inflammatory and anti - inflammatory conditions contributing to atherosclerosis are assessable through studying circulatory biological indices including interleukins ( ils ) , attracting molecules , and chemokines .
intercellular adhesion molecules-1 ( icam-1 ) , monocytes chemo tactic protein-1 ( mcp-1 ) , and il-10 are among independent and significant inflammatory and anti - inflammatory indices which , directly or indirectly , contribute to atherosclerosis process .
different approaches including exercise training and antioxidant supplementation have been used to reduce inflammatory cytokines . among physical activity programs , high - intensity interval training ( hiit )
hiit includes short - term intensive activities ( 6 s4 min ) with high intensity ( 90% of maximum aerobic capacity ) and active or passive short - term recovery intervals .
the influence of hiit on inflammatory markers shows contradictory results in literature , while some indicate attenuation of inflammation and others show no change .
it has been shown that 2 weeks of hiit improved mcp-1 and oxygen consumption to a maximum level , without any change in serum il-10 and icam-1 in obese and overweight men .
it has been shown that the main ginger elements such as gingerols ( gingerol-6 , -8 , and -10 ) and shogaols ( shogaol-6 and -8 ) reduced mcp-1 and icam-1 mrna in different cells by the inhibition of nuclear factor-b ( nf-b ) activation in response to inflammatory stimuli while there are many reasons supporting the effectiveness of ginger on inflammatory indices ; a few studies have reported contradictory results . although there are some evidences regarding the simultaneous implementation of ginger intake and physical activity on inflammatory indices , the outcomes are not in agreement .
observed no change in levels of lipid profile after 10-week of progressive resistance training , together with ginger supplement .
in contrast , ayaz and roshan demonstrated reduced plasmatic levels of il-6 and c - reactive protein following physical exercise together with ginger supplement .
however , the effect of ginger which has a potent anti - inflammatory effect has not been evaluated in hiit , exclusively on icam-1 , mcp-1 , and il-10 markers .
therefore , the present study aimed at answering the question whether or not high hiit solely or in combination with ginger supplement decrease chronic inflammation .
the study protocol was approved by the medical ethics committee of birjand university of medical sciences .
the study protocol of the current study is registered with the iranian registry of clinical trials ( www.irct.ir ; irct2016051027836n1 ) .
we included thirty female students aged between 20 and 30 years with overweight , according to morgan table .
all the participants were randomly assigned to three equal study groups ( n = 10 ) , namely hiit + ginger , hiit + placebo , and ginger , using a computer - based random digit generator using the admission numbers .
the female students were excluded from the study if they had cardiovascular diseases ( cvds ) , hypertension , diabetes , smoking , pregnancy , and regular physical activity 6 months before the research plan .
demographic data of the participants , determining their health statuses and acquiring written consent form , were obtained before starting the program .
the exercise protocol was taken from 40-m maximal shuttle run , which is a valid test for the assessment of anaerobic function . during this activity ,
each participant totally ran and returned a 20 m route at her maximum speed in 30 s. the exercise protocol was performed three times per week for 10 weeks as shown in table 1 .
the exercise was conducted at 90% maximum heart rate ( age - 220 ) intensity which was controlled by a telemetry ( polar , finland ) . according to specific doses in previous studies ,
participants in ginger and exercise + ginger groups daily received 3000 mg ginger tablets ( produced by iran dineh co. , tehran , iran ) , whereas the exercise + placebo group received nokhodchi flour tablets ( produced by iran dineh co. , tehran , iran ) in the same manner , for 10 weeks , 7 days / week , 30 min before each meal .
high - intensity interval exercise protocol baecke habitual physical activity questionnaire was used initially . a week before primary measurement of variables , the participants weights were assessed by laboratory scale with an accuracy of < 100 g ( tcm , china ) in a status without shoes and minimal clothes .
skin folds were measured using caliper ( eiyoken type , yagami , pat 376843 , japan ) according to pollock three sites methodology , then percent body fat ( pbf ) was calculated from appropriate formula .
