the risk of MetS. All statistical analyses were conducted using SAS 9.4 (SAS Institute, Inc., Cary, NC, USA), and p < 0.05 (two-tailed) was defined as statistical significance.  Table 1 presents the demographic and baseline characteristics of the quartile of UPF consumption. Compared with those in the bottom quartile of UPF consumption, those with higher UPF consumption were more likely to live in urban areas, have higher education levels, higher income, lower levels of physical activity, higher BMI, higher energy intake, higher protein intake, higher fat intake, higher sodium intake, and lower carbohydrate intake (p < 0.05). Baseline HDL-C and FPG were different between the quartile of groups (p < 0.05) while WC, TG, SBP, DBP as well as gender, age, smoking history, and drinking past year were not significantly different between the quartiles of UPF consumption groups (p > 0.05).  Table 2 explores the associations of UPF consumption with MetS and its components in diverse groups. During a median (IQR) 6.0 (3.0, 9.0) year follow-up with 31,878 personyears, 1712 MetS cases were identified, with an incidence of 33.26%. After adjustment for confounding factors, such as gender, age, education level, place of residence, region, income level, smoking history, drinking status, metabolic equivalents, urbanicity, BMI, total energy, protein, fat, carbohydrate, and sodium intake, the risk of MetS was increased by 17% in the highest quartile with UPF consumption (HR: 1.17, 95% CI: 1.01-1.35, p trend: 0.047), with the lowest quartile as a reference.  Table 3 presents the sensitivity analysis of MetS risk and UPF consumption. The results showed that the positive association of UPF consumption with risk of MetS was consistent in women, 45-59 years age group, subjects in urban areas, and southern regions. In addition, place of residence and urbanization had an interactive effect on the association between UPF consumption and risk of MetS (p < 0.05).

