Open Access Review

Article DOI: 10.7759/cureus.2947

Intermittent Fasting: The Choice for a

Healthier Lifestyle
Kavitha Ganesan 1 , Yacob Habboush 1 , Senan Sultan 2

1. Internal Medicine, Orange Park Medical Center, Jacksonville, USA 2. Endocrinology, Orange Park
Medical Center, Jacksonville, USA

 Corresponding author: Kavitha Ganesan, [email protected]

Disclosures can be found in Additional Information at the end of the article

Abstract
Obesity is a worldwide epidemic due to the availability of many unhealthy food options and
limited physical exercise. Restriction of the daily food intake results in weight loss, which is
also associated with better health outcomes including triglycerides, total cholesterol, low-
density lipoprotein cholesterol, blood pressure, glucose, insulin, and C-reactive protein. Our
aim is to briefly discuss the effects of intermittent fasting on weight and other biochemical
markers mentioned previously. The study is designed as a systematic review according to the
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. To
assess the effectiveness of intermittent fasting, related studies were reviewed between 2000
and 2018 and 815 studies were identified. Only four articles met the preset inclusion and
exclusion criteria. All four studies have shown a significant decrease in fat mass with P-values
<0.01. It was also noted that some biochemical markers were significantly reduced such as the
reduction in low-density lipoprotein and triglyceride with P-values < 0.05. Other biochemical
markers had inconsistent results. Based on the qualitative analysis, intermittent fasting was
found to be efficient in reducing weight, irrespective of the body mass index. Further studies
are needed to assess the ability to maintain the lost weight without regaining it and the long-
term effects of such dietary changes.

Categories: Endocrinology/Diabetes/Metabolism, Internal Medicine

Keywords: intermittent fasting, weight loss, exercise

Introduction And Background

In recent years, people worldwide have developed an increased popularity for weight loss
program, diet plans and weight maintenance programs with little research done on the
effectiveness of those programs. Meanwhile, obesity has been increasing in prevalence due to
many social determinants such as easy access to various fast foods, and lack of physical activity
Received 06/22/2018
[1]. In 2016, World Health Organization (WHO) reported that more than 1.9 billion people in
Review began 06/28/2018
Review ended 07/05/2018 the world were overweight and over 650 million people were obese which has tripled in number
Published 07/09/2018 since 1975 [1]. Also, obesity is a known risk factor for many metabolic disorders like coronary
heart disease, malignancies, osteoarthritis and respiratory disorders [2].
© Copyright 2018
Ganesan et al. This is an open
access article distributed under the As per the meta-analysis done by Galani and Schneider, it was suggested that lifestyle changes
terms of the Creative Commons
are one of the most effective methods in reducing weight and the risks for cardiovascular
Attribution License CC-BY 3.0.,
which permits unrestricted use,
diseases [3]. Weight loss usually leads to the improvement in the overall wellbeing of patients
distribution, and reproduction in any and their biomarkers such as systolic and diastolic blood pressure, blood sugar, insulin, total
medium, provided the original serum cholesterol, inflammatory biomarkers and low-density lipoprotein (LDL) [3]. There are
author and source are credited. many forms of diet and exercises programs available for weight loss, however, one of the least

How to cite this article

Ganesan K, Habboush Y, Sultan S (July 09, 2018) Intermittent Fasting: The Choice for a Healthier
Lifestyle. Cureus 10(7): e2947. DOI 10.7759/cureus.2947
 recognized diet changes is the alternate day fasting (ADF) which includes eating 20% of energy
requirements on a fast day and then consume food ad libitum on the feed days which has been
suggestive to be highly effective for weight loss.

The aim of our systematic review is to summarize the effects of ADF/intermittent fasting on
weight loss, the influence on biomarkers, and cardiovascular risk factors thereby assessing it as
a choice for a healthier lifestyle.

Review
Methods
Study Design

The design of the study is a rapid qualitative systematic review in line with the Preferred
Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. A literature
review was performed independently by two reviewers, Kavitha Ganesan (KG) and Yacob
Habboush (YH). The authors choose a wide range of search engines to use including PubMed,
Medline, Ovid, EBSCO, Clinical Key and Google Scholar. Set words and terms were used to
search for publications, including ‘intermittent fasting’, ‘weight loss’, and ‘low calorie’, to which
we applied relevant subheading such as ‘fasting’, ‘diet’, ‘intermittent’, ‘overweight’ and ‘obese’.
The search was limited by using the following filters: Human subjects, English language, and
since the year 2000. Irrelevant publications were eliminated from the title of those studies
which did not include the word fasting or dietary restriction. The present study is based on a
qualitative approach to assessing the effectiveness of intermittent fasting in reducing body
weight and adopting a healthier lifestyle. Therefore, the study design did not include the
calculation of the quantitative measures.

