Obesity has become a pandemic that affects all populations of all ages living in countries of all income levels.1 Attributed to sedentary lifestyle and energy dense diet, obesity is a risk factor for cardiovascular disease, insulin resistance, type 2 diabetes and even some types of cancer.2 These comorbidities also affect the immune system adversely and can exacerbate infectious diseases as observed in the most recent case of pandemic COVID‐19.3, 4 The need for effective solutions is urgent and diet is one of the most important targets for intervention,1 alongside education,1, 2 behavioural therapy,2, 5 exercise2, 6-8 and bariatric surgery.2, 9, 10 Dieting trends have indeed been many and varied. One such trend that has gained popularity in the past decade is intermittent fasting (IF).11

Not a novel concept in itself, IF has been followed all over the world in one form or the other since time immemorial.11 It is a broad term encompassing a wide range of protocols with one underlying principle—abstaining from food intake for longer periods than the usual overnight fast. Popular IF protocols fall in the following three categories: whole day fasting (WDF), alternate day fasting (ADF) and time‐restricted feeding (TRF). WDF protocols call for complete abstinence from food for 1 or 2 days per week with ad libitum food intake the rest of the week. ADF involves alternating 24 hours periods of fasting and ad libitum food intake while TRF involves following a routine every day where certain hours are designated as eating periods and the remaining hours as fasting periods (eg 8 hours eating period, 16 hours fasting period).12 IF is considered an easier alternative to traditional continuous energy restriction methods since it does not involve tedious calorie counting. This ease has been proposed to improve adherence to the diet regimen which in case of continuous energy restriction is known to decline within 1‐4 months irrespective of results.13

During IF, glucose levels decrease followed by the depletion of glycogen reserves in the liver. This triggers gluconeogenesis which leads to the release and catabolism of fats from adipocytes accompanied by a decrease in insulin secretion along with an increase in glucagon secretion.14 The role played by glucagon in the circadian rhythm of pancreatic islet cells was recently described by Petrenko et al15 Circadian rhythms are biological clocks that operate in all light sensitive organisms and are responsible for temporal coordination of physiological processes.16-18 They are a fundamental anticipatory mechanism that enable organisms to adapt to environmental changes.17 One of the factors that have a major effect on circadian rhythms and associated anticipatory behaviour is meal timings. For example, mice on a TRF regimen show an increased activity 1‐3 hours before the regular eating window.19 This effect of IF was initially thought to be controlled by both the central circadian clock (suprachiasmatic nucleus (SCN) of the hypothalamus) as well as the peripheral circadian clock viz. the endocrine signals from the liver, pancreas, intestine, muscles and adipose tissue.17, 20 That is, when food is provided during daytime, the SCN controls the metabolic activity and behaviour while the peripheral oscillators are in charge when food is provided during night‐time.20 However, an SCN‐independent feeding entrained oscillator in the form of dorsal striatum dopamine has recently been described. Briefly, when food is available for regular but time restricted intervals, the food entrained oscillator takes precedence over the SCN in controlling food anticipatory activity.19 It is important to note that short term disruptions of the circadian rhythm in humans were shown to decrease insulin sensitivity which is a risk factor for type 2 diabetes.21 In another study involving mice, synchronization of feeding windows with the circadian rhythm prevented weight gain even when fed with a high fat diet. Their counterparts, however, when fed ad libitum with the same diet gained weight. Interestingly, there was no difference in the total energy intake between the two groups.11

Another factor that plays a bidirectional role in maintaining circadian rhythms is gut microbiota.5 The circadian clock of the host brings about diurnal oscillations in the function and composition of the gut microbiota while signals from the microbiota in turn regulate the circadian rhythms of the host.22 In mice, IF was shown to reshape the gut microbiota which in turn promoted the browning of adipose tissue. The role played by the microbiota was confirmed by the absence of this phenotype in germ‐free mice and its induction after they received a microbiota transfer.23 Brown adipose tissue, specifically the activity of uncoupling protein 1 therein, mediates a process called non‐shivering thermogenesis which has been shown to counteract excessive energy intake by reinstating energy balance. Hence, IF mediated browning of adipose tissue could be an effective therapy for obesity and related metabolic diseases.23

