Acute or Short-term Effects of Whey Protein Alone
or Along with Carbohydrate on Inammation: A
Systematic Review of Clinical Trials
Ali Akbari 1, Mahsa Moazen 2, Siavash Babajafari 2, Seyedeh Maryam Abdollahzadeh 2, Maryam Ranjbar Zahedani
3, Najmeh Sasani 2, Asma Kazemi 2
1 Department of Anesthesiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
2 Nutrition Research Center, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
3 Department of Nutrition Sciences, School of Health, Larestan University of Medical Sciences, Larestan, Iran
GMJ.2023;12:e2441
www.gmj.ir
Correspondence to:
Mahsa Moazen, School of Nutrition and Food Sciences,
Razi Boulevard, Shiraz, Iran.
Telephone Number: +987137251001
Email Address: mahsa_moazen@yahoo.com
Received 2022-03-20
Revised 2022-04-02
Accepted 2022-05-08
Abstract
Background: Excessive inammatory response is associated with several diseases. Re-
cently, there has been an increasing trend for investigation of the acute or short-term
effects of whey protein alone or in combination with carbohydrates on inammato-
ry status, especially in athletes. This systematic review aimed to clarify these effects.
Materials and Methods: PubMed, Scopus, and Web of Science databases were searched from
January 1990 to September 2021, without language restriction. Adult studies examining the effects
of whey protein alone or together with carbohydrates on interleukin-6, tumor necrosis factor-α,
and C-reactive protein levels with a maximum duration of 15 days and with at least one comparison
group were included. The quality of studies was determined using the Cochrane risk of bias tool.
Results: Twenty-ve studies met the inclusion criteria. Signicant reductions in inammatory
markers was observed in seven out of 25 studies (28%). However, one out of 25 studies (4%) re-
ported a signicant increase in inammatory status. Among those studies comparing the effects of
whey protein alone with non-protein or protein-containing groups, 18.18% (two out of 11) and 10%
(one out of ten) of the trials revealed a signicant decrease in the markers, respectively. Moreover,
of those studies comparing whey protein plus carbohydrate with non-protein or protein-containing
groups, 33.33% (two out of six) and 40% (two out of ve) of them showed a signicant reduction
in the inammatory response, respectively. The quality of the majority of studies (84%) was poor.
Conclusion: It seems that whey protein alone or the combination of it with carbohydrates
may not affect the inammatory markers in the short run (PROSPERO registration number:
CRD42021273915).[GMJ.2023;12:e2441] DOI:10.31661/gmj.v12i0.2441
Keywords: Inammation; Whey Proteins; Carbohydrates; Acute; Systematic Review
Introduction
Inammation is one of the major processes
involved in the body’s defense against in-
juries or infections [1]. However, excessive
inammatory response and cytokine over-
production can result in the development of
several diseases including rheumatoid arthri-
tis, atherosclerosis, diabetes, obesity, Alzhei-
mer’s disease, and multiple sclerosis [2, 3].
GMJ
Copyright© 2021, Galen Medical Journal.
This is an open-access article distributed
under the terms of the Creative Commons
Attribution 4.0 International License
(http://creativecommons.org/licenses/by/4.0/)
Email:info@gmj.ir
Akbari A, et al. Acute Effects of Whey on Inammation
2GMJ.2023;12:e2441
www.gmj.ir
Acute Effects of Whey on Inammation Akbari A, et al.
Inammatory diseases can lead to high rates
of disability and mortality around the world,
accounting for over 50% of all deaths [4].
Several modiable factors have been linked to
altering inammatory status including smok-
ing, alcohol consumption, physical activi-
ty, and use of some medications [5]. Dietary
compounds are also one of the important fac-
tors inuencing systemic inammation.
For instance, Western-style diets are usually
associated with higher inammatory status,
while Mediterranean diets are related to lower
levels of inammation [6].
Whey protein, as a group of globular proteins,
is considered one of the major proteins in milk
[7]. It is composed of many proteins or pep-
tides including β-lactoglobulins, α-lactoalbu-
mins, glycomacropeptide, immunoglobulins,
serum albumins, and lactoferrin with several
functions in the body [8, 9]. Numerous po-
tential biological activities have also been
attributed to the consumption of this milk-de-
rived substance including cardiovascular
protection, antioxidative effects, immune-en-
hancing properties as well as weight loss ef-
fects [10, 11].
Moreover, the anti-inammatory effects of
whey protein have been reported in several
previous studies including those carried out
in dialysis patients [12] or obese women with
metabolic syndrome [13]. Cheese whey pro-
tein, as a source of threonine and cysteine, has
also reduced gut inammation in rats by pro-
moting mucin synthesis and changing intesti-
nal microora [14].
A previous meta-analysis, performed by Zhou
et al. [15], has evaluated the chronic effects
(≥4 weeks) of whey protein supplementation
on a single inammatory marker (i.e. C-reac-
tive protein (CRP)). Results from nine includ-
ed randomized trials in this study indicated
that whey protein signicantly reduced CRP
levels in those with high doses of intervention
or high baseline CRP concentrations.
In the past few years, however, there has been
an increasing trend to investigate the acute or
short-term effects of whey protein on inam-
matory status, especially in athletes [16-21].
Many of these interventions were also com-
bined with carbohydrate [16-19], as a source
of energy [22]. It has been reported that co-in-
gestion of protein and carbohydrates follow-
ing exercise may increase muscle glycogen
synthesis and functional capacity [23]. How-
ever, the research result obtained in this area
is contradictory. Several clinical trials indicat-
ed that supplementing whey protein alone or
along with carbohydrates can reduce inam-
matory markers for a short duration [24-27],
while some others could not show any bene-
cial effects [16, 28-30].
Accordingly, this review, for the rst time,
aimed to systematically evaluate the acute
or short-term effects of whey protein sup-
plementation alone or in combination with
carbohydrates on inammatory markers in-
cluding interleukin-6 (IL-6), tumor necrosis
factor-alpha (TNF-α) and CRP.
Materials and Methods
This systematic review was developed ac-
cording to the Preferred Reporting Items
for Systematic Reviews and Meta-analy-
ses (PRISMA) statement [31], and was reg-
istered in the database of the International
Prospective Registr of Systematic Reviews
(PROSPERO) with the registration number
CRD42021273915 (available at:https://www.
crd.york.ac.uk/prospero). The research proto-
col has not been yet published.
Search Strategy and Study Selection
The search strategy was developed based on
the medical subject heading (MeSH) database
and search terms of relevant review studies.
The full search strategy is included in Sup-
plementary le 1, which consists of two com-
ponents: i.e. the intervention (whey protein)
and the outcome (inammatory markers). The
systematic literature search was performed in
PubMed, Scopus, and Web of Science data-
bases from 1 January 1990 up to 23 Septem-
ber 2021 without language restriction. Refer-
ence lists of related review articles were also
searched for possible additional relevant stud-
ies [15, 32-34].
Studies meeting all the following criteria
were included in this systematic review: (1)
clinical trials with either parallel or cross-over
design; (2) healthy or unhealthy adult partic-
ipants (mean age>18 years); (3) oral admin-
istration of whey protein in any form (whey
protein concentrate, isolate, hydrolysate, etc.)
2GMJ.2023;12:e2441
www.gmj.ir
Acute Effects of Whey on Inammation Akbari A, et al.
GMJ.2023;12:e2441
www.gmj.ir
3
(WP group) or whey protein combined with
carbohydrate (WP+CHO group); (4) included
at least one comparison group; (5) assessed
serum inammatory markers including IL-
6, TNF-α, CRP or high-sensitivity CRP (hs-
CRP); and (6) a maximum duration of 15 days.