Study Selection

The inclusion criteria for publications included any published article assessing intermittent
fasting in 18-year-old patients or older, randomized controlled trials, studies measuring the
effect of intermittent fasting on body weight as a primary outcome, and body mass index. We
also assigned the Grading of Recommendations Assessment, Development and Evaluation
(GRADE) score of four or higher as an evaluation measure of the publications overall quality [4].
Exclusion criteria included any study with participants younger than 18 years of age, any study
that is not a randomized clinical, and those studies that did not score four or higher on the
GRADE framework. Table 1 shows the four selected studies with definitions of the
interventions.

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 Intervention
Author/year Detention of intervention type
type

Varady K. et Alternate A “fast day” where individuals consume 25% of energy needs, alternated with a “feed
al. 2013 [5] day fasting day” where subjects eat ad libitum.

Alternate A “fast day” where individuals consume 25% of energy needs, alternated with a “feed
day fasting day” where subjects eat ad libitum.
Bhutani S.
et al. 2013 Moderate intensity exercise program three times per week under supervised conditions
Exercise
[6] using an age-predicted heart rate maximum with a heart rate monitor.

Combined Combination of alternate day fasting and exercise.

Heilbronn L. A “fast day” where individuals consume 25% of energy needs, alternated with a “feed
Alternate
et al. 2005 day” where subjects eat ad libitum followed by two consecutive days a “feast” day and
day fasting
[7] following a “fast” day.

Daily energy intake of 450 kcal followed by refeeding phase, in which ordinary food was
Lantz H. et Very low-
gradually introduced. For the remaining treatment period all the patients were
al. 2003 [8] calorie diets
recommended an individualized hypocaloric diet of 500 kcal day.

TABLE 1: Types of interventions.

Outcomes

The outcome of interest is the effectiveness of intermittent fasting on weight loss and other
biomarkers, while also assessing for the overall quality of the selected clinical trials to ensure
high qualitative systematic review.

Results
Search Results and Study Characteristics

Both authors, KG and YH, cumulatively identified 815 studies since 2000 with a Kappa score of
0.689, which signifies a good strength of agreement. Of those, 258 articles were removed since
they were duplicates. Further, 439 studies were excluded (abstract, study in progress,
systematic reviews, and meta-analysis). Then we assessed 118 articles for eligibility. Figure 1
shows the PRISMA flow diagram. Finally, we included four randomized controlled trials in our
qualitative systematic review. Table 2 provides the demographic information about the selected
studies.

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 FIGURE 1: PRISMA flow diagram.
PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; K.G.: Kavitha
Ganesan; Y.H.: Yacob Habboush; GRADE: Grading of Recommendations Assessment,
Development and Evaluation.

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 Average
Number of Mean Diet Average Intervention
Study BMI per
Author/year Location participants in age per only/Exercise weight per period
design group
each group group only/Combination group (kg) (weeks)
(kg/m2)

Varady K. et
RCT US 15, 15 47, 48 Diet only 77, 77 26, 26 12
al. 2013 [5]

Bhutani S.
45, 42, Diet only/Exercise 91, 94, 93, 35, 35, 35,
et al. 2013 RCT US 18, 25, 24, 16 12
42, 49 only/Combination 93 35
[6]

Heilbronn L.
et al. 2005 RCT US 8, 8 34, 30 Diet only 80.6, 59.7 25.2, 22.6 3
[7]

Lantz H. et 41.9, 114.2,

RCT Sweden 161, 173 Diet only 39.9, 40.1 104
al. 2003 [8] 41.4 114.4

TABLE 2: Study characteristics of reviewed random controlled trials.

BMI: Body mass index; RCT: Randomized controlled trial; US: United States; kg: kilogram; kg/m2: kilogram per meter square.

