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Delfan et al. Nutrition & Metabolism (2024) 21:11
https://doi.org/10.1186/s12986-024-00785-0 Nutrition & Metabolism
*Correspondence:
Maryam Delfan
m.delfan@alzahra.ac.ir
Beat Knechtle
beat.knechtle@hispeed.ch
Hassane Zouhal
hassane.zouhal@univ-rennes2.fr
Full list of author information is available at the end of the article
Abstract
This study investigated the combined eects of 12 weeks of high-intensity interval training (HIIT) and spirulina
supplementation on adipokine levels, insulin resistance, anthropometric indices, and cardiorespiratory tness in
44 obese males (aged 25–40 years). The participants were randomly assigned to one of four groups: control (CG),
supplement (SG), training (TG), or training plus supplement (TSG). The intervention involved daily administration of
either spirulina or a placebo and HIIT three times a week for the training groups. Anthropometric indices, HOMA-IR,
VO2peak, and circulating adipokines (asprosin and lipocalin2, omentin-1, irisin, and spexin) were measured before
and after the 12-week intervention. Post-intervention analysis indicated dierences between the CG and the three
interventional groups for body weight, fat-free mass (FFM), percent body fat (%BF), HOMA-IR, and adipokine levels
(p < 0.05). TG and SG participants had increased VO2peak (p < 0.05). Spirulina supplementation with HIIT increased
VO2peak, omentin-1, irisin, and spexin, while causing decreases in lipocalin-2 and asprosin levels and improvements
in body composition (weight, %fat), BMI, and HOMA-IR. Notably, the combination of spirulina and HIIT produced
more signicant changes in circulating adipokines and cardiometabolic health in obese males compared to either
supplementation or HIIT alone (p < 0.05). These ndings highlight the synergistic benets of combining spirulina
supplementation with HIIT, showcasing their potential in improving various health parameters and addressing
obesity-related concerns in a comprehensive manner.
Enhancing cardiometabolic health:
unveiling the synergistic eects of high-
intensity interval training with spirulina
supplementation on selected adipokines,
insulin resistance, and anthropometric indices
in obese males
MaryamDelfan1*, AyoubSaeidi2, RashmiSupriya3, Kurt AEscobar4, IsmailLaher5, Katie M.Heinrich6, KatjaWeiss7,
BeatKnechtle7,8* and HassaneZouhal9,10*
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Page 2 of 13
Delfan et al. Nutrition & Metabolism (2024) 21:11
Introduction
Overweight and obesity describe the accumulation of
excessive or abnormal fat, with potential health risks.
Forecasts suggest that by 2035, more than half of the
global population will grapple with overweight or obe-
sity [1]. e incidence of obesity in Iran escalated from
2million in 1980 to 11million in 2015 [2]. Established
guidelines from entities like the World Health Organi-
zation and the U.S. Department of Health and Human
Services recommend that individuals partake in at least
150–300 min of moderate-intensity or 75–150 min of
vigorous-intensity physical activity weekly [3]. Along-
side traditional physical activity, high-intensity interval
training (HIIT) is a promising avenue for altering body
composition and triggering various metabolic responses
[4–7]. For instance, supervised HIIT involving 30-second
bursts at 90% VO2max followed by 30-second recovery
periods, conducted three times weekly for four weeks,
enhanced fat oxidation by approximately 31% after a
30-minute constant load exercise session at 45% intensity
in overweight and obese men [8].
Several studies [9–12] described the role of inflam-
mation in obesity, highlighting novel adipokines such as
asprosin, lipocalin2, omentin-1, irisin, and spexin. ese
adipokines play intricate roles in metabolic dysregulation,
cardiovascular conditions, and the inflammatory state
associated with obesity [9–12]. Serum levels of asprosin
correlate positively with BMI, waist circumference, and
glycemic and lipid parameters, particularly in individuals
with abdominal obesity [13]. In contrast, lipocalin2 levels
are approximately 60% higher in obese individuals [14].
e recently identified adipokine spexin, regarded as a
regulator of obesity and related comorbidities, is reduced
in obese patients [15]. Omentin-1, known for augmenting
insulin-mediated glucose uptake, is implicated in insulin
resistance [16, 17]. Similarly, irisin, a skeletal muscle glu-
cose uptake regulator, improves hepatic glucose and lipid
metabolism while mitigating obesity-related hyperlipid-
emia and hyperglycemia [18]. Irisin’s potential to enhance
insulin sensitivity correlates with a lower incidence of
type 2 diabetes mellitus [19, 20].
Moving beyond metabolic disturbances, chronic
inflammation and systemic oxidative stress also con-
tribute significantly to obesity and exacerbate cardio-
vascular dysfunction [21]. Spirulina, a cyanobacterium
commonly known as blue-green algae, can potentially
reduce various obesity-related parameters [22]. Studies,
primarily conducted in women, indicate that spirulina
elevates glutathione levels, fat oxidation, and exercise
performance while reducing exercise-induced lipid per-
oxidation [23]. A combined approach involving spirulina
supplementation (4.5g per day for six weeks) and HIIT
(performed thrice weekly) has beneficial effects on blood
lipids and BMI in sedentary men with excessive body
weight [24].
Our investigation aims to scrutinize the hypothesis that
an extended administration of spirulina supplementation
(over 12 weeks), coupled with HIIT, could potentially
mitigate obesity and induce favorable alterations in the
levels of pro-inflammatory adipokines (asprosin and lipo-
calin2) and anti-inflammatory adipokines (omentin-1,
irisin, and spexin) within obese males.
