Time-restricted eating

The clearest evidence for distinct physiological effects of intermittent fasting comes from TRE protocols that align food intake to the early part of the biological day – known as early time-restricted eating (eTRE). Sutton et al. ^{(Reference Sutton, Beyl and Early16)} demonstrated that restricting energy intake to a 6 h morning eating window (08:00–14:00) for 5-weeks improved insulin sensitivity, beta-cell responsiveness, blood pressure and oxidative stress, compared to an isoenergetic diet consumed over a 12 h window (08:00–20:00). These positive effects were achieved under energy intake-matched conditions without weight loss, indicating a mechanism of action independent of weight change. Supporting this, Jones et al. ^{(Reference Jones, Pabla and Mallinson17)} reported that 2-weeks of eTRE (08:00–16:00) improved whole body insulin sensitivity and skeletal muscle glucose uptake compared to energy-and weight loss matched CER intervention in healthy men. Other controlled eTRE studies have reported improvements to glucose-related outcomes, including fasted glucose concentrations, glycaemic variability, time-in-range, and 24-h mean concentrations^{(Reference Jamshed, Beyl and Della Manna18,Reference Bruno, Walker and Nasserifar19)} .

The mechanisms underlying these findings may reflect both extension of the overnight postabsorptive period and earlier nutrient intake, as insulin sensitivity is highest in the morning and declines over the course of the day^{(Reference Saad, Dalla Man and Nandy20–Reference Poggiogalle, Jamshed and Peterson22)}. Late TRE (lTRE) shifts the first caloric intake later in the day, prolonging the morning fasting interval. Studies that directly compare eTRE and lTRE suggest that nutrient intake timing may influence glycaemic outcomes, although these studies do not always isolate timing from changes in energy intake and weight loss.

In a 5-week three-arm study in healthy adults without obesity, eTRE (<8 h eating window; 06:00–15:00) reduced HOMA-IR compared to both lTRE (<8 h eating window; 11:00–20:00), and ad-libitum control, and reduced fasting glucose compared to control, whereas lTRE did not differ to control for either outcome^{(Reference Xie, Sun and Ye23)}. In adults with overweight or obesity, eTRE (07:00–13:00) also improved mean glucose concentrations relative to lTRE (12:00–18:00), and reduced fasting insulin and HOMA-IR relative to control, whereas lTRE did not. Weight loss was similar between TRE groups, although eTRE resulted in greater fat-free mass loss than lTRE^{(Reference Zhang, Liu and Wang24)}.

A large 12-week RCT comparing eTRE and lTRE in adults with overweight or obesity produced more equivocal findings. Glycaemic measures were more favourable with eTRE, but there were no between-group difference in cardiometabolic outcomes^{(Reference Dote-Montero, Clavero-Jimeno and Merchán-Ramírez25)}. In this study, the median end of the eTRE window was 17:30, which is later than other studies (i.e. 13:00–16:00), which may have reduced the degree of early day circadian alignment. Most of these studies report similar weight loss between eTRE and lTRE, indicating that earlier eating windows may exert a positive influence on glycaemic outcomes independent of weight loss.

Observational evidence provides an interesting and complementary perspective. Regular breakfast omission is associated with poorer cardiometabolic health and greater weight gain^{(Reference Odegaard, Jacobs and Steffen26)}. Although these associations are vulnerable to confounding by broader diet and lifestyle factors, and breakfast omission and lTRE are not necessarily the same^{(Reference Betts, Chowdhury and Gonzalez27,Reference Clayton, Mode and Slater28)} , these findings are consistent with the possibility that extending the morning fast and shifting intake later in the day may have consequences beyond its effect on daily energy intake alone.

Alternate-day fasting

In principle, zero-energy ADF provides the longest uninterrupted fasting period among the common IF approaches, with periods of 24–36 h without energy intake. Most trials, however, have used mADF, which permits around 25% of energy requirements to be consumed on restricted days. This approach was implemented after early studies reported challenges with the sustainability of complete fasting on alternate days^{(Reference Heilbronn, Smith and Martin29)}, but does call into question whether the approach can truly be considered fasting.