In human studies, IF has shown moderate weight loss and was as effective as traditional continuous energy restriction.13 Both ADF and WDF showed a weight loss of ~3%‐9% within 12‐24 weeks while data on TRF are not available. A reduction in total cholesterol (~5‐21%), triglycerides (~14%‐50%) as well as a reduction in the levels of low‐density lipoproteins was also observed.12 Plasma levels of adiponectin are often reduced in obese individuals.24 IF has been shown to reverse this trend.14 Moreover plasma levels of leptin, which positively correlate with increasing adipose tissue mass,25 decrease during IF.14 Adiponectin and leptin are cytokines secreted by adipocytes (adipokines) that regulate body weight by controlling glucose uptake, lipid accumulation and appetite.26 IF also leads to lowered levels of inflammatory markers such as interleukine‐6, homocysteine and C‐reactive protein.14 These changes along with the decrease in resting heart rate and blood pressure during IF limit the risk of cardiovascular disease.14, 27 IF was also associated with an increase in insulin sensitivity and a decrease in the levels of glycosylated haemoglobin (HbA1c) in patients with type 2 diabetes. However, these changes were transient and reversed upon returning to a normal diet.14 Studies in mice have shown that chronic ADF leads to improved brain function and structures as well as better outcomes of age‐related neurological disorders such as Alzheimer's disease, Parkinson's disease and stroke.20, 28

Despite the apparent health benefits, IF does come with its own set of drawbacks. The body requires time to adapt to ketones as a source of energy instead of glucose. Consequently, fatigue and dizziness leading to a general bad mood, especially at the beginning of an IF regimen, are not uncommon. IF in conjunction with antidiabetic drugs may cause fatally severe hypoglycaemia. In the elderly, fluctuations in glucose levels during IF are associated with an increased propensity to lose balance and fall, thereby increasing the risk of fractures. Besides, IF is contraindicative for children, pregnant people and people performing heavy physical work.14 A loss of muscle mass can occur if protein content of the meals consumed during IF is insufficient. In fact, a high‐protein diet might also improve satiety and reduce hunger.29 Information about the optimal duration of IF as well as its long‐term benefits is limited.12

To summarize, IF is promising not only as an alternative weight loss technique but also as a non‐pharmacological treatment method.12, 23 It is associated with several health benefits including regulation of circadian rhythms and gut microbiota,5, 22, 23 improved insulin sensitivity and decreased risk of cardiovascular disease,12, 14 as well as better outcomes of age‐related neurological diseases.20 However, at this stage of the epidemic, it is amply clear that a silver bullet to tackle obesity does not exist and it requires a concerted treatment involving dietary modification, education, behavioural therapy, exercise and sometimes even bariatric surgery.2 Therefore, future research combining IF with physical activity is paramount. Their combined effect on metabolism, behaviour, long‐term overall health as well as longevity perhaps also holds the answer to the titular question.

肥胖已成为一种流行病，影响到生活在所有收入水平国家中的所有年龄段的所有人口。1肥胖归因于久坐的生活方式和高能量饮食，肥胖是心血管疾病，胰岛素抵抗，2型糖尿病甚至某些类型癌症的危险因素。2这些合并症还会对免疫系统产生不利影响，并可能加剧最新的大流行COVID-19病例中观察到的传染病。3，4迫切需要有效的解决方案，饮食是最重要的干预目标之一，1除教育，1、2行为疗法，2、5锻炼2、6-8和减肥手术外。2，9，10节食趋势确实是多种多样的。在过去十年中越来越流行的一种趋势是间歇性禁食（IF）。11

IF本身并不是一个新颖的概念，但自远古时代开始就以一种或另一种形式在全世界范围内受到关注。11它是一个广义术语，涵盖具有基本原则的各种方案，与通常的通宵禁食相比，食物摄入的时间更长。流行的IF协议分为以下三类：全天禁食（WDF），隔日禁食（ADF）和限时喂食（TRF）。WDF协议要求每周禁食1或2天，在本周剩余时间内随意摄入食物。ADF涉及交替的24小时禁食和随意进食，而TRF涉及每天遵循例行程序，其中某些小时被指定为进食期，其余时间作为禁食期（例如8小时进食期，16小时禁食期）。12IF被认为是传统连续能量限制方法的更简便替代方法，因为它不涉及乏味的卡路里计数。有人提出这种缓解措施可改善对饮食方案的依从性，已知这种饮食方案会在持续的能量限制的情况下在1-4个月内降低饮食效果。13