Methods
Ethical approval
A written informed consent for study participation was
obtained from all study participants before the study
started. e study was approved by Sport Sciences
Research Institute Ethics Committee of Alzahra Univer-
sity (Tehran, Iran). (Ethics code: IR.SSRC.REC.1401.093).
All procedures were performed according to the latest
revision of the Declaration of Helsinki [25].
Participants
Following recruitment efforts in various settings, includ-
ing public spaces, laboratories, sports clubs, and social
networks, a total of 143 individuals volunteered to par-
ticipate in the study, of which 80 were deemed ineligible
for participation (aged 25–40 years). Inclusion criteria
for participation were: a body mass index (BMI) exceed-
ing 30kg/m², a lack of engagement in regular physical
activity during the preceding six months, no cardiovas-
cular and endocrine disorders, and non-consumption of
alcohol.
A subset of 80 individuals were carefully selected to
participate in the study after an initial evaluation of
volunteers. In order to meet inclusion criteria, all par-
ticipants underwent a thorough physical examination
conducted by a qualified medical professional and clini-
cal exercise physiologist during the initial visit. Follow-
ing the initial assessment and a detailed explanation of
the research components, 64 individuals were ultimately
chosen. e determination of the sample size was based
on the standardized effect size (SES), calculated utilizing
mean and standard deviation values from other compa-
rable studies [26].
is SES was analyzed using the G*Power (3.1.9.4)
program [two-sided, α = 0.05, power (1-β) = 0.95, effect
size = 1.43], which indicated a minimum required sam-
ple participant size per group of nine. For this study, we
opted to include 16 subjects in each group. Participants
provided a signed consent form and completed the
Keywords Spirulina, High-intensity interval training, Adipokines, Obesity
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Page 3 of 13
Delfan et al. Nutrition & Metabolism (2024) 21:11
Physical Activity Readiness Questionnaire (PAR-Q) [27].
is procedural step was implemented to uphold com-
pliance with established research standards and ethical
guidelines.
Experimental design
Before commencing the training programs, participants
engaged in a familiarization session one week in advance,
wherein a comprehensive explanation of all study proce-
dures was provided. e participants’ height, mass, and
body composition were measured. Following this, a ran-
dom assignment process was undertaken, placing indi-
viduals into one of four equally sized groups: Control
Group (CG), Supplement Group (SG), Training Group
(TG), and Training + Supplement Group (TSG). Over the
course of the study, 20 participants in different groups
withdrew due to medical reasons, job-related constraints,
and waning interest in the research. is attrition led to
11 participants remaining within each group for subse-
quent analysis.
All groups received instructions on the execution of the
training protocols during the third session, which coin-
cided with the measurement of body composition vari-
ables and peak oxygen uptake (VO2peak). e 12-week
exercise training program of three sessions per week, was
initiated in the two training groups (TG and TSG) after
baseline assessments. In contrast, participants in the
CG were instructed to maintain their existing lifestyles
throughout the study.
To ensure consistency and minimize confounding
factors, data collection occurred at identical times of
day, typically within an hour window, and under uni-
form environmental conditions of ~ 20°C and a relative
humidity of ~ 55%. Baseline measurements were acquired
48 h before the onset of the training protocols, while
post-tests were executed 48h after the final session in
all groups. Participants in the two training groups were
instructed to maintain a consistent dietary regimen dur-
ing the 48h preceding the baseline assessment and the
final measurements after training.
Body composition and cardio-respiratory tness
assessments
Body weight and stature were gauged using a calibrated
scale and stadiometer (Seca, Germany). ese measure-
ments were subsequently employed to compute BMI (kg/
m²). Determination of fat-free mass (FFM) and fat mass
(FM) was accomplished using a bio-impedance analyzer
(Medigate Company Inc., Dan-dong Gunpo, Korea).
e evaluation of VO2peak was conducted using a
modified Bruce protocol in a controlled environment
(21–23 °C), consistent with established practices for
overweight and obese cohorts [28, 29]. We utilized an
electronically motorized treadmill (H/P/Cosmos, Pulsar
med 3p- Sports & Medical, Nussdorf-Traunstein Ger-
many). Our approach followed the physiological criteria
outlined in the American College of Sports Medicine
(ACSM) guidelines. Participants were deemed to have
achieved VO2peak when indicating physical exhaustion
and maximal exertion (according to the Borg scale) or if
supervisory personnel identified severe dyspnea, dizzi-
ness, or other limiting symptoms, aligning with ACSM
and American Heart Association (AHA) protocols [30,
31].
Blood pressure measurements were acquired utilizing
an electronic sphygmomanometer (Kenz BPM AM 300P
CE, Japan), while heart rate was continuously monitored
using a Polar V800 heart monitor (Finland) throughout
the testing sessions. Gas analysis was conducted with a
gas analyzing system (Metalyzer 3B analyzer, Cortex:
biophysics, GMbH, Germany) that was calibrated before
each test.
Training protocols
e exercise intensity during training sessions was based
on VO2peak values based on a 32-minute running exercise
on a treadmill. Participants engaged in a 5-minute warm-
up phase of stretching maneuvers, walking, and running
prior to each training session. Participants performed
treadmill running at an intensity set at 65% of their
VO2peak during the first week, which was then progres-
sively increased to 75% of their VO2peak in the subsequent
week. e control of exercise intensities throughout the
sessions was managed by adjusting the treadmill settings
based on the specified percentages of VO2peak. is stan-
dardized approach was consistently maintained across
three weekly sessions.
