Open Access Review

Article DOI: 10.7759/cureus.53221

The Effect of Fasting on Cardiovascular Diseases:

A Systematic Review
Received 01/06/2024
Kirubel T. Hailu 1, 2 , Korlos Salib 1, Sanath Savithri Nandeesha 1, Alousious Kasagga 3 , Chnoor Hawrami 4,
Review began 01/24/2024 Erica Ricci 5, Pousette Hamid 6
Review ended 01/26/2024
Published 01/30/2024
1. Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA 2. Internal
© Copyright 2024 Medicine, Afet Speciality Clinic, Addis Ababa, ETH 3. Pathology, California Institute of Behavioral Neurosciences &
Hailu et al. This is an open access article Psychology, Fairfield, USA 4. Pediatric Surgery, California Institute of Behavioral Neurosciences & Psychology,
distributed under the terms of the Creative
Fairfield, USA 5. Anesthesiology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA 6.
Commons Attribution License CC-BY 4.0.,
Neurology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
which permits unrestricted use, distribution,
and reproduction in any medium, provided
the original author and source are credited. Corresponding author: Kirubel T. Hailu, [email protected]

Abstract
Among the leading causes of morbidity, disability, and death worldwide are cardiovascular diseases (CVDs).
Their risk factors usually include a variety of factors associated with cardiometabolic disorders. Many public
health organizations prioritize the prevention of CVDs and encourage people to maintain a healthy lifestyle.
It has been shown that fasting and a healthy diet can promote weight loss and improve cardiometabolic
health in various animal species. We want to know the impact of fasting on CVDs. The topic is examined in
this systematic review. We looked through a wide range of online sources, including PubMed, Cochrane
Library, and Google Scholar, to find randomized controlled trials (RCTs) that looked into the connection
between CVDs and fasting. We included human research that has been published in English in peer-
reviewed publications in the last five years, and then we screened by the title, abstract, and full-text
accessibility. We picked the final 10 articles for quality assessment using Cochrane Collaboration's tool for
risk-of-bias assessment of RCTs. The findings suggest that fasting is beneficial in lowering the
cardiovascular risk of a population. This result holds for all types of fasting used as an intervention in the
clinical trials we reviewed. The result is pronounced when fasting regimens are combined with a regular
exercise routine. More comprehensive data will come from larger-scale clinical trials and case-control
studies, and a thorough examination of all the potential health impacts of fasting is warranted.

Categories: Preventive Medicine, Internal Medicine, Cardiology

Keywords: intermittent fasting, calory deficit, prevention, cardiovascular diseases, fasting

Introduction And Background

Cardiovascular diseases (CVDs) stand as the foremost cause of morbidity, disability, and fatalities globally.
Their risk factors typically encompass a range of elements linked to cardiometabolic conditions [1]. The
most common risk factors and associated pathologies include metabolic syndrome [2,3],
obesity [4,5], hypertriglyceridemia [5,6], type 2 diabetes mellitus [7], circadian disruption [8], and
dyslipidemia [5,6]. Preventing CVDs is a primary focus for numerous public health organizations, advocating
for individuals to uphold a healthy lifestyle. The American Heart Association (AHA) and the American
College of Cardiology (ACC) have released a comprehensive report emphasizing CVD prevention
strategies [9].

Fasting is a broad term encompassing intermittent fasting (IF) [6], dietary protein restriction [2], energy
restriction [3], continuous calorie restriction (CCR) [5], time-restricted eating (TRE) [8], and calorie
restriction (CR) [10]. Fasting while ensuring adequate nutrition has demonstrated its effectiveness in aiding
weight loss and enhancing cardiometabolic health across diverse animal species. However, in human
studies, the impact of fasting on CVDs has been a topic of debate and remains inadequately comprehended.
In this document, we will systematically review clinical trials to study the effect of different types of fasting
on CVDs; this review seeks to provide a comprehensive understanding of the potential role of fasting in
preventing and managing CVDs.

