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REVIEW
Alternate-day versus daily energy restriction diets: which is more
effective for weight loss? A systematic review and meta-analysis
B. A. Alhamdan
1
, A. Garcia-Alvarez
1
, A. H. Alzahrnai
1
, J. Karanxha
2
, D. R. Stretchberry
3
, K. J. Contrera
4
,
A. F. Utria
4
and L. J. Cheskin
1
1
Department of Health, Behavior and Soci-
ety, Johns Hopkins Weight Management
Center, Johns Hopkins Bloomberg School
of Public Health, Baltimore, MD, USA;
2
Department of Biochemistry and Molecu-
lar Biology, Johns Hopkins Bloomberg
School of Public Health, Baltimore, MD,
USA;
3
Department of International Health,
Johns Hopkins Bloomberg School of Public
Health, Baltimore, MD, USA;
4
Johns
Hopkins University School of Medicine,
Baltimore, MD, USA
Received 23 November 2015; revised 3
June 2016; accepted 12 June 2016
Address for correspondence: B Alhamdan,
MD, MPH, Department of Health, Behavior
and Society, Johns Hopkins Bloomberg
School of Public Health, 550 N. Broadway
Suite 1001, Baltimore, MD 21205, USA.
E-mail: alhamdan2113@hotmail.com
Summary
Background
Alternate-day-fasting (ADF) has been proposed as an effective dieting method. Studies
have found that it also can increase life span in rodents, and reduce inflammation in
humans. The aim of this paper was to systematically review the efficacy of ADF com-
pared to very-low-calorie dieting (VLCD) in terms of weight loss, and reduction of fat
mass and fat-free mass.
Methods
Systematic review: PubMed literature searches were performed. Fixed review procedures
were applied. Studies were evaluated for quality. Twenty-eight studies were included.
Meta-analysis: 10/28 studies (four ADF and six matched VLCD) were further analyzed.
Results
After adjustment for BMI and duration, there was no significant difference in mean body
weight loss (VLCD 0.88 kg more weight loss than ADF, 95% CI: 4.32, 2.56) or fat-free
mass (VLCD 1.69 kg more fat-free mass loss than ADF, 95% CI: 3.62, 0.23); there
was a significant difference observed in fat mass (ADF 3.31 kg more fat mass loss than
VLCD, 95% CI: 0.05, 6.56). Meta-analysis showed that, among ADF studies, the pooled
change in body weight, fat mass and fat-free mass was 4.30 kg (95% CI: 3.41, 5.20),
4.06 kg (95% CI: 2.99, 5.13) and 0.72 kg (95% CI: 0.07, 1.51), respectively, while among
VLCD studies, the pooled change was 6.28 kg (95% CI: 6.08, 6.49), 4.22 kg (95% CI:
3.95, 4.50) and 2.24 kg (95% CI: 1.95, 2.52), respectively.
Conclusions
Our results from both the systematic review and the meta-analysis suggest that ADF is
an efficacious dietary method, and may be superior to VLCD for some patients because
of ease of compliance, greater fat-mass loss and relative preservation of fat-free mass.
Head-to-head randomized clinical trials are needed to further assess relative efficacy of
these two approaches.
Keywords: Alternate-day fasting, fat mass, obesity, very-low-calorie diet.
Introduction
In 2014, there were more than 1.9 billion adults classified
as overweight, of which 600 million were classified as
obese (11% of men and 15% of women). These figures
are double what they were in the 1980s, a clear indication
that obesity is spreading widely across the globe. The
obesity epidemic is now associated with more deaths
globally than underweight (1).
A widely used strategy to lose weight is caloric restriction
(CR) (2). A common CR method that became popular in
the 1980s was very-low-calorie dieting (VLCD) (3). VLCD
is by definition prescribing fewer than 800 calories to be
consumed daily (4). Although VLCD has been shown to
© 2016 The Authors.
