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J Gandhara Med Dent Sci
October - December 2026
SYSTEMATIC REVIEW
How to cite this article
PHYSIOLOGICAL AND BIOCHEMICAL EFFECTS OF INTERMITTENT FASTING ON INSULIN
SENSITIVITY AND GLUCOSE METABOLISM: A SYSTEMATIC REVIEW
Hina Hakim
1
, Sara Yar Khan
1
, Muhammad Ishraq
2
, Aizazullah
3
, Farzana Salman
4
, Marina Hidayat
5
ABSTRACT
OBJECTIVES
This
study
aimed
to
review
the
physiological
and
biochemical
eects
of
intermittent fasting
on
insulin
sensitivity and
glucose metabolism in human
studies published between 2019 and 2025.
METHODOLOGY
A literature search was conducted in electronic databases, such as PubMed,
Google
Scholar,
ScienceDirect,
SpringerLink,
Wiley
Online
Library
and
Cochrane Library, for original human
studies from January 2019 to December
2025. The studies included in the analysis were randomised controlled trials,
randomised
clinical
trials,
open-label
randomised
trials,
randomised
crossover trials and prospective interventional trials of intermittent fasting or
time-restricted
eating.
There
were
no
reviews,
meta-analyses,
narrative
articles,
case
reports,
animal
or
in
vitro
studies,
nor
pilot
studies.
The
following
data
were
collected
for
study
characteristics,
insulin
sensitivity,
glucose metabolism, physiological outcomes, biochemical markers, and risk of
bias.
RESULTS
Twenty-one original studies were included. Most studies reported favourable
eects of intermittent fasting on glucose regulation, fasting insulin, HOMA-IR,
HbA1c,
continuous
glucose
monitoring
outcomes,
body
weight,
waist
circumference, lipid prole, and cardiometabolic markers. Benets were more
consistent among adults with
obesity,
metabolic
syndrome,
type 2 diabetes,
polycystic ovary syndrome, and increased diabetes risk. Early time-restricted
eating
and
8–10-hour
eating
windows
showed
more
promising
metabolic
eects than less structured fasting patterns. However, the magnitude of benet
varied across studies.
CONCLUSION
Intermittent fasting may improve insulin sensitivity, glucose metabolism, and
related physiological and biochemical outcomes, especially in metabolically
high-risk
adults.
However,
heterogeneity
in
fasting
schedules,
intervention
duration,
population
characteristics,
and
outcome
measures
limits
direct
comparison.
Larger
long-term
randomised
trials
are
needed
to
identify
the
safest and most eective fasting protocols.
KEYWORDS:
Intermittent
Fasting;
Time-Restricted
Eating;
Insulin
Sensitivity;
Glucose
Metabolism;
HOMA-IR;
Hba1c;
Metabolic
Syndrome;
Type 2 Diabetes
INTRODUCTION
Intermittent
fasting
is
a
way
of
eating
that
involves
alternating
between
fasting
and
eating.
Intermittent
fasting is a method of eating that primarily emphasises
when to eat rather than how much to eat, in contrast to
the
other
diet
plans
mentioned,
which
are
calorie-
restricted diets.
1
Commonly used methods include time-
restricted eating, early time-restricted feeding, alternate-
day fasting, modied fasting, 5:2 fasting, and periodic
24-hour fasts. The concept of IF has gained signicant
traction in recent years, sparking an interest in its use for
weight
management,
metabolic
control,
and
cardiovascular
disease
prevention.
2
Many
aspects
of
metabolic health involve insulin sensitivity and glucose
metabolism. Lower insulin sensitivity is associated with
hyperinsulinaemia,
impaired
fasting
glucose,
type
2
diabetes
Mellitus,
metabolic
syndrome,
fatty
liver
disease
and
cardiovascular
risk.
Standard
therapies
involve
diet
change,
exercise,
weight
loss,
and/or
medications
(where
needed).
Long-term
sustaining
continuous
calorie
restriction,
however,
is
dicult.
Intermittent
fasting
has
thus
been
suggested
as
an
alternative or adjunct lifestyle strategy that would yield
beneficial
metabolic
eects
by
decreasing
meal
frequency, decreasing the amount of consumed energy,
Hakim H, Khan SY, Ishraq M,
Aizazullah, Salman F, Hidayat M.
Physiological and Biochemical Eects
of Intermittent Fasting on Insulin
Sensitivity and Glucose Metabolism:
A Systematic Review. J Gandhara
Med Dent Sci. 2026;13(4): 163-173.
Date Submission:
16-07-2026
Date Revised:
17-09-2026
Date Acceptance:
23-09-2026
2
Lecturer, Department of Physiology,
Peshawar Medical and Dental College,
Peshawar
3
Lecturer, Department of
Biochemistry, Peshawar Medical and
Dental College, Peshawar
4
Professor, Department of Physiology,
Peshawar Medical and Dental College,
Peshawar
5
Assistant Professor, Department of
Physiology, Peshawar Medical and
Dental College, Peshawar
Correspondence
1
Sara Yar Khan, Assistant Professor,
Department of Biochemistry,
Peshawar Medical and Dental College,
Peshawar
:
+92-332-4992929
:
asad_sarwar77@gmail.com
http://doi.org/10.37762/jgmds.13-4.968
164
J Gandhara Med Dent Sci
October - December 2026
increasing
circadian
rhythmicity,
improving
fat
oxidation, and modifying insulin and glucose responses.
