Nutrients: Energy Metabolism and Intermittent Fasting: The Ramadan Perspective
Nutrients: Energy Metabolism and Intermittent Fasting: The Ramadan Perspective
Nutrients: Energy Metabolism and Intermittent Fasting: The Ramadan Perspective
Review
Energy Metabolism and Intermittent Fasting: The
Ramadan Perspective
Nader Lessan * and Tomader Ali
Imperial College London Diabetes Center (ICLDC), Abu Dhabi 48338, UAE; tfali@icldc.ae
* Correspondence: nlessan@icldc.ae; Tel.: +971-2-4040-519
Received: 18 April 2019; Accepted: 9 May 2019; Published: 27 May 2019
Abstract: Intermittent fasting (IF) has been gaining popularity as a means of losing weight. The
Ramadan fast (RF) is a form of IF practiced by millions of adult Muslims globally for a whole lunar
month every year. It entails a major shift from normal eating patterns to exclusive nocturnal eating.
RF is a state of intermittent liver glycogen depletion and repletion. The earlier (morning) part of
the fasting day is marked by dominance of carbohydrate as the main fuel, but lipid becomes more
important towards the afternoon and as the time for breaking the fast at sunset (iftar) gets closer. The
practice of observing Ramadan fasting is accompanied by changes in sleeping and activity patterns,
as well as circadian rhythms of hormones including cortisol, insulin, leptin, ghrelin, growth hormone,
prolactin, sex hormones, and adiponectin. Few studies have investigated energy expenditure in the
context of RF including resting metabolic rate (RMR) and total energy expenditure (TEE) and found
no significant changes with RF. Changes in activity and sleeping patterns however do occur and are
different from non-Ramadan days. Weight changes in the context of Ramadan fast are variable and
typically modest with wise inter-individual variation. As well as its direct relevance to many religious
observers, understanding intermittent fasting may have implications on weight loss strategies with
even broader potential implications. This review examines current knowledge on different aspects of
energy balance in RF, as a common model to learn from and also map out strategies for healthier
outcomes in such settings.
1. Introduction
Fasting can be defined as the voluntary abstinence from or reduction of some or all food, drink,
or both (absolute) for a period of time lasting typically between 12 h and 3 weeks i.e., in a short
term, long term/prolonged or an intermittent pattern [1]. Fasting is a common practice in different
religious disciplines, including Islam, Christianity, Judaism and Hinduism. In Islam, the practice
entails abstinence from eating and drinking between dawn and sunset [2]. Fasting is distinct from
starvation, which is a chronic and severe deficiency in caloric energy intake below the level needed to
maintain life.
Health benefits of intermittent fasting have been demonstrated in both randomized controlled
trials and observational studies [3,4]. Caloric restriction (CR) has also been shown to prevent several
chronic degenerative and inflammatory diseases [5] and to prolong life in more primitive species
including Escherichia coli and yeast [6]. In humans, the evidence on the positive effects of CR on
longevity is indirect; for example the increased life expectancy in the Okinawan population, from the
Kyushu Island in Japan, has been attributed at least in part to low calorie intake [7]. Mechanistically,
the effect of CR on longevity has been attributed to fasting-induced modulation of neuroendocrine
systems, hormetic stress responses, increased systemic production of neurotrophic factors, reduced
mitochondrial oxidative stress, decreased pro-inflammatory cytokine production and insulin resistance,
as well as decreased aging-associated signals and autophagy promotion [5,8,9].
Prolonged fasting has also been associated with positive effects on mood due to the alteration in
physiology at a cellular level via increases in availability of central endogenous neurotransmitters,
endogenous opioids and endocannabinoids [10]. Cancer studies demonstrated that fasting and
fasting-mimicking diets (FMDs) positively promote differential effects in both normal and malignant
cells via reduction in insulin-like growth factor (IGF-1), insulin and glucose with paralleled increases
in ketone bodies [11]. In contrast, negative effects of fasting have been reported for instance on
non-communicable diseases [8,11,12], on changes to sleep patterns, cognitive function, [13,14] and
have also been associated with fluctuations in mood, weight and a plethora of other changes [15,16].
