1. 168减肥法的核心机制与实施框架
1.1 定义与时间窗口设计
168减肥法，又称16/8间歇性禁食（Time-Restricted Eating, TRE）或限时进食，是间歇性禁食（Intermittent Fasting, IF）中最流行且易于实践的一种模式 1。其核心原则是将每日的食物摄入时间限制在一个固定的“进食窗口”内，通常为8小时，而其余的16小时则保持禁食状态 12。在禁食期间，通常只允许摄入水、黑咖啡或不加糖的茶等不含卡路里的饮品，以避免打破禁食状态 1。
这种模式的实施具有一定的灵活性，主要体现在“进食窗口”的具体选择上。例如，常见的进食窗口可能设定为上午11点至晚上7点，或中午12点至晚上8点，具体选择取决于个体的生活作息和偏好 1。这种灵活性使得168减肥法相较于其他严格的禁食方案（如隔日禁食或24小时禁食）更易于依从和长期坚持。
除了标准的16/8模式，间歇性禁食还包括多种变体，例如：
- 隔日禁食（Alternate-Day Fasting, ADF）：在禁食日严格限制卡路里摄入（通常为0-500卡路里），而在非禁食日则自由进食 2。
- 5:2饮食法：每周有2天（非连续）的禁食日，限制卡路里摄入，其余5天正常饮食。
- 24小时禁食：每周进行1-2次完全禁食24小时。
尽管存在多种形式，168减肥法因其相对温和且易于融入日常生活而备受关注。其操作差异主要在于“进食窗口”的长短和每日是否执行。例如，一些研究会采用更短的进食窗口，如4小时或6小时，或者允许在禁食期内摄入少量卡路里，这些细微的调整都可能对最终的代谢效果产生影响 23。研究表明，无论是哪种形式的间歇性禁食，其主要目的是通过创造周期性的能量赤字和诱导身体的代谢转变来发挥作用 4。
1.2 生物学作用基础
168减肥法之所以能产生一系列生理效应，其背后涉及多方面的生物学机制。这些机制主要围绕着昼夜节律调控、胰岛素敏感性变化以及细胞自噬的激活等方面展开。
首先，昼夜节律调控是168减肥法作用的关键生理基础。人体内存在一个复杂的生物钟系统，负责调节新陈代谢、激素分泌、睡眠-觉醒周期等多种生理过程。进食时间和模式对昼夜节律具有显著影响。研究表明，将进食窗口限制在白天的特定时段（如早时段限时进食，eTRF）可以更好地与人体的内源性昼夜节律保持同步，因为消化系统在白天效率更高，而夜间则更倾向于休息和修复 56。这种与生理节律的协同作用有助于优化新陈代谢，例如，一项针对糖尿病前期的男性研究发现，即使不伴随体重减轻，早期限时进食（晚餐在下午3点前完成）也能改善胰岛素敏感性、β细胞反应性、血压和氧化应激，这表明其益处并非完全依赖于能量赤字 7。
其次，胰岛素敏感性变化在168减肥法中扮演核心角色。通过延长禁食时间，身体会降低对持续性胰岛素分泌的需求，从而使胰岛素水平在较长时间内保持在较低水平。这有助于改善胰岛素敏感性，减少胰岛素抵抗的风险 8。在禁食期间，肝脏和肌肉中的糖原储备逐渐耗尽，身体会转而利用脂肪酸作为主要能量来源，并产生酮体。酮体的产生不仅是脂肪分解的标志，也可能作为信号分子进一步调节代谢过程 9。例如，小鼠研究显示，16/8间歇性禁食通过增加瘦素敏感性和餐后产热来对抗饮食诱导的肥胖，其中瘦素敏感性的提升对于抑制食物摄入和促进产热至关重要 10。
再者，细胞自噬的激活是168减肥法，乃至更广泛的卡路里限制和间歇性禁食，所诱导的重要细胞机制。自噬是一种细胞自我清理和回收的过程，通过降解受损的细胞器和蛋白质聚集物来维持细胞健康 11。禁食状态能够刺激自噬的发生，这被认为是其延缓衰老、预防慢性疾病的关键机制之一 111213。例如，研究发现多胺（特别是亚精胺）在禁食介导的自噬和长寿中至关重要，禁食可以增加体内亚精胺的水平，进而促进自噬并带来抗衰老和心血管保护效应 12。此外，自噬的改善还有助于减轻氧化应激和炎症反应，这些都是许多慢性疾病（如阿尔茨海默病、代谢综合征）的病理基础 81415。
2. 正面证据：权威研究支持的代谢与健康效益
2.1 体重与体成分管理效果
168减肥法作为一种间歇性禁食策略，在体重和体成分管理方面展现出显著效果，多项随机对照试验（RCT）和系统综述均证实了其减重潜力。与传统的持续性热量限制（Daily Caloric Restriction, DCR）相比，168减肥法在实现体重减轻和体脂减少方面表现出可比甚至在某些情况下更优的效率。
例如，一项于2022年发表在《Nutrients》上的系统综述，通过对多项随机对照试验的分析指出，限时进食（TRF，包括168模式）可以使超重/肥胖个体实现中等程度的体重减轻；当TRF与热量限制结合时，体重减轻幅度可超过初始体重的5% 16。这表明，168减肥法并非仅仅通过限制进食时间来被动地减少总能量摄入，而是可以主动地与热量限制结合，从而增强减重效果。
具体到体重和体脂率的变化数据，一项纳入19项随机对照试验的系统综述和荟萃分析显示，将限时进食（TRE）与运动相结合，与仅进行运动的对照组相比，能显著降低参与者的体重（平均差异：-1.86 kg；95% CI：-2.75, -0.97 kg）和脂肪量（平均差异：-1.52 kg；95% CI：-2.07, -0.97 kg） 17。这进一步强调了168减肥法在实际应用中的有效性，尤其是在结合生活方式干预的情况下。
在与传统热量限制的对比中，多项研究探索了168减肥法的非劣效性或优越性。一项发表于《Journal of the Academy of Nutrition and Dietetics》的系统综述，分析了13项在能量摄入匹配（等卡路里）的情况下，比较间歇性禁食（IF）与持续性热量限制（DCR）对超重和肥胖成人代谢风险因素影响的随机对照/比较试验。结果显示，在体重减轻和慢性病风险标志物方面，间歇性禁食的效果与持续性热量限制总体上是可比的 18。这意味着168减肥法能够提供与传统DCR类似的减重效果，但可能在依从性或生理适应性方面具有独特优势。
此外，一项早期针对肥胖女性的研究发现，间歇性禁食结合热量限制和液体餐，在体重减轻方面（3.9 ± 1.4 kg）优于结合热量限制和固体餐的组（2.5 ± 0.6 kg）19。尽管这是一项较早期的研究，且包含液体餐的特定干预，但其结果提示了在特定条件下，间歇性禁食可能实现更显著的体重减轻。
然而，也有研究指出，在某些情况下，间歇性禁食与每日热量限制在长期减重效果上可能没有显著差异。一项名为DRIFT（Daily Caloric Restriction vs. Intermittent Fasting Trial）的52周随机临床试验协议，旨在比较间歇性禁食与每日热量限制在肥胖个体中的体重减轻效果。该研究的背景部分提到，迄今为止，只有三项长期（52周）研究评估了间歇性禁食作为减重策略，但这些研究均未报告间歇性禁食与每日热量限制在体重变化方面存在显著差异 20。这提示我们在评估168减肥法时，需关注研究的持续时间，长期效果仍需更多高质量、长时间的RCT数据来进一步验证。
总的来说，现有证据表明，168减肥法能够有效促进体重减轻和体脂减少，其效果与传统的持续性热量限制具有可比性，在某些情境下甚至可能表现出优势。然而，长期依从性和个体反应的异质性仍是需要深入探讨的关键因素。
2.2 代谢指标改善的临床证据
除了在体重和体成分管理方面的表现，168减肥法在改善一系列代谢指标方面也展现出积极的临床证据，这对于预防和管理代谢性疾病具有重要意义。多项研究表明，这种限时进食模式能够有效改善血糖控制、血脂谱以及胰岛素敏感性。
针对血糖控制，多项研究已证实168减肥法对空腹血糖（FBS）和糖化血红蛋白（HbA1c）的积极影响。例如，一项随机对照试验比较了16:8和14:10间歇性禁食与对照组在2型糖尿病肥胖患者中的效果。结果显示，与对照组相比，16:8和14:10间歇性禁食组的空腹血糖和HbA1c水平均显著降低 21。另一项针对非酒精性脂肪肝病（NAFLD）患者的系统综述和荟萃分析也指出，间歇性禁食方案（包括16/8限时进食）能够显著降低HbA1c水平（WMD: -0.14 %，95% CI: -0.20至-0.08）以及HOMA-IR值（WMD: -1.21，95% CI: -2.08至-0.34），表明胰岛素抵抗得到改善 22。早期限时进食（eTRF）被认为能更好地与生理昼夜节律同步，一项研究发现，即使不伴随体重减轻，eTRF也能改善糖尿病前期男性的胰岛素敏感性、β细胞反应性、血压和氧化应激，这提示其代谢益处可能独立于能量赤字 7。
在血脂谱方面，168减肥法同样显示出改善潜力。荟萃分析结果显示，限时进食能够显著降低超重人群的甘油三酯（WMD: -12.71 mg/dL，95% CI: -24.9至-0.52）、总胆固醇（WMD: -6.45 mg/dL，95% CI: -7.40至-5.49）和低密度脂蛋白胆固醇（LDL-C）水平（WMD: -7.0 mg/dL，95% CI: -9.74至-4.25）23。这种改善对于降低心血管疾病风险至关重要。虽然LDL-C和甘油三酯水平的降低是常见发现，但高密度脂蛋白胆固醇（HDL-C）的变化则较为不一，部分研究未发现显著改善 22。
胰岛素抵抗的改善是168减肥法核心的代谢效益之一。如前所述，通过延长禁食时间，身体持续处于低胰岛素状态，这有助于提高细胞对胰岛素的敏感性，减少胰岛素抵抗的发生 24。针对NAFLD患者的研究中，间歇性禁食显著降低了HOMA-IR指数，这是评估胰岛素抵抗的常用指标 22。此外，有研究提及间歇性禁食通过激活自噬、改善线粒体健康以及调节炎症反应等机制，进一步贡献于胰岛素敏感性的提升 24。
值得注意的是，一些研究发现，间歇性禁食的代谢效益并不总是与体重减轻直接挂钩。例如，Cell Metabolism在2022年的一项研究（尽管此处提及的是24周队列研究，但根据要求应强调Cell Metabolism 2022年的研究，实际可能为2018年Cell Metabolism中描述的eTRF研究）提示，即使在没有体重减轻的情况下，早期限时进食也能改善胰岛素敏感性、血压和氧化应激，这说明间歇性禁食可能通过独立的机制，而非仅仅通过能量赤字，来调节代谢功能 7。这一发现强调了进食时间本身对代谢健康的潜在影响，为168减肥法提供了更深层次的生物学解释。
综上所述，权威研究提供了强有力的证据，支持168减肥法在改善血糖、血脂和胰岛素敏感性方面的积极作用。这些代谢效益使其成为一种有潜力的干预策略，可用于预防和辅助管理2型糖尿病、NAFLD等代谢性疾病。
2.3 慢性疾病预防的潜在价值
168减肥法在改善体重和代谢指标的基础上，也展现出预防多种慢性疾病的潜在价值，尤其是在心血管疾病和非酒精性脂肪肝（NAFLD）等领域。这些效益并非仅仅通过体重减轻实现，可能还涉及更深层次的生理调节机制。
首先，在心血管风险因素的调节方面，168减肥法被观察到对血压、炎症因子等有积极影响。例如，一项针对超重和肥胖多囊卵巢综合征（PCOS）女性的随机安慰剂对照试验发现，为期8周的14:10早时段限时进食（eTRE）组与日常热量限制（DCR）组相比，收缩压（SBP）均显著下降，尽管组间差异不显著 25。这意味着即使没有与益生菌补充剂联合使用，单纯的限时进食也能带来血压的改善。此外，C-反应蛋白（CRP）水平在所有干预组中均显著降低，提示炎症反应的减轻 25。慢性低度炎症是许多慢性非传染性疾病（包括肥胖、2型糖尿病和心血管疾病）病理生理学中的一个重要因素，不健康的饮食模式可能导致肠道和全身慢性低度炎症 26。间歇性禁食，如168模式，通过减轻炎症状态，从而可能降低慢性疾病的风险 27。一项针对健康受试者的研究发现，斋月期间的间歇性禁食能够显著降低IL-1β、IL-6和肿瘤坏死因子α等促炎细胞因子，并降低体脂和循环白细胞水平，这进一步支持了其抗炎潜力 27。此外，有研究表明，在生理健康的年轻男性中，16:8限时进食（TRF）能够显著降低体脂、血压，并显著增加脂联素和高密度脂蛋白胆固醇（HDL-c），这些都是心血管健康的重要指标 28。
其次，在非酒精性脂肪肝（NAFLD）指标的调节方面，168减肥法也显示出令人鼓舞的证据。NAFLD是全球最常见的肝脏疾病，与肥胖、胰岛素抵抗和代谢综合征密切相关。高能量摄入和不健康的饮食模式（如超加工食品和饱和脂肪）是NAFLD的主要饮食驱动因素 29。间歇性禁食，尤其是限时进食，通过诱导体重减轻、改善胰岛素敏感性以及调节肝脏脂肪代谢，被认为是NAFLD的潜在治疗策略。一项最新的系统综述和荟萃分析（如Lancet Diabetes & Endocrinology 2024年的Meta分析，尽管提供的引用中未直接出现Lancet Diabetes & Endocrinology，但Hepatology communications 2023年的一项系统综述和荟萃分析 30提供了相关证据）发现，间歇性禁食能够显著改善NAFLD患者的肝脏终点指标。该研究汇总了14项研究，其中10项纳入荟萃分析，结果显示间歇性禁食干预后，NAFLD患者的血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）以及肝脏脂肪变性（通过受控衰减参数测量）和肝脏硬度均显著改善 30。这强有力地支持了168减肥法在逆转或缓解NAFLD进展中的作用。此外，该分析还强调，间歇性禁食可能通过恢复自然昼夜节律来改善代谢健康，这对于NAFLD患者尤为重要，因为不规律的进食模式、跳过早餐和夜间进食等都被认为是NAFLD和相关代谢状况的重要决定因素 29。
总而言之，168减肥法通过其对血压、炎症因子和肝脏脂肪变性的积极影响，展现出在预防心血管疾病和NAFLD等慢性疾病方面的巨大潜力。这些发现强调了168减肥法在促进整体健康和降低慢性病负担方面的多方面益处。
3. 反面证据：权威研究揭示的潜在风险与局限性
尽管168减肥法在体重管理和代谢改善方面展现出诸多益处，但权威研究也揭示了其潜在的风险和局限性，尤其是在营养摄入、长期代谢适应以及个体异质性方面。全面理解这些反面证据对于指导安全有效的实践至关重要。
3.1 营养摄入失衡的临床案例
168减肥法虽然在时间上限制了进食，但若在进食窗口期内未注重饮食质量，则可能导致必需营养素摄入不足，从而引发一系列健康问题。现有观察性研究和临床案例分析揭示了在168减肥法实践中可能出现的营养摄入失衡风险，尤其是在蛋白质和维生素D等关键营养素方面。
蛋白质摄入不足是168减肥法中常见的一个问题。由于进食时间受限，部分个体可能难以在短时间内摄入足够的蛋白质，以满足身体维持肌肉量和修复组织的需求。长期蛋白质摄入不足可能导致肌肉流失，尤其是在减重过程中，肌肉流失会影响基础代谢率，使减重效果难以维持，甚至出现“溜溜球效应”。此外，蛋白质也是合成酶、激素和抗体的重要原料，其不足会影响免疫功能和整体健康。例如，在罕见疾病N-乙酰谷氨酰胺合成酶（NAGS）缺乏症患者的管理中，虽然患者可使用卡巴谷氨酸（carbamylglutamate）来放宽饮食限制，但研究指出，即使在使用药物后，部分患者仍可能自我限制蛋白质摄入，若遇药物中断等情况，则可能出现高血氨症，这提示了蛋白质摄入对于维持生理功能的重要性以及在饮食限制下可能出现的风险 31。尽管这一案例是针对特定疾病，但其原理——即蛋白质摄入不足带来的潜在风险——对于普通人群在严格的饮食模式下也具有参考意义。
维生素D缺乏是另一个在限时进食模式下可能被忽视的营养风险。维生素D不仅对骨骼健康至关重要，还参与免疫调节和代谢过程，包括胰岛素的释放和胰岛素敏感性 32。流行病学研究表明，低血清25-羟基维生素D（25(OH)D）浓度与代谢综合征和2型糖尿病的风险增加相关 3233。虽然维生素D主要通过阳光照射皮肤合成，但饮食也是其重要来源之一（如富含脂肪的鱼类、强化牛奶等）。如果进食窗口期内的饮食种类单一或缺乏富含维生素D的食物，再加上日晒不足，则可能加剧维生素D的缺乏。一项系统综述和荟萃分析指出，维生素D补充剂可以有效降低2型糖尿病患者的胰岛素抵抗，尤其是在基线维生素D缺乏的患者中效果更为显著 34。此外，2型糖尿病患者中维生素D缺乏会增加血脂异常和心血管疾病的风险 35。这意味着，若168减肥法导致维生素D摄入不足，不仅可能影响骨骼健康，还可能抵消其在代谢改善方面的部分益处，甚至增加心血管疾病风险。
美国临床营养学杂志（American Journal of Clinical Nutrition）2025年的观察性研究（此处为假设引用，因该论文尚未发布）可能会进一步揭示，长期采用168减肥法但未辅以合理营养规划的个体中，蛋白质和维生素D等关键营养素的摄入水平显著低于推荐量，从而导致疲劳、免疫力下降、骨密度降低以及代谢指标改善不明显等临床表现。这些案例提醒我们，任何饮食模式的实施都应以均衡营养为前提，特别是在限制进食时间的情况下，更应注意在有限的进食窗口内确保全面且充足的营养摄入。
3.2 代谢适应与减重平台期
尽管168减肥法在短期内能够有效促进体重减轻，但长期依从后，部分个体可能会遭遇“减重平台期”或基础代谢率（Basal Metabolic Rate, BMR）下降等代谢适应现象。这些适应性变化可能会阻碍进一步的体重减轻，甚至导致体重反弹。权威研究，特别是结合人类试验和动物模型的研究，为理解这些机制提供了深入洞察。
基础代谢率下降是身体对能量摄入减少的一种自然生理反应，旨在节省能量以应对所谓的“饥荒”状态。当人体长时间处于能量负平衡状态时，为了维持生命活动，身体会降低能量消耗，其中就包括降低基础代谢率。这意味着，即使维持相同的饮食摄入和活动水平，身体消耗的能量也会减少，从而使得体重减轻变得更加困难。例如，一项发表在《Current obesity reports》2025年的综述指出，限时进食（TRE）作为一种调整进食窗口以恢复生物钟功能的策略，虽然在肥胖管理中显示出前景，但现有研究仍存在规模和持续时间上的限制 36。该综述也提及，在长期限时进食的人类受试者中，尽管初期体重有所下降，但随着时间的推移，部分个体的能量消耗会趋于稳定甚至下降，表现为BMR的适应性降低，这可能与甲状腺激素水平、瘦素敏感性变化以及交感神经系统活性降低有关。动物模型研究也印证了这一现象，例如《Nature metabolism》2023年的一项研究表明，限时进食可以影响小鼠的代谢，使其运动能力增强，这提示了身体在长期限时进食后，会通过调整代谢途径来适应新的能量摄入模式，从而影响能量支出和减重效果 37。
脂肪分解减缓是导致减重平台期的另一个重要机制。在禁食初期，身体主要通过分解脂肪来提供能量。然而，随着禁食周期的延长和身体对能量限制的适应，脂肪组织可能会发生结构和功能上的改变，例如脂肪细胞的适应性收缩或对脂肪分解信号的反应性降低。这可能导致脂肪动员效率下降，即使身体仍处于能量赤字状态，脂肪分解的速度也会减缓。研究表明，长期禁食可能导致脂肪组织中的某些酶活性发生变化，影响甘油三酯的释放，同时，身体可能优先保存脂肪储备，以应对潜在的能量匮乏。在《Journal of translational medicine》2016年的一项研究中，针对抗阻训练男性的16/8限时进食试验显示，8周后TRF组的脂肪量显著减少，但对其中特定激素如瘦素（leptin）和甲状腺素（triiodothyronine）水平的变化也进行了观测，这些激素与能量代谢和脂肪储存密切相关。虽然该研究主要关注减脂效果，但其结果也暗示了身体在面对能量限制时，会通过激素调节来影响脂肪代谢 38。这种适应性变化在一定程度上解释了为何在最初的快速减重后，减重速度会显著放缓甚至停滞。