Conference papers without available full texts
were excluded from the present review.
Two reviewers screened the titles and ab-
stracts of retrieved studies according to the
eligibility criteria. Subsequently, full-texts of
those studies without sufcient information
based on title and abstract were assessed by
two independent reviewers (MM and SMA).
Discrepancies were claried through discus-
sion and when clarication was not possible,
a third reviewer (AK) was consulted.
Data Extraction
Data extraction was performed by one re-
viewer (MM) and checked for accuracy by a
second reviewer (MRZ). Disagreements be-
tween the reviewers were eventually resolved
by discussion. The following data were ex-
tracted from the included studies:rst author,
year of publication, country (where the study
was done), study design, participants’ char-
acteristics, sample size, age, sex, body mass
index (BMI), intervention details including
dose and type of whey protein or carbohydrate
consumed (and concurrent exercise program,
if present), information on comparison group,
intervention duration, time points of inam-
matory marker assessments and the ndings
related to comparing the inammatory mark-
ers between the groups.
Quality Assessment
The quality (risk of bias) of all included study
was assessed by the Cochrane risk of bias tool
for randomized controlled trials [35]. The tool
comprises seven domains including random-
ized sequence generation, allocation conceal-
ment, blinding of participants and personnel,
blinding of outcome assessor, incomplete out-
come data, selective outcome reporting, and
other sources of bias.
Subsequently, the studies were classied
into three groups of qualities (good, fair, and
poor). The study’s risk of bias was assessed
independently by two reviewers (MM and
NS). Any disagreements were resolved by
consensus, and if necessary a third reviewer
(AK) arbitrated.
Results
Selection Process
A total of 4976 articles were retrieved from
electronic databases. After removing dupli-
cates, 2981 studies were screened by titles or
abstracts. The full texts of 156 potentially rel-
evant articles were then checked for eligibili-
ty. Ultimately, 25 clinical trials met the inclu-
sion and exclusion criteria for inclusion in this
systematic review. The selection procedure of
the studies is presented in Figure-1.
Study Characteristics
The study characteristics of the included stud-
ies are summarized in Table-1 and -2. Of the
25 studies included, 15 administered whey
protein alone and 10 provided whey protein
plus carbohydrates. These studies were pub-
lished between 2009 and 2021 and were per-
formed in different geographical locations:
seven in Europe, seven in Asia, ve in North
America, three in South America, and three in
Australia.
Regarding participant characteristics, about
half of the studies were conducted in athletes
or active adults (12 studies (48%); ve in WP
and seven in WP+CHO group), seven stud-
ies were carried out on different ill patients
and three studies were conducted in patients
with obesity or overweight ones. The remain-
ing three studies also studied sedentary men,
healthy males, or medical students.
The mean ages of participants ranged from
21.44-81.95 yrs. (22.3-76.2 yrs. in WP and
21.44-81.95 yrs. in WP+CHO group). More
than half of the studies (13 studies (52%); sev-
en in WP and six in WP+CHO group) were
conducted exclusively in males, nine studies
were carried out on both genders and the re-
maining three studies were only performed on
females. Among those studies assessed indi-
viduals’ BMI (ten studies), the mean of BMIs
was 20-35.61 kg/m2.
Considering the type of whey protein con-
sumed, whey protein isolate (WPI) was the
most common type of protein used in the stud-
ies (ten studies (40%); six in WP and four in
the WP+CHO group). Whey protein hydroly-
4GMJ.2023;12:e2441
www.gmj.ir
Akbari A, et al. Acute Effects of Whey on Inammation Acute Effects of Whey on Inammation Akbari A, et al.
sate (WPH), whey protein concentrate (WPC),
hydrolysate of WPI, yellow fermented whey
protein, and a blend of WPI and WPC were
other forms of reported protein. Nonetheless,
seven studies did not declare the type of whey
protein that was consumed.
Regarding intervention doses, a wide range of
whey protein or carbohydrate doses (CHO as
the intervention group) was used. Some stud-
ies had a xed dose for all the participants (7-
114 g/day for WP and 25-250 g/day for CHO),
and the others administered the interventions
based on the individuals’ body weight (0.6-2.3
g/kg/day for WP and 1-7 g/kg/day for CHO).
Each study had at least one comparison
group. Participants in these groups received
either protein-containing supplements (such
as casein, α-lactalbumin, or white bread and
sour milk cheese) or non-protein interven-
tions (such as maltodextrin, water, or having
no supplementation). Over half of the studies
(56%, 14 studies) reported a concurrent exer-
cise program in parallel with the supplement
protocol. This was even more pronounced in
the WP+CHO group where 70% (seven out of
ten) of the studies had a supplemental exercise
program, whereas 46.67% of the studies in the
WP group (seven out of 15) had an exercise
schedule.
The duration of the studies varied between one
to 15 days. One day acute intervention were
predominantly (90%, nine out of ten studies)
in the WP+CHO group, whereas nearly half
of the studies in the WP group (46.67%, seven
out of 15 studies) had an acute duration.
Besides, in more than half of the studies (13
studies (52%); seven in WP and six in the
WP+CHO group) the inammatory markers
were measured at multiple time points (>2
times), while in ten studies (seven in WP and
three in WP+CHO group) the markers were
assessed two times (before and after the sup-
plementation period).
Furthermore, in one study conducted by de
Carvalho et al. [30], the inammatory status
was evaluated only at the end of the interven-
tion, and in another one [38] although base-
line values were checked out but not reported
in the article.
Figure 1. Flow diagram of the literature search and selection of studies
GMJ.2023;12:e2441
www.gmj.ir
54 GMJ.2023;12:e2441
www.gmj.ir
Acute Effects of Whey on Inammation Akbari A, et al.
Table 1. Characteristics of Included Studies Evaluating the Acute or Short-term Effects of Whey Protein on Inammatory Markers
First
author,
Year, Ref Country/
study
design
§
Participants’
characteristic/
sample size
Age, Sex
and BMI
Intervention
group(s) (type and
dose)
Comparison group(s)
(type
and dose)
Duration/
Time points of
inammatory
marker
assessments
Outcome
assessed / result
Overall
Quality
Mizubuti,
2021 [28]
Brazil/
Parallel
Patients with
chronic liver
disease on
the waiting
list for liver
transplantation/
n=75
52.13,
M/F, NR
WPI (20 g twice a
day)
Casein (20 g twice a day) 15 days/before
and after
supplementation
period
IL-6, TNF-α/
no signicant
differences were
observed between
the groups.
Fair
Hilkens,
2021 [29]
Netherlands/
parallel
Recreationally
active, non-
obese young
men/n=39
23.51,M,
22.84
WPC received in
mid-morning (25 g/d)
and ~1h before sleep
(50 g/d) for 9 days.
On day 5 participants
performed a bout of
eccentric exercise
(100 drop jumps).
Maltodextrin received in
mid-morning and ~1h before
sleep (totally 72 g/d) for 9
days. On day 5 participants
performed a bout of eccentric
exercise (100 drop jumps).
9 days/on day 5 at
pre-exercise, and
0, 1, 24, 48 and
72h post-exercise
CRP/No
signicant
treatment×time
interaction effect
was observed.
Poor
Nieman,
2020 [36]
USA/
parallel
Non-athletic,
non-obese,
healthy men/
n=92
38.57, M,
25.4
Participants engaged
in two physical tness
tests and one 90-min
eccentric exercise
bout every day and
also supplemented
with WPI (0.3 g/kg)
three times a day.
a) Placebo (237 mL water)
three times a day. b) Pea
protein isolate (0.3 g/kg)
three times a day. Both
groups engaged in the same
exercise protocol as the
intervention group.