Using zero-energy ADF, Templeman et al. ^{(Reference Templeman, Smith and Chowdhury30)} compared 3-weeks of ADF with energy-matched CER and ADF without net energy restriction in lean adults, isolating the effects of fasting and energy restriction. ADF without energy restriction did not reduce fat mass or improve cardiometabolic outcomes from baseline. When combined with energy restriction, ADF led to similar weight loss to CER, but less fat-mass loss, and proportionally more fat-free mass loss than CER. Most cardiometabolic markers, gut hormones, and adipose tissue gene-expression responses did not differ between groups. Ingersen et al. ^{(Reference Ingersen, Helset and Calov31)} similarly found no improvement in insulin sensitivity following 3-weeks of energy balanced ADF in men with obesity. A subsequent ADF plus energy restriction phase improved body composition and insulin sensitivity in men with type 2 diabetes. Whilst potentially limited by a short duration, these studies challenge the concept that fasting per se offers distinct physiological benefits over CER.

Several mADF trials have reported improvements in cardiometabolic risk factors, such as blood pressure, lipids, fasting insulin, or HOMA-IR, particularly in participants with obesity or metabolic impairment^{(Reference Varady, Cienfuegos and Ezpeleta1)}. However, these findings should not be attributed to fasting-specific mechanisms, as mADF typically induces an energy deficit that leads to weight loss, and the prescription of energy intake on ‘fast’ days is variable^{(Reference Varady, Cienfuegos and Ezpeleta1)}. The most informative trial on the long-term effects of mADF is Trepanowski et al. ^{(Reference Trepanowski, Kroeger and Barnosky32)}, who randomised 100 adults with obesity to mADF, CER or a no-intervention control for 12-months. mADF required alternating daily between 25 and 125% of energy requirements, whereas CER participants consumed 75% of energy requirements daily. Despite the considerable differences in pattern of intake over a 12-month period, there were no differences in body composition or cardiometabolic outcomes between mADF and CER. Taken together with the zero-energy ADF findings, current evidence suggests clinical effects are predominantly driven by weight loss resulting from the energy deficit achieved.

5:2

5:2 is a twice-weekly modified fasting approach. It differs from mADF in the frequency of restriction days in the week, and in some cases, how restriction days are distributed, which can be consecutive or separated by non-restricted days. However, like mADF, most evidence indicates no superiority over CER^{(Reference Semnani-Azad, Khan and Chiavaroli10,Reference Schübel, Nattenmüller and Sookthai33)} . In the HELENA (Healthy nutrition and energy restriction as cancer prevention strategies) trial, 150 adults with overweight or obesity were randomised to two non-consecutive days per week consuming 25% of energy requirements (5:2), daily CER at 75% of requirements, or a control arm. Although there was a numerically greater weight loss after 12-weeks with the 5:2 approach, there were no differences found in weight loss, body composition, liver fat, or circulating cardiometabolic markers between 5:2 and CER^{(Reference Schübel, Nattenmüller and Sookthai33)}.

However, physiological differences have been shown when restriction days are scheduled consecutively, rather than separated by refeeding days. Restricting intake to 25% of energy requirements on two consecutive days is likely to prolong exposure to low energy and carbohydrate availability, with low insulin concentrations and greater reliance on endogenous lipid oxidation^{(Reference Templeman, Gonzalez and Thompson3)}. Studies implementing 5:2 in this manner have reported greater reductions in fasting insulin and HOMA-IR than CER, despite similar weight loss^{(Reference Harvie, Wright and Pegington34–Reference Antoni, Johnston and Collins36)}. Antoni et al. ^{(Reference Antoni, Johnston and Collins36)} also observed lower postprandial triglycerides and a trend toward lower c-peptide concentrations following matched 5% weight loss with two consecutive days of severe restriction per week, compared to CER. These findings suggest that the duration of the restriction period, rather than weekly frequency, may be physiologically important. However, these studies differ in absolute energy and carbohydrate intake and do not directly compare consecutive and non-consecutive approaches, while more recent work suggests that improvements in insulin sensitivity observed immediately after two days of severe energy restriction may not persist into subsequent non-restricted eating days^{(Reference Harvie, Coe and Higham37)}. As such, whilst consecutive days of severe energy restriction may generate transient metabolic benefits with the potential to improve aspects of metabolic health, the evidence for sustained superiority over CER remains limited.