each participant performed bruce maximum test using a treadmill ( t 150 cos10199 model , h - p - cosmos company ) .
maximum oxygen consumption ( vo2max ) was calculated using an extended form of the formula ; then , we have vo2max = ( 4.38  total exercised time )  3.9 the participants were asked to maintain their habitual diet during the protocol and refrain from consuming any antioxidant supplements , extra ginger , varying ordinary diet and ginger dose .
their 3 consecutive days diet , including a 1-day holiday and 2 working days in the 1 and last week of exercise program , was controlled through a questionnaire .
results showed no significant difference ( hiit + ginger : 1221  40.93 kcal , 141.19  5.22 g carbohydrate , 56.68  0.90 g fat , and 51.29  0.63 g protein ; hiit + placebo : 1209  40.93 cal , 132.60  5.22 g carbohydrate , 55.37  0.90 g fat , and 52.38  0.63 g protein ; ginger : 1275  40.93 cal , 134.72  5.22 g carbohydrate , 56.89  0.90 g fat , and 52.47  0.63 g protein ; energy p = 0.24 , carbohydrate p = 0.91 , fat p = 0.67 , protein p = 0.83 ) , between the three groups regarding macronutrient and calorie intake .
moreover , calorie intake from the last meal , before testing , was balanced to 500600 cal for all participants . at the end of the program ,
two cases from each group were eliminated due to irregular physical activity , taking hormonal tablets , traveling , and pregnancy .
consort flow diagram of the study venus blood samples ( 10 cc ) were withdrawn from all the participants 24 h before the 1 and 48 h after the last training session , whereas the participants were in their follicular phase of menstruation and fasting for 12 h. then , serum was stored at 80c for the following analysis .
we used 96-well enzyme - linked immunosorbent assay kits to measure the levels of icam 1 ( ka za bayoi , china , sensitivity < 15.6 pg / ml , intraassay cv < 8% ) , mcp 1 ( ka za bayoi , china , sensitivity < 30.184 pg / ml , intraassay cv < 8% ) , and il 10 ( diaclone sas , france , sensitivity
data were analyzed using statistical package for social sciences ( spss inc . , chicago , il , usa ) software version 16.0 and were expressed as mean  standard deviation or median ( 25 , 75 ) percentiles .
differences between the baseline means of the three groups in all variables were analyzed using one - way analysis of variance ( anova ) .
smirnov test and the levene 's test , respectively , the between - group differences were examined using either a one - way anova for normally distributed data , or kruskal  wallis test for nonnormal distributed data ( mcp-1 , il-10 , and vo2max ) .
then , to locate differences , tukey 's post hoc test was used ( p < 0.05 ) in the next step .
within - group differences were determined using either paired t - test for normally distributed data and wilcoxon signed - rank test for nonnormal distributed data ( mcp-1 , il-10 , and vo2max ) .
the study protocol was approved by the medical ethics committee of birjand university of medical sciences .
the study protocol of the current study is registered with the iranian registry of clinical trials ( www.irct.ir ; irct2016051027836n1 ) .
we included thirty female students aged between 20 and 30 years with overweight , according to morgan table .
all the participants were randomly assigned to three equal study groups ( n = 10 ) , namely hiit + ginger , hiit + placebo , and ginger , using a computer - based random digit generator using the admission numbers .
the female students were excluded from the study if they had cardiovascular diseases ( cvds ) , hypertension , diabetes , smoking , pregnancy , and regular physical activity 6 months before the research plan .
demographic data of the participants , determining their health statuses and acquiring written consent form , were obtained before starting the program .
the exercise protocol was taken from 40-m maximal shuttle run , which is a valid test for the assessment of anaerobic function . during this activity ,
each participant totally ran and returned a 20 m route at her maximum speed in 30 s. the exercise protocol was performed three times per week for 10 weeks as shown in table 1 .