Obesity Science & Practice published by John Wiley & Sons Ltd, World Obesity and The Obesity Society. Obesity Science & Practice 293
Obesity Science & Practice doi: 10.1002/osp4.52
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be an effective weight loss strategy in the short term (3), it
has also been argued that its risk of weight regain is
greater due to its association with binge eating disorder
(5), behavioural fatigue (6) and loss of fat free mass (7).
Intermittent CR regimens were designed to improve
adherence (8). An intermittent CR regimen that has
recently emerged is alternate-day-fasting (ADF). With
ADF, there is a fasting day, during which typically 25%
of the dieter’s estimated energy needs (typically <800
calories/day) are consumed, followed by a normal feeding
day when food and liquids are consumed ad libitum (9).
ADF has been associated with lower risk of weight regain,
perhaps due to better compliance (10) and with relative
preservation of fat-free mass (7).
Aside from the possible weight control benefits, at least
in some animal studies, fasting or ADF appears to have
multiple health-promoting effects, notably related to ag-
ing, cancer, inflammation and neurodegeneration (11).
With respect to aging, one study has suggested that
ADF can increase the life span of rodents by up to 80%.
The possible mechanism of this effect is that fasting de-
creases glucose levels and insulin-like growth factor
(IGF-1), which are aging promoters (12). With respect to
cancer, a study has suggested that ADF greatly reduces
the incidence of lymphoma in mice (13), and another
study found that fasting one day per week may delay on-
cogenesis in p53-missing mice (14). In addition, a recent
study concluded that by reducing glucose levels, insulin
and ketone bodies, intermittent fasting may create a diffi-
cult environment for cancer cells to survive, thus improv-
ing the action of chemotherapeutic agents (15).
In humans, a recent study has shown that intermittent
fasting reduces oxidative stress and inflammation and it
improves cellular glucose uptake and insulin sensitivity
(11). In addition, two studies have shown that fasting
may improve neurologic function in the following ways:
by increasing the levels of antioxidants, neurotropic fac-
tors and protein chaperones, and reducing the level of
pro-inflammatory markers (16), and by upregulating the
expression of synaptic plasticity-related proteins, as well
as anti-apoptotic pathways (17).
In terms of body composition, a study showed that in-
termittent fasting reduces body weight, fat mass, waist
circumference and blood pressure (18). The same authors
stated that the metabolic effects of intermittent fasting
include reductions in total cholesterol, LDL and trigly-
cerides, as well as improvement of satiety through re-
ductions in Leptin and Resistin, and increases in
Adiponectin (18).
A recent review comparing weight loss reported using
daily CR and intermittent CR found that intermittent CR
was as effective as daily CR in reducing body weight as
well as in preserving fat-free mass (7). In the present
review, we compared two types of severely energy-
restricted diets, achieved through either daily energy
restriction or every-other-day energy restriction.
We systematically reviewed the efficacy of ADF diets
compared to VLCD (the control) in terms of weight loss,
and reduction of fat mass and fat-free mass. Our objec-
tive was to explore the hypothesis that ADF could be an
effective alternative to more restrictive dieting ap-
proaches, namely VLCD.