Modified fasting: from prescribed to achieved energy restriction

Maintaining a daily energy deficit is a well-recognised challenge with CER and gradual attenuation of energy restriction is a common obstacle to long-term weight loss success^{(Reference Hall and Guo40,Reference Hall and Kahan41)} . Zero-energy fasting protocols may be relatively simple to understand and self-monitor, because adherence is framed around a binary decision to eat or not eat. However, modified fasting approaches that permit up to approximately 25% of energy requirements to be consumed on restriction days, such as mADF and 5:2, still require individuals to quantify and limit energy intake during these periods. As a result, the intended severity of restriction and adherence may decline over time.

Long-term studies illustrate the distinction between prescribed energy restriction and achieved energy restriction. In a 12-month mADF trial, participants were prescribed 25% of energy requirements on restricted days and 125% on non-restricted days^{(Reference Trepanowski, Kroeger and Barnosky32)}. In practice, food diary records at 6-months suggested participants’ intake was ∼50% of energy requirements on restricted days and ∼80% on unrestricted days, reducing the intended contrast between restricted and non-restricted intake days. Doubly labelled water also revealed that the overall deficit achieved was lower than the 25% prescribed, 21% with mADF, compared to 24% with CER^{(Reference Trepanowski, Kroeger and Barnosky32)}. This illustrates how the achieved pattern of restriction may differ substantially from the prescribed, reducing the absolute differences between mADF and CER, even when the overall energy deficit achieved is similar, and may partially explain why their outcomes are often comparable^{(Reference Semnani-Azad, Khan and Chiavaroli10,Reference Trepanowski, Kroeger and Barnosky32)} . A related challenge is whether eating patterns are maintained beyond the active intervention period. During the 12-week HELENA study utilising a 5:2 modified fasting protocol, participants achieved, on average, 1.8 days of restriction per week, close to the two days prescribed^{(Reference Schübel, Nattenmüller and Sookthai33)}. Follow-up evaluations at 24 and 50 weeks in a subset of participants indicated that only ∼33% and ∼21% of respondents, respectively, were still completing two days of severe restriction per week^{(Reference Pannen, Maldonado and Nonnenmacher42)}. These findings demonstrate the challenges to achieving a prescribed restriction with modified intermittent fasting protocols, particularly after intensive dietary support is withdrawn.

The energy deficit achieved across restriction and non-restriction periods also depends on the extent individuals compensate during non-restriction periods. Definitions of non-restriction periods vary, with some studies instructing a return to estimated energy requirements and others allowing ad-libitum food consumption. Acute studies of severe energy restriction have reported increased intake on the day after a 24-h period of restricted intake (25% of estimated energy requirements), compared to consuming an energy balanced diet^{(Reference James, James and Clayton43,Reference Clayton, Burrell and Mynott44)} . One study also found that anticipating a forthcoming period of severe energy restriction could also increase energy intake in the preceding 24-h, indicating that compensatory eating behaviour may also begin before restriction itself ^{(Reference James, James and Clayton43)}.

In contrast, longer-term studies have not consistently reported the same degree of compensatory eating^{(Reference Trepanowski, Kroeger and Barnosky32,Reference Pannen, Maldonado and Nonnenmacher42,Reference Beaulieu, Casanova and Oustric45)} , although estimating intake from food diaries limits confidence in this data^{(Reference Dhurandhar, Schoeller and Brown46)}. In women with overweight or obesity undertaking mADF, Beaulieu et al. ^{(Reference Beaulieu, Casanova and Oustric45)} found no increase in self-reported intake on non-restricted days, despite greater hunger on restriction days. However, fewer participants achieved 5% weight loss with mADF than CER within 12-weeks (67 vs. 95%), despite a nominally larger energy restriction prescribed with mADF (38 vs. 25%). These findings suggest that the larger prescribed deficit with mADF was not consistently achieved, although the contribution of undetected compensatory eating remains uncertain.