3
There
are
several
biological
mechanisms
that
could
account for the eect of intermittent fasting on glucose
metabolism.
Insulin
drops
during
fasting,
hepatic
glycogen
is
depleted
and
lipolysis
and
fatty
acid
oxidation increase. Frequent fasting may lead to better
metabolic
exibility,
decreased
ectopic
fat
deposition,
better
insulin
signalling
and
decreased
postprandial
glucose exposure.
4
Early time-restricted eating could be
even
more
benecial
due
to
the
fact
that
glucose
tolerance and insulin sensitivity tend to be higher in the
morning
compared
to
the
evening.
Thus,
the
time
of
eating could be crucial as well as the length of the fast.
1
Intermittent
fasting
has
been
clinically
tested
across
a
diverse
range
of
populations,
such
as
healthy
adults,
overweight
or
obese
individuals,
metabolic
syndrome
patients,
adults
with
type
2
diabetes,
women
with
polycystic
ovary
syndrome
and
patients
with
non-
alcoholic
fatty
liver
disease.
Results
reported
include
fasting
glucose,
fasting
insulin,
HOMA-IR,
HbA1c,
postprandial
glucose,
continuous
glucose
monitoring,
body
weight,
BMI,
waist
circumference,
lipid
prole,
inammatory
markers,
oxidative
stress
markers,
blood
pressure, and liver-related biochemical markers. There
are benecial eects reported in many studies, but the
results
are
not
entirely
consistent.
Some
trials
have
reported signicant improvements in glycaemic control
and
insulin
resistance.
In
contrast,
other
trials
have
reported
statistically
signicant
but
modest
changes
in
glycaemic
control
and
insulin
resistance,
particularly
those
trials
where
intervention
duration
was
brief
or
calorie
intake
was
controlled.
5,6
Differences
in
the
fasting
schedule,
eating
window,
intervention
period,
adherence,
baseline
metabolism,
medication,
physical
activity, and study design could be responsible for the
discrepancies among the reported results. For instance,
an early eating window could yield dierent metabolic
effects
than
a
late
eating
window;
fasting
and
calorie
restriction or exercising could have a greater eect than
fasting alone. Such dierences render it dicult to be
general when interpreting the results of each individual
study
and
give
arguments
for
the
need
for
systematic
synthesis
of
the
available
evidence.
7
This
systematic
review
was
therefore
conducted
to
evaluate
the
physiological
and
biochemical
eects
of
intermittent
fasting
on
insulin
sensitivity
and
glucose
metabolism.
The review focused on original human studies published
between
2019
and
2025
and
excluded
reviews,
meta-
analyses, narrative articles, case reports, animal studies,
and
pilot
studies.
The
aim
was
to
summarise
the
available evidence on fasting-related changes in glucose
regulation,
insulin
sensitivity,
HbA1c,
body
composition,
lipid
prole,
inammatory
markers,
oxidative stress markers, blood pressure, and tolerability,
while also considering variation in fasting protocols and
study populations.
METHODOLOGY
A
systematic
review
was
performed
to
assess
the
physiological
and
biochemical
changes
in
insulin
sensitivity
and
glucose
metabolism
seen
with
IF.
The
review was developed as a qualitative systematic review
without
meta-analysis
due
to
the
dierences
in
the
characteristics
of
the
population
studied,
fasting
protocols,
treatment
duration,
variables
measured
as
outcomes,
and
study
design.
The
methodology
was
designed following the general principles of reporting a
systematic
review,
paying
special
attention
to
the
transparent identication, selection, data extraction, and
risk
of
bias
assessment
of
studies.
A
comprehensive
literature
search
was
performed
to
identify
original
human
studies
published
from
January
2019
to
December
2025.
Electronic
databases
including
PubMed, Google Scholar, ScienceDirect, SpringerLink,
Wiley
Online
Library,
and
Cochrane
Library
were
searched.
The
search
terms
were
used
alone
and
in
combination:
"intermittent
fasting,"
"time-restricted
eating," "time-restricted feeding," "early time-restricted
feeding,"
"alternate-day
fasting,"
"5:2
diet,"
"insulin
sensitivity," "insulin resistance," "HOMA-IR," "fasting
glucose,"
"fasting
insulin,"
"HbA1c,"
"glucose
metabolism," "type 2 diabetes," "metabolic syndrome,"
and "obesity." Boolean operators such as AND and OR
were used to rene the search strategy. Reference lists of
relevant articles were also screened manually to identify
additional
eligible
studies.
The
studies
included
those
that
met
the
following
criteria:
They
were
original
human
studies
published
from
2019
to
2025,
and
examined the impact of IF or TRE on insulin sensitivity,
glucose
metabolism,
or
associated
physiological
or
biochemical responses. Study designs that were eligible
were randomised controlled trials (RCTs), randomised
clinical trials (RCTs), randomised crossover trials, open-
label
randomised
trials,
and
prospective
interventional
studies.
Adults
with
obesity,
overweight,
metabolic
syndrome, type 2 diabetes mellitus, non-alcoholic fatty
liver disease, polycystic ovary syndrome or raised risk of
diabetes were included in the studies. Studies in healthy
adult
subjects
were
also
included
if
they
mentioned
glucose-related
or
metabolic
outcomes.