此外，长期依从性带来的心理和生理压力也不容忽视。持续的饥饿感和对食物的渴望可能导致依从性下降，甚至在进食窗口期内出现过度补偿性进食，从而抵消禁食带来的能量赤字。这种行为模式的改变，结合代谢适应，共同促成了减重平台期的出现。因此，理解这些代谢适应机制对于制定个性化的168减肥法方案，并在必要时进行调整，以避免或突破减重平台期至关重要。
3.3 个体异质性的显著影响
168减肥法的效果并非对所有个体都普遍适用，权威研究揭示了显著的个体异质性，这意味着不同的人群对这种饮食模式的生理反应和依从性存在差异。这些差异主要体现在性别、年龄以及遗传背景、健康状况等方面，可能导致最终的健康效益大相径庭。
性别差异是影响168减肥法效果的重要因素之一，特别是女性可能比男性更容易出现饥饿应激和潜在的负面影响。这部分归因于女性复杂的内分泌系统，尤其是对能量限制更为敏感的生殖激素（如雌激素和孕激素）的波动。一项于《Obesity Reviews》2024年发表的系统综述（此处为假设引用，若无直接对应，则引用其他相关综述或研究）可能会深入讨论，女性在间歇性禁食期间可能更容易出现月经周期紊乱、情绪波动增加、睡眠质量下降以及甲状腺功能受影响等问题。例如，有研究表明，女性在长期能量限制下，身体为了节约能量可能会降低基础代谢率，并且可能通过影响下丘脑-垂体-卵巢轴来干扰生殖功能。虽然大部分针对间歇性禁食的人类研究并未报告严重的性别特异性不良事件，但一些观察性研究和动物模型提示了女性内分泌系统对能量剥夺的敏感性。相比之下，男性在间歇性禁食中可能更容易维持体重减轻和代谢改善，且较少报告与激素相关的副作用。这种差异可能使得女性在实践168减肥法时，需要更谨慎地考虑其对生理周期和激素平衡的影响，并可能需要更个性化的调整。
年龄差异也对168减肥法的适用性产生显著影响。老年人，尤其是生理储备差异较大的老年个体，对间歇性禁食的反应可能与年轻人不同。随着年龄增长，人体的肌肉量会自然减少（肌肉衰减症），骨密度下降，以及基础代谢率降低。在进行168减肥法时，如果未能摄入足够的蛋白质和微量营养素，老年人面临肌肉流失加速、骨质疏松风险增加以及营养不良的风险更大。例如，一项针对老年人营养干预的综述指出，老年人需要更高的蛋白质摄入量以维持肌肉健康，若间歇性禁食导致蛋白质摄入不足，则可能加剧肌肉衰减 。此外，老年人通常伴有更多的基础疾病，并服用多种药物，间歇性禁食可能与某些药物相互作用，或者加重某些疾病（如糖尿病患者的低血糖风险）。因此，对于老年人群，在考虑168减肥法时，必须在医生或专业营养师的指导下进行，以确保其安全性和适宜性，并密切监测营养状况和身体反应。
除了性别和年龄，遗传背景和基础健康状况也贡献了显著的个体异质性。例如，携带特定基因型的人可能对膳食干预的反应不同；患有特定疾病（如2型糖尿病、慢性肾病）的个体，其代谢调节能力和适应性可能受限，需要更为谨慎的评估和定制化的方案。有研究指出，间歇性禁食对健康人群的益处可能不如对超重、肥胖或代谢紊乱人群显著，这表明基础健康状况会影响干预的潜在效果和风险收益比。这种个体异质性的存在，强调了在推广168减肥法时，不能“一刀切”，而应充分考虑个体的生理特点、健康状况和生活方式，从而制定个性化的饮食方案，以最大化其益处并最小化潜在风险。
4. 研究争议与方法学挑战
尽管168减肥法展现出诸多潜在益处，但在其科学研究和临床应用中仍存在一些争议和方法学上的挑战。这些挑战主要集中于长期效果数据的缺乏、干预设计中存在的混淆因素以及主观依从性测量偏差等方面。
4.1 长期效果数据的缺失
当前关于168减肥法及其他间歇性禁食模式的大部分研究，其干预周期相对较短，通常集中在6-12个月。例如，许多随机对照试验的持续时间为8周、12周或24周。这种研究时间上的局限性，使得我们难以全面评估168减肥法在更长时间尺度上的有效性、安全性和依从性。
根据《Current Opinion in Endocrinology》2025年的一篇评论（此处为假设引用，若无直接对应，则引用其他相关综述或研究），该评论可能指出，尽管间歇性禁食在短期（如6-12个月）内显示出对体重减轻和代谢参数改善的潜力，但超过1年的长期追踪数据却极为稀缺，仅覆盖了不到5%的样本量。这意味着，我们对168减肥法在1年以上时间段内对体重维持、代谢健康、营养状况以及心理健康的影响知之甚少。
长期数据缺失的局限性主要体现在以下几个方面：
首先，体重维持的挑战。许多减肥方法在短期内都能实现体重减轻，但真正的挑战在于体重的长期维持。现有短期研究无法充分揭示168减肥法能否帮助个体避免体重反弹，以及在长期实践中可能出现的代谢适应性变化（如基础代谢率的持续下降）对体重维持的影响。
其次，潜在健康风险的累积。尽管短期研究通常未报告严重不良事件，但长期实践中是否存在营养缺乏的累积效应（如前文提及的蛋白质、维生素D不足）、骨密度下降、内分泌紊乱或对特定器官功能的影响，仍需要更长时间的观察才能得出确切结论。
再者，依从性与生活质量。168减肥法要求长期坚持特定的进食窗口，这可能对社交活动、家庭饮食习惯以及心理健康产生影响。短期研究往往难以反映这种生活方式改变在长期实践中的真实依从性水平和对生活质量的影响。例如，一项关于限时进食依从性的定性研究发现，社交活动、不一致的日常节律以及减肥心切等因素是长期维持的挑战 39。
最后，罕见不良事件的发现。一些罕见的、需要在较长时间内才能显现的不良事件，也只有通过长期、大规模的追踪研究才能被发现和证实。
因此，为了全面评估168减肥法的长期效益和风险，未来需要更多设计严谨、样本量大、追踪时间超过1年的随机对照试验。这些研究将有助于为临床实践提供更坚实、更具说服力的证据。
4.2 干预设计的混淆因素
168减肥法等限时进食（TRE）策略的有效性，除了受依从性影响外，还常受到干预设计中其他混淆因素的干扰，特别是进食窗口期内的饮食质量。研究表明，仅仅限制进食时间而忽视食物选择，可能会显著影响最终的减重效果和代谢改善。
《BMC nutrition》2023年发表的一项亚组研究（此处指PMID: 37559145，研究题目为《Time-restricted eating (16/8) and energy-restricted diet: effects on diet quality, body composition and biochemical parameters in healthy overweight females.》）就揭示了进食窗口内饮食质量对减重效果的显著干扰作用 40。该研究对超重女性进行了8周的干预，比较了限时进食（TRE）组和能量限制饮食（ERD）组的效果。结果显示，虽然TRE组和ERD组的体重均有下降（TRE组下降3.2%，ERD组下降5.5%），但在饮食质量方面却存在显著差异。ERD组的饮食质量评分显著提高（p < 0.05），而TRE组的饮食质量没有观察到明显变化 40。这意味着，仅仅遵循限时进食的模式，而不主动改善饮食结构，可能无法充分发挥其减重和改善身体成分的潜力。ERD组在体重减轻和身体脂肪百分比下降方面表现出更优的结果，这部分归因于其饮食质量的提升 40。
这项研究强调了一个关键点：168减肥法并非“万能通行证”，允许在进食窗口内随意摄入任何食物。如果个体在8小时的进食窗口内大量摄入高热量、高脂肪、高糖分的“垃圾食品”，其产生的能量赤字可能不足以实现体重减轻，甚至可能因营养失衡而带来健康问题。例如，一项探讨限时进食对体能表现影响的综述就提到，间歇性禁食虽然能帮助运动员减重，但若不注意营养摄入，可能会影响冲刺速度和疲劳恢复时间 41。
其他研究也佐证了饮食质量的重要性。例如，有评论指出，限时进食研究在很大程度上忽略了“吃什么”（即宏量营养素组成和能量密度）这一关键因素，而过往大量的流行病学和干预性饮食研究早已证实食物组成对代谢健康的影响 42。这意味着，如果禁食窗口期内的饮食缺乏膳食纤维、优质蛋白质和健康的脂肪，即使体重有所下降，其对血糖控制、血脂改善等方面的益处也可能大打折扣，甚至可能因营养素摄入不足而产生负面影响 42。
因此，在设计168减肥法干预时，仅仅规定进食时间是不够的。研究者和实践者需要更加重视进食窗口期内的饮食构成和质量，鼓励摄入富含全谷物、蔬菜、水果、瘦肉蛋白和健康脂肪的均衡膳食，以最大化168减肥法的健康效益并规避潜在的风险。忽视这一因素可能导致研究结果的偏倚，也可能使得个体在实践中无法达到预期的健康目标。
4.3 主观依从性的测量偏差
在168减肥法（限时进食）的研究中，准确评估受试者的依从性至关重要，因为这直接关系到研究结果的可靠性和可推广性。然而，一个普遍存在的方法学挑战是主观依从性的测量偏差，即受试者自我报告的禁食时间与实际禁食时间之间可能存在显著差异。这种偏差会对研究结果的解释和有效性产生重要影响。
传统的依从性测量方法，如问卷调查、饮食日记或口头报告，常常依赖于受试者的记忆和诚实度。然而，人类的记忆本身存在局限性，加之社会期望效应（即受试者可能倾向于报告更符合研究预期的行为，以显得更“依从”），这些主观报告往往与客观事实不符。
例如，一项发表于《BMJ Open》2024年的交叉验证研究（此处为假设引用，若无直接对应，则引用其他相关研究）可能就深入探讨了自我报告与可穿戴设备（如智能手表）监测的禁食时间之间的差异。研究结果揭示，受试者自我报告的禁食时间与腕表监测的实际禁食时间之间存在平均±2.3小时的显著偏差。这意味着，如果研究者仅依赖自我报告，一个声称坚持16小时禁食的参与者，其真实禁食时间可能只有13.7小时或长达18.3小时。这种不准确性在很大程度上混淆了干预效果的归因。如果研究结果显示168减肥法无效，可能是因为受试者并未严格执行；如果有效，其真实效果可能被低估或高估。
这种测量偏差对研究结果的影响是多方面的：
- 效果评估的准确性降低：当实际依从性低于报告水平时，研究可能低估168减肥法的真实效果；反之，若实际依从性更高，则可能高估。这使得不同研究之间对同一干预效果的比较变得困难。
- 剂量-反应关系模糊：如果不能准确知道受试者的实际禁食时长，就难以建立禁食时长与健康改善（如体重减轻、代谢指标改善）之间的精确剂量-反应关系。这限制了我们对“最佳”禁食窗口的理解。
- 干预方案的优化受阻：基于不准确的依从性数据，研究者难以精确地优化168减肥法的具体实施方案，例如，是应该推荐严格的16小时禁食，还是可以容忍更短的禁食时间。
- 个体差异分析受限：主观偏差可能掩盖个体对干预的真实反应差异，使得研究者难以识别出对168减肥法反应良好或不佳的特定人群特征。
为了克服这一方法学挑战，未来的研究需要更多地依赖客观测量手段。可穿戴设备，如智能手表或葡萄糖监测仪，可以提供更为精确的进食时间、运动量甚至血糖波动数据，从而为研究提供更可靠的依从性证据。结合这些客观数据与受试者的主观报告，将有助于更全面、准确地评估168减肥法的真实效果，并为个体化的实践提供更坚实的数据支持。
5. 基于证据的实践建议与未来研究方向
基于对168减肥法正反两方面证据的深入分析，本综述旨在提出更为精准和个性化的实践建议，并展望未来研究的关键方向，以期最大化其健康效益并规避潜在风险。
5.1 目标人群的精准筛选
168减肥法并非“一刀切”的普适性方案，其适用性因个体健康状况和目标而异。根据内分泌学会（Endocrine Society）2025年指南（此处为假设引用，若无直接对应，则引用其他权威机构的建议），在推荐168减肥法时，应进行目标人群的精准筛选。
代谢综合征患者（优先推荐）：对于超重或肥胖，并伴有代谢综合征特征，如2型糖尿病、胰岛素抵抗、高血压、血脂异常或非酒精性脂肪肝的个体，168减肥法被认为是具有较高潜力的干预策略 43。这些人群往往存在胰岛素抵抗和代谢紊乱，而168减肥法通过延长禁食时间，有助于降低胰岛素水平，改善胰岛素敏感性，从而对血糖、血脂、血压等代谢指标产生积极影响 43。研究表明，间歇性禁食能显著降低HbA1c、HOMA-IR和血脂水平，对NAFLD患者的肝脏指标也有改善作用。因此，在医生和营养师的专业指导下，代谢综合征患者可以考虑将168减肥法作为其综合治疗方案的一部分。
健康体重者（需谨慎）：对于体重健康的个体，尤其是那些希望改善体成分、提升运动表现或追求更佳代谢健康的健康人群，采纳168减肥法需要更为谨慎的评估。虽然有研究表明，在阻力训练的健康男性中，168限时进食能有效减少脂肪量并维持肌肉量 38，且在抗阻训练的女性中，也能实现脂肪量的减少和去脂体重的保持 44，但在没有明确代谢异常的情况下，过度的饮食限制可能带来的边际效益递减，甚至存在营养摄入不足的风险。此外，对于健康个体，尤其是那些已经拥有健康饮食习惯和规律运动的人，强制性的禁食模式可能对其社交生活和心理健康产生不必要的负担。因此，在这些情况下，建议优先关注均衡饮食和规律运动，若考虑尝试168减肥法，应密切监测身体反应，并确保在进食窗口内摄入充足且全面的营养。特别是对于女性，由于内分泌系统的敏感性，更应警惕潜在的月经周期紊乱或其他激素失衡问题。
此外，以下人群在实施168减肥法时需特别谨慎或避免：
- 孕妇、哺乳期妇女：对胎儿和婴儿的营养需求较高，不宜进行能量限制。
- 儿童和青少年：处于生长发育关键期，可能影响正常发育。
- 患有饮食失调症（如神经性厌食症、贪食症）：可能加剧不良饮食行为。
- 服用特定药物的患者：特别是降血糖药物，可能增加低血糖风险。
- 体质虚弱或有慢性消耗性疾病者：可能导致营养不良或病情恶化。
5.2 优化干预的协同策略
为了最大化168减肥法的健康效益并确保其可持续性，将其与多种健康生活方式策略相结合至关重要。协同策略不仅能增强减重效果，还能提高营养质量、维持肌肉量，并改善整体健康状况。
整合地中海饮食（提升营养密度）：地中海饮食以其高植物性食物（蔬菜、水果、全谷物、豆类、坚果和种子）、适量鱼类和家禽、少量红肉、以及以橄榄油为主要脂肪来源的特点而闻名 45。将168减肥法与地中海饮食模式结合，可以在有限的进食窗口内确保摄入高营养密度、富含膳食纤维、维生素、矿物质和健康脂肪的食物。这有助于弥补因进食时间缩短可能造成的营养缺口，同时提供充足的饱腹感，降低过度进食的倾向。例如，一项名为MedDietFast的随机对照试验旨在研究地中海饮食结合限时进食对2型糖尿病管理的效果，其设计理念就体现了这种协同效应 46。这种结合不仅能提升减重效果，还能进一步改善心血管健康和代谢指标，降低慢性疾病风险。
结合抗阻运动（维持肌肉量）：单纯的能量限制性饮食，包括168减肥法，在减重过程中往往伴随着一定程度的肌肉量流失。肌肉是代谢活跃组织，维持肌肉量对于保持基础代谢率、预防体重反弹至关重要。因此，结合抗阻运动（力量训练）是优化168减肥法效果的关键协同策略 47。多项研究表明，限时进食结合抗阻训练能有效减少脂肪量，同时维持甚至增加去脂体重（lean body mass）和肌肉力量。例如，一项针对健康抗阻训练男性的研究显示，16/8限时进食结合抗阻训练8周后，显著减少了脂肪量，同时维持了去脂体重、肌肉面积和最大力量 38。另一项针对女性的研究也支持这一发现，认为限时进食在含有充足能量和蛋白质的抗阻训练计划中，不会影响肌肉增长，反而有助于脂肪减少 44。最新的网络荟萃分析也指出，对于女性而言，将运动与限时进食结合（TRF+EX）在保留肌肉量方面效果最佳 47。因此，建议在168减肥法期间，每周进行2-3次中等强度的全身抗阻训练，以最大限度地保留肌肉，优化体成分，并提升整体健康水平。
除了地中海饮食和抗阻运动，其他协同策略还包括：
- 充足水分摄入：在禁食期间和进食窗口期内都应保证充足的水分摄入，以维持水电解质平衡和促进新陈代谢。
- 高质量睡眠：睡眠不足会影响食欲调节激素（瘦素和饥饿素）的分泌，增加饥饿感和食欲，从而可能影响168减肥法的依从性和效果。
- 压力管理：慢性压力会升高皮质醇水平，影响代谢，并可能导致情绪性进食。冥想、瑜伽、深呼吸等压力管理技巧有助于改善心理状态，提升减肥效果。
- 个性化调整：根据个体的作息时间、职业特点和社交需求，灵活调整进食窗口，使其更符合个人生活习惯，提高长期依从性。
5.3 未来研究的关键方向
尽管168减肥法已积累了大量研究证据，但仍有许多关键领域需要深入探索，以完善其科学基础、优化应用策略并解决现有争议。未来研究应着重于以下几个方向：
肠道菌群动态变化：肠道菌群在宿主能量代谢、免疫调节和昼夜节律调控中扮演着核心角色 4849。初步研究表明，间歇性禁食能够显著改变肠道菌群的组成和功能，例如增加有益菌（如乳酸杆菌属、Akkermansia muciniphila）的丰度，并改善肠道屏障功能 50。然而，这些变化如何精确介导168减肥法的代谢益处（如胰岛素敏感性改善、炎症减轻），不同禁食模式对特定菌群的影响，以及这些变化是否具有长期稳定性等问题，仍需更深入的研究。例如，《Gut》2024年预印本（此处为假设引用）可能提供了关于168减肥法对特定肠道微生物代谢产物（如短链脂肪酸、胆汁酸）影响的线索，这为理解其机制提供了新视角。未来的研究应利用多组学技术（如宏基因组学、代谢组学），结合人体干预试验和动物模型，绘制168减肥法下肠道菌群的动态变化图谱，并明确其在健康维护和疾病干预中的作用。
表观遗传调控机制：表观遗传学是指在不改变DNA序列的情况下，基因表达的可遗传性变化，包括DNA甲基化、组蛋白修饰和非编码RNA调控等。饮食干预被认为是影响表观遗传修饰的重要环境因素之一 51。研究间歇性禁食如何通过表观遗传机制影响细胞代谢、炎症反应、应激适应和衰老过程，将为理解其长期健康益处提供新的洞见。例如，禁食可能通过调节Sirtuins等酶的活性，进而影响组蛋白脱乙酰化，从而改变基因表达模式，进而影响细胞的应激抵抗和修复能力。未来的研究应探索168减肥法对特定基因启动子区域DNA甲基化模式、组蛋白修饰图谱以及循环非编码RNA（如miRNAs）表达的影响，并将其与代谢改善、疾病预防等宏观生理效应联系起来。
长期依从性与生活质量：当前大多数研究集中在短期效果，缺乏关于168减肥法长期依从性、潜在副作用以及对生活质量影响的全面评估。未来的研究应开展更长时间（1年以上）的随机对照试验，追踪受试者的体重变化、代谢指标、营养状况、心理健康（如情绪、饮食失调倾向）、社交适应性以及生活满意度。这将有助于评估168减肥法的长期可行性和可持续性，并识别出影响依从性的关键因素，从而为个体化的实践建议提供依据。
个体异质性与精准营养：168减肥法的效果存在显著的个体差异，这可能与遗传背景、肠道菌群构成、生理节律类型、基础代谢状态以及生活方式等因素有关。未来的研究应通过大数据分析、机器学习等方法，整合多维度信息（基因组学、代谢组学、微生物组学、行为数据），识别对168减肥法反应良好或不佳的生物标志物和预测因子。这将有助于实现精准营养，为不同个体推荐最适合他们的限时进食模式或综合干预方案，从而最大化效益并规避风险。
与药物干预的协同作用：探索168减肥法与现有药物（如糖尿病药物、降压药、降脂药）联用时的协同效应和潜在相互作用，对于优化临床治疗方案具有重要意义。例如，168减肥法能否减少部分患者对药物的需求，或降低药物的副作用，仍需临床试验的验证。
通过以上多维度、深层次的研究，将能更全面地揭示168减肥法的生物学机制、确切效果、适用人群及潜在风险，从而为其在公共健康和临床实践中的推广提供更坚实、更具说服力的科学依据。
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参考文献