Transitioning into the third week marked the com-
mencement of High-Intensity Interval Training (HIIT)
sessions. Over the third and fourth weeks, participants
executed intervals comprising 4min of running at 75%
of their VO2peak, followed by 4min of passive recovery,
for a 32-minute duration of HIIT. In weeks 5, 6, and 7,
intervals were extended to 4min of running at 85% of
their VO2peak, interspersed with 4-minute active recovery
intervals at 15% of their VO2peak, maintaining the 32-min-
ute HIIT duration. For weeks 8, 9, and 10, participants
engaged in 4-minute intervals at 90% of their VO2peak
and active recovery intervals at 30% of their VO2peak for
4min, all executed on the treadmill within the 32-minute
timeframe. e final stretch (weeks 11 and 12) consisted
of 4-minute intervals of running at 95% of their VO2peak
and 4-minute intervals of active rest at 50% of their
VO2peak for 32min. Participants performed a 5-minute
cool-down at 50% of their VO2peak after each training ses-
sion [32]. In contrast, the control group continued their
customary daily activities and did not engage in routine
physical exercise.
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Page 4 of 13
Delfan et al. Nutrition & Metabolism (2024) 21:11
Supplementation of spirulina and placebo
Spirulina (Hellenic Spirulina Net. Production unit: er-
mopigi, Sidorokastro, Serres, Greece) was prepared as
capsules for administration. Each subject ingested a daily
dosage of 6g of spirulina, divided into two equal por-
tions of three grams each, taken in the morning and eve-
ning, for 12 weeks [33]. Both the CG and the TG were
also provided with an equivalent quantity of placebo.
is placebo was constituted of corn starch, which was
appropriately colored with edible green dye to mimic
the appearance of spirulina powder, and further flavored
with essence of kiwi fruit. Participants’ adherence to the
supplement regimen was considered satisfactory when
consumption equaled or exceeded 80% of the stipulated
supplements.
Nutrient intake and dietary analysis
ree-day dietary records were procured, encompassing
two weekdays and one weekend day, before and after the
study. ese records monitored alterations in custom-
ary dietary patterns over the study duration [34]. Each
specific food item was entered in the Diet Analysis Plus
version 10 software (Cengage, Boston, MA, USA), which
calculated the total caloric intake and the proportion of
energy derived from proteins, fats, and carbohydrates
(Table1).
Blood markers
Standardized conditions were used for collecting blood
samples that were drawn between 8am and 10am. Blood
samples were obtained from the right arm after a 12-hour
fast, 48-hour before the initial exercise session and 48h
after the final session. e blood samples were collected
in EDTA-containing tubes. Subsequently, a centrifuga-
tion process lasting 10min at 3000rpm was performed,
and the resulting plasma was stored at -80°C.
Plasma glucose levels were quantified using a colori-
metric enzymatic kit (Pars Azmun, Tehran, Iran) with
a sensitivity of 5mg/dl. For insulin level assessment, an
ELISA kit (Demeditec, Germany) was used, with a sen-
sitivity of 1 ng/ml and a within-coefficient variations
of 5.1–8.4%. Insulin resistance was calculated with the
homeostasis model assessment of insulin resistance
(HOMA-IR), using the equation: (fasting insulin in μU/
mL × fasting glucose in mmol/L)/22.5.
Measurement of plasma lipocalin-2 levels was made
using an ELISA kit (Biovendor, Czech Republic; Cata-
logue No: RD191102200R), having a sensitivity of 0.02
ng/ml. e intra-assay coefficient of variation (CV) was
7.7%, while the inter-assay CV was 9.8%. Plasma omen-
tin-1 levels were quantified utilizing an ELISA kit (Bio-
vendor, Czech Republic; Catalogue No: RD191100200R)
having a sensitivity of 0.5 ng/ml, and an intra-assay CV of
3.7%, with an inter-assay CV of 4.6%.
An ELISA kit (Phoenix Pharmaceuticals Inc, USA;
Catalogue No: EK 067 − 16) was used to assess plasma
irisin levels; the kit had a sensitivity of 6.8 ng/ml. Intra-
assay CV was less than 10%, while the inter-assay CV was
less than 15%. Plasma spexin levels were measured with
an ELISA kit (Elabscience Biotechnology, USA; Cata-
logue No: E-EL-H5607) with an intra-assay CV of < 10%.
Plasma asprosin levels were determined using an ELISA
kit (Elabscience Biotechnology, USA; Catalogue No:
E-EL-H2266) having an intra-assay CV of < 10%.
Statistical analysis
Descriptive statistics, presented as means along with
standard deviations (SD), described the entirety of the
collected data. e Shapiro–Wilk test was used to ascer-
tain the normality of the data distribution. A two-way
ANOVA repeated measures test was used to evaluate
Group × Time interactions. Baseline data for the four
groups underwent assessment using one-way ANOVA
and Fisher LSD post hoc tests. In instances where
ANOVA detected a significant difference, pairwise com-
parisons were conducted to ascertain mean differences.
e determination of sample size was used to identify a
statistical difference in study variables, maintaining a 95%
confidence interval (CI) with a power value equal to or
exceeding 80%. Additionally, effect sizes were included in
the analysis, reported as partial eta-squared (η2). Adher-
ing to the classification by Hopkins et al. (2009) [32],
effect sizes were categorized as trivial (< 0.2), small (0.2–
0.6), moderate (0.6–1.2), large (1.2–2.0), and very large
(2.0–4.0). e threshold for statistical significance was
set at a p-value of < 0.05. All statistical analyses were con-
ducted using SPSS software, version 24 (Chicago, Illinois,
USA).