Time-restricted eating: timing, compensatory eating and lifestyle challenges

Comparable considerations apply to TRE, although the restricted and non-restricted eating periods both occur within the same day. Shortening the daily eating window often reduces daily energy intake, and acute laboratory-controlled studies consistently show that daily energy intake is reduced with morning fasting compared to breakfast consumption^{(Reference Clayton, Barutcu and Machin47–Reference Chowdhury, Richardson and Tsintzas49)}. However, compensatory eating behaviour after morning fasting differs, with lean adults typically increasing intake at subsequent meals^{(Reference Clayton, Barutcu and Machin47,Reference Chowdhury, Richardson and Tsintzas49)} , whilst no difference in subsequent energy intake was reported in adults with obesity^{(Reference Chowdhury, Richardson and Tsintzas48)}. Despite this, across six-weeks, daily energy intake was reduced with extended morning fasting in lean adults^{(Reference Betts, Richardson and Chowdhury50)}, but there was no difference in daily energy intake between morning fasting and breakfast consumption in adults with obesity^{(Reference Chowdhury, Richardson and Holman51)}. Similar results were reported in the 12-week TREAT trial, where adults with overweight or obesity adhered to an 8-h lTRE protocol with all energy consumed between 12:00–20:00, or a control arm instructed to consume three meals per day between 07:00–22:00. This study found no between-group differences in weight loss or estimated energy intake^{(Reference Lowe, Wu and Rohdin-Bibby38)}. Collectively these studies indicate that morning fasting/lTRE does not reliably produce a sustained energy deficit or greater weight loss, and compensatory eating later in the day may contribute in some contexts.

In contrast, eTRE retains morning food intake and restricts food intake later in the day, removing a different set of eating opportunities. Jones et al. ^{(Reference Jones, Pabla and Mallinson17)} found that restricting food intake to between 08:00–16:00 in healthy adults led to a spontaneous ∼400 kcal/day reduction in energy intake and produced modest weight loss from baseline after 2-weeks. Jamshed et al. ^{(Reference Jamshed, Steger and Bryan52)} randomised adults with obesity to an 8-h eTRE diet (07:00–15:00) or a > 12-h eating window for 14-weeks. Participants in both groups were prescribed an energy-restricted diet and provided dietary counselling throughout the intervention. Weight loss after 14-weeks was 2.3 kg greater in the eTRE group, with weight-change modelling estimating a reduction in energy intake of ∼215 kcal/day. These findings indicate that eTRE may be a particularly effective method for reducing energy intake and achieving weight loss.

A plausible explanation for the contrasting eating behaviour and weight loss findings between eTRE and lTRE is the time of day at which intake is restricted, and the foods that may consequently be omitted. lTRE retains evening intake, where meals and snacks tend to be more energy dense and discretionary intake more likely^{(Reference Flanagan12,Reference de Castro53)} . This is also the time of day associated with greater appetite and energy intake^{(Reference de Castro53,Reference Scheer, Morris and Shea54)} . Together, these factors may mean that energy omitted through morning fasting is more readily recovered later in the day. eTRE removes that later eating opportunity, potentially reducing intake of energy dense foods typically consumed in the evening.

However, the apparent efficacy of eTRE must be balanced against its potential incompatibility with everyday life. Consuming the final meal of the day by mid-afternoon may conflict with work schedules and social commitments. Family and social occasions often occur in the evening and involve food, potentially limiting adoption and maintenance of this approach. Jamshed et al. ^{(Reference Jamshed, Steger and Bryan52)} found that adherence to eTRE declined over the 14-week study, and only 28% of completers intended to continue with this eating schedule after the study had ended. Thus, whilst the physiological and behavioural responses to eTRE are compelling, the long-term acceptability of this approach remains uncertain.