Our review is particularly timely, as the global burden of CVDs continues to escalate [11,12,13], and there is
a growing interest in lifestyle modifications as a means to combat this trend [14,15]. The insights gained
from this systematic review could have significant implications for clinical practice and public health
policies, offering an alternative approach to CVD management that is grounded in lifestyle change.

Review
Methodology
This systematic review utilized the Preferred Reporting Items for Systematic Review and Meta-analysis
(PRISMA) guidelines [16]. The articles were systematically searched in PubMed, Google Scholar, and

How to cite this article

Hailu K T, Salib K, Savithri Nandeesha S, et al. (January 30, 2024) The Effect of Fasting on Cardiovascular Diseases: A Systematic Review. Cureus
16(1): e53221. DOI 10.7759/cureus.53221
 Cochrane Library trials. Only items that were published in English were taken into account. The most recent
search was conducted on October 29, 2023. The following search terms were used in combination:
intermittent fasting OR fasting OR water fasting OR autophagy, calory restriction OR time-restricted feeding
OR 16/8 fasting OR 5:2 diet OR eat-stop-eat OR warrior diet OR hunger OR extended fasting. The search was
limited to studies published between 2019 and 2023. In addition, the search inclusion in PubMed Medical
Subject Headings (MeSH) is shown in Table 1:

Database Strategies Number

Intermittent fasting OR fasting OR water fasting OR Autophagy, calory restriction OR Time-restricted feeding OR
16/8 fasting OR 5:2 diet OR eat-stop-eat OR warrior diet OR hunger OR extended fasting OR (( "Intermittent
Fasting/adverse effects"[Majr] OR "Intermittent Fasting/blood"[Majr] OR "Intermittent Fasting/metabolism"[Majr]
OR "Intermittent Fasting/physiology"[Majr] )) AND ( "Intermittent Fasting/adverse effects"[Majr:NoExp] OR
PubMed 392,366
"Intermittent Fasting/blood"[Majr:NoExp] OR "Intermittent Fasting/metabolism"[Majr:NoExp] OR "Intermittent
Fasting/physiology"[Majr:NoExp] ) AND Cardiovascular diseases OR coronary heart disease OR (("Cardiovascular
Diseases/prevention and control"[Majr]) AND "Cardiovascular Diseases/prevention and control"[Mesh:NoExp]) OR
"Cardiovascular Diseases/prevention and control"[Majr:NoExp])

Cochrane Fasting and cardiovascular diseases 60

Google
Fasting and cardiovascular diseases 12
scholar

TABLE 1: PubMed Medical Subject Heading (MeSH), Cochrane, and Google Scholar strategies

Eligibility Criteria and Study Selection

We conducted a thorough evaluation of the title and abstract of each paper to ascertain its suitability. The
results were screened using the following inclusion criteria: 1) full articles that are freely accessible, 2)
studies published in the English language in the past five years, 3) peer-reviewed randomized controlled
trials (RCTs) that explore the relationship between fasting and CVDs, and 4) studies conducted on human
irrespective of age, ethnicity, or study location. The exclusion criteria were 1) editorials, posters, and animal
research, and 2) gray literature was omitted from the analysis. Only studies that met the specified criteria
were considered for eligibility in the final review.

Data Extraction

We conducted data extraction from the chosen studies. The standardized recording tool was used to
investigate the following variables: study design, number of study participants, baseline characteristics of
participants, fasting type and treatment duration, mean follow-up in each group of participants, study
outcomes, and funding source (pharmaceutical company or not).

Quality Assessment Tool

We assessed the potential for bias by utilizing the Cochrane risk-of-bias method and only included studies
judged as “low-risk” bias in each domain. Disagreement was resolved by consensus.

Results
Upon thoroughly searching the databases, we obtained a total of 1,968 articles. Subsequently, we
meticulously examined and evaluated the titles, resulting in the selection of 101 research. After doing a
thorough review of the articles and eliminating 15 instances of repetition (10 articles from PubMed and five
articles from other sources), we were left with a total of 10 articles (as depicted in Figure 1).