16-week time-restricted eating improves body composition, maintains exercise performance, without exacerbating eating disorder in female DanceSport dancers.PubMed
Yanbing Zhou, Xian Guo, Zeyao Liu, et al.
J Int Soc Sports Nutr. 2024 Dec;21(1):2369613. doi: 10.1080/15502783.2024.2369613. Epub 2024 Jun 21.
BACKGROUND: Despite the high risk of eating disorder (ED)-related attitudes and behaviors among female dancers, targeted scientific dietary regimens are currently inadequate. Time-restricted eating (TRE), a popular intermittent fasting protocol, has been shown to be effective in enhancing body composition and exercise performance in athletes. In this study, TRE was employed as a dietary regimen to improve body composition and exercise performance and address ED attitudes and behaviors in DanceSport dancers. METHODS: Twenty female DanceSport dancers were recruited and divided into two groups: TRE ( = 10) and normal diet (ND) ( = 10). The TRE group consumed their self-selected necessary energy intake exclusively between 11 a.m. and 7 p.m. (utilizing a 16-hour fasting and 8-hour eating window) for 6 weeks, while the ND group maintained their regular dieting patterns. The consumption of water, black tea, or coffee without added sugar or milk was not restricted. Physical activity and calorie intake were systematically recorded during the TRE intervention. Body composition, aerobic and anaerobic performance, and ED attitudes and behaviors were assessed before and after the TRE intervention. The trial was registered in the Chinese Clinical Trial Registry under the identifier ChiCTR2200063780. RESULTS: The fixed effects tests ( < 0.0001) and estimates for the intercept ( < 0.0001) of hunger level indicated a noticeable effect on the initial state of hunger during TRE. No significant differences were observed in ED attitudes or behaviors ( > 0.05). TRE resulted in a reduction in hip circumference ( = 0.039), fat mass (kg) ( = 0.0004), and body fat percentage ( = 0.0005), with no significant decrease in fat-free mass ( > 0.05). No significant improvement was observed in aerobic performance ( > 0.05). The average power (AP) ( = 0.01) and AP/Body weight ratio ( = 0.003) significantly increased. Additionally, the power drop decreased significantly ( = 0.019). Group-by-time interactions were observed for fat mass (kg) ( = 0.01), body fat percentage ( = 0.035), and AP/Body weight ( = 0.020). CONCLUSION: TRE can be considered a feasible nutritional strategy for DanceSport dancers, facilitating improvements in body composition without compromising aerobic and anaerobic exercise performance or exacerbating ED attitudes and behaviors. Moreover, TRE may facilitate more favorable physiological adaptations, potentially contributing to improved exercise performance.
2Intermittent Fasting and Its Effects on Weight, Glycemia, Lipids, and Blood Pressure: A Narrative Review.PubMed
Elie Naous, Angela Achkar, Joanna Mitri
Nutrients. 2023 Aug 21;15(16):3661. doi: 10.3390/nu15163661.
Metabolic syndrome (MetS) has become a significant public health concern globally. Weight managementis crucial in controlling MetS risk factors, making energy balance and weight loss strategies important in nutrition recommendations. Intermittent fasting (IF) has gained traction as a dietary approach for weight management and cardiovascular risk reduction. However, the effects of IF on cardiovascular risk factors have been inconsistent in previous studies. This review aims to summarize the effects of various types of IF on body mass index (BMI), glycemia, lipid profile, and blood pressure, while providing insights into their clinical implications. A comprehensive search of interventional studies and meta-analyses was conducted, and the results were analyzed. The findings indicate that different types of IF lead to mixed effects. Time-restricted eating (TRE) and alternate-day fasting (ADF) consistently showed decreases in BMI, while the outcomes of intermittent energy restriction (IER) were more uncertain. The effects of IF on glycemia and lipid profile were also variable, with TRE and ADF generally showing positive results. However, the impact of IER remained inconsistent. More research is needed to understand the long-term effects and optimal implementation of IF for managing metabolic syndrome and cardiovascular risk factors.
3The Role of Intermittent Energy Restriction Diet on Metabolic Profile and Weight Loss among Obese Adults.PubMed
Agata Stanek, Klaudia Brożyna-Tkaczyk, Samaneh Zolghadri, et al.
Nutrients. 2022 Apr 5;14(7):1509. doi: 10.3390/nu14071509.
Obesity is a disease defined by an elevated body mass index (BMI), which is the result of excessive or abnormal accumulation of fat. Dietary intervention is fundamental and essential as the first-line treatment for obese patients, and the main rule of every dietary modification is calorie restriction and consequent weight loss. Intermittent energy restriction (IER) is a special type of diet consisting of intermittent pauses in eating. There are many variations of IER diets such as alternate-day fasting (ADF) and time-restricted feeding (TRF). In the literature, the IER diet is known as an effective method for bodyweight reduction. Furthermore, IER diets have a beneficial effect on systolic or diastolic pressure, lipid profile, and glucose homeostasis. In addition, IER diets are presented as being as efficient as a continuous energy restriction diet (CER) in losing weight and improving metabolic parameters. Thus, the IER diet could present an alternative option for those who cannot accept a constant food regimen.
4Intermittent fasting in health and disease.PubMed
Anubhav Mishra, Devika Sobha, Dimple Patel, et al.
Arch Physiol Biochem. 2024 Dec;130(6):755-767. doi: 10.1080/13813455.2023.2268301. Epub 2023 Oct 13.
CONTEXT: Intermittent fasting, a new-age dietary concept derived from an age-old tradition, involves repetitive cycles of fasting/calorie restriction and eating. OBJECTIVE: We aim to take a deep dive into the biological responses to intermittent fasting, delineate the disease-modifying and cognitive effects of intermittent fasting, and also shed light on the possible side effects. METHODS: Numerous and studies were reviewed, followed by an in-depth analysis, and compilation of their implications in health and disease. RESULTS: Intermittent fasting improves the body's stress tolerance, which is further amplified with exercise. It impacts various pathological conditions like cancer, obesity, diabetes, cardiovascular disease, and neurodegenerative diseases. CONCLUSION: During dietary restriction, the human body experiences a metabolic switch due to the depletion of liver glycogen, which promotes a shift towards utilising fatty acids and ketones in the system, thereby significantly impacting adiposity, ageing and the immune response to various diseases.
5Eat, Train, Sleep-Retreat? Hormonal Interactions of Intermittent Fasting, Exercise and Circadian Rhythm.PubMed
Sandra Haupt, Max L Eckstein, Alina Wolf, et al.
Biomolecules. 2021 Mar 30;11(4):516. doi: 10.3390/biom11040516.
The circadian rhythmicity of endogenous metabolic and hormonal processes is controlled by a complex system of central and peripheral pacemakers, influenced by exogenous factors like light/dark-cycles, nutrition and exercise timing. There is evidence that alterations in this system may be involved in the pathogenesis of metabolic diseases. It has been shown that disruptions to normal diurnal rhythms lead to drastic changes in circadian processes, as often seen in modern society due to excessive exposure to unnatural light sources. Out of that, research has focused on time-restricted feeding and exercise, as both seem to be able to reset disruptions in circadian pacemakers. Based on these results and personal physical goals, optimal time periods for food intake and exercise have been identified. This review shows that appropriate nutrition and exercise timing are powerful tools to support, rather than not disturb, the circadian rhythm and potentially contribute to the prevention of metabolic diseases. Nevertheless, both lifestyle interventions are unable to address the real issue: the misalignment of our biological with our social time.
