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Intermittent fasting: eating by the clock
for health and exercise performance
Sumona Mandal ‍ ‍,1 Niall Simmons,1 Sidra Awan,2 Karim Chamari,3
Irfan Ahmed ‍ ‍4

To cite: Mandal S, Simmons N, ABSTRACT

Awan S, et al. Intermittent Key messages
Intermittent fasting (IF) is an increasingly popular dietary
fasting: eating by the clock
practice, and its implementation is found throughout
for health and exercise What is already known?
performance. BMJ Open human civilisation in various cultural, spiritual and religious
► Intermittent fasting (IF) consists of alternating peri-
Sport & Exercise Medicine traditions. Emerging evidence has shown that the health
ods of voluntary fasting and unrestricted caloric con-
2022;8:e001206. doi:10.1136/ benefits of IF stretch beyond calorie restriction and weight
sumption and is used in various religious, cultural
bmjsem-2021-001206 loss. These benefits include metabolic shifts in energy
and personal contexts.
production, the optimisation of peripheral circadian
► IF has been shown to facilitate weight-­ loss and
clocks, and overall improvement in physiological markers
improve glycaemic control among other metabolic
of metabolic health. IF has been proposed to reduce
processes.
systemic inflammation and have a role in the prevention
► The exact mechanisms of how IF can improve health
and treatment of chronic disease. For the athlete, IF
are unknown, however, theories derived largely from
protocols offer a potential new frontier for maintaining
animal studies suggest increased ketosis, reduction
performance in the fasted state. They may allow athletes
in reactive oxidative species production and/or opti-
to optimise training adaptions, while respecting individual
misation of central and peripheral circadian physio-
cultural, religious, and/or spiritual preferences to fast and
logical processes.
exercise. Below, we discuss the physiological impact of
fasted exercise while highlighting areas for future work What are the new findings?
to improve our understanding and implementation of ► Alongside weight-­loss, IF has been proposed to re-

by copyright.
the practice for the benefit of both the active general duce systemic inflammation and may be of benefit in
community and sporting populations. patients with certain chronic conditions associated
with inflammation, such as metabolic syndrome.
► IF may have metabolic benefits resulting in reduc-
tions in weight and waist circumference that are
independent of calorie restriction.
INTRODUCTION ► The benefits of IF on body mass and cardiovascular
Intermittent fasting (IF) is a popular dietary risk factors may be further optimised with the addi-
practice, which consists of regular alternating tion of aerobic exercise.
periods of unrestricted dietary consumption ► Modified alternate day fasting has been shown to
and abstinence from caloric intake. Emerging reduce calorie intake on unrestricted caloric con-
evidence shows IF has short and long-­term sumption days when individuals practice IF in real
benefits for health and exercise performance world conditions.
© Author(s) (or their
that go beyond facilitating weight-­ loss.1–4
employer(s)) 2022. Re-­use
permitted under CC BY-­NC. No Despite its widespread use, there remains
commercial re-­use. See rights inconclusive evidence on how best to use (TRE) patterns or alternate day fasting
and permissions. Published by IF for health and well-­being. We discuss the (ADF), with or without purposeful caloric
BMJ. restriction. TRE involves continuous short
1
emerging evidence related to IF and the
University College London, potential for its use in personalised medicine. periods of IF, with food consumption typi-
Medical School, London, UK
2 cally within an 8 to 10-­hour window period,
University College London
Hospitals NHS Foundation Trust, What is IF? for example, the 16/8 diet.5 ADF comprises
London, UK IF practices have been commonly performed an alternating pattern between non-­restricted
3
Aspetar, Orthopaedic and across both ancient and modern societies days and fasted days with no caloric intake.5
Sports Medicine Hospital, Doha, for religious, spiritual and cultural reasons However, in real world conditions these are
Qatar
4 (table 1). Modern iterations of IF involve poorly tolerated and have recently been
Sports Medicine Department,
Homerton University Hospital, refraining from normal societal patterns of replaced with modified ADF (mADF) proto-
London, UK eating that follow the 24-­hour period of light cols, which allow for an intake of up to 40%
and day and restrict caloric intake to defined of the recommended daily caloric intake on
Correspondence to
window periods. fasted days.6
Dr Irfan Ahmed; These IF protocols can be divided into Many individuals who undertake IF report
i​ rfan.​ahmed5@n​ hs.​net those that encourage time restricted eating gaining psychological and spiritual health

Mandal S, et al. BMJ Open Sp Ex Med 2022;8:e001206. doi:10.1136/bmjsem-2021-001206 1

 Open access

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Table 1 Examples of fasting practices from ancient and modern societal practices
Fasting practice Pattern of fasting Dietary restriction during fasting

