nutrients

Article
The Effects of Intermittent Fasting and Continuous Energy
Restriction with Exercise on Cardiometabolic Biomarkers,
Dietary Compliance, and Perceived Hunger and Mood:
Secondary Outcomes of a Randomised, Controlled Trial
Stephen Keenan 1, *, Matthew B. Cooke 1 , Won Sun Chen 1 , Sam Wu 1 and Regina Belski 1,2

1 School of Health Sciences, Swinburne University of Technology, Hawthorn, VIC 3122, Australia;
[email protected] (M.B.C.); [email protected] (W.S.C.); [email protected] (S.W.);
[email protected] (R.B.)
2 School of Allied Health, Human Services and Sport, La Trobe University, Bundoora, VIC 3086, Australia
* Correspondence: [email protected]

Abstract: (1) Background: Excess weight in the form of adiposity plays a key role in the pathogenesis
of cardiometabolic diseases. Lifestyle modifications that incorporate continuous energy restriction
(CER) are effective at inducing weight loss and reductions in adiposity; however, prescribing daily
CER results in poor long-term adherence. Over the past decade, intermittent fasting (IF) has emerged
as a promising alternative to CER that may promote increased compliance and/or improvements in
cardiometabolic health parameters independent of weight loss. (2) Methods: This paper presents a
secondary analysis of data from a 12-week intervention investigating the effects of a twice-weekly
Citation: Keenan, S.; Cooke, M.B.; fast (5:2 IF; IFT group) and CER (CERT group) when combined with resistance exercise in 34 healthy
Chen, W.S.; Wu, S.; Belski, R. The participants (17 males and 17 females, mean BMI: 27.0 kg/m2 , mean age: 23.9 years). Specifically,
Effects of Intermittent Fasting and changes in cardiometabolic blood markers and ratings of hunger, mood, energy and compliance
Continuous Energy Restriction with within and between groups were analysed. Dietary prescriptions were hypoenergetic and matched for
Exercise on Cardiometabolic energy and protein intake. (3) Results: Both dietary groups experienced reductions in total cholesterol
Biomarkers, Dietary Compliance, and
(TC; mean reduction, 7.8%; p < 0.001), low-density lipoprotein cholesterol (LDL-C; mean reduction,
Perceived Hunger and Mood:
11.1%; p < 0.001) and high-density lipoprotein cholesterol (mean reduction 2.6%, p = 0.049) over the
Secondary Outcomes of a
12 weeks. Reductions in TC and LDL-C were greater in the IFT group after adjustment for baseline
Randomised, Controlled Trial.
Nutrients 2022, 14, 3071. https://
levels and change in weight. No significant changes in markers of glucose regulation were observed.
doi.org/10.3390/nu14153071 Both groups maintained high levels of dietary compliance (~80%) and reported low levels of hunger
over the course of the intervention period. (4) Conclusions: Secondary data analysis revealed that
Academic Editor: Susanne Klaus
when combined with resistance training, both dietary patterns improved blood lipids, with greater
Received: 22 June 2022 reductions observed in the IFT group. High levels of compliance and low reported levels of hunger
Accepted: 22 July 2022 throughout the intervention period suggest both diets are well tolerated in the short-to-medium term.
Published: 26 July 2022
Keywords: intermittent fasting; continuous energy restriction; compliance; cardiometabolic
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1. Introduction
Overweight and obesity, conditions generally accompanied by excessive body fat,
are a common and growing health concern worldwide [1]. Excess adiposity is associated
Copyright: © 2022 by the authors. with insulin resistance [2], derangement of blood lipids [3] and systemic inflammation [4],
Licensee MDPI, Basel, Switzerland.
which can increase an individual’s risk of developing cardiovascular disease [5], insulin
This article is an open access article
resistance [6] and type 2 diabetes [7]. Whereas excess adiposity is a common phenotypic
distributed under the terms and
characteristic of overweight and obesity, individuals that fall within the normal-weight
conditions of the Creative Commons
body mass index (BMI) category can also display high body fat percentage. These indi-
Attribution (CC BY) license (https://
viduals, typically referred to as metabolically obese, normal-weight (MONW), are often
creativecommons.org/licenses/by/
characterized by excess visceral adipose tissue and ectopic fat deposition and show some
4.0/).

Nutrients 2022, 14, 3071. https://doi.org/10.3390/nu14153071 https://www.mdpi.com/journal/nutrients

Nutrients 2022, 14, 3071 2 of 18

degree of metabolic dysregulation [8]. Given the deleterious effects of excess adiposity on
disease risk, it is clear that regardless of BMI, reducing weight, especially in the form of adi-
pose tissue, could be an important strategy for improving the health of a large proportion
of the population.
Individuals can utilise various strategies to lose weight. Lifestyle interventions that
promote reduced energy intake and increased physically activity are amongst those most
commonly prescribed by health and clinical practitioners. Whereas continuous energy
restriction (CER) has been the more traditional method to decrease energy intake, intermit-
tent fasting (IF) has emerged over the past 10 years as a potential alternative [9]. Unlike
CER, which consists of a daily energy restriction (approx. 25% below estimated energy
requirements), IF generally alternates days or periods of time of complete fasting (no energy
intake) or modified fasting (small amounts of energy intake) with unrestricted periods of
eating or restricts normal intake to certain time periods each day. Although the benefits
of these diets are often linked to weight loss induced by energy restriction, it has been
suggested that IF may provide metabolic health benefits that are independent of weight
loss [9] and therefore may be superior to CER in this regard. Indeed, some types of IF
have been shown to improve markers of insulin sensitivity over and above that seen with
CER, although this may depend on timing of consumption (i.e., early time-restricted feed-
ing) [10] or length of fasting (i.e., consecutive fasting days versus single-day fasting) [11].
Conversely, there appears to be a general equivalence between CER and IF with respect to
their impact on blood lipids [12,13]. Given the high variability in the application of IF, it is
not surprising that effects may vary.
Whereas pattern of energy restriction may impact changes in cardiometabolic health,
these changes can be amplified by the addition of exercise [14]. Both endurance and
resistance training have been shown to improve various health outcomes with or without
energy restriction and weight loss, although the impact may differ depending on the type
of exercise [14]. The majority of studies that have investigated the combined effects of
CER or IF with exercise have utilised endurance-type training, with the exception of those
employing time-restricted feeding, in which resistance training has been more popular [15].
This is particularly true of 5:2 IF, and to date, no study has directly compared the effect of
this style of IF with that of CER when combined with resistance training on cardiometabolic
health parameters. Due to the variability in impact on health shown associated with both
type of IF and exercise, it is important to investigate the effects of various combinations of
exercise and dietary patterns.
Although exercise and energy restriction are well-known to improve cardiometabolic
health, the success of any lifestyle intervention is largely dependent on an individual’s abil-
ity to comply [16], and dietary compliance, in particular over the long-term, is notoriously
poor [17]. Because IF includes some periods of relief from dietary restriction, it has been pro-
posed that it may facilitate increased compliance in some individuals [18]. However, many
factors are likely to influence long-term adherence to and success of lifestyle modification,
including those of a biological, behavioural, psychosocial and environmental nature [18].
For example, the degree of hunger experienced during weight loss has been shown to be
a predictor of future weight regain [19], whereas mood and emotional state are also key
drivers in some individuals, particularly amongst regular dieters [20]. It is important to
consider how any diet targeting weight loss affects each of these variables, as it may help to
determine the likelihood of compliance and therefore long-term success. This knowledge
may also assist health practitioners in identifying and overcoming potential deterrents for
individuals when prescribing energy-restricted diets. Unfortunately, measures of these
factors are inconsistently employed in IF studies.
The purpose of this study is to present secondary outcomes from a 12-week ran-
domised, controlled trial investigating the impact of isocaloric 5:2 IF and CER diets paired
with resistance training on body composition in untrained young adults [21]. The aim
of this secondary data analysis is to determine the effects of both interventions on car-
diometabolic health markers, as well as the impact on self-reported dietary compliance,
Nutrients 2022, 14, 3071 3 of 18