5 days/all the 5
days in fasting
state and also in
day 1 following
the 90-min
eccentric exercise
CRP/no
signicant
treatment effect
or treatment×time
interaction effect
was observed.
Poor
continue on the next page
continue of Table 1. Characteristics of Included Studies Evaluating the Acute or Short-term Effects of Whey Protein on Inammatory Markers
Saracino,
2020 [37]
USA/
Parallel
Middle-aged,
recreationally
active healthy
men/n=27
55,
M,
NR
a)WPH b)WPI
Participants
performed maximal
voluntary eccentric
contractions of the
knee extensors and
exors. WPH or WPI
were provided after
exercise (25 g) and
also before sleep for 3
days (40 g/night).
a) A avor matched, non-
caloric placebo b) Plant-
based protein (rice and
pea combination) Both
supplements were provided
after exercise (25 g) and also
before sleep for 3 days (40
g/night). Exercise protocols
were the same as the
intervention groups.
3 dayspre-
exercise and at 0,
4, 6, 24, 48, and
72h post-exercise
IL-6/No
signicant
group×time
interaction or
main effect
of group was
observed.
Poor
Celik,
2019 [38]
Turkey/
parallel
Third grade
medical
students/n=36
NR, M/F,
NR
Whey protein (44 g/d) a) No nutritional
supplementation b) Casein
(33 g/d)
15 days/at
baseline and on
the examination
day (day 16).
However, the
baseline values
were not reported.
IL-6, TNF-α/
TNF-α in the
whey group was
signicantly
higher than the
group consuming
nothing. No
signicant change
in IL-6 was
observed between
the groups.
Poor
Snipe,
2017 [21]
Australia/
crossover
Non-heat
adopted
endurance-
trained runners/
n=9
31,
M/F,
NR
WPH consumed pre-
exercise (15 g) and
every 20 min (15 g)
during 2 h running at
35.5 °C.
a) Glucose b) Water, They
were consumed pre-exercise
and every 20 min during 2h
running at 35.5°C (15 g for
glucose; ad lib for water at
each time)
1 day/before and
immediately after
exercise
IL-6, TNF-α/
whey protein
group was not
signicantly
different
compared to
other groups.
Poor
continue on the next page
Akbari A, et al. Acute Effects of Whey on Inammation Acute Effects of Whey on Inammation Akbari A, et al.
6GMJ.2023;12:e2441
www.gmj.ir
continue of Table 1. Characteristics of Included Studies Evaluating the Acute or Short-term Effects of Whey Protein on Inammatory Markers
Mariotti,
2015
[39]
France/
crossover
Healthy overweight
young men with waist
circumference >94 cm/
n=10
34,
M,
30.2
Whey protein (55 g;
consumed in a high fat
meal)
a) Casein (54 g; consumed in a
high fat meal) b) α-lactalbumin-
enriched whey protein (49 g;
consumed in a high fat meal)
1 day/Before the
meal and at 2, 4
and 6h after the
meal
IL-6, TNF-α/
No signicant
meal effects
or meal×time
interaction
effects were
found.
Poor
Schroer,
2014
[20]
USA/
crossover
Endurance-trained
cyclists/n=8
22.3,
M/F,
NR
*Participants had 120
min of constant-load
cycling and a 30-km time
trial. WPH was received
before exercise and every
15 min during the 120
min cycling; Total WPH
received was 101.25 g.
a) Non-caloric articially
sweetened solution (250 ml
each time) b) L-alanine (Totally
received 33.75 g) The exercise
protocols and time points of
supplementations were similar to
the intervention group.
1 day/Before and
after constant-load
cycling
IL-6/The fold-
change was
attenuated
(92%
likelihood)
with whey
protein
compared to
non-caloric
solution.
Poor
Kinsey,
2014
[40]
USA/
parallel
Sedentary overweight
or obese healthy
women/n=42
28.71,
F,
35.61
Night-time intake of
whey protein (30 g whey
protein as the main
ingredient- 50% blend of
WPI and WPC)
a) Night-time intake of
maltodextrin (30 g maltodextrin
as the main ingredient) b)
Night-time intake of casein (30
g micellar casein as the main
ingredient)
1 day/Baseline and
also in the morning
after night-time
ingestion of the
supplement
hs-CRP/No
signicant
differences
were observed
between the
groups.
Poor
Baba,
2014
[41]
Japan/
crossover
Non-athletic adults, but
capable of running for
at least 1 h at 10 km/h
and able to maintain
an intensity of at least
70% of VO2max /n=14
31,
M,
22.8
Once before, 3 times
during, and once after a
60-min running session,
a powder consumed that
contained 22.8 g of WPI
as the main ingredient.
Once before, 3 times during,
and once after a 60-min running
session, a placebo consumed
that contained 5.2 g of the same
powder in the intervention
group, after removal of whey
protein.
1 day/30
min before,
immediately after,
and at 0.5, 2, 4,
6, and 24h after
the completion of
running
IL-6/No
signicant
differences
were observed
between the
groups.
Poor
continue on the next page
Acute Effects of Whey on Inammation Akbari A, et al.
6GMJ.2023;12:e2441
www.gmj.ir
GMJ.2023;12:e2441
www.gmj.ir
7
continue of Table 1. Characteristics of Included Studies Evaluating the Acute or Short-term Effects of Whey Protein on Inammatory Markers
Singh, 2014
[42]
India/
parallel
Severe acute
pancreatitis
patients/n=68
38.27,
M/F,
NR
Whey protein (10 g twice a
day)
Glutamine (10 g twice a day) 7 days/before
and after
supplementation
period
hs-CRP/no
signicant
differences
were
observed
between the
groups.
Good
Pal, 2011
[43]
Australia/
crossover
Healthy
overweight
or obese
postmenopausal
women/n=20
57.5,
F,
32.5
WPI (45 g; consumed with a
breakfast meal).
a) Glucose (45 g; consumed
with a breakfast meal). b)
Sodium caseinate (45 g;
consumed with a breakfast
meal).
1 day/before
and at 1, 2, 3,
4 and 6h after
supplementation
IL-6, TNF-α,
CRP/no
signicant
group
effects were
observed.
Poor
de Aguilar-
Nascimento,
2011 [24]
Brazil/
parallel
Elderly patients
admitted to
ICU due to
acute ischemic
stroke/n=25
76.2,
M/F,
NR
Early nasogastric feeding with
standard formula containing
WPH (1.2 g of protein/kg/d)
Early nasogastric feeding
with standard formula
containing hydrolyzed casein
(1.2 g of protein/kg/d)
5 days/before
and after
supplementation
period
IL-6, CRP/
IL-6 was
signicantly
decreased
in the whey
group than
the casein
group. No
differences
were
observed for
CRP.
Fair
continue on the next page
Akbari A, et al. Acute Effects of Whey on Inammation Acute Effects of Whey on Inammation Akbari A, et al.
8GMJ.2023;12:e2441
www.gmj.ir
continue of Table 1. Characteristics of Included Studies Evaluating the Acute or Short-term Effects of Whey Protein on Inammatory Markers
Kullisaar,
2011 [25]
Estonia/
parallel
Patients
with light to
moderate lower
urinary tract
symptoms/
benign prostatic
hypertrophy/
n=51
50-60,
M,
NR
Yellow fermented whey
product (50 g/d)
Apple juice (50 g/d) 2 weeks/
before and after
supplementation
period
hs-CRP/
hs-CRP
signicantly
decreased
after
consumption
of whey in
comparison
with apple
juice.