2024 Hailu et al. Cureus 16(1): e53221. DOI 10.7759/cureus.53221 2 of 8

 FIGURE 1: Preferred Reporting Items for Systematic Review and Meta-
analysis (PRISMA) 2020 flow diagram

We employed Cochrane quality assessment instruments for the remaining 10 papers after comprehensively
examining all articles. Table 2 displays the assessment for the 10 articles.

2024 Hailu et al. Cureus 16(1): e53221. DOI 10.7759/cureus.53221 3 of 8

 Tang Ferraz- Maroofi and Chair
Kunduraci Schroder Ahmed Manoogian Kraus et Moro et
et al. Bannitz et al. Nasrollahzadeh et al.
and Ozbek [3] et al. [4] et al. [6] et al. [8] al. [10] al. [11]
[1] [2] [5] [7]

Random sequence
L L H L L H L L L L
generation?

Blinding? H L L L H L L H H H

Concurrent therapies
H H H H H H U H H H
similar?

Incomplete outcome
H H H H H U U H H H
data addressed?

Uniform and explicit

H H H H H H H H H H
outcome definitions?

Free of selective
H H L H H L H H H H
outcome reporting?

Free of other bias? H L L U H U L H H H

Overall risk of bias? L L L L L L L L L L

TABLE 2: Cochrane Collaboration's tool for risk-of-bias assessment of randomized controlled

trials
Risk of bias: L = low, H = high, U = unclear

Table 3 displays the key characteristics and conclusions of the 10 articles.

Journal and
Type of
Author publication Title Conclusion
research
year

A pilot
randomized
“Effects of Caloric Restriction In young adults, calorie restriction and rope-
Nutrients, controlled
Tang et al. [1] and Rope-Skipping Exercise on skipping exercise can both help with weight loss
2021 trial in
Cardiometabolic Health” and body composition improvement.
young
adults

“Dietary Protein Restriction

Randomized
Ferraz-Bannitz et Nutrients, Improves Metabolic Dysfunction The main factor underpinning the advantages of
controlled
al. [2] 2022 in Patients with Metabolic diet restriction is protein.
trial
Syndrome”

“Does the Energy Restriction No significant differences were observed in

Randomized
Kunduraci and Nutrients, Intermittent Fasting Diet Alleviate metabolic syndrome biomarkers between the
controlled
Ozbek [3] 2020 Metabolic Syndrome Intermittent and Continuous energy restriction
trial
Biomarkers?” groups.

Journal of “Effects of time-restricted feeding Non-

A time-restricted feeding regimen lowers body
Translational in weight loss, metabolic randomized
Schroder et al. [4] weight without altering metabolic syndrome-related
Medicine, syndrome and cardiovascular controlled
biomarkers.
2021 risk in obese women” trial

“Effect of intermittent versus A three-day-per-week intermittent caloric restriction

continuous calorie restriction on diet is similar to a continuous caloric restriction diet
Lipids in
body weight and cardiometabolic for lowering triglyceride levels in patients with
Maroofi and Health and Randomized
risk markers in subjects with hypertriglyceridemia. Additionally, short-term
Nasrollahzadeh [5] Disease, trial
overweight or obesity and mild- benefits of intermittent caloric restriction over
2020
to-moderate continuous dieting include improved insulin
hypertriglyceridemia” resistance.

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 Frontiers in By improving the lipid profile and raising the high- Quasi-
“Impact of Intermittent Fasting on
Ahmed et al. [6] Nutrition, density lipoprotein (HDL), intermittent fasting may randomized
Lipid Profile”
2020 safeguard cardiovascular health. clinical trial

Journal of The results suggest that incorporating intermittent

“Intermittent Fasting in Weight Randomized
Nursing fasting regimens into regular eating patterns may
Chair et al. [7] Loss and Cardiometabolic Risk controlled
Research, be beneficial in lowering the population's risk of
Reduction” trial
2022 diabetes and cardiovascular disease.