Religious practices
 Ramadan (Islam) 29 or 30 consecutive days of fasting during No food or liquids consumed
daylight hours
 Yom-­Kippur (Judaism) 1 day of fasting for 24 hours No food or liquids
 Proşadhopavāsa (Jainism) Fasting on day 8 and 14 of the lunar cycle Abstinence from the four categories of
consumables:
1. Food that satisfies entire hunger such as
rice, wheat, vegetables.
2. Water.
3. Sweets.
4. Oral fresheners after meals.
 Lent (Christianity) Fasting for 40 days, fast during the day and Abstinence from meat, eggs, dairy products,
breaking fast at sunset olive oil and alcohol
 Baguan zhai (Buddhism: eightfold fast) Do not eat after noon (midday), break-­fast Abstinence from meat and fish
the next morning
Non-­religious practices
 Time-­restricted eating, for example, 16/8 Fasting for 16 hours and eating within an No particular dietary restriction during feeding
8-­hour period window, however, typically results in un-­
intentional total caloric reduction
 Alternate day fasting, for example, 5:2 Calorie restriction on 2 days of the week No particular dietary restriction but significant
protocol calorie restriction
 Modified alternate day fasting for example, Intake of up to 40% of energy requirements Up to 40% of recommended energy
modified 5:2 protocol on 2 days of the week requirements but no particular dietary
restriction

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benefits from periods of abstinence from food. Recent greater fat metabolism and reduced fat storage5 (figure 1).
data have shown that there may also be physiological Studies on IF have also been shown to enhance insulin
benefits to fasting, with murine studies showing that it sensitivity, increase high-­density lipoprotein cholesterol
is associated with increased life expectancy; a reduction and decrease levels of low-­density lipoproteins.5
in the production of reactive oxygen species; improved The longer-­term benefits of IF have also been attributed
inflammatory marker profiles (TNF-α and ceramides) to reduced systemic inflammation (oxidative stress
and metabolic profiles (reduced body weight and fat theory). This theory suggests the decreased energy intake
mass).1 7 It is thought that IF may improve health by and production of reactive oxidative species by the mito-
reducing systemic inflammation or by promoting auto- chondria results in a diminished cellular inflammatory
phagy (internal cellular degeneration and regeneration process.5 There are also additional circadian benefits on
processes).1 8 9 the timing of food intake, as the performance and func-
tion of key physiological processes (food absorption and
Exploring the mechanism behind IF
metabolism) vary in keeping with our internal 24-­hour
TRE practices are increasing in popularity in the general
circadian rhythm. These processes are highly sensitive to
population, with recent evidence supporting their use
for diabetes and weight management in clinical popula- the time-­of-­day impact at both a central and peripheral
tions under medical guidance.3 These regimes have been cellular level and require distinct periods of fasting for
shown to be well-­tolerated, and lead to an average of 20% optimal physiological function (circadian rhythm hypoth-
unintentional reduction in caloric intake.10 It has been esis).5 IF has been shown to increase the expression of a
suggested that TRE may have additional benefits beyond circadian rhythm regulating gene, NR1D1, which lowers
calorie restriction, with several studies showing that these fat accumulation in the liver and adipose tissues, as well
dietary patterns can improve insulin sensitivity and meta- as reducing inflammation and decreasing susceptibility
bolic markers such as systolic blood pressure, HbA1c, fat to metabolic syndrome.1
mass and triglycerides, even in eucaloric conditions.10 Understanding these circadian effects in detail will
There are three main theories that have been suggested provide us with practical recommendations of how best
to explain this metabolic effect; (i) the Ketosis theory, (ii) to implement IF. This may involve matching caloric
oxidative stress hypothesis and (iii) the circadian rhythm intake to diurnal patterns of hormone secretion (eg,
hypothesis. The ‘Ketosis theory’ has the greatest traction insulin secretion or sensitivity), or times of day when gut
both in mainstream and scientific communities.3 5 7 The motility and absorption are optimised, or when higher
theory postulates that IF leads to a reduction of total proportions of energy are produced by carbohydrate
calorie intake, causing a metabolic shift which results in metabolism.11 A practical example of this is abstaining

2 Mandal S, et al. BMJ Open Sp Ex Med 2022;8:e001206. doi:10.1136/bmjsem-2021-001206

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Figure 1 An overview of current theories on how intermittent fasting may impact health or performance.

