Impact of Intermittent Fasting on Lipid Profile-A Quasi-Randomized Clinical

Abstract

Background: Sub-optimal HDL is a prognostic marker of cardiovascular disease. South Asia has a high prevalence of sub-optimal HDL compared to other parts of the world. Intermittent fasting (IF) is a type of energy restriction which may improve serum HDL and other lipids thereby reducing the risk of cardiovascular diseases.
Objective: The aim of the study was to evaluate the effect of IF on lipid profile and HDL-cholesterol in a sample of South Asian adults.
Methods: A 6-week quasi-experimental (non-randomized) clinical trial was conducted on participants with low HDL (< 40 mg/dl for men and < 50 mg/dl for women). Participants of the control group were recommended not to change their diet. The intervention group was recommended to fast for ~12 h during day time, three times per week for 6 weeks. Pulse rate, blood pressure, body weight, waist circumference, serum lipid profile, and blood glucose levels were measured at baseline and after 6 weeks.
Result: A total of 40 participants were enrolled in the study ( N = 20 in each group), while 35 (20 control and 15 intervention) completed the trial and were included in data analysis of the study. Body measurements, including body weight, BMI and waist circumference, showed significant interaction effects ( p 's < 0.001), indicating that there were larger reductions in the IF group than in the control group. Significant interaction effects were also observed for total ( p = 0.033), HDL ( p = 0.0001), and LDL cholesterol ( p = 0.010) with larger improvements in the IF group.
Conclusion: This study suggests that intermittent fasting may protect cardiovascular health by improving the lipid profile and raising the sub-optimal HDL. Intermittent fasting may be adopted as a lifestyle intervention for the prevention, management and treatment of cardiovascular disorders.
Clinical Trial Registration: NCT03805776, registered on January 16, 2019, https://clinicaltrials.gov/ct2/show/NCT03805776

Full text

CLINICAL TRIAL
published: 01 February 2021
doi: 10.3389/fnut.2020.596787
Frontiers in Nutrition | www.frontiersin.org 1February 2021 | Volume 7 | Article 596787
Edited by:
Kelly Costello Allison,
University of Pennsylvania,
United States
Reviewed by:
Ulrich Schweiger,
Helios Hanseklinikum, Germany
Marie-Pierre St-Onge,
Columbia University, United States
Jena Shaw Tronieri,
University of Pennsylvania,
United States
*Correspondence:
Naseer Ahmed
dr.naseer99@gmail.com
Specialty section:
This article was submitted to
Eating Behavior,
a section of the journal
Frontiers in Nutrition
Received: 20 August 2020
Accepted: 23 December 2020
Published: 01 February 2021
Citation:
Ahmed N, Farooq J, Siddiqi HS,
Meo SA, Kulsoom B, Laghari AH,
Jamshed H and Pasha F (2021)
Impact of Intermittent Fasting on Lipid
Profile–A Quasi-Randomized Clinical
Trial. Front. Nutr. 7:596787.
doi: 10.3389/fnut.2020.596787
Impact of Intermittent Fasting on
Lipid Profile–A Quasi-Randomized
Clinical Trial
Naseer Ahmed 1
*, Javeria Farooq 1, Hasan Salman Siddiqi 1, Sultan Ayoub Meo 2,
Bibi Kulsoom 3, Abid H. Laghari 4, Humaira Jamshed 5and Farooq Pasha 6
1Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan, 2Department of Physiology,
College of Medicine, King Saud University, Riyadh, Saudi Arabia, 3Postgraduate Programme-Training and Monitoring, Bahria
University Medical and Dental College, Karachi, Pakistan, 4Department of Medicine, Section of Cardiology, Aga Khan
University, Karachi, Pakistan, 5Integrated Sciences and Mathematics, Dhanani School of Science and Engineering, Habib
University, Karachi, Pakistan, 6Economics, Boston College, Chestnut Hill, MA, United States
Background: Sub-optimal HDL is a prognostic marker of cardiovascular disease. South
Asia has a high prevalence of sub-optimal HDL compared to other parts of the world.