Methods
Data sources
Literature searches were conducted using PubMed,
with the time frame of publication 1 January 2000 to 30
September 2015. An example of search commands is
detailed as follows:
(Caloric restriction [tiab] OR VLED [tiab] OR LED [tiab]
OR very low energy diet [tiab] OR low energy diet [tiab]
OR LCD [tiab] OR 25% energy deficit weight loss diet
[tiab] OR calorie restriction [tiab] OR Modifast [tiab] OR
very-low-calorie diet [tiab] OR dietary restriction [tiab]
OR daily energy restriction [tiab] OR VLCD [tiab] OR
energy restriction [tiab] OR low calorie [tiab] OR very low
calorie dietary intervention [tiab] OR continuous energy
restriction [tiab] OR CER [tiab] OR continuous diet[tiab]
OR alternate day fasting[tiab] OR ADF[tiab] OR every
other day fast[tiab] OR ADMF[tiab] OR ad libitum every
other day[tiab] OR ADCR diet[tiab] OR alternate day calo-
rie restriction[tiab] OR modified alternate fasting[tiab] OR
intermittent fasting[tiab] OR diet in every other day[tiab] )
AND "weight loss"[Mesh]
Study selection and criteria
The following exclusion criteria were applied: case re-
ports, letters, comments, reviews or animal studies;
languages other than English; and publication date other
than from 1 January 2000 to 30 September 2015. The
following inclusion criteria were applied: adults aged
18–70 years, with BMI ≥25 kg/m
2
, good general state of
health (i.e. without a diagnosed condition), on only very-
low-energy diets (<800 calories/d) for VLCD studies and
interventions lasting between 3 and 12 weeks.
Data extraction
Studies were selected for data extraction if they met the
above inclusion and exclusion criteria and reported at
least weight loss data. We only included study arms
where diet only was used; we excluded any arms that
used physical activity or drugs to ensure better
294 Alternate-day fasting versus daily energy restriction B. A. Alhamdan et al. Obesity Science & Practice
© 2016 The Authors.
Obesity Science & Practice published by John Wiley & Sons Ltd, World Obesity and The Obesity Society. Obesity Science & Practice
comparability between study interventions. Sample size
and intervention length were recorded. Characteristics
of the initial study sample (e.g. age, sex and weight),
baseline body weight, fat mass, fat-free mass and waist
circumference were captured when available. Conversion
of units to keep data comparable was implemented when
necessary. Two reviewers independently reviewed the
studies, extracted data and then resolved disparities by
agreement (Supplementary Table S1, available as Sup-
plementary data at OSP online).
Quality assessment
Two reviewers used the Downs and Black quality check-
list to assess the risk of study bias (ROB) for each in-
cluded study (19): (i) low ROB: when a study fulfilled all
the following criteria: stated the objective, described the
main outcomes, described the characteristics of the en-
rolled subjects, clearly described the interventions, de-
scribed the main findings, randomized the subjects to
the intervention groups, concealed the intervention as-
signments until recruitment was complete and partially
or fully described the distribution of potential confounders
in each treatment group; (ii) moderate ROB: if a study did
not fulfil one of the above criteria, or if such could not be
verified and (iii) high ROB: if a study did not fulfil more
than one of the above criteria.
Statistics and meta-analysis
All statistical analysis were pre-specified. The dietary in-
terventions were grouped into two sets: ADF and VLCD.
Study-level data were summarized using descriptive sta-
tistics. If not reported, the standard error of means were
computed using the following formula: SE = SD/ √n.
STATA 14 was used both for the meta-analysis and the
meta-regression. The random-effects meta-analysis ap-
proach was performed to estimate the overall difference
in each intervention. Meta-regression models were used
to adjust for BMI and length of intervention. The residual
maximum-likelihood method was used to estimate the
additive (between-study) component of variance Tau
2
.
Heterogeneity was tested using I
2
test. The p-values cal-
culated by Monte Carlo permutation test were used to ad-
dress multiple testing. A statistically significant difference
was defined by a p-value less than 0.05.
Results
Data retrieval
A flow chart showing the systematic review process is
provided in Figure 1. The initial search resulted in 2,357
publications. After applying the exclusion criteria, 627
remained. The full text of these studies was then re-
trieved, and after screening for inclusion criteria, data
were extracted from 28 studies, 6 ADF and 22 VLCD
studies. Four articles contributed to more than one arm
of the analysis. Only the 10 studies that reported the
change with standard errors for all three outcomes of in-
terest (i.e. weight loss, fat mass and fat-free mass were
included in the meta-analysis) (Figure 1).