Systematic
reviews,
animal
studies,
in
vitro
studies,
pilot
studies,
editorials,
letters,
commentaries,
case
reports,
case
studies,
narrative
and
scoping
reviews
were
excluded
from the studies. Moreover, studies that did not evaluate
intermittent fasting as a primary intervention and studies
that
did
not
report
insulin
sensitivity,
glucose
metabolism,
or
biochemical
metabolic
markers
were
excluded.
Duplicate
records
and
articles
lacking
methodological
and/or
outcome
information
were
Physiological and Biochemical Eects of Intermittent Fasting
165
J Gandhara Med Dent Sci
October - December 2026
removed during screening. The selection process for the
study
was
done
in
a
graduated
manner.
Captions
and
abstracts of the articles were rst read to exclude those
that
were
obviously
out
of
scope.
Second,
full-text
articles were screened for inclusion and exclusion based
on the pre-established inclusion and exclusion criteria.
Qualitative synthesis of studies included only those that
met
all
the
criteria.
Twenty-one
original
studies
were
included
in
the
nal
review.
The
studies
featured
a
variety
of
dierent
types
of
intermittent
fasting,
including
16:8,
early
time-restricted
feeding,
8-hour
fasting,
10-hour
fasting,
once-weekly
24-hour
fasting,
modified
intermittent
fasting,
calorie
restriction
or
exercise intermittently, and early time-restricted feeding.
A
structured
format
was
used
to
extract
data.
The
information extracted was author,
year, country,
study
design,
sample
size,
study
population,
age
group,
intervention
period,
fasting
protocol,
and
feeding
window.
Data
on
fasting
glucose,
fasting
insulin,
HOMA-IR,
insulin
sensitivity,
glycated
haemoglobin
(HbA1c),
continuous
glucose
monitoring,
adverse
effects, postprandial glycemia, body weight, BMI, waist
circumference,
lipid
prole,
inammatory
markers,
oxidative
stress
markers,
blood
pressure,
and
cardiometabolic
markers
were
collected.
Data
were
summarised
in
tabular
form
for
comparison
between
studies. Insulin sensitivity and glucose metabolism were
the major outcomes to be measured. These encompass
changes
in
fasting
blood
glucose,
fasting
insulin,
HOMA-IR,
HbA1c,
postprandial
glucose,
continuous
glucose
monitoring
parameters
and
β
-cell
function
(if
reported). The secondary outcomes were physiological
and
biochemical
parameters
like
body
weight,
BMI,
waist
circumference,
body
composition,
lipid
prole,
inammatory markers, oxidative stress markers, blood
pressure,
liver-related
biochemical
markers,
and
tolerability of intermittent fasting interventions. Due to
the variability of the fasting schedules, fasting duration,
participants'
characteristics
and
reported
results
of
the
included
studies,
a
meta-analysis
was
not
conducted.
Rather, ndings were brought together in a "narrative"
way.
Study
characteristics,
glucose-related
outcomes,
and
overall
physiological
and
biochemical
eects
categorised
the
outcomes.
This
approach
enabled
the
patterns
to
be
interpreted
across
studies
and
the
heterogeneity of the fasting protocols and populations.
The methodological domains of the included studies that
were deemed relevant to interventional studies were used
to
evaluate
the
risk
of
bias.
These
domains
included
randomisation
process;
selection
bias;
blinding
or
performance
bias;
completeness
of
outcome
data;
attrition
bias;
reliability
of
outcome
measurement;
selective
reporting;
and
overall
study
conduct.
In
randomised
studies,
Cochrane
RoB
2
style
judgement
was done with the categories of low risk, some concerns,
and high risk. Selection of participants, comparability,
clarity
of
intervention,
outcome
measurement,
and
follow-up
were
the
criteria
for
the
assessment
in
the
prospective
interventional
study.
These
domains
were
then
used
to
determine
an
overall
judgment
for
each
study.
Overall,
this
methodology
was
a
systematic
approach
to
identifying,
selecting,
extracting
and
synthesising
evidence
pertaining
to
the
eect
of
intermittent
fasting
on
insulin
sensitivity
and
glucose
metabolism.
The
use
of
predened
eligibility
criteria,
structured data
extraction, and risk
of bias
assessment
ensured
that
there
was
greater
transparency
and
reliability of the review ndings.
Figure 1: PRISMA Flow Diagram Showing the Study Selection
Process for the Systematic Review
A total of 515 records were identied, 385 records were
screened after removal of duplicates and other ineligible
records, 91 full-text reports were assessed for eligibility,
and
21
original
studies
were
included
in
the
nal
qualitative synthesis.
RESULTS
Table
1
summarises
21
original
studies
published
between
2019
and
2025
that
evaluated
intermittent
fasting
and
glucose-related
metabolic
outcomes.
The
majority of studies were
randomised controlled trials or
randomised
clinical
trials;
some
were
crossover
and
a
few
were
prospective
interventional
designs.
Studies
were
carried
out
in
various
countries
and
involved
various
populations,
including
adults
with
obesity,
metabolic syndrome, type 2 diabetes, non-alcoholic fatty
liver disease, polycystic ovary syndrome and people who
are
at
risk
of
developing
type
2
diabetes. The
sample
sizes
ranged
from
small
to
large,
and
the
intervention
Physiological and Biochemical Eects of Intermittent Fasting
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J Gandhara Med Dent Sci
October - December 2026
periods ranged from short-term studies to up to 6 months.