Table 1 Mean (± SD) values of nutritional intake in the four study groups
CG SG TG TSG
Pre Post Pre Post Pre Post Pre Post
Energy (kcal/d) 2321 ± 47 2342 ± 56 2354 ± 101 2314 ± 100 2349 ± 117 2297 ± 117 2375 ± 157 2301 ± 126
CHO (g/d) 292 ± 30.4 295 ± 31.3 288.4 ± 25.1 278 ± 26.5 298 ± 41.6 270 ± 37.2 297 ± 39.6 269 ± 30.1
Fat (g/d) 91.2 ± 16.0 92 ± 19.8 95.5 ± 17.7 84 ± 16.2 94.4 ± 19.4 84.1 ± 15.2 918 ± 15.87 75.2 ± 18.3
Protein (g/d) 115 ± 17.0 119 ± 19.3 112 ± 15.5 105 ± 16.6 113 ± 13.8 103 ± 11.7 112 ± 11.5 101 ± 12.5
CG: Control group; SG: Supplement group; TG: Training group; TSG: Training supplement group
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Page 5 of 13
Delfan et al. Nutrition & Metabolism (2024) 21:11
Results
Anthropometric indices, and VO2peak
e baseline differences between the four groups were
not significant for body mass (p = 0.46) or BMI (p = 0.46).
Body mass was different from baseline in the TSG
(p = 0.039), but not in the SG (p = 0.72), TG (p = 0.12)
or CG groups (p = 0.70) ( Table 2). Values of BMI were
not different from baseline for any of the four groups
(p > 0.05) (Table 2). ere were no significant interac-
tions between group and time for either weight (p = 0.28,
η2 = 0.08) or BMI (p = 0.36, η2 = 0.07). Values of FFM
(p = 0.99) and FAT (p = 0.33) did not differ in the four
groups at baseline. ere was an increase in FFM in
TSG (p = 0.002) but not in SG (p = 0.067), TG (p = 0.056),
or CG (p = 0.42). ere was an interaction between time
and groups for FFM (p = 0.046, η2 = 0.18). A Bonferroni
post hoc test indicated that FFM in the TSG was higher
than in CG (p = 0.039) (Table 2). ere were reductions
from baseline FAT in SG (p = 0.004), TG (p < 0.0001) and
TSG (p < 0.0001), but not in CG (p = 0.28). e time x
group interaction for FAT was also significant (p < 0.001,
η2 = 0.46). Fat percentage was higher in CG compared
to SG (p = 0.036), TG (p = 0.0001) and TSG (p = 0.0001),
while there were no differences between the TSG and SG
(p = 0.078) and TG (p = 0.99) or between the TG and SG
(p = 0.83) (Table2).
ere were no differences in VO2peak between the four
study groups at baseline (p = 0.10). ere were significant
increases in VO2peak from baseline in TG (p = 0.001) and
TSG (p = 0.0001) after 12 weeks, but with no changes in
CG (p = 0.29) or SG (p = 0.15). e interaction between
time and groups was significant for VO2peak (P = 0.001,
η2 = 0.35). In comparison to the CG, VO2peak was higher
in TG (p = 0.003) and TSG (p = 0.001) after 12 weeks, but
not in SG (p = 0.51). ere were no differences in VO2peak
between the SG and TG (p = 0.30) or between the TSG
and TG (p = 0.99) or SG (p = 0.15) (Table2).
Glucose, insulin, and HOMA
Baseline values for glucose (p = 0.66), insulin (p = 0.53),
and HOMA-IR (p = 0.49) were not different between
the groups. e time x group interaction for glucose
(p = 0.0001, η2 = 0.60), insulin (p = 0.0001, η2 = 0.73)
and HOMA-IR (p = 0.0001, η2 = 0.76) were significant.
Reductions in glucose levels in the SG (p = 0.0001), TG
(p = 0.0001), and TSG (p = 0.0001) were significant com-
pared to baseline, while there were no changes in CG
(p = 0.62). Blood glucose was different in SG (p = 0.006),
TG (p = 0.0001) and TSG (p = 0.0001) compared to CG.
In addition, the reduction in blood glucose in TSG
was greater than in SG (p = 0.005) but not than in TG
(p = 0.99). e differences between glucose in the SG and
TG were not significant (p = 0.10) ( Table1).
ere were no differences for insulin at base-
line (p > 0.05) in the four study groups. Insulin lev-
els decreased after 12 weeks in SG (p = 0.0001), TG
(p = 0.0001) and TSG (p = 0.0001) compared to baseline,
while there was no change in CG (p = 0.31). A Bonfer-
roni test indicated that the reductions in insulin after
12 weeks in SG (P = 0.006), TG (P = 0.0001) and TSG
(P = 0.0001) were different from CG. e reduction in
the TSG was greater than in SG (p = 0.0001) but not com-
pared to TG (p = 0.58). e reduction in insulin levels in
SG was greater compared to TG (p = 0.001) (Table1).