在中频期间，葡萄糖水平降低，随后肝中糖原储备的耗尽。这触发糖异生，导致脂肪从脂肪细胞释放和分解代谢，伴随胰岛素分泌减少以及胰高血糖素分泌增加。14胰高血糖素胰岛细胞中的生理节律所起的作用最近被Petrenko的等描述15个昼夜节律是，在所有的光敏感的生物体操作并负责生理过程的时间协调生物钟。16-18它们是使生物适应环境变化的基本预期机制。17进餐时间是影响昼夜节律和相关预期行为的主要因素之一。例如，采用TRF疗法的小鼠在常规进食窗口之前1-3小时显示出增加的活动。19 IF的这种作用最初被认为是由中央昼夜节律时钟（下丘脑的视交叉上核（SCN））以及周围的昼夜节律时钟控制的。来自肝脏，胰腺，肠，肌肉和脂肪组织的内分泌信号。17，20，即，白天提供食物时，SCN控制代谢活动和行为，而夜间提供食物时由外围振荡器负责。20然而，最近已描述了背纹状体多巴胺形式的不依赖SCN的进食夹带振荡器。简而言之，当可以定期但有时间限制的时间获取食物时，在控制食物的预期活动方面，携带食物的振荡器比SCN优先。19重要的是要注意，人类昼夜节律的短期破坏显示会降低胰岛素敏感性，这是2型糖尿病的危险因素。21在另一项涉及小鼠的研究中，即使以高脂肪饮食喂养，饲喂窗与昼夜节律的同步也会阻止体重增加。然而，他们的同龄人在随意进食相同饮食的情况下体重会增加。有趣的是，两组之间的总能量摄入没有差异。11

在维持昼夜节律中双向作用的另一个因素是肠道菌群。5宿主的昼夜节律在肠道菌群的功能和组成方面引起昼夜振荡，而微生物群的信号又调节宿主的昼夜节律。22在小鼠中，IF被证明可重塑肠道菌群，进而促进脂肪组织的褐变。无菌小鼠中没有这种表型，并且在它们接受了微生物群转移后被诱导，从而证实了微生物群的作用。23棕色脂肪组织，特别是其中的解偶联蛋白1的活性，介导了一种称为“不颤抖的生热”的过程，该过程已显示可通过恢复能量平衡来抵消过多的能量摄入。因此，IF介导的脂肪组织褐变可能是肥胖症和相关代谢疾病的有效疗法。23

在人体研究中，中频减肥已显示出中等程度的减肥效果，并且与传统的持续能量限制一样有效。13 ADF和WDF在12-24周内均显示体重减轻约3％-9％，而TRF数据不可用。还观察到总胆固醇（〜5-21％），甘油三酸酯（〜14％-50％）的降低以及低密度脂蛋白水平的降低。12肥胖个体的血浆脂联素水平通常降低。已显示24 IF可逆转这种趋势。14此外，瘦素的血浆水平与脂肪组织质量的增加呈正相关，在IF期间血浆水平降低25。14脂联素和瘦素是由脂肪细胞（脂肪因子）分泌的细胞因子，通过控制葡萄糖的摄取，脂质的积累和食欲来调节体重。26 IF还导致炎症标记物水平降低，例如白细胞介素-6，高半胱氨酸和C反应蛋白。14这些变化以及IF期间静息心率和血压的下降限制了心血管疾病的风险。14,27 IF也与增加胰岛素敏感性和在糖基化血红蛋白的（糖化血红蛋白）水平的患者的降低2型糖尿病有关。但是，这些变化是短暂的，在恢复正常饮食后会逆转。14对小鼠的研究表明，慢性ADF可以改善脑功能和结构，并改善与年龄有关的神经系统疾病（例如阿尔茨海默氏病，帕金森氏病和中风）的结局。20、28

尽管有明显的健康益处，但IF确实有其自身的缺点。人体需要时间来适应酮作为能量来源，而不是葡萄糖。因此，疲劳和头晕导致普遍的不良情绪，尤其是在中风治疗开始时，并不少见。如果与抗糖尿病药联合使用，可能会导致致命的严重低血糖症。在老年人中，中频时血糖水平的波动与失去平衡和跌倒的倾向增加有关，从而增加了骨折的风险。此外，IF对于儿童，孕妇和从事繁重体力劳动的人是禁忌的。14如果在中频过程中进食的蛋白质含量不足，可能会导致肌肉质量下降。实际上，高蛋白饮食还可以改善饱腹感并减少饥饿感。29有关中频最佳持续时间及其长期利益的信息有限。12

综上所述，中频不仅有望作为一种替代性减肥技术，而且有望作为一种非药物治疗方法。12，23它与一些健康益处，包括昼夜节律的调节和肠道菌群，相关联的5，22，23改善胰岛素敏感性和降低的心血管疾病的风险，12，14以及与年龄相关的神经疾病的更好的结果。20然而，在这个流行病的现阶段，很清楚地没有解决肥胖症的灵丹妙药，它需要采取一致的治疗措施，包括饮食调整，教育，行为疗法，运动，甚至减肥手术。2因此，将IF与身体活动相结合的未来研究至关重要。它们对新陈代谢，行为，长期总体健康以及寿命的综合影响也许也为标题问题提供了答案。