it is seen that a large population of the healthy adult population has low or borderline low serum 25(oh)d levels which further increases the risk of falls and fracture . optimization of vitamin d status is therefore an essential component of preventing and managing osteoporosis especially in vulnerable groups like postmenopausal women . definition of optimum levels of vitamin d for maintenance of bone health has been a matter of debate . however , the evolving consensus is to define vitamin d deficiency ( vdd ) as a serum 25(oh)d level of less than 20 ng / l ( 50 nmol / l ) and insufficiency as a level of 25(oh)d of 21 - 29 ng / ml ( 525 to 725 nmol / l ) . vitamin d intoxication is observed when serum levels of 25(oh)d are greater than 150 ng / ml ( 374 nmol / l ) . vitamin d synthesis is affected by geographical location ( latitude and altitude ) , atmospheric pollution , clothing , melanin pigmentation , and sunlight exposure . vitamin d deficiency is rampant . in india , it has been reported from all over the country ( both rural and urban ) , in all age groups including toddlers , school children , adolescent girls , pregnant women , and postmenopausal women . the indian council of medical research ( icmr ) recommends daily intake of 600 mg of calcium in adults and 800 mg of calcium in postmenopausal age group . the typical indian diet is deficient in calcium , which becomes more important in postmenopausal women where calcium requirement is more . the icmr recommended daily allowance data states that habitual indian diet does not provide even 10% daily vitamin d requirement and sunlight is the main source of vitamin d. it continues to recommend 400 iu / day of oral vitamin d regardless of the special requirement . considering these facts , in typical indian clinical practice it is standard to recommend calcium tablets , each containing 500 mg of calcium and 250 iu of vitamin d3 , twice daily as supplementation in the postmenopausal women . the current study was planned to see the effect of two different daily doses ( 500 iu  the standard and 1000 iu ) of vitamin d supplementation added to standard calcium dose ( 1000 mg / day ) , on vitamin d levels and parameters of calcium homeostasis ( calcium , phosphorus , and alp ) in postmenopausal women . we hypothesized that 1000 iu vitamin d was superior in comparison to 500 iu , which is the commonly used daily dose , for achieving serum 25(oh)d level > 20 ng / ml . the study was conducted at a tertiary care hospital at new delhi , india , after ethical clearance from the institutional review board . post - menopausal women volunteers ( mainly attendants of patients who presented in the out - patient department or medical and paramedical staff and their relatives , representing a relatively high socioeconomic strata relative to the national average ) who were not taking calcium or vitamin d supplementation for minimum 3 months and were permanent residents of the city for past 3 months were enrolled . at induction , subjects on calcium or vitamin d replacement or any drugs affecting vitamin d status , chronic renal failure , chronic liver disease , chronic smokers , and chronic alcoholics were excluded . a total 92 subjects were enrolled from the months of september to november . at induction , morning fasting samples were collected for serum calcium , phosphorus , alkaline phosphatase , albumin , and 25(oh)d after written informed consent . the group a ( n = 30 ) served as control and received only 1000 mg calcium carbonate daily in equally divided two doses , group b ( n = 31 ) received 1000 mg of calcium carbonate and 500 iu of vitamin d ( as a combination tablet containing 500 mg calcium carbonate and 250 iu vitamin d ) daily in equally divided two doses , and group c ( n = 31 ) received 1000 mg of calcium carbonate and 1000 iu of vitamin d ( as a combination tablet containing 500 mg calcium carbonate and 500 iu vitamin d ) daily in equally divided two doses . the tablets were procured from eris pharmaceuticals which were market preparations decal ( a combination tablet containing 500 mg calcium carbonate and 250 iu vitamin d ) , d-500 cal ( a combination tablet containing 500 mg calcium carbonate and 500 iu vitamin d ) , while plain calcium tablets containing 500 mg calcium carbonate were manufactured for the study after appropriate approval . compliance was considered as consumption of at least 80% of the supplied tablets . at the end of three months morning fasting samples were collected for measurement of serum calcium , phosphorus , alkaline phosphatase , albumin , and serum 25(oh)d levels in subjects who were considered to be compliant . serum albumin , calcium , phosphorus , and alkaline phosphatase estimation was performed on the auto - analyzer immediately . serum 25(oh)d concentrations were estimated by radioimmunoassay after storage at 20c ( diasorin , stillwater , mn 55082 - 0285 , usa ; kit , normal range : 9.3 - 37.9 ng / ml ) . the sensitivity of this assay was 1.5 ng / ml , within - run coefficient of variation ( cv ) was 10.5% , and the total imprecision cv was 8.2% at 22.7 ng / ml . primary outcome was the change