perceived hunger, cravings, mood and energy levels. Finally, we report on participants’
intentions to continue with their prescribed diets post intervention.

2. Materials and Methods

Detailed intervention methods have been previously described [21]. Briefly, 34 gener-
ally healthy (17 men and 17 women), recreationally active but untrained individuals with
a BMI of 22.0–35.0 kg/m2 aged between 18 and 35 years were randomised to undertake
12 weeks of resistance training (3 sessions per week; two 45-minute supervised session
and one 30-minute unsupervised session) and either a continuous energy restriction (CERT
group) or 5:2 intermittent fasting (IFT group) diet. The aim of both diet prescriptions was
to provide an average 20% energy restriction and ≥1.4 g of protein per kilogram of body
weight per day. Those in the IFT group were asked to fast on non-consecutive, non-training
days each week. Fasting days involved consumption of high-protein shakes and soups,
as well as non-starchy vegetables, in order to maintain moderate protein intake while
providing ~20% of energy requirements. Participants aimed for 100% energy requirements
on the remaining 5 days. Those in the CERT group aimed to consume 80% of energy
requirements daily for the entirety of the intervention. In order to assess dietary intake,
participants were asked to complete a 3-day food diary using a mobile phone applica-
tion during weeks 1, 6 and 12. Results of are reported in the primary outcomes study for
this intervention [21]. The original study was powered to detect differences in the pri-
mary outcome (lean body mass). This study was retrospectively registered with ACTRN:
ACTRN12620000920998, September 2020.

2.1. Cardiometabolic Health Blood Markers

Fasted blood samples were taken from each participant prior to and after the comple-
tion of the 12-week intervention in order to assess the impact of each intervention on blood
markers of cardiometabolic health. Samples were taken between 7.00 a.m. and 11.00 a.m.
after a minimum 8 h fast (although participants were encouraged to consume water on the
night before and the morning of testing). Approximately 20 mL of blood was drawn into a
serum-separating tube from a vein in the antecubital region. The tube was left to sit for at
least 20 min but less than 40 min to allow for clotting. The samples were then centrifuged
for 12 min at 3000 RPM to separate the serum. Serum was then aliquoted and stored at
−84 degrees Celsius before being packed in dry ice and sent via courier to an external lab
for analysis (Melbourne Pathology, Victoria, Australia). Serum samples were analysed
for total serum cholesterol (TC), low-density lipoprotein cholesterol (LDL-C; calculated
via Friedewald’s formula), high-density lipoprotein cholesterol (HDL-C), triglycerides,
blood glucose, insulin and high-sensitivity C-reactive protein (hsCRP). Homeostatic model
assessment of insulin resistance (HOMA-IR) was calculated using the equation ([blood
glucose x insulin]/22.5) [22].

2.2. Self-Reported Dietary Compliance, Mood, Hunger and Satiety Levels and Post-Intervention
Intentions
For each day of the 12-week intervention, participants were asked to complete an
online survey. Participants were asked to complete the survey just prior to going to bed each
day, consistent with previous research [23]. In order to promote completion of the survey,
participants were sent as many as 5 text message reminders per week. Each participant
received a unique survey link that included a total of 17 questions to assess levels of hunger,
satiety, energy, mood and compliance. These questions were adapted from previously
validated visual analogue scales [24,25] into 0-to-10-point Likert scales in order to facilitate
use on a mobile phone. In the survey, 4 questions pertained to hunger, 4 to cravings, 4 to
energy levels and 4 to mood. Additionally, there was a final question asking participants
to rate, on a scale of 0 to 10, how compliant they felt they were with their diet that day,
based on meeting their predefined energy and protein requirements. For analysis, these
Nutrients 2022, 14, 3071 4 of 18

questions were combined into 5 distinct measures; hunger, cravings, energy levels, mood
and compliance, which are shown in Table 1.

Table 1. Questions included within each survey category for hunger, cravings, mood and energy
levels.

Questions Included within Each Survey Category

1. How hungry do you feel? (+ve)
Hunger 2. How satisfied do you feel? (−ve)
(maximum score possible 40) 3. How full do you feel? (−ve)
4. How much do you think you can eat? (+ve)
1. Would you like something sweet? (+ve)
Cravings 2. Would you like something salty? (+ve)
(maximum score possible 40) 3. Would you like something savoury? (+ve)
4. Would you like something fatty? (+ve)
1. How alert do you feel? (+ve)
Energy levels 2. How much of an effort is it to do anything? (−ve)
(maximum possible score 40) 3. How weary do you feel? (−ve)
4. How sleepy do you feel? (−ve)
1. How sad do you feel? (−ve)
Mood 2. How tense do you feel? (−ve)
(maximum score possible 40) 3. How happy do you feel? (+ve)
4. How calm do you feel? (+ve)
Compliance
1. How compliant do you feel you were with your diet today? (+ve)
(maximum score possible 10)
+ve: values are positively associated with the domain; −ve: values are negatively associated with the domain and
were transformed for subsequent analysis.

Scoring of each measure was undertaken by combining the responses (0–10) from
the Likert scale for each of the 4 questions. For ease of interpretation, when higher scores
indicated a negative response for a question category (e.g., How sleepy do you feel? for
the energy levels category), values were transformed into positive scores by subtracting
the recorded Likert scale score from 10. Thus, all scores were presented as positive values,
and each survey category had a maximum score of 40, except for compliance (maximum
score of 10). Additionally, because the original cravings questions were validated in such
a way that higher scores indicated lower cravings, all questions for this section were also
transformed (as per Table 1) when presenting results to ensure easier interpretation. Thus,
higher scores on the cravings scale presented in the data represent higher levels of cravings.
Finally, at the end of the intervention, participants were asked to rate how easy they
found the diet to comply with on a scale of 0 to 10, whether they thought they would
continue with the diet after the intervention had finished and whether or not they would have
preferred to be in the alternate intervention group. In an open-ended question, participants
were also asked to explain what they felt was the most difficult part of the intervention.

