The Role of Chrononutrition in Global Wellness
Article information
Abstract
Chrononutrition aligns dietary patterns with the body’s circadian rhythms, optimizing metabolic processes and promoting health. The human body operates on a 24-hour biological clock, regulating metabolism, hormone secretion, and cellular repair. Disruptions caused by irregular eating habits, shift work, or jet lag can negatively impact health. Chrononutrition aims to synchronize food intake with these rhythms, enhancing energy balance, glucose metabolism, and cardiovascular health. Research suggests that meal timing influences body weight, insulin sensitivity, and chronic disease risk, including obesity, type 2 diabetes, and cardiovascular diseases. Consuming meals during periods of peak insulin sensitivity can help prevent metabolic disorders. As modern lifestyles promote round-the-clock activity, integrating chrononutrition into dietary guidelines and public health policies becomes crucial. By raising awareness and promoting strategic meal timing, individuals can enhance metabolic health and cognitive function, reducing the global burden of lifestyle-related diseases. Governments and healthcare organizations must advocate for chrononutrition as a key component of preventive health strategies. Embracing this approach can foster a healthier, more resilient population, supporting global wellness initiatives. This review aims to explore chrononutrition’s impact on human health, disease prevention, and global well-being.
INTRODUCTION
Circadian rhythms are inherent 24-hour cycles regulating physiological processes, notably controlled by the suprachiasmatic nucleus (SCN) in the anterior hypothalamus of mammals. Serving as the “master clock,” the SCN synchronizes with environmental cues, particularly light detected by retinal ganglion cells. This synchronization allows the SCN to coordinate cellular oscillations across various organs and tissues, influencing numerous physiological functions [1]. Chrononutrition is an emerging field that examines how the timing of food intake influences metabolism, health, and disease prevention. It is based on the principle that our body’s internal biological clocks, known as circadian rhythms, play a critical role in regulating various physiological processes, including digestion, insulin sensitivity, and energy expenditure. By aligning eating patterns with the body’s natural circadian rhythm, chrononutrition seeks to optimize metabolic outcomes and overall health. For instance, consuming meals earlier in the day when metabolic efficiency is higher has been shown to improve glycemic control and reduce the risk of obesity and cardiovascular disease (CVD). This approach aligns well with modern dietary guidelines, which emphasize balanced eating patterns, reduced late-night food intake, and mindful meal timing as essential components of a healthy lifestyle. Chrononutrition, therefore, offers a time-sensitive dimension to traditional nutritional science, providing a holistic perspective that integrates when we eat with what and how much we eat. While circadian rhythms’ role in mammalian physiology has long been acknowledged [2], their impact on nutrition and metabolism has emerged as a burgeoning area of interest in recent years, signaling a new frontier of research and understanding [3]. It is widely acknowledged that food intake, appetite, digestion, and metabolism each follow circadian patterns [4]. Food intake itself acts as a regulator of the circadian clock, particularly affecting the peripheral circadian clock in tissues like the liver and intestine [5–7]. Conversely, the central circadian clock, synchronized by the dark-light cycle, extends its influence on food absorption. For instance, small peptides derived from dietary protein are transported in a circadian-driven process in the intestine [8]. Similar observations apply to glucose [9] and lipid transport [10]. Despite advancements in understanding circadian rhythms, further insight is needed into how the nutrient composition of mixed meals interacts to affect health.
The historical discourse on meal timing spans diverse civilizations. Ancient Greeks typically consumed three to four meals, with breakfast and the evening meal deemed paramount. In Roman times, breakfast was customary at dawn, yet emphasis shifted towards later meals, particularly among the upper echelons of society. Conversely, the working class aligned meals with labour patterns, synchronizing with the day-night cycle [11]. In the Islamic world, meal timing often followed the dark-light cycle, with pre-sunrise consumption considered a sacred ritual promoting health. Avicenna recommended two daily meals, one before sunrise and another at dusk. Ancient Andalusian physicians advocated two to three meals separated by 6–12 hour intervals, tailored to individual needs [12]. In medieval Europe, breakfast garnered skepticism, viewed as detrimental until its recognition as essential in the 16th century. Proverbs like “Eat breakfast like a king...” underscored its newfound importance [13]. Recent research, including randomized controlled trials (RCTs) and observational studies, underscores the significance of breakfast consumption for health benefits [14]. Investigations into night eating habits have also explored their association with cardio-metabolic disorders, notably obesity [15]. Moreover, studies examining the distribution of daily energy intake reveal altered physiological responses [16,17]. While the precise mechanisms remain unclear, emerging evidence suggests that circadian rhythms directly influence genes involved in substrate metabolism, affecting their oxidation or storage fate [18].