A similar pattern of changes was observed in HOMA-
IR. No differences in HOMA-IR were observed between
the groups at baseline, but HOMA-IR was lower in SG
(p = 0.001), TG (p = 0.001) and TSG (p = 0.001) after
12 weeks, with no change in CG (p = 0.36). e reduc-
tions in HOMA-IR in SG (p = 0.0001), TG (p = 0.0001)
and TSG (p = 0.0001) were different from changes in
Table 2 Mean (± SD) values of glucose, insulin, lipid prole, body composition, and VO2peak in the four study groups
CG SG TG TSG
Pre Post Pre Post Pre Post Pre Post
Body height (cm) 175.7 ± 4.2 -171.3 ± 4.2 -173.3 ± 8.2 -175.2 ± 6.5 -
Body mass (kg) 101.2 ± 5.3 102.0 ± 2.5 97.8 ± 4.7 97.05 ± 2.45 99.5 ± 10.1 96.2 ± 2.4 101.5 ± 7.9 96.9 ± 1.9 &
BMI (kg/m2)32.8 ± 1.2 33.1 ± 1.4 33.3 ± 0.6 33.13 ± 1.99 33.0 ± 0.8 32.2 ± 2.7 33.0 ± 1.0 31.7 ± 2.2
FFM (kg) 26.4 ± 2.8 25.7 ± 2.8 26.2 ± 2.2 27.86 ± 1.18 26.5 ± 1.8 28.2 ± 2.4 26.4 ± 2.1 29.2 ± 2.3 &,*,#
FAT (kg) 31.1 ± 1.5 31.8 ± 2.1 31.1 ± 1.6 29.08 ± 0.80 &,* 31.4 ± 1.5 27.9 ± 0.9 &, * 32.1 ± 1.4 27.6 ± 1.2 &,*,#
VO2peak
(mL⋅kg− 1⋅min− 1)
26.6 ± 1.8 25.7 ± 1.7 26.7 ± 1.4 27.92 ± 2.32 &,* 26.4 ± 1.3 29.9 ± 2.1&, * 26.5 ± 1.8 30.4 ± 1.9 &,*,#
Glucose (mg/dl) 96.4 ± 13.1 98.0 ± 9.4 98.9 ± 10.7 84.77 ± 4.50 &,* 99.3 ± 5.7 74.1 ± 5.44 &,* 101.6 ± 7.1 71.5 ± 7.7 &,*,#
Insulin (ng/ml) 18.8 ± 0.7 19.1 ± 0.6 18.8 ± 0.8 17.60 ± 0.52 &,* 18.8 ± 0.4 15.8 ± 1.1 &,* 19.1 ± 0.5 15.3 ± 0.8 &,*,#
HOMA -IR 4.5 ± 0.7 4.6 ± 0.5 4.6 ± 0.5 3.69 ± 0.25 &,* 4.6 ± 0.3 2.9 ± 0.3 &,* 4.8 ± 0.4 2.7 ± 0.3 &,*,#
CG: Control group; SG: Supplement group; TG: training group; TSG: training + Supplement gro up BMI: Body Mass Index ; FFM: Fat-Free Mass; HOMA-IR: Hom eostatic
Model Ass essment of Insulin Resist ance
& Signicant dierence compared to pre-test values (p < 0.05)
* Signicant d ierence from the contro l group (p < 0.05)
# Signicant i nteraction betwe en time and groups (p < 0.05)
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Page 6 of 13
Delfan et al. Nutrition & Metabolism (2024) 21:11
CG. Reductions in HOMA-IR in TSG (p = 0.0001) and
TG (p = 0.0002) were greater than changes in SG, while
there were no differences between TG and TSG (p = 0.59)
(Table1).
ere were no differences at baseline between the four
groups for asprosin (p = 0.92), spexin (p = 0.88), lipo-
calin2 (p = 0.89), omentin (p = 0.35), or irisin (p = 0.71).
e results of repeated measures ANOVA indicated a
significant interaction between time and groups asprosin
(p = 0.001, η2 = 0.33) (Fig. 1). An analysis using Bonfer-
roni post hoc test indicated that the increases in asprosin
after 12 weeks in CG were different from the reduction
in SG (p = 0.017), TG (p = 0.038) and TSG (p = 0.001),
while the differences between TSG and TG (p = 0.99) and
SG (p = 0.99) and also between TG and SG (P = 0.99) for
reductions after 12 weeks were not significant. In terms
of within-group changes, there were increases in aspro-
sin after 12 weeks in CG (p = 0.049) and the decreases
in asprosin in SG (p = 0.018), TG (p = 0.007) and TSG
(p = 0.047) (Fig.1).
e interaction between time and groups was signifi-
cant for spexin (p = 0.014, η2 = 0.23) (Fig.2). e post hoc
test results indicated that spexin levels only increased
after in TSG compared to changes in CG (p = 0.011),
but other between-group changes were not significant
(p = 0.99). Pre-post changes in TG (p = 0.007) and TSG
(p = 0.0001) were significant, while the decrease of spexin
in CG (p = 0.53) and the increase in SG (p = 0.095) were
not significant (Fig.2).
ere was a significant interaction between time and
groups for lipocalin-2 (p = 0.005, η2 = 0.27) (Fig. 3). ere
were differences between decreased lipocalin-2 lev-
els in TSG and the increased level of lipocalin-2 in CG
(p = 0.004) after 12 weeks, while other between-group
changes were not statistically significant (p = 0.99). In
comparison with pre-test levels, the decreased post-
test values of lipocalin-2 in TG (p = 0.005) and TSG
(p = 0.0001) were significant, while the increase of lipo-
calin-2 in CG (p = 0.40) and decreased levels in SG
(p = 0.08) were not significant (Fig.3).
ere were significant time and group interactions for
omentin (p = 0.0001, η2 = 0.50) (Fig. 4). e increase in
CG was lower than in SG (p = 0.032), TG (= 0.0001), and
TSG) (p = 0.0001). Moreover, increases in omentin levels
in TG were not greater than in SG (p = 0.17). Addition-
ally, increases in omentin levels in TSG did not differ
from either TG (p = 0.99) or SG (p = 0.07). Omentin values
increased in SG (p = 0.0001), TG (p = 0.0001), and TSG
(p = 0.0001), whereas no change occurred in CG (p = 0.34)
(Fig.4).