“Feasibility of time-restricted There were no notable variations found in

Cell
Manoogian et al. eating and impacts on metabolic syndrome indicators between the groups Randomized
Metabolism,
[8] cardiometabolic health in 24-h that underwent intermittent and continuous calorie control trial
2022
shift workers” restriction.

“2 years of calorie restriction and

cardiometabolic risk The results hold promise for significant long-term
Lancet Phase 2,
comprehensive Assessment of population health benefits and point to a possible
Diabetes randomized
Kraus et al. [10] Long-term Effects of Reducing significant benefit of moderate calorie restriction for
Endocrinol, controlled
intake of Energy (CALERIE): cardiovascular health in young and middle-aged
2019 trial
exploratory outcomes of a healthy adults.
multicentre.”

Medicine Our findings imply that a resistance exercise

“Twelve Months of Time-
and Science program in conjunction with a long-term time
restricted Eating and Resistance Single-blind
in Sports restriction on eating is a realistic, safe, and efficient
Moro [11] Training Improves Inflammatory randomized
and way to lower inflammatory markers and risk factors
Markers and Cardiometabolic study
Exercise, associated with metabolic and cardiovascular
Risk Factors”
2021 disorders.

TABLE 3: Characteristics of studies included in this system review

HDL: high-density lipoprotein, CALERIE: Comprehensive Assessment of the Long-Term Effects of Reducing Intake of Energy

The clinical trials in our study have used different types of fasting as an intervention in conducting the
trials: The first one is IF [5,6,7]; the second is a dietary restriction from calories, protein, or energy [1,2,3,10],
and the last one is time-restricted feeding [4,8,11].

Body weight loss, waist circumference reduction, and improved lipid profiles are all possible outcomes of
IF [6]. The method of fasting used here was fasting for approximately 12 hours throughout the day, from 6
A.M. to 6 P.M., three days a week for six weeks [6]. Compared to other types of IF, this method seems safe,
successful, and feasible to incorporate into regular life without causing additional financial or physical
strain. With IF, people do not have to worry about making extra effort to cook meals that are low in calories.
A reasonable dinnertime and an early breakfast can help you keep the 12-hour fast, and this strategy works
both on weekdays and weekends. It could be challenging for those with night-shift jobs, a busy social
schedule, or a regular dining-out schedule. This was also seen in the current trial when five participants left
because they could not keep up a three-day weekly fast due to their demanding schedules [6]. One of the
studies investigated the two IF strategies, alternate-day fasting, and 16/8 time-restricted fasting. The results
showed that during the trial, both intervention groups considerably outperformed the control group
regarding lowering body weight, BMI, and waist circumference. Over time, the 16/8 time-restricted fasting
group did not achieve as large of reductions in body weight and BMI as the alternate-day fasting group
did [7].

The effect of IF versus continuous fasting on blood triglyceride levels was assessed. The trial's findings
showed that intermittent CR three days a week is equivalent to a continuous energy restriction diet for
lowering plasma triglyceride levels. Moreover, it seemed more successful than continuous dieting at
improving a marker of insulin resistance in this group of hypertriglyceridemia patients [5]. The two cohorts
had no discernible variation in plasma lipids and lipoproteins. Both diets showed beneficial modifications in
lipid levels. Our investigation indicated that intermittent CR reduced plasma triglyceride levels. In terms of
plasma high-density lipoprotein cholesterol (HDL-C) concentration, at eight weeks, there was no
statistically significant difference between the groups; however, the CCR group's concentration dropped
while the intermittent CR group's concentration remained unchanged. Since there was no drop in the ratio
of HDL compared to the total cholesterol (TC/HDL-C), it is doubtful that this decrease is harmful. Insulin
and the homeostasis model assessment of insulin resistance (HOMA-IR), a measure of insulin resistance,
showed positive modulations under the intermittent CR diet [5].