2.3. Statistics
2.3.1. Cardiometabolic Health Data
All results are presented as mean (±SD). Normality of variables was assessed utilising
the Shapiro-Wilk test and visual inspection of Q-Q plots. Assumptions of normality were
violated for hsCRP, triglycerides, insulin and HOMA-IR. Insulin and HOMA-IR were
log10-transformed to achieve normality; however, normality could not be achieved for
hsCRP and triglycerides. Three outlying hsCRP values (>10.0 mg/L) were removed, as
these were likely to be due to acute illness. The Wilcoxon signed rank test was used
to analyse differences in non-normal variables from baseline to post intervention. For
normally distributed variables, linear mixed models were used to test for main effects of
time, group and sex, as well as all 2- and 3-way interactions. As there was a significant
difference between groups for baseline TC and a trend toward a difference in LDL-C,
baseline values were centred and included as covariates in the model when analysing effects
Nutrients 2022, 14, 3071 5 of 18

of the intervention on TC and LDL-C. Additionally, in order to account for the impact of
weight loss, changes in weight from pre- to post intervention were also centred and included
in the model for these variables. All model assumptions for linear mixed modelling were
verified for all analyses. Individual changes are also represented graphically for each
variable. Baseline data were analysed for differences between groups using independent
t-tests and Mann–Whitney U tests for normal and non-normal data, respectively. All
analyses were conducted using IBM SPSS Statistics version 25 (IBM Corp., Armonk, NY,
USA). A two-tailed p-value of <0.05 was considered significant for all tests.

2.3.2. Self-Reported Dietary Compliance, Mood, Hunger and Satiety Levels and
Post-Intervention Intentions
Cronbach’s alpha was used to quantify the internal consistency of survey questions
within the same measure (hunger, cravings, energy levels and mood). Alpha coefficients
above 0.7 were indicated high internal consistency. Linear mixed models were used to
analyse survey responses for main effects of time, group and sex, and all 2- and 3-way
interactions using the mean of each week’s responses. Furthermore, the same method was
used to analyse differences on fasting and non-fasting (fed) days for the IFT group, with the
effect of group replaced by condition (fasted or fed). Subsequently, pairwise comparisons
using Sidak’s adjustment for multiple comparisons were utilised to determine in which
weeks mean values were significantly different when a main effect of time was noted. All
model assumptions for linear mixed modelling were verified for all analyses. The means
for weeks 1, 6 and 12 are presented, as well as continuous weekly data, which are presented
graphically using mean values and 95% confidence intervals. Approximately 30% of data
in this study were missing. Unfortunately, due to the small sample size, no imputation
was conducted. Correlations between survey responses for each group were calculated
by Spearman’s rank order correlation due to the non-normal nature of the survey data.
Post-intervention questionnaire responses were analysed using descriptive analysis of
responses or, for the question regarding ease of compliance, using a Mann–Whitney U
test due to non-normality of the data. Similarly, compliance with the exercise routine was
analysed using the Mann–Whitney U test. All analyses were conducted using IBM SPSS
Statistics version 25 (IBM Corp., Armonk, NY, USA). A two-sided p-value of <0.05 was
considered significant for all tests.

3. Results
3.1. Participants
Baseline characteristics of participants are reported in Table 2. A total of 34 participants
completed the intervention (IFT = 17, CERT = 17). There were no significant differences
between groups in terms of age, height, weight or BMI.

Table 2. Participant baseline characteristics.

Baseline IFT CERT

p-Value a
Variable (n = 17; 9 Males, 8 Females) (n = 17; 8 Males, 9 Females)
Age (years) 24.7 (4.8) 23.2 (3.9) 0.31
Height (m) 1.72 (0.1) 1.71 (0.1) 0.82
Weight (kg) 80.1 (13.8) 79.6 (13.5) 0.92
BMI (kg/m2 ) 27.0 (2.7) 27.1 (2.9) 0.93
Note: Mean (SD). a p-values reported are for independent t-tests between intervention groups. BMI = body mass index.

Participants completed, on average, 22.4 ± 1.76 of a possible 24 supervised resistance

training sessions and 7.5 ± 2.1 of a possible 12 home workout sessions (the latter was
self-reported). There was no difference between groups (supervised sessions: IFT group
22.0 ± 2.1, CERT group 22.8 ± 1.3, p = 0.47; unsupervised sessions: IFT group 7.8 ± 2.2,
CERT group 7.1 ± 2.0, p = 0.24).
Nutrients 2022, 14, 3071 6 of 18

3.2. Baseline Cardiometabolic Blood Markers

Of the 34 participants, only 31 successfully had blood taken (IFT = 15, CERT = 16).
Blood draws were attempted and failed on 3 participants. Baseline values for blood lipids,
glucose, insulin, HOMA-IR and hsCRP for the remaining participants (n = 31) are presented
in Table 3. Total cholesterol levels were significantly higher in the IFT group compared to
the CERT group (p = 0.04), independent of sex. No other significant differences were noted
between groups at baseline.

Table 3. Baseline values of cardiometabolic blood markers according to intervention group and sex.

IFT Males CERT Males IFT Females CERT Females IFT Group CERT Group p-Value
Baseline Variable
(n = 8) (n = 8) (n = 7) (n = 8) (n = 15) (n = 16) (Group)
hsCRP (mg/L) 0.94 (0.64) 1.41 (1.63) 2.00 (1.82) 2.43 (1.72) 1.39 (1.34) 1.92 (1.69) 0.26 2
TC (mmol/L) 4.49 (0.79) 4.18 (0.60) 5.17 (1.02) 4.18 (0.75) 4.81 (0.94) 4.18 (0.66) 0.04 1
Triglycerides
0.94 (0.26) 1.20 (0.51) 1.01 (0.36) 0.90 (0.36) 0.97 (0.30) 1.05 (0.45) 0.86 2
(mmol/L)
HDL-C (mmol/L) 1.35 (0.47) 1.15 (0.32) 1.83 (0.46) 1.57 (0.43) 1.57 (0.51) 1.36 (0.42) 0.22
LDL-C (mmol/L) 2.71 (0.63) 2.49 (0.60) 2.86 (0.78) 2.19 (0.45) 2.78 (0.68) 2.34 (0.53) 0.05
Glucose (mmol/L) 4.88 (0.33) 4.90 (0.35) 4.84 (0.42) 4.76 (0.52) 4.86 (0.36) 4.83 (0.44) 0.84
Insulin (mU/L) 3 8.55 (4.54) 10.26 (6.22) 10.40 (2.73) 11.89 (7.69) 9.41 (3.80) 11.08 (6.81) 0.59
HOMA-IR 3 1.88 (1.07) 2.29 (1.60) 2.27 (0.75) 2.61 (2.02) 2.06 (0.92) 2.45 (1.77) 0.64
Note: Mean (SD). 1 Significantly different between IFT and CERT. 2 Data from Mann–Whitney U test. 3 Presented
values are non-transformed, and all analyses were conducted on Log10-transformed values to achieve normality.
HDL-C = high-density lipoprotein cholesterol, hsCRP = high-sensitivity C-reactive protein, HOMA-IR = homeostatic
model assessment of insulin resistance, LDL-C = low-density lipoprotein cholesterol, TC = total serum cholesterol.

