**1. Introduction**

Central obesity, elevated blood pressure, dyslipidemia, and insulin resistance are cardiometabolic risk factors grouped together in metabolic syndrome (MetS). Since the WHO defined MetS in 1999, there have been multiple other definitions of MetS, with the most recent harmonized definition [1,2]. All components of MetS are plaguing the world with an increasing incidence and prevalence [3–5]. Obesity, mostly of the central type, is a pathophysiological cornerstone of MetS and is considered to be the main culprit that leads to other metabolic disturbances found in MetS [4,6–8]. Epidemiological studies have shown that in the last 40 years, obesity prevalence has doubled, to such a degree that nearly a third of the world's population is now considered overweight or obese [5,9]. Before the start of the globalization trend, obesity was most prevalent in the US and the countries of Western Europe, while currently we are witnessing an increase in obesity rates in all ages and sexes, regardless of geographical location, socioeconomic status, and ethnicity [5,10]. Likewise, the prevalence of MetS in the US is also high, at 34.7% (95% CI, 33.1–36.3%) [11].

**Citation:** Vrdoljak, J.; Kumric, M.; Vilovic, M.; Martinovic, D.; Rogosic, V.; Borovac, J.A.; Ticinovic Kurir, T.; Bozic, J. Can Fasting Curb the Metabolic Syndrome Epidemic?. *Nutrients* **2022**, *14*, 456. https://doi.org/10.3390/ nu14030456

Academic Editors: Abeer M. Mahmoud and Shane Phillips

Received: 16 December 2021 Accepted: 19 January 2022 Published: 20 January 2022

**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

Similar trends in prevalence are also found in other countries across the globe, with the highest MetS prevalence in Mexico (41%) [12–15].

Furthermore, the prevalence of hypertension is also on the rise, particularly in lowmiddle income countries [16–18]. In addition, the same is true for the prevalence of insulin resistance/diabetes mellitus type 2 and dyslipidemia [19,20]. The cost of treating these comorbidities is substantial. According to the American Diabetes Association (ADA), the total costs of diagnosed diabetes have risen from \$245 billion in 2012 to \$327 billion in 2017, resulting in a 26% increase over a five-year period [21]. Moreover, adults with obesity in the US experienced \$2505 higher annual health care costs, which is a 100% higher cost paid compared to those with lesser weight [22]. Similarly, according to American Heart Association (AHA) and Medical Expenditure Panel Survey (MEPS) data from (2016–2017), the costs of treating cardiovascular disease (CVD) in the US were estimated to be \$363.4 billion (or \$406 billion, inflation-adjusted) [23].

There are no studies directly examining the economic burden of MetS per se. Still, since other studies have shown how the prevalence of MetS among obese adolescents and adults ranges from 30.3% up to 52%, we may postulate that the direct medical costs of MetS are around 1/3 to 1/2 of the costs of obesity (from \$78 billion to \$135 billion) in the US [24,25]. Since MetS and obesity mostly precede CVD and type II diabetes, there is a growing need for cheap and effective treatment strategies to combat this increasing burden.

Lifestyle and dietary changes (physical activity, calorie intake/bodyweight reduction) are at the forefront of metabolic syndrome treatment [26–28]. One of the dietary methods proposed for controlling metabolic risk factors is fasting [29]. Intermittent fasting (IF) and time-restricted feeding (TRF) describe an array of feeding patterns in which calorie intake is restricted to a specific time period (8 h feed/16 h fast, 4 h feed/20 h fast, alternate day fasting, etc.) [30]. Recently, IF/TRF has shown promising results in managing cardiometabolic risk factors [29,31,32].

Hence, in the first part of this comprehensive review, we present the latest data on MetS epidemiology and pathophysiology, while in the second part, we explore the viability of IF and TRF for managing MetS.

### **2. The Definition of Metabolic Syndrome**

In 1988, during his Banting lecture, Reaven characterized a cluster of conditions related to insulin resistance. He called the cluster "Syndrome X" or "the deadly quartet", and it consisted of obesity, non-insulin-dependent diabetes mellitus, hypertension, and dyslipidemia [26,33]. Since then, multiple definitions have been brought forward to better encompass this clustering of cardiometabolic risk factors. These include the WHO definition from 1998, the NCEP (National Cholesterol Education Program) definition from 2003, and the IDF (International Diabetes Federation) definition from 2006 [20]. To avoid further discrepancies and to standardize the diagnostic criteria, several major health organizations jointly produced the harmonized definition of MetS that is currently in use [34].

According to the harmonized definition, MetS is defined by the following criteria:

(1) The presence of insulin resistance/prediabetes (glucose level > 100 mg/dL (5.6 mmol/L)), or diagnosed type 2 DM.

(2) Enlarged waist circumference (the exact values of which are adjusted according to population-specific and country-specific criteria).

(3) HDL-C < 40 mg/dL (1.03 mmol/L) in men and <50 mg/dL (1.29 mmol/L) in women or triglycerides ≥ 150 mg/dL (1.69 mmol/L) (with the inclusion of those taking medicine to treat dyslipidemia).

(4) Systolic blood pressure ≥ 130 mm Hg or diastolic blood pressure ≥ 85 mm Hg (including patients on anti-hypertensive therapy).
