title: The vitamin D content of fortified milk and infant formula Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. The association of calcium and vitamin D with risk of colorectal adenomas. Calcium plus vitamin D supplementation and the risk of breast cancer. Vitamin D supplementation during infancy is associated with higher bone mineral mass in prepubertal girls. A prospective nested case-control study of vitamin D status and pancreatic cancer risk in male smokers. Vitamin D, calcium supplementation, and colorectal adenomas: results of a randomized trial. Bone mineral content and serum 25-hydroxyvitamin D concentrations in breast-fed infants with and without supplemental vitamin D: one-year follow-up. Calcium plus vitamin D supplementation and the risk of colorectal cancer. Interaction of estrogen therapy with calcium and vitamin D supplementation on colorectal cancer risk: reanalysis of Women's Health Initiative randomized trial. Prospective study of vitamin D supplementation and rickets in China.
abstract: BACKGROUND The fortification of milk and infant formula with vitamin D has had an important role in eliminating rickets in children and osteomalacia in adults . A recent outbreak of vitamin D intoxication caused by drinking milk fortified with excess vitamin D has led to questions about the level of vitamin D in milk from other producers . METHODS We used high-performance liquid chromatography to measure vitamin D in sample s of 13 br and s of milk with various fat contents and 5 br and s of infant formula purchased at r and om from local supermarkets in five Eastern states . RESULTS Only 12 ( 29 percent ) of the 42 sample s of the 13 br and s of milk and none of the 10 sample s of the 5 br and s of infant formula contained 80 to 120 percent of the amount of vitamin D stated on the label . Twenty-six of the 42 milk sample s ( 62 percent ) contained less than 80 percent of the amount cl aim ed on the label . No vitamin D was detected in 3 of the 14 sample s of skim milk tested ( lower limit of assay , 4.7 IU per quart [ 5.0 IU per liter ] ) . One milk sample labeled as containing vitamin D2 ( ergocalciferol ) contained vitamin D3 ( cholecalciferol ) . Seven of the 10 sample s of infant formula contained more than 200 percent of the amount stated on the label ; the sample with the highest concentration contained 419 percent of the stated amount . None of the sample s of infant formula contained less than the amount stated . CONCLUSIONS Milk and infant-formula preparations rarely contain the amount of vitamin D stated on the label and may be either underfortified or overfortified . Since both underfortification and overfortification are hazardous , better monitoring of the fortification process is needed BACKGROUND Numerous observational studies have found supplemental calcium and vitamin D to be associated with reduced risk of common cancers . However , interventional studies to test this effect are lacking . OBJECTIVE The purpose of this analysis was to determine the efficacy of calcium alone and calcium plus vitamin D in reducing incident cancer risk  of all types . DESIGN This was a 4-y , population -based , double-blind , r and omized placebo-controlled trial . The primary outcome was fracture incidence , and the principal secondary outcome was cancer incidence . The subjects were 1179 community-dwelling women r and omly selected from the population of healthy postmenopausal women aged > 55 y in a 9-county rural area of Nebraska centered at latitude 41.4 degrees N. Subjects were r and omly assigned to receive 1400 - 1500 mg supplemental calcium/d alone ( Ca-only ) , supplemental calcium plus 1100 IU vitamin D3/d ( Ca + D ) , or placebo . RESULTS When analyzed by intention to treat , cancer incidence was lower in the Ca + D women than in the placebo control subjects ( P < 0.03 ) . With the use of logistic regression , the unadjusted relative risks ( RR ) of incident cancer in the Ca + D and Ca-only groups were 0.402 ( P = 0.01 ) and 0.532 ( P = 0.06 ) , respectively . When analysis was confined to cancers diagnosed after the first 12 mo , RR for the Ca + D group fell to 0.232 ( CI : 0.09 , 0.60 ; P < 0.005 ) but did not change significantly