very recent studies in iran displayed the prevalence of the obesity , hypertension , and hypercholesterolemia are 30.9% , 23% , and 41.6% , respectively .
the statin group of drugs is widely used to treat hypercholesterolemia in patients at cvd risk .
statins inhibit the rate - limiting enzyme in cholesterol biosynthesis , hydroxymethylglutaryl - coenzyme a ( hmg - coa ) reductase , and reduce serum low - density lipoprotein cholesterol ( ldl - c ) levels substantially .
further to their conventional lipid - modulating effects , statins possess so - called  pleiotropic  properties , which comprise improvement of endothelial function , antioxidant properties , anti - inflammatory properties , plaque stabilization , and inhibition platelet aggregation and thrombus formation .
it has been reported that statins treatment may be associated with an improved vitamin d status , but this is not a consistent finding .
there is emerging evidence suggesting that a decreased vitamin d concentration might rise the possibility of several conditions including cancers and cvd .
if statins do have an impact on vitamin d concentration this could be a reasonable elucidation of the described results of diminished risk of fracture ; moreover , reduced risk of malignant illnesses in patients on this class of drugs . thus , the present randomized controlled study set out to investigate the effects of treatment with simvastatin on serum vitamin d in a group of dyslipidemic patients who were suitable for statin therapy .
a total of 102 male and female patients , age ( 2088 old ) , who were not formerly receiving lipid - lowering drugs , registered from the clinics of ghaem hospital , a teaching hospital located in mashhad , iran , between june 2010 and august 2012 .
the study was a randomized placebo - controlled cross - over trial ; in this study , each patient took simvastatin or a placebo and next crossed over to the substitute .
cardiovascular risk factors were defined as age more than 65 years old , receiving antihypertensive medication or systolic blood pressure of more than 140 mmhg or diastolic blood pressure of more than 90 mmhg , fasting blood glucose ( fbg ) greater than or equal to 126 mg / dl , positive family history of cvd , smoking , male sex , body mass index ( bmi ) more than or equal to 30 kg / m .
history of malignancy , recent history of infections , connective tissue disorders , treatment with immunomodulatory drugs ( e.g. , corticosteroids ) , liver or renal disease , leukocytosis ( white blood cell count > 10,000/l ) , thrombocytosis ( platelet count > 450,000  10/l ) , and anemia ( hematocrit < 40% ) were the exclusion criteria .
each subject gave informed written consent to participate in the study , which had previously been approved by the ethics committee of mashhad university of medical sciences ( code : 88585 ) .
each treatment period takes 1 month and there was a 14-day washout between the treatment periods .
we asked the people to do not change the lifestyles during the trial also medications . at the first visit ,
patients were randomly assigned ( random number tables ) to one of the two treatment regimens .
fifty - one patients received 40 mg / day simvastatin for 1 month , and another group ( 51 ) received a placebo ( same size and color with treatment capsules and filled with starch ) for 30 days . after a further 2-week washout period
the sample size was based on the between - group mean comparison formula , according to the study conducted by hu et al . with confidence interval of 95% , and power of 80%
serum vitamin d levels were measured using a competitive electroluminescence protein binding assay with the roche diagnostics vitamin d total assay kit ( roche diagnostics , mannheim , germany ) .
the interday precision of this assay has been reported to be 4.9% and 1.9% at mean concentrations of 43.3 and 105
nmol / l , respectively , using the manufacturer 's original control material . as previously described for each subject , weight , height , and bmi
were measured two times ( before randomization and at the end of each period observation ) according to standard methods previously described .
sas software ( version 8) ( sas institute inc . , cary , nc ) was used for statistical analysis .
t - test was used for a comparison between before and after treatments . for the analysis ,
the differences of these cross - over analyses were compared ; they were normally distributed .
the primary end - point was the change in serum fasting lipid profile and vitamin d after treatment for 4 weeks .
the secondary endpoints were changes in fasting blood glucose and high sensitive c - reactive protein ( hscrp ) .
a total of 102 male and female patients , age ( 2088 old ) , who were not formerly receiving lipid - lowering drugs , registered from the clinics of ghaem hospital , a teaching hospital located in mashhad , iran , between june 2010 and august 2012 .
the study was a randomized placebo - controlled cross - over trial ; in this study , each patient took simvastatin or a placebo and next crossed over to the substitute .
cardiovascular risk factors were defined as age more than 65 years old , receiving antihypertensive medication or systolic blood pressure of more than 140 mmhg or diastolic blood pressure of more than 90 mmhg , fasting blood glucose ( fbg ) greater than or equal to 126 mg / dl , positive family history of cvd , smoking , male sex , body mass index ( bmi ) more than or equal to 30 kg / m .