the exercise was conducted at 90% maximum heart rate ( age - 220 ) intensity which was controlled by a telemetry ( polar , finland ) . according to specific doses in previous studies ,
participants in ginger and exercise + ginger groups daily received 3000 mg ginger tablets ( produced by iran dineh co. , tehran , iran ) , whereas the exercise + placebo group received nokhodchi flour tablets ( produced by iran dineh co. , tehran , iran ) in the same manner , for 10 weeks , 7 days / week , 30 min before each meal .
baecke habitual physical activity questionnaire was used initially . a week before primary measurement of variables , the participants weights were assessed by laboratory scale with an accuracy of < 100 g ( tcm , china ) in a status without shoes and minimal clothes .
skin folds were measured using caliper ( eiyoken type , yagami , pat 376843 , japan ) according to pollock three sites methodology , then percent body fat ( pbf ) was calculated from appropriate formula .
each participant performed bruce maximum test using a treadmill ( t 150 cos10199 model , h - p - cosmos company ) .
maximum oxygen consumption ( vo2max ) was calculated using an extended form of the formula ; then , we have vo2max = ( 4.38  total exercised time )  3.9 the participants were asked to maintain their habitual diet during the protocol and refrain from consuming any antioxidant supplements , extra ginger , varying ordinary diet and ginger dose .
their 3 consecutive days diet , including a 1-day holiday and 2 working days in the 1 and last week of exercise program , was controlled through a questionnaire .
results showed no significant difference ( hiit + ginger : 1221  40.93 kcal , 141.19  5.22 g carbohydrate , 56.68  0.90 g fat , and 51.29  0.63 g protein ; hiit + placebo : 1209  40.93 cal , 132.60  5.22 g carbohydrate , 55.37  0.90 g fat , and 52.38  0.63 g protein ; ginger : 1275  40.93 cal , 134.72  5.22 g carbohydrate , 56.89  0.90 g fat , and 52.47  0.63 g protein ; energy p = 0.24 , carbohydrate p = 0.91 , fat p = 0.67 , protein p = 0.83 ) , between the three groups regarding macronutrient and calorie intake .
moreover , calorie intake from the last meal , before testing , was balanced to 500600 cal for all participants . at the end of the program ,
two cases from each group were eliminated due to irregular physical activity , taking hormonal tablets , traveling , and pregnancy .
venus blood samples ( 10 cc ) were withdrawn from all the participants 24 h before the 1 and 48 h after the last training session , whereas the participants were in their follicular phase of menstruation and fasting for 12 h. then , serum was stored at 80c for the following analysis .
we used 96-well enzyme - linked immunosorbent assay kits to measure the levels of icam 1 ( ka za bayoi , china , sensitivity < 15.6 pg / ml , intraassay cv < 8% ) , mcp 1 ( ka za bayoi , china , sensitivity < 30.184 pg / ml , intraassay cv < 8% ) , and il 10 ( diaclone sas , france , sensitivity
data were analyzed using statistical package for social sciences ( spss inc . , chicago , il , usa ) software version 16.0 and were expressed as mean  standard deviation or median ( 25 , 75 ) percentiles .
differences between the baseline means of the three groups in all variables were analyzed using one - way analysis of variance ( anova ) .
smirnov test and the levene 's test , respectively , the between - group differences were examined using either a one - way anova for normally distributed data , or kruskal  wallis test for nonnormal distributed data ( mcp-1 , il-10 , and vo2max ) .
then , to locate differences , tukey 's post hoc test was used ( p < 0.05 ) in the next step .
within - group differences were determined using either paired t - test for normally distributed data and wilcoxon signed - rank test for nonnormal distributed data ( mcp-1 , il-10 , and vo2max ) .
there was no significant difference between three groups regarding the baseline characteristics [ tables 1 and 2 ] .
wallis test showed vo2max changes ( pre- to post - test ) were significantly different between groups ( p < 0.001 ) .
