Compared to 173 million obese people in 2014, 257 million adults worldwide (6% of men and 9% of women) are predicted to be living with severe obesity, showing a rapid increase in the number of obese people [1
]. Obesity is now replacing malnutrition and infectious diseases as the most critical cause of suboptimal health. Obesity has been linked to diabetes, coronary heart disease, cancer, metabolic syndrome, and sleep-disordered breathing [2
]. In addition, obesity can also cause the elevation of oxidative stress, inflammatory state, and hypoxia, which leads to the dysfunction of perivascular adipose tissue (PVAT) [3
Metabolic syndrome is also a growing concern characterized by pathological metabolism of protein, fat, carbohydrates, and other substances; it is a risk factor for diabetes, cardiovascular, and cerebrovascular diseases [5
]. The amount and quality of many types of cells found in adipose tissue, including adipose stem cells (ASC), is altered as a result of obesity. These changes in the function and nature of ASC impair adipose tissue remodeling and adipose tissue function, leading to metabolic disorders [6
]. The common causes of these diseases are insulin resistance and hyperinsulinemia secondary to obesity, especially central obesity [7
Most obese people rarely choose to exercise because of work stress or psychological reasons; they are more enthusiastic about dietary intervention. Dietary adjustment is the heart of obesity treatment. Weight loss diets include various permutations of energy restriction, macronutrients, and food and dietary intake patterns [8
]. In recent years, various dietary adjustment methods have become increasingly popular. Current guidelines recommend continuous calorie restriction (CCR; about 500 or 750 kcal of energy deficiency per day, or 30% of baseline energy requirements limits) and comprehensive lifestyle interventions as the cornerstone of obesity treatments [9
]. On average, this method produces moderate weight loss (5–10% ≥ 1 year) [9
Because traditional CCR methods are relatively ineffective in achieving and sustaining weight loss, there has been growing interest in identifying alternative dietary weight-loss strategies that limit the energy intake to specific periods of the day or extend the gap between meals (i.e., intermittent calorie restriction, ICR) [10
]. Intermittent fasting (IF) comes in many forms and includes regular breaks. A common form of IF includes fasting once or twice a week for up to 24 h, followed by discretionary food intake for the remainder of the day, known variously as periodic long-term fasting, ICR, intermittent energy restriction (IER) [11
], time-restricted eating (TRE, i.e., eating only for 8 h and then fasting for another 16 h a day), and alternate-day fasting (ADF) [12
]. However, it is not yet certain whether TRE has the same health effects as other forms of IF [10
]; therefore, we omitted TRE in this study.
Continuous fasting has become widespread in daily life, and intermittent fasting has become increasingly popular. Intermittent fasting is a dietary pattern alternating between normal energy and energy restriction (or complete fasting) and has attracted substantial attention from scholars [14
]. IF reduces body mass and improves glucose and lipid metabolism. Its benefits include reducing the risk of diabetes, cardiovascular disease, and stroke, inhibiting tumor growth, and preventing Alzheimer’s disease and Parkinson’s disease [15
A study discovered that IF might be comparable to, but not superior to, CCR for weight loss and metabolic illness prevention [10
]. However, another study suggested that IF is a more effective strategy in managing the body weight, fat mass, and waist circumference of individuals with metabolic syndrome [16
]. These authors found that, compared with CCR, IF decreased the levels of high-sensitivity C-reactive protein and prothrombin and thromboplastin times. A review suggested that IF might be superior to CCR because it helps conserve lean body mass at the expense of fat mass [17
]. A growing body of evidence suggests that IF has more benefits and can be more effective than CCR. Nevertheless, IF versus CCR on weight loss in overweight and obese people remains controversial.
At present, there are a variety of obesity evaluation indicators in the home and abroad; the most commonly used are: body mass index (BMI in kg/m2), body fat rate (body fat percentage, BF%), waist circumference (WC), body weight (BW), etc. Among them, BMI is widely used to evaluate generalized obesity. The BF% is widely applied to evaluate the proportion of body fat, WC is widely used to evaluate valence abdominal obesity, and BW is mainly used to evaluate abdominal obesity and health risk. Therefore, our research mainly looked at the BMI, BW, WC, etc.
Because of the growing concern regarding obesity and the diseases it causes, a literature review was carried out to compare these weight-loss strategies. Therefore, our study aimed to compare IF and CCR regarding effectiveness for weight loss in people with obesity or metabolic syndrome.