Characteristics of study participants
A total of 1,193 study participants were included in the
analyses, 132 who underwent ADF and 1,060 who
underwent VLCD. For ADF studies reporting this informa-
tion, mean age of participants was 42.33 years, 92.42%
were female, mean BMI was 33.17 kg/m
2
, mean baseline
body weight was 90.28 kg, mean fat mass was 38.06 kg,
mean fat-free mass was 48.32 kg and mean waist circum-
ference was 97.70 cm. For the VLCD studies, mean age of
participants was 40.04 years, 67.76% were female, mean
BMI was 31.15 kg/m
2
, mean baseline body weight was
83.55 kg, mean fat mass was 31.34 kg, mean fat-free
mass was 44.52 kg and mean waist circumference was
100.56 cm (Table 1A).
Characteristics of included studies
For the included ADF studies, one was published be-
tween 2000 and 2010, and five between 2011 and 2015.
Two studies had intervention durations of 3–8 weeks,
and four 9–12 weeks. Four studies were conducted in
North America and two in Asia. Of the included VLCD
studies, 14 were published between 2000 and 2010,
and eight between 2011 and 2015. Eighteen had interven-
tion durations of 3–8 weeks, and four 9–12 weeks. Nine-
teen were conducted in Europe and three in Australia
(Table 1B).
Of the 28 studies included in the systematic review
(Supplementary Table S2, available as Supporting Infor-
mation at OSP online), after applying quality assessment
based on Downs and Black criteria (19), 20 had high
ROB, 7 had moderate ROB and 1 had low ROB. Of the
10 studies used in the meta-analysis, 5 had high ROB
and 5 had moderate ROB.
Missing data
Gender reporting was missing in three studies, age
reporting in six and BMI reporting in one study. Baseline
body weight was missing in 3 studies, fat mass in 11,
fat-free mass in 18 and waist circumference in 12 studies.
Obesity Science & Practice Alternate-day fasting versus daily energy restriction B. A. Alhamdan et al. 295
© 2016 The Authors.
Obesity Science & Practice published by John Wiley & Sons Ltd, World Obesity and The Obesity Society. Obesity Science & Practice
Characteristics of the studies included in the
meta-analysis
Table 2A details the 10 studies included in the meta-
analysis: 4 ADF and 6 VLCD. Mean age of the 662 par-
ticipants included in the meta-analysis was 44.69
± 1.9years, mean BMI was 31.31kg/m
2
and 78.06% were
females. ADF studies were all grant funded, while all of
the VLCD studies were industry funded.
Meta-analysis results
Unadjusted values show that compared to the VLCD
studies, ADF participants had a smaller loss in body
weight (1.99 kg, 95% confidence interval [CI]: 2.94,
1.04) and a smaller loss in fat-free mass (1.60 kg,
95% CI: 2.40, 0.80), while no significant change was
observed between diet interventions in fat mass
(0.16 kg, 95% CI: 1.19, 0.87) (Table 2B).
After adjustment for BMI and duration of the dietary
intervention, there was no significant difference between
interventions in body weight (0.88 kg, 95% CI: 4.32,
Figure 1 Flow chart of the systematic review process.
Table 1A Patient characteristics
Patient characteristics ADF (132) VLCD (1,060)
Age (years) 42.33 40.04
Females (%) 92.42 67.76
BMI (kg/m
2
) 33.17 31.15
Body weight (kg) 90.28 83.55
Fat mass (kg) 38.06 31.34
Fat-free mass (kg) 48.32 44.52
Waist circumference (cm) 97.70 100.56
ADF, alternate-day fasting; BMI, body mass index; VLCD, very-low-
calorie-diets.
Table 1B Study characteristics
Study
characteristics
Number of
studies
(ADF)
Number of
participants
Number
of studies
(VLCD)
Number of
participants
Publication year
2000–2010 1 16 14 883
2011–2015 5 116 8 177
Intervention
length
3–8 weeks 2 41 18 917
9–12 weeks 4 91 4 143
Study location
North America 4 91
Europe 19 1,000
Asia 2 41
Other 3 60
ADF, alternate-day fasting; VLCD, very-low-calorie-diets.