3.3. Cardiometabolic Blood Markers before and after Diet and Exercise Invervention
Average values for blood lipids, glucose, insulin, HOMA-IR and hsCRP before and
after the dietary and exercise intervention are shown in Table 4. A main effect for time was
found for TC (p ≤ 0.001), LDL-C (p ≤ 0.001) and HDL-C (p = 0.049), indicating reductions in
each of these markers. There was a significant time x group interaction for TC (p = 0.01) and
LDL-C (p = 0.01), with those in the IFT groups experiencing a reduction compared to those
in the CERT group after adjustment for baseline levels and changes in weight. Furthermore,
there was a significant time x sex x group interaction for TC (p = 0.04), indicating that the
effect of the intervention over time varied depending on sex of the participants, with a
trend towards a time x sex x group interaction for LDL-C (p = 0.07) (time x sex x group
interactions not shown in table). There was a significant main effect of sex on HDL-C levels
(p = 0.049), as well as a time x sex interaction (p = 0.001), with women demonstrating a
greater reduction in HDL-C levels compared to men, irrespective of intervention group.
No other main effects or interactions were found for any other variable.

Table 4. The effects of 12 weeks of IFT or CERT with resistance exercise on cardiometabolic blood markers.

Post P
Diet variable Group Baseline ∆ ∆ (%) P (Time) P (I) P (S)
Intervention (Group)
IFT group (n = 15) 4.81 (0.94) 4.18 (0.71) −0.63 −13.1 0.20 <0.001 1 0.01 2 0.92
CERT group (n = 16) 4.18 (0.66) 3.98 (0.67) −0.20 4.8
TC IFT males (n = 8) 4.49 (0.79) 4.03 (0.68) −0.46 −10.2
(mmol/L) 5 CERT males (n = 7) 4.18 (0.60) 3.79 (0.44) −0.39 −9.3
IFT females (n = 8) 5.17 (1.02) 4.36 (0.76) −0.81 −15.7
CERT females (n = 8) 4.18 (0.75) 4.18 (0.82) 0.00 0.0
IFT group (n = 15) 2.78 (0.68) 2.26 (0.53) −0.52 −18.7 0.19 <0.001 1 0.01 2 0.20
CERT group (n = 16) 2.34 (0.53) 2.17 (0.46) −0.17 −7.3
IFT males (n = 8) 2.71 (0.63) 2.23 (0.51) −0.48 −17.7
LDL-C
CERT males (n = 7) 2.49 (0.60) 2.10 (0.48) −0.39 −15.7
(mmol/L) 5
IFT females (n = 8) 2.86 (0.78) 2.30 (0.58) −0.56 −19.6
CERT females (n = 8) 2.19 (0.45) 2.24 (0.47) 0.05 2.3
IFT group (n = 15) 1.57 (0.51) 1.47 (0.41) −0.10 −6.4 0.23 0.049 1 0.08 0.001 3
Nutrients 2022, 14, 3071 7 of 18

Table 4. Cont.

Post P
Diet variable Group Baseline ∆ ∆ (%) P (Time) P (I) P (S)
Intervention (Group)
CERT group (n = 16) 1.36 (0.42) 1.35 (0.38) −0.01 −0.7
IFT males (n = 8) 1.35 (0.47) 1.38 (0.44) 0.03 2.2
HDL-C
CERT males (n = 7) 1.15 (0.32) 1.21 (0.35) 0.06 5.2
(mmol/L)
IFT females (n = 8) 1.83 (0.46) 1.58 (0.38) −0.25 −13.7
CERT females (n = 8) 1.57 (0.43) 1.50 (0.37) −0.07 −4.6
IFT group (n = 15) 4.86 (0.36) 4.94 (0.30) 0.08 1.6 0.91 0.09 0.55 0.35
CERT group (n = 16) 4.83 (0.44) 4.99 (0.34) 0.16 3.3
IFT males (n = 8) 4.88 (0.33) 4.95 (0.28) 0.07 1.4
Glucose
CERT males (n = 7) 4.90 (0.35) 4.94 (0.27) 0.04 0.8
(mmol/L)
IFT females (n = 8) 4.84 (0.42) 4.93 (0.32) 0.09 1.9
CERT females (n = 8) 4.76 (0.52) 5.05 (0.41) 0.29 6.1
IFT group (n = 15) 9.41 (3.80) 8.89 (2.76) −0.52 −5.5 0.95 0.21 0.29 0.79
CERT group (n = 16) 11.08 (6.81) 8.71 (4.94) −2.37 −21.4
IFT males (n = 8) 8.55 (4.54) 7.38 (2.13) −1.17 −13.7
Insulin
CERT males (n = 7) 10.26 (6.22) 8.56 (5.59) −1.70 −16.6
(mU/L) 4
IFT females (n = 8) 10.40 (2.73) 10.61 (2.43) 0.21 2.0
CERT females (n = 8) 11.89 (7.69) 8.85 (4.59) −3.04 −25.6
IFT group (n = 15) 2.06 (0.92) 1.95 (0.60) −0.11 −5.3 0.96 0.36 0.36 0.73
CERT group (n = 16) 2.45 (1.77) 1.99 (1.30) −0.46 −18.8
IFT males (n = 8) 1.88 (1.07) 1.62 (0.49) −0.26 −13.8
HOMA-IR 4 CERT males (n = 7) 2.29 (1.60) 1.93 (1.38) −0.36 −15.7
IFT females (n = 8) 2.27 (0.75) 2.32 (0.51) 0.05 2.2
CERT females (n = 8) 2.61 (2.02) 2.05 (1.31) −0.56 −21.5
Non-normal Post Signed rank Wilcoxon test (paired samples)
Group Baseline ∆ ∆ (%)
variables Intervention Group/sex Diet group
IFT group (n = 15) 1.39 (1.34) 1.39 (1.66) 0.00 0.0 Z = −1.13, p = 0.26 Z = 0.00, p = 1.00
CERT group (n = 17) 1.92 (1.69)) 1.21 (1.07) −0.71 −37.0 Z = −1.16, p = 0.25 Z = −1.73, p = 0.08
hsCRP IFT males (n = 8) 0.94 (0.64) 0.59 (0.35) −0.35 −37.2 Z = 0.94, p = 0.35
(mg/L) CERT males (n = 7) 1.41 (1.63) 1.07 (1.26) −0.34 −24.1 Z = −1.36, p = 0.17
IFT Females (n = 6) 2.00 (1.82) 2.45 (2.14) 0.45 25.6
CERT females (n = 7) 2.43 (1.72) 1.36 (0.91) −1.07 −44.0
IFT group (n = 17) 0.97 (0.30) 0.98 (0.38) 0.01 1.0 Z = −0.53, p = 0.60 Z = −0.36, p = 0.71
CERT group (n = 17) 1.05 (0.45) 1.02 (0.41) −0.03 −2.9 Z = −1.02, p = 0.31 Z = −0.35, p = 0.73
Triglycerides IFT males (n = 8) 0.94 (0.26) 0.93 (0.35) −0.01 −1.1 Z = −0.18, p = 0.85
(mmol/L) CERT males (n = 7) 1.20 (0.51) 1.06 (0.47) −0.14 −11.7 Z = −0.84, p = 0.40
IFT females (n = 8) 1.01 (0.36) 1.04 (0.44) 0.03 3.0
CERT females (n = 8) 0.90 (0.36) 0.98 (0.37) 0.08 8.9
Note: Mean (SD). 1 Significantly different than baseline at week 12 in all groups combined. 2 Significant time x diet
group interaction. 3 Significant time x sex interaction. 4 Presented values are non-transformed, and all analysis
were conducted on Log10-transformed values to achieve normality. 5 Analysis for TC and LDL-C adjusted
for baseline values and weight change. Group = main effect for diet group, I = time x group interaction,
S = time x sex interaction, Time = main effect for time, HDL-C = high-density lipoprotein cholesterol,
hsCRP = high-sensitivity C-reactive protein, HOMA-IR = homeostatic model assessment of insulin resistance,
LDL-C = low-density lipoprotein cholesterol, TC = total serum cholesterol, IFT = Intermittent Fasting Diet Group,
CERT = Continuous Energy Restriction Diet Group.