We performed a systematic review and meta-analysis comparing IF and CCR regimens regarding BMI and body weight reduction. IF is beneficial for weight loss, and the effect was significant. If dietary intervention is well studied, it will substantially impact society. Our findings are consistent with those of Enríquez Guerrero et al. [34
Calorie restriction involves reduced caloric intake of about 25–30% without eliminating essential nutrients [35
]; this approach prolongs health and life in rodent and primate models [36
]. The mechanisms of these benefits are related to the inhibition of anabolism, improvement of mitochondrial energy metabolism, and the conversion of substrate utilization. These processes are related to the reduced dependence on glucose metabolism and increased fatty acid oxidation [35
]. IF is an effective dietary intervention because it improves the lipid profile and reduces body weight [38
]. IF has a positive effect on glycolipid metabolism in obese individuals. A study showed that eight consecutive weeks of ADF in obese adults led to a 6.8% reduction in blood glucose levels after fasting and a 22.6% reduction in insulin concentrations [12
]. ADF improved insulin signaling and altered the proportion of α and β cells in obese mouse pancreases by reducing β cell apoptosis, increasing Akt (serine/threonine) phosphorylation, and improving diet-induced obesity islet tissue remodeling and β cell function [39
]. IF improved glucose homeostasis through autophagy in a rodent model; TRE promoted the expression of glycolytic genes (Hk2, PFK, and PK) in obese mice and inhibited the expression of gluconeogenesis (G6pc, Pck1, and Fbp1), thereby promoting glucose uptake in peripheral tissues, and inhibited gluconeogenesis, ultimately reducing the blood glucose levels [40
]. IF regulates glucose homeostasis by the intestinal flora [41
]. ADF improves blood lipid levels whilst reducing the body mass and body weight, related to the depletion of liver glycogen reserves during fasting; triglyceride levels indicated that free fatty acids are released into liver cells to produce ketone energy [42
]. IF (1 day of fasting followed by 2 days of feeding) promotes browning of white adipose tissue; the possible mechanisms include the activation of type II cell signaling through increasing the secretion of IL-5, stimulation of M2 macrophages, and reduction of M1/M2 macrophage ratios [43
In addition to its positive effects of fasting, side effects are inevitable, such as muscle pain, sleep disturbances, headaches, and hunger, occurring mainly in the first few days of fasting [44
]. In the group with longer fasting periods, baseline values for emotional well-being (EWB) and physical well-being (PWB) were lower [44
]. These side effects of fasting do not occur for all people because of different physical fitness levels, including personal health, physiological mechanisms, lifestyle, etc.
Identifying long-term effective dietary interventions is critical to reducing the range of diseases caused by obesity [45
]. Many people lead sedentary lifestyles because of office work, and exercise may be challenging. Therefore, dietary interventions are becoming more popular.
Elevated BMI is correlated with disease prevalence, suggesting that reducing BMI will reduce the disease burden. Epidemiological studies showed that elevated BMI could cause cardiovascular disease, diabetes mellitus, chronic kidney disease [46
], cancers [48
], and musculoskeletal disorders [49
]. In the studies we considered, all subjects had BMIs greater than 25 kg/m2
. Our meta-analysis found that IF and CCR improved BMI, and weights decreased significantly. While our analysis showed no difference between the two interventions for improvement in BMI, we can draw some inferences from the analysis. Of the eleven studies, seven showed a relatively significant decrease in BMI with CCR [23
], and four showed a relatively significant decrease with IF [26
]; however, the differences in these comparisons were relatively small. In the analysis of BMI, heterogeneity was 45% (moderate). The source of heterogeneity was different fasting days of IF. Therefore, we suspect that the weight loss effect is more significant when the number of fasting days in a week is greater than two.
We considered age as a possible source of heterogeneity. The heterogeneity of three studies, including subjects older than 60, was zero. Age is correlated with BMI to some extent [51
]; as people age, their BMI increases. We speculate that CCR may be more appropriate in older people, especially the elderly. Their autoimmunity is relatively low, they require food to replenish energy, and their ability to endure hunger is relatively weak. Because their bodies have poor metabolic capacity, extremely low-calorie restriction throughout the day can be harmful. Therefore, persistent calorie restriction is a safer dietary intervention for them. This view was also mentioned in a review [52
]. Studies showed that ADF did not produce superior adherence to daily calorie restriction [53
]. In previous studies on other forms of IF, abandonment was reported in up to 40% of participants [54
]. Therefore, future studies should determine the appropriate dietary intervention method according to the population and individual wishes.
We also analyzed changes in body weight. As articulated in the results, the differences in weight between the two interventions showed significance. The analysis showed that IF was more effective for weight loss. This finding suggests that IF requires further study and in-depth exploration. The weight loss effect of IF has been demonstrated in clinical trials. A strict IF of 4 to 24 weeks reduced subject body mass by 4–10% [55
]. Other scholars pointed out that the role of IF in weight loss is not significantly different from that of a calorie-restricted diet, consistent with our analysis; however, IF was better at maintaining lean body mass [17
11 May was declared World Obesity Day by the World Health Organization. Today, obesity is no longer merely a threat to individual health; it is also a social problem that has attracted worldwide attention for over 30 years, as overweight and obesity continues to grow. All sectors of society should work together to create a healthy environment that supports the active adoption of healthy lifestyles.
IF and CCR have powerful weight loss effects. Although weight and fat mass decreased in most studies, it is crucial to consider protocol adherence and exit rates. Sundfør et al. showed that IF subjects were hungrier than CCR subjects, and their willingness to persist decreased [56
]. However, IF also offers some benefits. There are several studies on the effects of IF on cardiovascular disease in humans. A rat study found that IF improved glycemic control and protected the myocardium from ischemia-induced cell damage and inflammation more than daily CR [57
]. These findings suggest that IF has substantial clinical significance, and it is a dietary intervention method that deserves in-depth research.
Our meta-analysis has some limitations. Firstly, the sample sizes of some of the included studies were small, leading to heterogeneity. More largescale studies are necessary to enhance the accuracy of our meta-analysis. Second, the follow-up time varied widely, and some did not follow-up.
In our study, it seems that ADF produces better results. More research is therefore needed to assess the mechanism of intermittent fasting regimens, and the safety of each type of them is also to be valued to finally determine applicable dietary interventions for specific groups of people.
In summary, we found that IF was more effective than CCR for weight loss; however, there was no difference in BMI improvement. Although the data are insufficient, our study shows that IF is superior to CCR in metabolism in obese people. We hope that there will be more long-term studies of dietary interventions and further investigation on cognitive function, which may reduce the economic burdens caused by obesity. Studies need to compare IF and CCR with controlled patient characters to confirm the effectiveness of these weight-loss methods and to determine whether IF is more appropriate for specific populations.