296 Alternate-day fasting versus daily energy restriction B. A. Alhamdan et al. Obesity Science & Practice
© 2016 The Authors.
Obesity Science & Practice published by John Wiley & Sons Ltd, World Obesity and The Obesity Society. Obesity Science & Practice
2.56) or fat-free mass (1.69 kg, 95% CI: 3.62, 0.23)
(Table 2B). There was a significant difference between in-
terventions in that the adjusted loss of fat mass on the
ADF regimens was 3.31 kg greater than on the VLCD reg-
imens (95% CI: 0.05, 6.56).
Regarding change in body weight, Figure 2 shows that,
among ADF studies, the smallest reduction was 3.00 kg
(95% CI: 1.04, 4.96) and the greatest reduction was
5.60 kg (95% CI: 3.64, 7.56). The pooled change was
4.30 kg (95% CI: 3.41, 5.20). Among the VLCD studies,
the smallest reduction in body weight was 5.79 kg (95%
CI: 4.92, 6.65) and greatest reduction was 6.40 kg (95%
CI: 5.81, 6.98). The pooled change was 6.28 kg (95% CI:
6.08, 6.49).
With regard to change in fat mass, Figure 3 shows that,
among ADF studies, the smallest reduction was 2.00 kg
(95% CI: 0.04, 3.96) and the greatest was 5.40 kg (95%
CI: 3.83, 6.97). The pooled change was 4.06 kg (95% CI:
2.99, 5.13). For the VLCD studies, the smallest reduction
in fat mass was 3.90 kg (95% CI: 3.31, 4.49) and greatest
was 5.00 kg (95% CI: 4.41, 5.59). The pooled change was
4.22 kg (95% CI: 3.95, 4.50).
For change in fat-free mass, Figure 4 shows that,
among ADF studies, the smallest reduction was 0.10 kg
(95% CI: 0.1, 0.30) and the greatest 1.60 kg (95% CI:
0.62, 2.58). The pooled change was 0.72 kg (95% CI:
0.07, 1.51). Among the VLCD studies, the smallest re-
duction was 1.33 kg (95% CI: 0.59, 2.07) and the greatest
2.50 kg (95% CI: 2.10, 2.89). The pooled change was
2.24 kg (95% CI: 1.95, 2.52).
Discussion
This is the first paper to perform a systematic review to-
gether with a meta-analysis comparing ADF and VLCD
regimens in terms of weight, fat mass and fat-free mass
reduction.
Our meta-analysis shows that both dietary inter-
ventions are efficacious, resulting in substantial body
weight loss. Although the magnitude of weight loss by
Table 2A Studies included in the meta-analysis
Name Sample
size (n)
Females
(%)
Age *
(years)
Baseline
BMI*
Length
(weeks)
Change in body
weight* (kg)
Change in fat mass*
(kg)
Change in fat-free
mass* (kg)
ADF
Varady, 2013 (20) 15 66 47 ± 3.0 26 ± 1.0 12 5.20 ± 0.9 3.60 ± 0.7 1.60 ± 0.5
Bhutani, 2013 (21) 25 96 40 ± 2.0 35 ± 1.0 12 3.00 ± 1.0 2.00 ± 1.0 1.00 ± 1.0
Klemple, 2013 (HF) (9) 17 100 42 ± 3.0 35 ± 0.7 8 4.30 ± 1.0 5.40 ± 1.5 1.10 ± 1.3
Klemple, 2013 (LF) (9) 18 100 43 ± 2.0 36 ± 0.7 8 3.70 ± 0.7 4.20 ± 0.6 0.50 ± 0.7
Varady, 2009 (10) 16 75 46 ± 2.0 34 ± 1.0 8 5.60 ± 1.0 5.40 ± 0.8 0.10 ± 0.1
VLCD
Munro, 2013 (placebo)
(22)
19 79 47 ± 2.0 34 ± 0.8 4 5.79 ± 0.4 4.19 ± 0.4 1.33 ± 0.4
Munro, 2013 (fish oil)
(22)