while no significant between - group differences in mcp-1 , icam-1 , and il-10 changes were determined ( p = 0.178 , p = 0.07 , and p = 0.14 ; respectively ) , and the results are summarized in table 3 . on the other hand ,
the results of wilcoxon signed - rank test showed significant increase in vo2max ; p = 0.012 and p = 0.012 , and a significant decrease in mcp-1 concentration ; p = 0.025 and p = 0.012 in  exercise + ginger  and  exercise + placebo ,  respectively , after 10 weeks of intervention [ table 3 ] . baseline comparison of demographic characteristics comparison of inflammatory indices of the participants in the three studied groups after a 10-week exercise and taking ginger supplement
although popular suggestions regarding health improvement recommend moderate - intensity physical activity on most preferably all days , today experts are more concerned with high - intensity interval exercises , either in healthy participants or cardiovascular patients .
icam-1 , mcp-1 , and il-10 act as primary markers in the first stages of progression , adhesion , and attraction of monocytes to intima and involve in systemic inflammation . in the present study
, we found that although 10 weeks of hiit , by itself or in combination with ginger supplement , resulted in improved mcp-1 and vo2max in overweight women , it did not affect significantly serum - soluble icam ( sicam)-1 and il-10 .
regarding the effectiveness of intensive interval exercise and ginger consumption , our findings were consistent with other studies that showed a significant reduction in circulating mcp-1 in 12 overweight men following 2 weeks of hiit on ergometer with 89.5% vo2max and lack of a significant change in serum il-10 and icam-1 .
in addition , bartlett et al . showed that 10 weeks of hiit on ergometer reduced serum mcp-1 level in inactive 2060 years participants .
in contrast , ahmadizad et al . did not observe any change in young men 's inflammatory indices after 6 weeks of hiit .
the short length of training in the mentioned study may be the relevant cause of discrepancy .
very few studies have dealt with the combined effect of exercises and ginger consumption on inflammatory indices .
black et al . and mashhadi et al . did not find a combined effect of ginger and physical activity on inflammatory indices , in contrast to the studies of atashak et al . and
ayaz and roshan that mentioned decreased values of inflammatory markers following physical exercises together with ginger consumption .
inflammatory indices such as icam-1 , mcp-1 , and il-10 play a significant role in cvds .
il-10 exerts its anti - inflammatory effect on icam-1 through influence on nf-b factor activation , and as a result , the icam-1 gene expression decreases . in the current study , a significant decrease of il-10 in the exercise + placebo group
exercise + ginger  and  ginger  groups , consumption of ginger ( gingerol and shogaol ) for 10 weeks has had decisive anti - inflammatory effects on nuclear transcription factor resulting in insignificant reduction of icam-1 expression .
, participants were suffering from different disorders and pretest icam-1 values were two to three times more than present participants . while the participants in the current study were healthy and probably , the effects of exercise and ginger have little been observed .
it has been said that the anti - inflammatory properties of il-10 relate to its capacity to reduce the production of pro - inflammatory cytokines ( such as il-1  , tumor necrosis factor- , and mcp-1 ) from monocytes through decreasing nf-b activity and increasing interleukin -1 receptor antagonist production .
however , in the current study , decrease in mcp-1 was not parallel to il-10 increase ; perhaps this mechanism was not so effective .
of course , some scholars hold that mcp-1 as potentially independent diagnostic index regarding cvds .
the other aspect of mcp-1 to carry out its pro - inflammatory role is the fatty tissue , which has been reported .
mcp-1 is secreted from intestinal fatty tissue and attracts an increasing number of macrophages to the fatty tissue , thus , organizes the inflammatory process .
mcp-1 reduction in the  exercise + ginger group  in the present study might be due to insignificant decrease of waist : hip girth ratio and significant decrease of body fat . regarding the relationship between aerobic fitness and improvement of inflammatory indices to lower cvds , in the current study , significant improvement in vo2max , probably related to the improvement of mcp-1 in the training groups .
frequent touching of legs with the ground and producing stress - fracture in legs because of brisk running is associated with muscular injuries and inflammation .
present exercise protocol was a form of intense - shuttle running , which is a reason for the insignificant reduction in icam-1 value .
an example of this phenomenon is seen in the study by akimoto et al . , which assessed the effect of different exercises on sicam-1 in healthy men .
lack of change in serum icam-1 levels after an ergometer exercise , while increased values following endurance running have been observed .