Poor
Buckley,
2010 [44]
Australia/
parallel
Sedentary men/
n=28 18-30,
M,
NR
a)WPI b)WPIHD 100 maximal
eccentric contractions of
the knee extensors were
performed. Soon after, 6h,
and 22h after the contractions,
25 g of WPI or WPIHD were
consumed.
100 maximal eccentric
contractions of the knee
extensors were performed.
Soon after, 6h, and 22h after
contractions, a avored water
was consumed.
1 day/Prior to
maximal eccentric
contractions,
immediately after
it, and at 1, 2, 6 and
24h post-eccentric
contractions
TNF-α/No
signicant
treatment×time
interaction
effect was
observed.
Poor
§ Since in some studies the inammatory markers were not assessed for all the included participants, the sample size of the evaluated inammatory markers was considered.
* WPH, non-caloric solution and L-alanine were also given at three points during the time trial but without blood sampling. All the three products contained sodium chloride,
potassium chloride, and avoring.
¶ In cases where the mean age of the participants was not reported, the inclusion criteria for age of the participants were specied.
Ad lib: Ad libitum; BMI: Body mass index; CRP: C-reactive protein; F: Female; Hs-CRP: High-sensitivity C-reactive protein; ICU: Intensive care unit; IL-6: Interleukin-6; M:
Male; NR: Not reported; Ref: Reference; TNF-α: Tumor necrosis factor-alpha; VO2max: Maximal oxygen uptake; WPC: Whey protein concentrate; WPH: Whey protein
hydrolysate; WPI: Whey protein isolate; WPIHD: Hydrolysate of whey protein isolate.
Acute Effects of Whey on Inammation Akbari A, et al.
GMJ.2023;12:e2441
www.gmj.ir
98 GMJ.2023;12:e2441
www.gmj.ir
Table 2. Characteristics of Included Studies Evaluating the Acute or Short-term Effects of Whey Protein in Combination with Carbohydrate on Inammatory Markers
First
author,
Year, Ref
Country/
Study
design
§Participants’
characteristic/
Total sample
size
Age,
Sex,
BMI
Intervention group(s)
(type and dose)
Comparison group(s)
(type and dose)
Duration/
Time points of
inammatory
marker assessments
Outcome assessed /
Result
Overall
Quality
de
Carvalho,
2021 [30]
Brazil/
Parallel
Patients ≥20
years with head
and neck cancer
and candidates
for elective
surgery/n=49
59.84,
M/F,
25.44
Clear uid containing
whey protein (7 g)
and maltodextrin (25
g) received 4h before
surgery.
Clear uid containing
maltodextrin (25 g)
received 4h before
surgery.
1 day/On the second
post-surgery day
CRP/No signicant
differences were
observed between
the groups.
Poor
Deng,
2020 [26]
China/
Parallel
Aged patients
undergoing
elective hip
fracture surgery/
n=35
81.95,
M/F,
20
400 mL of WPH (14%)
with glucose solution
(10%) 24 h before
surgery, and 200 mL
of the same solution 3
h before surgery were
received.
Distilled water (400
mL 24 h before surgery,
and 200 mL 3 h before
surgery)
1 day/On the day
before surgery and 24
h after surgery
CRP/After
surgery, CRP was
signicantly lower
in the intervention
group than the
control group.
Poor
Yi, 2020
[27]
Malaysia/
Parallel
Ambulated
patients
scheduled for
elective surgery
for suspected
gynecologic
cancer/n=118
50.31,
F,
26.57
12 and 3 h before, and
4 h after operation, a
formulated drink with
whey protein (totally
45 g) and CHO (totally
250 g) received. When
at least 500 mL of the
formulated clear uid
with another additional
clear uid was tolerated,
solid food was allowed.
Dinner was consumed 12
h before operation. After
operation and presence
of bowel sounds, patients
were allowed to receive
clear uid, nourishing
uid, soft diet, and
a regular solid diet
according to tolerance.
1 day/Baseline and
after operation
CRP/The
intervention
signicantly
prevented the post-
operational increase
in CRP compared
with the control.
Fair
continue on the next page
Akbari A, et al. Acute Effects of Whey on Inammation Acute Effects of Whey on Inammation Akbari A, et al.
10 GMJ.2023;12:e2441
www.gmj.ir
continue of Table2. Characteristics of Included Studies Evaluating the Acute or Short-term Effects of Whey Protein in Combination with Carbohydrate on Inammatory
Markers.
Isenmann,
2019 [45]
Germany/
Crossover
Healthy
physically
active sports
students (amateur
sportsmen)/n=27
23.2,
M,
NR
After testing leg strength
(by back squat) and
ingesting a breakfast,
participants performed
a 10 km run. Then,
whey protein (52 g)
plus glucose (45 g) was
ingested.
a) No supplementation
b) White bread and
sour milk cheese The
protocols were the same
as the intervention group
except for the type of
supplement.
1 day/Baseline and 3 h
after supplementation IL-6/ IL-6 levels were
signicantly lower
in “whey protein
plus glucose” and
“white bread and sour
milk cheese” groups
compared with “no
supplementation”
group.
Poor
Qin, 2019
[16]
Hong
Kong/
Crossover
Healthy
endurance
runners/n=11
31,
M,
NR
Participants ingested WPI
(0.34 g/kg/h) and CHO
(0.66 g/kg/h) within 2 h.
Then they ran 21 km on a
treadmill.
Participants ingested
α-lactalbumin (0.34 g/
kg/h) and CHO (0.66 g/
kg/h) within 2 h. Then
they ran 21 km on a
treadmill.
1 day/2 h before
exercise, immediately
before exercise,
immediately post-
exercise, and 24 h
post-exercise
IL-6/No signicant
treatment effect
or treatment×time
interaction effect was
observed.
Poor
Qin, 2017
[17]
Hong
Kong/
Crossover
Healthy
endurance
runners/n=12
30.4,
M,
NR
Participants ran for 90
min. During the rst 2 h
of recovery, WPI (0.34 g/
kg/h) and CHO (0.66 g/
kg/h) were consumed.
Participants ran for
90 min. During the
rst 2 h of recovery,
α-lactalbumin (0.34 g/
kg/h) and CHO (0.66 g/
kg/h) were consumed.
1 day/Pre- and post-
exercise, every 2
h during the 4 h
recovery, and 24 h
post-exercise
IL-6/No signicant
differences were
observed between the
groups.
Poor
Dahlquist,
2017 [18]
Canada/
Crossover
Highly trained
cyclists/n=10
26.9,
M,
NR
Participants performed
a cycling test that had
warm-up and cooling-
down periods. Then they
consumed WPI (25 g) and
CHO (75 g).
a) non-nitrogenous, zero
calorie drink (550 ml) b)
WPI (25g), CHO (75g),
vitamin D3 (5000IU) and
vitamin K2 (1000µg).
The exercise protocols
were the same as the
intervention group.
1 day/Baseline,
immediately post-
exercise and 3h post-
exercise
IL-6/No signicant
differences were
observed between the
groups.
Poor
continue on the next page
Acute Effects of Whey on Inammation Akbari A, et al.
GMJ.2023;12:e2441
www.gmj.ir
1110 GMJ.2023;12:e2441
www.gmj.ir
Acute Effects of Whey on Inammation Akbari A, et al.
continue of Table2. Characteristics of Included Studies Evaluating the Acute or Short-term Effects of Whey Protein in Combination with Carbohydrate on Inammatory
Markers
Hansen,
2015 [19]
Denmark
and
Portugal /
Parallel
Elite
orienteering
runners/n=10
for IL-6;n=5 for
TNF-α
21.44,
M/F,
NR
Thirteen exercise sessions
were performed during
1-week training camp.
