according to recent estimates , developing countries in asia and in the middle east will have the largest increase in the prevalence of diabetes by 2030 ( 1 ) . the prevalence of type 2 diabetes ( t2d ) is reported to be more than 14% in tehran , iran , with an estimated incidence of new cases in about 1% of population per year ( 2 ) . there is a strong genetic predisposition but the risk is greatly increased when companied with lifestyle factors such as overweight or obesity , high blood pressure , insufficient physical activity , poor diet and visceral fat . there are some characteristics such as hyper - glycemia , insulin resistance , hyperlipidemia , oxidative stress and inflammation attributed to dm ( 3 ) . among these characteristics , hyperglycemia may lead to oxidative stress which can cause cellular damage , pancreatic beta cell dysfunction and insulin resistance ( 4 ) . oxidative stress ( os ) plays a critical role in development and progression of diabetes and complications such as atherosclerosis , coronary heart and renal diseases ( 3 ) . vitamin e and c supplementation may improve oxidative stress and glycemic control in t2 dm patients ( 58 ) . royal jelly ( rj ) is a bee product , secreted from the hypopharingeal and mandibular glands of worker bees . rj produced by honey bees is known to contain three major nutrients including amino acids , vitamins and minerals ( 3 ) . additionally , rj has various biological activities such as a hypotensive effect , insulin - like action and antitumor activity ( 9 ) . therefore , it is possible that rj may have some effects on insulin resistance , which is considered to be the major cause of dm . in a study , supplementation of rats with different doses of royal jelly ( 10 , 30 , and 300 mg / kg ) led to a decrease in systolic blood pressure and significantly decreased serum levels of insulin and the homeostasis model assessment ratio , an index of insulin resistance ( 10 ) . only one human study reported that 1000 mg royal jelly for 8 weeks reduced malondialdehyde , glucose and hba1c but this dose was not sufficient to influence antioxidant status , on the other hand this study had some limitation especially it was done only in women and insulin resistant as the most important deleterious factor in diabetes , was not assessed ( 11 ) . although several animal studies have showed the effects of royal jelly on insulin resistance or oxidative stress , to our knowledge , human studies with respect to insulin resistance as a main cause of diabetes in both sexes is lacking . we hypothesized that rj supplementation can improve insulin resistance and oxidative stress in type 2 diabetic patients . the randomized controlled trial ( rct ) was conducted in endocrine and metabolism institute of iran university of medical sciences , tehran , iran . a randomized double blind placebo - controlled trial aiming to compare royal jelly effect on insulin resistance ( homa - ir ) , total antioxidant capacity ( tac ) and malondialdehyde ( mda ) level in type 2 the inclusion criteria were : ( a ) ages 2565 years , ( b ) bmi of 2030 kg / m2 , ( c ) iranian ethnicity , ( d ) diagnosis of type 2 diabetes for 510 years ( e ) hba1c of 68% , and ( f ) receiving oral hypoglycemic drugs . the exclusion criteria were : ( a ) serum triglyceride level ( tg ) > 400 mg / dl , serum cholesterol level > 240 mg / dl ( b ) lactating or pregnancy , ( c ) diagnosis of heart , liver and renal failure , cancer , acute myocardial infarction , stroke , or serious injuries , ( d ) receiving vitamin or mineral supplements at least 3 months before the beginning of the study , ( e ) smoking / alcohol consumption ( f ) taking oral contraceptive or lipid lowering drugs , ( g ) insulin infusion , ( h ) allergy to royal jelly and ( i ) any other conditions not suitable for trial as evaluated by the physician . the study was approved by the bioethics committee of iran university of medical sciences ( irct201103012709n18 ) . written consent forms were signed and handed back from all participants before participation . forty - six patients were randomly assigned to receive royal jelly supplements ( natural life . frengrove co. australia ) ( group a ) 1000 mg , 3 times daily or exactly the same placebo ( glycerin ) ( pars minoo inc . tehran iran ) ( group b ) 1000 mg , 3 times daily for 8 weeks . participants were instructed to maintain an isocaloric diet , continue their previous eating habits , and not to change their routine physical activities during the study period . throughout the study period , subjects were directed to continue taking the same dose of any prescribed hypoglycemic agents unless hypoglycemia occurred , in which case they were directed to reduce their dose immediately . daily food intake was obtained by a 24 hour dietary recall questionnaire and physical activity level by ipaq questionnaire in three days ( two regular days and one holiday ) at the beginning and end of the study . participants were randomly assigned