Individual changes for participants where main effects were noted (TC, LDL-C and
HDL-C) are shown in Figure 1.
 Nutrients
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14, x FOR 14, 3071
PEER REVIEW 9 of 20 8 of 18

(a)

(b)

(c)
Figure 1. Cont.
 Nutrients
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14, x FOR 14, 3071
PEER REVIEW 10 of 20 9 of 18

(d)

(e)

(f)
Figure 1. Individual
Figure 1. changes from
Individual baseline
changes to post
from intervention
baseline in (a) TC (IFT
to post intervention in group), (b) TC
(a) TC (IFT (CERT
group), (b) TC (CERT
group), (c) group),
LDL-C (IFT group), (d) LDL-C (CERT group), (e) HDL-C (IFT group) and (f) HDL-C
(c) LDL-C (IFT group), (d) LDL-C (CERT group), (e) HDL-C (IFT group) and (f) HDL-C
(CERT group).
(CERT group).

3.4. Self-Reported Dietary Compliance, Hunger, Craving and Mood Levels during the
Intervention Period
3.4.1. Internal Consistency
Nutrients 2022, 14, 3071 10 of 18

3.4. Self-Reported Dietary Compliance, Hunger, Craving and Mood Levels during the Intervention
Period
3.4.1. Internal Consistency
Cronbach’s alpha was used to measure the level of internal consistency for survey
questions grouped in the hunger, cravings, energy levels and mood scores. Based on week
1 responses, alpha values for hunger (0.902), cravings (0.728), energy levels (0.626) and
mood (0.911) indicate relatively high internal consistency for most domains.

3.4.2. Self-Reported Dietary Compliance, Hunger, Cravings and Mood in IFT and CERT
Participants
Self-reported ratings for hunger, cravings, energy levels, mood and compliance were
collected each day over the 12-week intervention period. Although this was a continuous
measure (i.e., surveys were completed daily), for ease of reading, only results from weeks 1,
6 and 12 are reported in Table 5. A graphical representation of the weekly mean values can
be found in Figure 2. There was a main effect found for sex for hunger, indicating higher
values in men (p = 0.03). Furthermore, a main effect for time for mood (p = 0.02) was found,
indicating an increase in mood over time in both groups. No other main effects or any
interactions were found.

Table 5. The effects of 12 weeks of IFT and CERT with resistance exercise on mean ratings of hunger,
cravings, energy levels, mood and compliance.

Survey
Group Week 1 Week 6 Week 12 ∆ ∆ (%) P (Group) P (Time) P (I) P (S)
Variable
IFT group (n = 17) 14.7 (3.9) 13.6 (4.4) 13.7 (5.2) −1.0 −6.8 0.63 0.22 0.49 0.03 2
CERT group (n = 17) 15.0 (5.2) 11.3 (5.1) 13.3 (6.4) −1.7 −11.3
Hunger IFT males (n = 9) 16.5 (3.3) 15.2 (4.9) 13.9 (5.4) −2.6 −15.8
(max. 40) CERT males (n = 8) 15.2 (4.6) 11.4 (3.3) 14.1 (4.7) −1.1 −7.2
IFT females (n = 8) 12.8 (3.8) 11.8 (3.1) 13.6 (5.4) 2.1 6.3
CERT females (n = 9) 14.9 (5.8) 11.2 (6.5) 12.6 (7.8) −2.3 −15.4
IFT group (n = 17) 26.5 (5.0) 30.2 (6.1) 28.7 (8.2) 2.2 8.3
CERT group (n = 17) 28.1 (6.1) 31.4 (7.0) 31.0 (4.6) 2.9 10.3
Cravings IFT males (n = 9) 25.2 (4.9) 29.2 (7.3) 27.9 (5.2) −2.7 −10.7 0.46 0.08 0.96 0.20
(max. 40) CERT males (n = 8) 29.3 (6.1) 30.9 (8.4) 30.6 (5.0) 1.3 4.4
IFT females (n = 8) 28.0 (5.0) 31.4 (4.7) 29.5 (10.8) 1.5 5.4
CERT females (n = 9) 27.1 (6.4) 31.9 (6.0) 31.3 (4.6) 4.2 15.52
IFT group (n = 17) 20.4 (4.6) 22.2 (4.5) 20.4 (6.8) 0.0 0.0
CERT group (n = 17) 20.1 (4.9) 18.8 (4.1) 18.9 (7.7) −1.2 −6.0
Energy
IFT males (n = 9) 21.1 (4.0) 23.2 (3.7) 20.3 (5.5) −0.8 −3.8 0.61 0.77 0.37 0.18
levels
CERT males (n = 8) 21.5 (5.2) 20.2 (5.2) 21.7 (9.0) 0.2 0.9
(max. 40)
IFT females (n = 8) 19.7 (5.3) 21.0 (5.3) 20.6 (8.3) 0.9 4.6
CERT females (n = 9) 18.9 (4.7) 17.6 (2.3) 16.4 (5.8) −2.5 −13.2
IFT group (n = 17) 29.6 (4.5) 29.0 (3.8) 30.7 (4.5) 1.1 3.7 0.06 0.02 1 0.14 0.07
CERT group (n = 17) 25.6 (5.8) 24.0 (7.6) 27.8 (6.8) 2.2 8.6
Mood IFT males (n = 9) 30.0 (5.7) 29.8 (3.6) 31.1 (4.8) 1.1 3.7
(max. 40) CERT males (n = 8) 27.6 (3.0) 24.0 (7.4) 30.7 (2.8) 3.1 11.2
IFT females (n = 8) 29.2 (3.0) 28.2 (4.2) 30.2 (4.5) 1.0 3.4
CERT females (n = 9) 23.8 (7.1) 24.1 (8.1) 25.3 (8.5) 1.5 6.3
IFT group (n = 17) 8.1 (1.1) 8.4 (1.2) 8.7 (1.6) 0.6 7.4
CERT group (n = 17) 8.1 (1.0) 7.6 (1.8) 8.1 (1.3) 0.0 0.0
Compliance IFT males (n = 9) 8.3 (0.8) 8.8 (1.4) 9.4 (0.8) 1.1 13.3 0.25 0.31 0.90 0.08
(max. 10) CERT males (n = 8) 8.5 (0.8) 7.8 (1.6) 8.3 (1.6) −0.2 −2.4
IFT females (n = 8) 8.0 (1.2) 8.1 (0.8) 8.0 (2.0) 0.0 0.0
CERT females (n = 9) 7.7 (1.0) 7.5 (2.0) 7.8 (1.1) 0.1 1.3
Note: Mean (SD). ∆ represents change from week 1 to week 12. 1 Significantly different from weeks 4 and 9 in week
12 in all groups combined. 2 Significant main effect for sex. I = time x group interaction, S = main effect for sex,
Time = main effect for time.
Nutrients 2022, 14, 3071 11 of 18