The
most
frequently
used
intervention
was
time-
restricted
feeding,
but
the
5:2
fasting
diet,
modied
intermittent
fasting,
once-weekly
fasting
and
fasting
with exercise or calorie restriction were also employed.
The table reveals a wide variety of evidence relevant to
this
study,
and
appropriate for
narrative synthesis, but
not for meta-analysis.
Table 1: Characteristics of Included Studies Evaluating Intermittent Fasting and Glucose
-Related
Metabolism
Study
Country
Design / n
Population
Duration
Fasting protocol
Jamshed et al., 2019
[8]
USA
Randomised crossover
trial; n=11
Overweight adults
4 days
Early time-restricted
feeding, eating
between 8:00 am and
2:00 pm
Tinsley et al., 2019 [9]
USA
Randomised trial; n=40
Active/resistance-trained
females (Young adults)
8 weeks
Time-restricted
feeding with
resistance training
Lowe et al., 2020 [10]
USA
Randomised clinical
trial; n=116
Adults with overweight or
obesity
12 weeks
16:8 time-restricted
eating
Cienfuegos et al., 2020
[11]
USA
Randomised controlled
trial; n=58
Adults with obesity
8 weeks
4-hour and 6-hour
time-restricted
feeding
Kunduraci and Ozbek,
2020 [12]
Turkey
Randomised controlled
trial; n=70
Adults with metabolic
syndrome
12 weeks
Energy-restricted
intermittent fasting
diet
Guo et al., 2021 [13]
China
Randomised clinical
trial; n=39
Patients with metabolic
syndrome (3050 years)
8 weeks
Two-day modified
intermittent fasting
Che et al., 2021 [14]
China
Randomised controlled
trial; n=120
Overweight adults with type 2
diabetes mellitus (1870
years)
12 weeks
10-hour time-
restricted feeding,
eating between 8:00
am and 6:00 pm
Li et al., 2021 [15]
China
Prospective
interventional study;
n=18
Women with anovulatory
polycystic ovary syndrome
(Reproductive age)
5 weeks
8-hour time-restricted
feeding
Bartholomew et al.,
2021 [16]
USA
Randomised controlled
trial; n=103
Adults with elevated LDL-C
and metabolic risk features
(2170 years)
26 weeks
Water-only 24-hour
fasting twice weekly
initially, then once
weekly
Xie et al., 2022 [17]
China
Randomized controlled
trial; n=90 randomized;
82 completed
Healthy adults without
obesity
5 weeks
Early time-restricted
feeding and mid-day
time-restricted
feeding
Zhang et al., 2022 [18]
China
Randomised controlled
trial; n=60
Overweight and obese young
adults (Young adults)
8 weeks
6-hour early or late
time-restricted eating
Jamshed et al., 2022
[19]
USA
Randomised clinical
trial; n=90
Adults with obesity
14 weeks
Early time-restricted
eating plus energy
restriction
Andriessen et al., 2022
[20]
Netherlands
Randomised crossover
trial; n=14
Adults with type 2 diabetes
mellitus
3 weeks
10-hour time-
restricted eating
Kord Varkaneh et al.,
2022 [21]
Iran
Randomised controlled
trial; n=80
Patients with non-alcoholic
fatty liver disease
12 weeks
5:2 intermittent
fasting diet
Teong et al., 2023 [22]
Australia
Randomised controlled
trial; n=209
Adults at increased risk
of
type 2 diabetes
6 months
Intermittent
fasting
plus early time-
restricted eating
Pavlou et al., 2023 [23]
USA
Randomised clinical
trial; n=75
Adults with type 2 diabetes
mellitus and obesity
6 months
8-hour time-restricted
eating
Parr et al., 2023 [24]
Australia
Randomised crossover
trial; n=14
Adults with type 2 diabetes
mellitus
Short-term
intervention
Time-restricted
eating compared with
habitual eating
pattern
Quist et al., 2024 [25]
Denmark
Open-label randomised
controlled trial; n=100
Adults at high risk of type 2
diabetes
3 months plus
follow-up
10-hour time-
restricted eating
Manoogian et
al., 2024
[26]
USA
Randomised controlled
trial; n=108
Adults with metabolic
syndrome
3 months
Personalised 810-
hour time-restricted
eating
Kramer et al., 2025 [6]
Canada
Randomised crossover
trial; n=39
Adults with type 2 diabetes
mellitus
Short-term
intervention
Time-restricted
eating
Bravo-Garcia et al.,
2025 [27]
Australia
Randomised controlled
trial; n=Not specied in
abstract
Adults with type 2 diabetes
mellitus
Short-term
intervention
Time-restricted
eating combined with
exercise
Physiological and Biochemical Eects of Intermittent Fasting
167
J Gandhara Med Dent Sci
October - December 2026
Across studies, early TRE and 8-10-hour eating windows were most consistently associated with favourable changes
in
glucose
regulation,
fasting
insulin,
HOMA-IR/insulin
sensitivity,
HbA1c,
or
continuous
glucose-monitoring
outcomes. Eects were more apparent in metabolically high-risk populations than in healthy adults, although several
trials reported modest or non-signicant changes, demonstrating substantial between-study variability.