they suggested that exercises associated with muscular injuries and inflammation increased the plasma concentration of sicam-1 .
however , it is certain that quality and intensity of exercising stimulus , individuals genetic flexibility , various exercise protocols , and other factors of lifestyle influence the interpretation of the obtained results .
the significant increase observed in training groups , vo2max compared to the  ginger group  is a reason supporting the beneficial effects of hiit on exercise performance and recovering from cvds .
butcher reported the effectiveness of such exercises on vo2max of the old and youth through exercising for 215 weeks .
improved stroke volume relates to increased heart muscle contraction capacity during maximum pressure and increase in mitochondria biogenesis which are the main possible mechanisms of vo2max advance as a result of hiit protocols .
the main characteristic of interval exercises , which makes it more valuable than continuous ones , is their more energy outcome of peripheral muscles without interfering with cardiopulmonary increasing capacity .
the recovery intervals between intensive activity intervals , while reforming phosphocreatine and myoglobin stores influences the blood lactate concentration through delectating it .
therefore , interval exercises compared with continuous ones with the same volume can impose maximum pressure on peripheral muscles and oxygen delivery organs without employing anaerobic metabolism and lactic acid concentration .
a 10-week intensive interval exercise , by itself or together with ginger supplement , improved mcp-1 and vo2max in overweight women ; without any significant effect on sicam-1 and il-10 .
these findings indicate the relative and efficient role of hiit in overweight women without the necessity to combine with ginger as an antioxidant / anti - inflammatory supplement . since the present study lacked a
 placebo group  and the participants diets were not accurately controlled during the research , further investigations are required .
sn contributed in the conception of the work , conducting the study , revising the draft , approving the final version of the manuscript , and agreed for all aspects of the work data and final approval of the version to be published .
mea and tk contributed in the conception of the work , conducting the study , revising the draft , approving the final version of the manuscript , and agreed for all aspects of the work data .
sha contributed in biochemical analyzing , approval of the final version of the manuscript , and agreed for all aspects of the work data .
mm contributed in the conception of the work , consulting and conducting the study and agreed for all aspects of the work data .
 background : most of the cardiovascular diseases can be prevented by doing regular physical exercises and using herbal supplements . the present study is aimed at assessing ginger supplement and high - intensity interval training ( hiit ) on inflammatory indices contributing to atherosclerosis in overweight women.materials and methods : the present study is a randomized , experimental , and controlled one in which thirty healthy overweight women aged 2030 years were randomly divided into three equal groups , namely , ginger , ginger + hiit , and placebo + hiit . 
 the training groups performed high - intensity interval exercises ( i.e. 40-m maximal shuttle run ) for ten consecutive weeks . 
 the supplement groups daily took 3 g of ginger pills and the third group took placebo.results:paired t - test revealed a significant decrease in the density of type 1 monocytes chemo tactic protein ( mcp-1 ) in hiit + ginger ( p = 0.026 ) and hiit + placebo ( p = 0.001 ) groups . 
 besides , maximum aerobic capacity in the two training groups significantly increased p = 0.002 and p = 0.000 , respectively . in spite of this , 
 analysis of variance showed no significant differences in three groups regarding the three indices such as intercellular adhesion molecule-1 ( icam-1 ) ( p = 0.093 ) , mcp-1(p = 0.075 ) , and serum interleukin-10 ( il-10 ) ( p = 0.164).conclusion : a 10-week intensive interval exercise , by itself or together with ginger supplement , improved mcp-1 and maximum oxygen consumption in overweight women , without any significant effect on soluble icam-1 and il-10 . 
 these findings indicate the relative and efficient role of hiit in overweight women without the necessity to combine with ginger as an antioxidant / anti - inflammatory supplement . 
INTRODUCTION
MATERIALS AND METHODS
Study population
Intervention
Study protocol
Sample collection and biochemical determination
Statistical analysis
RESULTS
DISCUSSION
CONCLUSIONS
Financial support and sponsorship
Conflicts of interest
AUTHORS CONTRIBUTION