ere was an interaction between time and groups for
irisin levels (p = 0.0001, η2 = 0.39) (Fig. 5). Changes in iri-
sin levels in CG after 12 weeks were different from the
increased levels of irisin in SG (p = 0.006), TG (p = 0.002)
Fig. 1 Pre- and post-training values (mean ± SD) for asprosin in control (CG), supplement (SG), training (TG), training + supplement (TSG) groups
&: dierent from pretest values (p < 0.05)
*: dierent from control group (p < 0.05)
#: interaction between time and groups (p < 0.05)
Correct “&” in TSG bar graphs
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Page 7 of 13
Delfan et al. Nutrition & Metabolism (2024) 21:11
Fig. 3 Pre- and post-training values (mean ± SD) for lipocalin-2 in control (CG), supplement (SG), training (TG), training + supplement (TSG) groups
&: dierent from pretest values (p < 0.05)
*: dierent from control group (p < 0.05)
#: interaction between time and groups (p < 0.05)
Correct “&” in TSG bar graphs
Fig. 2 Pre- and post-training values (mean ± SD) for spexin in control (CG), supplement (SG), training (TG), training + supplement (TSG) groups
&: dierent from pretest values (p < 0.05)
*: dierent from control group (p < 0.05)
#: interaction between time and groups (p < 0.05)
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Page 8 of 13
Delfan et al. Nutrition & Metabolism (2024) 21:11
and TSG (p = 0.0001). e increase in irisin levels in TG
were not higher than in SG (p = 0.99). Irisin levels in TSG
were higher than in TG (p = 0.99) or CG (p = 0.99). e
reduction in irisin levels in CG after 12 weeks was differ-
ent from pretest values (p = 0.46). ere were increases in
irisin levels in SG (p = 0.0001), TG (p = 0.0001) and TSG
(p = 0.0001) after 12 weeks (Fig.5).
Discussion
is study indicates that a 12-week intervention of HIIT
and spirulina supplementation, individually or in com-
bination, improves the levels of some circulating adipo-
kines in obese men. Notably, the combined intervention
of HIIT and spirulina yielded greater improvements in
the measured outcomes compared with each interven-
tion alone. Specifically, we report reductions in plasma
lipocalin-2 and asprosin levels combined with increases
in irisin, omentin, and spexin levels produced by HIIT
and spirulina supplementation. Furthermore, this com-
bined approach increased VO2peak and FFM while
decreasing body fat levels and insulin resistance.
Anthropometric indices and cardiorespiratory parameters
Our findings provide insights into the intricate relation-
ship between spirulina supplementation, HIIT, and body
composition, with a particular focus on the interplay of
these factors on fat percentage. e combined use of
spirulina and HIIT enhanced FFM and simultaneous FAT
reductions. Notably, HIIT alone induced changes specifi-
cally in FAT, while sole supplementation with spirulina
failed to elicit modifications in either FFM or FAT. is
observation suggests a synergistic interaction between
spirulina’s antioxidant effects and the physiological ben-
efits of HIIT, which leads to nuanced alterations in body
composition.
e reductions in FAT can be reasonably attributed
to the greater energy expenditure associated with HIIT.
Despite not providing daily energy expenditure details,
our analysis indicated no energy intake discrepancies
between pre- and post-intervention reporting peri-
ods. is alignment with our results corroborates find-
ings from previous studies showcasing the efficacy of a
12-week HIIT regimen leading to decreases in abdomi-
nal, trunk, and visceral fat in overweight young males
[32, 33].
Furthermore, the increase in FFM in the combined
HIIT and supplement group in our study aligns with pre-
vious reports that underscored spirulina’s benefits on lean
body mass and body composition, particularly in middle-
aged and elderly individuals [24, 35]. Additionally, prior
studies highlighted spirulina’s potential to enhance body
fat percentage, reduce fat mass, and modulate myostatin,
follistatin, and insulin-like growth factor 1 (IGF-1) levels,
factors that are pivotal in regulating muscle mass [24, 35].
Fig. 4 Pre- and post-training values (mean ± SD) for omentin in control (CG), supplement (SG), training (TG), training + supplement (TSG) groups
&: dierent from pretest values (p < 0.05)
*: dierent from control group (p < 0.05)
#: interaction between time and groups (p < 0.05)
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Page 9 of 13
Delfan et al. Nutrition & Metabolism (2024) 21:11
Our findings align with this body of work, suggesting spi-
rulina’s positive influence on lean body mass in the con-
text of training and weight loss regimens.
e preservation or promotion of muscle mass has
important implications for metabolic health by fend-
ing off an array of obesity-associated ailments, such as
insulin resistance, type 2 diabetes, and cardiovascular
disorders [36–38]. Likewise, there is much evidence to
support a link between cardiorespiratory fitness, cardio-
metabolic health, and all-cause mortality [39]. While our
study demonstrated a boost in VO2peak due to HIIT, it
is important to note that the incorporation of spirulina
failed to yield further increases in VO2peak compared to
HIIT alone. e existing literature describing spirulina’s
impact on aerobic exercise performance remains incon-
clusive, with conflicting evidence proposing both ergo-
genic and non-ergogenic effects [40].
Asprosin
Asprosin, a glucogenic adipokine secreted by white
adipocytes, participates in numerous physiological
processes, including hepatic glucose production and
modulation of metabolic dysfunction in obesity [41, 42].
e impact of asprosin on obesity remains unclear, but
studies suggest its involvement in the early stages of dys-
glycemia and obesity-related disorders [41]. Notably,
aerobic exercise reduces hepatic asprosin expression,
indicating a potential link between exercise and asprosin
regulation [42].