A 4-km run-test was
performed before and
on the last day. Before
and after each session,
WPH (0.3 g/kg) and
WPH+CHO (0.3 and
1 g/kg) were provided,
respectively.
The exercise protocol
was the same as the
intervention group.
Before and after each
exercise session, 0.3
and 1.3 g/kg CHO were
provided, respectively.
7 days/Baseline pre
-test, baseline post
-test, day 1 and day
7 in the morning
and day 7 post-test
IL-6, TNF-α/
No signicant
treatment×time
interaction effect was
observed. The levels
of cytokines were
not affected by the
treatments.
Poor
Kerasioti,
2013 [46]
Greece/
Crossover
Physically
active men/n=9
28,
M,
23
Participants underwent 2
h cycling, 4 h recovery,
1 h cycling, cycling until
exhaustion (time Trial)
and 1 h recovery. During
the 4 h recovery a cake
with 0.26 g whey protein/
kg/h and 0.9 g CHO/kg/h
was consumed.
The exercise protocol
was the same as the
intervention group.
During the 4h recovery a
cake with 1.1 g CHO/kg/h
and 0.1 g protein/kg/h
was consumed.
1 day/Pre-
exercise, 30 min
post-exercise, 4h
post-exercise,
immediately post-
time Trial and 48h
post-time Trial
IL-6, CRP/The
experimental cake
signicantly reduced
IL-6 and CRP at 4 h
post-exercise than the
placebo cake.
Poor
Betts, 2009
[47]
UK/
Crossover
Highly trained
healthy young
athletes
(cyclists or
team-sport
players) /n=17
26,
M,
NR
Participants underwent
a 20 min of warm-
up period, 90 min of
shuttle-running, and a 4 h
recovery period. During
all phases they ingested
0.4 g/kg/h WPI plus 1.2
g/kg/h CHO.
Participants underwent
a 20 min of warm-
up period, 90 min of
shuttle-running, and a 4 h
recovery period. During
all phases they ingested
1.2 g/kg/h CHO.
1 day/CRP was
measured pre and
post exercise, after
4 h recovery and 24
h post exercise. IL-6
was measured pre
and post exercise,
4 times during
recovery and 24 h
post exercise.
IL-6, CRP/No
signicant differences
were observed
between the groups.
Poor
§ Since in some studies the inammatory markers were not assessed for all the included participants, the sample size of the evaluated inammatory markers was considered.
BMI:Body mass index; CHO:Carbohydrate; CRP: C-reactive protein; F:Female; IL-6:Interleukin-6; M:Male; NR:Not reported; Ref: Rreference; TNF-α:Tumor necrosis factor-
alpha; WPH:Whey protein hydrolysate; WPI:Whey protein isolate.
Akbari A, et al. Acute Effects of Whey on Inammation
12 GMJ.2023;12:e2441
www.gmj.ir
Acute Effects of Whey on Inammation Akbari A, et al.
Effects of Interventions on Inammation
In the current review, seven out of 25 studies
(28%) observed a signicant reduction in at
least one inammatory marker (IL-6 in four
studies, CRP in three studies and hs-CRP in
one study) following whey protein consump-
tion or combination of it with carbohydrate.
On the other hand, one study (4%) reported
a signicant increase in inammatory sta-
tus (TNF-α levels) after supplementing with
whey protein.
It is worth mentioning that three out of seven
studies (42.86%) with signicant protective
effects, administered whey protein in the form
of hydrolysate (Table-1 and -2).
Of the studies comparing the interventions
(WP or WP+CHO) with non-protein controls
(17 trials), four studies (23.53%) showed sig-
nicant improvements in the inammatory
markers. It should be noted that the one study
carried out by Celik et al. [38] that observed
deterioration in inammatory status (one out
of 17) belonged to the non-protein compari-
son group.
Furthermore, among those trials comparing
the interventions (WP or WP+CHO) with
protein-containing groups (15 studies), three
studies (20%) reported a signicant decrease
in inammatory biomarkers. One of the com-
parison groups in this category (one out of 15
studies) included participants who consumed
dinner, clear uid, nourishing uid, a soft
diet and regular solids during the intervention
period [27]. We categorized this group as a
protein-containing comparison group since
dinners and regular solid diets usually contain
some protein.
Among those studies compared the effects of
whey protein alone with non-protein or pro-
tein-containing comparison groups, 18.18%
(two out of 11) and 10% (one out of ten) of
the trials revealed a signicant reduction in
the inammatory markers, respectively. The
only study that reported elevated TNF-α lev-
els (one out of 11), comparing the effects of
whey protein alone with a control group, in
which the the control group was given no nu-
tritional supplementation.
Moreover, of those studies comparing whey
protein and carbohydrate with non-protein or
protein-containing comparison groups, 33.33
% (two out of six) and 40% (two out of ve)
of the articles, a signicant decrease in the in-
ammatory response was observed.
The Overall Quality of Studies
Using the Cochrane risk of bias tool, most
studies (84%) were rated as ‘poor’ (21 stud-
ies; 12 in the WP group, nine in the WP+CHO
group); three studies were classied as ‘fair’
(two in the WP group, one in the WP+CHO
group) and one study (in the WP group) was
rated as ‘good’. Supplementary le 2 provides
quality assessment details of mentioned stud-
ies.
Discussion
The present systematic review indicated that
whey protein alone or in combination with
carbohydrates may not affect the inammato-
ry response after a short time. Less than one-
third (28%) of the included studies reported
signicant reductions in inammatory mark-
ers. Moreover, less than one-fourth of the tri-
als comparing the interventions with non-pro-
tein controls or protein-containing comparison
groups observed signicant improvements in
inammatory status (23.53% and 20%, re-
spectively).
The most remarkable nding was related to
the studies comparing the effects of whey
protein plus carbohydrate with protein-con-
taining comparison groups, in which 40% of
the articles (two out of ve) indicated a sig-
nicant decrease in the inammatory markers.
However, the percentage is not high enough
and this subgroup of studies included very few
trials (only ve) to make a denite conclusion.
In a meta-analysis carried out in 2015 [15] re-
sults of nine included studies with a duration
of at least four weeks demonstrated that whey
protein and its derivate signicantly decreased
CRP levels in participants supplemented with
≥20 g/day or in those with baseline CRP con-
centrations ≥3 mg/L. The supplementation
also showed a small but nonsignicant effect
on reducing CRP considering all the nine in-
cluded studies.
Another meta-analysis in 2021 [48] evaluated
the effects of chronic ingestion (>4 weeks) of
whey protein on TNF-α and IL-6 status. Acute
and communicable conditions as well as
non-English language articles were excluded
GMJ.2023;12:e2441
www.gmj.ir
1312 GMJ.2023;12:e2441
www.gmj.ir
Akbari A, et al. Acute Effects of Whey on Inammation
from this review. Results of the eleven includ-
ed studies showed no signicant effect of this
protein on the markers compared to carbohy-
drate or protein comparison groups. More-
over, a narrative review in older individuals
by Ticinesi, et al. in 2016 [34] investigated the
effects of whey protein intake on inammato-
ry markers and included four randomized con-
trolled trials. But the ndings did not support
an anti-inammatory effect for this protein in
aged participants, and no denite conclusion
was made.