The rising global burden of diseases such as diabetes, obesity, atherosclerosis, and non-alcoholic fatty liver disease presents a pressing challenge for healthcare systems [19–21]. Chronic misalignment of circadian rhythms, influenced by factors like prolonged exposure to artificial light and sedentary lifestyles, has been linked to an elevated risk of metabolic disorders [22,23]. Addressing these complex health issues requires comprehensive and tailored interventions. The intricate relationship between circadian rhythms and metabolism, coupled with the central regulation of feeding behavior, suggests that circadian dysfunction or disruption of normal rhythmicity may play a role in the onset of cardiometabolic diseases. The current challenge lies in comprehensively understanding the bidirectional nature of this interaction and exploring the potential benefits of timed dietary interventions and chrononutrition for managing diabetes, obesity, and cardiometabolic disorders. Various factors, including a higher proportion of daily energy intake during the evening, irregular meal patterns, increased meal frequency, and prolonged eating durations, could contribute to the development of cardiometabolic diseases [24–26]. Conversely, emerging research suggests that timed feeding strategies present a promising behavioral intervention to mitigate cardiometabolic risk [27,28]. These studies underscore the significance of understanding circadian rhythms and chronobiology in nutrition and their potential to influence physiological status. Despite the unclear driver behind such alterations, the complex interplay among various eating occasions emphasizes the need for a comprehensive approach. This approach should consider the circadian rhythms of eating and evaluate the timing of energy intake across all eating occasions, as energy intake at one occasion is interconnected with intake at previous and subsequent occasions. The timing of meals appears to influence the progression of non-communicable diseases, making chrononutrition a promising approach for their management. It’s essential to emphasize adherence to dietary guidelines, focusing on whole grains, plant-based foods, and limiting ultra-processed foods, during chrononutrition. Thus, this review aims to explore the potential of chrononutrition as a nutritional intervention to regulate circadian rhythms,
METHODS
A systematic review of the literature was conducted to evaluate the role of chrononutrition in promoting global wellness, particularly in relation to metabolic health, circadian alignment, cardiovascular risk, and lifestyle outcomes. A comprehensive search was performed across several electronic databases, including PubMed, Scopus, Web of Science, ScienceDirect, and Google Scholar, for gray literature and relevant reviews. The search strategy used a combination of keywords and Boolean operators, such as “chrono-nutrition,” “meal timing,” “circadian rhythm AND nutrition,” “eating time AND metabolic health,” “chrono-biological eating,” and “time-restricted feeding AND health outcomes.” The search was limited to articles published in English between January 2000 and April 2025. Studies were included if they met the following criteria: human-based research (involving adults or adolescents), original articles including RCTs, cohort studies, cross-sectional studies, systematic reviews, or meta-analyses that evaluated the impact of meal timing or chrononutritional practices on health-related outcomes. Exclusion criteria included non-English publications, animal or in vitro studies, studies focused solely on nutrient composition without consideration of timing, and non-peer-reviewed sources such as editorials, commentaries, or abstracts without full-text availability. Duplicate studies and those lacking sufficient methodological detail were also excluded. The selection process involved two independent reviewers who screened titles and abstracts for relevance, followed by full-text review to confirm eligibility. Any disagreements were resolved through discussion or third-party arbitration. For each included study, data on study design, population characteristics, dietary intervention or meal timing protocol, outcome measures, and key findings were extracted and synthesized narratively.
UNDERSTANDING CHRONOBIOLOGY
Life on Earth has evolved to synchronize with the natural light/dark cycles driven by the planet’s rotation. Organisms possess an intrinsic 24-hour circadian clock, aligning their daily behaviors with external conditions. These internal rhythms, derived from the Latin “circa diem,” meaning “about a day,” regulate various bodily processes, including sleep/wake patterns, immune function, metabolism, body temperature, and blood pressure (BP). The circadian clock operates through a complex system of molecular mechanisms driven by various environmental cues, known as zeitgebers. Central to this system is the interplay between key proteins, namely the circadian locomotor output cycles kaput (CLOCK) and brain and muscle Arnt-like protein-1 (BMAL1), which form heterodimers to regulate the transcription of numerous clock-dependent genes. These genes, including PER (Period), CRY (Cryptochrome), REV-ERBα (a protein encoded by the NR1D1 gene), RORα (receptor-related orphan receptor α), PPARα (peroxisome proliferator-activated receptor α), PPARγ (peroxisome proliferator-activated receptor γ), SIRT1 (sirtuin 1), and others, participate in a sophisticated feedback loop that influences the activity of CLOCK and BMAL1 themselves. This intricate network of interactions, depicted by solid and dotted arrows, ultimately determines the amplitude, period, phase, and MESOR (midline estimating statistic of rhythm) of the circadian oscillations, thereby defining the rhythmicity and robustness of the circadian clock. In addition, molecules such as nicotinamide phosphoribosyltransferase (NAMPT), nicotinamide adenine dinucleotide (NAD+), AMP-activated protein kinase (AMPK), and PPARγ coactivator 1α (PGC1α) also play crucial roles in modulating the circadian system by influencing metabolic processes and energy balance. Together, these components orchestrate the precise timing of physiological and behavioral rhythms, ensuring synchronization with the external environment (Figure 1).
Mechanism of circadian clock. The circadian clock regulates daily physiological rhythms through a complex network involving various molecular components. ROR (retinoic acid receptor-related orphan receptor) proteins promote the expression of genes like REV-ERBα and PPAR (peroxisome proliferator-activated receptor), which influence metabolic processes. ROR binds to RORE (ROR response elements) in gene promoters, while BMAL1 (brain and muscle ARNT-like 1) and CLOCK proteins form a complex that drives the expression of clock-controlled genes (CCGs). Additionally, NAMPT (nicotinamide adenine dinucleotide biosynthesis enzyme) plays a critical role in maintaining NAD+ levels, supporting cellular energy metabolism and circadian rhythm.
External cues known as zeitgebers, such as light/dark cycles, play a crucial role in entraining or synchronizing the circadian system. By responding to these environmental signals, organisms adjust their internal clocks to match the external world, ensuring optimal adaptation and survival. This intricate interplay between internal biological rhythms and external cues underscores the importance of maintaining alignment with the natural cycles of the Earth for overall health and well-being. The circadian clock in mammals comprises two main subsystems: the core and the peripheral clocks. The core circadian clock, located in the anterior hypothalamus, includes the SCN, consisting of approximately 20,000 neurons, with light acting as the primary zeitgeber [29]. Light signals are transmitted from the eyes to the SCN, where they are integrated with non-photic cues such as food intake and external temperature. This integration generates an endogenous rhythm, which is then synchronized with other parts of the brain and peripheral organs through direct neuronal connections and endocrine signalling, ensuring alignment of the entire body’s circadian clock with the light-dark cycle [30]. In addition to the core pacemaker, individual cells throughout the body possess their own local clocks, exhibiting autonomous daily rhythmicity. While these peripheral clock systems are influenced by the SCN, they can also be entrained by other zeitgebers independent of the SCN, such as meal timing, locomotor activity, and body temperature fluctuations [31].
During the nighttime, the SCN regulates the synthesis and release of melatonin by the pineal gland. Melatonin, a hormone with sleep-inducing properties, displays a 24-hour rhythmicity, with its production inhibited by exposure to light, leading to low circulatory levels during the day [32]. Approximately 2–3 hours before habitual nocturnal sleep, melatonin levels begin to rise, coinciding with the onset of dim light conditions in the evening. This rise in melatonin levels, known as dim light melatonin onset (DLMO), serves as a reliable marker for circadian entrainment [33,34]. Melatonin exerts its biological effects by binding to specific receptors, including human melatonin receptor 1A and 1B (MTNR1A and MTNR1B). Sleep duration and quality, influenced by melatonin levels, are integral modulators of various metabolic and endocrine pathways, with implications for conditions such as obesity [35,36]. Moreover, melatonin plays a role in glucose-mediated insulin secretion inhibition and acts as a free radical scavenger, directly contributing to the regulation of metabolic and immune functions [37]. The intricate regulation of circadian rhythms, involving both central and peripheral clocks, highlights the critical role of light and other environmental cues in maintaining optimal physiological function. Melatonin, as a key mediator of circadian entrainment and sleep regulation, exerts profound effects on metabolic and immune processes, underscoring the interconnectedness of circadian biology with overall health and well-being.