Fasting is a state of negative energy balance, and as such different fasting regimens have been
used to achieve weight loss, as well as other health benefits. In the context of Muslim Ramadan-type
fasting, changes in energy intake depend on social, cultural and individual factors and can range
from a reduction to an increase in weight [17–19]. Whether this is accompanied by changes in energy
expenditure is not well-known and merits further exploration for its possible implications in weight
loss management strategies in general [20].
This review will be examining current knowledge about different aspects of energy balance in the
context of the Ramadan fast as a commonly practiced model of intermittent fasting. In the broader
context, potential positive implications include the use of for such strategies to help with weight
maintenance, is not weight loss, and thus a multitude of other consequential positive health benefits.
Relevant literature (Tables 1 and 2) directly and indirectly related to the Ramadan fast, including short-
and long-term fasting and also prolonged and intermittent type fasting will be explored. In the context
of Ramadan, changes in energy dynamics (intake versus expenditure) have been extrapolated based
on our previous quantitative studies, knowledge of physiology and alterations in energy utilization
during feeding and non-feeding periods. The aim of this review is firstly, to discuss the various aspects
influencing energy modulations during Ramadan fasting; secondly, to shed light on key knowledge
gaps in our understanding of energy balance in relation to changes in both body composition and
physiological adaptation in various models of fasting to include key periods such as the Ramadan
fasting period and; lastly, to contribute to the focused directionality of future studies in key aspects
that warrant further detailed investigations.
a greater rise in EE than fat or carbohydrates. Although TEF is normally a small component of TEE
(~10%) it is nonetheless an important component in energy imbalance states as it is influenced by meal
size and composition, the nature of the previous diet, insulin resistance, physical activity, and ageing
influence TEF [27].
gluconeogenic phase occurs ~1–10 days after beginning fasting. Here, protein catabolism is used to
feed glucose to the CNS while other tissues feed on ketones and fat. Lipolysis and ketogenesis increase
and then plateau, gluconeogenesis on the other hand begins to decrease and no glycogenolysis occurs.
Stage 3: is a protein conservation phase that occurs when fasting extends beyond 10 days. Protein
catabolism is decreased to a minimum, fatty acids are used ubiquitously and ketones are utilized as
fuel in the CNS. Lipolysis and ketogenesis plateaus while gluconeogenesis decreases and then plateaus
but to a much lower extent when compared to ketogenesis [33,34].
Figure 1. Time-dependent Changes in Weight during Prolonged Fasting (31 Days). Adapted from:
Francis Gano Benedict: A study of Prolonged Fasting. (a), Daily Net Weight Loss: calculation of daily
weight reduction in 31 days (D) of fasting. Initial weight was 59.86 kg at D1, final weight was 47.47 kg at
D31, total weight loss −12.4 kg. R2 = 9798 indicated a linear relationship between time and net weight
loss. (b) Changes in Rate of Daily Weight Loss: relative to starting rate of weight loss, rate of weight
loss per day indicates various changes whereby a steep rate of weight loss we observed in the first five
days of fasting (D1–5; Maximum Rate 0.67), followed by a slower rate of weight loss in the following 10
days (D5–15; Maximum Rate 0.64), which decreased further in the next 10 days (D15–25; Maximum
Rate 0.47) before reaching a plateau in the last five days of the fasting month (D25–30; Maximum Rate
0.42).
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In 1916, Spriggs reported various cases of fasting used as a method to treat diabetes whereby
fasting was ‘continued in bed until the urine has been sugar-free for twenty-four hours, unless there is
some definite contraindication, such as nausea, vomiting, insomnia, or faintness’ [37]. Early studies
also indicated a progressive decrease in daily urinary nitrogen excretion suggestive of an increase in
conservation of body protein [38] and that urine output gradually decreased throughout the fasting
period [39].