Outcomes

A randomized controlled trial by Varady et al. [5] evaluated the role of ADF to lose weight in
overweight and normal weight individuals. Subjects had a feed day alternated with a fast day
with 25% of total energy intake. Alternate day fasting group has a decrease in fat mass (P <
0.001) by 3.6 ± 0.7 kg, C-reactive protein (13 ± 17%, P < 0.05), leptin and triacylglycerol (TG)
concentrations (20 ± 8%, P < 0.05), increase in low density lipoprotein (LDL) particle size (4 ± 1,
P < 0.01) and plasma adiponectin (6 ± 10%, P < 0.01) while leptin decreased (40 ± 7%, P < 0.05)
when compared to the control group [5]. However, there was no change in low-density
lipoprotein, high-density lipoprotein, and homocysteine at the end of study period. Cases and
controls did not have any issues in adhering to the study diet for 12 weeks. Reported
hyperphagia on the feed day in turn leads to overall higher energy restriction throughout the
study period which was a major cause of the weight loss. Dietary satisfaction and sense of
feeling fullness increased at the end of 12 weeks which may have played a role in adherence to
diet in the long-term. Few limitations of this study were the low number of study subjects (15
patients in each group), no physical activity measurement, the possibility of under-reporting of
dietary intake as the reports were taken via food records [5].

The second study done by Bhutani et al. [6] measured the combination of ADF and exercise
which was found to be superior to fasting or exercise alone in terms of lipid levels and changes
in body mass composition. Sixty-four obese patients were divided into four groups as
mentioned in Table 2. There was a reduction in body weight in the exercise only group and the
combination groups. Moreover, the combination group had a reduction in LDL (5%, P < 0.05),
the proportion of small high-density lipoprotein (HDL) particles (P < 0.01), fat mass, and waist
circumference, however, the lean mass remained the same. There was also an increase in LDL
particle size in ADF only group and the combination group. The dietary intervention had two
periods; a controlled feeding period (25% of baseline energy requirements) for four weeks, and

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 a self-selected feeding period (food ad libitum) for next eight weeks [6]. Participants in the
exercise group and combination group had a moderate intensity supervised exercise program
three times per week for 12 weeks. Initially, they were exercising for 25 minutes which was
gradually increased to the duration of 40 minutes by week 10. Few limitations of the study were
that it might take more than 16 weeks for HDL cholesterol to be altered supervised endurance
training. Also, exercise frequency and intensity mentioned in the study may not be sufficient to
change the risk indicators of coronary artery disease [6].

Heilbronn et al. [7] conducted a study to determine whether ADF is a good model of dietary
restriction in non-obese people and whether there is any improvement in longevity of the
people. They recruited 16 people with eight men and eight women who fasted every other day
for 22 days. Individuals lost about 2.5% (P 0.001) of their initial body weight and 4% of initial
fat mass (P 0.001). Fat oxidation was increased more than or equal to 15 grams in non-obese
subjects, but the hunger did not decrease on non-fasting days. They recommended that adding
one small meal on fasting days will make alternate fasting more feasible. Resting metabolic rate
and respiratory quotient did not change significantly from baseline to day 21 and 22 of ADF.
There was no significant change in ghrelin and glucose from baseline in alternate fasting
subjects while fasting insulin was decreased by 57% (P < 0.001). Level of physical activity varied
among the subjects. Seven people were sedentary, three had moderate activity level and three
people had very active life (four to five times of exercise per week) [7].

The last study is a two-year randomized controlled trial by Lantz et al. [8] consisted of 334
patients who were evaluated for the effect of intermittent versus on-demand intake of very
low-calorie diet (VLCD) for maintenance of weight in obese patients for 16 weeks. The
intermittent group had VLCD for two weeks every third month, while on-demand group
patients had VLCD when the body weight has passed the individual cut off level. They had
hypocaloric diet during other periods. VLCD-based regimen had clinically significant weight
loss after two years (7.0 ± 11.0 kg (6.2 ± 9.5%) with P < 0.001). Many risk factors for
cardiovascular disease were improved during the first year including HDL, LDL, and insulin
were improved significantly at the end of two years of the study. Calorie level of VLCD was 450
kilocalories. In the refeeding phase of three weeks, ordinary food was introduced gradually,
then subjects were given individualized hypocaloric diet (500 calories per day) for up to two
years [8]. Tables 3 and 4 summarize some of the significant outcomes.

