diabetes mellitus is one of the most common metabolic disorders in the world ( 1 , 2 ) .
the number of patients with this disease is predicted to reach over 366 million people in 2030 ( 4 ) . in recent years , increasing prevalence of diabetes mellitus as a chronic disease has prompted investigators to find ways to control it .
researchers are always looking for non - pharmacologic and nutritional approaches to improve the control of type 2 diabetes with a lower cost . in 1958
, mertz discovered that brewer s yeast has a potent effect on hypoglycemic role of insulin ( 5).this discovery led to the isolation of glucose tolerance factor ( gtf ) from brewer s yeast .
nowadays , in gtf - related studies , the yeast is used as an applicable matter ( 6 ) .
gtf facilitates binding of insulin to the target cells by creating a triple complex between gtf , insulin , and its receptors on target cell membranes .
gtf not only potentially increases insulin effects , but also may reduce cholesterol and triglyceride levels ( 8) .
different results have been reported from various studies about effects of brewer s yeast on lipid profile .
a study reported no significant changes in the levels of serum lipoproteins after supplementation with brewer s yeast ( 9 ) .
other studies showed beneficial effects of brewer s yeast on serum total cholesterol , triglyceride and hdl - c levels in comparison with chromium chloride ( 10 , 11 ) . in a clinical trial in iran , the authors observed significant reductions in triglyceride levels , total cholesterol and ldl - c and significant increased in hdl - c levels after supplementation with brewer s yeast ( 12 ) .
moreover , hypertension is one of the complications of type 2 diabetes mellitus , which will accelerate cardiovascular , and nephropathy complications in diabetes mellitus ( 13 , 14 ) .
also high triglycerides and low hdl - c levels are among the complications of diabetes , so monitoring the rate of their changes is of special importance ( 15 ) .
the current study is different in terms of sample size , research method , number of tablets , duration of intervention , and age of samples comparing with previous research studies .
this study aimed to investigate the effect of brewer s yeast supplementation on blood pressure and serum lipoproteins in patients with type 2 diabetes .
among 1200 cases with type 2 diabetes mellitus referring to diabetes clinic of dezful ganjavian hospital , 90 patients with type 2 diabetes were recruited by simple random sampling .
six participants were excluded , 4 of them due to irregular consumption of pills , one patient due to lack of willingness to continue collaboration , and one due to pregnancy .
inclusion criteria were diagnosis of type 2 diabetes by a physician , age range of 3555 years and diabetes lasted more than two years .
exclusion criteria were cardiovascular diseases , hepatitis , renal diseases , gout , parkinson s , depression , consumption of steroidal and non steroidal anti - inflammatory drugs or monoamine oxidase inhibitors and insulin therapy .
this trial was registered in iranian registry of clinical trials ( irct ) , no.irct138807062513n1 .
medical , drugs & supplements history , anthropometric measurements and demographic data were collected at the first interview .
then , in a double - blind clinical trial , included individuals were randomly divided into 2 groups receiving brewer s yeast tablets ( 42 patients ) and placebo ( 42 patients ) .
the brewer s yeast group received 6 tablets of brewer s yeast daily manufactured by health aid ltd .
placebo group received 6 placebo tablets daily with similar shape , color and size to the brewer s yeast tablets .
placebo tablets consisted of cellulose microcrystalline compounds , magnesium stearate , caramel , malt and stearic acid , and were manufactured by health aid ltd .
the subjects were asked not to make any changes in their diet , oral diabetes medications , blood pressure - lowering drugs , lipid lowering agents and their usual physical activity during the intervention .
weight , body mass index , systolic and diastolic blood pressure levels , fasting serum triglyceride , total cholesterol , ldl - c and hdl - c were measured before and after 12 weeks of intervention in both groups .
twenty - four hour dietary recall questionnaires were completed by a trained dietitian at baseline and at the twelfth week for both groups . in addition , the researchers followed up consumption of the pills regularly every 2 weeks by telephone .
furthermore , tablets were delivered to the subjects alternately in three stages ( once per month ) to better control and to ensure the correct and regular consumption of tablets by patients . of all patients ,
height and weight were measured before and after the treatments by a trained dietitian in the same and standard situations .
german ) while patients were in fasting state with minimal clothing and height was measured by seca wall height gauge ( seca 206 , seca gmbh & co. kg .
systolic and diastolic blood pressures were measured by a trained physician by using a mercury sphygmomanometer ( diplomat - presameter desk model by error tolerance of + / 3 mmhg , rudolf riester gmbh  bruckstr .