Intermittent fasting (IF) is a type of energy restriction which may improve serum HDL and
other lipids thereby reducing the risk of cardiovascular diseases.
Objective: The aim of the study was to evaluate the effect of IF on lipid profile and
HDL-cholesterol in a sample of South Asian adults.
Methods: A 6-week quasi-experimental (non-randomized) clinical trial was conducted
on participants with low HDL (<40 mg/dl for men and <50 mg/dl for women).
Participants of the control group were recommended not to change their diet. The
intervention group was recommended to fast for ∼12 h during day time, three times per
week for 6 weeks. Pulse rate, blood pressure, body weight, waist circumference, serum
lipid profile, and blood glucose levels were measured at baseline and after 6 weeks.
Result: A total of 40 participants were enrolled in the study (N=20 in each group), while
35 (20 control and 15 intervention) completed the trial and were included in data analysis
of the study. Body measurements, including body weight, BMI and waist circumference,
showed significant interaction effects (p’s <0.001), indicating that there were larger
reductions in the IF group than in the control group. Significant interaction effects were
also observed for total (p=0.033), HDL (p=0.0001), and LDL cholesterol (p=0.010)
with larger improvements in the IF group.
Conclusion: This study suggests that intermittent fasting may protect cardiovascular
health by improving the lipid profile and raising the sub-optimal HDL. Intermittent fasting
may be adopted as a lifestyle intervention for the prevention, management and treatment
of cardiovascular disorders.
Clinical Trial Registration: NCT03805776, registered on January 16, 2019, https://
clinicaltrials.gov/ct2/show/NCT03805776
Keywords: intermittent fasting, lipid profile, weight reduction, cardioprotection, healthy life style

Ahmed et al. Intermittent Fasting Effect on Lipid Profile
INTRODUCTION
It is well-documented that dyslipidemia, characterized by high
concentration of serum total cholesterol (TC), low-density
lipoprotein cholesterol (LDL-C) and triglycerides (TG) with low
levels of high-density lipoprotein cholesterol (HDL-C), is linked
to cardiovascular disease (CVD) (1). Some studies have shown
that low HDL-C, with normal LDL-C and triglyceride levels can
be as dangerous for coronary health as high LDL-C (2,3). HDL-
C reverses cholesterol transport and reduces the atherosclerotic
burden. HDL-C also has anti-inflammatory, anti-oxidative, anti-
thrombotic, anti-apoptotic, and vasodilatory properties (4).
Various alternative ways for managing dyslipidemia include
life style modification, regular exercise and moderate alcohol
consumption (5).
Intermittent fasting (IF) can be adopted as a life style
modification for good health and balanced lipid profile. IF is
type of energy restricted feeding protocol known since long
from religious and cultural backgrounds. IF has been extensively
studied in animal models. Such studies indicate that IF improves
lipid profile (6), protects the heart from ischemic injury, and
attenuates post-MI cardiac remodeling (7). Various scientific
studies have been conducted on humans to identify the role
of different IF methods including alternate day fasting, caloric
restriction, Ramadan fasting and periodic fasting etc. Alternate-
day fasting (ADF) reduces body weight by 3–7% over 2–3
month, and improves lipid profiles and blood pressure. It was
suggested that fasting positively impacts metabolic biomarkers
and cardiovascular health while long term effects should be
explored (8). A clinical trial of ADF in adults with obesity found
it as an effective method for weight reduction and reduction in
coronary artery disease risks (9). Additionally, one clinical trial
found ADF effective for weight reduction in people with normal
and overweight (10). Combination of alternate day fasting with
physical activity reports greater changes in body composition and
plasma lipid profile and reduces cardiovascular risk as compared
to individual treatments (11). Keogh et al. found that IF is as
effective for weight management as continuous calorie restriction
for 8 weeks (12). The reduced caloric intake and weight loss
might explain the effects of IF on the lipid profile which may be
translated to improvements in cardio metabolic health (13).
Ramadan fasting studies have shown mixed effects on health.