to one of the two groups via computer - generated numbers . homeostasis model assessment for insulin resistance ( homa - ir ) ( fasting glucose ( mg / dl )  fasting insulin ( mol / ml ) /405 ) was used as the major outcome measurement . at baseline and after 8 weeks of treatment the tac , mda and fasting insulin level were measured for both groups . serum tac was measured by frap method ( 12 ) , and serum mda was measured by spectroscopy ( 13 ) . fasting blood sugar was measured by an enzymatic method ( pars azmon co. kit , tehran , iran ) using liasys autoanalyzer while insulin was measured by irma method ( immunotech co. kit ) . height was measured with a wall - mounted stadiometer to the nearest 0.1 cm , weight was measured on a calibrated balance beam scale to the nearest 0.1 kg , and bmi was calculated according to the formula : bmi = weight/ height2 ( kg / m2 ) . demographic data was collected during the initial anthropometric assessment . in designing the study , we considered power of 90% with a two - sided test with  = 0.05 ( type i error ) to detect a 5% difference in serum glucose between the two groups . on the basis of sds , reported in similar studies ( 14 ) , the number of subjects needed to treat to detect this difference was 20/group . given an anticipated dropout rate of 25 percent , we set the enrollment target at 25 subjects . statistical analyses were performed with pc spss 16 ( chicago , il , usa ) . normal distribution of the variables was checked by kolmogorov smirnov test ; student s t test was used to test whether the differences between the mean values of the items studied in both groups were significant . the mean differences in both groups of participants were compared before and 8 weeks after the intervention were evaluated by paired t - test . the randomized controlled trial ( rct ) was conducted in endocrine and metabolism institute of iran university of medical sciences , tehran , iran . a randomized double blind placebo - controlled trial aiming to compare royal jelly effect on insulin resistance ( homa - ir ) , total antioxidant capacity ( tac ) and malondialdehyde ( mda ) level in type 2 the inclusion criteria were : ( a ) ages 2565 years , ( b ) bmi of 2030 kg / m2 , ( c ) iranian ethnicity , ( d ) diagnosis of type 2 diabetes for 510 years ( e ) hba1c of 68% , and ( f ) receiving oral hypoglycemic drugs . the exclusion criteria were : ( a ) serum triglyceride level ( tg ) > 400 mg / dl , serum cholesterol level > 240 mg / dl ( b ) lactating or pregnancy , ( c ) diagnosis of heart , liver and renal failure , cancer , acute myocardial infarction , stroke , or serious injuries , ( d ) receiving vitamin or mineral supplements at least 3 months before the beginning of the study , ( e ) smoking / alcohol consumption ( f ) taking oral contraceptive or lipid lowering drugs , ( g ) insulin infusion , ( h ) allergy to royal jelly and ( i ) any other conditions not suitable for trial as evaluated by the physician . the study was approved by the bioethics committee of iran university of medical sciences ( irct201103012709n18 ) . written consent forms were signed and handed back from all participants before participation . forty - six patients were randomly assigned to receive royal jelly supplements ( natural life . frengrove co. australia ) ( group a ) 1000 mg , 3 times daily or exactly the same placebo ( glycerin ) ( pars minoo inc . tehran iran ) ( group b ) 1000 mg , 3 times daily for 8 weeks . participants were instructed to maintain an isocaloric diet , continue their previous eating habits , and not to change their routine physical activities during the study period . throughout the study period , subjects were directed to continue taking the same dose of any prescribed hypoglycemic agents unless hypoglycemia occurred , in which case they were directed to reduce their dose immediately . daily food intake was obtained by a 24 hour dietary recall questionnaire and physical activity level by ipaq questionnaire in three days ( two regular days and one holiday ) at the beginning and end of the study . participants were randomly assigned to one of the two groups via computer - generated numbers . homeostasis model assessment for insulin resistance ( homa - ir ) ( fasting glucose ( mg / dl )  fasting insulin ( mol / ml ) /405 ) was used as the major outcome measurement . at baseline and after 8 weeks of treatment the tac , mda and fasting insulin level were measured for both groups . serum tac was measured by frap method ( 12 ) , and serum mda was measured by spectroscopy ( 13 ) . fasting blood sugar was measured by an enzymatic method ( pars azmon co. kit , tehran , iran ) using liasys autoanalyzer while insulin was measured by irma method ( immunotech co. kit ) . height was measured with a wall - mounted stadiometer to the nearest 0.1 cm , weight was measured on a calibrated balance beam scale to the nearest 0.1 kg , and bmi was calculated according to the formula : bmi = weight/ height2 ( kg / m2 ) . in