Table 2: Eects of Intermittent Fasting on Insulin Sensitivity and Glucose Metabolism
Study
Glycaemic control
Fasting insulin
HOMA-IR / insulin
sensitivity
HbA1c
Jamshed et al., 2019 [8]
Improved 24-hour
glucose prole
Reduced insulin
response
Insulin-related metabolic
response improved
NR
Tinsley et al., 2019[9]
No major adverse
change reported
No clear change
No consistent
improvement
NR
Lowe et al., 2020 [10]
No significant
dierence vs control
No meaningful change
No clear improvement
NR
Cienfuegos et al., 2020
[11]
Mild improvement in
metabolic prole
Reduced fasting insulin
Insulin resistance
improved
NR as a primary outcome
Kunduraci and Ozbek,
2020 [12]
Fasting glucose
decreased
Variable
HOMA-IR improved
HbA1c decreased
Guo et
al., 2021 [13]
Fasting glucose
improved
Insulin level improved
Insulin resistance
decreased
NR
Che et al., 2021 [14]
Blood glucose control
improved
Fasting insulin
decreased
Insulin sensitivity
improved
HbA1c improved
Li et al., 2021 [15]
Glucose metabolism
improved
Insulin level reduced
HOMA-IR improved
NR
Bartholomew et al.,
2021 [16]
No strong consistent
glucose benet reported
Not consistently
improved
No clear insulin-
sensitivity benet
reported
No major improvement
reported
Xie et al., 2022 [17]
Fasting glucose
improved, especially
with early eating
Insulin-related markers
improved
Insulin sensitivity
improved more with
early eating
Not the main outcome
Zhang et al., 2022 [18]
Glucose markers
improved modestly
Insulin response
improved
Insulin sensitivity
improved
Not clearly reported
Jamshed et al., 2022 [19]
No major independent
fasting glucose
advantage
No major independent
improvement
No clear additional
improvement beyond
weight loss
Not strongly improved
Andriessen et al., 2022
[20]
Glucose homeostasis
improved
Not clearly improved
Insulin sensitivity did
not significantly improve
Not the main outcome
Kord Varkaneh et al.,
2022 [21]
Glucose-related markers
improved
Insulin markers
improved
HOMA-IR improved
Not clearly reported
Teong et al., 2023 [22]
Postprandial glucose
improved
Variable eect
Insulin-related response
improved
Not the main primary
outcome
Pavlou et al., 2023 [23]
Glycaemic control
improved
Not consistently
reported
Not clearly improved in
all markers
HbA1c decreased
Parr et al., 2023 [24]
Daily glucose control
improved
Not the main nding
Not clearly reported
CGM-based glucose control
improved
Quist et al., 2024 [25]
Glucose markers
showed limited or
modest change
No consistent major
improvement
No strong improvement
reported
No clear sustained
improvement
Manoogian et al., 2024
[26]
Glucose regulation
improved modestly
No major change in
fasting insulin
No major HOMA-IR
improvement
HbA1c decreased slightly
Kramer et al., 2025 [6]
Glycaemic control
improved in selected
measures
Insulin-secretory
response assessed
β
-cell function improved
HbA1c/glucose markers
assessed
Bravo-Garcia et al.,
2025 [27]
Short-term blood
glucose management
improved
NR
NR
Short-term glucose indices
improved
Physiological and biochemical eects extended beyond glycaemic outcomes. Many studies reported reductions in
body weight or waist circumference and selected improvements in lipid or cardiometabolic markers, whereas changes
in inammatory and oxidative-stress outcomes were less consistently reported. Tolerability was generally acceptable,
although adherence and intervention
duration varied.
Physiological and Biochemical Eects of Intermittent Fasting
168
J Gandhara Med Dent Sci
October - December 2026
Table 3: Physiological and biochemical outcomes reported in the included studies
Study
Weight / body
composition
Lipids
Inflammation /
oxidative stress
BP /
cardiometabolic
Tolerability
Jamshed et al., 2019
[8]
No major weight-
loss eect due to
short duration
No major lipid
change reported
Markers related to
circadian rhythm,
aging, and
autophagy were
affected
Some improvement
in metabolic rhythm
was noted
Well tolerated
Tinsley et al.,
2019[9]
Body weight was
largely maintained;
Lean mass was
preserved with
resistance training
No major harmful
lipid change
reported
NR
No major adverse
cardiometabolic
effect
Well tolerated
among active
females
Lowe et al., 2020
[10]
Modest weight
reduction was
observed; Lean mass
reduction was a
concern
No major lipid
improvement
reported