Some studies found reduction in body weight (14) while others
report minimal change (15). Similar inconsistencies are reported
for the lipid profile and blood glucose levels as well. One
explanation could be the confounding variables such as the
fasting duration, medications, dietary habits, cultural norms and
physical activity (16). Other factors may include methodological
differences, seasonal changes, geographical location, daylight
exposures etc.
The current study trial was designed to investigate the effects
of IF on lipid profile in adults. It was hypothesized that IF
will improve the lipid profile and might prevent cardiovascular
diseases. The study protocol was different from other previously
studied IF methods as it required day time 12 h fasting for 3 days
a week for 6 weeks. It had similarity with Ramadan fasting in that
the fast was kept from sunrise to sunset but it was different from
Ramadan fasting in the aspect that Ramadan fasting requires
daily fasting for four continuous weeks. In this study, IF was
defined as fasting for 3 days in a week for 6 weeks.
METHODS
Study Design
This was a quasi-experimental clinical study conducted on
employees of the Aga Khan University Hospital. People were
informed through emails, phone calls and personal contacts. The
Declaration of Helsinki and Good Clinical Practice guidelines
was followed. After explaining the study protocol to the
participants, written informed consent was collected. Participants
did not receive any incentive, monetary or otherwise, for
participating in this study. Sample size was calculated by
reviewing the previous intermittent fasting trial sample sizes
(17,18). The power of the study for significant improvement in
HDL cholesterol was 80%, with a significance level of 5%.
Participants
Inclusion criteria included age of 20–70 years, with serum HDL <
40 mg/dl for men and <50 mg/dl for women. Pregnant women
and individuals with self-reported cardiovascular diseases or any
other co-morbidity were excluded. Screening was performed and
lipid profile was conducted to confirm HDL levels. A total of 40
subjects (20 in each group) were enrolled in the study.
Data Collection
The employees who agreed to participate in the trial were called
for screening. They were asked to bring their lipid profile result
from the last 4 weeks, if available. The individuals without such
previous lipid profile reports were asked to come after 10–12 h of
fasting so that a lipid profile test could be performed. Individuals
with low HDL levels indicated either by the previous reports
or by currently performed screening lipid profiles were enrolled
in the study. Screening and enrolment were completed in 3–4
weeks. Then enrolled participants were invited to a designated
room in the Multidisciplinary laboratory of Aga Khan University
where questionnaires regarding participants’ eating routine and
physical activity of participant were completed. Body weight,
waist circumference, height and blood pressure were measured.
Body fat and water content were measured by an impedance
scale. Blood was collected for lipid profile testing and glucose
estimation. Participants were called again after 6-weeks whereby
the same body parameters were measured and fasting blood
was collected.
Intervention and Control
The participants were distributed into two groups according
to their group preference; Control and Intervention. Informed
consent form was signed by all the participants. Intervention
group was advised to fast for ∼12 h during day time (6 A.M.−6
P.M.) for only 3 days/week for 6 weeks. The intervention group
was instructed to take their routine diet in the non-fasting
period. The control group continued their usual dietary pattern
and were advised to make no changes in lifestyle. Compliance
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Ahmed et al. Intermittent Fasting Effect on Lipid Profile
was monitored through phone calls and messages every week
for 6 weeks. Although there are no reported adverse effects of
intermittent fasting, the contact number of a doctor was given
to participants in case of any emergency or concern.
TABLE 1 | Baseline description of participants.
Parameters Control Intermittent
fasting
Intermittent
fasting
Enrolled
(n=20)
Completed
trial (n=15)
Age (year) 42.30 ±13.50 36.05 ±12.06 37.80 ±12.25
Gender
Male 12 13 8
Female 8 7 7
BMI (kg/m2)
Underweight 1 1 1
Normal 8 6 2
Overweight 10 11 10
Obese 1 2 2
Blood Pressure
(mmHg)
Systolic 120.90 ±15.41 115.11 ±13.69 114.93 ±13.86
Diastolic 80.65 ±8.18 80.39 ±6.71 79.80 ±5.73
Health condition
(ratio)
Yes: No Yes: No Yes: No
Dyslipidemia 20:00 20:00 15:00
Hypertension 3:17 0:20 0:15
Diabetes mellitus 0:20 0:20 0:15
Cigarette smoking 2:18 0:20 0:15
Family history of
IHD/CVD
2:18 3:17 3:12
Ethical Consideration
The clinical trial was approved by Ethics Review
Committee of Aga Khan University Hospital with
registration number ERC # 2019-0633-2318. The trial
TABLE 3 | Mean difference in parameters after (post) and before (baseline)
intermittent fasting with Control (n=20) and IF (n=15).