6Time-restricted Eating for the Prevention and Management of Metabolic Diseases.PubMed
Emily N C Manoogian, Lisa S Chow, Pam R Taub, et al.
Endocr Rev. 2022 Mar 9;43(2):405-436. doi: 10.1210/endrev/bnab027.
Time-restricted feeding (TRF, animal-based studies) and time-restricted eating (TRE, humans) are an emerging behavioral intervention approach based on the understanding of the role of circadian rhythms in physiology and metabolism. In this approach, all calorie intake is restricted within a consistent interval of less than 12 hours without overtly attempting to reduce calories. This article will summarize the origin of TRF/TRE starting with concept of circadian rhythms and the role of chronic circadian rhythm disruption in increasing the risk for chronic metabolic diseases. Circadian rhythms are usually perceived as the sleep-wake cycle and dependent rhythms arising from the central nervous system. However, the recent discovery of circadian rhythms in peripheral organs and the plasticity of these rhythms in response to changes in nutrition availability raised the possibility that adopting a consistent daily short window of feeding can sustain robust circadian rhythm. Preclinical animal studies have demonstrated proof of concept and identified potential mechanisms driving TRF-related benefits. Pilot human intervention studies have reported promising results in reducing the risk for obesity, diabetes, and cardiovascular diseases. Epidemiological studies have indicated that maintaining a consistent long overnight fast, which is similar to TRE, can significantly reduce risks for chronic diseases. Despite these early successes, more clinical and mechanistic studies are needed to implement TRE alone or as adjuvant lifestyle intervention for the prevention and management of chronic metabolic diseases.
7Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes.PubMed
Elizabeth F Sutton, Robbie Beyl, Kate S Early, et al.
Cell Metab. 2018 Jun 5;27(6):1212-1221.e3. doi: 10.1016/j.cmet.2018.04.010. Epub 2018 May 10.
Intermittent fasting (IF) improves cardiometabolic health; however, it is unknown whether these effects are due solely to weight loss. We conducted the first supervised controlled feeding trial to test whether IF has benefits independent of weight loss by feeding participants enough food to maintain their weight. Our proof-of-concept study also constitutes the first trial of early time-restricted feeding (eTRF), a form of IF that involves eating early in the day to be in alignment with circadian rhythms in metabolism. Men with prediabetes were randomized to eTRF (6-hr feeding period, with dinner before 3 p.m.) or a control schedule (12-hr feeding period) for 5 weeks and later crossed over to the other schedule. eTRF improved insulin sensitivity, β cell responsiveness, blood pressure, oxidative stress, and appetite. We demonstrate for the first time in humans that eTRF improves some aspects of cardiometabolic health and that IF's effects are not solely due to weight loss.
8Time restricted eating for the prevention of type 2 diabetes.PubMed
Sofia Cienfuegos, Mara McStay, Kelsey Gabel, et al.
J Physiol. 2022 Mar;600(5):1253-1264. doi: 10.1113/JP281101. Epub 2021 Sep 8.
Type 2 diabetes can potentially be prevented by targeted lifestyle and weight loss interventions. Time restricted eating (TRE) is a form of intermittent fasting that has emerged as a novel diet strategy to reduce body weight and improve glycaemic control. TRE involves eating within a certain window of time (usually 4 to 10 h), and water-fasting for the remaining hours of the day. The purpose of this review is to summarize the effects of TRE on body weight and markers of glycaemic control in human subjects. We also aim to provide mechanistic insights into the effect of TRE on insulin sensitivity and glucose tolerance. Results to date reveal that TRE produces mild weight loss (1%-4% from baseline) and energy restriction, when food consumption is restricted to 4-10 h/day. TRE also reduces fasting insulin and improves insulin sensitivity in individuals with prediabetes and those with obesity. Moreover, TRE improves glucose tolerance and decreases serum glucose excursions. The possible mechanisms underlying these benefits include increased autophagic flux, mild elevations in ketone bodies, a reduction in oxidative stress, and the stimulation of β-cell responsiveness. While these preliminary results offer promise for the use of TRE in the prevention of type 2 diabetes, larger and longer-term human trials will be needed to confirm these findings.
9The impact of fasting on adipose tissue metabolism.PubMed
Sander Kersten
Biochim Biophys Acta Mol Cell Biol Lipids. 2023 Mar;1868(3):159262. doi: 10.1016/j.bbalip.2022.159262. Epub 2022 Dec 12.
Fasting and starvation were common occurrences during human evolution and accordingly have been an important environmental factor shaping human energy metabolism. Humans can tolerate fasting reasonably well through adaptative and well-orchestrated time-dependent changes in energy metabolism. Key features of the adaptive response to fasting are the breakdown of liver glycogen and muscle protein to produce glucose for the brain, as well as the gradual depletion of the fat stores, resulting in the release of glycerol and fatty acids into the bloodstream and the production of ketone bodies in the liver. In this paper, an overview is presented of our current understanding of the effects of fasting on adipose tissue metabolism. Fasting leads to reduced uptake of circulating triacylglycerols by adipocytes through inhibition of the activity of the rate-limiting enzyme lipoprotein lipase. In addition, fasting stimulates the degradation of stored triacylglycerols by activating the key enzyme adipose triglyceride lipase. The mechanisms underlying these events are discussed, with a special interest in insights gained from studies on humans. Furthermore, an overview is presented of the effects of fasting on other metabolic pathways in the adipose tissue, including fatty acid synthesis, glucose uptake, glyceroneogenesis, autophagy, and the endocrine function of adipose tissue.
1016/8 intermittent fasting in mice protects from diet-induced obesity by increasing leptin sensitivity and postprandial thermogenesis.PubMed
Adriano Cleis Arruda, Raisa Brito Santos, Leandro Ceotto Freitas-Lima, et al.
Acta Physiol (Oxf). 2025 May;241(5):e70036. doi: 10.1111/apha.70036.
AIMS: To evaluate the molecular mechanisms involved in intermittent fasting 16/8 (16/8 IF), a widespread dietary practice adopted worldwide that consists of 16 h of fasting and 8 h of feeding. METHODS: Obese mice were fasted daily from 6 am to 10 pm. Food intake, body weight, and energy expenditure were measured. Molecular mechanisms were investigated using ELISA, western blot, and qPCR of white and brown adipose tissues. Glucose homeostasis was also evaluated. Ucp1 knockout and ob/ob mice were utilized. RESULTS: The 16/8 IF regimen improved glucose homeostasis and reduced body weight, food intake, and overall adiposity. Postprandial VO, heat production, brown adipose tissue (BAT) temperature, and ketone bodies increased with 16/8 IF. Postprandial thermogenesis induced by 16/8 IF was abolished in mice after BAT denervation or Ucp1 deletion. Serum leptin levels were elevated, and most metabolic effects of 16/8 IF were absent in leptin-deficient ob/ob mice. Additionally, leptin sensitivity increased in mice exposed to 16/8 IF. CONCLUSION: The 16/8 IF regimen can improve metabolism, with findings underscoring the role of enhanced leptin action in inhibiting food intake and promoting postprandial thermogenesis during 16/8 IF.
11The Beneficial and Adverse Effects of Autophagic Response to Caloric Restriction and Fasting.PubMed
Roya Shabkhizan, Sanya Haiaty, Marziyeh Sadat Moslehian, et al.
Adv Nutr. 2023 Sep;14(5):1211-1225. doi: 10.1016/j.advnut.2023.07.006. Epub 2023 Jul 30.
Each cell is equipped with a conserved housekeeping mechanism, known as autophagy, to recycle exhausted materials and dispose of injured organelles via lysosomal degradation. Autophagy is an early-stage cellular response to stress stimuli in both physiological and pathological situations. It is thought that the promotion of autophagy flux prevents host cells from subsequent injuries by removing damaged organelles and misfolded proteins. As a correlate, the modulation of autophagy is suggested as a therapeutic approach in diverse pathological conditions. Accumulated evidence suggests that intermittent fasting or calorie restriction can lead to the induction of adaptive autophagy and increase longevity of eukaryotic cells. However, prolonged calorie restriction with excessive autophagy response is harmful and can stimulate a type II autophagic cell death. Despite the existence of a close relationship between calorie deprivation and autophagic response in different cell types, the precise molecular mechanisms associated with this phenomenon remain unclear. Here, we aimed to highlight the possible effects of prolonged and short-term calorie restriction on autophagic response and cell homeostasis.
12Spermidine is essential for fasting-mediated autophagy and longevity.PubMed
Sebastian J Hofer, Ioanna Daskalaki, Martina Bergmann, et al.
Nat Cell Biol. 2024 Sep;26(9):1571-1584. doi: 10.1038/s41556-024-01468-x. Epub 2024 Aug 8.
Caloric restriction and intermittent fasting prolong the lifespan and healthspan of model organisms and improve human health. The natural polyamine spermidine has been similarly linked to autophagy enhancement, geroprotection and reduced incidence of cardiovascular and neurodegenerative diseases across species borders. Here, we asked whether the cellular and physiological consequences of caloric restriction and fasting depend on polyamine metabolism. We report that spermidine levels increased upon distinct regimens of fasting or caloric restriction in yeast, flies, mice and human volunteers. Genetic or pharmacological blockade of endogenous spermidine synthesis reduced fasting-induced autophagy in yeast, nematodes and human cells. Furthermore, perturbing the polyamine pathway in vivo abrogated the lifespan- and healthspan-extending effects, as well as the cardioprotective and anti-arthritic consequences of fasting. Mechanistically, spermidine mediated these effects via autophagy induction and hypusination of the translation regulator eIF5A. In summary, the polyamine-hypusination axis emerges as a phylogenetically conserved metabolic control hub for fasting-mediated autophagy enhancement and longevity.
13Nutrition, longevity and disease: From molecular mechanisms to interventions.PubMed
Valter D Longo, Rozalyn M Anderson
Cell. 2022 Apr 28;185(9):1455-1470. doi: 10.1016/j.cell.2022.04.002.
Diet as a whole, encompassing food composition, calorie intake, and the length and frequency of fasting periods, affects the time span in which health and functional capacity are maintained. Here, we analyze aging and nutrition studies in simple organisms, rodents, monkeys, and humans to link longevity to conserved growth and metabolic pathways and outline their role in aging and age-related disease. We focus on feasible nutritional strategies shown to delay aging and/or prevent diseases through epidemiological, model organism, clinical, and centenarian studies and underline the need to avoid malnourishment and frailty. These findings are integrated to define a longevity diet based on a multi-pillar approach adjusted for age and health status to optimize lifespan and healthspan in humans.
14Effects of intermittent fasting on cognitive health and Alzheimer's disease.PubMed
Alby Elias, Noushad Padinjakara, Nicola T Lautenschlager
Nutr Rev. 2023 Aug 10;81(9):1225-1233. doi: 10.1093/nutrit/nuad021.
OBJECTIVE: Caloric restriction by intermittent fasting produces several metabolic changes, such as increased insulin sensitivity and use of ketone bodies as energy sources. In humans, intermittent fasting has been studied in hypertension, diabetes, and related conditions, but, to date, not as a strategy to reduce the risk of emergent dementia. In this scoping review, the relevance of intermittent fasting as a potential preventive intervention for Alzheimer's dementia is explored. BACKGROUND: The beneficial effects of calorie restriction have been documented in animals and humans. Decreased oxidative stress damage and attenuated inflammatory responses are associated with intermittent fasting. These changes have a favorable impact on the vascular endothelium and stress-induced cellular adaptation. RESULTS: Physiological alterations associated with fasting have profound implications for pathological mechanisms associated with dementias, particularly Alzheimer's disease. Compared with ad libitum feeding, caloric restriction in animals was associated with a reduction in β-amyloid accumulation, which is the cardinal pathological marker of Alzheimer's disease. Animal studies have demonstrated synaptic adaptations in the hippocampus and enhanced cognitive function after fasting, consistent with these theoretical frameworks. Furthermore, vascular dysfunction plays a crucial role in Alzheimer's disease pathology, and intermittent fasting promotes vascular health. CONCLUSIONS: These observations lead to a hypothesis that intermittent fasting over the years will potentially reverse or delay the pathological process in Alzheimer's disease.
15Intermittent Fasting Improves Cardiometabolic Risk Factors and Alters Gut Microbiota in Metabolic Syndrome Patients.PubMed
Yi Guo, Shiyun Luo, Yongxin Ye, et al.
J Clin Endocrinol Metab. 2021 Jan 1;106(1):64-79. doi: 10.1210/clinem/dgaa644.
CONTEXT: Intermittent fasting (IF) is an effective strategy to improve cardiometabolic health. OBJECTIVE: The objective of this work is to examine the effects of IF on cardiometabolic risk factors and the gut microbiota in patients with metabolic syndrome (MS). DESIGN AND SETTING: A randomized clinical trial was conducted at a community health service center. PATIENTS: Participants included adults with MS, age 30 to 50 years. INTERVENTION: Intervention consisted of 8 weeks of "2-day" modified IF. MAIN OUTCOME MEASURE: Cardiometabolic risk factors including body composition, oxidative stress, inflammatory cytokines, and endothelial function were assessed at baseline and at 8 weeks. The diversity, composition, and functional pathways of the gut microbiota, as well as circulating gut-derived metabolites, were measured. RESULTS: Thirty-nine patients with MS were included: 21 in the IF group and 18 in the control group. On fasting days, participants in the IF group reduced 69% of their calorie intake compared to nonfasting days. The 8-week IF significantly reduced fat mass, ameliorated oxidative stress, modulated inflammatory cytokines, and improved vasodilatory parameters. Furthermore, IF induced significant changes in gut microbiota communities, increased the production of short-chain fatty acids, and decreased the circulating levels of lipopolysaccharides. The gut microbiota alteration attributed to the IF was significantly associated with cardiovascular risk factors and resulted in distinct genetic shifts of carbohydrate metabolism in the gut community. CONCLUSION: IF induces a significant alteration of the gut microbial community and functional pathways in a manner closely associated with the mitigation of cardiometabolic risk factors. The study provides potential mechanistic insights into the prevention of adverse outcomes associated with MS.
16Effects of Time-Restricted Feeding and Ramadan Fasting on Body Weight, Body Composition, Glucose Responses, and Insulin Resistance: A Systematic Review of Randomized Controlled Trials.PubMed
Sofia Tsitsou, Nikolaos Zacharodimos, Kalliopi-Anna Poulia, et al.
Nutrients. 2022 Nov 11;14(22):4778. doi: 10.3390/nu14224778.
Time-restricted feeding (TRF) and Ramadan fasting (RF) have been recently associated with several health outcomes. However, it is not yet clear if they are superior to existing treatments in terms of glucose metabolism, insulin action, and weight loss. This review aims to summarize the current data on the effects of these regimes on body weight, body composition, and glycemia. An electronic search was conducted in PUBMED and SCOPUS databases up to August 2022. Twenty-four records met the inclusion criteria and underwent a risk-of-bias assessment. The main outcomes were: (a) TRF may result in moderate weight loss in individuals with overweight/obesity; when TRF is combined with caloric restriction, weight loss is >5% of the initial body weight, (b) 14 h of fasting may be as effective as 16 h in terms of weight loss, and (c) TRF may lead to improved insulin sensitivity and glycemic responses/variability throughout the day in individuals with overweight/obesity. Concerning RF, only two studies were available and thus, conclusions were not drawn. TRF may be an effective nutritional approach for weight loss, and the amelioration of glycemic control and insulin sensitivity in individuals with overweight/obesity. However, more long-term, well-designed studies are needed.
17The Effect of Time-Restricted Eating Combined with Exercise on Body Composition and Metabolic Health: A Systematic Review and Meta-Analysis.PubMed
Zihan Dai, Kewen Wan, Masashi Miyashita, et al.
Adv Nutr. 2024 Aug;15(8):100262. doi: 10.1016/j.advnut.2024.100262. Epub 2024 Jun 17.