Do appetite and food reward influence eating behaviour?

Appetite is a biopsychological system in which homeostatic signals, such as gastrointestinal, metabolic, and endocrine cues, interact with hedonic, social, and environmental influences to shape motivation to eat^{(Reference Casanova, Finlayson and Blundell55)}. Periods of severe energy restriction during IF may influence appetite through several pathways, affecting tolerance of restriction and susceptibility to compensatory eating during non-restriction periods.

Across 17 RCTs, a meta-analysis found no clear evidence that IF altered subjective appetite ratings differently from CER^{(Reference Elsworth, Monge and Perry56)}. However, most included studies used only isolated pre-and post-intervention measurements, providing little insight into appetite responses across repeated restriction and refeeding cycles. More granular data on mADF found hunger was greater during restricted than non-restricted days; average hunger was also greater during mADF than CER, and craving control improved less^{(Reference Beaulieu, Casanova and Oustric45)}. Although hunger does not always translate to altered eating behaviour, it can provide insight into the tolerability of energy restriction, with these findings suggesting that modified fasting may impose a greater subjective burden than CER.

Food reward encompasses the hedonic pleasure derived from eating (‘liking’) and the motivational value of food (‘wanting’)^{(Reference Finlayson, King and Blundell57)}. An acute fast has been shown to increase both liking and wanting for food, as well as the relative reinforcing value of snack foods, and ad-libitum energy intake, compared to a fed condition^{(Reference Cameron, Goldfield and Finlayson58)}. Similarly, extended morning fasting increases subjective appeal for high-calorie foods and activation of brain regions associated with reward, in response to food cues^{(Reference Goldstone, Prechtl de Hernandez and Beaver59)}. These responses may increase susceptibility to cue-driven compensatory eating during IF.

However, direct long-term evidence remains limited. In women achieving >5% weight loss through mADF or CER, explicit liking decreased after weight loss, wanting was unchanged, and there were no differences between dietary approaches^{(Reference Oustric, Beaulieu and Casanova60)}. Similarly, a 12-month 4:3 modified fasting intervention found greater reductions in binge and uncontrolled eating, compared to CER, but there were no between-group differences in reward-based eating scores^{(Reference Breit, Caldwell and Ostendorf61)}. Therefore, whilst appetite and food reward are plausible influences on adherence and compensatory eating during IF, the available evidence does not indicate that either is consistently altered differently from CER.

Movement as a compensatory response

Compensatory behavioural responses to fasting or severe energy restriction are not confined to energy intake. Resting metabolic rate (RMR) declines with weight loss, often more than would be predicted from body compositional changes alone (known as adaptive thermogenesis)^{(Reference Camps, Verhoef and Westerterp62)}, whereas diet-induced thermogenesis (DIT) will fluctuate across restricted and unrestricted eating periods. Neither appears to differ between IF and CER to an extent that could meaningfully affect total energy expenditure^{(Reference Westerterp, Wilson and Rolland63)}.

Physical activity energy expenditure (PAEE) is the most malleable component of energy expenditure and comprises both structured exercise, and non-exercise activity, such as walking, standing and spontaneous movements^{(Reference Levine, Vander Weg and Hill64)}. Reduced nutrient availability during zero-energy or modified fasting could lead to conscious or unconscious changes in physical activity, attenuating the energy deficit created by the diet^{(Reference Templeman, Gonzalez and Thompson3)}. Extended morning fasting reduced PAEE during the morning in both lean adults and adults with obesity, compared to a control condition in which a > 700 kcal morning meal was consumed before 11:00^{(Reference Betts, Richardson and Chowdhury50,Reference Chowdhury, Richardson and Holman51)} . Extending the fasting period further in a well-controlled study, Templeman et al. ^{(Reference Templeman, Smith and Chowdhury30)} found that PAEE declined from baseline in participants undertaking ADF with net 25% energy restriction, whereas no within-group reductions were evident with energy-matched CER or ADF without energy restriction. Exploratory analysis indicated that PAEE responses were mostly evident during fasting periods, but a reduction was also detected during eating periods. An acute study also found reduced PAEE in the 24-h preceding a planned period of severe energy restriction, indicating that behavioural compensatory changes in PAEE can occur in anticipation of severe energy restriction^{(Reference James, James and Clayton43)}.