31  d-72417 jungingen germany ) while the patients were sitting on the chair for at least 5 minutes before the measurements . to be more accurate ,
an average of three times measured values in each session was reported . to minimize human measurement errors between before and after the intervention
measurement of total serum cholesterol was done by colorimetric method using commercially available kit ( cat no.10 - 508 ziestchem diagnostics tehran , iran ) with sensitivity of 1 mg / dl .
serum triglyceride was measured by colorimetric method using biochemistry kit ( cat no.10 - 525 ziestchem diagnostics tehran , iran ) with sensitivity of 4 mg / dl .
serum hdl - c concentrations were measured by enzymatic methods using biochemistry kit ( cat no.10 - 507 ziestchem diagnostics tehran , iran ) , with sensitivity of 1 mg / dl .
ldl - c concentrations in serum were automatically measured using enzymatic methods by elitech kits ( cat no.ldld-0230 seppim.france ) with sensitivity of 0.3 mg / dl by autoanalyzer hitachi 911 .
data from 24-hour food recall were analyzed by using food processor ii software ( fpii , ver2 .
kolmogorov smirnov test was used for assessing the normality of data distribution . to compare qualitative data , chi - square test and to compare quantitative data , independent t- test , pair t - test and analysis of covariance were used .
among 1200 cases with type 2 diabetes mellitus referring to diabetes clinic of dezful ganjavian hospital , 90 patients with type 2 diabetes were recruited by simple random sampling .
six participants were excluded , 4 of them due to irregular consumption of pills , one patient due to lack of willingness to continue collaboration , and one due to pregnancy .
inclusion criteria were diagnosis of type 2 diabetes by a physician , age range of 3555 years and diabetes lasted more than two years .
exclusion criteria were cardiovascular diseases , hepatitis , renal diseases , gout , parkinson s , depression , consumption of steroidal and non steroidal anti - inflammatory drugs or monoamine oxidase inhibitors and insulin therapy .
this trial was registered in iranian registry of clinical trials ( irct ) , no.irct138807062513n1 .
medical , drugs & supplements history , anthropometric measurements and demographic data were collected at the first interview .
then , in a double - blind clinical trial , included individuals were randomly divided into 2 groups receiving brewer s yeast tablets ( 42 patients ) and placebo ( 42 patients ) .
the brewer s yeast group received 6 tablets of brewer s yeast daily manufactured by health aid ltd .
placebo group received 6 placebo tablets daily with similar shape , color and size to the brewer s yeast tablets .
placebo tablets consisted of cellulose microcrystalline compounds , magnesium stearate , caramel , malt and stearic acid , and were manufactured by health aid ltd .
the subjects were asked not to make any changes in their diet , oral diabetes medications , blood pressure - lowering drugs , lipid lowering agents and their usual physical activity during the intervention .
weight , body mass index , systolic and diastolic blood pressure levels , fasting serum triglyceride , total cholesterol , ldl - c and hdl - c were measured before and after 12 weeks of intervention in both groups .
twenty - four hour dietary recall questionnaires were completed by a trained dietitian at baseline and at the twelfth week for both groups .
in addition , the researchers followed up consumption of the pills regularly every 2 weeks by telephone .
furthermore , tablets were delivered to the subjects alternately in three stages ( once per month ) to better control and to ensure the correct and regular consumption of tablets by patients . of all patients ,
height and weight were measured before and after the treatments by a trained dietitian in the same and standard situations .
german ) while patients were in fasting state with minimal clothing and height was measured by seca wall height gauge ( seca 206 , seca gmbh & co. kg .
systolic and diastolic blood pressures were measured by a trained physician by using a mercury sphygmomanometer ( diplomat - presameter desk model by error tolerance of + / 3 mmhg , rudolf riester gmbh  bruckstr .
31  d-72417 jungingen germany ) while the patients were sitting on the chair for at least 5 minutes before the measurements . to be more accurate ,
an average of three times measured values in each session was reported . to minimize human measurement errors between before and after the intervention
measurement of total serum cholesterol was done by colorimetric method using commercially available kit ( cat no.10 - 508 ziestchem diagnostics tehran , iran ) with sensitivity of 1 mg / dl .
serum triglyceride was measured by colorimetric method using biochemistry kit ( cat no.10 - 525 ziestchem diagnostics tehran , iran ) with sensitivity of 4 mg / dl .
serum hdl - c concentrations were measured by enzymatic methods using biochemistry kit ( cat no.10 - 507 ziestchem diagnostics tehran , iran ) , with sensitivity of 1 mg / dl .
ldl - c concentrations in serum were automatically measured using enzymatic methods by elitech kits ( cat no.ldld-0230 seppim.france ) with sensitivity of 0.3 mg / dl by autoanalyzer hitachi 911 .
data from 24-hour food recall were analyzed by using food processor ii software ( fpii , ver2 .