Our 12-week study involving HIIT, with or without
daily spirulina supplementation, reduced circulating
asprosin levels in obese males, a reduction that was also
observed with spirulina supplementation alone. Both
exercise and spirulina supplementation enhance anti-
oxidant capacity, reduce oxidative stress, and decrease
markers of inflammation [42–45]. Our findings suggest
that the changes in asprosin levels may be associated with
reduced oxidative stress in white adipocytes, potentially
leading to an improved proinflammatory secretory pro-
file [46, 47]. Importantly, our study highlights the poten-
tial synergistic effects of spirulina and HIIT in decreasing
asprosin levels, contributing to improved blood glucose,
insulin levels, and increased insulin sensitivity in obesity.
Further exploration and large-scale clinical studies are
warranted to validate these effects and understand the
underlying mechanisms.
Fig. 5 Pre- and post-training values (mean ± SD) for irisin in control (CG), supplement (SG), training (TG), training + supplement (TSG) groups
&: dierent from pretest values (p < 0.05)
*: dierent from control group (p < 0.05)
#: interaction between time and groups (p < 0.05)
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Page 10 of 13
Delfan et al. Nutrition & Metabolism (2024) 21:11
Spexin
Spexin, a recently identified secretion from adipose tis-
sue, plays a pivotal role in regulating energy homeostasis
and adipocyte function. Levels of spexin are decreased
in adipocytes and also in the circulation in obesity [15].
Emerging evidence from animal studies suggests that
spexin protects against obesity by impeding adipogen-
esis, modulating the expression of pro-adipogenic genes
[48], reducing weight and improving insulin sensitivity
[49]. Notably, spexin is believed to participate in coun-
teracting obesity through mechanisms involving appetite
suppression and enhanced physical activity [50, 51].
Human studies indicate that circulating spexin levels
are reduced in obesity, exhibiting a negative correlation
with multiple markers such as leptin, ghrelin, total cho-
lesterol, LDL, blood pressure, insulin, HOMA-IR, BMI,
and waist-to-hip ratio [15]. Conversely, there are also
positive correlations between adiponectin, glucagon-like
peptide 1, and insulin sensitivity [48, 52]. Intriguingly,
obese subjects undergoing a combination of aerobic
and resistance training have increases in spexin levels,
mostly in individuals with maximal oxygen consump-
tion, C-reactive protein, total cholesterol, HbA1c, and
HOMA-IR, underscoring the potential of spexin as a bio-
marker for obesity and its related cardiometabolic mani-
festations [15].
Our study reports increases in circulating spexin levels
after 12 weeks of HIIT independent of supplementation
with spirulina. To the best of our knowledge, our investi-
gation is the first to report a beneficial effect of HIIT on
circulating spexin levels. is phenomenon is presumed
to contribute to the favorable health outcomes associated
with HIIT in obese individuals.
Lipocalin-2
e peptide lipocalin-2 is expressed in various tissues,
including adipose tissue, and is released into circulation
as an adipokine [53], and plays a role in metabolic dys-
regulation associated with obesity and diabetes; however,
its precise function remains unclear [54]. For instance,
some studies suggest that lipocalin-2 reduces food intake,
fat mass, and body weight gain in rodent, while simul-
taneously enhancing glucose metabolism [54, 55]. Fur-
thermore, lipocalin-2 may have protective effects against
obesity-related metabolic impairments, fatty liver dis-
ease, atherogenic dyslipidemia, insulin resistance, and is
also associated with the modulation of hepatic gluconeo-
genesis, adaptive thermogenesis, activation of brown fat,
and fatty acid oxidation [56–59].
Reports on the impact of exercise on lipocalin-2 levels
are inconsistent; some studies reported no changes after
concurrent training or endurance/resistance training
[60, 61], while other studies report either increased lipo-
calin-2 levels following 12 weeks of HIIT in obese males
[62] or observed decreases with endurance and resis-
tance training in sedentary young men [63]. Our study,
involving 12 weeks of HIIT in obese males, demonstrated
a reduction in lipocalin-2 levels. Discrepancies in find-
ings may be attributed to differences in HIIT protocols,
including work interval durations and overall exercise
duration. Notably, spirulina supplementation did not
enhance lipocalin-2 levels during HIIT or as a standalone
supplement.
Omentin-1
Our investigation provides intriguing insights into the
modulation of omentin-1 levels, which diverge from our
prior study outcomes indicating that 12 weeks of HIIT
reduced omentin-1 levels in obese males [63], whereas
our study suggests incrreases in omentin-1 levels both in
the presence and absence of spirulina supplementation.
Notably, spirulina supplementation in isolation increased
omentin-1 levels, corroborating similar observations
where plasma omentin-1 concentrations were increased
after four weeks of HIIT, regardless of spirulina incorpo-
ration [24].
Findings on the impact of exercise on circulating
omentin-1 levels remain intricate and heterogeneous,
with a spectrum of findings, where some investigations
reporting heightened omentin-1 levels due to exercise
[64], while others observed decreases [65, 66]. is vari-
ability may be due to multifaceted factors inherent to the
populations and methodologies employed.
Circulating omentin-1 levels, often attenuated in indi-
viduals grappling with obesity, serve as a potential bio-
marker for metabolic risk, given their inverse correlation
with cardiometabolic risk factors [17, 67, 68]. e intri-
cate interplay between omentin-1 expression, plasma
concentrations, and visceral adipose tissue is under-
scored by diminished omentin-1 expression in visceral
adipocytes in those afflicted by obesity [67]. Emerging
evidence suggests that omentin-1 has beneficial effects
on insulin sensitivity, affording protection against athero-
genesis through its involvement in macrophage differen-
tiation, inflammation, arterial calcification, and plaque
formation [68]. Furthermore, decreased omentin-1 con-
centrations correlate with elevated carotid intima-media
thickness in healthy males [68] and are implicated in cor-
onary artery disease [69, 70]. ese beneficial metabolic
and atherogenic effects are postulated to emanate from
the inherent anti-inflammatory and antioxidant proper-
ties of omentin-1 [68, 71]. While the precise impact of
exercise, particularly HIIT, on omentin-1, remains to be
elucidated, the decreases in circulating omentin-1 lev-
els potentially signify improvements in metabolic and
cardiovascular health, accompanied by reduced disease
susceptibility.