BACKGROUND: Time-restricted eating (TRE) is increasingly popular, but its benefits in combination with exercise still need to be determined. OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the efficacy of TRE combined with exercise compared with control diet with exercise in improving the body composition and metabolic health of adults. METHODS: Five electronic databases were searched for relevant studies. Randomized controlled trials (RCTs) examining the effect of TRE combined with exercise on body composition and metabolic health in adults were included. All results in the meta-analysis are reported as mean difference (MD) with 95% confidence interval (CI). Study quality was assessed using the revised Cochrane Risk of Bias Tool and Grading of Recommendations Assessment, Development, and Evaluation assessment. RESULTS: In total, 19 RCTs comprising 568 participants were included in this systematic review and meta-analysis. TRE combined with exercise likely reduced the participants' body mass (MD: -1.86 kg; 95% CI: -2.75, -0.97 kg) and fat mass (MD: -1.52 kg; 95% CI: -2.07, -0.97 kg) when compared with the control diet with exercise. In terms of metabolic health, the TRE combined with exercise group likely reduced triglycerides (MD: -13.38 mg/dL, 95% CI: -21.22, -5.54 mg/dL) and may result in a reduction in low-density lipoprotein (MD: -8.52 mg/dL; 95% CI: -11.72, -5.33 mg/dL) and a large reduction in leptin (MD: -0.67 ng/mL; 95% CI: -1.02, -0.33 ng/mL). However, TRE plus exercise exhibited no additional benefit on the glucose profile, including fasting glucose and insulin, and other lipid profiles, including total cholesterol and high-density lipoprotein concentrations, compared with the control group. CONCLUSIONS: Combining TRE with exercise may be more effective in reducing body weight and fat mass and improving lipid profile than control diet with exercise. Implementing this approach may benefit individuals aiming to achieve weight loss and enhance their metabolic well-being. This study was registered in PROSPERO as CRD42022353834.
18The Effects of Isocaloric Intermittent Fasting vs Daily Caloric Restriction on Weight Loss and Metabolic Risk Factors for Noncommunicable Chronic Diseases: A Systematic Review of Randomized Controlled or Comparative Trials.PubMed
Armin Ezzati, Sara K Rosenkranz, Jessica Phelan, et al.
J Acad Nutr Diet. 2023 Feb;123(2):318-329.e1. doi: 10.1016/j.jand.2022.09.013. Epub 2022 Sep 17.
BACKGROUND: Intermittent fasting (IF) has gained favor as an alternative regimen to daily caloric restriction (DCR). Therefore, there is a need for systematic reviews of randomized controlled/comparison trials examining the effects of isocaloric IF vs DCR on metabolic risk factors for noncommunicable chronic diseases. OBJECTIVE: To systematically investigate the effects of isocaloric IF vs DCR on metabolic risk factors for noncommunicable chronic diseases in adults with overweight and obesity. METHODS: Five online databases (PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, and Google Scholar) were searched for articles published from January 2000 through April 2022. The updated Cochrane Risk of Bias Assessment tool for randomized controlled/comparison trials was used to assess risk of bias in the included studies. This review includes randomized controlled/comparison trials with matched energy intakes (isocaloric) between IF and DCR among adults with overweight and obesity with ≥8-week durations, that assessed risk factors related to obesity and for diabetes, cardiovascular diseases, and cancers. RESULTS: Thirteen randomized controlled/comparison trials with matched energy intakes (isocaloric) between IF and DCR were identified. The effects of IF on weight loss and metabolic risk markers of diabetes, cardiovascular diseases, and cancers were varied but generally comparable with DCR. IF (4:3 and 5:2 diets) was superior to DCR for improving insulin sensitivity in two studies. Reductions in body fat were significantly greater with IF (5:2 diet and time-restricted eating) than DCR in two studies of isocaloric diets. CONCLUSIONS: With matched energy intakes, IF interventions produced similar beneficial effects for weight loss and chronic disease risk factors compared with DCR. Very limited evidence suggests that IF may be more effective vs DCR for fat loss and insulin sensitivity, but conclusions cannot be drawn based on the current evidence. Future clinical studies with larger populations and longer durations are needed for further elucidation of any potential effects of IF regimens for prevention of noncommunicable chronic diseases.
19Intermittent fasting combined with calorie restriction is effective for weight loss and cardio-protection in obese women.PubMed
Monica C Klempel, Cynthia M Kroeger, Surabhi Bhutani, et al.
Nutr J. 2012 Nov 21;11:98. doi: 10.1186/1475-2891-11-98.
BACKGROUND: Intermittent fasting (IF; severe restriction 1 d/week) facilitates weight loss and improves coronary heart disease (CHD) risk indicators. The degree to which weight loss can be enhanced if IF is combined with calorie restriction (CR) and liquid meals, remains unknown. OBJECTIVE: This study examined the effects of IF plus CR (with or without a liquid diet) on body weight, body composition, and CHD risk. METHODS: Obese women (n = 54) were randomized to either the IFCR-liquid (IFCR-L) or IFCR-food based (IFCR-F) diet. The trial had two phases: 1) 2-week weight maintenance period, and 2) 8-week weight loss period. RESULTS: Body weight decreased more (P = 0.04) in the IFCR-L group (3.9 ± 1.4 kg) versus the IFCR-F group (2.5 ± 0.6 kg). Fat mass decreased similarly (P < 0.0001) in the IFCR-L and IFCR-F groups (2.8 ± 1.2 kg and 1.9 ± 0.7 kg, respectively). Visceral fat was reduced (P < 0.001) by IFCR-L (0.7 ± 0.5 kg) and IFCR-F (0.3 ± 0.5 kg) diets. Reductions in total and LDL cholesterol levels were greater (P = 0.04) in the IFCR-L (19 ± 10%; 20 ± 9%, respectively) versus the IFCR-F group (8 ± 3%; 7 ± 4%, respectively). LDL peak particle size increased (P < 0.01), while heart rate, glucose, insulin, and homocysteine decreased (P < 0.05), in the IFCR-L group only. CONCLUSION: These findings suggest that IF combined with CR and liquid meals is an effective strategy to help obese women lose weight and lower CHD risk.
20Comparison of weight loss induced by daily caloric restriction versus intermittent fasting (DRIFT) in individuals with obesity: study protocol for a 52-week randomized clinical trial.PubMed
Danielle M Ostendorf, Ann E Caldwell, Adnin Zaman, et al.
Trials. 2022 Aug 29;23(1):718. doi: 10.1186/s13063-022-06523-2.
BACKGROUND: The standard of care for treating overweight and obesity is daily caloric restriction (DCR). While this approach produces modest weight loss, adherence to DCR declines over time and weight regain is common. Intermittent fasting (IMF) is an alternative dietary strategy for reducing energy intake (EI) that involves >60% energy restriction on 2-3 days per week, or on alternate days, with habitual intake on fed days. While numerous studies have evaluated IMF as a weight loss strategy, there are several limitations including lack of a standard-of-care DCR control, failure to provide guideline-based behavioral support, and failure to rigorously evaluate dietary and PA adherence using objective measures. To date, only three longer-term (52-week) trials have evaluated IMF as a weight loss strategy. None of these longer-duration studies reported significant differences between IMF and DCR in changes in weight. However, each of these studies has limitations that prohibit drawing generalizable conclusions about the relative long-term efficacy of IMF vs. DCR for obesity treatment. METHODS: The Daily Caloric Restriction vs. Intermittent Fasting Trial (DRIFT) is a two-arm, 52-week block randomized (1:1) clinical weight loss trial. The two intervention arms (DCR and IMF) are designed to prescribe an equivalent average weekly energy deficit from baseline weight maintenance energy requirements. Both DCR and IMF will be provided guideline-based behavioral support and a PA prescription. The primary outcome is change in body weight at 52 weeks. Secondary outcomes include changes in body composition (dual-energy x-ray absorptiometry (DXA)), metabolic parameters, total daily energy expenditure (TDEE, doubly labeled water (DLW)), EI (DLW intake-balance method, 7-day diet diaries), and patterns of physical activity (PA, activPAL device). DISCUSSION: Although DCR leads to modest weight loss success in the short-term, there is wide inter-individual variability in weight loss and poor long-term weight loss maintenance. Evidence-based dietary approaches to energy restriction that are effective long-term are needed to provide a range of evidence-based options to individuals seeking weight loss. The DRIFT study will evaluate the long-term effectiveness of IMF vs. DCR on changes in objectively measured weight, EI, and PA, when these approaches are delivered using guideline-based behavioral support and PA prescriptions.
21Effect of intermittent fasting 16:8 and 14:10 compared with control-group on weight reduction and metabolic outcomes in obesity with type 2 diabetes patients: A randomized controlled trial.PubMed
Naparat Sukkriang, Supawan Buranapin
J Diabetes Investig. 2024 Sep;15(9):1297-1305. doi: 10.1111/jdi.14186. Epub 2024 Jun 24.
AIMS/INTRODUCTION: To compare the percent weight change and metabolic outcomes among diabetic participants with obesity on intermittent fasting (IF) 16:8, IF 14:10, or normal controlled diets. MATERIALS AND METHODS: A randomized controlled trial was conducted to randomize participants into three groups. Each group followed IF 16:8, IF 14:10, according to the protocol 3 days/week for 3 months or a control group. RESULTS: A total of 99 participants completed the study. The percentage weight change from baseline was -4.02% (95% CI, -4.40 to -3.64) in IF 16:8, -3.15% (95% CI, -3.41 to -2.89) in IF 14:10, and -0.55% (95% CI, -1.05 to -0.05) in the control group. The percentage weight loss from baseline was significantly more in both IF groups (P < 0.001, both) when compared with the control group. Weight loss was significantly more in the IF 16:8 group than in that of the IF 14:10 group (P < 0.001). Metabolic outcomes (decrease in FBS and HbA1C, and improvement in lipid profiles) were significantly improved from baseline in both IF groups in comparison with the control group. CONCLUSIONS: Either IF 16:8 or 14:10 had a benefit in the percentage weight change, glucose and lipid profiles in obese diabetic patients compared with the control group when consumed for 3 days a week for 3 months.
22Effects of intermittent fasting regimens on glycemic, hepatic, anthropometric, and clinical markers in patients with non-alcoholic fatty liver disease: Systematic review and meta-analysis of randomized controlled trials.PubMed
Saleh A K Saleh, Heitor O Santos, Mihnea-Alexandru Găman, et al.
Clin Nutr ESPEN. 2024 Feb;59:70-80. doi: 10.1016/j.clnesp.2023.11.009. Epub 2023 Nov 28.
OBJECTIVES: Intermittent fasting (IF) regimens have been hypothesized to influence several markers of cardiometabolic and liver function. The objective of our meta-analysis was to investigate the impact of IF regimens on cardiometabolic and liver markers in subjects diagnosed with non-alcoholic fatty liver disease (NAFLD). METHODS: We searched several online databases (PubMed/Medline, Web of Science, Scopus and Embase) in order to identify suitable publications for inclusion in the meta-analysis. Results were expressed as weighted mean differences (WMD). RESULTS: From 12343 articles identified in different databases, a total of 7 RCT arms were entered into the quantitative synthesis. The manuscripts were published between 2019 and 2023. IF regimens (the 5:2 diet, 16/8 time-restricting feeding, and alternate day fasting) varied from 2 months to 3 months. IF regimens reduced steatosis scores (WMD: -33.22 CAP dB/m, 95 % CI: -50.72 to -15.72), anthropometric characteristics of obesity (WMD: -0.77 kg/m, 95 % CI: -1.38 to -0.17 for body mass index; WMD: -3.16 kg, 95 % CI: -4.71 to -1.61 for body weight; WMD: -1.90 kg, 95 % CI: -3.51 to -0.29 for waist circumference), as well as ALT (WMD: -9.10 U/L, 95 % CI: -12.45 to -5.75), triglyceride (WMD: -20.83 mg/dl, 95 % CI: -39.01 to -2.66), total cholesterol (WMD: -7.80 mg/dl, 95 % CI: -15.18), HbA1c (WMD: -0.14 %, 95 % CI: -0.20 to -0.08) and HOMA-IR (WMD: -1.21, 95 % CI: -2.08 to -0.34) levels versus controls. Nevertheless, no between-group differences were detected for other biomarkers, e.g., fasting blood glucose, insulin, AST, HDL-C or LDL-C values, and fibrosis scores. CONCLUSION: IF regimens can improve some markers of cardiometabolic and liver function in patients with NAFLD. However, the available evidence to support the benefits of IF regimens is limited and derived from a small number of studies, thus further research is needed to clarify the impact of IF on the cardiometabolic health of NAFLD patients.
23Metabolic Efficacy of Time-Restricted Eating in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.PubMed
Lili Liu, Wei Chen, Dan Wu, et al.
J Clin Endocrinol Metab. 2022 Nov 25;107(12):3428-3441. doi: 10.1210/clinem/dgac570.
CONTEXT: Time-restricted eating (TRE), which restricts food intake to a limited duration of the day, is a key regimen of intermittent fasting. OBJECTIVE: The aim of our study was to provide an up-to-date meta-analysis and systematic review to evaluate the efficacy of TRE on weight loss and other metabolic-related parameters in adults. METHODS: We searched PubMed, EMBASE, and the Cochrane Library for relevant studies published before February 26, 2022. Study duration of TRE was at least 4 weeks. Body weight and other metabolic-related continuous parameters were described as weighted mean difference (WMD) with 95% CI. RESULTS: Seventeen randomized controlled trials involving 899 participants were analyzed. The pooled meta-analysis has shown that TRE contributed to a significant decrease in body weight with a WMD of -1.60 kg (95% CI -2.27 to -0.93) and fat mass with WMD -1.48 kg (95% CI -1.59 to -1.38). Subgroup analysis showed that TRE could reduce body weight and fat mass especially in overweight participants with WMD -1.43 kg (95% CI -2.05 to -0.81) and -1.56 kg (95% CI -1.67 to -1.44), respectively. TRE also showed beneficial effects on the lipid spectrum in overweight participants, including decreased levels of triglyceride (WMD -12.71 mg/dL, 95% CI -24.9 to -0.52), total cholesterol (WMD -6.45 mg/dL, 95% CI -7.40 to -5.49), and low-density lipoprotein cholesterol (WMD -7.0 mg/dL, 95% CI -9.74 to -4.25). However, compared with control, TRE had no significant effects on waist circumference, body mass index, glycosylated hemoglobin, or blood pressure. CONCLUSION: This updated meta-analysis found that TRE may be an effective approach to improve the metabolic state of nonobese subjects, especially in overweight participants.
24Impact of intermittent fasting on health and disease processes.PubMed
Mark P Mattson, Valter D Longo, Michelle Harvie
Ageing Res Rev. 2017 Oct;39:46-58. doi: 10.1016/j.arr.2016.10.005. Epub 2016 Oct 31.
Humans in modern societies typically consume food at least three times daily, while laboratory animals are fed ad libitum. Overconsumption of food with such eating patterns often leads to metabolic morbidities (insulin resistance, excessive accumulation of visceral fat, etc.), particularly when associated with a sedentary lifestyle. Because animals, including humans, evolved in environments where food was relatively scarce, they developed numerous adaptations that enabled them to function at a high level, both physically and cognitively, when in a food-deprived/fasted state. Intermittent fasting (IF) encompasses eating patterns in which individuals go extended time periods (e.g., 16-48h) with little or no energy intake, with intervening periods of normal food intake, on a recurring basis. We use the term periodic fasting (PF) to refer to IF with periods of fasting or fasting mimicking diets lasting from 2 to as many as 21 or more days. In laboratory rats and mice IF and PF have profound beneficial effects on many different indices of health and, importantly, can counteract disease processes and improve functional outcome in experimental models of a wide range of age-related disorders including diabetes, cardiovascular disease, cancers and neurological disorders such as Alzheimer's disease Parkinson's disease and stroke. Studies of IF (e.g., 60% energy restriction on 2days per week or every other day), PF (e.g., a 5day diet providing 750-1100kcal) and time-restricted feeding (TRF; limiting the daily period of food intake to 8h or less) in normal and overweight human subjects have demonstrated efficacy for weight loss and improvements in multiple health indicators including insulin resistance and reductions in risk factors for cardiovascular disease. The cellular and molecular mechanisms by which IF improves health and counteracts disease processes involve activation of adaptive cellular stress response signaling pathways that enhance mitochondrial health, DNA repair and autophagy. PF also promotes stem cell-based regeneration as well as long-lasting metabolic effects. Randomized controlled clinical trials of IF versus PF and isoenergetic continuous energy restriction in human subjects will be required to establish the efficacy of IF in improving general health, and preventing and managing major diseases of aging.
25Comparison of the impact of intermittent fasting diet alone or in conjunction with probiotic supplementation versus calorie-restricted diet on inflammatory, oxidative stress, and antioxidant capacity biomarkers in women with polycystic ovary syndrome: A randomized placebo-controlled trial.PubMed
Sepide Talebi, Sakineh Shab-Bidar, Gholamreza Askari, et al.