history of malignancy , recent history of infections , connective tissue disorders , treatment with immunomodulatory drugs ( e.g. , corticosteroids ) , liver or renal disease , leukocytosis ( white blood cell count > 10,000/l ) , thrombocytosis ( platelet count > 450,000  10/l ) , and anemia ( hematocrit < 40% ) were the exclusion criteria .
each subject gave informed written consent to participate in the study , which had previously been approved by the ethics committee of mashhad university of medical sciences ( code : 88585 ) .
each treatment period takes 1 month and there was a 14-day washout between the treatment periods .
we asked the people to do not change the lifestyles during the trial also medications . at the first visit ,
patients were randomly assigned ( random number tables ) to one of the two treatment regimens .
fifty - one patients received 40 mg / day simvastatin for 1 month , and another group ( 51 ) received a placebo ( same size and color with treatment capsules and filled with starch ) for 30 days . after a further 2-week washout period
the sample size was based on the between - group mean comparison formula , according to the study conducted by hu et al . with confidence interval of 95% , and power of 80%
serum vitamin d levels were measured using a competitive electroluminescence protein binding assay with the roche diagnostics vitamin d total assay kit ( roche diagnostics , mannheim , germany ) .
the interday precision of this assay has been reported to be 4.9% and 1.9% at mean concentrations of 43.3 and 105
as previously described for each subject , weight , height , and bmi were measured two times ( before randomization and at the end of each period observation ) according to standard methods previously described .
t - test was used for a comparison between before and after treatments . for the analysis ,
the differences of these cross - over analyses were compared ; they were normally distributed .
the primary end - point was the change in serum fasting lipid profile and vitamin d after treatment for 4 weeks .
the secondary endpoints were changes in fasting blood glucose and high sensitive c - reactive protein ( hscrp ) .
from 102 patients , who came into the trial , 25 ( 24.5% ) dropped out ; hence , the final sample size was 77 ( 78.2% ) .
noncompliance with the study protocol ( n = 21 ) , drug intolerance ( n = 2 ) , and relocation ( n = 2 ) were the reasons for the drop - out .
we failed to find any significant difference ( p > 0.05 ) when we compared the baseline data of biochemical and anthropometric factors before the first treatment period with those before the second treatment period .
moreover , no significant difference was found for age , sex , presence of hyperlipidemia , bmi , presence of hypertension , presence of diabetes , and smoking status between the two groups [ table 1 ] .
comparison of baseline characteristics of subjects statin therapy did not have a significant effect on serum levels of vitamin d in either the statin - placebo or the placebo - statin group [ p = 0.90 , table 2 ] .
bivariate correlations were assessed between baseline values of vitamin d and other evaluated biochemical parameters ( total cholesterol , ldl - c , high - density lipoprotein cholesterol [ hdl - c ] , triglycerides [ tgs ] , fbg , and hs - crp ) , as well as between changes in vitamin d and other parameters during each study period .
no significant correlation was found between baseline values of vitamin d and evaluated biochemical parameters ( p > 0.05 ) [ table 3 ] .
furthermore , significant correlations were observed between serum vitamin d and the following parameters : fbg ( statin - placebo group , second period ; p < 0.01 ) , tgs ( placebo - statin group , second period ; p < 0.05 and statin - placebo first period ; p < 0.01 ) , ldl - c ( placebo - statin group , first period ; p < 0.05 ) , and hdl - c ( statin - placebo group , first period ; p < 0.05 ) [ table 4 ] .
effect of simvastatin versus placebo on vitamin d status correlation between baseline biochemical parameters and vitamin d in placebo - statin group and statin - placebo group correlation between changes in biochemical parameters in two periods of placebo - statin group and statin - placebo
statin therapy did not have a significant effect on serum levels of vitamin d in either the statin - placebo or the placebo - statin group [ p = 0.90 , table 2 ] .
bivariate correlations were assessed between baseline values of vitamin d and other evaluated biochemical parameters ( total cholesterol , ldl - c , high - density lipoprotein cholesterol [ hdl - c ] , triglycerides [ tgs ] , fbg , and hs - crp ) , as well as between changes in vitamin d and other parameters during each study period .
no significant correlation was found between baseline values of vitamin d and evaluated biochemical parameters ( p > 0.05 ) [ table 3 ] .