kolmogorov smirnov test was used for assessing the normality of data distribution . to compare qualitative data , chi - square test and to compare quantitative data , independent t- test , pair t - test and analysis of covariance were used .
eighty - four subjects ( 21 men and 63 women ) with mean age of 46.3  6.1 years finished the study .
the group taking brewer s yeast included 42 patients ( 11 men and 31 women ) and the group - taking placebo included 42 patients ( 10 men and 32 women ) .
there was not any statistically significant differences between two groups regarding gender distribution ( p=0.8 , chi - square test ) .
no significant differences observed between recipient of brewer s yeast and placebo groups in terms of age and anthropometric measurements ( independent sample t - test ) .
moreover , at the end of the intervention differences of anthropometric variables between two study groups were not statistically significant .
there was not any statistically significant differences between two groups regarding anti - hypertensive drug usage ( =0.513 , p=0.632 ) , anti - dyslipidemia drug usage ( =0.431 , p=0.662 ) before intervention ( table 1 ) . in terms of energy , macronutrients and micronutrients in the beginning and at the end of the intervention , study groups were not significantly different from each other ( independent t - test , table 2 ) .
there were no significant differences within each group in terms of energy , macro - and micronutrients during the intervention ( paired t - test , table 2 ) .
there were no significant differences for blood pressure and serum lipoproteins between two groups at baseline ( independent t - test , table 3 ) .
after the intervention , systolic and diastolic blood pressures significantly decreased in the group taking brewer s yeast ( p=0.007 and p=0.001 respectively , paired t - test ) . after adjusting for baseline systolic and diastolic blood pressures ,
the final systolic and diastolic blood pressures were statistically significant between the groups ( p=0.05 and p=0.03 respectively , ancova , table 3 ) .
percents of changes for systolic and diastolic blood pressures during intervention in brewer s yeast group were significantly different from placebo group ( p=0.02 and p= 0.002 respectively , independent t - test , fig .
, triglyceride , ldl - c and hdl - c levels were significantly reduced in - group taking brewer s yeast ( p=0.002 , p= 0.001 and p= 0.001 respectively , paired t - test , table 3 ) .
eighty - four subjects ( 21 men and 63 women ) with mean age of 46.3  6.1 years finished the study .
the group taking brewer s yeast included 42 patients ( 11 men and 31 women ) and the group - taking placebo included 42 patients ( 10 men and 32 women ) .
there was not any statistically significant differences between two groups regarding gender distribution ( p=0.8 , chi - square test ) .
no significant differences observed between recipient of brewer s yeast and placebo groups in terms of age and anthropometric measurements ( independent sample t - test ) .
moreover , at the end of the intervention differences of anthropometric variables between two study groups were not statistically significant .
there was not any statistically significant differences between two groups regarding anti - hypertensive drug usage ( =0.513 , p=0.632 ) , anti - dyslipidemia drug usage ( =0.431 , p=0.662 ) before intervention ( table 1 ) .
in terms of energy , macronutrients and micronutrients in the beginning and at the end of the intervention , study groups were not significantly different from each other ( independent t - test , table 2 ) .
there were no significant differences within each group in terms of energy , macro - and micronutrients during the intervention ( paired t - test , table 2 ) .
there were no significant differences for blood pressure and serum lipoproteins between two groups at baseline ( independent t - test , table 3 ) .
after the intervention , systolic and diastolic blood pressures significantly decreased in the group taking brewer s yeast ( p=0.007 and p=0.001 respectively , paired t - test ) . after adjusting for baseline systolic and diastolic blood pressures ,
the final systolic and diastolic blood pressures were statistically significant between the groups ( p=0.05 and p=0.03 respectively , ancova , table 3 ) .
percents of changes for systolic and diastolic blood pressures during intervention in brewer s yeast group were significantly different from placebo group ( p=0.02 and p= 0.002 respectively , independent t - test , fig .
, triglyceride , ldl - c and hdl - c levels were significantly reduced in - group taking brewer s yeast ( p=0.002 , p= 0.001 and p= 0.001 respectively , paired t - test , table 3 ) .
in this study , taking 1800 mg of brewer s yeast per day reduced systolic and diastolic blood pressures in patients with type 2 diabetes .
dietary sodium , potassium , magnesium and calcium are among factors influencing blood pressure . according to table 2
no changes can be seen in these micronutrients between the two study groups during the intervention .
thus , significant reduction in systolic and diastolic blood pressures can be due to supplementation with brewer s yeast . in a study conducted by hata and colleagues , fermented milk containing the yeast saccharomyces cerevisiae
after 8 weeks , systolic and diastolic blood pressures were significantly reduced ( 16 ) .
however this study was performed with a shorter time , its results , is confirmed by ours .