20 75 45 ± 2.0 31 ± 0.6 4 6.12 ± 0.3 4.36 ± 0.3 1.68 ± 0.3
Westerterp-P, 2005
†
(23)
76 70 28 ± 0.3 4 5.90 ± 0.2 5.00 ± 0.2 2.50 ± 0.5
Lejeune, 2005 (24) 113 45 ± 1.0 29 ± 0.2 4 6.30 ± 0.3 4.00 ± 0.3 2.30 ± 0.2
Westerterp-P, 2004
(25)
148 44 ± 0.8 30 ± 0.2 4 6.40 ± 0.1 3.90 ± 0.3 2.50 ± 0.2
Kovacs, 2004 (26) 104 75 30 ± 0.3 4 6.40 ± 0.3 4.00 ± 0.3 2.40 ± 0.3
Lejeune, 2003 (27) 91 29 ± 0.3 4 6.60 ± 0.2 4.10 ± 0.2 2.50 ± 0.2
*Mean + SEM.
†
Numbers were computed from one figure of the article.
ADF, alternate-day fasting; BMI, body mass index; HF, high fat group; LF, low fat group; VLCD, very-low-calorie-diets.
Table 2B Meta-regression results
Variables Unadjusted (95% CI) P-value Adjusted (95% CI) P-value
Body weight (kg)
ADF 1.99 (2.94, 1.04) <0.01 0.88 (4.32, 2.56) 0.57
BMI 0.08 (0.26, 0.09) 0.28
Length 0.14 (0.68, 0.40) 0.56
Fat mass (kg)
ADF 0.16 (1.19, 0.87) 0.73 3.31 (0.05, 6.56) 0.05
BMI 0.10 (0.27, 0.06) 0.19
Length 0.57 (1.08, 0.05) 0.03
Fat-free mass (kg)
ADF 1.60 (2.40, 0.80) <0.01 1.69 (3.62, 0.23) 0.07
BMI 0.18 (0.33, 0.03) 0.02
Length 0.06 (0.28, 0.41) 0.68
ADF, alternate-day fasting; BMI, body mass index; CI, confidence in-
terval; VLCD, very-low-calorie-diets.
Obesity Science & Practice Alternate-day fasting versus daily energy restriction B. A. Alhamdan et al. 297
© 2016 The Authors.
Obesity Science & Practice published by John Wiley & Sons Ltd, World Obesity and The Obesity Society. Obesity Science & Practice
VLCD is somewhat greater, ADF results in greater rela-
tive reduction of fat mass and lesser reduction of fat-
free mass.
While magnitude of initial weight loss is greater using
VLCD, studies have shown, however, that VLCD may in-
crease the risk of headache, fatigue, dizziness, hair loss,
Figure 3 ADF versus VLCD: fat mass difference pooled results.
Figure 2 ADF versus VLCD: body weight difference pooled results.
298 Alternate-day fasting versus daily energy restriction B. A. Alhamdan et al. Obesity Science & Practice
© 2016 The Authors.
Obesity Science & Practice published by John Wiley & Sons Ltd, World Obesity and The Obesity Society. Obesity Science & Practice
constipation and dehydration. As a result, it requires reg-
ular medical supervision (28–31). Also, VLCD has been
associated with an increased risk of developing gall-
stones; one study showed that after 8 weeks of VLCD,
25% of patients developed gallstones and 6% required
cholecystectomy (32). VLCD may also be associated with
development of binge eating disorder. Following a VLCD
regimen one study showed that the disorder developed
among 62% of subjects, but decreased among 39%
(33). However, Wadden et al. (1994) found no difference
in binge-eating occurrence or in weight loss among binge
eaters versus non-binge eaters who were both following a
VLCD regimen. Their hypothesis was that binge eaters
might find VLCD easier to follow than conventional
calorie-restrictive diets (34).