NR
No clear
improvement in
cardiometabolic
markers
Generally
acceptable, but
metabolic
advantage was
limited
Cienfuegos et al.,
2020 [11]
Decreased; Waist
circumference and
fat mass decreased
Triglycerides and
oxidative-stress-
related markers
improved in some
groups
Oxidative stress
markers improved
Blood pressure and
insulin resistance
improved
Mild hunger and
adjustment
symptoms may
occur
Kunduraci and
Ozbek, 2020 [12]
Weight and BMI
decreased; Central
obesity markers
improved
Total cholesterol,
triglycerides, and
LDL-C improved
Inammatory
markers showed
favourable change
Blood pressure and
metabolic syndrome
components
improved
Generally
acceptable
Guo et al., 2021
[13]
Decreased;
Abdominal obesity
markers improved
Lipid parameters
improved
Gut microbiota
composition
changed favourably
Cardiometabolic risk
prole improved
No serious safety
concern reported
Che et al., 2021 [14]
Decreased; Waist
circumference
decreased
Lipid prole
showed
improvement
NR
Blood pressure and
metabolic risk
markers improved
Well tolerated
Li
et al., 2021 [15]
Weight and BMI
decreased; Waist
circumference
improved
Lipid abnormalities
improved
NR
Endocrine and
metabolic markers
improved
Well tolerated
Bartholomew et al.,
2021 [16]
Weight change was
modest
LDL-C and other
lipid markers were
assessed
NR
Cardiovascular risk
markers were
evaluated
Water-only fasting
was
feasible for
selected participants
Xie et al., 2022 [17]
Modest decrease;
Body fat and body
composition
improved
Lipid changes were
modest
Inammatory
markers were not
central outcomes
Blood pressure and
metabolic rhythm
improved, especially
with early feeding
Generally safe
Zhang et al., 2022
[18]
Weight and BMI
decreased; Fat mass
and waist measures
improved
Lipid prole
improved in
selected markers
NR
Cardiometabolic
indicators improved
No major adverse
effects reported
Jamshed et al., 2022
[19]
Weight decreased;
Fat mass and body
composition
improved
Lipid changes were
modest
Not the main focus
Blood pressure and
mood-related
outcomes improved
Generally
acceptable
Andriessen et al.,
2022 [20]
Weight decreased
slightly
Lipid prole
showed limited
change
NR
Twenty-four-hour
glucose prole
improved
Feasible
Kord Varkaneh et
al., 2022 [21]
Body weight and
BMI decreased;
Waist circumference
improved
Lipid prole
improved
Liver-related
biochemical markers
improved
Metabolic risk
prole improved
Well tolerated
Teong
et al., 2023
[22]
Decreased; Body fat
and waist measures
improved
Lipid response
varied
Not central to the
main outcome
Postprandial
metabolic control
improved
Acceptable
adherence reported
Pavlou et al., 2023
[23]
Decreased; Waist
circumference and
fat mass improved
Lipid prole
changes were
variable
NR
HbA1c and
metabolic health
improved
Generally safe and
acceptable
Parr et al., 2023 [24]
Not the main
outcome; Not the
main outcome
NR
NR
Continuous glucose
monitoring outcomes
improved
Short-term
intervention was
feasible
Physiological and Biochemical Eects of Intermittent Fasting
169
J Gandhara Med Dent Sci
October - December 2026
Study
Weight / body
composition
Lipids
Inflammation /
oxidative stress
BP /
cardiometabolic
Tolerability
Quist et al., 2024
[25]
Modest decrease;
Slight improvement
Limited change
NR
Modest/partly
sustained
Well tolerated
Manoogian et al.,
2024 [26]
Decreased; Waist
circumference and
body composition
improved
Modest
improvement
NR
Improved
Feasible with
personalised
schedule
Kramer et al., 2025
[6]
Weight change was
not the central
outcome; Not a
main outcome
NR
NR
β
-cell function and
glucose regulation
were assessed
Acceptable short
term
Bravo-Garcia et al.,
2025 [27]
Exercise-related
body changes were
assessed; Body
composition
outcomes were
linked with exercise
Lipid outcomes
were not the main
focus
NR
Short-term
glycaemic control
improved when
fasting was
combined with
exercise
Feasible
Risk-of-bias assessment classied 10 studies as low overall risk and 11 as having some concerns; no study was judged
to be at high overall risk. The most frequent concerns related to the inability to blind behavioural dietary interventions,
small
samples,
short
intervention
periods,
limited
adherence
reporting,
and
incomplete
follow
-
up.
Objective
biochemical and clinical outcomes reduced
concern regarding outcome measurement in many studies.