in the mean serum 25(oh)d level from baseline in the group receiving 1000 iu of vitamin d per day as compared to the group receiving 500 u of vitamin d per day and the group not receiving any vitamin d supplementation , at the end of three months of intervention . secondary outcome was the change in mean serum calcium ( corrected for serum albumin ) , phosphorus , and alkaline phosphatase level from baseline in the three groups at the end of 3 months of intervention . the data are presented in mean  sd , and non - parametric test , kruskal wallis test , was used to assess the significance level of the percentage change in serum 25(oh)d , corrected calcium , phosphorus , and alkaline phosphatase within and between the groups . the data are presented in mean  sd , and non - parametric test , kruskal wallis test , was used to assess the significance level of the percentage change in serum 25(oh)d , corrected calcium , phosphorus , and alkaline phosphatase within and between the groups . a total of 92 postmenopausal women were enrolled from the months of september to november and followed up for 3 months from the date of enrolment . the mean age of the subjects in the study population was 54.8  6.7 years ( range 40 - 73 ) . their mean daily calcium intake was 1076.43  376.2 mg and median of daily sun exposure was 5 ( range 0 - 38 ) min with exposure of about 20% body surface area . the mean daily calcium intake was relatively higher than the national average probably due to a higher socioeconomic status of the subjects included . 83.7% subjects ( n = 77 ) had vitamin d deficiency ( 25(oh)d < 20 ng / ml ) and 8.7% ( n = 8) subjects had vitamin d insufficiency ( 25(oh)d 20 - 30 ng / ml ) and 7.6% subjects ( n = 7 ) had normal vitamin d defined as 25(oh)d > 30 ng / ml [ table 1 ] . baseline parameters ( meansd ) in three groups thirty ( 30 ) subjects were randomized to group a , while 31 subjects each were randomized to groups b and c. the baseline parameters were not significantly different in the three groups as assessed by the kruskal wallis test to evaluate the significance [ table 2 ] . studied parameters at three months follow up ( meansd ) at the end of follow up , 26 from group a , 29 from group b , and 23 from group c presented for second sampling . four subjects from group a , two from group b , and six from group c withdrew consent during the course of the study and two subjects from group c were lost to follow up . data for subjects with less than 80% compliance ( five subjects from group a and c each and four from group b ) were excluded . data for 21 ( 70% ) , 25 ( 80.6% ) , and 18 ( 58.06% ) subjects from groups a , b , and c , respectively , were finally analyzed [ figure 1 ] . at 3 months , the difference in percentage change in mean serum 25(oh)d level from baseline in between the three groups was statistically significant ( p < 0.05 ) with percentage change being maximum in group c ( 178.78% ) and group a actually showing a decline [ table 3 ] . figure 2 shows the comparison in mean serum 25(oh)d level at baseline and at 3 months in between the three groups . percentage change in various parameters at 3 months from baseline ( meansd ) mean levels of 25(oh)d at baseline and 3 months in the three groups although not significantly different ( p > 0.05 ) , the mean serum calcium attained in group c was highest ( 8.67 mg / dl ) from the average baseline corrected calcium of 8.49 mg / dl . the mean serum phosphorus and alkaline phosphatase in the three groups were not significantly different within or between the groups at the end of follow up [ table 2 ] . twelve subjects ( four in group a , three in group b , and five in group c ) reported minor gastritis and abdominal discomfort but did not result in discontinuation of the supplementation . this study evaluates the response of different doses ( 500 iu daily , 1000 iu daily or control ) of vitamin d along with 1000 mg of calcium daily on the parameters of calcium homeostasis in healthy postmenopausal women . it was carried out in new delhi ( location 28.38n , 77.12e ) . this city experiences marked seasonal variation . subjects were recruited from september to november , prior to the onset of peak winter . since the subjects were randomly divided into the three groups , any effect of season was equally distributed . in the present study , 83.7% subjects ( n = 77 ) had vitamin d deficiency ( 25(oh)d < 20 ng / ml ) , 8.7% ( n = 8) subjects had vitamin d insufficiency ( 25(oh)d 20 - 30 ng / ml ) , and 7.6% subjects ( n = 7 ) had normal vitamin d defined as 25(oh)d > 30 ng / ml . our results are in accordance with other studies which have demonstrated high prevalence of vitamin d deficiency in india although limited data is available regarding postmenopausal women . from a study conducted in delhi , the authors reported vdd in 91.2% among older indian adults ( more than 50 years age ) of both sexes despite the fact that more than half the subjects studied were taking 200 - 400 iu of oral vitamin d daily . in a study from the southern part of the country , vitamin d deficiency ( < 20 ng / ml ) , insufficiency ( 20 - 30 ng / ml ) and