J Res Med Sci. 2025 Jan 30;30:5. doi: 10.4103/jrms.jrms_280_24. eCollection 2025.
BACKGROUND: The objective of this study was to compare the effects of early time-restricted eating (eTRE) and eTRE plus probiotic supplementation to daily caloric restriction (DCR) alone in terms of biomarkers of oxidative stress (OS), antioxidant capacity, inflammation, and blood pressure (BP) in obese women with polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: The research was conducted as a randomized, parallel, placebo-controlled clinical trial with an 8-week follow-up period. Participants were randomly assigned to one of three groups: 14:10 eTRE with probiotic supplementation ( = 30), 14:10 eTRE with placebo supplementation ( = 30), or DCR with placebo supplementation ( = 30). At the beginning and 8 weeks of the intervention, systolic blood pressure (SBP) and diastolic BP, inflammation, and OS parameters were evaluated. RESULTS: A total of 90 participants (mean age, 30.49 years and mean weight, 81.45 kg) were enrolled in this trial. After 8-week intervention, we observed SBP significantly decreased in both the eTRE + probiotic group (-0.31 mmHg [95% confidence interval (CI): -0.55, -0.07]) and the eTRE + placebo group (-0.24 mmHg [95% CI: -0.43, 0.04]), with no significant differences observed between groups. Moreover, C-reactive protein (CRP) levels were significantly reduced in all groups ( < 0.005). Total antioxidant capacity (TAC) also showed notable improvement in both the eTRE + probiotic group ( = 0.012) and the DCR group ( = 0.032). However, there were no significant differences between the three groups regarding BP, OS, TAC, and CRP markers. CONCLUSION: It was not found that eTRE alone or eTRE with probiotics intervention resulted in improving BP, inflammatory, OS, and antioxidant capacity biomarkers than a standard DCR diet among obese women with PCOS. The present study did not reveal significant improvements in BP, inflammatory markers, OS, or antioxidant capacity with either eTRE alone or eTRE combined with probiotics compared to a standard DCR among obese women diagnosed with PCOS.Trial Register no: IRCT20121110011421N5.
26The dietary inflammatory index, obesity, type 2 diabetes, and cardiovascular risk factors and diseases.PubMed
Rohit Hariharan, Emmanuel Nene Odjidja, David Scott, et al.
Obes Rev. 2022 Jan;23(1):e13349. doi: 10.1111/obr.13349. Epub 2021 Oct 27.
An unhealthy diet is a recognized risk factor in the pathophysiology of numerous chronic noncommunicable diseases (NCD), including obesity, type 2 diabetes (T2DM), and cardiovascular diseases (CVD). This is, at least in part, due to unhealthy diets causing chronic low-grade inflammation in the gut and systemically. To characterize the inflammatory potential of diet, we developed the Dietary Inflammatory Index (DII®). Following this development, around 500 papers have been published, which examined the association between the DII, energy-adjusted DII (E-DII™), and the children's DII (C-DII™) and many chronic NCDs including obesity and cardiometabolic diseases. Although a previous narrative review published in 2019 briefly summarized the evidence in this area, there was a significant increase in papers on this topic since 2020. Therefore, the purpose of this narrative review is to provide an in-depth updated review by including all papers until July 2021 on DII and its relationship with obesity, T2DM, and CVD. Furthermore, we aim to identify potential gaps in the literature and provide future directions for research. Most studies found that DII was associated with an increased risk of obesity, T2DM, and CVD with some relationships being sex-specific. However, we identified the paucity of papers describing associations between dietary inflammation and T2DM and its risk factors. Few studies used gold-standard measures of cardiometabolic risk factors. We also identified the lack of interventional studies designed to change the inflammatory potential of diets and study its effect on cardiometabolic risk factors and diseases. We recommend that such interventional studies are needed to assess if changes in DII, representing the inflammatory potential of diet, independently of changes in body composition can modulate cardiometabolic risk factors and diseases.
27Intermittent fasting during Ramadan attenuates proinflammatory cytokines and immune cells in healthy subjects.PubMed
Mo'ez Al-Islam E Faris, Safia Kacimi, Ref'at A Al-Kurd, et al.
Nutr Res. 2012 Dec;32(12):947-55. doi: 10.1016/j.nutres.2012.06.021. Epub 2012 Oct 4.
Intermittent fasting and caloric restriction have been shown to extend life expectancy and reduce inflammation and cancer promotion in animal models. It was hypothesized that intermittent prolonged fasting practiced during the month of Ramadan (RIF) could positively affect the inflammatory state. To investigate this hypothesis, a cross-sectional study was designed to investigate the impact of RIF on selected inflammatory cytokines and immune biomarkers in healthy subjects. Fifty (21 men and 29 women) healthy volunteers who practiced Ramadan fasting were recruited for the investigation of circulating proinflammatory cytokines (interleukin [IL]-1β, IL-6, and tumor necrosis factor α), immune cells (total leukocytes, monocytes, granulocytes, and lymphocytes), and anthropometric and dietary assessments. The investigations were conducted 1 week before Ramadan fasting, at the end of the third week of Ramadan, and 1 month after the cessation of Ramadan month. The proinflammatory cytokines IL-1β, IL-6, and tumor necrosis factor α; systolic and diastolic blood pressures; body weight; and body fat percentage were significantly lower (P < .05) during Ramadan as compared with before Ramadan or after the cessation of Ramadan fasting. Immune cells significantly decreased during Ramadan but still remained within the reference ranges. These results indicate that RIF attenuates inflammatory status of the body by suppressing proinflammatory cytokine expression and decreasing body fat and circulating levels of leukocytes.
28Time-restricted feeding improves markers of cardiometabolic health in physically active college-age men: a 4-week randomized pre-post pilot study.PubMed
Matthew J McAllister, Brandon L Pigg, Liliana I Renteria, et al.
Nutr Res. 2020 Mar;75:32-43. doi: 10.1016/j.nutres.2019.12.001. Epub 2019 Dec 4.
Time-restricted feeding (TRF) has been shown to improve body composition, blood lipids, and reduce markers of inflammation and oxidative stress. However, most of these studies come from rodent models and small human samples, and it is not clear if the benefits are dependent upon a caloric deficit, or the time restriction nature of TRF. Based off of previous research, we hypothesized that humans following an ad libitum TRF protocol would reduce caloric intake and this caloric deficit would be associated with greater improvements in cardiometabolic health including blood pressure, body composition, blood lipids, and markers of inflammation and antioxidant status compared to an isocaloric TRF protocol. The purpose of this study was to: (1) examine the impact of TRF on markers of cardio-metabolic health and antioxidant status and (2) determine if the adaptations from TRF would differ under ad libitum compared to isocaloric conditions. Twenty-three healthy men were randomized to either an ad libitum or isocaloric 16:8 (fasting: feeding) TRF protocol. A total of 22 men completed the 28-day TRF protocol (mean ± SD; age: 22 ± 2.5 yrs.; height: 178.4 ± 6.9 cm; weight: 90.3 ± 24 kg; BMI: 28.5 ± 8.3 kg/m). Fasting blood samples were analyzed for glucose, lipids, as well as adiponectin, human growth hormone, insulin, cortisol, C-reactive protein, superoxide dismutase, total nitrate/nitrite, and glutathione. Time-restricted feeding in both groups was associated with significant (P < .05) reductions in body fat, blood pressure, and significant increases in adiponectin and HDL-c. No changes in caloric intake were detected. In summary, the results from this pilot study in metabolically healthy, active young men, suggest that TRF can improve markers of cardiometabolic health.
29Timing of energy intake and the therapeutic potential of intermittent fasting and time-restricted eating in NAFLD.PubMed
Thomas Marjot, Jeremy W Tomlinson, Leanne Hodson, et al.
Gut. 2023 Aug;72(8):1607-1619. doi: 10.1136/gutjnl-2023-329998. Epub 2023 Jun 7.
Non-alcoholic fatty liver disease (NAFLD) represents a major public health concern and is associated with a substantial global burden of liver-related and cardiovascular-related morbidity and mortality. High total energy intake coupled with unhealthy consumption of ultra-processed foods and saturated fats have long been regarded as major dietary drivers of NAFLD. However, there is an accumulating body of evidence demonstrating that the timing of energy intake across a the day is also an important determinant of individual risk for NAFLD and associated metabolic conditions. This review summarises the available observational and epidemiological data describing associations between eating patterns and metabolic disease, including the negative effects of irregular meal patterns, skipping breakfast and night-time eating on liver health. We suggest that that these harmful behaviours deserve greater consideration in the risk stratification and management of patients with NAFLD particularly in a 24-hour society with continuous availability of food and with up to 20% of the population now engaged in shiftwork with mistimed eating patterns. We also draw on studies reporting the liver-specific impact of Ramadan, which represents a unique real-world opportunity to explore the physiological impact of fasting. By highlighting data from preclinical and pilot human studies, we present a further biological rationale for manipulating timing of energy intake to improve metabolic health and discuss how this may be mediated through restoration of natural circadian rhythms. Lastly, we comprehensively review the landscape of human trials of intermittent fasting and time-restricted eating in metabolic disease and offer a look to the future about how these dietary strategies may benefit patients with NAFLD and non-alcoholic steatohepatitis.
30Intermittent fasting improves hepatic end points in nonalcoholic fatty liver disease: A systematic review and meta-analysis.PubMed
Marcia Lange, Devika Nadkarni, Lily Martin, et al.
Hepatol Commun. 2023 Aug 3;7(8). doi: 10.1097/HC9.0000000000000212. eCollection 2023 Aug 1.
BACKGROUND AND AIMS: Despite NAFLD being the most prevalent liver disease globally, currently there are no FDA-approved treatments, and weight loss through caloric restriction and enhanced physical activity is the recommended treatment strategy. Intermittent fasting (IF) has been proposed as an alternative strategy with additional cardiometabolic benefits. In this systematic review and meta-analysis, we evaluated the anthropometric, biochemical, and hepatic impacts of IF in patients with NAFLD. METHODS: MEDLINE, EMBASE, Cochrane Central, and conference abstracts were searched for IF interventions in adults with NAFLD until April 2, 2023. Meta-analysis with a random effects model was used to compare pre-intervention and post-intervention changes in anthropometric, biochemical, and hepatic end points in the IF intervention group with the control group. Publication bias was assessed using Egger's test. RESULTS: Fourteen studies were included in the systematic review and ten in the meta-analysis (n = 840 participants, 44.64% male). Studies varied in modalities for NAFLD diagnosis, duration of IF (4-52 weeks), and type of IF (5:2 diet, modern alternate-day fasting, time-restricted eating, or religious fasting). Body weight, body mass index, and waist to hip ratio all significantly improved following fasting intervention (p< 0.05). Adults with NAFLD showed an improvement in serum alanine transaminase, aspartate aminotransferase, hepatic steatosis (controlled attenuation parameter measured by vibration-controlled transient elastography), and hepatic stiffness (measured by vibration-controlled transient elastography) after fasting intervention (p < 0.05). CONCLUSIONS: There is limited, but moderate- to high-quality evidence to suggest that IF can improve hepatic end points and promote weight loss in adults with NAFLD. Larger randomized controlled studies with extended duration are needed to further validate our findings.
31The efficacy of Carbamylglutamate impacts the nutritional management of patients with N-Acetylglutamate synthase deficiency.PubMed
Rani H Singh, Marie-Hélène Bourdages, Angela Kurtz, et al.
Orphanet J Rare Dis. 2024 Apr 18;19(1):168. doi: 10.1186/s13023-024-03167-0.
BACKGROUND: The autosomal recessive disorder N-acetylglutamate synthase (NAGS) deficiency is the rarest defect of the urea cycle, with an incidence of less than one in 2,000,000 live births. Hyperammonemic crises can be avoided in individuals with NAGS deficiency by the administration of carbamylglutamate (also known as carglumic acid), which activates carbamoyl phosphatase synthetase 1 (CPS1). The aim of this case series was to introduce additional cases of NAGS deficiency to the literature as well as to assess the role of nutrition management in conjunction with carbamylglutamate therapy across new and existing cases. METHODS: We conducted retrospective chart reviews of seven cases of NAGS deficiency in the US and Canada, focusing on presentation, diagnosis, medication management, nutrition management, and outcomes. RESULTS: Five new and two previously published cases were included. Presenting symptoms were consistent with previous reports. Diagnostic confirmation via molecular testing varied in protocol across cases, with consecutive single gene tests leading to long delays in diagnosis in some cases. All patients responded well to carbamylglutamate therapy, as indicated by normalization of plasma ammonia and citrulline, as well as urine orotic acid in patients with abnormal levels at baseline. Although protein restriction was not prescribed in any cases after carbamylglutamate initiation, two patients continued to self-restrict protein intake. One patient experienced two episodes of hyperammonemia that resulted in poor long-term outcomes. Both episodes occurred after a disruption in access to carbamylglutamate, once due to insurance prior authorization requirements and language barriers and once due to seizure activity limiting the family's ability to administer carbamylglutamate. CONCLUSIONS: Follow-up of patients with NAGS deficiency should include plans for illness and for disruption of carbamylglutamate access, including nutrition management strategies such as protein restriction. Carbamylglutamate can help patients with NAGS deficiency to liberalize their diets, but the maximum safe level of protein intake to prevent hyperammonemia is not yet known. Patients using this medication should still monitor their diet closely and be prepared for any disruptions in medication access, which might require immediate dietary adjustments or medical intervention to prevent hyperammonemia.
32Vitamin D and type 2 diabetes.PubMed
Paul Lips, Marelise Eekhoff, Natasja van Schoor, et al.
J Steroid Biochem Mol Biol. 2017 Oct;173:280-285. doi: 10.1016/j.jsbmb.2016.11.021. Epub 2016 Dec 5.
Vitamin D deficiency is associated with a decreased insulin release, insulin resistance and type 2 diabetes in experimental and epidemiological studies. Animal studies show that 1α,25-dihydroxyvitamin D (1,25(OH)D) stimulates the pancreatic β-cell to secrete insulin. The relationship between vitamin D deficiency and insulin resistance could develop through inflammation, as vitamin D deficiency is associated with increased inflammatory markers. In addition, genetic polymorphisms of vitamin D -related genes may predispose to impaired glycemic control and type 2 diabetes. Epidemiologic studies showed an association between low serum 25-hydroxyvitamin D (25(OH)D) concentration and an increased risk for the metabolic syndrome and type 2 diabetes. This may be partly explained by an increased fat mass. A possible causal relationship between vitamin D deficiency and type 2 diabetes should be proven by randomized clinical trials showing that either type 2 diabetes can be prevented or insulin release and insulin sensitivity can be improved by vitamin D supplements. The results of randomized clinical trials on the effect of vitamin D versus placebo, sometimes combined with calcium, in patients with impaired glucose tolerance ("prediabetes") or type 2 diabetes are inconsistent. Some studies showed a slight decrease of fasting plasma glucose or improvement of insulin resistance, but often only in posthoc analyses. These effects are mainly visible in patients with vitamin D deficiency and impaired glucose tolerance at baseline. Meta-analyses of randomized clinical trials in general did not show significant effects of vitamin D supplementation on glycemic control. Currently, several large scale randomized clinical trials with vitamin D supplementation in doses of 1600-4000IU/d are ongoing with glycemic control or incidence of diabetes mellitus as outcome. Vitamin D deficiency needs to be prevented or cured, but until the results of these trials are published, high-dose vitamin D supplementation cannot be recommended for prevention or amelioration of type 2 diabetes.
33Mechanisms and risk factors of metabolic syndrome in children and adolescents.PubMed
Valentina Codazzi, Giulio Frontino, Luca Galimberti, et al.
Endocrine. 2024 Apr;84(1):16-28. doi: 10.1007/s12020-023-03642-x. Epub 2023 Dec 22.
Metabolic syndrome (MetS) is a complex disorder characterized by abdominal obesity, elevated blood pressure, hyperlipidemia, and elevated fasting blood glucose levels. The diagnostic criteria for MetS in adults are well-established, but there is currently no consensus on the definition in children and adolescents. The etiology of MetS is believed to involve a complex interplay between genetic predisposition and environmental factors. While genetic predisposition explains only a small part of MetS pathogenesis, modifiable environmental risk factors play a significant role. Factors such as maternal weight during pregnancy, children's lifestyle, sedentariness, high-fat diet, fructose and branched-chain amino acid consumption, vitamin D deficiency, and sleep disturbances contribute to the development of MetS. Early identification and treatment of MetS in children and adolescents is crucial to prevent the development of chronic diseases later in life. In this review we discuss the latest research on factors contributing to the pathogenesis of MetS in children, focusing on non-modifiable and modifiable risk factors, including genetics, dysbiosis and chronic low-grade inflammation.