In 2006, a study on prolonged absolute fast (44-days) on a healthy non-obese man shed light on
changes in various metabolic parameters [40]. The TEE was not measured, but was estimated to be
1638–2155 kcal/day of which 13.0–17.1% was from protein oxidation. Total weight loss was 24.5 kg and
body mass decreased by 25.5%; a quarter to a third was fat mass and the remainder to fat-free mass
which was predominantly muscle and approximately 20% was total body protein.
More recently, in 2015, Müller and colleagues investigated effects of caloric restriction (CR) and
weight loss on 32 subjects aged between 20–37 years old in a controlled environment. Patterns of
habitual food intake, resting energy expenditure and physical activity were assessed. The 10 week
(week) dietary intervention period duration included 1 week of overfeeding (at +50% of daily energy
requirements; 4059 ± 52 kcal/day) followed by 3 weeks of CR (at −50% of energy requirements; 1353 ±
154 kcal/day) and a subsequent 2 weeks of re-feeding (at +50% of energy requirements; 4059 ± 452
kcal/day). Protein intake was 97 ± 11 g/day (baseline); 146 ± 17 g/day (overfeeding), 49 ± 6 g/day (CR),
and 146 ± 17 g/day (re-feeding), respectively. The study reports a +1.8 kg weight gain (overfeeding),
−6.0 kg (CR), and +3.5 kg (re-feeding). CR reduced fat mass and fat-free mass from skeletal muscle
(−5%), liver (−13%), and kidneys (−8%) by a total of 114 and 159 g/day, respectively. CR also led to
reductions in resting energy expenditure (−266 kcal/d) and respiratory quotient (−15%). The study
concluded that during early weight loss, adaptive thermogenesis is associated with a fall in insulin
secretion and body fluid balance [41].
Figure 2. Changes in Feeding Patterns and Energy Intake during Various Fasting Periods. The five
feeding and fasting patterns are: (I) normal feeding, (II), calorie restriction, (III) intermittent fasting (e.g.,
5:2), (IV) Ramadan fast and (V) prolonged fasting and starvation. (a) Hourly Differences in Feeding
Patterns between Various Fasting Models: hourly timings of feeding and energy intake (meals) are
indicated per day in relation to fasting periods (arrows) and reflected in glycaemic control (traces).
(b), Daily and Weekly Differences in Feeding Patterns Between Various Fasting Models: daily and
weekly feeding patterns are mapped against calorie intake which can be regular such as in in normal
feeding (I), indicated by single colour arrows or a combination of low, normal or high calorie intake
as in intermittent fasting (III), indicated by mixed colour arrows. Ramadan fast (IV) is unique as it
combined low and high calorie intake as indicated by the two single colour arrows. The first week is
broken down into seven individual days. Weekly indications follow thereafter.
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Figure 3. Energy intake (EI) recommendations and resultant weight changes in Ramadan and
non-Ramadan periods. Energy intake recommended guidelines for female and male adults. (a)
indicates values for the (1) UK 2250 kcal/day (female 2000 and male 2500 kcal/day), (2) the USA 2300
kcal/day (female 2000 and male 2600 kcal/day) and (3) for Australia 2225 kcal/day (female 2010 and
male 2600 kcal/day). Collectively, an average adult consumes ~2270 kcal/day (female 2003 and male
2533 kcal/day). (b), Energy intake recommendations during Ramadan in comparison to standard and
low calorie diets. in order of left to right: based on the calculated average of 2270 kcal/day as a standard
adult EI (Figure 3A), a healthy Ramadan diet matched calorie intake is achievable. In reality, a higher
EI is experienced in Ramadan (~3000 calories). However, weight maintenance (at 1800 kcals/day) is
achievable during Ramadan as suggested by Diabetes and Ramadan (DaR) Alliance Ramadan Nutrition
Plans (RNP) recommendations. This holds true for weight loss at the 1500 and 1200 kcals/day calorie EI
for both non-Ramadan and Ramadan periods.