Parameters Groups Mean difference P-value
Body weight (kg) Control −0.05 ±0.16 0.757
IF −3.10 ±0.19 0.0001**
BMI (kg/m2) Control −0.04 ±0.11 0.725
IF −0.98 ±0.13 0.0001**
Waist circumference(cm)∧Control −0.11 ±0.16 0.480
IF −0.98 ±0.18 0.0001**
Body Fat (%) Control 0.11 ±0.35 0.760
IF −0.51 ±0.40 0.215
Total cholesterol (mg/dl)∧Control −2.69 ±3.92 0.498
IF −16.08 ±4.53 0.001*
Triglycerides (mg/dl)∧Control −1.68 ±3.95 0.673
IF −12.82 ±4.57 0.008*
LDL (mg/dl)∧Control 2.49 ±1.85 0.187
IF −5.24 ±2.14 0.020*
HDL (mg/dl)∧Control −0.46 ±0.24 0.062
IF 3.04 ±0.27 0.0001**
Blood glucose (mg/dl)∧Control −0.63 ±1.63 0.703
IF 0.62 ±1.89 0.745
Results are presented as mean±SEM. IF, intermittent fasting group; *p<0.05, **p<
0.001; parameters with ∧symbol represents adjustment with body weight.
TABLE 2 | Changes in parameters before (baseline) and after (post) intermittent fasting with Control (n=20) and IF (n=15).
Parameters Groups Baseline Post Interaction effect Time effect
(Time x group)
Body weight (kg) Control 73.07 ±11.63 73.03 ±11.56 0.0001** 0.0001**
IF 75.73 ±12.78 72.63 ±12.23
BMI (kg/m2) Control 25.67 ±3.58 25.63 ±3.50 0.0001** 0.0001**
IF 27.62 ±4.14 26.64 ±4.01
Waist circumference(cm)∧Control 34.57 ±4.39 34.44 ±4.46 0.001* 0.111
IF 34.73 ±4.74 33.77 ±4.75
Body fat (%) Control 31.29 ±8.02 31.40 ±7.94 0.255 0.456
IF 31.87 ±6.14 31.36 ±7.17
Total cholesterol (mg/dl)∧Control 185.00 ±36.27 182.40 ±34.48 0.033* 0.859
IF 198.29 ±38.82 182.09 ±30.56
Triglycerides (mg/dl)∧Control 138.70 ±78.30 137.00 ±74.57 0.075 0.662
IF 135.60 ±60.13 122.80 ±61.48
LDL (mg/dl)∧Control 102.32 ±26.27 104.69 ±24.42 0.010* 0.333
IF 111.04 ±40.71 105.95 ±33.04
HDL (mg/dl)∧Control 34.45 ±6.81 34.01 ±6.48 0.0001** 0.055
IF 35.60 ±6.45 38.62 ±6.45
Blood glucose (mg/dl)∧Control 82.35 ±11.90 81.83 ±7.69 0.623 0.339
IF 80.40 ±10.78 80.87 ±10.04
Results are presented as mean ±SD. IF, intermittent fasting group; *p<0.05, **p<0.001; parameters with ∧symbol represents adjustment with baseline body weight of the entire sample.
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Ahmed et al. Intermittent Fasting Effect on Lipid Profile
was registered at NIH, US National Library of Medicine
as NCT03805776. The study protocol was explained in
detail to all the participants. Privacy and confidentiality
was maintained.