furthermore , significant correlations were observed between serum vitamin d and the following parameters : fbg ( statin - placebo group , second period ; p < 0.01 ) , tgs ( placebo - statin group , second period ; p < 0.05 and statin - placebo first period ; p < 0.01 ) , ldl - c ( placebo - statin group , first period ; p < 0.05 ) , and hdl - c ( statin - placebo group , first period ; p < 0.05 ) [ table 4 ]
. effect of simvastatin versus placebo on vitamin d status correlation between baseline biochemical parameters and vitamin d in placebo - statin group and statin - placebo group correlation between changes in biochemical parameters in two periods of placebo - statin group and statin - placebo
the aim of this study was to investigate the impact of simvastatin therapy on serum vitamin d levels in dyslipidemic patients .
our results showed that simvastatin therapy for 4 weeks ( 40 mg / day ) does not alter serum vitamin d levels .
previous investigations on the impact of statin therapy on circulating vitamin d levels have been inconsistent .
while atorvastatin and rosuvastatin have been shown to raise 25(oh ) vitamin d levels , there are reports with opposite findings showing that hmg - coa reductase inhibitors do not affect serum vitamin d concentrations .
it is not well known how statins might affect vitamin d concentration , and numerous potential mechanisms have been put forward .
the first and by far the most plausible mechanism regards to the common metabolic fate of statins and vitamin d. both 25(oh ) vitamin d , and statins are metabolized in the liver by cyp3a4 .
therefore , the occupation of the active site of this enzyme by statins may account for the elevated 25(oh ) vitamin d levels reported in some trials .
indicated that rosuvastatin ( 40 mg / day ) as monotherapy and rosuvastatin ( 10 mg / day ) plus fenofibrate ( 200 mg / day ) or omega-3 fatty acids ( 2 g / day ) cause substantial elevations in the 25(oh ) vitamin d levels ( 53% , 64% , and 61% , respectively ) .
moreover , in study by thabit et al . , they found that simvastatin and atorvastatin , at any dose for duration of more than 1 year , have no additive effect on 25(oh)d level .
unlike rosuvastatin and atorvastatin , no considerable change in vitamin d concentration has been reported in patients that used fluvastatin .
a new randomized controlled trial could not prove an effect of 12 months simvastatin therapy ( 40 mg / day ) on vitamin d concentration .
the physicochemical characteristics of different statins may also play a role in their differential effects on vitamin d metabolism .
first , the study design did not allow adequate time for a new steady - state level of vitamin d , did not control or report vitamin d intake , did not analyze for seasonal effects , and the 25(oh ) vitamin d assay was not the ms / ms gold standard .
the main strength of the present study was being based on a robust placebo - controlled and cross - over design as well as being conducted in a target population , not under concomitant lipid - lowering therapy .
therefore , many of the confounding factors that may generally affect lipid alterations were eliminated from the present trial .
we found that statin had no significant effect on serum vitamin d status in dyslipidemic patients .
further research might explore the effects of long - term statin therapy on vitamin d status .
 background : hydroxymethylglutaryl - coenzyme a reductase inhibitors ( statins ) are antihyperlipidemic drugs with an established efficacy in stabilizing atherosclerotic plaques and preventing atherogenesis and reducing cardiovascular events . 
 the purpose of this study was to determine the effect of simvastatin on serum vitamin d status in dyslipidemic patients as vitamin d status has an impact on monocyte / macrophage function and may also contribute to cardiovascular risk.methods:selected individuals ( n = 102 ) were treated with simvastatin ( 40 mg / day ) , or matching placebo in a randomized , double - blind , placebo - controlled , crossover trial . each treatment period ( with simvastatin or placebo ) 
 lasted for 30 days and was separated by a 2-week washout phase . 
 serum vitamin d concentration was assessed pre- and post-treatment.results:seventy-seven completed the trial , noncompliance with the study protocol and drug intolerance or relocation were the causes for drop - out . 
 no significant carry - over effect was observed for the assessed parameters . 
 there was a reduction in the serum levels of low - density lipoprotein cholesterol ( p < 0.001 ) , total cholesterol ( p < 0.001 ) , and triglycerides ( p < 0.05 ) . 
 nevertheless , simvastatin therapy did not significantly affect serum level of high - density lipoprotein cholesterol and vitamin d level ( p > 0.05).conclusions : short - term treatment with simvastatin ( 40 mg / day ) does not have a significant affect on serum levels of vitamin d. 
INTRODUCTION
METHODS
Study design and participants
Vitamin D measurement
Anthropometric and biochemical evaluation
Statistical analysis
RESULTS
Effects of simvastatin versus placebo on Vitamin D
DISCUSSION
CONCLUSIONS
Financial support and sponsorship
Conflicts of interest