Accelerometer-measured physical activity provides complementary evidence that movement patterns can change in response to severe energy restriction. Reduced light-intensity physical activity was observed during restricted days with mADF^{(Reference Beaulieu, Casanova and Oustric45)}, whilst a separate study found an increase in sedentary time and reduced physical activity on restricted compared to non-restricted days^{(Reference Deru, Jacobsen and Gipson65)}. However, neither of these studies found differences in average activity patterns or estimated energy expenditure, compared to CER^{(Reference Beaulieu, Casanova and Oustric45)} or control^{(Reference Deru, Jacobsen and Gipson65)}.

However, these responses are not universal. Two weeks of eTRE did not alter PAEE relative to energy-matched CER which may suggest that physical activity responses may depend on the temporal structure of fasting^{(Reference Jones, Pabla and Mallinson17)}. Overall, controlled studies provide evidence that fasting or severe energy restriction can reduce PAEE in some contexts. Such responses could compromise the energy deficit achieved by IF and could attenuate weight loss outcomes.

Exercise behaviours, performance and affective responses

Regular exercise contributes to energy expenditure and can support weight maintenance, cardiometabolic health, and preservation of lean mass and physical function during weight loss^{(Reference Swift, McGee and Earnest66–Reference Sunde, Hesseberg and Skelton68)}. However, these benefits depend on sustained willingness to engage in exercise. Fasting and severe energy restriction can alter habitual activity patterns, so could also influence the experience of, and motivation to undertake, planned exercise, with implications for diet and exercise adherence.

Evidence on the direct effects of intermittent fasting on exercise engagement is limited, but acute studies have demonstrated that morning or daytime fasting can impair endurance and resistance exercise performance^{(Reference Clayton, Barutcu and Machin47,Reference Slater, Mode and Pinkney69–Reference Bin Naharudin, Yusof and Shaw71)} , and may reduce motivation and readiness to exercise, as well as exercise enjoyment^{(Reference Slater, Mode and Pinkney69)}. These behavioural responses indicate a mechanism through which fasting could influence exercise behaviour.

Longer-term studies indicate that strength and lean mass responses to resistance exercise performed alongside lTRE are similar to those observed with a non-restrictive eating pattern in trained adults^{(Reference Tinsley, Moore and Graybeal72,Reference Moro, Tinsley and Bianco73)} . This is broadly supported by a meta-analysis showing IF or CER can be combined with exercise without negatively affecting most physical performance outcomes relative to exercise alone^{(Reference Kazeminasab, Sharafifard and Bahrami Kerchi74)}. This suggests acute performance decrements with fasting do not necessarily translate into impaired training adaptation. There may also be metabolic implications of exercising in the fasted state. Fasting increases lipolysis and endogenous lipid utilisation which is potentiated under an exercise stimulus^{(Reference Slater, Mode and Bonnard75)}. This can lead to improved insulin sensitivity when performed over several weeks^{(Reference Edinburgh, Bradley and Abdullah76,Reference Van Proeyen, Szlufcik and Nielens77)} . As such, whilst a decrease in exercise performance might be expected with fasting, this should be considered against potential metabolic benefits that could be incurred.

Whether acute performance decrements accumulate to influence long-term adaptation and compromise health benefits is unknown. Perhaps more importantly, impaired motivation, readiness, and enjoyment could compromise exercise engagement, as more positive affective responses to exercise are associated with subsequent physical activity participation^{(Reference Rhodes and Kates78)}.