Sample Analysis
Blood samples were centrifuged on the day of collection at 2500
RPM for 15 min at 4◦C. Serum was separated in aliquots and was
stored at −20◦C for lipid analysis. For performing lipid profile
test, cobas c 111 kits (Roche diagnostics, made in Germany) was
used with cobas c 111 automated analyzer (Roche Cobas).
Data Analysis
Data were analyzed using IBM SPSS Statistics 20 and GraphPad
Prism 8. Data are presented as mean ±standard deviation (SD)
in Tables 1,2and figures. However, in Table 3 data is presented
as mean difference ±standard error mean (SEM). The level of
significance was set to α < 0.05 for all performed two-sided
tests. To detect changes over time and respective differences
between the groups, a repeated-measures ANOVA (rmANOVA)
with factors time (pre, post) ×group (IF, Control) was performed
to test for interaction effects. In the case of significant interaction
effects from the rmANOVA, Bonferroni corrected Student’s t-
tests were calculated for any pre to post differences. For metabolic
risk factors, data have been adjusted with mean of body weight of
the entire sample at baseline.
RESULTS
Out of 70 individuals, 40 fulfilled the inclusion criteria and
were enrolled in the study – 20 in each group. Thirty-five
FIGURE 1 | Flow chart of the study trial.
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Ahmed et al. Intermittent Fasting Effect on Lipid Profile
FIGURE 2 | Multiplot figure of body measurements and blood glucose level of control and intervention group at baseline and post study. *p<0.05, **p<0.001.
participants (87.5%) completed the study. Five dropouts from the
intervention group were due to personal reasons or inability to
comply with the fasting regime. Figure 1 summarized the flow of
participants through the study.
The baseline description of participants including age, gender,
blood pressure, BMI level and details of their existing medical
condition is represented in Table 1. The detailed questionnaire
regarding eating routines and physical activity at baseline level
and after post study showed no difference, all the participants
followed their same daily routines as advised.
Table 2 summarize the changes in parameters at baseline
and post 6 weeks study. Body measurements including body
weight and BMI showed significant interaction effects (p=
0.0001) and time effects (p=0.0001) while waist circumference
showed significant interaction effect (p=0.001) only. Significant
interaction effects were exhibited by HDL (p=0.0001), total
cholesterol (p=0.033) and LDL (p=0.010) with non-significant
time effects. Furthermore, body fat, triglycerides and blood
glucose did not show any significant interaction effects.
Table 3 shows the mean changes in body measurements,
lipids, and blood glucose levels from baseline to post-treatment
for the control and intervention groups and the results of post-hoc
analyses of within-group change. The IF group had significant
reductions in body weight (−3.10 ±0.19 kg; p=0.0001), BMI
(−0.98 ±0.13 kg/m2;p=0.0001) and waist circumference
(−0.98 ±0.18 cm; p=0.0001). The mean differences for IF
group were also significant for total cholesterol (−16.08 ±4.53
mg/dl; p=0.001), HDL (3.04 ±0.27 mg/dl (p=0.0001), LDL
(−5.24 ±2.14 mg/dl; p=0.020) and triglycerides (−12.82 ±
4.57 mg/dl; p=0.008). There were no significant changes for any
of the parameters for the control group. However, it should be
noted that the between-group difference in change did not reach
statistical significance for triglycerides.
Figures 2,3represent the comparison of changes in body
measurements, lipid and blood glucose levels of control and
intervention groups at baseline and post intervention with
significance level of interaction effect.
DISCUSSION
The study suggests that IF has the potential of improving the
lipid profile and reducing body weight and waist circumference.
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Ahmed et al. Intermittent Fasting Effect on Lipid Profile
FIGURE 3 | Multiplot figure of lipid levels of control and intervention group at baseline and post study. *p<0.05, **p<0.001.
These results are in line with other studies showing that different
types of IF, including Ramadan fasting and alternative day fasting,
reduce body weight and lipid levels (17,19). Studies combining
IF with physical activity (11) and comparing different types of IF
(12) also suggest that IF can be an effective lifestyle modification
for reducing the risks of cardiovascular diseases. However, most
of the IF clinical trials in the literature were conducted for short
periods of time and large scale randomized controlled trials
with longer duration and follow-ups are not available. Long
term studies should be conducted to validate their effectiveness
and safety.