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from night-­time eating, which decreases post-­ prandial This finding may also provide a practical example of the
glucose levels, increases insulin sensitivity and reduces aforementioned ‘circadian rhythm’ hypothesis.5
the incidence of cardiovascular disease.5 It has been postulated that TRE, with its limited feeding
windows, allows for the synchronisation of mealtimes to
Benefits of fasting for metabolic health and beyond the circadian clock and hence optimises metabolic func-
IF practices have demonstrated short-­ term positive tion.1 10 Interest into this circadian effect is growing, with
impacts on patients’ metabolic health, with a recent recent studies exploring early TRE and delayed TRE.10
systematic review reporting significant reductions in A greater understanding of the time-­of-­day impact of IF
weight (average body mass index decrease of 4.3%) and on metabolic function, and the influence of individual
waist circumference in overweight/obese patients.12 patients phenotype (ie, thinness), will allow us to imple-
These findings were reproduced in both calorie restricted ment these protocols better into personalised diets.13
and eucaloric regimes, indicating a physiological benefit For IF diets to be sustainable they must also be accom-
independent of reduced caloric intake.12 Thirty days of panied by continued lifestyle and behaviour change.
eucaloric IF in healthy volunteers has been associated mADF diets may provide this, with one study reporting
with improved proteomic signatures and the upregula- a spontaneous 19% reduction in energy intake on unre-
tion of proteins involved in immune system regulation stricted days in overweight patients completing the
and DNA repair (short-­ term studies).1 It is hypothe- diet for weight loss.6 It is thought that IF patterns lead
sised that this effect may improve individuals’ health by to a better awareness of eating habits and hunger, and
reducing the risk of developing long-­ term conditions improve eating behaviours on unrestricted days.6 The
related to chronic inflammation.1 addition of tailored exercise programmes have also been
The interplay between IF and metabolic regulation shown to further enhance the health benefits of IF when
may involve the circadian system. Recent studies on circa- taken with continued lifestyle changes.14
dian rhythms have shown a diurnal variation of insulin
and blood glucose levels.5 This raises the possibility of a IF for exercise performance
time-­of-­day variation in the metabolic response to calorie In the era of personalised medicine, some athletes have
consumption which is independent of the amount seen IF as a way to optimise performance and maximise
eaten.5 This hypothesis is supported by the finding of an training benefits. Coordinating the timing of meals with
increase in adiponectin (a key circadian system regulator athletes’ circadian rhythms and training demands could
linked to improved glycaemic control and insulin sensi- be used to help maintain weight, improve sleep and aid
tivity) following TRE in physically active participants.10 recovery. This practice may be most applicable in short

Mandal S, et al. BMJ Open Sp Ex Med 2022;8:e001206. doi:10.1136/bmjsem-2021-001206 3

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periodisation blocks, where nutritional strategies are Provenance and peer review Not commissioned; externally peer reviewed.
used to aid specific training goals (ie, weight mainte- Open access This is an open access article distributed in accordance with the
nance or aerobic capacity).2 Creative Commons Attribution Non Commercial (CC BY-­NC 4.0) license, which
permits others to distribute, remix, adapt, build upon this work non-­commercially,
Short-­term eucaloric and hypocaloric TRE studies in phys-
and license their derivative works on different terms, provided the original work is
ically active and resistance-­ trained adults, with adequate properly cited, appropriate credit is given, any changes made indicated, and the
protein intake and hydration, have shown that IF prac- use is non-­commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
tices are not detrimental to strength training adaptions
ORCID iDs
such as muscle cross sectional area and fat free mass.2 4 8 Sumona Mandal http://orcid.org/0000-0002-6031-8091
Exercise in the fasted state has been shown to increase fat Irfan Ahmed http://orcid.org/0000-0003-2146-4114
metabolism without impacting resting energy expenditure
when compared with diets with continuous caloric intake
throughout the day.2 8 There may also be additional bene- REFERENCES
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Twitter Irfan Ahmed @irfan_sem
of human thinness compared to severe obesity. PLoS Genet
Contributors IA: devised the main conceptional ideas of the manuscript.IA, NS 2019;15:e1007603.
and SM: drafted the manuscript.IA, NS, SM, KC and SA: involved in structuring, 14 Bhutani S, Klempel MC, Kroeger CM, et al. Alternate day fasting and
researching and editing of the manuscript.I.A approved the final version of the endurance exercise combine to reduce body weight and favorably
alter plasma lipids in obese humans. Obesity 2013;21:1370–9.
manuscript.SM and NS contributed equally to this paper.
15 Moro T, Tinsley G, Longo G, et al. Time-­restricted eating effects
Funding The authors have not declared a specific grant for this research from any on performance, immune function, and body composition in elite
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4 Mandal S, et al. BMJ Open Sp Ex Med 2022;8:e001206. doi:10.1136/bmjsem-2021-001206