These results are in agreement with the nd-
ings of the present review. Several review
studies have also been conducted on dairy
protein (such as a combination of casein and
whey protein) intakes. Nevertheless, these re-
views did not interpret their results for each
type of protein alone. In a systematic review
by Nieman et al. [33], the impact of dairy pro-
tein was assessed on inammatory biomarkers
in those without severe inammatory-related
diseases. The results of eight included studies
showed neutral effects on the biomarkers sim-
ilar to our ndings. Besides, a non-systematic
literature review [49] evaluated the effects of
ingesting milk proteins on the management of
cardiometabolic diseases. Of the nine trials
investigating the effects of dairy protein (in-
cluding casein, whey, whey-derived peptide,
ribonuclease-enriched lactoferrin, etc.) on in-
ammatory status, no decisive and clear con-
clusion was obtained for the efcacy of these
proteins.
Oxidative stress and inammatory processes
are closely related. Reactive oxygen or reac-
tive nitrogen species can increase pro-inam-
matory gene expression by affecting intracel-
lular signaling pathways [50]. The antioxidant
activity of whey protein is revealed by cysteine
residues, which are essential for glutathione
synthesis [51, 52]. Consequently, this dairy
protein may also be involved in reducing the
inammatory response. Moreover, immuno-
modulatory properties have been attributed to
lactoferrin and immunoglobulins, which are
isolated from whey. These immune proteins
have been reported to modulate inammatory
processes by reducing intestinal permeability
or affecting gene expression [53]. Whey pro-
tein is also a rich source of branched-chain
amino acids (BCAAs), especially leucine and
isoleucine [54]. Depending on blood levels,
Leucine can stimulate both anti-inammatory
and pro-inammatory processes [55].
It has been suggested that acute ingestion of
β-hydroxy β-methyl butyrate, a metabolite
of leucine breakdown, before and after resis-
tance training may reduce the pro-inamma-
tory response [56].
On the other hand, an in-vitro study performed
on cultured peripheral blood mononuclear
cells showed that BCAAs induced the activa-
tion of nuclear factor-κB, causing the release
of pro-inammatory cytokines such as IL-6
and TNF-α [57].
Therefore, these contradictory proposed
mechanisms may be one of the contributing
factors explaining the ineffectiveness of whey
protein on inammatory responses. Addition-
ally, it should be noted that there are some
methodological inconsistencies among the
studies included in this review that may affect
the results.
For instance, types and doses of whey protein
consumed, types of comparison groups (either
non-protein or protein-containing groups),
participants’ characteristics (including health
status, age, sex, and BMI), sample sizes and
presence of concurrent exercise programs
were different among the articles. Further-
more, the neutral conclusions may have been
due to the poor quality of most studies or the
insufcient duration of the study to observe
the signicant results. Therefore, research-
ers are encouraged to focus on conducting
high-quality studies with longer durations in
the future.
In this review, almost half of the studies show-
ing signicant protective effects had adminis-
tered WPH in the form of hydrolysate (WPH).
It has been reported that protein hydrolysates
can have several biological characteristics in-
cluding antimicrobial, anti-thrombotic or an-
tioxidative effects [58]. Besides, in line with
the ndings of our study, results of in vitro
research indicated that whey protein hydroly-
sate can downregulate TNFα-induced inam-
mation by altering gene expression [59].
It should be noted that ten trials of this review
provided whey protein along with carbohy-
drate, and 70% of them had a concurrent ex-
ercise program. It has been demonstrated that
carbohydrates consumption replenishes gly-
Acute Effects of Whey on Inammation Akbari A, et al.
14 GMJ.2023;12:e2441
www.gmj.ir
cogen stores and can enhance endurance per-
formance in athletes [60, 61]. When protein is
also ingested with carbohydrates, insulin se-
cretion and muscle glycogen synthase activity
can be increased, which may lead to speeding
up muscle glycogen resynthesis following ex-
ercise [62].
In the present study, no quantitative analysis
was performed on the data. Some of the in-
cluded studies did not have adequate criteria
for conducting a meta-analysis. For example,
in some articles the exact values for inam-
matory markers or measurement of variabil-
ity were not clear on the graphs [37, 43, 46];
baseline values were not assessed or reported
[30, 38]; or the measurement unit for variabil-
ity was not specied [25].
The high diversity of the comparison groups
was another reason for not performing a me-
ta-analysis. Furthermore, more than half of
the included studies (52%) measured the in-
ammatory markers at multiple time points
during the intervention. As a result, conduct-
ing a systematic review could have provided
comprehensive insight to compare all time
points.
To the best of our knowledge, this is the rst
systematic review that analyzed the acute
or short-term effects of whey protein sup-
plementation alone or in combination with
carbohydrates on inammatory biomarkers.
Besides, no restriction was placed on the lan-
guage of retrieved studies or the health status
of the participants, which could increase the
generalizability of the ndings. However, this
review had some limitations.
First of all, the majority of the included stud-
ies had low quality. Thus the obtained results
should be interpreted with caution. Secondly,
some other mediators except those common
ones assessed in this study can be categorized
as inammatory (such as IL-1β or serum amy-
loid A [1]). Finally, this review included stud-
ies performed only on adult participants and
trials performed on children were excluded.
Conclusion
In conclusion, it seems that consumption of
whey protein alone or in the combination
with carbohydrates for a short duration may
not alter the inammatory status. However,
conducting further primary studies with high
quality as well as performing quantitative
analysis in this area (if possible in the future)
is required to make a denite conclusion.
Conict of Interest
The authors declare that they have no compet-
ing interests.
References
disease across the life span. Nat Med.
2019;25(12):1822-32.
5. Kantor ED, Lampe JW, Kratz M White.
Lifestyle factors and inammation asso-
ciations by body mass index. PLoS One.
2013;8(7):e67833.
6. Wirth MD, Hébert JR, Shivappa N, Hand
GA, Hurley TG, Drenowatz C, et al.
Anti-inammatory Dietary Inammatory
Index scores are associated with healthier
scores on other dietary indices. Nutr Res.
2016;36(3):214-9.
7. Davoodi SH, Shahbazi R, Esmaei-
li S, Sohrabvandi S, Mortazavian A,
Jazayeri S, et al. Health-related aspects
of milk proteins. Iran J Pharm Res.
1. Abdulkhaleq LA, Assi MA, Abdullah R,
Zamri-Saad M, Tauq-Yap YH, Hezmee
MNM. The crucial roles of inammatory
mediators in inammation: A review.
Vet World. 2018;11(5):627-35.
2. Oke SL, Tracey KJ. The inammatory
reex and the role of complementary and
alternative medical therapies. Ann N Y
Acad Sci. 2009;1172:172-80.
3. Zhang K, Kaufman RJ. From endoplas-
mic-reticulum stress to the inammatory
response. Nature. 2008;454(7203):455-
62.
4. Furman D, Campisi J, Verdin E, Carre-
ra-Bastos P, Targ S, Franceschi C, et al.
Chronic inammation in the etiology of
Acute Effects of Whey on Inammation Akbari A, et al.
GMJ.2023;12:e2441
www.gmj.ir
1514 GMJ.2023;12:e2441
www.gmj.ir
16 GMJ.2023;12:e2441
www.gmj.ir
Akbari A, et al. Acute Effects of Whey on Inammation
2016;15(3):573-91.
8. Patel SJ. Functional food relevance of
whey protein: A review of recent nd-
ings and scopes ahead. J Funct Foods.
2015;19:308-19.
9. León-López A, Pérez-Marroquín XA,
Campos-Lozada G, Campos-Montiel
RG, Aguirre-Álvarez GJF. Characteriza-
tion of whey-based fermented beverages
supplemented with hydrolyzed collagen:
Antioxidant activity and bioavailability.
Foods. 2020;9(8):1106.