In their meta-analysis, Tsai and Wadden (2006) con-
cluded that VLCD may be a viable option to lose weight
in the short term; however, they found that patients failed
to maintain 15 to 25% of VLCD-associated initial weight
loss, due to difficult compliance, adaptive hormonal
changes and our toxic food environment (3).
We found that ADF may be as effective as even the
very restrictive VLCD with respect to fat-mass reduction,
and provides relative preservation of fat-free mass. Two
recent reviews have evaluated the effects of intermittent
diets versus daily CR on weight loss, fat mass and fat-
free mass (7,35). One (non-systematic) reported fat-free
mass preservation by the intermittent diets (7), while the
other one (systematic) reported no difference between
the diets (35).
In our review, efficacy of ADF for weight- and fat-mass
reduction was an expected finding, and it is most likely
explained by the substantial overall decrease in energy in-
take that adherence to alternate-day energy restriction
will provide. It is noteworthy, however, that as prescribed,
VLCD would provide somewhat greater levels of energy
restriction than ADF, as it generally provides a >50% re-
duction in estimated energy needs (4). This implies logi-
cally that in order for mean weight and fat loss on ADF
regimens to be as good as that achieved on VLCD regi-
mens, average compliance with ADF must have been su-
perior to compliance with VLCD.
On the other hand, preservation of fat-free mass, at the
cost of fat mass during weight reduction (18) is unexpected
with the level of energy restriction that ADF prescribes. To
our knowledge, this is the first review to report this find-
ing. The mechanism for this effect, if confirmed by other
studies, is unclear, although it is possible that either the
fasting period is brief enough that there is less loss of lean
tissue in the first place, or that the days where full energy
needs are met allow for recovery of fat-free mass by re-
building lean tissue lost on the fasting days.
Several studies have reported that ADF did not appear
to cause a hyperphagic response on the feeding day
Figure 4 ADF versus VLCD: fat-free mass difference pooled results.
Obesity Science & Practice Alternate-day fasting versus daily energy restriction B. A. Alhamdan et al. 299
© 2016 The Authors.
Obesity Science & Practice published by John Wiley & Sons Ltd, World Obesity and The Obesity Society. Obesity Science & Practice
(9,20,21), which may have facilitated the subjects’ability
to maintain a substantial level of mean energy restriction.
In line with this, Klempel et al. (2010) conducted a modi-
fied ADF study and found that, on feeding days, subjects
only consumed 95% of their calculated energy intake
(36). ADF has also been found to decrease hunger and in-
crease satiety and dieting satisfaction in 8 to 12-week
studies, all of which may enhance the adherence to the
diet (7,9). The possible mediators of these appetite effects
include reductions in Leptin and Resistin, and increases
in Adiponectin (18). While a counter-intuitive approach
to weight control, it has been argued that ADF regimens
may achieve relatively high levels of dietary adherence
because they require energy restriction only every other
day (10) and do not require a change in the types of food
consumed, but rather a change in the pattern of con-
sumption (9). Varady et al. (2009) reported ADF efficacy
for weight reduction even during self-implementation
periods (10). For all the reasons presented earlier, we con-
sider ADF a viable alternative approach to weight control,
as also suggested by others (37).
As with any diet for weight loss, ADF reduction in body
weight was related to the level of adherence to this dietary
intervention (18,38,39). Its efficacy in at least one of the
reviewed studies was maximized when combined with
exercise at least three times per week (21). However, a
very recent study by Barnoski et al. (2015) –who exam-
ined whether ADF improves eating behaviours in a way
that promotes successful weight loss and weight loss
maintenance –observed a reduction in body weight even
without a change in physical activity (40). The same study
observed no changes in appetite ratings (hunger, satis-
faction and fullness), dietary restraint, emotional eating,
uncontrolled eating or self-efficacy in the ADF or the cal-
orie restriction groups as compared to the control. The
authors concluded that the role of beneficial eating
behaviours in body weight reduction through ADF or CR
remains unclear (40), hence warranting further research.