CHRONOTYPES AND CHRONODISRUPTION ON METABOLIC EQUILIBRIUM
In the pursuit of global wellness, understanding the impact of chronotypes and chronodisruption on metabolic equilibrium is paramount. Chronotypes dictate optimal times for physiological processes, including metabolism, while chronodisruption, such as irregular sleep patterns, disrupts these rhythms. By aligning meal timing with individual chronotypes and addressing chronodisruption through interventions like time-restricted eating (TRE), we can optimize metabolic health across diverse populations and time zones. The human circadian cycle typically spans around 24.2 hours, yet this period varies significantly among individuals, defining their chronotype [38]. Chronotypes range from early birds (morning people/advanced sleep phase/early chronotypes) to night owls (evening people/delayed sleep phase/late chronotypes), with about 40% of the population falling into either extreme [38,39]. An intermediate or neutral chronotype encompasses individuals between these extremes, constituting approximately 60% of the population [40]. Melatonin rhythms and DLMO can differ by up to 2 hours across chronotypes [41]. Some rare genetic forms of extreme chronotypes have been identified, such as delayed sleep phase disorder, characterized by delayed sleep patterns, and familial advanced sleep phase disorder, marked by earlier-than-usual sleep times [42]. Influences on an individual’s chronotype extend beyond age, gender, and societal norms to include genetic factors. Genome-wide association studies (GWAS) and candidate-gene approaches have linked over 350 loci to the morning chronotype, including components of the circadian clock machinery [43]. Genetic variations within the clock machinery have been linked to sleep patterns, energy intake variations, waist circumference, obesity, and metabolic diseases [44–46].
Morning and evening chronotypes are polygenic traits influenced by both genetic and environmental factors, with non-genetic influences like artificial light and social pressures playing a significant role in evening chronotypes [47]. While these chronotypes dictate preferred sleep and activity patterns, they do not directly contribute to metabolic disease pathogenesis. However, recent studies have suggested associations between morningness or eveningness tendencies and metabolic health. Evening chronotypes are linked to unhealthy food choices, binge eating, nighttime snacking, and various metabolic disorders, including obesity, whereas morning individuals show lower rates of depression and better mental health [48–53]. An individual’s chronotype shapes their sleep, dietary, and activity patterns, indirectly influencing sleep duration and quality, which are distinct from sleep duration [54]. Disruptions to normal sleep patterns, such as shift work or frequent travel across multiple time zones (jet lag), can lead to circadian misalignment and are associated with various metabolic diseases. Evening chronotype individuals, who typically retire late, may have their sleep duration shortened due to external demands like work or school schedules, leading to misalignment with their biological circadian rhythm and potentially affecting metabolic health. Furthermore, variations in bedtime between weekdays and weekends contribute to social jet lag, indirectly impacting metabolic health.
The intricate and bidirectional relationship between the circadian clock and metabolism is essential for maintaining overall metabolic homeostasis. Optimal alignment between the central and peripheral clocks requires energy intake to coincide with the active phase or biological day for diurnal organisms like humans (and during the night for nocturnal animals such as rodents). Studies show that mice consume approximately 80% and humans about 100% of their nutrients during the wake/active phase [55]. This consumption pattern reflects the metabolic oscillations observed in primitive hunter-gatherer humans, who experienced feast/famine cycles aligned with their active/rest phases. During the active phase, when food was abundant, energy intake was higher, and metabolic pathways prioritized energy storage replenishment. Conversely, periods of famine, associated with rest, necessitated metabolic adaptation to food scarcity, leading to catabolic processes and energy store mobilization. Human genetics are attuned to these energy store oscillations, a trait incompatible with modern lifestyles characterized by constant access to high-energy foods. Coupled with sedentary behaviors, this mismatch blunts metabolic oscillations, leading to various metabolic disturbances and associated diseases [56–58].
Misalignment between active/rest and feast/famine phases can arise from endogenous factors, such as genetic variants in the core clock machinery, or external lifestyle factors like extended exposure to artificial light, increased shift work, sedentarism, untimely and frequent snacking, and jetlag, rendering individuals vulnerable to various diseases [49,59–62]. The overarching term for circadian disruptions is “chronodisruption,” with short-term disturbances termed circadian disruption, long-term disturbances leading to adaptations without adverse health effects termed chronodisturbance, and long-term desynchronization contributing to disease termed chronodisruption [63]. Even low levels of artificial light exposure, such as from electronic devices like phones, can disrupt DLMO and melatonin levels, impacting sleep onset and duration [16,47,64]. Moreover, behaviors like night eating and irregular eating patterns, or feeding during resting periods, regardless of evening chronotype presence, can induce misalignment, compromising metabolic homeostasis and increasing the risk of higher body mass index (BMI) and disease development (Figure 2) [65–75].
Factors affecting the circadian clock system. Meal timing and dietary components (chrononutrition) play an integral part in regulating the circadian clock to enhance metabolic health.
UNVEILING CHRONONUTRITION: A CONCISE OVERVIEW
Understanding the molecular underpinnings of chronodisruption holds promise for developing practical strategies to enhance circadian alignment and alleviate the burden of metabolic diseases. A relatively novel approach in this regard is termed “chrononutrition,” which comprises two key elements: dietary components that regulate the circadian system and meal timings aimed at synchronizing misaligned molecular clocks. These interventions, which may also include physical activity, have the potential to positively influence metabolic activity. The circadian system, governed by endogenous molecular clocks, orchestrates physiological processes in a rhythmic manner to maintain homeostasis. Disruptions to this system, known as chronodisruption, can arise from various factors such as genetic variants in the core clock machinery, extended exposure to artificial light, shift work, sedentarism, and irregular eating patterns. These disruptions can lead to misalignment of internal clocks and perturbations in metabolic processes, contributing to the development of metabolic diseases [76–78]. Chrononutrition seeks to address these disruptions by leveraging insights into the interaction between dietary components, meal timings, and the circadian system. Dietary factors such as macronutrient composition, meal timing, and nutrient intake have been shown to influence circadian rhythms and metabolic outcomes. For example, studies have demonstrated that the timing of nutrient intake can modulate circadian gene expression and metabolic pathways [79–81].
Meal timing is a critical component of chrononutrition, as it can influence the alignment of internal clocks with external cues such as light-dark cycles. Research suggests that aligning meal timings with the body’s natural circadian rhythms may promote metabolic health. For instance, consuming larger meals earlier in the day when metabolic activity is high and tapering food intake towards the evening may help synchronize internal clocks and optimize metabolic function [82,83]. In addition to meal timing, dietary components play a crucial role in regulating circadian rhythms and metabolic processes. Certain nutrients, such as vitamins, minerals, and phytochemicals, exhibit circadian variation in absorption, metabolism, and utilization. For example, studies have shown that micronutrients like vitamin D and magnesium influence circadian gene expression and contribute to the regulation of metabolic pathways [84,85]. Moreover, the timing of nutrient intake can impact circadian clock gene expression and metabolic function. For instance, studies have demonstrated that timing-restricted feeding, where food is consumed within specific time windows, can reset circadian rhythms and improve metabolic health in animal models [86,87]. Similarly, time-restricted feeding regimens in humans have shown promising results in improving metabolic parameters such as insulin sensitivity and body weight [88,89]. Physical activity is another important component of chrononutrition that can influence circadian rhythms and metabolic health. Exercise has been shown to affect the expression of circadian clock genes and enhance circadian alignment. Regular physical activity can improve sleep quality, which in turn regulates circadian rhythms and metabolic processes [90,91]. Overall, chrononutrition offers a holistic approach to improving metabolic health by optimizing the alignment of internal clocks with external cues through strategic dietary interventions and meal timings.
CHRONONUTRITION AND MEAL TIMING
Chrononutrition underscores the importance of aligning meal timing, frequency, and energy intake patterns with the circadian rhythm [92]. Franz Halberg first proposed the concept of “when you eat,” linking meal timing with energy metabolism and chronic diseases [93,94]. Food consumption strongly entrains peripheral circadian clocks, and optimal health requires aligning energy intake with the biological day and active phase to establish a feed/fast cycle adapted by human physiology. Transitioning between these cycles involves different transcription factors and associated proteins, with daytime genes mainly involved in glycogenesis and lipogenesis, while fasting phase genes are associated with growth, repair, glycogenolysis, and lipolysis [95,96]. Perturbations in the availability of key players in these phases and dietary intake can dysregulate energy metabolism. The timing of meals within the circadian cycle can significantly impact energy metabolism. Modern lifestyles with constant nutrient availability disrupt human circadian physiology. Eating window for over 50% of the population spans approximately 15 hours a day, with a minority of energy consumption occurring before noon and a significant portion during dinner and post-dinner snacks, overlapping with the circadian rest period [97–99]. This extended eating window and shorter overnight fast contribute to increased energy intake. Mistimed eating, combined with erratic sleep patterns, can dampen circadian rhythms and increase the risk of metabolic disorders. Interestingly, the dampening effect of circadian rhythms by a high-fat diet can be mitigated by restricting food intake during the biological active phase, underscoring the importance of meal timing in aligning with our biological clocks [100].
Circadian rhythm and glucose metabolism
Circadian rhythms intricately regulate glucose metabolism in humans, exhibiting diurnal variation with peak glucose tolerance during daylight hours when food consumption occurs and decreasing during nighttime fasting periods [101]. Hormones involved in glucose metabolism, including insulin and cortisol, undergo circadian oscillations [102,103]. Studies have highlighted the crucial role of the circadian system in glucose metabolism, showing rhythmic changes in insulin sensitivity and secretion patterns that impact blood glucose levels [104–106]. Consequently, insulin secretion and sensitivity are tightly regulated by circadian control, profoundly influencing glucose metabolism. Disrupted meal timings can induce glucose intolerance by altering the phase relationship between the central circadian pacemaker and peripheral oscillators in liver and pancreas cells [107]. Meal timing is governed by the SCN, contributing to the synchronization of circadian rhythms in peripheral tissues and thereby influencing glucose metabolism [108]. The interplay between diet and circadian rhythmicity involves factors such as meal timings and nutrients (chrononutrition), contributing to circadian perturbations and influencing the development of metabolic disorders such as type 2 diabetes. The timing of meals and the composition of diets, often referred to as chrononutrition, wield significant influence over the regulation of circadian rhythms. This practice holds promise in bolstering metabolic well-being and mitigating the likelihood of developing type 2 diabetes. By aligning meal timing with the body’s internal clock, known as the circadian clock, individuals can optimize metabolic processes and promote overall health. Additionally, the nutritional components of meals contribute to this regulation, influencing the body’s energy balance and metabolic pathways. Embracing chrononutrition involves not only paying attention to when meals are consumed but also considering the types of foods ingested. By adhering to this approach, individuals may enhance their metabolic health, potentially reducing the risk of developing type 2 diabetes and other metabolic disorders (Figure 2).
Chrononutrition, circadian rhythm, and CVD
The prevailing risk factors for CVD, including obesity, diabetes mellitus, and hypertension, are closely tied to unhealthy dietary habits and sedentary lifestyles [109,110]. Consequently, adopting a healthy balanced diet and achieving weight reduction have emerged as critical strategies for minimizing the impact of CVD [111]. Modern awareness emphasizes the importance of embracing health-related behaviors, overcoming previous unhealthy dietary patterns, and prioritizing physical activity [112]. Notably, the use of smartphone-based methods and wearable devices has surged, enabling real-time monitoring of physical activity and energy balance, leading to successful body weight reduction and enhanced quality of life [113,114]. Central to cardiometabolic health is not only the composition of the diet but also the distribution of energy, meal frequency, meal regularity, and the timing of eating and fasting periods throughout the day [115]. Metabolic processes exhibit circadian rhythmicity, and the timing of food consumption significantly influences circadian rhythms [116]. Irregular food timing may disrupt energy balance, increasing energy intake while reducing energy expenditure, thereby predisposing individuals to obesity and metabolic disorders [117,118]. Notable examples of irregular eating habits, such as skipping breakfast and consuming late-night meals, are associated with an elevated risk of heart disease and obesity [119]. In this context, the concept of “chrononutrition” has gained traction as a means to improve metabolic health. Chrononutrition entails aligning the timing of food intake with the rhythms dictated by the circadian clock, optimizing metabolic processes involved in nutrition [115,120,121]. Moreover, the concept of chrononutrition can encompass timed eating interventions, which aim to promote cardiometabolic benefits by adjusting food intake according to the circadian rhythm [115,122]. Current human studies indicate that chrononutrition interventions yield varied and sometimes conflicting effects on cardiovascular outcomes, underscoring the need for further research to draw definitive conclusions. Therefore, the aim of this article is to explore the anticipated benefits of chrononutrition in promoting cardiometabolic health. To achieve this goal, we present a concise review of the most recent evidence concerning the effects of chrononutrition and specific chrononutrition-based dietary interventions on body weight and other risk factors associated with CVD.
CHRONONUTRITION, CIRCADIAN RHYTHM, AND OBESITY
Obesity, classified as a BMI of ≥30 kg/m2, is not only a major risk factor but also recognized as a disease [123,124]. Its prevalence is escalating globally, contributing significantly to the burden of chronic non-communicable diseases, including metabolic syndrome, diabetes, CVDs, and cancer [125]. The burgeoning costs associated with treating obesity and its related comorbidities pose substantial challenges to both healthcare systems and society at large. Projections indicate that without concerted action, over 45% of the global population may be overweight or obese by 2035 [126]. The etiology of obesity is multifaceted, involving intricate interactions between genetic predispositions and environmental factors. While genetic factors contribute to 40%–70% of obesity cases, environmental influences, particularly dietary habits and physical activity levels, play pivotal roles in its onset and progression [127]. The modern prevalence of obesity is propelled by a combination of positive energy balance, characterized by abundant and inexpensive energy-dense foods, and increasingly sedentary lifestyles. Moreover, contemporary societal norms, such as round-the-clock work schedules and erratic sleep and eating patterns, disrupt the synchronization between the biological clock, metabolic processes, and external environmental cues, exacerbating the obesity crisis [128,129]. Addressing the obesity epidemic requires comprehensive and sustainable strategies. While lifestyle interventions focusing on diet and physical activity have been central to weight management efforts, their long-term effectiveness remains limited, largely due to challenges with adherence. The body’s internal clocks, present in virtually every cell, orchestrate physiological and biochemical functions to align with light-dark cycles, temperature variations, and food availability. Disruption of this intricate coordination leads to adverse metabolic outcomes. In this context, the emerging concept of chrononutrition, which explores the interplay between dietary composition, timing, and circadian rhythms, holds promise as a novel approach to designing effective and enduring weight management strategies.
CHRONONUTRITIONAL INTERVENTIONS AND THEIR NOVELTY
Chrononutritional interventions, including intermittent fasting (IF) and TRE, offer innovative approaches to weight management and metabolic health. IF involves alternating between fasting periods and unrestricted eating days, with variations like alternate day fasting and the 5:2 diet, while TRE restricts the feeding window to align with the circadian clock [130,131]. Research indicates that these interventions have favorable effects on metabolism, weight loss, BP, and cardiovascular health [132–136]. Chrononutrition presents a promising strategy for tailored weight management programs, offering adaptability to long-term lifestyle changes without the need for weight management drugs. Given the challenges of drug adherence, safety concerns, and limited efficacy in sustaining weight loss, chrononutrition may offer cardiovascular benefits independently of pharmacological interventions [137,138]. This is particularly relevant as anti-obesity drugs have not consistently demonstrated reductions in major adverse cardiovascular events or outcomes.
The effects of food timing in metabolism
Research underscores the critical impact of meal timing on metabolic rhythms crucial for human health [139]. Food intake influences molecular oscillators known as circadian clocks, present in nearly all cells and tissues, orchestrating rhythmic coordination of metabolic processes [140]. Irregular eating times can disrupt circadian system synchrony, leading to metabolic dysregulation and heightened cardiometabolic risks, including obesity, type 2 diabetes, and CVD [141,142]. Multiple mechanisms likely contribute, involving energy-regulating hormones such as cortisol, insulin, IGF-1, ghrelin, leptin, PYY, GLP-1, and adiponectin, which exhibit circadian rhythmicity [143]. Cortisol peaks at 8 AM; ghrelin at 8 AM, 1 PM, and 6 PM; adiponectin at 11 AM; insulin at 5 PM; and leptin at 7 PM. Time-of-day-dependent variation in these hormones optimizes nutrient metabolism, suggesting early-day meal timing may be advantageous [144]. Among these hormones, adiponectin’s role is noteworthy. Secreted by adipocytes, it exerts anti-diabetic, anti-inflammatory, and anti-atherogenic effects, enhancing insulin sensitivity [145]. Reduced adiponectin levels play a central role in obesity, insulin resistance, type 2 diabetes, hypertension, and CVD progression, while weight loss or caloric restriction increases adiponectin levels, enhancing insulin sensitivity [146]. Considering this, TRE applied earlier in the day may better align with circadian clock pulsatile rhythms, potentially offering benefits. Studies exploring TRE often discuss the role of adiponectin in metabolic health. TRE studies hypothesize that early-day eating could optimize adiponectin levels, promoting improved metabolic outcomes [145]. However, further research is needed to elucidate the specific impact of TRE on adiponectin levels and its broader implications for metabolic health. Overall, understanding the interplay between meal timing, circadian rhythms, and adiponectin regulation sheds light on potential strategies for mitigating cardiometabolic risks. By aligning meal timing with circadian rhythms, interventions like TRE hold promise for improving metabolic health outcomes. Further investigation into the mechanisms underlying these effects will be essential for refining chrononutritional strategies and optimizing their impact on metabolic health.
Impacts of irregular meal timing on health outcomes
Abnormal eating patterns, characterized by irregular meal timing and extended eating windows, are increasingly prevalent in modern societies [147]. Around 50% of adults have daily eating windows exceeding 14 hours, deviating from traditional breakfast-lunch-dinner patterns [113]. These irregularities often involve greater energy intake in the evening, more frequent eating occasions, and prolonged daily eating periods [147,148]. Notably, breakfast skipping represents a common manifestation of irregular eating habits. Regular breakfast consumption has been linked to improved nutritional status throughout the day, including lower added sugar intake [149]. However, skipping breakfast is associated with an increased risk of heart disease [150], type 2 diabetes [151], obesity [152], and CVD mortality [153]. Despite these associations, systematic reviews and meta-analyses of RCTs examining breakfast skipping have yielded conflicting results. Breakfast skipping leads to weight gain [154] or exacerbates cardiometabolic risk factors [155]. Additionally, recent meta-analyses indicate that participants assigned to breakfast consumption tend to have a higher total daily energy intake compared to those who skip breakfast [156]. Moreover, the complex interplay between breakfast skipping and overall dietary patterns, physical activity levels, and other lifestyle factors complicates the interpretation of findings. Future research should aim to address these gaps in knowledge and provide evidence-based recommendations for optimizing meal timing and promoting metabolic health and overall well-being.
Effects of TRE on cardiometabolic parameters
TRE, a novel approach in chrononutrition, not only shows promise in managing obesity but also offers diverse metabolic benefits by influencing circadian rhythms, potentially improving key indicators of CVD [157–160]. However, the existing literature on the impact of TRE on CVD outcomes in humans is limited, with only a few RCTs demonstrating low risk of bias [160]. Notably, there were no significant differences observed among participants in terms of important parameters such as gender and age, which directly influence metabolism and CVD development. In the following sections, we delve into the effects of TRE on weight management, hypertension, dyslipidemia, diabetes, and overall CVD.
TRE and effects on adiposity and obesity
TRE has emerged as a potential strategy for reducing adiposity and obesity, which are independent risk factors for various cardiovascular and metabolic diseases [161]. IF and TRE often lead to weight loss [160,162]. A meta-analysis involving 294 participants following TRE demonstrated a significant reduction in body weight compared to those on a regular diet [160]. Interestingly, this weight loss was more pronounced in individuals with metabolic abnormalities, while healthy participants did not show significant changes in body weight [160]. Among obese individuals, TRE regimens of 4–10 hours per day over 1–16 weeks resulted in modest weight reductions of 1%–4% [163]. These reductions were primarily attributed to unintentional decreases in energy intake, typically ranging from 350 to 500 kcal per day [163]. In obese adults undergoing 8-hour TRE with unrestricted energy intake, there was a notable decrease in the number of eating occasions by approximately 20%, indicating involuntary reductions in energy intake [164]. Importantly, TRE has been shown to promote weight loss even in the absence of deliberate calorie restriction [165,166].
Contrary to some findings, certain studies on TRE have reported no significant effects on body weight. One study implementing 8-hour TRE over 12 weeks in overweight and obese individuals found no differences in weight loss compared to controls on isoenergetic continuous hypocaloric diets or consistent meal timing [167]. Similarly, a small study of overweight pre-diabetic men undergoing early time-restricted eating (eTRE) observed improvements in insulin sensitivity and β-cell responsiveness but no significant effects on weight loss or glucose levels [168]. Another investigation comparing eTRE to standard dietary advice reported no differences in weight loss and energy intake but noted an improvement in glycemic control independent of weight loss [169]. Interestingly, TRE has been shown to enhance glycemic control regardless of the timing of the eating window in some studies [170]. In an RCT comparing 12-hour TRE to standard dietary advice in adults with metabolic syndrome, no significant difference in weight loss was observed between groups [171]. The inefficiency of the 12-hour TRE in promoting weight loss may be attributed to the extended duration of eating in this study. Data on changes in body weight based on the timing of the eating window are limited due to the novelty of the topic and challenges in adherence to TRE in daily life. Although 4–10 hour TRE is generally associated with modest weight loss (around 4%) in overweight and obese subjects, shorter eating windows (4–6 hours) do not appear to induce greater weight loss compared to longer windows (8–10 hours) [158,172].
Regarding body composition outcomes, findings on the effects of TRE on fat mass and fat-free (lean) mass are conflicting. While some studies have reported significantly reduced body weight and fat mass with TRE, attributed to increased adiponectin levels [160,173], others have found no drastic differences in fat loss compared to controls [113,163,172]. A recent study on overweight adults showed no significant changes in fat mass and visceral fat with TRE after adjusting for body weight loss, suggesting that TRE’s effect may be mediated by weight loss [164]. Additionally, this study observed a significant reduction in lean (muscle) mass, particularly in the legs, with no significant loss in trunk or arm lean mass, even after adjusting for body weight loss [164]. Other research has indicated preserved fat-free mass with TRE and suggested that 4–8 hour TRE may lead to spontaneous calorie restriction and reduced fat mass without affecting muscle mass in young resistance-trained adults [174].
Effects of TRE on glucose metabolism in diabetes
TRE has demonstrated significant reductions in fasting glucose levels, fasting insulin levels, and insulin resistance, alongside improvements in insulin sensitivity, although these effects were not universally observed [175–177]. Particularly, eTRE, typically between 8 AM and 2 PM, appears to offer more pronounced benefits for glycemic control. Studies have indicated that eTRE enhances whole-body insulin sensitivity, augments skeletal muscle glucose uptake, decreases 24-hour glucose levels, and enhances lipid metabolism, independent of caloric restriction or weight loss [178–180]. These improvements have been attributed to a significant increase in adiponectin levels [181]. Recent research suggests that IF regimens incorporating TRE are well tolerated as non-pharmacological treatments for patients with type 2 diabetes, with some individuals able to discontinue insulin therapy during therapeutic IF/TRE protocols [182]. However, initiation of an IF/TRE regimen in diabetic patients should be supervised by a physician to adjust medication titration and provide essential safety advice to prevent adverse effects [182,183].
Impact of TRE on lipid profile
Data from large public health databases indicate that commencing energy intake earlier in the day yields favourable effects on lipid profiles and cardiometabolic endpoints [184]. While most studies on TRE suggest beneficial effects on lipid profiles, indicating a potential reduction in CVD risk associated with dyslipidemia, the observed outcomes have exhibited considerable variability [175]. However, a meta-analysis of 10 studies assessing lipid profiles found no significant changes in low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels among participants following TRE, although triglyceride levels showed a significant decrease [160]. Available evidence suggests that TRE does not substantially impact HDL-C levels or inflammatory markers such as C-reactive protein [163]. Furthermore, a study investigating the effects of 12 weeks of 8-hour TRE from 10:00 to 18:00, with unrestricted food intake, compared to a no-intervention control group, reported that metabolic biomarkers, including LDL-C and HDL-C, as well as triglycerides, did not significantly differ from controls in obese patients [166].
Impact of TRE on BP levels
Emerging evidence suggests that TRE may have beneficial effects on BP levels, leading to consistent reductions in some studies [160,163,166,168,173,185]. For instance, a study involving men with prediabetes revealed a significant reduction in systolic BP by 11±4 mm Hg and diastolic BP by 10±4 mm Hg following a 6-hour TRE intervention over 5 weeks [168]. Similarly, another study utilizing a smartphone application to monitor meal timing observed a notable decrease in systolic BP (12±11 mm Hg, p= 0.002) alongside weight loss [186]. However, a systematic review and meta-analysis evaluating the impact of fasting and energy restriction on BP levels in a larger population (1,400 participants) reported a more modest average reduction in both systolic (3.3 mm Hg) and diastolic (1.6 mm Hg) BP [187]. Notably, greater reductions in BP were often observed in studies where participants experienced at least a 3% reduction in baseline body weight [166,185]. Despite these findings, some studies have presented mixed results regarding the effect of TRE on BP compared to non-TRE groups [164,167,170,171,172]. This variability in outcomes could be attributed to various factors, including potential confounders, adherence to the intervention, duration of TRE, and differences in BP measurement methodologies. Overall, while TRE shows promise in improving BP levels, further research is warranted to elucidate its precise effects and optimize its implementation for individuals seeking to manage their BP through dietary interventions.
RECENT DEVELOPMENTS IN CHRONONUTRITION: A LOOK AT “WATCH THE CLOCK” DIETS
Chrononutrition, an emerging field, explores the impact of meal timing on health outcomes, particularly in the context of CVD. Among the various chrononutrition strategies, TRE has garnered attention for its potential to induce weight loss and improve metabolic parameters. However, the evidence supporting its efficacy and safety for long-term CVD outcomes remains limited and debatable. Adafer et al. [188] conducted a meta-analysis of recent RCTs, indicating that TRE resulted in an average weight loss of 3% along with a reduction in fat mass, independent of caloric restriction. This suggests a promising avenue for weight management without stringent dietary limitations. Moreover, TRE exhibited favourable metabolic effects beyond weight loss, suggesting its potential in improving cardiometabolic health irrespective of nutritional quantity or quality [188,189]. These findings highlight the intrinsic benefits of aligning feeding patterns with the circadian rhythm.
Additionally, a meta-analysis of 19 studies, including 11 RCTs with low bias risk, corroborated the beneficial effects of TRE on cardiometabolic parameters [160]. This underscores the potential of chrononutrition-based interventions in mitigating CVD risk factors. However, despite these promising findings, concerns persist regarding the long-term safety, efficacy, and compliance of IF/TRE regimens. Critics argue that the short intervention periods in existing studies limit our understanding of the sustained effects of these dietary patterns. Lowe et al. [167] cautioned that TRE, in isolation, may not confer superior weight loss outcomes compared to conventional dietary patterns. Moreover, Allaf et al. [190] conducted a meta-analysis comparing various IF regimens with ad-libitum feeding and continuous energy restriction. While chrononutrition-based regimens showed superiority over ad-libitum feeding in weight reduction, the clinical significance of this effect remains debatable compared to continuous energy restriction for improving cardiometabolic risk factors. This underscores the need for comprehensive assessment of long-term outcomes in future research. Furthermore, continuous energy restriction diets pose challenges due to potential increases in appetite and energy intake following periods of severe energy restriction [191]. Moreover, calorie restriction may lead to disproportionate loss of fat-free mass, subsequently lowering metabolic rate and necessitating sustained efforts to maintain weight loss in older adults [192]. These observations highlight the complexity of dietary interventions and the importance of considering their holistic effects on metabolism and body composition. While preliminary evidence suggests potential benefits of chrononutrition-based “Watch the Clock” diets in improving cardiometabolic health, several limitations and challenges warrant consideration. Future research should focus on long-term RCTs with robust methodologies and larger sample sizes to elucidate the sustained effects and safety profile of these dietary interventions. Moreover, comprehensive assessments of metabolic parameters, cardiovascular events, and patient adherence are imperative for guiding clinical recommendations effectively. Ultimately, integrating chrononutrition principles into personalized dietary strategies may hold promise in combating the rising burden of CVD globally.
IS TRE SAFE?
TRE stands out as a potentially milder and more feasible approach compared to more intense IF regimens or conventional daily caloric restriction diets. Its simplicity and ease of implementation could enhance compliance among individuals seeking dietary interventions for health benefits [163]. TRE has demonstrated safety and tolerability, with no reported adverse events concerning lean mass, bone density, or nutrient intake [180]. TRE may be suitable for a broad demographic, including older adults, without compromising essential aspects of health. Moreover, even in older populations with comorbidities, TRE has been implemented safely, with fasting periods of less than 10 hours showing no detrimental effects on cognitive function [193]. However, caution is warranted regarding the duration of fasting periods within TRE protocols. Daily fasting periods lasting 14 hours or longer may pose challenges or potential risks [176]. Therefore, while TRE shows promise as a safe and beneficial dietary approach, careful consideration of fasting duration is essential to optimize its effectiveness and minimize potential adverse effects. Therefore, TRE offers a relatively mild and feasible dietary strategy with potential benefits for various populations, including older adults and individuals at risk for CVD. Its safety profile and ease of implementation make it an attractive option for those seeking sustainable dietary interventions. Nevertheless, further research is needed to elucidate the optimal fasting durations and long-term effects of TRE on health outcomes.
Novel aspects of chrononutrition
While numerous reviews have summarized the foundational principles of this field, focusing on novel aspects can provide a deeper understanding of its implications for health and disease management. This emphasizes emerging research trends, mechanisms of action, personalized nutrition, and technological innovations.