designing the study , we considered power of 90% with a two - sided test with  = 0.05 ( type i error ) to detect a 5% difference in serum glucose between the two groups . on the basis of sds , reported in similar studies ( 14 ) , the number of subjects needed to treat to detect this difference was 20/group . given an anticipated dropout rate of 25 percent , we set the enrollment target at 25 subjects . all data were expressed by means  sd . the level of significance was determined at p<0.05 . statistical analyses were performed with pc spss 16 ( chicago , il , usa ) . normal distribution of the variables was checked by kolmogorov smirnov test ; student s t test was used to test whether the differences between the mean values of the items studied in both groups were significant . the mean differences in both groups of participants were compared before and 8 weeks after the intervention were evaluated by paired t - test . among the 50 type 2 diabetic patients screened at our outpatient clinic , four patients withdrew because they did not want to continue the supplementation program . then , 46 patients were allocated equally into groups a and b. the mean and standard deviation of demographic and nutrients intake data are shown in table 1 and 2 . there were no significant differences in age , body mass index ( bmi ) , diabetes duration ( table 1 ) , energy and nutrient intake ( table 2 ) , in each group and between two groups before and after the intervention . the level of physical activity and lipid lowering drugs was not different between two groups at baseline . differences between groups were evaluated by independent t- test comparison of dietary intake of some nutrients between two groups of study data are expressed as means sd . differences between groups were evaluated by independent t- test/ sfa : saturated fatty acid , mufa : monounsaturated fatty acid , pufa : polyunsaturated fatty acid as shown in table 3 , there was no significant difference in serum glucose , tac , mda and homa - ir between two groups before the intervention . however , after 8 weeks of rj supplementation , serum tac ( p=0.016 ) increased compared with the initial values and serum glucose ( p=0.006 ) and homa - ir ( p = 0.015 ) decreased at the end of study in rj group compared with placebo . there was also significant decrease in mean differences of homa - ir between two groups ( p = 0.023 ) as shown in table 3 . there was no significant difference after rj supplementation compared to before values in serum glucose , insulin levels , tac , mda and homa - ir . effects of 8 weeks rj supplementation on serum glucose , insulin , tac , mda and homa - ir in type 2 diabetic patients data expressed as a mean  standard deviation . before , after and mean differences and p values are mentioned in the table.-/ ( p value * ) comparison in each group between before and after values by paired t - test / ( p value * * ) comparison between two groups of before values and also after 8 weeks values of two groups and also comparison of mean differences by independent t - test among the 50 type 2 diabetic patients screened at our outpatient clinic , four patients withdrew because they did not want to continue the supplementation program . then , 46 patients were allocated equally into groups a and b. the mean and standard deviation of demographic and nutrients intake data are shown in table 1 and 2 . there were no significant differences in age , body mass index ( bmi ) , diabetes duration ( table 1 ) , energy and nutrient intake ( table 2 ) , in each group and between two groups before and after the intervention . the level of physical activity and lipid lowering drugs was not different between two groups at baseline . differences between groups were evaluated by independent t- test comparison of dietary intake of some nutrients between two groups of study data are expressed as means sd . differences between groups were evaluated by independent t- test/ sfa : saturated fatty acid , mufa : monounsaturated fatty acid , pufa : polyunsaturated fatty acid as shown in table 3 , there was no significant difference in serum glucose , tac , mda and homa - ir between two groups before the intervention . however , after 8 weeks of rj supplementation , serum tac ( p=0.016 ) increased compared with the initial values and serum glucose ( p=0.006 ) and homa - ir ( p = 0.015 ) decreased at the end of study in rj group compared with placebo . there was also significant decrease in mean differences of homa - ir between two groups ( p = 0.023 ) as shown in table 3 . there was no significant difference after rj supplementation compared to before values in serum glucose , insulin levels , tac , mda and homa - ir . effects of 8 weeks rj supplementation on serum glucose , insulin , tac , mda and homa - ir in type 2 diabetic patients data expressed as a mean  standard deviation . before , after and mean differences and p values are mentioned in the table.