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Page 11 of 13
Delfan et al. Nutrition & Metabolism (2024) 21:11
Irisin
e adipokine irisin improves metabolic functional-
ity induced by exercise in various tissues such as skele-
tal muscle, adipose tissue, the pancreas, liver, bone, the
central nervous system, and the endothelium. Exercise
augments PCG1-α expression in skeletal muscle, and
triggers the synthesis of fibronectin type III domain-
containing protein 5 (FNDC5) which is secreted into the
bloodstream after cleavage [72]. Notably, irisin improves
glucose and lipid metabolism, mitigating the impacts of
obesity-related inflammation, metabolic syndrome, and
diabetes [73, 74].
Our study indicates that 12 weeks of HIIT, either cou-
pled with daily spirulina supplementation or pursued
independently, leads to an elevation in circulating irisin
levels among obese males. Other studies report increases
in in irisin concentrations following high-intensity exer-
cise, albeit with a limited focus on the implications of
HIIT [72, 75, 76]. A separate study by Murawska-Cialo-
wicz et al. observed heightened irisin levels in non-obese,
prediabetic men after an eight-week HIIT regimen [76].
To our knowledge, there is a dearth of data on the impact
of dietary antioxidant supplementation, such as that
involving spirulina, on the modulation of circulating iri-
sin levels.
e therapeutic potential of irisin extends across vari-
ous health domains, including obesity, type 2 diabetes,
cardiovascular ailments, stroke, neurodegenerative dis-
orders, cancer, and sarcopenia [77–80], underscoring
the notion that the amalgamation of HIIT and spirulina
supplementation-induced elevations in irisin levels may
furnish protection against the adverse consequences
associated with obesity.
Study limitations
Our study has several limitations that warrant consid-
eration: [1] e exclusive inclusion of male participants
with obesity raises questions about the generalizability of
our findings, particularly to females and individuals with
varied demographic profiles; [2] e emphasis on blood
levels of adipokines may limit insights into tissue-specific
changes. To provide a more comprehensive understand-
ing, future research should consider incorporating addi-
tional factors, such as a detailed exploration of oxidative
stress and energy expenditure, to further contextualize
our findings.
Conclusions
Our findings contribute to the expanding body of evi-
dence that underscores the potential of HIIT in ame-
liorate adipokine profiles in the context of obesity.
Moreover, our study suggests that supplementation
with spirulina may be a promising approach for dimin-
ishing pro-inflammatory adipokines while concurrently
enhancing anti-inflammatory adipokines. is holds sig-
nificance due to emerging indications of the important
role of adipokines in mediating the metabolic, cardiovas-
cular, and inflammatory imbalances inherent in obesity.
eir secretory composition is implicated in either exac-
erbating or safeguarding against a spectrum of obesity-
associated disorders. Further investigations are needed to
establish more robustly the impact of therapeutic inter-
ventions using HIIT and dietary antioxidants on refining
adipokine profiles in obesity.
Acknowledgements
The authors thank Professor Jonathan P little (University of British Colombia)
for constructive feedback on the manuscript.
Author contributions
MD, RS, AS and HZ designed the study. MD, RS and AS conducted the study.
RS analyzed the obtained data. MD, AS, KE and HZ wrote the rst draft of the
manuscript. IL, HZ, RS, MD, KMH, KW and BK read, revised, and approved the
nal version of the manuscript.
Funding
The authors acknowledge the support of the Alzahra University.
Data availability
No datasets were generated or analysed during the current study.
Declarations
Ethics approval and consent to participate
We conrmed that written informed consent for study participation was
obtained from all study participants before the study started. The study was
approved by Sport Sciences Research Institute Ethics Committee of Alzahra
University (Tehran, Iran). (Ethics code: IR.SSRC.REC.1401.093). All procedures
were performed according to the latest revision of the Declaration of Helsinki.
Competing interests
The authors declare no competing interests.
Author details
1Department of Exercise Physiology, Faculty of Sport Sciences, Alzahra
University, Tehran, Iran
2Department of Physical Education and Sport Sciences, Faculty of
Humanities and Social Sciences, University of Kurdistan, Sanandaj,
Kurdistan, Iran
3Centre for Health and Exercise Science Research, SPEH, Hong Kong
Baptist University, Kowloon Tong, Hong Kong SAR, China
4Department of Kinesiology, California State University, Long Beach,
CA 90840, USA
5Department of Anesthesiology, Pharmacology, and Therapeutics, Faculty
of Medicine, University of British Columbia, Vancouver, Canada
6Department of Kinesiology, Kansas State University, Manhattan,
KS 66502, USA
7Institute of Primary Care, University of Zurich, Zurich, Switzerland
8Medbase St. Gallen Am Vadianplatz, Vadianstrasse 26, St. Gallen
9001, Switzerland
9Univ Rennes, M2S (Laboratoire Mouvement, Sport, Rennes,
Santé EA 1274, F-35000, France
10Institut International des Sciences du Sport (2I2S), Irodouer
35850, France
Received: 5 December 2023 / Accepted: 16 February 2024
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Page 12 of 13
Delfan et al. Nutrition & Metabolism (2024) 21:11
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