replete states ( > 30 ng / ml ) were seen in 70% , 23% , and 7% , respectively , among postmenopausal women , similar to levels in reproductive age women . similarly , in another study conducted among postmenopausal south indian women ( n = 164 ) , the author found that only 18% patients had  normal 25(oh)d levels ( > 20 ng / ml ) , 52% had 25(oh)d  insufficiency  ( 10 - 20 ng / ml ) , and 30% had 25(oh)d  deficiency  ( < 10 ng / ml ) . data from other study populations suggests the universal presence of low vitamin d levels even though variable cut - offs were used . in the study conducted in delhi , at the same institute where the present study was conducted , among 100 healthy volunteers from the hospital staff , the mean 25(oh)d was 4.7  3.4 ng / ml . all the subjects had hypovitaminosis d ( < 20 ng / ml ) and more than 90% subjects had 25(oh)d levels < 10 ng / ml . in a study conducted among healthy hospital staff , in lucknow , a city south east of delhi , the authors found 66.3% of their subjects to be vitamin d deficient , using a cut - off value of 15 ng / ml . of these , 20.6% had severe vitamin d deficiency ( < 5 ng / ml ) , 27.2% had moderate ( 5 - 9.9 ng / ml ) , while 18.5% had mild vitamin d deficiency ( 10 - 14.9 ng / ml ) . when a serum 25(oh)d level of 20 ng / ml was used as a cut - off value similar data has been reported from other parts of the country . in a study among healthy adult native population , from kashmir , 83% of the subjects studied had vitamin d deficiency ( serum 25(oh)d concentration of < 50 nmol / l equivalent to 20 ng / ml ) . 25% , 33% , and 25% had mild ( 25 - 50 nmol / l equivalent to 10 - 20 ng / ml ) , moderate ( 12.5 - 25 nmol / l equivalent to 5 - 10 ng / ml ) , and severe ( < 12.5 nmol / l equivalent to 5 ng / ml ) deficiency , respectively . the prevalence of vdd ranged from 69.6% in the employed group to 100% in the household group with equal prevalence of vdd in subjects from rural and urban areas . similarly , high prevalence of vitamin d deficiency was reported among pregnant women and adolescent girls from a rural indian community . boys were found to be relatively protected . the age - adjusted community prevalence of vitamin d deficiency , defined as 25(oh)d < 50 a significant urban and rural difference is seen in the serum level of 25(oh)d but despite long hours of sun exposure , the rural population is also deficient . in a study conducted among residents of a north indian village with 200 families , males had significantly higher 25(oh)d values than females . when compared to urban subjects , the mean serum 25(oh)d value of rural males and females was six- and threefolds higher , respectively . however , even with 5 hours of daily sunshine exposure only 31.5% had serum 25(oh)d levels 50 nmol / l ( 20 ng / ml ) . in a study conducted among urban and rural population in andhra pradesh , they found that the 25(oh)d levels of rural adult subjects were significantly higher ( p < 0.001 ) than that of urban adult subjects in both males and female groups . the icmr recommends daily intake of 600 mg of calcium in adults and 800 mg of calcium in postmenopausal age group . the typical indian diet is deficient in calcium , which becomes more important in postmenopausal women where calcium requirement is more . the icmr recommended daily allowance data states that habitual indian diet does not provide even 10% daily vitamin d requirement and sunlight is the main source of vitamin d. it continues to recommend 400 iu per day of oral vitamin d regardless of the special requirement like in postmenopausal women . the iof recommends that vitamin d intake may need to be adjusted upward to as much as 2000 iu / day in individuals who are obese , and in those with osteoporosis , limited sun exposure ( institutionalized , homebound ) , and malabsorption , and in non - european populations known to be at high risk for vitamin d deficiency such as those in the middle east and south asia , or immigrants from such regions living in europe . at the end of follow up , the mean 25(oh)d level was highest in group c at 23.71 ng / ml . in group a it was 8.07 ng / ml , in group b it was 13.34 ng / ml , while at baseline the average 25(oh)d level was 13.43 ng / ml . the percentage change in mean serum 25(oh)d level from baseline was significantly different in between the three groups ( p = 0.000 ) with percentage change being maximum in group c ( 178.78% ) and group a actually showing a decline . the decline probably reflects the effect of season as the follow - up period was winters . whatever the effect of season , it was presumed that it would be uniform in the three groups . our results suggest that 1000 iu vitamin d is better as compared to the currently prescribed doses of 500 iu daily . however , even this dose is not sufficient to optimize the levels in a severely deficient population . the number of subjects who attained serum 25(oh)d level 30 ng / ml was four ( 22.2% ) in group c , one ( 4% ) in group b , and none in the control group . the percentage of subjects who attained serum 25(oh)d level of 20 - 30 ng / ml in the three groups was 38.9% ( n = 7 ) , 12% ( n = 3 ) , and 4.7% ( n = 1 ) , respectively . there percentage change in the blood levels of corrected serum calcium , phosphorus and total alkaline phosphatase from baseline was not different between the three groups . our results are in line with the results of previous studies . in a study conducted among older adults , it was seen that there was no difference in the prevalence of vitamin d deficiency among subjects who were and those who were not receiving vitamin d supplementation in dose ranging from 200 to 400 iu / day . in a previously conducted study from delhi in healthy adults , the authors concluded that monthly oral administration of 60,000 iu cholecalciferol ( ~2000 iu / day or 50 g / day ) is effective in raising serum 25(oh)d to desired levels ( > 30 ng / ml ) during summer . however , higher doses of cholecalciferol120,000 iu / month administered orally ( ~4000 iu / day or 100 g / day)may be more appropriate during winter . from their study among ambulatory elderly in finland , the authors concluded that 10 g / d ( 400 iu ) is not enough to maintain 25(oh)d above 40 an optimal daily dose of 115 g / d ( 4600 iu ) was predicted statistically , to obtain 25(oh)d levels within the range of 75 - 220 our study suggests that even 1000 iu daily for 3 months may not be enough to attain optimum levels of serum 25(oh)d ; and probably a higher dose is required to attain optimum levels . in our study , the mean 25(oh)d level in group c after 3 months of supplementation was less than 30 ng / ml ( 23.71 ng / ml ) suggesting that even 1000 iu may not be sufficient to attain normal levels of 25(oh)d and a higher dose as much as 2000 iu / day may be required in special populations as postmenopausal women especially in the indian subcontinent . as previously seen , the effects of calcium and vitamin d are not sustained and levels decline after some time . the subjects included in the study were based on convenience sampling and not population based sampling . our study was a non - blinded and the subjects knew the nature of supplementation they were receiving . it sometimes could have affected compliance as the subjects were given the background information related to the study . the number of subjects for final analysis after excluding the dropouts and subjects with less than 80% compliance was relatively small . standard dose of vitamin d available in calcium tablets ( 250 iu per 500 mg calcium carbonate ) is not adequate for achieving optimum serum 25(oh)d levels . higher dose of vitamin d supplementation with 1000 iu / day ( 500 iu per 500 mg calcium carbonate ) daily was superior to the standard dose therapy and resulted in serum 25(oh)d values > 20 ng / ml in postmenopausal women in our study . for achievement of optimum serum 25(oh)d levels ( > 30 ng / ml ) , it is possible that the standard recommended dose may be adequate for maintenance in a however , in the indian population which is severely deficient , even 1000 iu daily cholecalciferol supplementation is not adequate . at this point therefore , it is recommended to make the population sufficient by giving therapeutic doses of vitamin d to the diagnosed cases . further studies are required to evaluate higher doses in indian postmenopausal women which will achieve and maintain optimal vitamin d levels without risk of toxicity .
aim : to compare the effect of two different doses ( 500 and 1000 iu / day ) of oral vitamin d3 ( cholecalciferol ) on serum 25-hydroxy vitamin d [ 25(oh)d ] levels in apparently healthy postmenopausal indian women.materials and methods : serum 25(oh)d , calcium with albumin , phosphorus , and alkaline phosphatase were measured in 92 apparently healthy postmenopausal women . 
 the subjects were randomly assigned to one of the three groups and received supplementation for 3 months each . 
 each group received 1000 mg calcium carbonate daily while groups b and c received 500 and 1000 iu of cholecalciferol in addition , respectively . 
 the tests were repeated after 3 months.results:at baseline , 83.7% subjects had vitamin d deficiency ( 20 ng / ml ) . 
 the difference in the percentage change in mean serum 25(oh)d levels from baseline in group a ( 30.5  5.3% ) , group b ( + 8.9  19.7% ) , and in group c ( + 97.8  53.3% ) was statistically significant ( p < 0.001 ) between the three groups . 
 serum 25(oh)d level > 20 ng / ml was achieved in 4.7% ( 1/21 ) , 16% ( 4/25 ) , and 66.67% ( 12/18 ) subjects in groups a , b , and c , respectively . 
 no significant change was found in serum calcium , phosphorus , and alkaline phosphatase levels at 3 months in either of the groups from baseline.conclusions:standard dose of cholecalciferol available in  calcium tablets 
 ( 250 iu per 500 mg calcium carbonate ) is not adequate for achieving optimum serum 25(oh)d levels in indian postmenopausal women . 
 higher dose of vitamin d supplementation with 1000 iu / day ( 500 iu per 500 mg calcium carbonate ) daily is superior to the standard dose therapy . for achievement of optimum serum 25(oh)d levels ( > 30 ng / ml ) in indian postmenopausal women , still 
 higher doses of vitamin d are likely to be required .