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Ramadan nutrition planning (RNP) is encouraged as per DaR guidelines, which take into
consideration variations in cultural food choice and calorie consumption (range of 1200 kcal/day for
weight reduction for females to maximum of 2000 kcal/day weight maintenance for males) [46]. Due to
the inevitable changes in feeding patterns and associated physiological shifts in circadian rhythms,
hormone levels fluctuations and overall daily lifestyle, Ramadan meal planning becomes an essential
component for healthy Ramadan fasting. This is of particular importance for patients with chronic
conditions, such as diabetes. A ‘Ramadan Plate’ is recommended to contain a balanced selection of
carbohydrates (40–50% of total daily calorie intake (TDCI) of low glycaemic index and high-fibre
containing foods), protein (20–30% of TDCI of non-red meat sources and legumes) and reduced fat
intake (35% of TDCI of mostly mono- and poly-saturated fatty acids). Suhoor, the pre-dawn meal,
is recommended to constitute 30–40% energy intake for the day, iftar 40–50% and snacks 10–20%
as necessary.
In theory, in terms of energy intake, skipping one main meal in a 24-h period should be associated
with a major reduction in food content and energy intake. This is the principle in the intermittent
5:2 fasting diet where fasting can be up to 18 h (Figure 2(AIII,BIII)). Therefore, during Ramadan, in
addition to eating healthily, this reduction in energy intake could lead to weight loss but in practice
this does not occur in most cultures (Figure 3B). Many studies indicate a great variability in Ramadan
diets [30,47] in different cultures, age groups, geographical locations and duration of fasting hours as
well as the impact of physiological and pathological conditions (e.g., diabetes) and associated with
modest reduction of energy intake in most but not all groups studied.
El Ati and colleagues investigated a group of 16 healthy female volunteers fasting during Ramadan
and reported 84% of total daily energy intake was taken at the evening meal, and the remaining 16%
was taken between 8 p.m and midnight. This is in contrast to periods before Ramadan where breakfast,
lunch and dinner constituted 9.4, 41.6 and 21.8% of total daily energy intake. Although the findings of
this small study cannot be generalized to the larger population of fasting Muslims, the observation of
a disproportionately large meal at iftar time is a common finding [31,48]; often reflected in feeding
patterns (Figure 2) and in glycaemic profiles.
Figure 4. Energy expenditure and physical activity pre-, during and post-Ramadan. (a) Box plot of
daily total number of steps during and post-Ramadan. The effect of Ramadan fasting on activity in
11 participants. (b) Box plot of total number of steps at different periods within one day (per night,
morning, afternoon, and evening) during and post-Ramadan in 11 participants. Comparisons made
with the Wilcoxon signed-rank test. Total mean ± SD number of steps per day (9950 ± 1152 compared
with 11,353 ± 2053, p = 0.001), activity in the morning (1974 ± 583 compared with 3606 ± 715, p =
0.001) and afternoon (3193 ± 783 compared with 4164 ± 670, p = 0.002) were significantly lower during
Ramadan compared with post-Ramadan. Nocturnal activity was higher during Ramadan (1261 ±
629 compared with 416 ± 279, p = 0.001). No significant difference in evening activity levels between
during and post-Ramadan periods was observed. (c) TEE and RMR during and post-Ramadan: the
correlation between TEE and weight during and post-Ramadan in 10 participants. No significant
difference between Ramadan and post-Ramadan regression lines (ANCOVA; t = 0.35, p = 0.727); the
main factor influencing TEE was body weight (t = 2.72, p = 0.015).