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 Study Groups FM/FFM Mean mass change from baseline/Kg (SEM or CI) P-value

FM -3.6 (± 0.7) <0.001

Varady K. et al. [5] ADF vs. Control
FFM 0 -

FM -2 (± 1) 0.008
ADF
FFM -1 (± 1) 0.031

FM -1 (± 0) 0.182
Exercise
FFM -1 (± 0) 0.321
Bhutani S. et al. [6]
FM -5 (± 1) <0.001
Combination
FFM 0 (± 1) 0.299

FM 0 (± 1) 0.570
Control
FFM -1 (± 1) 0.693

FM -0.8 <0.001
Heilbronn L. et al. [7] ADF vs. Control
FFM -0.6 <0.05

FM -6.46 (-8.1; -4.8) <0.05

Lantz H. et al. [8] ADF vs. Control
FFM -2.64 (-5.5; -3.6) <0.05

TABLE 3: The mean change in weight.

ADF: Alternate day fasting; FM: Fat mass; FFM: Fat free mass; SEM: Standard error of mean; CI: Confidence interval.

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 Total cholesterol LDL HDL TG SBP (mm DBP (mm
Study Groups
(mg/dl) (mg/dl) (mg/dl) (mg/dl) Hg) Hg)

Varady K. et al. ADF -26 ± 6 -18 ± 6 -2 ± 3 -22 ± 11 -25 ± 5 4±1

[5] Control -9 ± 5 -9 ± 4 1±2 10 ± 7 -9 ± 5 -2 ± 1

ADF 7±4 -1 ± 6 0±4 6±6 -3 ± 1 -2 ± 2

Bhutani S. et al. Exercise 0±3 0±5 2±3 7±6 2±2 0±2

[6] Combination -2 ± 5 -12 ± 5 18 ± 9 13 ± 11 -2 ± 2 0±3

Control 1±4 3±5 8±5 5±7 -2 ± 3 -2 ± 3

Heilbronn L. et ADF vs.

- - - - - -
al. [7] Control

ADF vs.
Lantz H. et al. [8] -0.1 -0.2 0.2 -0.1 0±3 0±2
Control

TABLE 4: Changes in lipid and blood pressure compositions.

LDL: Low-density lipoprotein; HDL: High density lipoprotein; TG: Triglyceride; SBP: Systolic blood pressure; DBP: Diastolic blood
pressure; ADF: Alternate day fasting.

Discussion
A systematic review of the four studies discussed showed that intermittent fasting was effective
for short-term weight loss. However, there was increased variability in our included studies,
ranging from 16 to 334 participants with a follow-up period ranging from three weeks to 104
weeks. Baseline characteristics of the study population were also different in terms of body
mass index which included normal weight subjects, overweight and obese subjects. Mode of
interventions was also different for each individual study as shown in Table 1 [5-8].

A systematic review by Davis et al. found that dietary plans had significant weight loss in
intermittent fasting groups [9]. Seimon et al. in his systematic review found that intermittent
fasting diet was as effective as daily restriction of calories both for short and long-term
interventions [10]. Most common issues with continuous calorie restriction diet are that
restriction of food continuously is a trigger for higher hunger and additional eating. In these
situations, ADF is a better solution which might be an optimal solution so that people can eat
in their usual ways on non-fast days. This also depends on the type of the ADF used which
minimizes the fatigue associated with continuous calorie restriction [11].

There are limited data available in the literature regarding the consistency, tolerability, and
safety of ADF among the general population when used as an intervention for weight loss.
Varady et al. mentioned that minimal adverse effects such as mild headaches and constipation
were experienced in three patients and only one patient was dropped out of the study because
of difficulty in adhering to the diet [5]. A systematic review by Heilbronn and Ravussin [12]
mentioned that there were few adverse effects related to the study such as lightheadedness and
constipation. Few people were irritable during fast days. Lantz et al. study had a dropout rate of
about 65%, also there was a lack of very low-calorie diet free treatment group during the
maintenance phase to serve as a control group [8].

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 The dietary program called continuous energy restriction (CER) is another effective mean of
weight reduction in obese and normal weight individuals. It includes restriction of daily calorie
intake by 15-60% of baseline energy requirements which is typically very hard to maintain over
a long period of time because of the need to exercise self-regulation and tracking of the calories
[13, 14]. In addition, CER may cause physiologic adaptations in the body to adapt for calorie
restriction which might prevent further weight loss. Therefore, the alternate form of dieting
intermittent energy restriction (IER) has been gaining popularity due to its superior efficacy
[13, 14].