Discussion
In this study, the association between UPF consumption and MetS of Chinese adults aged 18 years and above has been evaluated through longitudinal prospective data from the CHNS. In the present study, higher UPF consumption was found to be positively correlated with MetS. The association was stronger in women, adults aged 45-59, and those living in urban areas.
The results of multiple previous studies were consistent with our findings. Lavigne-Robichaud et al. showed that comparing the lowest quintiles diet quality score, adults with the highest contribution of UPF to total daily dietary energy intake can effectively increase the risk of MetS (OR: 1.9, 95% CI: 1.14-3.17) from a 2005-2009 cross-sectional study in Canada [37]. Dana et al. also found that in adults, high consumption of UPF was associated with a higher risk for MetS (OR: 1.88, 95% CI: 1.31-2.71) and its components [38]. Previous systematic reviews and meta-analyses have shown that the highest UPF consumption was associated with a significant increase in the risk of MetS (OR: 1.79, 95% CI: 1.10-2.90) [39,40].
There are several potential plausible mechanisms that may explain the correlation between UPF consumption and MetS. Firstly, UPFs are typically high in added sugars, salt, and saturated and trans fats; excessive intake of UPFs could result in an increase in C-reactive protein (CRP) levels [41]. Moreover, further inflammatory responses may occur, and it increases the risk of MetS [42]. Secondly, higher UPF consumption is inversely associated with a poor nutritional profile and quality and deficiency intake of dietary fiber, fruit, vegetables, and legumes [43]. In addition, ingredients in UPFs such as artificial sweeteners could result in dysbiosis of gut microbiota, glucose intolerance, insulin resistance, and diverse metabolic disturbance, which then leads to the development of MetS [44,45]. Thirdly, the physical properties of food were altered by a series of industrial processes, which could result in a higher glycemic load and reduction of gut-brain satiety signaling [46,47]. The release of incretin hormones and gastric inhibitory polypeptide may increase insulin secretion and promote a greater appetite and overconsumption [48,49].
In the present study, higher UPF consumption was positively associated with the risk of central obesity (33%), raised TG (26%), reduced HDL-C (25%), and raised BP (16%), while no statistical association was found between the highest quartile group and raised FPG. An increasing body of evidence shows that UPF consumption is linked with overweight/obesity/WC [16,[50][51][52]. Li et al. found that higher UPF consumption (≥50 g/d) was associated with an increased risk of overweight/obesity by 45-50% in Chinese adults aged 20 years and above using CHNS (1997-2011) [28]. The poor nutritional profile of diets with saturated fat and free sugar from UPFs contributes to more energy, weight gain, and higher odds of BMI [53]. A prospective Spanish cohort showed that adults with the highest tertile consumption of UPFs had a higher risk of developing hypertension (HR: 1.21, 95% CI: 1.06-1.37) [19]. Similarly, decreased potassium intake and increased sodium intake with UPF consumption may cause sodium/potassium imbalance, thus improving blood pressure levels [54]. In a systematic review and meta-analysis, Pagliai et al. found that no significant correlation was found between the highest UPF consumption and hyperglycemia. However, in two prospective cohort studies of UK and French adults, a diet with a higher proportion of UPFs was associated with an increased risk of type 2 diabetes (T2D) [20,21]. Of note, substances present in food packaging materials such as bisphenol-A (BPA) have been found to have endocrine-disrupting properties and a positive association with increased T2D in previous meta-analyses [55]. Collectively, higher UPF consumption has a certain adverse effect on the components of MetS. The specific mechanism and long-term health outcomes with UPF are warranted to explore.
Our findings suggest that UPF consumption was more associated with higher education levels and higher income. In Western countries, however, the situation is different. People with lower socio-economic profiles or educational levels are more likely to have higher UPF consumption [20,51]. As dietary patterns transition, UPFs are more widely available in China. People can afford to choose more food types due to the improvement in economic level while insufficient nutritional knowledge might lead them to choose durable, Nutrients 2023, 15, 752 9 of 12 palatable, and ready-to-eat UPFs. We also found that adults aged 45-59 years who live in urban areas with higher UPF consumption had higher odds of MetS. With economic growth and development, China has been undergoing a rapid urbanicity and nutrition transition [56,57]. Although urbanization promotes civilization progress, it also brings about some negative consequences on health, such as low physical activity and weight gain [58]. Coincidentally, the high palatability, convenience, and easy availability of UPFs make them more accessible in urban areas and promote overconsumption. There is accumulating evidence implicating UPFs with poor dietary quality [59]. In consequence, residents in urban areas with higher UPF consumption need more attention, thereby reducing the incidence of chronic non-communicable diseases.
To the best of our knowledge, this is the first population-based prospective cohort study to examine the association between UPF consumption and the risk of MetS in Chinese adults. UPFs were classified by an updated NOVA classification system. Robust analysis was performed using three 24 h dietary recalls and data from weighing foods and condiments in household inventories. Nevertheless, there are still some limitations in this study that should be noted. First, there may be a misclassification owing to a lack of food packaging and labeling information for some uncertain food items. Second, dietary information collected by the 24 h retrospective method may lead to recall bias. Third, although potential confounding factors were adjusted, the possibility of residual confusion cannot be completely avoided. Last, the results of 24 h dietary recall may not represent long-term diet habits completely. Future studies are needed to add data from food frequency questionnaires (FFQs) and explore the correlation between UPFs and health outcomes.

Conclusions
In conclusion, this study provides prospective evidence that higher UPF consumption is positively correlated with MetS and its single component. Meanwhile, adults aged 45-59 years who live in urban areas with higher UPF consumption had a higher risk of MetS. Further studies such as intervention trials are needed to confirm the mechanism of correlation between UPF consumption and health-related outcomes. From a public health point of view, considering the gradual upward trend of UPF consumption in Chinese residents, nutrition education is warranted to promote a balanced diet and improve the overall dietary quality of residents to reduce the risk of MetS effectively.  Informed Consent Statement: Informed consent was obtained from all subjects involved in the study.

Data Availability Statement:
Data sharing is not applicable to this study according to the National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention.