The impact of meal timing on body composition: The role of Chrononutrition O impacto do horário das refeições na composição corporal: O papel da Crononutrição

Rita Barracosa da Costa Silva ORIENTADO POR: Dr.ª Maria Raquel Soares de Carvalho Roriz COORIENTADO POR: Prof. Doutor Nuno Pedro Garcia Fernandes Bento Borges REVISÃO TEMÁTICA 1.º CICLO EM CIÊNCIAS DA NUTRIÇÃO | UNIDADE CURRICULAR ESTÁGIO FACULDADE DE CIÊNCIAS DA NUTRIÇÃO E ALIMENTAÇÃO DA UNIVERSIDADE DO PORTO

TC PORTO, 2021

i

Abstract

Chrononutrition is an emerging research topic in nutrition that embraces

the relationship established between temporal eating patterns, daily circadian

rhythms and metabolic health. Preliminary data from observational and

experimental studies suggest that changes in the timing of food intake can impact

body composition and the success of weight loss approaches, regardless of total

daily energy intake and dietary composition, raising the question if when to eat

matters as much as food quantity and quality. This narrative review assesses the

effect of food intake timing on body composition in adults and briefly explores the

mechanisms underlying the impact of meal timing on body composition.

In conclusion, recent data supports that late eating may impair the success

of weight loss strategies and morning loaded energy distribution seems to be a

valuable approach for weight control. In detail, higher morning diet induced

thermogenesis, circadian misalignment, genetic variants, metabolic changes,

differences in sleep duration and individual´s chronotype may be implicated in

the observed differences in weight loss between late and early eaters.

Novel therapeutic strategies should consider this contributor in the

prevention of the obesity pandemic and dietary guidelines should be pointed at

meal timing as an alternative approach to encourage bodyweight control.

Keywords: Chrononutrition, circadian rhythm, meal timing, body composition,

obesity

ii

Resumo

A Crononutrição é um tema de pesquisa emergente na nutrição que abrange

a relação estabelecida entre os padrões temporais de alimentação, os ritmos

circadianos e a saúde metabólica. Dados preliminares de estudos observacionais e

experimentais sugerem que, alterações no padrão de ingestão alimentar podem

impactar a composição corporal e o sucesso das estratégias de perda de peso,

independentemente da ingestão energética total e da composição nutricional,

levantando a questão se quando comer importa tanto quanto a qualidade e

quantidade alimentar. Esta revisão narrativa avalia o efeito do horário das

refeições na composição corporal em adultos e explora os mecanismos subjacentes

ao impacto do horário da ingestão alimentar na composição corporal.

Em suma, dados recentes apoiam que, a ingestão alimentar diária tardia,

pode prejudicar o sucesso das estratégias de perda de peso e a maior distribuição

de energia pela manhã parece ser uma estratégia valiosa para o controlo de peso.

Em particular, o aumento matinal do efeito térmico dos alimentos, a disrupção do

ciclo circadiano, as variantes genéticas, as alterações metabólicas, as diferenças

na duração e padrão do sono e o cronótipo do indivíduo podem estar implicados

nas diferenças observadas na perda de peso entre os comedores matinais e tardios.

Novas estratégias terapêuticas devem considerar este fator na prevenção

da pandemia da obesidade e deverão ser criadas recomendações direcionadas para

o horário das refeições como estratégia promotora do controlo de peso corporal.

Palavras-Chave: Crononutrição, ritmo circadiano, horário das refeições,

composição corporal, obesidade

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Abbreviations

BMI – Body mass index

CRD – Circadian Rhythm disruption

DIT – Diet induced thermogenesis

DLMO – Dim-light-melatonin-onset

DG – Dinner group

LG – Lunch group

MCQT – Munich Chronotype Questionnaire

MEQ - Horne-Östberg Morningness-Eveningness Questionnaire RMR – Resting metabolic rate

RQ – Respiratory quotient

SCN – Suprachiasmatic nucleus

TDEI – Total daily energy intake

TDEE – Total daily energy expenditure

TEF – Thermic effect of food

WC – Waist circumference

95% CI – 95% Confidence interval

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Summary

Abstract and keyword ........................................................................ i

Resumo e palavras-chave ................................................................... ii

Abbreviations ................................................................................ iii

Summary ..................................................................................... iv

1. Introduction ............................................................................. 1

2. Methods .................................................................................. 2

3. Circadian clocks and rhythms ........................................................ 3

3.1. Anatomical and molecular clock networks ...................................... 3

3.2. Circadian rhythm disruption .................................................... 3

3.3. Assessment of an individual´s chronotype .................................... 5

3.4. Circadian rhythm’s role in metabolism and nutrient uptake .............. 6

4. Effect of timing of food intake on changes in body composition ............... 7

5. Physiological mechanisms underlying the impact of meal timing on

bodyweight ................................................................................. 11

6. Critical Analysis ...................................................................... 13

7. Conclusions ............................................................................ 15

8. References ............................................................................ 16

1

1. Introduction

Several physiological processes in the human body, including energy regulation

and metabolism, are managed by endogenous circadian rhythms. These rhythms

control many metabolically relevant hormones such as cortisol, insulin, ghrelin

and leptin(1). Food is considered a major synchronizer of peripheral circadian

clocks and delayed feeding can disrupt optimal physiology and metabolism(2, 3).

Even though body weight is mainly determined by total daily energy intake (TDEI)

and total daily energy expenditure (TDEE), recent data suggest that not only what

and how much we eat, but when we eat plays a role in body composition(4).

In the last years, growing evidence suggests an association between timing of

food intake and obesity in humans and animals, proposing that changes in meal

timing can impact body composition and the effectiveness of weight loss

strategies(3), independently of TDEI and dietary composition(5).

Modern life demands changes in eating patterns causing delayed morning meals

and evening-loaded-energy intake(6). For instance, late lunch eating(7), breakfast

skipping(8, 9) and having the largest meal later in the day (4, 7, 10-18) have been

associated with increased markers of adiposity. Recent data in humans suggest

that consuming a larger proportion of TDEI earlier in the day, may be more

beneficial for weight loss, under iso-caloric conditions(3, 19). The mechanisms

underlying the impact of meal timing on body composition are not yet clear,

although it may outcome from behavioural adaptations or circadian variations in

physiology and energy metabolism(19).

2

Proper nutrition, where TDEI is aligned with TDEE and feeding/fasting cycles

are synchronized with clock-regulated metabolic changes, helps maintain

behavioural and physiological circadian rhythms and health(20).

This study aims to review meta-analysis, systematic-reviews, observational and

experimental studies in humans assessing the effect of different meal timings on

body composition in adults and explore the mechanisms underlying the impact of

timing of food intake on body composition.

2. Methods

The construction of the search strategy was performed using database-specific

subject headings and keywords in PubMed and Scopus. The heading terms included

combinations of “meal timing” or “timing of food” or “food timing” or

“chrononutrition” with “body mass index” (BMI) or “obesity” or “body weight” or

“body composition” or “body fat”. Articles published until May 2021 were

selected, whose title or abstract addressed issues related to the topic. This search

strategy was supplemented by hand searching the references cited in the targeted

articles. Searches were limited to meta-analysis, systematic reviews, clinical trials

and observational studies. Studies that met all the following inclusion criteria

were embraced: (1) different meal timing, patterns or habits (early eaters/late

eaters or different timing of daily energy intake distribution) impact in the risk of

obesity, overweight or changes in BMI, body weight or body composition was

reported; (2) included healthy volunteers or individuals with obesity/overweight

and other comorbidities; (3) included participants with 18 years or more. The

references were exported to the bibliographic reference management program,

EndNote X9, duplicates were eliminated, and the full texts were obtained.

3

3. Circadian clocks and rhythms

3.1. Anatomical and molecular clock networks

Circadian rhythm (from the Latin circa and diem, about a day) also known as

biological/circadian clock refers to behavioural, physiological, molecular and

metabolism fluctuations within a cycle length around 24h(12, 21-23). It is divided

into 2 parts: (1) a master clock in the suprachiasmatic nucleus (SCN) in the anterior

hypothalamus and (2) the peripheral clocks throughout body tissues including

liver, pancreas, skeletal muscle and adipose tissue(19, 21-23).

Each circadian phase is determined via internal and external factors, a process

known as entrainment(22). The master clock is primarily entrained by light signals

via a monosynaptic pathway from intrinsically photosensitive retinal ganglion cells

in the inner retinae to the SCN and regulate many body functions (e.g., core body

temperature, blood pressure and sleep)(22, 24). Whereas the peripheral clocks

integrate inputs from the central clock, external factors (light exposure,

sleep/awake cycles, physical activity and feeding/fasting) and metabolites

regulating several metabolic processes (e.g., metabolism and glucose

homeostasis)(19-22, 24, 25). Recently, the timing of food consumption appears to be

one of the external factors that stimulate the peripheral clocks, known as

zeitgebers(22). Not only postprandial responses depend on circadian regulation as

well as food intake can itself entrain circadian clocks in the liver, gut, intestine

and adipose tissue(19).

3.2. Circadian rhythm disruption

Humans are a diurnal species, and the light phases stimulate wakefulness and

feeding and darkness initiates sleeping and fasting. This implies that an irregular

4

exposure to light, a change in eating time or sleep deprivation can disrupt daily

rhythms(24). Therefore, circadian rhythm disruption (CRD) can be defined as a

misalignment in the timing of and/or change in the duration of ambient

illumination, sleep, and period of eating from a reference range(24).

Misalignments in circadian rhythms may lead to a disturbance of body

homeostasis(26), impair metabolism pathways, worsen glycemic control and

undesirably affect factors involved in energy balance and weight loss, increasing

the risk of diabetes, obesity and metabolic disorders(19, 22, 24, 27).

In populations with chronic CRD, such as shift workers, there is an increased

risk of obesity, higher rates of type 2 diabetes, cardiovascular disease and

metabolic syndrome(2, 6). An increased TDEI could explain the observed tend to

weight gain in this population, however evidence from two recent meta-analyses

suggests that shift-workers are 23% more likely to have overweight/obesity and

the risk of having abdominal obesity was 35% higher(26), regardless of the amount

of TDEI(27). The authors suggested that factors such as CRD, meal timing, poorer

food quality, use of sugar and caffeine to improve alertness, an increase in

snacking behaviour, evening loaded energy intake and diurnal variations of TDEE

might be underlying the increased overweight and obesity rates in this population

(24, 26-28).

However, circadian disruption is not only limited to shift workers. Recent data

found that minor but chronic shifts in mealtimes and sleep pattern on weekdays

versus weekends, denominated eating jet lag, can induce a mild kind of

misalignment and has been associated with higher BMI, adiposity, odds of being

obese, metabolic syndrome, type 2 diabetes(6, 24) and unhealthy eating habits(29).

5

In a cross-sectional study, in a population with obesity-related chronic diseases,

eating jet lag has been associated with later mealtimes consumption for breakfast,

afternoon snack and dinner, higher caloric intakes and poorer diet quality (with

higher total and saturated fat and cholesterol)(30). Rugerio et al. in another cross-

sectional study with a sample of 1106 young adults reported that eating jet lag

above 3.5h was associated with higher BMI (1,34 kg/m2 95% CI: [0,026;2,40];

p=0,015), when adjusted for age, gender, nationality, physical activity, diet

quality and sleep duration(24).

3.3. Assessment of an individual´s chronotype

Chronotype refers to an individual’s circadian phenotype that reflects

preference for morningness or eveningness. It is a subjective measurement based

on the timing of reported behaviors related to the sleep-awake cycle. It can be

assessed by multiple methods, such as from biological measures as dim-light-

melatonin-onset (DLMO), to validated questionnaires based on self-reported

information, such as the Munich Chronotype Questionnaire (MCTQ), the Horne-

Östberg Morningness-Eveningness Questionnaire (MEQ), the reduced Morningness-

Eveningness Questionnaire, the Composite Scale of Morningness, and the

Preferences Scale. DLMO is the most reliable measure of the circadian phase in

humans and consists of the measurement of melatonin in samples of blood, saliva

or urine collected under dim-light conditions in the hours before typical sleep

onset. Other methods range from metabolomics and transcriptomics approaches

to noninvasive techniques that estimate chronotype based on motor activity, body

position and body temperature(31).

6

An emergent number of evidence have examined the link between an

individual’s chronotype and dietary intake(32). In fact, evening types present a

lower adherence towards a healthy diet(33), higher odds of skipping breakfast(34),

delayed meal timing(35), a lower intake of vegetables and fruits(36) and a greater

preference for alcohol, sugary food and beverages(37).

3.4. Circadian rhythm’s role in metabolism and nutrient uptake

Circadian rhythms influence a large number of genes involved in rate-limiting

steps of metabolism(19, 38, 39).

The thermic effect of food (TEF), also entitled diet induced thermogenesis

(DIT), is defined as the increase in resting metabolic rate (RMR) after the ingestion

of a meal(5) and is reportedly higher in the morning compared to the evening(5, 19,

20, 40). DIT accounts for a small fraction of the TEE (~10%)(5) and has 2 components:

(1) obligatory (energy expenditure needed for digestion, absorption and nutrient

storage) and (2) facultative (energy expenditure related to increased postprandial

sympathetic nervous system activity)(5, 38, 41). Richter et al. in a single-blind,

randomized, crossover design in a sample of 16 healthy young men, showed that

DIT is 2,5 times higher after breakfast than dinner unrelatedly to high or low-

calorie meals and regardless of influence of sleep disturbances and carbohydrates

preloads. This study also reveals that an eating pattern with an extensive

breakfast and a less caloric dinner has a favourable effect on glucose

metabolism(41). In another randomized crossover trial, the same standard meal

(100g white bread, 100g ham, 50g cheese, 125g yoghurt, 200ml fruit juice, plus

25g protein supplement) ingested in the morning (8am) and in the evening (8pm),

7

resulted in after-meal RMR and DIT values significantly higher after the morning

meal, under calorimetric evaluation(5).

Nutrient oxidation is also under circadian control. Respiratory quotient (RQ),

an index of macronutrient oxidation, peaks in the biological morning, suggesting

higher carbohydrate oxidation, and lowers during the biological evening, implying

greater lipid oxidation later in the day(40, 42). The consumption of identical meals

at different times of the day, results in higher plasmatic levels of glucose, and

free fatty acid in the evening, indicating a lower absorption and storage of

nutrients later in the day(5). Circadian clock gene regulation in peripheral tissues

is responsible for reducing nutrient uptake in the evening, allowing more readily

available energy to prepare for the beginning of fasting(38). Moreover, early insulin

secretion after a meal is meaningfully superior in the morning, to promote

efficient nutrient storage during this phase of the day, whereas insulin sensitivity

decreases throughout the day(5, 43). Also, faster gastric emptying and

gastrointestinal motility and improved intestinal absorption are observed in the

morning compared to the evening(19, 20).

These findings robustly corroborate the role of circadian regulation in energy

metabolism and nutrient uptake and mismatched behaviours related to these

endogenous processes can consequently result in unfavourable health outcomes(6).

4. Effect of timing of food intake on changes in body composition

Due to circadian variations in energy uptake and utilization, the same meal

eaten at different times of the day may produce distinct responses(12).

In a 20-week weight loss intervention, in a sample of 420 overweight/obese

individuals, those with an overall food intake earlier in the day (before 3pm) lost

8

twice as much weight that participants consuming their largest meal after 3pm

and displayed faster weight loss rate after 5th week treatment despite similar

TDEI, TDEE, dietary composition, physical activity, appetite hormones and sleep

duration(7). Surprisingly, there were no significant differences for lunch and dinner

energy intake between early and later eaters, however late eaters had less caloric

breakfasts (p=0.031) and skipped this meal more often than early eaters (6,6%

versus 2,6%; p=0.039). Late eaters were more evening types (lower MEQ score)

than early eaters, as evaluated by the MEQ (p=0.032)(7).

In another 12-week weight loss intervention, 93 overweight and obese women

with metabolic syndrome were randomized to two isocaloric diets (1400 kcal)

differing in the distribution of calories during the day. The breakfast group had

higher energy breakfast and lower energy dinner (700 kcal breakfast, 500 kcal

lunch, 200 kcal dinner) and the dinner group had low-energy breakfast and high

energy dinner (200 kcal breakfast, 500 kcal lunch, 700 kcal dinner). Jakubowicz

et al. found in the breakfast group, versus the dinner group, a 2,5 times greater

weight loss (-8.7 ± 1.4 vs. -3.6 ±1.5 kg, respectively), a greater reduction in BMI

(10% vs. 5%, respectively) and a greater waist circumference (WC) reduction (-8.5

± 1.9 vs. -3.9 ± 1.4 cm, respectively), both at 6 and 12-week follow-ups(14).

Madjd et al. in a two-arm randomized clinical trial, compared the effects of a

high energy intake at lunch, the lunch group (LG) (breakfast 15% + snacks 15% +

lunch 50% + dinner 20%) with a high energy intake at dinner, the dinner group (DG)

(breakfast 15% + snacks 15% + lunch 20% + dinner 50%) in 69 overweight and obese

women in a 12-week weight loss intervention. The authors observed a significant

weight reduction in both groups after the intervention. The LG had greater

9

reductions in weight (LG: -5.85 ± 1.96 kg; DG: -4.35 ± 1.98 kg; p=0.003) and

greater decline in BMI (LG: 2.27 ± 0.76 kg/m2; DG: 1.68 ± 0.76 kg/m2; p=0.003),

while no significant differences were found in WC between the groups. As

expected, estimated energy intake measurements showed a significant reduction

over the time in both groups, and there were no significant differences between

groups for TDEI and macronutrients from baseline to 12 weeks(13). These findings

corroborate the idea that having the main meal at lunch when compared to dinner

appears to be an important factor to consider in weight loss treatments.

In the US Adventist Health Study 2 (N=50 660), the authors aimed to

longitudinally investigate the link between meal timing and frequency and

changes in BMI per year (kg.m-2.y-1), among healthy population in the United States

and Canada, in a follow-up period of 7 years. Individuals who consumed breakfast

as the major meal of the day experienced the largest relative reduction in BMI

(−0.04 kg.m-2.y-1, 95% CI [ −0.05; −0.03]) compared with those who had their

largest meal at dinner. Consuming the main meal at lunch compared to dinner,

was also associated with decreased BMI (−0.02 kg.m-2.y-1, 95% CI [−0.03 to

−0.01])(15).

A meta-analysis of observational and experimental studies showed a minor

trend between higher BMI and greater evening intake (p=0.06), in observational

data. Even though most of the clinical trials indicated that a less caloric evening

meal resulted in greater weight loss, the meta-analysis of these studies revealed

no significant differences between early and late eaters (95% CI [ −2.52; 0,75]

p=0.29). Due to high heterogeneity (I2 = 93%) and considering the small sample of

experimental studies (N=5), the authors were unable to make a meaningful

10

interpretation concerning the relationship between the evening meal and its

effect on weight loss(4). The authors considered the high heterogeneity as a

limitation of the study and reflected about the fact that the clinical trial with

lower risk of bias(13) demonstrated that a reduced evening energy intake can

increase weight loss(4).

Regarding body fat, higher levels of adiposity have been cross-sectionally

associated with a mid-point of calorie intake, defined as the time at which 50% of

TDEI was reached, happening closer to DLMO. Also, non-lean individuals have

shown to consume a greater proportion of TDEI at a later circadian phase, when

compared to lean participants(16, 17). Even though no associations in calorie

midpoint nor last calorie intake were found when measured by clock time(16, 17),

Xiao et al. discovered that a greater energy distribution closer to bedtime

increased the risk of being overweight or obese by 82% (OR=1,82 95% CI [1,07-

3,08]), mainly in people with a later chronotype, assed by MCQ. This data supports

the idea that higher energy intake after waking up and lower dietary feeding near

bedtime is associated with lower BMI, with differences between chronotypes.

However, these results were not adjusted to possible confounders such as

smoking, medical factors or sleep disorders(18). Lombardo et al. randomized 36

individuals into two groups during 3 months (G1:70% breakfast + morning snack+

lunch and 30% afternoon snack + dinner and G2: 55% breakfast+ morning snack +

lunch and 45% afternoon snack + dinner) to evaluate the effect of two hypocaloric

Mediterranean diets in body composition assessed by dual-energy X-ray

absorptiometry. The authors found significant improvements for both groups,

however G1 had greater weight loss (G1: −8.2 ± 3.0 kg; G2: −6.5 ± 3.4 kg; p=0.028),

11

waist circumference reduction (G1: −7 ± 0.6 cm; G2: −5 ± 0.3 cm; p=0.033), and

fat mass loss (G1: −6.8 ± 2.1 kg, G2: −4.5 ± 2.9 kg, p=0.031; mean ± SD). These

data reinforce that a low-calorie Mediterranean diet with an upper amount of

energy in the first part of the day could determine a greater reduction in major

obesity-related metabolic parameters(44).

5. Physiological mechanisms underlying the impact of meal timing on

bodyweight

Even though the mechanisms underlying the impact of meal timing on

bodyweight remain unclear, some hypotheses have been suggested(45):

(1) The time when a meal is consumed affects the thermogenic response and

must be considered in the energy balance(19, 41, 46). Previous studies have

shown that DIT is higher in the morning comparative to the evening, after

identical meals(5, 41). The higher obligatory DIT in the morning, can be

explained since various gastrointestinal functions exhibits circadian

rhythmicity, including faster morning gastric emptying and increased

intestinal absorption of peptides, lipids and carbohydrates at the beginning

of the active phase(19). The elevated facultative DIT earlier in the day may

be a result of higher concentrations of adrenaline and noradrenaline during

this time of the day, which increases the metabolic rate and the RQ(41, 47).

Under controlled laboratory conditions, using indirect calorimetry, the DIT

is 40% higher after breakfast than after dinner(41).

12

(2) Misalignment between food timing and light/dark cycles can impair satiety

mechanisms throughout leptin and ghrelin(41, 48) and affect thyroid

hormones(49) inducing higher caloric intake(45).

(3) Modification of gene expression in genes responsible for evening eating

preference and weight loss resistance (e.g., SIRT1, CLOCK 3111T/C(50), and

Perilipin1(51)).

(4) The association between evening eating and weight gain can be explained

because insulin sensitivity and glucose tolerance decline gradually

throughout the day with insulin sensitivity reaching a nadir in the

evening(14).

(5) When sleep is restricted and food is provided ad libitum, in controlled

laboratory conditions, participants increase their TDEI, and this extra

consumption of energy occurs after dinner and closer to or after DLMO(52-

54), which contributes to an obesogenic ambient(43). A recent systematic

review, meta-analysis and meta-regression with a cumulative total of

5171710 participants collected from 153 studies revealed that short

sleepers (<6h of sleep) were 38% more likely to have obesity(55).

(6) The individual chronotype may be another factor involved in this equation.

The majority of the studies, considering the chronotype, have shown that

late eaters were more evening types and previous studies suggested that

evening types have more susceptibility to gain weight and have more

struggle to lose it(56, 57). In individuals with morning chronotypes (high

caloric intake during morning hours) the odds of being obese decrease by

13

50%, while in evening chronotypes (individuals who eat during the two hours

before sleep) the probability of being obese increases five times(58).

6. Critical Analysis

Clarifying the effect of meal timing on body composition is highly complex and

presents a challenge in the field of nutrition. This narrative review is in line with

prior findings revealing that timed caloric intake can impact body weight and

adiposity markers(4, 7, 13-18). In the present study, later eating in the day was

negatively associated with the success of weight loss therapies and morning loaded

energy intake revealed to be a bright approach to control body weight. Supporting

these conclusions, Garaulet et al. revealed that late lunch eaters lost fewer

weight and displayed a slower weight-loss rate during the treatment(7). Other

studies corroborate the hypothesis that individuals with high energy breakfast lose

more weight and have a greater WC reduction, when compared with high energy

at dinner(14, 15) and high energy lunch results in greater reductions in weight and

BMI comparing to high energy dinner(13, 15). Even though one meta-analysis

included in this study considered it difficult to draw a clear conclusion, the high

heterogeneity and small number of experimental studies could be responsible for

it(4). Regarding body fat, McHill et al. found that non-lean individuals consume a

greater proportion of TDEI at a later circadian phase, when compared to lean

participants, assessed by DLMO(16, 17) and Lombardo et al. showed that those who

consume most of the energy in the first time of the day lost more body fat. As

plausible mechanisms, eating closer to or after DLMO may decrease TEF(16, 46),

which would contribute to a positive energy balance and weight gain. Also,

misalignment between food timing and light/dark cycles can impair satiety

14

mechanisms and induce higher caloric intake(41, 45, 48, 49). Other factors such as

genetic variants(50, 51), metabolic changes(14), differences in sleep duration(52-54)

and individual´s chronotype (56-58) may be implicated in the observed differences

in body composition between late and early eaters.

Regarding circadian rhythm disruption, the strongest evidence of metabolic

misalignment is in night shift-workers. Data from two meta-analyses proposes that

these individuals are more likely to be obese, independently of TDEI(25, 26).

Surprisingly, milder circadian disruption in individuals with eating jet lag was also

associated with overweight and obesity(6, 24, 30). Zéron-Rugerio et al. found that

BMI was 1.34 kg/m2 higher in subjects who reported more than 3.5 h of eating jet

lag(24). In these populations, later mealtime consumption and poorer diet can

explain the differences in body weight between the groups(6, 24, 30), however, the

majority of the studies related to eating jet lag were cross-sectional. In future

research it will be imperative to confirm the direction of these associations and

evaluate the impact of the chronic variability in meal timing on bodyweight over

the time. Regarding this is an emerging topic, one of the main limitations has been

the lack of standardized definition for ‘meals’ and ‘snacks’, which may result in

inconsistent findings when the outcomes of interest are timing, frequency or

regularity of food intake. The majority of the studies have focused on conventional

meal categories (i.e., breakfast, lunch, and dinner), which differ cross-culturally,

and may not reflect the real eating pattern of diverse people. Furthermore,

considering the exogenous clock time to assess the link between timing of food

intake and individual´s circadian rhythms may not be physiologically significant to

accurately characterize meal timing in the context of the internal circadian timing

15

system. Another challenge has been failure to adjust for energy misreporting in

several studies and the lack of well-defined evidence considering the underlying

mechanisms for greater weight loss with earlier meal consumption. Finally, future

research should emphasis on human clinical trials and aimed to clarify the role of

eating time in mechanisms of energy balance, such as in TDEI, appetite and TDEE,

such as RMR, TEF and physical activity. Upcoming interventions should also assess

the individual´s chronotype, as a valuable addition to the evidence, given the

higher risk of adverse cardiometabolic health in evening chronotypes.

7. Conclusions

In conclusion, literature describing the impact of meal time is in its early

stages, however there is an increasing number of publications exposing the effect

of meal timing on obesity and adiposity markers(4, 7, 13-18). Early evidence supports

that late eating may impair the success of weight loss strategies and morning

loaded energy distribution seems to be a helpful approach for weight control. In

theory, morning enhanced DIT, circadian misalignment with consequent impaired

satiety mechanisms, genetic variants, metabolic changes, differences in sleep

duration and individual´s chronotype may be implicated in the observed

differences in weight loss between late and early eaters. These findings emphasize

the relevance of taking into account the internal circadian timing of food

consumption. Novel therapeutic approaches should combine not only the daily

caloric intake, macronutrient distribution and physical activity but as well

implementing dietary guidelines directed at meal timing and at the reduction of

the variability between meal timing on weekends versus weekdays for the

prevention of obesity among general population.

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