-/ ( p value * ) comparison in each group between before and after values by paired t - test / ( p value * * ) comparison between two groups of before values and also after 8 weeks values of two groups and also comparison of mean differences by independent t - test to our knowledge , this is the first rct conducted to assess the effect of royal jelly supplementation on homa - ir , oxidative stress and mda in both sexes of human subjects . oxidative stress is associated with type 2 diabetes , and there is compelling biochemical evidence suggesting that ros may even play a role , even if only secondary , in the pathogenesis of type 2 diabetes ( 15 ) . in this study , rj intake reduced serum glucose and homa - ir while it increased serum tac significantly after 8 weeks of intervention in comparison to placebo group but no significant difference was shown before and after rj supplementation in serum glucose , insulin level , tac , mda and homa - ir . rj reduces the index of insulin resistance ( homa - ir ) but not blood glucose levels in rats ( 17 ) . insulin resistance associates with changes in oxidative stress levels and rj has protective effects against oxidative stress due to its antioxidant peptides . for example , in one study , supplementation with rj for 16 weeks significantly reduced 8-hydroxy-2-deoxyguanosine as a marker of oxidative stress and the average life span was extended by about 25% compared to the control group ( 18 ) . in another study supplementation with rj was reported to have beneficial effects against genotoxicity and oxidative damages induced by cadmium in albino mice . rj had a protective effect on the chromosome aberration , micronucleus , and oxidative stress , and this effect was connected with dose . the protective effect of rj on toxicity induced by cadmium may be explained by the therapeutic properties and antioxidant capacity of rj , which is a product of honeybees ( 20 ) . in another study , yeast cells were cultivated with different concentrations of rj . in the rj treated cells , lower atp pool size did not cause growth decline , which might be due to decreased cell requirements for energy , since decreased intracellular oxidant level was observed in a dose dependent manner indicating lower energy consumption for induction of endogenous antioxidant defending and repair systems . this was also confirmed by 2-d gels ( electrophoresis ) , where down - regulation of enzymatic antioxidant system cu decreased cell requirement for energy in rj treated cells was observed also by glucose consumption rate measured at 6 h , which was for 14.5% lower compared with controls ( 21 ) . the protecting effects of rj against oxidative status may be related to scavenging abilities of the superoxide radical ( 20 ) . study ( 11 ) , but increase of tac and decrease of insulin resistance which was occurred in our study was not shown in that study . on the contrary , of course , participants of pourmoradian s study were only women and baseline values of mda were higher than of our study , so these might be responsible for mda decreasing . to our knowledge , this is the first randomized , controlled trial on rj supplementation in both sexes of dm patients but it is limited in that it had a small sample size and short duration . therefore , larger sample size and longer duration are needed before reaching conclusive results . however , administration of rj in diseases accompanied with oxidative stress history is suggested . moreover , the effect of 10-hydroxydecanoic acid as an unsaturated fatty acid in royal jelly , on homa - ir , oxidative stress and mda needs further investigation . so , administration of rj in diseases accompanied with oxidative stress history may be useful . ethical issues ( including plagiarism , informed consent , misconduct , data fabrication and/or falsification , double publication and/or submission , redundancy , etc . ) have been completely observed by the authors .
background : animal studies have shown antioxidant effects of royal jelly ( rj ) and its effect on insulin resistance as the most common complication of type 2 diabetes . this study was conducted to determine the effect of rj intake on serum total antioxidant capacity , malondialdehyde and insulin resistance in t2dm.methods:in this randomized controlled trial , forty - six type 2 diabetic patients , aged 2565 years , with bmi of 2030 kg / m2 , and hba1c of 68% were included . 
 the patients were randomly assigned to receive 1000 mg of rj supplement or placebo , 3 times daily for 8 weeks . 
 homa - ir , anthropometric measurements , fasting blood glucose , serum insulin , total antioxidant capacity and malondialdehyde level were measured.results:in comparison with placebo , homa - ir decreased ( p=0.015 ) while serum total antioxidant capacity increased significantly in rj group ( p=0.016 ) . 
 no significant difference was detected for serum insulin and mda in two groups.conclusions:rj intake may have favorable effects on serum tac and homa - ir in diabetic patients .