Santos et al. have compiled data from different trials and
concluded that different types of IF can increase HDL by 1–
14 mg/dl, decrease LDL by 1–47 mg/dl, decrease TC by 5–88
mg/dl and decrease TG by 3–64 mg/dl (18). As compared to
the other types of IF, our method appears safe, effective and
can be adopted in daily life, without any additional financial
or physical burden. Individuals can incorporate IF into their
lifestyles without worrying about any extra efforts to prepare
low calorie meals. The 12-h fast might be maintained by an
early breakfast and having dinner at an appropriate time, which
works for weekdays and weekends. However, it might be difficult
for people working late nights or having an active social life
with frequent dining out routines. This was also observed in the
current study; 5 people dropped out from the study due to their
hectic and busy schedule and could not maintain fasting period
for 3 day/week.
Previously conducted trials have mentioned that intermittent
fasting of 12–36 h results in a metabolic switch (20) leading to
a break down of triglycerides into fatty acids and glycerol and
conversion of fatty acids to ketone bodies in the liver (21). During
fasting, fatty acids and ketone bodies provide energy to cells
and tissues (22). Studies suggested that molecule modulation
in the liver leads to expression of PPARa and PGC-1a that
increases fatty acid oxidation and apoA production leading to
increased HDL levels, whereas apoB decreases which causes
decreased hepatic triglycerides and LDL levels (23,24). Shibata
and colleagues worked on SREPB-2, Sterol regulatory element-
binding protein in mice, and suggested that intermittent fasting
can lead to reduction in cholesterol by regulating SREPB-2 (25).
The main limitations of this study included non-
randomization of the study population. Moderate to severe
dyslipidemic patients were not included in the study. Other
major limitation was the drop out of five participants from the
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Ahmed et al. Intermittent Fasting Effect on Lipid Profile
intervention group of the study which may have inflated the
size of the results. It was a single centered and small-scale study
lacking data on food intake and record of caloric intake.
CONCLUSION
Restriction of food intake for ∼12-h/day for 3 days/week leads to
weight reduction and improvement in lipid profile, particularly
HDL, which can reduce the risk of cardiovascular diseases. Future
studies including randomized controlled trials with more diet
control, longer follow ups and individuals with cardiovascular
diseases and type 2 diabetes mellitus are warranted to validate
these findings.
DATA AVAILABILITY STATEMENT
The raw data supporting the conclusions of this article will be
made available by the authors, without undue reservation.
ETHICS STATEMENT
The studies involving human participants were reviewed and
approved by Ethical Review Committee of Aga Khan University.
The patients/participants provided their written informed
consent to participate in this study.
AUTHOR CONTRIBUTIONS
NA conceived the idea, designed and conducted the trial,
provided the funding support, and supervised the study. JF
conducted the study, managed the project and participants, and
drafted the manuscript. HS, BK, and AHL helped in conducting
the clinical trial, data interpretation, and manuscript review. HJ
reviewed and revised the draft of the manuscript. FP performed
the statistical analysis. SAM provided intellectual input and
resources for performing some analysis. All authors contributed
to the article and approved the submitted version.
ACKNOWLEDGMENTS
We would like to acknowledge the Researchers Supporting
Project Number (RSP-2019/47), King Saud University, Riyadh,
Saudi Arabia. We are also thankful to Prof. Anwar-ul Hassan
Gilani and Prof. Perwaiz Iqbal for their intellectual input,
mentorship and constant support and guidance, and Mr. Ghulam
Haider and MDL/ML lab staff for technical support.
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Conflict of Interest: The authors declare that the research was conducted in the
absence of any commercial or financial relationships that could be construed as a
potential conflict of interest.
Copyright © 2021 Ahmed, Farooq, Siddiqi, Meo, Kulsoom, Laghari, Jamshed and
Pasha. This is an open-access article distributed under the terms of the Creative
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