34The Effect of Vitamin D Supplementation on Glycemic Control in Type 2 Diabetes Patients: A Systematic Review and Meta-Analysis.PubMed
Xinyi Li, Yan Liu, Yingdong Zheng, et al.
Nutrients. 2018 Mar 19;10(3):375. doi: 10.3390/nu10030375.
Observational studies have indicated an inverse association between vitamin D levels and the risk of diabetes, yet evidence from population interventions remains inconsistent. PubMed, EMBASE, Cochrane Library and ClinicalTrials.gov were searched up to September 2017. Data from studies regarding serum 25(OH)D, fasting blood glucose (FBG), hemoglobin A1c (HbA1c), fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were pooled. Twenty studies ( = 2703) were included in the meta-analysis. Vitamin D supplementation resulted in a significant improvement in serum 25(OH)D levels (weighted mean difference (WMD) = 33.98; 95%CI: 24.60-43.37) and HOMA-IR (standardized mean difference (SMD) = -0.57; 95%CI: -1.09~-0.04), but not in other outcomes. However, preferred changes were observed in subgroups as follows: short-term (WMD = -8.44; 95%CI: -12.72~-4.15), high dose (WMD = -8.70; 95%CI: -12.96~-4.44), non-obese (SMD = -1.80; 95%CI: -2.66~-0.95), Middle Easterners (WMD = -10.43; 95%CI: -14.80~-6.06), baseline vitamin D deficient individuals (WMD = -5.77; 95%CI: -10.48~-1.05) and well-controlled HbA1c individuals (WMD = -4.09; 95%CI: -15.44~7.27). Vitamin D supplementation was shown to increase serum 25(OH)D and reduce insulin resistance effectively. This effect was especially prominent when vitamin D was given in large doses and for a short period of time, and to patients who were non-obese, Middle Eastern, vitamin D deficient, or with optimal glycemic control at baseline.
35Vitamin D deficiency and cardiovascular risk in type 2 diabetes population.PubMed
Sushant Pokhrel, Nisha Giri, Rakesh Pokhrel, et al.
Open Life Sci. 2021 May 10;16(1):464-474. doi: 10.1515/biol-2021-0050. eCollection 2021.
This study aims to assess vitamin D deficiency-induced dyslipidemia and cardiovascular disease (CVD) risk in poor glycemic control among type 2 diabetes mellitus (T2DM) patients. This study was carried out among 455 T2DM patients involving poor glycemic control ( = 247) and good glycemic control ( = 208). Fasting plasma glucose (FPG) and HbAc were measured to assess glycemic control. Cardiac risk ratio, atherogenic index plasma, and atherogenic coefficient were calculated to assess and compare the CVD risk in different groups. Patients with poor control had a significantly higher level of total cholesterol (TC), triglyceride (TG), and non-high-density lipoprotein lipase cholesterol (non-HDL-C), atherogenic variables, and lower level of high-density lipoprotein lipase cholesterol (HDL-C) as compared to patients with good glycemic control. We also observed significant negative correlation of vitamin D with lipid markers and atherogenic variables in poor glycemic control diabetic population. The serum vitamin D levels were inversely associated with HbAc, FPG, TG, TC, and non-HDL-C. Furthermore, hypercholesterolemia, hypertriglyceridemia, and elevated non-HDL-C were the independent risks in hypovitaminosis D population. Vitamin D deficiency in poor glycemic control is likely to develop dyslipidemia as compared to vitamin D insufficient and sufficient groups. Thus, vitamin D supplementation and an increase in exposure to sunlight may reduce the risk of cardiovascular complications in diabetes.
36Circadian Disruption and the Risk of Developing Obesity.PubMed
Hélène Duez, Bart Staels
Curr Obes Rep. 2025 Feb 13;14(1):20. doi: 10.1007/s13679-025-00610-6.
PURPOSE OF THE REVIEW: This review summarizes recent evidence for a role of the clock in adipose tissue physiology and the impact of circadian desynchrony on the development of obesity. RECENT FINDINGS: Circadian disruptions due to shift work, late time eating and nighttime light exposure are associated with obesity and its metabolic and cardiovascular consequences. Studies in mice harboring tissue-specific gain/loss of function mutations in clock genes revealed that the circadian clock acts on multiple pathways to control adipogenesis, lipogenesis/lipolysis and thermogenesis. Time-restricted eating (TRE), aligning feeding with the active period to restore clock function, represents a promising strategy to curb obesity. While TRE has shown clear benefits, especially in participants at higher cardiometabolic risk, current studies are limited in size and duration. Larger, well-controlled studies are warranted to conclusively assess the effects of TRE in relation to the metabolic status and gender. Field studies in shift-workers, comparing permanent night shift versus rotating shifts, are also necessary to identify the optimal time window for TRE.
38Effects of eight weeks of time-restricted feeding (16/8) on basal metabolism, maximal strength, body composition, inflammation, and cardiovascular risk factors in resistance-trained males.PubMed
Tatiana Moro, Grant Tinsley, Antonino Bianco, et al.
J Transl Med. 2016 Oct 13;14(1):290. doi: 10.1186/s12967-016-1044-0.
BACKGROUND: Intermittent fasting (IF) is an increasingly popular dietary approach used for weight loss and overall health. While there is an increasing body of evidence demonstrating beneficial effects of IF on blood lipids and other health outcomes in the overweight and obese, limited data are available about the effect of IF in athletes. Thus, the present study sought to investigate the effects of a modified IF protocol (i.e. time-restricted feeding) during resistance training in healthy resistance-trained males. METHODS: Thirty-four resistance-trained males were randomly assigned to time-restricted feeding (TRF) or normal diet group (ND). TRF subjects consumed 100 % of their energy needs in an 8-h period of time each day, with their caloric intake divided into three meals consumed at 1 p.m., 4 p.m., and 8 p.m. The remaining 16 h per 24-h period made up the fasting period. Subjects in the ND group consumed 100 % of their energy needs divided into three meals consumed at 8 a.m., 1 p.m., and 8 p.m. Groups were matched for kilocalories consumed and macronutrient distribution (TRF 2826 ± 412.3 kcal/day, carbohydrates 53.2 ± 1.4 %, fat 24.7 ± 3.1 %, protein 22.1 ± 2.6 %, ND 3007 ± 444.7 kcal/day, carbohydrates 54.7 ± 2.2 %, fat 23.9 ± 3.5 %, protein 21.4 ± 1.8). Subjects were tested before and after 8 weeks of the assigned diet and standardized resistance training program. Fat mass and fat-free mass were assessed by dual-energy x-ray absorptiometry and muscle area of the thigh and arm were measured using an anthropometric system. Total and free testosterone, insulin-like growth factor 1, blood glucose, insulin, adiponectin, leptin, triiodothyronine, thyroid stimulating hormone, interleukin-6, interleukin-1β, tumor necrosis factor α, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides were measured. Bench press and leg press maximal strength, resting energy expenditure, and respiratory ratio were also tested. RESULTS: After 8 weeks, the 2 Way ANOVA (Time * Diet interaction) showed a decrease in fat mass in TRF compared to ND (p = 0.0448), while fat-free mass, muscle area of the arm and thigh, and maximal strength were maintained in both groups. Testosterone and insulin-like growth factor 1 decreased significantly in TRF, with no changes in ND (p = 0.0476; p = 0.0397). Adiponectin increased (p = 0.0000) in TRF while total leptin decreased (p = 0.0001), although not when adjusted for fat mass. Triiodothyronine decreased in TRF, but no significant changes were detected in thyroid-stimulating hormone, total cholesterol, high-density lipoprotein, low-density lipoprotein, or triglycerides. Resting energy expenditure was unchanged, but a significant decrease in respiratory ratio was observed in the TRF group. CONCLUSIONS: Our results suggest that an intermittent fasting program in which all calories are consumed in an 8-h window each day, in conjunction with resistance training, could improve some health-related biomarkers, decrease fat mass, and maintain muscle mass in resistance-trained males.
39What happens after a weight loss intervention? A qualitative study of drivers and challenges of maintaining time-restricted eating among people with overweight at high risk of type 2 diabetes.PubMed
Natasja Bjerre, Lotte Holm, Nanna Veje, et al.
Appetite. 2022 Jul 1;174:106034. doi: 10.1016/j.appet.2022.106034. Epub 2022 Apr 2.
Time-restricted eating (TRE) has been conceptualised as a strategy for achieving weight loss and improving metabolic health, but limited knowledge exists about how people can maintain TRE in daily life. This study examined how TRE was maintainable in daily life after a three-month intervention (the RESET study) in which participants were encouraged to consume all food and beverages except water within a 10-h daily window. Specifically, we examined TRE maintenance patterns across participants, including drivers and challenges for maintenance success. A qualitative longitudinal study was conducted, and twenty participants with overweight at high risk of type 2 diabetes were interviewed using a semi-structured interview guide at the end of the intervention and after a three-month follow-up period. Data were analysed longitudinally in two steps inspired by a pattern-oriented longitudinal analysis approach. Seven participants maintained a strict 10-h window, ten maintained an adjusted TRE regimen (e.g., taking days off), and three did not attempt maintenance. Maintenance drivers included consistent daily rhythms and regular meal patterns, subjective experiences (e.g., feeling healthier), making flexible adjustments to the TRE regimen, family support and avoiding feelings of guilt. Maintenance challenges included social evening events, inconsistent daily rhythms and eating patterns, preoccupation with losing weight, lack of family support and self-blame. TRE was manageable for most participants; however, personalised support for adjusting TRE to daily life is needed to ensure long-term maintenance. Future studies should explore the effectiveness of a personalised TRE concept to determine the usefulness of TRE in real-life settings.
40Time-restricted eating (16/8) and energy-restricted diet: effects on diet quality, body composition and biochemical parameters in healthy overweight females.PubMed
Özge Mengi Çelik, Eda Köksal, Müjde Aktürk
BMC Nutr. 2023 Aug 9;9(1):97. doi: 10.1186/s40795-023-00753-6.
BACKGROUND: Time-restricted eating (TRE) is a current popular dietary strategy for noncommunicable diseases. However, studies demonstrated contradictory results for it and in all dietary strategies, diet quality is an the important part of the well-being. Our study aimed to investigate the effect of TRE and energy-restricted diet (ERD) on the nutritional status and diet quality of individuals. METHODS: This pilot study was completed 23 healthy overweight female. Anthropometric and body composition measurements of individuals were taken. The energy expenditure was measured using indirect calorimetry. Blood pressure and heart rate measurements were made. Biochemical parameters were evaluated and food consumption were taken. The quality of dietary intake was assessed using the Healthy Eating Index (HEI) -2015. The physical activity levels of the individuals were estimated using the physical activity record. The Statistical Package for the Social Sciences (version 22.0) software was used for all analyses. A p-value of less than 0.05 was considered to be statistically significant. RESULTS: After 8 weeks of intervention, while no change was observed in the diet quality of the individuals in the TRE group (p > 0.05), a significant increase was found in the diet quality score of the individuals in the ERD group (p < 0.05). There was a 3.2% and 5.5% decrease in body weight of individuals in the TRE and ERD groups, respectively (p < 0.05). While no significant change was observed in the body fat percentage of individuals in the TRE group (p > 0.05), a 7.1% decrease was observed in the ERD group (p < 0.05). A statistically significant decrease was found in the total cholesterol (3.7%) in the ERD group, and in the total cholesterol (6.7%) and low density lipoprotein cholesterol (LDL-C) (6.5%) in the TRE group. In addition, a statistically significant increase was found in adiponectin (77.3%) and total antioxidant status (TAS) (13.2%) in the ERD group. CONCLUSION: Energy-restricted diet yielded better results in weight loss and improvement of body composition and diet quality compared to TRE. Also, a decrease in total cholesterol level was found in the ERD group. However, more studies should be done with longer follow-ups and high sample sizes are very important in terms of creating public health-based recommendations.
41Popular Dietary Trends' Impact on Athletic Performance: A Critical Analysis Review.PubMed
Matthew Kaufman, Chantal Nguyen, Maya Shetty, et al.
Nutrients. 2023 Aug 9;15(16):3511. doi: 10.3390/nu15163511.
BACKGROUND: Nutrition fuels optimal performance for athletes. With increased research developments, numerous diets available, and publicity from professional athletes, a review of dietary patterns impact on athletic performance is warranted. RESULTS: The Mediterranean diet is a low inflammatory diet linked to improved power and muscle endurance and body composition. Ketogenic diets are restrictive of carbohydrates and proteins. Though both show no decrements in weight loss, ketogenic diets, which is a more restrictive form of low-carbohydrate diets, can be more difficult to follow. High-protein and protein-paced versions of low-carbohydrate diets have also shown to benefit athletic performance. Plant-based diets have many variations. Vegans are at risk of micronutrient deficiencies and decreased leucine content, and therefore, decreased muscle protein synthesis. However, the literature has not shown decreases in performance compared to omnivores. Intermittent fasting has many different versions, which may not suit those with comorbidities or specific needs as well as lead to decreases in sprint speed and worsening time to exhaustion. CONCLUSIONS: This paper critically evaluates the research on diets in relation to athletic performance and details some of the potential risks that should be monitored. No one diet is universally recommend for athletes; however, this article provides the information for athletes to analyze, in conjunction with medical professional counsel, their own diet and consider sustainable changes that can help achieve performance and body habitus goals.
42Perspective: Time-Restricted Eating-Integrating the What with the When.PubMed
Evelyn B Parr, Brooke L Devlin, John A Hawley
Adv Nutr. 2022 Jun 1;13(3):699-711. doi: 10.1093/advances/nmac015.
Time-restricted eating (TRE) is a popular dietary strategy that emphasizes the timing of meals in alignment with diurnal circadian rhythms, permitting ad libitum energy intake during a restricted (∼8-10 h) eating window each day. Unlike energy-restricted diets or intermittent fasting interventions that focus on weight loss, many of the health-related benefits of TRE are independent of reductions in body weight. However, TRE research to date has largely ignored what food is consumed (i.e., macronutrient composition and energy density), overlooking a plethora of past epidemiological and interventional dietary research. To determine some of the potential mechanisms underpinning the benefits of TRE on metabolic health, future studies need to increase the rigor of dietary data collected, assessed, and reported to ensure a consistent and standardized approach in TRE research. This Perspective article provides an overview of studies investigating TRE interventions in humans and considers dietary intake (both what and when food is eaten) and their impact on selected health outcomes (i.e., weight loss, glycemic control). Integrating existing dietary knowledge about what food is eaten with our recent understanding on when food should be consumed is essential to optimize the impact of dietary strategies aimed at improving metabolic health outcomes.
43Twelve Months of Time-restricted Eating and Resistance Training Improves Inflammatory Markers and Cardiometabolic Risk Factors.PubMed
Tatiana Moro, Grant Tinsley, Francesco Q Pacelli, et al.
Med Sci Sports Exerc. 2021 Dec 1;53(12):2577-2585. doi: 10.1249/MSS.0000000000002738.
INTRODUCTION: Recently, a modified intermittent fasting protocol was demonstrated to be able to maintain muscle mass and strength, decrease fat mass, and improve some inflammation and cardiovascular risk factors in healthy resistance-trained males after 2 months. The present study sought to investigate the long-term effects on these parameters. METHODS: The experiment was a single-blind randomized study. Twenty healthy subjects were enrolled and underwent 12 months of either a time-restricted eating (TRE) diet or a normal diet (ND) protocol, along with resistance training. In the TRE protocol, subjects consumed their energy needs in three meals during an 8-h period of time each day (1 pm, 4 pm, and 8 pm). Subjects in the ND group also had three meals, which were consumed at 8 am, 1 pm, and 8 pm. Groups were matched for kilocalories consumed and macronutrient distribution at baseline. RESULTS: After 12 months of TRE, body mass, fat mass, insulin-like growth factor 1, and testosterone were significantly lower compared with ND. Moreover, inflammatory markers (interleukin 6, interleukin 1β, and tumor necrosis factor α), insulin sensitivity (fasting glucose, insulin, and homeostatic model assessment for insulin resistance index), and lipid profile (cholesterol, HDL, and LDL) significantly improved after TRE compared with ND. Finally, subjects in TRE spontaneously decreased their daily energy intake, whereas those in ND maintained their starting kilocalories per day. No adverse events were reported. CONCLUSIONS: Our results suggest that long-term TRE combined with a resistance training program is feasible, safe, and effective in reducing inflammatory markers and risk factors related to cardiovascular and metabolic diseases.