for the Ca-only group . In multiple logistic regression models , both treatment and serum 25-hydroxyvitamin D concentrations were significant , independent predictors of cancer risk . CONCLUSIONS Improving calcium and vitamin D nutritional status substantially reduces  all-cancer risk in postmenopausal women . This trial was registered at clinical trials.gov as NCT00352170 The Polyp Prevention Trial ( PPT ) was a multicenter r and omized clinical trial design ed to determine the effects of a high-fiber , high-fruit and vegetable , low-fat diet on the recurrence of adenomatous polyps in the large bowel . Detailed dietary intake and supplement use data were collected at baseline and at each of 4 annual study visits . Adenoma recurrence was ascertained by complete colonoscopy at baseline and after 1 and 4 y. Recurrence was found in 754 of the 1905 trial participants . We evaluated the association between calcium and vitamin D intake and adenomatous polyp recurrence after adjusting for intervention group , age , gender , nonsteroidal anti-inflammatory drug use , total energy intake , and the interaction of gender and intervention group . Vitamin D models were also adjusted for the location of the clinic site . Dietary variables were adjusted for total energy intake via the residual method . There were no overall significant associations between adenoma recurrence and dietary calcium intake [ odds ratio ( OR ) for the 5th compared with the lowest quintile = 0.91 ; 95 % CI = 0.67 - 1.23 ; P-trend = 0.68 ] , total calcium intake ( OR = 0.86 ; 95 % CI = 0.62 - 1.18 ; P-trend = 0.20 ) , or  dietary vitamin D intake ( OR = 0.93 ; 95 % CI = 0.69 - 1.25 ; P-trend = 0.43 ) averaged over follow-up . Total vitamin D intake was weakly inversely associated with adenoma recurrence ( OR = 0.84 ; 95 % CI = 0.62 - 1.13 ; P-trend = 0.03 ) . Supplemental calcium and vitamin D use during follow-up also were inversely associated with adenoma recurrence ( OR for any compared with no use = 0.82 ; 95 % CI = 0.68 - 0.99 ; and OR = 0.82 ; 95 % CI = 0.68 - 0.99 ; for calcium and vitamin D , respectively ) . Slightly stronger associations were noted for the prevention of multiple recurrences . Our analyses did not suggest a significant effect modification between total calcium and total vitamin D intake ( P = 0.14 ) on risk for adenoma recurrence . This trial cohort provides some evidence that calcium and vitamin D may be inversely associated with adenoma recurrence BACKGROUND Although some observational studies have associated higher calcium intake and especially higher vitamin D intake and 25-hydroxyvitamin D levels with lower breast cancer risk , no r and omized trial has evaluated these relationships . METHODS Postmenopausal women ( N = 36 282 ) who were enrolled in a Women 's Health Initiative clinical trial were r and omly assigned to 1000 mg of elemental calcium with 400 IU of vitamin D(3 ) daily or placebo for a mean of 7.0 years to determine the effects of supplement use on incidence of hip fracture . Mammograms and breast exams were serially conducted . Invasive breast cancer was a secondary outcome . Baseline serum 25-hydroxyvitamin D levels were assessed in a nested case-control study of 1067 case patients and 1067 control subjects . A Cox proportional hazards model was used to estimate the risk of breast cancer associated with r and om assignment to calcium with vitamin D(3 ) . Associations between 25-hydroxyvitamin D serum levels and total vitamin D intake , body mass index ( BMI ) , recreational physical activity , and breast cancer risks were evaluated using logistic regression models . Statistical tests were two-sided . RESULTS Invasive breast cancer incidence was similar in the two groups ( 528 supplement vs 546 placebo ; hazard ratio = 0.96 ; 95 % confidence interval = 0.85 to 1.09 ) . In the nested case-control study , no effect of supplement group assignment on breast cancer risk was seen . Baseline 25-hydroxyvitamin D levels were modestly correlated with total vitamin D intake ( diet and supplements ) ( r = 0.19 , P < .001 ) and were higher among women with lower BMI and higher recreational physical activity ( both P < .001 ) . Baseline 25-hydroxyvitamin D