10. Wirunsawanya K, Upala S, Jaruvongvan-
ich V, Sanguankeo A. Whey protein
supplementation improves body compo-
sition and cardiovascular risk factors in
overweight and obese patients: A sys-
tematic review and meta-analysis. J Am
Coll Nutr. 2018;37(1):60-70.
11. Zhang J, Tong X, Wan Z, Wang Y, Qin
L, Szeto IMY. Effect of whey protein on
blood lipid proles: a meta-analysis of
randomized controlled trials. Eur J Clin
Nutr. 2016;70(8):879-85.
12. Hassan K. Does whey protein sup-
plementation improve the nutritional
status in hypoalbuminemic peritoneal
dialysis patients? Ther Apher Dial.
2017;21(5):485-92.
13. Aghamohammadi V, Haidari F, Mo-
hammadshahi M, Ahmadi-Angali K,
Asghari-Jafarabadi M. Whey supplemen-
tation combined with energy-restricted
diet alleviates 2-arachidonoylglycerol,
adipocytokines, inammatory factors
and body composition in obese women
with metabolic syndrome: a randomized
controlled trial. Endocrinol Metab Syndr.
2018;7(295):2161-1017.
14. Sprong R, Schonewille A, Van der Meer
R. Dietary cheese whey protein protects
rats against mild dextran sulfate sodium–
induced colitis: Role of mucin and mi-
crobiota. J Dairy Sci. 2010;93(4):1364-
71.
15. Zhou L-M, Xu J-Y, Rao C-P, Han
S, Wan Z, Qin L-Q. Effect of whey
supplementation on circulating C-re-
active protein: A meta-analysis of
randomized controlled trials. Nutrients.
2015;7(2):1131-43.
16. Qin L, Sun F-H, Huang Y, Sheridan
S, Sit CH-P, Wong SH-S. Effect of
pre-exercise ingestion of α-lactalbu-
min on subsequent endurance exercise
performance and mood states. Br J Nutr.
2019;121(1):22-9.
17. Qin L, Wong SHS, Sun F-H, Huang Y,
Sheridan S, Sit CHP. Effects of al-
pha-lactalbumin or whey protein isolate
on muscle damage, muscle pain, and
mood states following prolonged stren-
uous endurance exercise. Front Physiol.
2017;8:754.
18. Dahlquist DT, Stellingwerff T, Dieter
BP, McKenzie DC, Koehle MS. Effects
of macro-and micronutrients on exer-
cise-induced hepcidin response in highly
trained endurance athletes. Appl Physiol
Nutr Metab. 2017;42(10):1036-43.
19. Hansen M, Bangsbo J, Jensen J, Bibby
BM, Madsen K. Effect of whey protein
hydrolysate on performance and recovery
of top-class orienteering runners. Int J
Sport Nutr Exerc Metab. 2015;25(2):97-
109.
20. Schroer AB, Saunders MJ, Baur DA,
Womack CJ, Luden ND. Cycling time
trial performance may be impaired by
whey protein and L-alanine intake during
prolonged exercise. Int J Sport Nutr Ex-
erc Metab. 2014;24(5):507-15.
21. Snipe RM, Khoo A, Kitic CM, Gibson
PR, Costa RJ. Carbohydrate and protein
intake during exertional heat stress ame-
liorates intestinal epithelial injury and
small intestine permeability. Appl Physi-
ol Nutr Metab. 2017;42(12):1283-92.
22. Livesey G. Assessment of carbohydrate
availability, fermentability, and food
energy value in humans using measure-
ments of breath hydrogen. J Am Coll
Nutr. 2021;40(5):480-2.
23. Alghannam AF, Gonzalez JT, Betts JA.
Restoration of muscle glycogen and
functional capacity: role of post-exercise
carbohydrate and protein co-ingestion.
Nutrients. 2018;10(2):253.
24. de Aguilar-Nascimento JE, Prado Sil-
veira BR, Dock-Nascimento DB. Early
enteral nutrition with whey protein or
casein in elderly patients with acute isch-
emic stroke: A double-blind randomized
trial. Nutrition. 2011;27(4):440-4.
Acute Effects of Whey on Inammation Akbari A, et al.
16 GMJ.2023;12:e2441
www.gmj.ir
25. Kullisaar T, Punab M, Türk S, Veskioja
A, Songisepp E, Zilmer M. A fermented
whey product benets male patients with
lower urinary tract symptoms. Food tech-
nologists, biotechnologists and nutrition-
ists. 2011:63-8.
26. Deng Y, Fang Y, Li H, Chen J, An J,
Qiao S, et al. A preoperative whey pro-
tein and glucose drink before hip fracture
surgery in the aged improves symptom-
atic and metabolic recovery. Asia Pac J
Clin Nutr. 2020;29(2):234-8.
27. Yi HC, Ibrahim Z, Abu Zaid Z, Mat
Daud ZA, Md Yusop NB, Omar J, et
al. Impact of enhanced recovery after
surgery with preoperative whey pro-
tein-infused carbohydrate loading and
postoperative early oral feeding among
surgical gynecologic cancer patients an
open-labelled randomized controlled
trial. Nutrients. 2020;12(1):264.
28. Mizubuti Y, Vieira E, Silva T, d’Ales-
sandro M, Generoso S, Teixeira A, et
al. Comparing the effects of whey and
casein supplementation on nutritional
status and immune parameters in patients
with chronic liver disease: a randomised
double-blind controlled trial. Br J Nutr.
2021;125(7):768-79.
29. Hilkens L, De Bock J, Kretzers J, Kardi-
naal AF, Floris-Vollenbroek EG, Schol-
tens PA, et al. Whey protein supplemen-
tation does not accelerate recovery from
a single bout of eccentric exercise. J
Sports Sci. 2021;39(3):322-31.
30. de Carvalho CS, Silva TH, André JCS,
de Barros LAS, Ferreira AA, Murad LB,
et al. Preoperative fasting abbreviation
with whey protein reduces the occur-
rence of postoperative complications in
patients with head and neck cancer: a
randomized clinical trial. Nutr Clin Pract.
2021;36(3):665-72.
31. Moher D, Liberati A, Tetzlaff J, Altman
DG, PRISMA Group. Preferred report-
ing items for systematic reviews and
meta-analyses: the PRISMA statement.
PLoS Med. 2009;6(7):e1000097.
32. Moosavian SP, Rahimlou M, Saneei
P, Esmaillzadeh A. Effects of dairy
products consumption on inammatory
biomarkers among adults: A systematic
review and meta-analysis of randomized
controlled trials. Nutr Metab Cardiovasc
Dis. 2020;30(6):872-88.
33. Nieman KM, Anderson BD, Cifelli
CJ. The effects of dairy product and
dairy protein intake on inammation: A
systematic review of the literature. J Am
Coll Nutr. 2021;40(6):571-82.
34. Ticinesi A, Meschi T, Lauretani F, Felis
G, Franchi F, Pedrolli C, et al. Nutrition
and inammation in older individuals:
focus on vitamin D, n-3 polyunsaturated
fatty acids and whey proteins. Nutrients.
2016;8(4):186.
35. Higgins JP, Altman DG, Gøtzsche PC,
Jüni P, Moher D, Oxman AD, et al. The
Cochrane Collaboration’s tool for as-
sessing risk of bias in randomised trials.
BMJ. 2011;343:d5928.
36. Nieman DC, Zwetsloot KA, Simonson
AJ, Hoyle AT, Wang X, Nelson HK,
et al. Effects of whey and pea protein
supplementation on post-eccentric exer-
cise muscle damage: a randomized trial.
Nutrients. 2020;12(8):2382.
37. Saracino PG, Saylor HE, Hanna BR,
Hickner RC, Kim J-S, Ormsbee MJ.