Study
Design
Randomisation /
selection
Blinding /
performance
Missing data
Outcome
measurement /
reporting
Overall risk
Table 4: Risk-of-Bias Assessment of Included Studies
Jamshed et al.,
2019 [8]
Randomised
crossover trial
Low
Some concerns
Low
Low / Low
Some concerns
Tinsley et al.,
2019[9]
Randomised trial
Some concerns
Some concerns
Low
Low / Low
Some concerns
Lowe et al., 2020
[10]
Randomised
clinical trial
Low
Some concerns
Low
Low / Low
Low
Cienfuegos et al.,
2020 [11]
Randomised
controlled trial
Low
Some concerns
Low
Low / Low
Low
Kunduraci and
Ozbek, 2020 [12]
Randomised
controlled trial
Low
Some concerns
Some concerns
Low / Some concerns
Some concerns
Guo et al., 2021
[13]
Randomised
clinical trial
Low
Some concerns
Low
Low / Low
Low
Che et al., 2021
[14]
Randomised
controlled trial
Low
Some concerns
Low
Low / Low
Low
Li et al., 2021 [15]
Prospective
interventional study
Some concerns
Some concerns
Some concerns
Low / Some concerns
Some concerns
Bartholomew et al.,
2021 [16]
Randomised
controlled trial
Low
Some concerns
Some concerns
Low / Low
Some concerns
Xie et al., 2022 [17]
Randomised
controlled trial
Low
Some concerns
Low
Low / Low
Low
Zhang et al., 2022
[18]
Randomised
controlled trial
Low
Some concerns
Low
Low / Low
Low
Jamshed et al.,
2022 [19]
Randomised
clinical trial
Low
Some concerns
Low
Low / Low
Low
Andriessen et al.,
2022 [20]
Randomised
crossover trial
Low
Some concerns
Low
Low / Low
Some concerns
Kord Varkaneh et
al., 2022 [21]
Randomised
controlled trial
Low
Some concerns
Some concerns
Low / Some concerns
Some concerns
Teong et al., 2023
[22]
Randomised
controlled trial
Low
Some concerns
Low
Low / Low
Low
Pavlou et al., 2023
[23]
Randomised
clinical trial
Low
Some concerns
Low
Low / Low
Low
Parr et al., 2023
[24]
Randomised
crossover trial
Some concerns
Some concerns
Low
Low / Low
Some concerns
Quist et al., 2024
[25]
Open-label
randomised
controlled trial
Low
Some concerns
Low
Low / Low
Some concerns
Manoogian et al.,
2024 [26]
Randomised
controlled trial
Low
Some concerns
Low
Low / Low
Low
Kramer et al., 2025
[6]
Randomised
crossover trial
Low
Some concerns
Low
Low / Low
Some concerns
Bravo-Garcia et al.,
2025 [27]
Randomised
controlled trial
Low
Some concerns
Some concerns
Low / Low
Some concerns
Physiological and Biochemical Eects of Intermittent Fasting
170
J Gandhara Med Dent Sci
October - December 2026
DISCUSSION
The
present
systematic
review
found
that
intermittent
fasting, especially time-restricted eating and early time-
restricted
feeding,
was
generally
associated
with
favourable eects on glucose regulation, fasting insulin,
HOMA-IR,
HbA1c,
continuous
glucose
monitoring
outcomes,
body
weight,
waist
circumference,
and
broader
cardiometabolic
markers.
These
ndings
are
supported
by
recent
external
evidence
showing
that
fasting-based
dietary
approaches
may
improve
metabolic control through reduced eating duration, lower
total energy intake, circadian alignment, and improved
substrate
utilisation.
For
example,
Oldenburg
et
al.
reported that self-selected 8-hour time-restricted eating
was
comparable
to
calorie
restriction
for
several
glycaemic and body composition outcomes, although it
did not produce superior metabolic exibility compared
with
calorie
restriction.
28
Similarly,
Maruthur
et
al.
showed
in
a
controlled
feeding
randomised
trial
that
isocaloric time-restricted eating alone may not produce
marked
weight
loss
when
calories
are
held
constant,
suggesting that part of the benet of fasting may depend
on spontaneous calorie reduction rather than meal timing
alone.
29
This supports the
interpretation
of
the
present
review that intermittent fasting is benecial, but its eect
size
depends
on
fasting
protocol,
calorie
intake,
and
participant
adherence.
The
review
also
identied
potential greater benets on glucose measures in adults
with
obesity,
metabolic syndrome,
prediabetes,
type
2
diabetes,
and
polycystic
ovary
syndrome
than
in
metabolically
healthy
adults.
This
is
similar
to
other
external studies of high-risk metabolic groups. In adults
with early type 2 diabetes, an intermittent fasting meal-
replacement
diet
resulted
in
a
greater
reduction
in
HbA1C
compared
to
adults
who
were
treated
with
metformin or empagliflozin, reported Guo et al.
30
Zheng
et
al.
also
discovered
that
the
group
receiving
8-hour
time-restricted
eating
and
the
calorie-restricted
eating
regimen lost weight and had enhanced insulin resistance
in overweight or obese women with PCOS.
31
Our present
review
results
are
in
line
with
the
non-randomised
controlled trial conducted by Ekberg et al., which found
that a 5:2 diet led to a change in insulin secretion and
insulin
sensitivity
markers
in
obese
and
overweight
adults.
32
They
also
indicate
that
the
combined
interventions, like fasting and calorie restriction or meal
replacement,
can
lead
to
more
pronounced
metabolic
effects than fasting. The timing of food intake appears to
be
an
important
factor
in
the
metabolic
response
to
intermittent fasting. The present review has noted that
early
time-restricted
eating
and
810
hour
eating
windows were most consistently linked to improvements
in glucose regulation, while later or unrestricted eating
windows
were
not
linked.
This
is
plausible
from
a
biological standpoint, as insulin sensitivity and glucose
tolerance tend to be higher in the morning. This idea is
further
reinforced
by
external
evidence.
Karras
et
al.
identified an improvement in body weight, lipid prole
and
glycaemic
markers
during
Orthodox
religious
fasting and compared it
with a
combined energy- and
time-restricted
dietary
pattern.
33
Based
on
recent
metabolic evidence, Lange et al. concluded that
although
weight loss is benecial, intermittent fasting's eects on
glucose and lipid metabolism are not necessarily directly
proportional
to
the
actual
amount
of
weight
lost.
5
Likewise, Horne et al. found that individual hormonal
status, such as baseline human growth hormone (hGH),
could
inuence
the
insulin-resistance
response
to
repeated fasting.
8
These results indicate the importance
of taking into account the fasting timing, hormonal status
and
metabolic
phenotype
when
interpreting
results
of
dierent studies. The current review also conrmed that
intermittent fasting can induce benecial eects in other
physiological and biochemical parameters, such as body
weight,
body
mass
index,
waist
circumference,
lipid
profile,
blood
pressure,
liver-related
parameters,
oxidative
stress,
and
inammatory
prole.