levels were not associated with breast cancer risk in analyses that were adjusted for BMI and physical activity ( P(trend ) = .20 ) . CONCLUSIONS Calcium and vitamin D supplementation did not reduce invasive breast  cancer incidence in postmenopausal women . In addition , 25-hydroxyvitamin D levels were not associated with subsequent breast cancer risk . These findings do not support a relationship between total vitamin D intake and 25-hydroxyvitamin D levels with breast cancer risk The objective of this study was to determine whether vitamin D supplementation of breast-fed infants during the first year of life is associated with greater bone mineral content and /or areal bone mineral density ( aBMD ) in later childhood . The design was a retrospective cohort study . One hundred and six healthy prepubertal Caucasian girls ( median age , 8 yr ; range , 7 - 9 yr ) were classified as vitamin D supplemented or unsupplemented during the first year of life on the basis of a question naire sent to participating families and their pediatricians . Bone area ( square centimeters ) and bone mineral content ( grams ) were determined by dual energy x-ray absorptiometry at six skeletal sites . Vitamin D receptor ( VDR ) 3'-gene polymorphisms ( BsmI ) were also determined . The supplemented ( n = 91 ) and unsupplemented ( n = 15 ) groups were similar in terms of season of birth , growth in the first year of life , age , anthropometric parameters , and calcium intake at time of dual energy x-ray absorptiometry . The supplemented group had higher aBMD at the level of radial metaphysis ( mean + /- SEM , 0.301+/-0.003 vs. 0.283+/-0.008 ; P = 0.03 ) , femoral neck ( 0.638+/-0.007 vs. 0.584+/-0.021 ; P = 0.01 ) , and femoral trochanter ( 0.508+/-0.006 vs. 0.474+/-0.016 ; P = 0.04 ) . At the lumbar spine level aBMD values were similar ( 0.626+/-0.006 vs. 0.598+/-0.019 ; P = 0.1 ) . In a multiple regression model taking into account the effects of vitamin D supplementation , height , and VDR genotype on aBMD ( dependent variable ) , femoral neck aBMD remained higher by 0.045 g/cm2 in the supplemented group ( P = 0.02 ) . Vitamin D supplementation in infancy was found to be associated with increased aBMD at specific skeletal sites later in childhood in prepubertal Caucasian girls Sun exposure is associated with lower death rates for pancreatic cancer in some ecological studies . Skin exposure to UVB light induces cutaneous production of precursors to 25-hydroxyvitamin D [ 25(OH)D ] . Pancreatic islet and duct cells express 25(OH)D(3)-1alpha-hydroxylase that generates the biologically active 1,25(OH)(2 ) vitamin D form . Thus , 25(OH)D concentrations could affect pancreatic function and possibly pancreatic cancer etiology . We conducted a prospect i ve nested case-control study in the Alpha-Tocopherol , Beta-Carotene Cancer Prevention cohort of male Finnish smokers , ages 50 to 69 years at baseline , to test whether more adequate vitamin D status , as determined by prediagnostic serum 25(OH)D concentrations , was associated with lower pancreatic cancer risk . Two hundred incident exocrine pancreatic cancer cases that occurred between 1985 and 2001 ( up to 16.7 years of follow-up ) were matched by age and date of blood draw to 400 controls who were alive and free of cancer at the time the case was diagnosed .  Odds ratios ( OR ) and 95 % confidence intervals ( 95 % CI ) were calculated using conditional logistic regression . Higher vitamin D concentrations were associated with a 3-fold increased risk for pancreatic cancer ( highest versus lowest quintile , > 65.5 versus < 32.0 nmol/L : OR , 2.92 ; 95 % CI , 1.56 - 5.48 , P(trend ) = 0.001 ) that remained after excluding cases diagnosed early during follow-up . Contrary to expectations , subjects with higher prediagnostic vitamin D status had an increased pancreatic cancer risk compared with those with lower status . Our findings need to be replicated in other population s and caution is warranted in their interpretation and implication . Our results are intriguing and may provide clues that further the underst and ing of the etiology of this highly fatal cancer BACKGROUND Calcium and vitamin D both appear to have antineoplastic