Figure 2. Weekly mean ratings for hunger (a), cravings (b), energy levels (c), mood (d) and com-
pliance (e) over 12 weeks for CERT and IFT participants. IFT = Intermittent Fasting Diet Group,
CERT = Continuous Energy Restriction Diet Group. * No overlap in 95% confidence intervals.

Weekly mean reported scores over the 12 weeks for hunger, cravings, energy levels,
mood and compliance are shown graphically according to diet group in Figure 2.

3.4.3. Self-Reported Dietary Compliance Hunger, Cravings and Mood Levels in IFT
Participants on Fasting Versus Fed Days
Self-reported ratings for hunger, cravings, energy levels, mood and compliance for
the IFT group according to sex and condition (fasting days versus fed days) are presented
in Table 6. There was a main effect for the conditions of hunger (p ≤ 0.001) and cravings
(p ≤ 0.001), indicating lower scores for hunger and cravings on fed versus fasting days.
Furthermore, there was a main effect of sex for hunger (p = 0.006), cravings (p = 0.04) and
compliance (p = 0.02), indicating lower overall hunger, cravings and compliance ratings in
women than men (including both fasting and fed days).
Nutrients 2022, 14, 3071 12 of 18

Table 6. Mean ratings for hunger, cravings, energy levels, mood and compliance separated by fasting
and fed days in IFT participants over 12 weeks.

Survey
Group Week 1 Week 6 Week 12 ∆ ∆ (%) P (C) P (Time) P (CS) P (S)
Variable
IFT Males (n = 9) fed 11.2 (3.2) 9.7 (3.6) 9.2 (3.5) −2.0 −17.9 <0.001 1 0.32 0.34 0.01 2
Hunger IFT Males (n = 9) fasted 26.5 (5.2) 27.0 (6.3) 26.7 (7.6) 0.2 0.8
(max. 40) IFT Females (n = 8) fed 7.7 (3.1) 6.9 (4.0) 7.6 (2.7) −0.1 −1.3
IFT Females (n = 9) fasted 23.6 (6.0) 21.8 (6.4) 22.4 (5.3) −0.8 −3.4
IFT Males (n = 9) fed 11.9 (4.6) 7.0 (4.9) 8.2 (4.8) −3.7 −31.1 <0.001 1 0.21 0.94 0.04 2
Cravings IFT Males (n = 9) fasted 19.1 (5.4) 18.6 (5.3) 21.8 (6.7) 2.7 14.1
(max 40.) IFT Females (n = 8) fed 7.8 (4.7) 4.6 (3.1) 4.5 (3.6) −3.3 −42.3
IFT Females (n = 9) fasted 19.9 (7.1) 17.4 (8.7) 17.6 (10.6) −2.3 −11.6
IFT Males (n = 9) fed 21.8 (4.7) 23.2 (4.6) 21.8 (4.8) 0.0 0.0 0.31 0.27 0.66 0.69
Energy levels IFT Males (n = 9) fasted 19.3 (5.4) 22.2 (5.0) 19.4 (7.4) 0.1 0.5
(max. 40) IFT Females (n = 8) fed 20.9 (6.7) 21.6 (5.5) 20.8 (7.2) −0.1 −0.5
IFT Females (n = 9) fasted 17.8 (3.7) 19.6 (5.8) 20.4 (7.9) 2.6 14.6
IFT Males (n = 9) fed 30.7 (4.7) 30.4 (3.7) 30.0 (3.8) −0.7 −2.3 0.06 0.09 0.59 0.06
Mood IFT Males (n = 9) fasted 28.5 (6.7) 29.1 (4.2) 28.0 (4.8) −0.5 −1.8
(max. 40) IFT Females (n = 8) fed 30.0 (2.8) 29.1 (3.2) 28.4 (3.8) −1.6 −5.3
IFT Females (n = 9) fasted 26.4 (5.9) 26.5 (4.4) 27.4 (5.7) 1.0 3.8
IFT Males (n = 9) fed 8.1 (0.7) 8.6 (0.9) 8.7 (0.9) 0.6 7.4 0.06 0.26 0.68 0.02 2
Compliance IFT Males (n = 9) fasted 9.1 (1.1) 9.1 (1.2) 9.5 (0.6) 0.4 4.4
(max. 10) IFT Females (n = 8) fed 7.9 (1.4) 7.9 (0.6) 8.0 (1.2) 0.1 1.3
IFT Females (n = 9) fasted 8.6 (1.2) 8.4 (1.9) 8.3 (2.3) −0.3 −3.5

Note: Mean (SD). 1 Significant main effect for condition (fasted/fed). 2 Significant main effect for sex. C = main effect
for condition (fasted/fed), CS = condition x sex interaction, S = main effect for sex, Time = main effect for time.

Correlations between each of the survey measures according to diet group are shown
in Table 7. In the CERT group, there were significant positive correlations between energy
levels and mood (p ≤ 0.001), as well as mood and compliance (p ≤ 0.001). There were also
significant negative correlations between hunger and cravings (p ≤ 0.001), hunger and
mood (p ≤ 0.001) and compliance (p ≤ 0.001); cravings and mood (p ≤ 0.05), and cravings
and compliance (p ≤ 0.001). In the IFT group, there was a significant negative correlation
between: hunger and cravings (p ≤ 0.001), and significant positive correlations between
energy levels and mood (p ≤ 0.001); and mood and compliance (p ≤ 0.001).

Table 7. Bivariate correlations between survey measures according to intervention group.

Survey Variable Hunger Cravings Energy Levels Mood Compliance

CERT
Hunger 1.00 −0.52 1 0.04 −0.39 1 −0.26 1
Cravings 1.00 −0.07 −0.15 2 −0.33 1
Energy Levels 1.00 0.51 1 0.11
Mood 1.00 0.34 1
Compliance 1.00
IFT
Hunger 1.00 −0.71 1 0.10 −0.12 −0.05
Cravings 1.00 0.02 0.10 −0.02
Energy Levels 1.00 0.54 1 0.06
Mood 1.00 0.26 1
Compliance 1.00
Note: Spearman’s rho. 1 Significant correlation (p < 0.001). 2 Significant correlation (p < 0.05)

Responses to the post-intervention questionnaire are presented in Table 8. There

was no significant difference between how easy each group found it to comply with their
allocated diet. Only four participants in the IFT group and three in the CERT group reported
that they would have preferred to have been in the other dietary group. Additionally,
whereas 14 participants in the IFT group and 15 in the CERT group indicated that they
would continue with their diet after the intervention period, only 3 indicated that they
would keep their diet the same as it had been prescribed. Common modifications that
participants intended to make to their diets were lowering protein intake (n = 4) or, in the
IFT group specifically, reducing the number of fasting days (n = 5) or changing intake to
Nutrients 2022, 14, 3071 13 of 18

solid food or no intake at all on fasting days (n = 5). The most common difficulty noted by
participants was complying with their diet during social encounters (IFT = 13, CERT = 14).