The clinical outcomes of a 12-week intermittent fasting treatment in individuals with metabolic syndrome

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 are reported for the first time. Intermittent energy restriction was an effective intervention that resulted in
a mean weight loss of 8%, a decreased waist/hip ratio, and no negative side effects. All participants saw
improvement in every metabolic indicator except HDL. Regarding alterations in the patients' glycemic
readings, lipid profile, and blood pressure, the intermittent energy-restriction diet was not substantially
better than the continuous calorie-restricted diet [3].

For the first time, a two-year multicenter randomized clinical trial examined the course of cardiometabolic
adaptations to two years of moderate CR in healthy, non-obese young and middle-aged people with
clinically normal risk factors at baseline. The trial's findings showed that even in healthy young and middle-
aged individuals with normal baseline values, CR combined with adequate nutrition improves multiple
cardiometabolic risk factors. Moreover, they discovered that CR in this population improved previously
normal risk factors, suggesting improvement in long-term cardiovascular risk. Furthermore, these findings
show that maintaining CR for two years positively impacts cardiometabolic health in addition to those
brought about by the corresponding reduction in body weight. No pharmaceutical medication has such a
dramatic influence on such a wide spectrum of cardiometabolic risk variables. These ought to give medical
professionals a new weapon in their arsenal against the devastations of the American way of life in the 21st
century [10].

They demonstrated the numerous clinical benefits that patients with metabolic syndrome who undergo
short-term (i.e., 27-day) protein restriction or CR interventions appreciate, such as decreased adiposity,
blood pressure normalization, improved insulin sensitivity, decreased glucose and lipid levels, and
decreased systemic inflammation. The effects of protein restriction or CR last for at least a month following
hospital discharge. We discovered that improving a number of metabolic metrics does not need CR. Rather
than requiring a decrease in calorie intake, protein restriction is adequate to provide nearly the same clinical
results as CR [2].

The protein and CR diets achieved weight loss, mainly due to decreased fat mass and preservation of free fat
mass, despite the disparities in calorie intake between the two regimes. The findings demonstrated that
individuals with metabolic syndrome who underwent 27 days of protein or CR had a normalization of their
blood pressure and a decrease in the levels of circulating lipids, indicating that the diets under evaluation
may be able to reduce the risk of CVDs. Our findings suggest that dietary protein restriction may be a
workable blood pressure control method, even though it is well-established that CR lowers risk factors linked
to the development of CVDs, such as high blood pressure and heart rate [2].

Protein restriction resulted in improvements in insulin sensitivity and beta-cell function (as measured by
HOMA-Beta) and decreases in blood glucose and hemoglobin A1c (HbA1c) levels. These findings imply that
dietary proteins might be crucial for maintaining glucose homeostasis in metabolic syndrome patients. Since
eating behavior is connected to social relationships and produces enjoyment, long-term compliance with CR
interventions is considered poor. This obstacle might be more difficult for obese people to overcome. This
research proposes an alternate eating regimen that does not involve CR to assist people with metabolic
syndrome in losing weight and managing their blood pressure, cholesterol, and blood sugar levels [2].

A separate investigation examined the short-term impacts of CR, rope-skipping (RS) exercise, and combined
therapies on young adults' cardiometabolic health. While there was no discernible difference between the
three groups, we discovered that the combined CR and CR-RS intervention could significantly lower weight,
BMI, body fat index, and body fat mass in young people. In addition, the CR-RS combined intervention could
dramatically lower low-density lipoprotein concentration (LDL-C) and interleukin eight (IL-8) levels.
Crucially, the results of the subgroup analysis for the participants who were already overweight or obese at
baseline demonstrated that the CR-RS combination intervention was more effective than either CR or RS in
raising the levels of insulin, HOMA-IR, IL-8, systolic blood pressure (SBP), and diastolic blood pressure
(DBP). More importantly, the current study demonstrated that combining CR and exercise could have more
protective effects on young adults' CV health. The study also confirmed the preventative benefits of CR and
exercise on the cardiovascular health of young adults [1].