In line with other recent studies, the first finding of our
review is that ADF appears to be an effective strategy
for initial weight loss (at least the first eight weeks) in over-
weight and subjects with obesity. But most importantly,
our review suggests that ADF may be superior to daily
CR in terms of type of weight lost (fat vs. non-fat), and
adherence.
Health risks may also be affected favourably by ADF.
Waist circumference, a marker of visceral obesity which
is associated with coronary heart disease and diabetes
(41,42), was reduced by 4–10% from baseline in the stud-
ies reviewed, and correlated with overall weight reduction
(7,10,43). Adherence to this regimen was also associated
with a decrease in triglycerides, total cholesterol and LDL.
These effects were also correlated with the reduction in
body weight and visceral fat. The possible mechanism
by which ADF alters lipids is via an increase in oxidation
of free fatty acids during periods of weight loss, while free
fatty acid synthesis is reduced (44). This leads to a reduc-
tion in very low density lipoprotein (VLDL) synthesis by the
liver and thus reduced circulating levels of LDL (45). Thus,
adherence to an ADF diet may be cardio protective.
This review was limited by the small number of ADF
studies published to date, necessitating the inclusion of
non-randomized clinical trials. Furthermore, of the studies
that were included in this review, there was an over repre-
sentation of women on the ADF regimens (92%). Glucose
response in women is adversely affected following a fast
(46); therefore, it is possible that gender differences in
physiologic response to the ADF regimen may have af-
fected our analysis. Animal studies have suggested that
gender plays an important role in the evolutionary adapta-
tion to fasting. One study found that only female mice
demonstrated increases in arousal and reduced Gherlin,
suggesting that women may stand to achieve greater
benefit from ADF (47). While these differences, on a phys-
iologic level, are important in determining which diet may
be most appropriate for a given patient, it is important to
note that no gender differences in weight loss have yet
been shown in human studies (48). Better responses to
the ADF have, however, been shown in older individuals
and Caucasians, but we were unable to assess this from
the papers included in this review (48).
Conclusion
Among individuals with obesity, ADF is an efficacious di-
etary method, and may be superior to VLCD for some pa-
tients because of ease of compliance, greater fat-mass
loss and relative preservation of fat-free mass. However,
further studies comparing ADF to VLCD (ideally head-to-
head randomized clinical trials) that also control for
patient characteristics, are needed to confirm the effica-
ciousness of these two approaches for weight loss, and
to determine if ADF is better suited to certain populations.
This information is of interest to health care providers and
dietitians, as well as individuals with obesity seeking ef-
fective and potentially easier to follow methods to lose
weight.
Conflict of interests
None declared.
Author contributions
BA, AGA, JK and DS did the literature search and the
systematic review of the studies. AGA did the quality
300 Alternate-day fasting versus daily energy restriction B. A. Alhamdan et al. Obesity Science & Practice
© 2016 The Authors.
Obesity Science & Practice published by John Wiley & Sons Ltd, World Obesity and The Obesity Society. Obesity Science & Practice
assessment. BA and AA did the statistical analysis and
the meta-analysis. BA and LC wrote the manuscript. BA,
AGA, AA, KC, AU and LC contributed to the interpretation
and discussion of the results and reviewed and edited
drafts of the manuscript.
Acknowledgements
Our sincere gratitude to Dr. John McGready and Gayene
Yenokyan for their help with data analysis, and the Saudi
Arabian Cultural Mission (SACM) for financial support.
Our gratitude to Drs. John McGready and Gayene
Yenokyan from the Johns Hopkins Bloomberg School of
Public Health, Department of Biostatistics, for their help
with data analysis.
Funding
BA was funded by a postdoctoral fellowship from Saudi
Arabian Cultural Mission (SACM).
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