External
studies
with
models
based
on
Ramadan
or
religious
fasting conrm this more general eect. Among adults
with
obesity,
Oueslati
et
al.
found
changes
in
cardiometabolic
and
inammatory
markers
related
to
Ramadan
intermittent fasting.
34
Ahmed et al. found that
Ramadan
fasting
in
individuals
with
metabolic
dysfunction-associated
steatotic
liver
disease
was
associated
with changes in
metabolic and liver-related
parameters.
35
In addition, Faris et al. identied that there
were
signicant
plasma
metabolomic
dierences
in
overweight and obese individuals during the Ramadan
diurnal
intermittent
fasting
period,
and
Shatila
et
al.
demonstrated changes in dietary intake patterns during
Ramadan
fasting
in
healthy
adults
throughout
the
year.
36,37
These results are consistent with the fact that
fasting
has
been
found
to
impact
several
biological
pathways
as
observed
in
the
current
review:
energy
balance, lipid handling, oxidative stress, inammation,
and hepatic metabolism. Overall results were favourable;
however, data were not consistent and should be viewed
with caution. Inconsistent ndings of robust eects of
fasting
and
moderate
eects
have
been
attributed
to
variations in the fasting regimen (such as the number of
hours or days of fasting), duration of fasting intervention,
calorie
intake,
baseline
metabolic
health
status,
medication
use,
physical
activity
levels,
sex,
sleep
pattern, and cultural fasting practices. This variation has
also
been
identied
by
recent
external
research.
The
authors of the study reported by Nofal et al. observed
positive outcomes of IF in metabolic syndrome, although
the interventions took place in the context of a culturally
Physiological and Biochemical Eects of Intermittent Fasting
171
J Gandhara Med Dent Sci
October - December 2026
defined fasting cycle.
37
Pathan et al. demonstrated that
patients with type 2 diabetes receiving ertugliozin had
good
glycaemic
control
during
Ramadan
fasting,
indicating
that
medication
status
aected
glycaemic
outcomes
during
the
fasting
period.
7
Skarstad
et
al.
showed that time-restricted eating was possible in breast
cancer
survivors,
but
feasibility
and
metabolic
eects
could
be
dierent
from
the
group
with
diabetes
or
obesity.
38
Overall,
the
evidence
is
promising
but
heterogeneous.
Dierences
in
fasting
duration
and
timing,
intervention
length,
energy
intake,
adherence,
baseline
metabolic
status,
medication
use,
physical
activity,
sex,
sleep,
and
cultural
context
limit
direct
comparison.
Future
trials
should
use
standardized
definitions,
longer
follow-up,
objective
adherence
measures,
continuous
glucose
monitoring
where
appropriate, and prespecied subgroup analyses.
LIMITATIONS
This
review
was
limited
by
substantial
clinical
and
methodological
heterogeneity,
which
precluded
meta-
analysis. Many included trials had small samples or short
intervention
periods,
and
adherence
reporting
was
variable.
The
review
also
applied
a
2019-2025
publication window, which may have excluded earlier
relevant evidence.
These
factors
should
be
considered
when
interpreting
the
direction
and
magnitude
of
reported benets.
CONCLUSIONS
Intermittent
fasting
may
improve
insulin
sensitivity,
glucose
metabolism,
body
weight,
and
selected
cardio
metabolic outcomes, particularly in adults with obesity,
metabolic syndrome, type 2 diabetes, non-alcoholic fatty
liver disease, polycystic ovary
syndrome,
or increased
diabetes risk. Early time-restricted eating and 8-10-hour
eating windows showed the most consistently favourable
patterns,
but
eects
varied
across
populations
and
protocols.
Larger,
longer-term
randomised
trials
are
needed to determine the safest and most effective fasting
strategies
and
to
establish
the
durability
of
metabolic
benet.
CONFLICT OF INTEREST:
None
FUNDING SOURCES:
None
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AUTHORS CONTRIBUTION
The authors accept responsibility for all aspects of the work
and will ensure that any concerns regarding the accuracy or
integrity of any part are properly investigated and resolved.
Hina
Hakim
-
Concept
&
Design;
Data
Acquisition;
Data
Analysis/Interpretation; Drafting Manuscript;
Critical Revision;
Supervision; Final Approval
Sara Yar Khan
-
Concept & Design; Data
Acquisition;
Data
Analysis/Interpretation; Drafting Manuscript;
Critical Revision;
Supervision; Final Approval
Muhammad Ishraq
-
Concept & Design; Data Acquisition; Data
Analysis/Interpretation; Drafting Manuscript;
Critical Revision;
Supervision; Final Approval
Aizazullah
-
Concept
&
Design;
Data
Acquisition;
Data
Analysis/Interpretation; Drafting Manuscript;
Critical Revision;
Supervision; Final Approval
Farzana Salman
-
Concept
& Design; Data Acquisition; Data
Analysis/Interpretation; Drafting Manuscript;
Critical Revision;
Supervision; Final Approval
Marina Hidayat
-
Concept & Design; Data Acquisition; Data
Analysis/Interpretation; Drafting Manuscript;
Critical Revision;
Supervision; Final Approval
Physiological and Biochemical Eects of Intermittent Fasting