Table 8. Post-intervention questionnaire responses to the dietary intervention in IFT and CERT
participants.

How Easy Was It to Comply with Your Diet? Mean Score

p-Value
(0 = Not Easy at All 10 = Extremely Easy) (SD)
IFT 6.6 (1.8)
0.36
CERT 7.1 (1.3)
Would you have preferred to have been in the other
Yes No
diet group?
IFT 4 13
CERT 3 14
Will you continue with your diet after the
Yes No
intervention period has finished?
IFT 14 * 3
CERT 15 * 2
* Only one participant in the IFT group and two in the CERT group indicated that they would continue with their
diet as prescribed; the remainder from each group noted that they would modify it in some way.

4. Discussion
The main findings from this secondary outcomes analysis were that both energy-
restricted diets significantly reduced TC and LDL-C levels over the 12-week intervention
period. These reductions were significantly greater in the IFT group compared to the
CERT group, even after adjustment for baseline values and weight loss. HDL-C was also
significantly decreased, albeit only in females. There were no significant differences in
triglycerides, hsCRP or measures of insulin resistance over time or between interventions.
Both groups reported high levels of dietary compliance and low levels of hunger. Finally,
the majority of participants displayed an intention to continue with their respective diets,
albeit generally in modified forms, emphasising that flexibility may be required when
considering the long-term feasibility of different energy-restricted diets.

4.1. Cardiometabolic Biomarkers

The cohort of participants enrolled in the present study was, on average, overweight
but metabolically healthy according to their baseline BMI and cardiometabolic blood
markers, respectively. Over the 12-week intervention period, individuals undertaking IF
displayed significantly greater reductions in TC and LDL-C compared to those undertaking
CER. These results are somewhat in contrast to results of a recent systematic review and
meta-analysis that found CER to be more effective at reducing TC compared to IF, although
comparable effects on LDL-C levels were noted between diets [26]. In the present analysis,
there was a significant time x group x sex interaction for TC and a trend toward significance
for LDL-C, indicating that differences in TC and LDL-C levels between the IFT and CERT
groups were likely driven by a varying response to the intervention, depending on sex.
There was a notable lack of change in females undertaking CER (TC: 0.0% and LDL-
C: +2.5%), whereas all other intervention/sex combinations demonstrated reductions in
the order of ~10% to 20% in these markers. Although it is known that the amount of
weight loss [27] and baseline values of TC and LDL-C [26] can influence changes in these
markers during lifestyle interventions, this interaction remained significant after adjusting
for both. It is not readily apparent why women in the IFT group experienced greater
changes compared to those in the CERT group. Some previous studies in animal models
have demonstrated sex-specific changes in response to calorie restriction [28,29], and it
is possible that hormonal, divergent nutrient-sensing pathway activation in response to
energy restriction and other mechanisms may be at play [30]. Nonetheless, in humans,
research comparing CER and IF in females specifically have shown no differences in
changes to TC or LDL-C (albeit utilizing endurance rather than resistance training) [31,32].
Nutrients 2022, 14, 3071 14 of 18

Given the limited number of studies in females within this area and the limited sample size
in our study, more research is clearly needed to clarify potential sex differences.
Markers of glucose regulation were not significantly impacted over the 12-week period,
regardless of dietary intervention and exercise training. However, male participants in
both dietary groups demonstrated an average reduction in HOMA-IR of approximately
14–16%. Similarly, females also demonstrated an average reduction in HOMA-IR of ~22%
but only within the CERT group. This is in contrast to the observations in TC and LDL-C
levels discussed above, where changes were observed in females in the IFT group only. The
absence of improvement in HOMA-IR among females undertaking IF was likely driven by
a lack of change in insulin levels (+2%), whereas all other groups demonstrated reductions
of between 14–26%, on average. Whereas this potentially points to sex-specific responses,
as discussed previously, the findings are congruent with some previous human research
demonstrating increases in fasting insulin in overweight females following a period of
IF [33]. Hutchison and colleagues [33] observed increased fasting insulin levels when
measured after a fed day (although decreased levels after a fasted day) following 8 weeks
of alternate-day fasting in individuals who were prescribed a protocol designed to maintain
weight. The participants in the Hutchison study, who were, on average, much older than
the participants in the current analysis (~50 vs. ~24 years old) did show similar modest
weight loss compared to the IFT women in our group (~2.7 kg; see previously published
findings [21]), and this could explain the lack of beneficial effects on glucose regulation.
Hutchison et al. [33] included another energy-restricted alternative day fasting intervention
group that experienced greater amounts of weight loss (5.4 kg), who experienced significant
reductions in fasting insulin when measured after both a fed and fasted day. Differences
between these groups in terms of insulin levels were only significant when tested after a
fed day. As our participants were only tested after a fed day, we cannot determine whether
a reduction in insulin would have been observed if tested after a fasted day. Nonetheless,
this raises the possibility that meaningful amounts of weight loss may be required for IF to
confer consistently beneficial effects on glucose homeostasis. It is important to note that
the length (i.e., consecutive fasting days) [11] or timing of fasts (i.e., early time-restricted
feeding) [10,34] may be a determining factor with respect to whether or not IF provides
additional benefits for glucose homeostasis. When utilizing a 5:2 IF regime that involved
consecutive fasting days, Harvie et al. [31] showed a benefit over that of CER for HOMA-IR,
despite similar weight loss between groups. Thus, it is possible that the protocol in the
present study did not invoke fasting periods of sufficient duration or promote consumption
at appropriate times to result in improvements in glucose regulation over and above that
caused by weight loss.

