**3. Epidemiology of Metabolic Syndrome**

The central type of obesity is the most common characteristic found in MetS; therefore, the incidence and prevalence of MetS closely follow that of obesity [35,36]. Every two

years, the US conducts the National Health and Nutrition Examination Survey (NHANES), in which they obtain obesity rates among people aged two or older. The latest data for 2017–2018 show that obesity prevalence among adults was 42.4% [37]. By contrast, the obesity rates for adults at the start of the decade were 35.7%, with a rising trend of approximately 2% every two years. The rising trend is slower for the pediatric population, with the 2009–2010 obesity rate at 16.9% and the 2017–2018 obesity rate at 19.3% [37]. In a study by Hirode et al., where the authors examined NHANES data form 2011 to 2016, among 17048 participants, the MetS weighted prevalence was 34.7% (95% CI, 33.1–36.3% [*n* = 5885]) [11]. In other words, as much as one-third of the US adult population suffers from MetS.

The large prevalence is not restricted to the US, as comparable data were found in Brazil, where the latest MetS prevalence was 38.4% [13]. High waist circumference (65.5%) and low HDL cholesterol (49.4%) were the most prevalent MetS components among the Brazilian population. In addition, MetS was more frequent among women (41.8%), individuals with less education (47.5%), and older adults (66.1%) [13]. Similarly, in Mexico, investigators performed a systematic meta-analysis on 15 studies in which the pooled prevalence of MetS was 41% (95% CI 0.34–0.47) [12].

In Asia, a metanalysis in which investigators pooled MetS prevalence data from the Chinese population from 2008–2015 found that the pooled prevalence for subjects aged 15 years and older was 24.5% (95% CI: 22.0–26.9%). This metanalysis on the Chinese population also saw a similar trend, according to which the MetS prevalence was higher in females 27.0% (95% CI: 23.5–30.5%) vs. males 19.2% (95% CI: 16.9–21.6%) [38]. However, another study on the Chinese population showed marked differences in MetS prevalence between various ethnic groups. The Korean population featured the highest MetS prevalence (35.42%), the Hui population the second highest (22.82%), while the Mongolian and Tibetan populations featured the lowest (11.61%) and (6.17%) respectively [39].

Furthermore, in a European study examining data from two cohorts, one from Russia and the other from Italy, the MetS prevalence was 37% for the former and 21% for the latter [40]. In addition, another study examined the data from 34,821 subjects from 12 cohorts from 10 European countries and one cohort from the USA. MetS prevalence was 24.3% (8468 subjects: 23.9% in men vs. 24.6% in women, *p* < 0.001), with an age-related increase in prevalence across all cohorts [15]. Furthermore, in a study on the Portuguese population, in which data were gathered from 2007 to 2009, MetS prevalence was 36.5%, 49.6%, and 43.1%, using the Adult Treatment Panel III, International Diabetes Federation, and Joint Interim Statement definitions, respectively [14]. MetS prevalence was significantly higher in women and the older population in Portugal, as shown in the aforementioned studies. At the same time, it was also more frequent in non-urban areas than in urban areas (*p* = 0.001) [14]. Interestingly, in contrast to these findings, a study on the Czech population found that MetS is less common in females 25.5%, then in males 37.6% [41]. Akin to these findings, MetS prevalence was also higher in Slovakian males (30.2%), than in females (26.6%), with an increasing trend from 2003 to 2012 [42].

When examining the data we mentioned, we can see large differences in MetS prevalence among various populations, from the low of 11.61% in the Tibetan population, to the high of 41% in the Mexican population [12,39]. The reasons behind the observed discrepancies are probably a result of different lifestyles, with Western dietary habits making people more susceptible to MetS. If we take a closer look at migrant populations (from countries with low to countries with high rates of obesity) we observe a rather interesting twist. Namely, although migrants arrive with a health advantage, including generally healthier body weight, intrinsic and environmental factors combine to cause unhealthy weight gain, often to beyond the levels seen in native populations [43]. According to Neel et al., this observation may be explained from an evolutionary standpoint. Although the loss of uricase may have provided a survival advantage by amplifying the effects of fructose to enhance fat stores, and by increasing blood pressure in response to salt, the absence of the "thrifty" uricase gene may have caused a range of detrimental metabolic effects on modern

humans (characterized by excessive caloric intake), thus explaining the current epidemic of obesity and diabetes [44]. The putative mechanism associating fructose and loss of uricase lies in the observation that uric acid may regulate fructose metabolism by affecting fructose transporters in the intestines and fructokinase in the liver [45]. Nevertheless, with the Western lifestyle prevailing in most of the world, there is an increasing global trend of MetS prevalence, with approximately one-quarter of the world's population currently suffering from MetS [11,20,46].