One form of IER is ADF which involves a fast-day where participants reduce or completely
withhold any food intake and feed-day in which there is an ad libitum food consumption. The
second form consists of a whole day fasting including complete fasting for one or two days in a
week or with 25% of calorie intake in a day with no restriction of food for other days in a week.
The third form is time restricted feeding where meals are eaten during specific times in the day,
for example, from 8 am to 5 pm while people will remain on fasting for other hours in the same
day [15].

Few biochemical changes associated with ADF in terms of weight loss change in mu (μ) opioid
receptor characteristics, activation of the mesocorticolimbic dopamine system, and reduction
of D2 dopamine receptor expression [16]. One of the proposed mechanisms for the small HDL
particles to cause an increase in coronary heart disease may be related to alteration in the
activity of lipases which are associated with the maturation and transformation of lipoproteins.
Increase in proportion of the small LDL particles increases the risk of coronary artery disease by
augmenting oxidization and increase in permeability of endothelial barrier [17, 18].

Advantages of ADF include subject satisfaction without food restriction, anxiety, and no
reported hyperphagia. Subjects tend to watch what they eat even beyond the period of calorie
restriction as they were used to ADF. People who either eat one or two meals per day or do not
eat anything for long stretches of time may show better compliance of ADF diet which may
result in greater weight loss [5-8].

Potential disadvantage of ADF is that it is not appropriate for individuals who are required to
eat meals at regular intervals such as type 1 diabetes, pregnant and breastfeeding women,
elderly, individuals with eating disorders and those in need of regular food intake to take
medications. Weight loss generally plateau in six months, thus focus on weight maintenance
after the initial period of weight loss is important by adherence to low-calorie diet and regular
physical activity for a longer period of time [5-8].

There were few studies regarding alternating fasting that was conducted for a short duration of
three weeks [19]. Redman et al. [20] conducted a study in obese people similar to Bhutani et al.
[6] with a combined calorie restriction (reduction in energy intake by 25%) and supervised
exercise program (moderate intensity exercise for about 60 minutes for five days in a week) for
twelve weeks. It showed a weight loss of about 6% from the baseline in the study group. As per
Bhutani et al. [6], combination therapy may cause retention of lean mass at the expense of fat
mass during the energy restriction period which in turn helps to maintain resting metabolic
rate thereby led to increases in energy burning capacity and weight loss. Seimon et al.
mentioned that intermittent energy restriction is effective when compared to CER for short-
term weight loss with three to five kilograms weight loss in approximately 10 weeks [10].

There are a few limitations associated with this systematic review. Studies that were published
in other languages were excluded. Also, the location of these studies were university-based
settings where participants had access to high-quality foods, dietician consultants, and
counseling from behavioral health person. Thus, the external validity of these studies was

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 doubtful in terms of applying it to the rural population who would like to achieve weight loss. It
was difficult to ascertain for publication bias in our included primary studies, which may have
reported successful interventions and selection bias as they might have enrolled subjects who
had high motivation for adherence to diet. Lastly, our included studies were highly variable in
terms of study design, the composition of the diet, amount of energy restriction, the timing of
fasting period in a day and physical activity inclusion as mentioned in Table 2.

Conclusions
The systematic review of the aforementioned four studies found that intermittent fasting was
effective for short-term weight loss among normal weight, overweight and obese people.
Randomized controlled trials with long-term follow-up period are needed to follow the
adherence to diet and long-term maintenance of weight loss without regaining the lost weight.
Future studies should also include specific subgroups of the population such as individuals with
cardiovascular risk factors and type 2 diabetes mellitus as these patient population benefit more
from weight loss which may modify the disease process. In summary, obesity and overweight is
an international health crisis, and interventions such as ADF are needed to help people to
achieve weight loss.

Additional Information
Disclosures
Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors
declare the following: Payment/services info: All authors have declared that no financial
support was received from any organization for the submitted work. Financial relationships:
All authors have declared that they have no financial relationships at present or within the
previous three years with any organizations that might have an interest in the submitted work.
Other relationships: All authors have declared that there are no other relationships or
activities that could appear to have influenced the submitted work.

Acknowledgements
Dr. Ganesan and Dr. Habboush have contributed equally to the design, review, and write-up of
this study.

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