in addition , kanauchi and colleagues conducted an in vitro trial on spontaneous hypertensive rats as case and mild hypertensive rats as control group .
significant decrease in systolic blood pressure in spontaneous hypertensive rats was shown in this study ( 17 ) .
masuda in a study on the shr rats observed that after feeding the rats with sour milk containing brewer s yeast and lactobacillus helveticus , blood pressure decreased significantly ( 18 ) .
there are different theories on the mechanism of brewer s yeast effects on blood pressure .
blood pressure lowering effects of brewer s yeast is attributed to its biological peptides , potassium , magnesium and calcium ( 17 , 19 ) .
it seems that the biological peptide named krf814 is derived from hydrolysis of brewer s yeast by alkaline phosphatase .
this biological peptide can reduce the activity of angiotensin - converting enzyme and thereby may decrease blood pressure ( 17 ) .
in the present study , despite significantly decreased triglyceride and ldl - c and significantly increased hdl - c in brewer s yeast consumers , no significant differences could be detected compared with placebo group at the end of the study . in explorations , which studied the effects of brewer s yeast on serum triglyceride in people with normal levels of triglyceride , no significant difference has been found ( 9 , 10 , 20 ) .
although , in studies on the effects of brewer s yeast on serum triglyceride in patients with hypertriglyceridemia , significant difference has been found ( 11,12 ) .
it seems that lack of significant changes in serum triglyceride levels may be due to their normal initial levels . in the case of brewer
s yeast effects on serum cholesterol , several studies have been done , but no significant decreases observed in total cholesterol levels and neither did we ( 10 , 12 ) . related to brewer s yeast effects on ldl - c , other studies did not show any significant changes between the intervention groups . in present study ,
despite significant increases in hdl - c levels in - group receiving brewer s yeast , no significant differences between the two trial groups were observed . in studies conducted by racek and colleagues and
wang and colleagues also , no significant change in hdl - c level of the subjects was obtained ( 9 , 10 ) . in some studies ,
hdl - c increased significantly after consumption of brewer s yeast compared with controls . in comparison with ours , in mentioned studies , the subjects were older and were suffering from dyslipidemia ( 11 , 14 ) . among factors affecting serum lipoproteins , are intake of macronutrients , micronutrients and their ratios that in the above - mentioned studies , have not been well controlled .
so it seems that one of the strengths of current study is controlling nutrient intake by statistical analyses . in a meta - analysis study , on brewer s yeast effects in patients with type 2 diabetes from 1996 to 2008 revealed that conflicting results in various studies were due to major limitations including : small size ( 7 , 20 ) , short duration of intervention ( 21 ) , non - randomized design ( 11 ) and different doses of supplementation ( 12 , 21 ) . therefore , it is suggested that these limitations must be eliminated in future clinical trials ; also nutrients intake and correlation between biopeptides and blood pressure should take into the account ( 22 ) .
supplementation with 1800 mg / day brewer s yeast in addition to usual treatments can have a modest beneficial effect on systolic and diastolic blood pressure in patients with type 2 diabetes .
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 .
 backgroundthis study was conducted to investigate the effects of brewer s yeast supplementation on serum lipoproteins and blood pressure in patients with type 2 diabetes mellitus.methods:in a randomized double blind clinical trial , 90 adults with type 2 diabetes mellitus were recruited , and divided randomly into 2 groups , trial group received brewer s yeast ( 1800 mg / day ) and control group received placebo for 12 weeks . 
 weight , bmi , food consumption ( based on 24 hour food recall ) , fasting serum lipoproteins ( cholesterol , triglyceride , ldl - c , hdl - c ) , systolic and diastolic blood pressures were measured before and after the intervention . 
 data analyses were performed by statistical package for social sciences ver . 
 18.0 , and the statistical tests included independent t - test , paired t - test , kolmogorov - smirnov and analysis of covariance . 
 this trial was registered in iranian registry of clinical trials ( irct ) , no.irct138807062513n1.results:eighty-four subjects ( 21 men and 63 women ) aged 46.36.1 years completed the study . 
 after 12 weeks supplementation , systolic and diastolic blood pressures were decreased in the group receiving brewer s yeast ( 4.11.5 , p=0.007 and 5.70.6 , p=0.001 respectively ) . 
 no - significant changes in ldl - c , hdl - c , triglyceride and cholesterol were shown.conclusion:supplementation with brewer s yeast besides the usual treatment of type 2 diabetes mellitus can reduce systolic and diastolic blood pressures in diabetic patients . 
Introduction
Materials and Methods
Subjects:
Study design:
Clinical and laboratory setting:
Data analysis:
Results
Demographic and anthropometric characteristics
Nutrients intake
Blood pressure and Serum lipid profile
Discussion
Conclusion
Ethical considerations