Personalized nutrition
The concept of personalized nutrition has emerged as a promising area within chrononutrition. Research suggests that individual differences in circadian rhythms can inform tailored dietary recommendations. For instance, studies have shown that individuals with different chronotypes (morning vs. evening preference) may benefit from specific meal timing strategies. By considering an individual’s unique biological clock, healthcare providers can design more effective nutritional interventions that optimize metabolic health. This personalized approach could lead to improved outcomes in managing obesity, diabetes, and other metabolic disorders. Technological advancements are facilitating the application of chrononutrition in daily life. Wearable devices and smartphone applications can track dietary habits and sleep patterns, providing real-time feedback on meal timing and its alignment with circadian rhythms. For example, apps that analyze eating patterns and offer reminders for meal timing can help individuals adhere to healthier dietary practices. Research suggests that integrating technology into dietary interventions can enhance adherence and improve metabolic outcomes. These innovations represent a significant step forward in applying chrononutrition principles in practical settings [194]. As chrononutrition continues to evolve, focusing on novel aspects can provide valuable insights into its role in promoting metabolic health. By exploring emerging research trends, elucidating mechanisms of action, embracing personalized nutrition, and leveraging technological innovations, researchers and practitioners can better understand and apply the principles of chrononutrition. Future studies should aim to investigate these areas further, potentially leading to more effective dietary strategies and improved health outcomes.
DISCUSSION
Chrononutrition has emerged as a pivotal concept in nutritional science, emphasizing not only what we eat but also when we eat. Much of the current literature, as reflected in this review, has established robust links between meal timing and metabolic health outcomes such as glucose regulation, obesity, cardiovascular risk, and insulin sensitivity. However, the implications of chrononutrition extend beyond metabolic health, warranting attention toward its influence on mental well-being and cognitive performance. Aligning food intake with circadian rhythms can significantly impact mood, sleep quality, stress regulation, and cognitive sharpness [164–168]. Irregular eating patterns and late-night meals have been associated with increased risk of depression, anxiety, and impaired cognitive function. Conversely, TRE and earlier meal timing appear to support better hormonal balance, neuroplasticity, and resilience to mental fatigue. This highlights chrononutrition not just as a metabolic tool, but also as a potential intervention in neuropsychiatric and neurodegenerative conditions. Furthermore, exploring chrononutritional practices across cultures provides important insights into their global relevance. In Mediterranean countries, for instance, the tradition of consuming a hearty breakfast and lunch, followed by a lighter dinner, aligns well with chrononutritional principles. In contrast, East Asian cultures, while often incorporating balanced and nutrient-dense diets, tend to consume late dinners, which may pose challenges when viewed through the lens of circadian alignment. In India, religious fasting and Ayurvedic dietary practices often promote early eating and digestive rest at night, reflecting traditional understanding of circadian principles. Similarly, the concept of “hara hachi bu” in Japanese culture, encouraging mindful and moderate eating, complements chrononutritional objectives. These cultural perspectives reveal that while the core circadian biology remains universal, dietary timing and habits are deeply embedded in social and traditional norms [154]. Integrating chrononutrition with culturally sensitive dietary models could significantly enhance public health interventions worldwide. Importantly, future research should delve deeper into how socio-cultural eating behaviors interact with circadian biology, and how personalized or culturally adapted chrononutritional strategies could be designed. In sum, chrononutrition holds promise not only for addressing global metabolic syndromes but also for improving mental health, cognitive vitality, and overall wellness. A broader, more inclusive framework that merges biological timing with cultural dietary wisdom may be the key to unlocking its full potential.
CONCLUSION
Chrononutrition stands poised as a pivotal component in optimizing global wellness by aligning food intake with circadian rhythms. The burgeoning field offers promising avenues for enhancing health outcomes across diverse populations and time zones. Through practices like TRE and mindful consideration of meal timing, individuals can potentially reap significant benefits, including weight management, improved metabolic health, and reduced risk of CVD. However, while initial evidence is encouraging, further research is imperative to elucidate the long-term effects, safety, and efficacy of chrononutrition interventions. High-quality trials with robust methodologies, longer durations, and larger sample sizes are needed to firmly establish the associations between chrononutrition and health outcomes. Moreover, exploring the applicability of chrononutrition principles in culturally diverse settings and among individuals with varying lifestyles is essential for promoting inclusivity and accessibility in global wellness initiatives. By fostering collaboration between researchers, healthcare professionals, and policymakers, we can advance our understanding of chrononutrition’s role in optimizing health across different time zones and cultures. Ultimately, integrating chrononutrition principles into holistic wellness strategies holds promise for improving overall health and well-being on a global scale. The timing of food intake plays a crucial role in metabolic regulation, interacting intricately with our circadian clock. Chrononutrition, a burgeoning field, investigates how aligning food intake with circadian rhythms could offer promising benefits, including body weight reduction, controlling diabetes and mitigating CVD risk factors. As we delve deeper into this realm, it becomes increasingly evident that chrononutrition, particularly through practices like TRE, could emerge as a pivotal component in multidisciplinary approaches aimed at combating metabolic diseases. While initial findings are promising, it’s imperative to underscore the need for robust evidence to firmly establish the associations between chrononutrition and metabolic disease risk factors.
FUTURE DIRECTIONS
Future trials of high quality, featuring solid designs capable of detecting significant differences in CVD, diabetes, and obesity outcomes, are essential. These trials should extend over longer durations (beyond 6 months) and involve larger sample sizes to yield meaningful and reliable conclusions. Moreover, there’s a pressing need to investigate how chrononutrition and TRE specifically impact individuals with distinct CVD risk factors. Additionally, exploring the applicability and benefits of ‘Watch the clock’ diets in healthy populations, targeting weight reduction and potentially harnessing anti-aging properties, is a promising avenue for research. Comparative studies between TRE and other fasting regimens warrant further exploration to elucidate their respective impacts comprehensively. Furthermore, understanding the sustainability of weight loss achieved through these dietary approaches in the long term is crucial for informing clinical practice. As we unravel these complexities within the realm of chrononutrition, we anticipate accumulating innovative evidence that could significantly contribute to metabolic disease prevention strategies. By addressing these research gaps and accumulating robust data, we move closer to realizing the anticipated beneficial impact of chrononutrition in combating diabetes, obesity, and CVD.
Notes
The author has no potential conflicts of interest to disclose.
Availability of Data and Material
Data sharing not applicable to this article as no datasets were generated or analyzed during the study.
Funding Statement
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Acknowledgments
We extend our sincere gratitude to Era University for their generous provision of logistics support, which greatly facilitated the execution of this Article.