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Weight loss strategies including many dietary interventions are often unsuccessful in the medium
and the long term. One explanation for this is the phenomenon of adaptive thermogenesis. This occurs
by promoting optimization of energy reserves while preserving protein pools via reduction in basal
metabolism, decrease in secretion of anabolic factors (e.g., insulin) and increase in catabolic hormones
(e.g., adrenaline and glucagon) [3]. Along with protein loss, weight loss also occurs; initially at a higher
rate (~1 kg/day) which then decreases (~0.7 kg/day by 24 h, 0.5 kg/day by day 6 and 0.3 kg/day from day
21 onwards) [33]. Importantly, the few small studies of energy expenditure in the context of Ramadan
fast have found no evidence of a metabolic adaptation [24]. This finding needs to be investigated in
larger studies and if confirmed, may have important implications on Ramadan and IF as potential
weight loss strategies. Admittedly, overcompensation with an increase in energy intake at the evening
meal is common practice in observers of the Ramadan fast [31]. Although the increased appetite at
the end of the fasting day [49] is the main drive for this phenomenon, this is in many ways voluntary.
With appropriate education and a shift in food choices it may be possible to limit this increase in intake
of energy dense food and make the prospect of weight loss with the Ramadan fast more realistic.
Aside from weight changes, Ramadan fasting induces a plethora of physiological and metabolic
alterations. The impact of Ramadan on sleep alone includes decreased total sleep time, delayed sleep,
decreased sleep period time (decreased REM sleep duration, decreased proportion of REM sleep) and
increased proportion of non-REM sleep [13]; also reported with high inter-individual variation.
An important issue on interpretation of Ramadan studies is the potential hypohydration that
would be expected towards the end of the Ramadan fasting day. A study investigating the effects of
prolonged fasting and fluid deprivation reported a loss of body weight of around 1.5 kg in individuals
fasting between 10 pm and 4 pm the next day; the weight loss was presumed to be due to loss of
body water [39]. Fluid homeostasis during Ramadan fast has been investigated in several studies and
has been reviewed elsewhere [58]. Water turnover has been shown to increase during Ramadan fast
with concomitant increases in indicators of body hydration including haematocrit, serum urea and
creatinine and urine osmolality. However, total body water appears to be conserved and aside from
potentially contributing to weight loss that might be observed in Ramadan, no detrimental effects
on health have been directly attributed to negative water balance and hypohydration at the levels
experienced during Ramadan [58]. Furthermore, hypohydration has been shown to have no significant
effect on RMR and blood glucose in healthy subjects [59].
Studies of Ramadan fasting in general need to be interpreted carefully and with consideration for
certain factors such as the timing of previous meal, methodological differences and also hydration status.
An important and relevant factor in studies of Ramadan fasting is the duration of the fast, and hence
geographical location; the impact tends to be most marked in countries at higher altitudes and with
more daylight hours [60]. Fasting hours also include the seasonal changes whereby fasting Ramadan
during winter months for instance would have physiologically different effects when compared to
fasting Ramadan during summer months. Although the literature specifically pertaining to energy
expenditure changes during Ramadan is steadily mounting, it is currently small in number. Therefore,
future studies need to address these variables to tackle the inter-variability issues that continually
arises in the current literature.
In conclusion, although the metabolic consequences of Ramadan fast are complex, there is
potential for using this month as a weight reduction model provided the fasting is carried out
mindfully; balancing food type, quantity and levels of physical activity. Pre-Ramadan planning
(nutrition plans, medication and health checks) is necessary; more so for individuals with chronic
conditions such as diabetes who need specialist advice should Ramadan fast be deemed suitable in the
first place. The long-term effects are thus of interest and studies are necessary for elucidation.
Author Contributions: The authors have contributed equally to the writing and editing of the manuscript.
Funding: This research received no external funding.
Acknowledgments: This work has been supported by Imperial College London Diabetes Centre (ICLDC).
Nutrients 2019, 11, 1192 14 of 16
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