Effects of pre-sleep whey vs plant-based
protein consumption on muscle recovery
following damaging morning exercise.
Nutrients. 2020;12(7):2049.
38. Celik R, Kaymakci MS, Akalin D, Kara-
demir E, Tuncer B, Bicim G, et al. Effect
of casein and whey proteins on examina-
tion stress. Marmara Med J. 2019:58-61.
39. Mariotti F, Valette M, Lopez C, Fouillet
H, Famelart M-H, Mathé V, et al. Casein
compared with whey proteins affects
the organization of dietary fat during
digestion and attenuates the postprandial
triglyceride response to a mixed high-fat
meal in healthy, overweight men. J Nutr.
2015;145(12):2657-64.
40. Kinsey AW, Eddy WR, Madzima TA,
Panton LB, Arciero PJ, Kim J-S, et
al. Inuence of night-time protein and
carbohydrate intake on appetite and
cardiometabolic risk in sedentary over-
weight and obese women. Br J Nutr.
2014;112(3):320-7.
41. Baba S, Ebihara S, Sakano K, Natsume
M. Whey protein-containing product
Acute Effects of Whey on Inammation Akbari A, et al.
GMJ.2023;12:e2441
www.gmj.ir
17
reduces muscle damage induced by
running in male adults. Sport Sci Health.
2014;10(2):85-95.
42. Singh N, Mishra SK, Sachdev V, Sharma
H, Upadhyay AD, Arora I, et al. Effect
of oral glutamine supplementation on
gut permeability and endotoxemia in
patients with severe acute pancreatitis:
a randomized controlled trial. Pancreas.
2014;43(6):867-73.
43. Pal S, Ellis V. Acute effects of whey
protein isolate on blood pressure, vascu-
lar function and inammatory markers in
overweight postmenopausal women. Br J
Nutr. 2011;105(10):1512-9.
44. Buckley JD, Thomson RL, Coates AM,
Howe PR, DeNichilo MO, Rowney MK.
Supplementation with a whey protein
hydrolysate enhances recovery of muscle
force-generating capacity following
eccentric exercise. J Sci Med Sport.
2010;13(1):178-81.
45. Isenmann E, Blume F, Bizjak D, Hunds-
dörfer V, Pagano S, Schibrowski S, et al.
Comparison of pro-regenerative effects
of carbohydrates and protein adminis-
trated by shake and non-macro-nutrient
matched food items on the skeletal
muscle after acute endurance exercise.
Nutrients. 2019;11(4):744.
46. Kerasioti E, Stagos D, Jamurtas A,
Kiskini A, Koutedakis Y, Goutzourelas
N, et al. Anti-inammatory effects of a
special carbohydrate–whey protein cake
after exhaustive cycling in humans. Food
Chem Toxicol. 2013;61:42-6.
47. Betts JA, Toone RJ, Stokes KA, Thomp-
son D. Systemic indices of skeletal mus-
cle damage and recovery of muscle func-
tion after exercise: effect of combined
carbohydrate–protein ingestion. Appl
Physiol Nutr Metab. 2009;34(4):773-84.
48. Jamshidi S, Mohsenpour MA, Masoumi
SJ, Fatahi S, Nasimi N, Zahabi ES, et al.
Effect of whey protein consumption on
IL-6 and TNF-α: A systematic review
and meta-analysis of randomized con-
trolled trials. Diabetes Metab Syndr.
2021;16(1):102372.
49. Fekete ÁA, Givens DI, Lovegrove JA.
Can milk proteins be a useful tool in
the management of cardiometabolic
health An updated review of human
intervention trials. Proc Nutr Soc.
2016;75(3):328-41.
50. Biswas SK. Does the interdepen-
dence between oxidative stress and
inammation explain the antioxidant
paradox? Oxid Med Cell Longev.
2016;2016:5698931.
51. Veskoukis AS, Kerasioti E, Skaperda Z,
Papapostolou PA, Nepka C, Spandidos
DA, et al. Whey protein boosts the anti-
oxidant prole of rats by enhancing the
activities of crucial antioxidant enzymes
in a tissue-specic manner. Food Chem
Toxicol. 2020;142:111508.
52. Corrochano AR, Buckin V, Kelly PM,
Giblin L. Invited review: Whey proteins
as antioxidants and promoters of cellu-
lar antioxidant pathways. J Dairy Sci.
2018;101(6):4747-61.
53. Brimelow RE, West NP, Williams LT,
Cripps AW, Cox AJ. A role for whey-de-
rived lactoferrin and immunoglobulins in
the attenuation of obesity-related inam-
mation and disease. Crit Rev Food Sci
Nutr. 2017;57(8):1593-602.
54. Elovaris RA, Hajishaee M, Ullrich SS,
Fitzgerald PC, Lange K, Horowitz M, et
al. Intragastric administration of leu-
cine and isoleucine does not reduce the
glycaemic response to, or slow gastric
emptying of, a carbohydrate-containing
drink in type 2 diabetes. Diabetes Res
Clin Pract. 2021;171:108618.
55. Liberman K, Njemini R, Luiking Y, Forti
LN, Verlaan S, Bauer JM, et al. Thirteen
weeks of supplementation of vitamin
D and leucine-enriched whey protein
nutritional supplement attenuates chronic
low-grade inammation in sarcopenic
older adults: the PROVIDE study. Aging
Clin Exp Res. 2019;31(6):845-54.
56. Arazi H, Taati B, Suzuki K. A review
of the effects of leucine metabolite
(β-hydroxy-β-methylbutyrate) supple-
mentation and resistance training on
inammatory markers: A new approach
to oxidative stress and cardiovascu-
lar risk factors. Antioxidants (Basel).
2018;7(10):148.
57. Zhenyukh O, Civantos E, Ruiz-Ortega
M, Sánchez MS, Vazquez C, Peiro C, et
Acute Effects of Whey on Inammation Akbari A, et al.Akbari A, et al. Acute Effects of Whey on Inammation
18 GMJ.2023;12:e2441
www.gmj.ir
al. High concentration of branched-chain
amino acids promotes oxidative stress,
inammation and migration of human
peripheral blood mononuclear cells via
mTORC1 activation. Free Radic Biol
Med. 2017;104:165-77.
58. Athira S, Mann B, Saini P, Sharma R,
Kumar R, Singh AK. Production and
characterisation of whey protein hy-
drolysate having antioxidant activity
from cheese whey. J Sci Food Agric.
2015;95(14):2908-15.
59. Da Silva MS, Bigo C, Barbier O, Rud-
kowska I. Whey protein hydrolysate
and branched-chain amino acids down-
regulate inammation-related genes in
vascular endothelial cells. Nutr Res.
2017;38:43-51.
60. Kloby Nielsen LL, Tandrup Lambert
MN, Jeppesen PB. The effect of ingest-
ing carbohydrate and proteins on athletic
performance: a systematic review and
meta-analysis of randomized controlled
trials. Nutrients. 2020;12(5):1483.
61. Lawler TP, Cialdella-Kam L. Non-carbo-
hydrate dietary factors and their inu-
ence on post-exercise glycogen storage:
a review. Curr Nutr Rep. 2020;9(4):394-
404.
62. McCartney D, Desbrow B, Irwin C.
Post-exercise ingestion of carbohydrate,
protein and water: a systematic review
and meta-analysis for effects on subse-
quent athletic performance. Sports Med.
2018;48(2):379-408.
Acute Effects of Whey on Inammation Akbari A, et al.
GMJ.2023;12:e2441
www.gmj.ir
1918 GMJ.2023;12:e2441
www.gmj.ir