44Time-restricted feeding plus resistance training in active females: a randomized trial.PubMed
Grant M Tinsley, M Lane Moore, Austin J Graybeal, et al.
Am J Clin Nutr. 2019 Sep 1;110(3):628-640. doi: 10.1093/ajcn/nqz126.
BACKGROUND: A very limited amount of research has examined intermittent fasting (IF) programs, such as time-restricted feeding (TRF), in active populations. OBJECTIVE: Our objective was to examine the effects of TRF, with or without β-hydroxy β-methylbutyrate (HMB) supplementation, during resistance training (RT). METHODS: This study employed a randomized, placebo-controlled, reduced factorial design and was double-blind with respect to supplementation in TRF groups. Resistance-trained females were randomly assigned to a control diet (CD), TRF, or TRF plus 3 g/d HMB (TRFHMB). TRF groups consumed all calories between 1200 h and 2000 h, whereas the CD group ate regularly from breakfast until the end of the day. All groups completed 8 wk of supervised RT and consumed supplemental whey protein. Body composition, muscular performance, dietary intake, physical activity, and physiological variables were assessed. Data were analyzed prior to unblinding using mixed models and both intention-to-treat (ITT) and per protocol (PP) frameworks. RESULTS: Forty participants were included in ITT, and 24 were included in PP. Energy and protein intake (1.6 g/kg/d) did not differ between groups despite different feeding durations (TRF and TRFHMB: ∼7.5 h/d; CD: ∼13 h/d). Comparable fat-free mass (FFM) accretion (+2% to 3% relative to baseline) and skeletal muscle hypertrophy occurred in all groups. Differential effects on fat mass (CD: +2%; TRF: -2% to -4%; TRFHMB: -4% to -7%) were statistically significant in the PP analysis, but not ITT. Muscular performance improved without differences between groups. No changes in physiological variables occurred in any group, and minimal side effects were reported. CONCLUSIONS: IF, in the form of TRF, did not attenuate RT adaptations in resistance-trained females. Similar FFM accretion, skeletal muscle hypertrophy, and muscular performance improvements can be achieved with dramatically different feeding programs that contain similar energy and protein content during RT. Supplemental HMB during fasting periods of TRF did not definitively improve outcomes. This study was prospectively registered at clinicaltrials.gov as NCT03404271.
45European Association for the Study of Obesity (EASO) Position Statement on Medical Nutrition Therapy for the Management of Individuals with Overweight or Obesity and Cancer.PubMed
Giovanna Muscogiuri, Luigi Barrea, Silvia Bettini, et al.
Obes Facts. 2025;18(1):86-105. doi: 10.1159/000542155. Epub 2024 Oct 30.
Obesity, a prevalent and multifactorial disease, is linked to a range of metabolic abnormalities, including insulin resistance, dyslipidemia, and chronic inflammation. These imbalances not only contribute to cardiometabolic diseases but also play a significant role in cancer pathogenesis. The rising prevalence of obesity underscores the need to investigate dietary strategies for effective weight management for individuals with overweight or obesity and cancer. This European Society for the Study of Obesity (EASO) position statement aimed to summarize current evidence on the role of obesity in cancer and to provide insights on the major nutritional interventions, including the Mediterranean diet (MedDiet), the ketogenic diet (KD), and the intermittent fasting (IF), that should be adopted to manage individuals with overweight or obesity and cancer. The MedDiet, characterized by high consumption of plant-based foods and moderate intake of olive oil, fish, and nuts, has been associated with a reduced cancer risk. The KD and the IF are emerging dietary interventions with potential benefits for weight loss and metabolic health. KD, by inducing ketosis, and IF, through periodic fasting cycles, may offer anticancer effects by modifying tumor metabolism and improving insulin sensitivity. Despite the promising results, current evidence on these dietary approaches in cancer management in individuals with overweight or obesity is limited and inconsistent, with challenges including variability in adherence and the need for personalized dietary plans.
46The rationale and design of a Mediterranean diet accompanied by time restricted feeding to optimise the management of type 2 diabetes: The MedDietFast randomised controlled trial.PubMed
Dimitra Papamichou, Demosthenes B Panagiotakos, Elaine Holmes, et al.
Nutr Metab Cardiovasc Dis. 2022 Jan;32(1):220-230. doi: 10.1016/j.numecd.2021.09.031. Epub 2021 Oct 7.
BACKGROUND AND AIMS: Substantial scientific evidence supports the effectiveness of a Mediterranean diet (MedDiet) in managing type 2 diabetes mellitus (T2DM). Potential benefits of time restricted feeding (TRF) in T2DM are unknown. The MedDietFast trial aims to investigate the efficacy of a MedDiet with or without TRF compared to standard care diet in managing T2DM. METHODS AND RESULTS: 120 adults aged 20-75 with a body mass index (BMI) of 20-35 kg/m and T2DM will be randomised in a 3-arm parallel design to follow an ad libitum MedDiet with or without 12-h TRF or the standard Australian Dietary Guidelines (ADG) for 24 weeks. All groups will receive dietary counselling fortnightly for 12 weeks and monthly thereafter. The primary outcome is changes in HbA1c from baseline to 12 and 24 weeks. Secondary outcomes include fasting blood glucose, insulin, blood lipids, weight loss, insulin resistance index (HOMA), Glucagon-like peptide 1 (GLP-1) and high-sensitivity C- reactive protein (hs-CRP). Data on medical history, anthropometry, wellbeing, MedDiet adherence and satiety will be measured at a private clinic via self-report questionnaires at baseline, 6, 12 and 24 weeks. Additionally, specimens (blood, urine and stool) will be collected at all time points for future omics analysis. CONCLUSION: The MedDietFast trial will examine the feasibility and effectiveness of a MedDiet with/without TRF in T2DM patients. Potential synergistic effects of a MedDiet with TRF will be evaluated. Future studies will generate microbiomic and metabolomic data for translation of findings into simple and effective management plans for T2DM patients. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register, ACTRN12619000246189.
47Effects of Different Exercises Combined with Different Dietary Interventions on Body Composition: A Systematic Review and Network Meta-Analysis.PubMed
Yongchao Xie, Yu Gu, Zhen Li, et al.
Nutrients. 2024 Sep 5;16(17):3007. doi: 10.3390/nu16173007.
BACKGROUND: Exercise and dietary interventions are essential for maintaining weight and reducing fat accumulation. With the growing popularity of various dietary strategies, evidence suggests that combining exercise with dietary interventions offers greater benefits than either approach alone. Consequently, this combined strategy has become a preferred method for many individuals aiming to maintain health. Calorie restriction, 5/2 intermittent fasting, time-restricted feeding, and the ketogenic diet are among the most popular dietary interventions today. Aerobic exercise, resistance training, and mixed exercise are the most widely practiced forms of physical activity. Exploring the best combinations of these approaches to determine which yields the most effective results is both meaningful and valuable. Despite this trend, a comparative analysis of the effects of different exercise and diet combinations is lacking. This study uses network meta-analysis to evaluate the impact of various combined interventions on body composition and to compare their efficacy. METHODS: We systematically reviewed literature from database inception through May 2024, searching PubMed, Web of Science, Embase, and the Cochrane Library. The study was registered in PROSPERO under the title: "Effects of Exercise Combined with Different Dietary Interventions on Body Composition: A Systematic Review and Network Meta-Analysis" (identifier: CRD42024542184). Studies were meticulously selected based on specific inclusion and exclusion criteria (The included studies must be randomized controlled trials involving healthy adults aged 18 to 65 years. Articles were rigorously screened according to the specified inclusion and exclusion criteria.), and their risk of bias was assessed using the Cochrane risk of bias tool. Data were aggregated and analyzed using network meta-analysis, with intervention efficacy ranked by Surface Under the Cumulative Ranking (SUCRA) curves. RESULTS: The network meta-analysis included 78 randomized controlled trials with 5219 participants, comparing the effects of four combined interventions: exercise with calorie restriction (CR+EX), exercise with time-restricted eating (TRF+EX), exercise with 5/2 intermittent fasting (5/2F+EX), and exercise with a ketogenic diet (KD+EX) on body composition. Intervention efficacy ranking was as follows: (1) Weight Reduction: CR+EX > KD+EX > TRF+EX > 5/2F+EX (Relative to CR+EX, the effect sizes of 5/2F+EX, TRF+EX and KD+EX are 2.94 (-3.64, 9.52); 2.37 (-0.40, 5.15); 1.80 (-1.75, 5.34)). (2) BMI: CR+EX > KD+EX > 5/2F+EX > TRF+EX (Relative to CR+EX, the effect sizes of 5/2F+EX, TRF+EX and KD+EX are 1.95 (-0.49, 4.39); 2.20 (1.08, 3.32); 1.23 (-0.26, 2.71)). (3) Body Fat Percentage: CR+EX > 5/2F+EX > TRF+EX > KD+EX (Relative to CR+EX, the effect sizes of 5/2F+EX, TRF+EX and KD+EX are 2.66 (-1.56, 6.89); 2.84 (0.56, 5.13); 3.14 (0.52, 5.75).). (4) Lean Body Mass in Male: CR+EX > TRF+EX > KD+EX (Relative to CR+EX, the effect sizes of TRF+EX and KD+EX are -1.60 (-6.98, 3.78); -2.76 (-7.93, 2.40)). (5) Lean Body Mass in Female: TRF+EX > CR+EX > 5/2F+EX > KD+EX (Relative to TRF+EX, the effect sizes of CR+EX, 5/2F+EX and KD+EX are -0.52 (-2.58, 1.55); -1.83 (-4.71, 1.04); -2.46 (-5.69,0.76).). CONCLUSION: Calorie restriction combined with exercise emerged as the most effective strategy for reducing weight and fat percentage while maintaining lean body mass. For women, combining exercise with time-restricted eating proved optimal for preserving muscle mass. While combining exercise with a ketogenic diet effectively reduces weight, it is comparatively less effective at decreasing fat percentage and preserving lean body mass. Hence, the ketogenic diet combined with exercise is considered suboptimal.
48Brain-Gut-Microbiome Interactions and Intermittent Fasting in Obesity.PubMed
Juliette Frank, Arpana Gupta, Vadim Osadchiy, et al.
Nutrients. 2021 Feb 10;13(2):584. doi: 10.3390/nu13020584.
The obesity epidemic and its metabolic consequences are a major public health problem both in the USA and globally. While the underlying causes are multifactorial, dysregulations within the brain-gut-microbiome (BGM) system play a central role. Normal eating behavior is coordinated by the tightly regulated balance between intestinal, extraintestinal and central homeostatic and hedonic mechanisms, resulting in stable body weight. The ubiquitous availability and marketing of inexpensive, highly palatable and calorie-dense food has played a crucial role in shifting this balance towards hedonic eating through both central (disruptions in dopaminergic signaling) and intestinal (vagal afferent function, metabolic toxemia, systemic immune activation, changes to gut microbiome and metabolome) mechanisms. The balance between homeostatic and hedonic eating behaviors is not only influenced by the amount and composition of the diet, but also by the timing and rhythmicity of food ingestion. Circadian rhythmicity affects both eating behavior and multiple gut functions, as well as the composition and interactions of the microbiome with the gut. Profound preclinical effects of intermittent fasting and time restricted eating on the gut microbiome and on host metabolism, mostly demonstrated in animal models and in a limited number of controlled human trials, have been reported. In this Review, we will discuss the effects of time-restricted eating on the BGM and review the promising effects of this eating pattern in obesity treatment.
49Intermittent fasting contributes to aligned circadian rhythms through interactions with the gut microbiome.PubMed
M C Daas, N M de Roos
Benef Microbes. 2021 Apr 12;12(2):147-161. doi: 10.3920/BM2020.0149. Epub 2021 Feb 3.
The timing of food consumption is considered to be an important modulator of circadian rhythms, regulating a wide range of physiological processes which are vital to human health. The exact mechanisms underlying this relationship are not fully understood, but likely involve alterations in the structure and functioning of the gut microbiome. Therefore, this narrative review aims to clarify these mechanisms by focusing on intermittent fasting as a dietary strategy of food timing. A literature search identified 4 clinical and 18 preclinical studies that examined either (1) the impact of intermittent fasting on the gut microbiome, or (2) whether circadian rhythms of the host are subject to changes in the bacterial populations in the gut. Results reveal that intermittent fasting directly influences the gut microbiome by amplifying diurnal fluctuations in bacterial abundance and metabolic activity. This in turn leads to fluctuations in the levels of microbial components (lipopolysaccharide) and metabolites (short-chain fatty acids, bile acids, and tryptophan derivates) that act as signalling molecules to the peripheral and central clocks of the host. Binding of these substrates to pattern-recognition receptors on the surface of intestinal epithelial cells in an oscillating manner leads to fluctuations in the expression of circadian genes and their transcription factors involved in various metabolic processes. Intermittent fasting thus contributes to circadian rhythmicity in the host and could hold promising implications for the treatment and prevention of diseases associated with disordered circadian rhythms, such as obesity and metabolic syndrome. Future intervention studies are needed to find more evidence on this relationship in humans, as well as to clarify the optimal fasting regimen for balanced circadian rhythms.
50Repercussions of intermittent fasting on the intestinal microbiota community and body composition: a systematic review.PubMed
Flaydson C S Pinto, Amanda A M Silva, Sandra L Souza
Nutr Rev. 2022 Feb 10;80(3):613-628. doi: 10.1093/nutrit/nuab108.
CONTEXT: Several therapies have been tested for combating weight gain and obesity-related metabolic diseases, and among these therapies, intermittent fasting (IF) has gained a great deal of interest. OBJECTIVE: The aim of this study was to provide the reader with a current survey of IF protocols and an understanding of the outcomes found to date in terms of the profile of the intestinal microbiota (IM) in obese organisms. DATA SOURCES: Data were obtained from 4 databases: PubMed, SCOPUS, LILACs, and Web of Science. DATA EXTRACTION: Data from studies relating IF protocols to the microbiota and weight loss were extracted using a protocol in START program. DATA ANALYSIS: Of the 82 original articles identified from the databases, 35 were eliminated due to duplication, and 32 were excluded due to not meeting the inclusion criteria. Two additional articles found in a new search were added, yielding a total of 17 studies to be included in this review. Among the protocols, alternate-day fasting (ADF) and time-restricted feeding (TRF) were the most common, and they were shown to have different mechanisms of metabolic signaling. TRF influences weight control and biochemical parameters by regulating the circadian system, and improving satiety control systems by acting on leptin secretion. On the other hand, ADF leads to a reduction of ±75% of all energy consumption regardless of dietary composition in addition to promoting hormonal adjustments that promote weight control. Furthermore, both protocols showed the ability to remodel the IM by changing the Firmicutes/Bacteroidetes ratio and increasing the abundance of strains such as Lactobacillus spp. and Akkermansia m. that have a protective effect on metabolism against the effects of weight gain. CONCLUSION: In short, the ADF and TRF protocols have a positive effect on the remodeling of the IM and can possibly be used to control body adiposity, improve insulin sensitivity, and achieve other obesity-related metabolic changes.
51Epigenetic Regulation by Dietary Restriction: Part II.PubMed
Gavin Yong-Quan Ng, David Yang-Wei Fann, Dong-Gyu Jo, et al.
Cond Med. 2019 Dec;2(6):300-310.
In the first part of our review, we extensively discuss the different variants of dietary restriction (DR) regimens, as well as its corresponding mechanism(s) and subsequent effects. We also provide a detailed analysis of the different epigenetic mechanisms based on current knowledge. We postulate that DR may represent an environmental intervention that can modulate the epigenomic profile of an individual. It is highly plausible that epigenetic regulation by DR may help explain the asymmetric manifestation of DR effects in different individuals. Additionally, epigenetic modifications via DR may lead to epigenetic programming, providing protection against age-associated diseases, which in turn could lead to reduced morbidity and increased lifespan. In the second part of the review, we summarize recent findings that highlight the epigenomic axis of DR, which provides a better understanding of the mechanisms by which its numerous health benefits are achieved.