effects in the large bowel . Although these nutrients are inter-related metabolically in bone and in the normal intestine , their potential interactions in large-bowel carcinogenesis are not well understood . METHODS We assessed independent and joint effects of calcium supplementation and vitamin D status on  adenoma recurrence in 803 subjects in a multi-center , placebo-controlled r and omized clinical trial of calcium supplementation for the prevention of colorectal adenoma recurrence . Serum levels of 25-hydroxy [ 25-(OH ) ] vitamin D and 1,25-dihydroxy [ 1,25-(OH)2 ] vitamin D levels were determined , and the Taq I and Fok I polymorphisms in the vitamin D receptor ( VDR ) gene were analyzed by polymerase chain reaction . Risk ratios ( RRs ) for any adenoma recurrence were computed for calcium supplementation within groups defined by serum vitamin D levels and for serum vitamin D levels within treatment groups . Associations of VDR polymorphisms with recurrence risk were also evaluated . All statistical tests were two-sided . RESULTS Among subjects with baseline 25-(OH ) vitamin D levels at or below the median ( 29.1 ng/mL ) , calcium supplementation was not associated with adenoma recurrence , whereas among those with levels above the median , calcium supplementation was associated with a reduced risk ( RR = 0.71 , 95 % confidence interval [ CI ] = 0.57 to 0.89 , P for interaction = .012 ) . Conversely , serum 25-(OH ) vitamin D levels were associated with a reduced risk only among subjects receiving calcium supplements ( RR per 12 ng/mL increase of vitamin D = 0.88 , 95 % CI = 0.77 to 0.99 , P for interaction = .006 ) . VDR polymorphisms were not related to adenoma recurrence and did not modify the associations with vitamin D or calcium . CONCLUSIONS Calcium supplementation and vitamin D status appear to act largely together , not separately , to reduce the risk of colorectal adenoma recurrence . VDR genotype does not appear to be associated with risk in association with hypothyroidism . We did not obtain parietal cell or intrinsic factor antibodies . There was no evidence of other au to immune diseases or deficiencies in the mother ( or int2ant ) on the basis of routine clinical and laboratory tests . Breast-fed infants are at risk for nutr i t ional deficiencies if the mother is malnourished , a vegan , or if she has an abnormali ty in nut r ien t metabolism . Physicians should be aware tha t even with a well-balanced mate rna l diet , an occasional breast-fed infant can develop a serious nutritional deficiency BACKGROUND Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials . However , r and omized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking . METHODS We conducted a r and omized , double-blind , placebo-controlled trial involving 36,282 postmenopausal women from 40 Women 's Health Initiative centers : 18,176 women received 500 mg of elemental calcium as calcium carbonate with 200 IU of vitamin D3 [ corrected ] twice daily ( 1000 mg of elemental calcium and 400 IU of vitamin D3 ) and 18,106 received a matching placebo for an average of 7.0 years . The incidence of pathologically confirmed colorectal cancer was the design ated secondary outcome . Baseline levels of serum 25-hydroxyvitamin D were assessed in a nested case-control study . RESULTS The incidence of invasive colorectal cancer did not differ significantly between women assigned to calcium plus vitamin D supplementation and those assigned to placebo ( 168 and 154 cases ; hazard ratio , 1.08 ; 95 percent confidence interval , 0.86 to 1.34 ; P=0.51 ) , and the tumor characteristics were similar in the two groups . The frequency of colorectal-cancer screening and abdominal symptoms was similar in the two groups . There were no significant treatment interactions with baseline characteristics . CONCLUSIONS Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer  among postmenopausal women . The long latency associated with the development of colorectal cancer , along with the seven-year duration of the trial , may have contributed to this null finding . Ongoing follow-up will assess the longer-term effect of this intervention . ( Clinical Trials.gov number , NCT00000611 . ) Although calcium and vitamin-D intake were consistently shown to be inversely associated with  colorectal cancer risk  in several large prospect i ve studies and protective against adenoma and cancer in multiple r and omized trials , the Women 's Health Initiative ( WHI ) of calcium and low-dose vitamin-D supplementation trial found no overall effects on colorectal cancer . However , the previous report did not recognize an important biologic interaction with estrogen therapy . We investigated the treatment interaction of estrogen with calcium and vitamin-D on risk of colorectal cancer via a re analysis of primary data results from the WHI calcium and vitamin-D supplementation trial ( 1,000 mg elemental calcium , 400 IU of vitamin-D3 , or placebo ) , reanalyzing results from women concurrently r and omized to estrogen interventions  and placebo . Results indicate that concurrent estrogen therapy was a strong effect modifier of calcium and vitamin-D supplementation on colorectal cancer risk . While calcium plus vitamin-D supplementation among women concurrently assigned to estrogen therapies suggested increased risk ( Hazard Ratio = 1.50 , 95 % CI : 0.96 - 2.33 ) , among women concurrently assigned to placebos arms of the estrogen trials , calcium plus vitamin-D indicated suggestive benefits ( HR = 0.71 , 95 % CI : 0.46 - 1.09 ) ( p-for-estrogen-interaction = 0.018 ) . Consistent interaction was also found by reported estrogen use ( p interaction = 0.037 ) . Results indicate contrasting effects of calcium and vitamin-D by concurrent estrogen therapy on colorectal cancer risk . Although further clinical and mechanistic studies are warranted , the potential clinical implication s of the apparent interaction of estrogen therapy with calcium and vitamin-D supplementation should be recognized . Important biological mechanisms related to the key membrane receptor megalin and estrogen-dependent protein calbindin are discussed To determine whether amounts of vitamin D lower than recommended doses are effective in preventing rickets , 256 term infants from two northern and two southern cities in China were studied in a r and omized trial of vitamin D supplementation ( 100 , 200 , or 400 IU/day ) during the first 6 months of life . Cord blood and 6-month blood sample s were collected and radiographs were obtained at 3 to 5 days and at 6 months of age . Cord serum 25-hydroxyvitamin D concentrations were lower in the north than in the south ( 5 vs 14 ng/ml ( 12.5 vs 35.0 nmol/L ) ; p less than 0.01 ) . Wrist ossification centers were less likely to be present at birth in the northern children than in the southern children ( p = 0.009 ) and were more likely to be present in infants born in the fall who had higher cord serum concentrations of 25-hydroxyvitamin D ( p = 0.04 ) . Serum 25-hydroxyvitamin D concentrations were lower in northern children 6 months of age than in southern children ( p = 0.005 ) and were higher with an increasing supplemental dosage of vitamin D ( p less than 0.001 ) , particularly in infants in the north . None of the infants had rickets at 6 months of age . Because of the low serum 25-hydroxyvitamin D concentrations , especially among infants in the north , it may be prudent to supplement the diet with vitamin D at a dose of 400 IU/day
target: Whether or not outcomes such as osteoporosis ( or low bone mass ) and specific types of cancer may be prevented by ' generous ' vitamin D supplementation is unclear and mostly based on indirect epidemiologic data not clearly substantiated by r and omized controlled trials SUMMARY The dose of daily vitamin D supplements needed to prevent rickets is probably much lower than that recommended by most expert committees .
background: PURPOSE OF REVIEW To underst and the basis for current recommendations for  vitamin D supplementation in childhood and the differences between the recommendations published by major expert committees , using the Medline engine of the US National Library of Medicine and the National Institutes of Health .
  Most trials have examined the question of whether a specific daily vitamin D dose is capable or not to prevent rickets ( by study ing surrogate markers of rickets ) .