4.2. Dietary Compliance, Mood, Hunger and Cravings

Participants reported similarly high rates of dietary compliance (~80%) in both the IFT
and CERT groups. These results are comparable to those of most other studies that have
compared 5:2 IF and CER, which reported compliance rates in the range of 56–97% over
3 months, with no differences between diets [31,35–37]. However, a number of factors in
the present study likely promoted high levels of dietary compliance in both groups. First,
participants were in regular contact with the study dietitian, who was also the strength
and conditioning coach, during the supervised resistance training sessions, and frequency
of contact likely improves compliance in dieting individuals [38]. Secondly, customised
meal plans for each participant that were tailored to individual preferences and habitual
diet [39,40], as well as the provision of meal replacement shakes [41] on fasting days for
those in the IFT group. may have further helped to promote compliance. Lastly, partici-
pants were asked to self-record their dietary intake three times during the course of the
study; however, many decided to track their intake continuously throughout the 12-week
intervention. Self-monitoring dietary intake has been consistently shown to improve com-
pliance with weight-loss regimens [42]. Importantly, these strategies are largely consistent
with previous studies that have compared 5:2 and CER, which have generally provided
Nutrients 2022, 14, 3071 15 of 18

regular dietary counselling or motivational support while also providing meal plans or
food portion lists for individuals [31,32,36,37,43]. Although these strategies may help
improve study fidelity, it is intriguing to consider how these diets might compare without
the same level of support. Nonetheless, our findings add further weight to the notion that
individuals show high levels of compliance to either diet in the short-to-medium term
when combined with adequate professional support.
In the current study, participants reported relatively low levels of hunger. It is often
proposed that hunger may be a limiting factor with respect to the success of restrictive diets,
especially with IF [43]. Whereas a number of other studies have shown that hunger does not
differ between those following an IF-style diet compared to CER [32,35], one longer-term
intervention (1 year) showed that hunger levels were higher in those undertaking IF [43].
Together with our results, this suggests that hunger is unlikely to undermine compliance
with either diet, at least in the short-to-medium term, although more longer-term studies
including measures of hunger are necessary. Conversely, cravings appeared to be relatively
high in both groups in the current study, which could compromise long-term compliance
with either diet. Despite similar levels of hunger and cravings reported between dietary
groups, there were clear differences in such ratings between fasting and fed days in the
IFT group. Participants reported significantly higher levels of hunger and cravings, as
well as slightly reduced mood and energy levels on fasting days compared to fed days.
However, compliance was still high on fasting days, potentially indicating the acceptability
of short-term, severe restriction.
Mood was positively correlated with compliance in both groups, perhaps signifying
greater ability of participants to comply with their assigned diet when their mood was
better (although not precluding the possibility that greater compliance led to improved
mood). The CERT group showed a significant negative correlation between hunger and
mood, as well as between hunger and compliance—associations not observed in the IFT
group. On the other hand, participants in the IFT group appeared to experience a reprieve
from high levels of hunger and poorer mood on non-fasting days, reporting significantly
lower ratings compared to fed days. This is an important consideration for practitioners
when recommending dietary interventions, given that an individual’s capacity to self-
regulate may be limited. Furthermore, given the tendency of individuals to adopt an ‘all-or-
nothing’ approach to dieting, a dietary lapse can often lead to reactionary overeating [44],
compromising weight loss. CER provides a greater opportunity for this to occur than IF,
which could be exacerbated if this type of dieting also causes poorer mood. Nonetheless,
this is speculative, and there remains a paucity of long-term studies that include measures
of compliance, hunger and mood.
Following the completion of the intervention period, participants were asked to rate
the ease with which they were able to comply with their diet. Participants rated IFT and
CERT as a 6.6 and 7.1 out of 10, respectively. These values are lower than those reported
in other studies at 3, 6 and 12 months when comparing 5:2 IF and CER [43]. This may
have been due to the nature of the prescribed diets, namely a higher recommended protein
intake and liquid meals on fasting days for the IFT group. Nearly half of all participants in
the current study reported difficulty meeting the protein targets (IFT = 5, CERT = 10), and
half of those in the IFT group noted that they would have preferred solid foods instead of
liquid meals on fasting days. This was reflected further in the intentions of the participants
at the end the intervention period. Whereas a large majority indicated they would continue
with their diet protocols post intervention, only a few intended to continue as originally
prescribed. Common changes that participants planned to make were a reduction in protein,
regardless of dietary group, as well as a reduction in the number of fasting days and/or
the use of solid meals instead of liquid meals on fasting days for those in the IFT group.
Interestingly, in one of the few other studies to utilise liquid meals for their 5:2 IF fasting
group, Harvie et al. [31] showed that a much smaller proportion of 5:2 IF participants
(58%) planned to continue with their diet after the 6-month intervention compared to the
CER group (85%). Conversely, Sundfør et al. [4] showed that participants in both 5:2 IF
Nutrients 2022, 14, 3071 16 of 18

(utilising consumption of solid food on fasting days) and CER diet groups had comparably
strong intentions to continue with their diet after 12 months. Thus, although both diets
appear to be tolerable, flexibility and customisation with regard to how energy deficits are
implemented may be important for long-term compliance. It should also be noted that the
vast majority of participants from both groups (CERT = 14, IFT = 13) reported difficulty
complying with their diet during social situations, with 1 participant in the IFT group
also reporting avoiding going out on fasting days. This could also have implications for
long-term compliance and quality of life, further emphasising the need for interventions
that allow for some flexibility.
There were a number of strengths of this study. First, both diets were matched for
protein intake and energy restriction; therefore, any differences observed between groups
may be more likely due to differing intake patterns (i.e., IF versus CER) rather than major
differences in nutrient intake. Secondly, we utilised continuous data to analyse dietary
compliance, as well as changes in hunger, cravings and mood, with questionnaires based
on previously validated scales. However, our study is also subject to several limitations. De-
spite the continuous nature of the questionnaires, the frequency of the collection (i.e., daily)
also led to decreased response rates over time and potentially introduced habituality to
the nature of responses. Furthermore, a lack of preintervention testing precluded analysis
of baseline differences in hunger, cravings and mood. We also failed to take into account
menstrual cycles in women, which may impact a number of the variables we measured, in
particular, hunger, cravings and mood. Finally and importantly, this study was powered to
detect differences in the primary outcome for this intervention (lean body mass); therefore
the results should be interpreted with caution and considered exploratory.
The results from our secondary outcome analysis demonstrate that IF and CER com-
bined with resistance exercise can improve cardiometabolic risk biomarkers in overweight
but metabolically healthy adults, with greater improvements in IF independent of weight
change and baseline TC and LDL-C levels. Both energy restriction strategies resulted in
low levels of hunger over the 12 weeks, which may have contributed to the high levels of
compliance, along with the support and guidance provided in the study. Importantly, both
dietary strategies were viewed favourably, with participants indicating that they would con-
tinue with their prescribed diets. However, most planned to do so with minor modifications,
indicating that flexibility and customisation may be important for long-term compliance.

Author Contributions: Conceptualization, S.K., R.B., M.B.C. and S.W.; methodology, S.K., R.B.,
M.B.C. and S.W.; formal analysis, W.S.C. and S.K.; investigation, S.K, R.B. and M.B.C.; writing—
original draft preparation, S.K. and M.B.C.; writing—review and editing, S.K., R.B., M.B.C., S.W. and
W.S.C. All authors have read and agreed to the published version of the manuscript.
Funding: SK was supported by a student scholarship from Swinburne University.
Institutional Review Board Statement: This study was approved by the Swinburne University of
Technology Human Research Ethics Committee (project #2018/322).
Informed Consent Statement: Informed consent was obtained from all subjects involved in the
study.
Data Availability Statement: The data presented in this study are available on request from the
corresponding author. The data are not publicly available due to ethical considerations.
Acknowledgments: The authors would like to acknowledge Josef Sullivan for his contribution to the
statistical analysis. We would also like to acknowledge Formulite for providing all meal replacement
shakes given to participants in the initial trial.
Conflicts of Interest: The authors declare no conflict of interest.

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