The first RCT of TRE focused on those involved in 24-hour shift work, including firefighters who have a
higher susceptibility to cardiometabolic illnesses. The study found that a 10-hour TRE intervention was
feasible in firefighters on 24-hour shifts, with participants showing adherence to the eating window and
occasional eating outside the designated window to accommodate extended evening or night calls. The study
observed remarkable changes in activity, sleep, and quality of life, with a significant decrease in self-
reported sleep disturbances in the TRE arm and improvements in subjective views of sleep and health.
Subgroup analyses conducted on participants with elevated cardiometabolic disease risks indicated that
TRE may have a more pronounced and rapid effect on persons who are at a higher risk for developing
cardiometabolic disease. The study estimates that the outcomes of the TRE intervention will effectively
transfer to real-life situations, specifically benefiting persons who work in shifts and those with atypical
sleep-wake patterns [8].

In addition, one research examined the impact of a 12-month long-term TRE regimen on weight
management and cardiovascular and metabolic risk factors in the context of a resistance exercise routine.

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 After 12 months of TRE, the body mass was reduced by 3.4%, and inflammatory markers, lipid profile, and
insulin resistance significantly improved compared with a normal diet (ND) without affecting muscle
performance [11]. However, this improvement in blood biomarkers associated with metabolic and
cardiovascular risk was not seen in a study to evaluate the short-term effects of time-restricted feeding. Even
with short-term interventions, TRF was proven beneficial in promoting weight loss and modifications in
body composition [4].

Despite the comprehensive data, our systematic evaluation has inherent limitations. We exclusively
incorporated data published in English within the past five years. We specifically omitted articles that were
not randomized trials. We exclusively incorporated clinical studies involving human subjects, excluding gray
literature and non-peer-reviewed materials. Some of the research mentioned may suffer from recollection
bias. We need further research on the effect of fasting on preventing CVDs. With the knowledge that we
have right now, incorporating different forms of fasting in diet plans should be encouraged to decrease the
alarming rise in the burden of CVDs.

Conclusions
Fasting and CVDs have a close relationship. We have evidence suggesting that fasting is beneficial in
lowering the cardiovascular risk of a population. This is achieved by improving the lipid profile, improving
metabolic syndrome indicators, improving insulin resistance, and lowering body weight and inflammatory
biomarkers. These results hold for the different types of fasting, i.e., IF, continuous fasting, CR, protein
restriction, and time-restricted eating. The fact that no pharmaceutical medication has such a dramatic
influence on such a wide spectrum of cardiometabolic risk variables makes these findings revolutionary. The
result is pronounced when fasting regimens are combined with a regular exercise routine. Additional clinical
trials and case-control studies, including a bigger sample size, are necessary to obtain more comprehensive
data before reaching a definitive conclusion. It is imperative that we thoroughly investigate all potential
health consequences of fasting.

Additional Information
Author Contributions
All authors have reviewed the final version to be published and agreed to be accountable for all aspects of the
work.

Concept and design: Kirubel T. Hailu, Korlos Salib, Pousette Hamid

Acquisition, analysis, or interpretation of data: Kirubel T. Hailu, Korlos Salib, Sanath Savithri
Nandeesha, Alousious Kasagga, Chnoor Hawrami, Erica Ricci, Pousette Hamid

Drafting of the manuscript: Kirubel T. Hailu, Korlos Salib, Sanath Savithri Nandeesha, Alousious Kasagga,
Chnoor Hawrami, Erica Ricci, Pousette Hamid

Critical review of the manuscript for important intellectual content: Kirubel T. Hailu, Korlos Salib,
Sanath Savithri Nandeesha, Alousious Kasagga, Chnoor Hawrami, Erica Ricci, Pousette Hamid

Supervision: Kirubel T. Hailu, Pousette Hamid

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
KS located relevant studies and contributed to the initial draft of the manuscript. SS helped with the
introduction and background sections. AK aided with the method section, including defining the eligibility
criteria and devising the search strategy. CS contributed to the result section, including the Preferred
Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. Furthermore, ER
provided valuable insights and expertise during the development of the discussion section and the
exploration of limitations associated with the study. All authors read and approved the final manuscript.

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