Multinutrient-Fortified Juices Improve Vitamin D and Vitamin E Status in Children: A Randomized Controlled Trial

BackgroundProvision of fortified juices may provide a convenient method to maintain and increase blood fat-soluble vitamins.ObjectiveTo determine whether children consuming orange juice fortified with calcium and combinations of vitamins D, E, and A could increase serum 25-hydroxyvitamin D [25(OH)D], α-tocopherol, and retinol levels.DesignA 12-week randomized, double-blind, controlled trial.Participants/settingOne hundred eighty participants (aged 8.04±1.42 years) were recruited at Tufts (n=70) and Boston University (n=110) during 2005-2006. Of those recruited, 176 children were randomized into three groups: CaD (700 mg calcium+200 IU vitamin D), CaDEA (700 mg calcium+200 IU vitamin D+12 IU vitamin E+2,000 IU vitamin A as beta carotene), or Ca (700 mg calcium). Children consumed two 240-mL glasses of CaD, CaDEA, or Ca fortified orange juice daily for 12 weeks.Main outcome measuresSerum 25(OH)D, α-tocopherol, and retinol concentrations.Statistical analysesChanges in 25(OH)D, α-tocopherol, retinol, and parathyroid hormone concentrations were examined. Covariates included sex, age, race/ethnicity, body mass index, and baseline 25(OH)D, α-tocopherol, retinol, or parathyroid hormone levels. Multivariate models and repeated measures analysis of variance tested for group differences with pre–post measures (n=141).ResultsBaseline 25(OH)D was 68.4±27.7 nmol/L (27.4±11.10 ng/mL) ), with 21.7% of participants having inadequate 25(OH)D (<50 nmol/L [20.03 ng/mL]). The CaD group's 25(OH)D increase was greater than that of the Ca group (12.7 nmol/L [5.09 ng/mL], 95% CI 1.3 to 24.1; P=0.029). The CaDEA group's increase in α-tocopherol concentration was greater than that in the Ca or CaD groups (3.79 μmol/L [0.16 μg/mL], 95% CI 2.5 to 5.1 and 3.09 μmol/L [0.13 μg/mL], 95% CI −1.8 to 4.3), respectively (P<0.0001). Retinol levels did not change, and body weight remained as expected for growth.ConclusionsDaily consumption of orange juice providing 200 IU vitamin D and 12 IU vitamin E increased 25(OH)D and α-tocopherol concentrations in young children within 12 weeks.     

The bioavailability of vitamin D from fortified cheeses and supplements is equivalent in adults

There is a need to increase the options for vitamin D fortification. We have developed a method to fortify hard cheese with vitamin D. Our aim was to characterize the bioavailability of vitamin D from fortified cheeses. Eighty adults were randomized to weekly servings of fortified cheddar cheese (DC) (34 g; n = 20); fortified low-fat cheese (DLF) (41 g; n = 10); liquid vitamin D supplement (1 mL), taken with food (DS+) (n = 20) or without food (DS-) (n = 10); placebo cheddar cheese (n = 10); or placebo supplement (n = 10). The treatments contained 28,000 IU cholecalciferol (vitamin D3), equivalent to 4000 IU (100 microg/d). The primary outcome was the comparison of vitamin D bioavailability, as measured by the serum 25-hydroxyvitamin D [25(OH)D] response, between fortified cheeses and supplement. In the placebo groups, initial 25(OH)D, 55.0 +/- 25.3 nmol/L, declined over the 8-wk winter protocol, to 50.7 +/- 24.2 nmol/L (P = 0.046). In the vitamin D-treated groups, the mean increases in 25(OH)D over 8 wk were: 65.3 +/- 24.1 (DC), 69.4 +/- 21.7 (DLF), 59.3 +/- 23.3 (DS+), and 59.3 +/- 19.6 nmol/L (DS-); these changes differed from the placebo groups (P < 0.0001) but not from one another (P = 0.62). Compared with baseline, serum parathyroid hormone decreased with both fortification (P = 0.003) and supplementation (P = 0.012). These data demonstrate that vitamin D is equally bioavailable from fortified hard cheeses and supplements, making cheese suitable for vitamin D fortification.     

An updated systematic review and meta-analysis of the efficacy of vitamin D food fortification

Food fortification is a potentially effective public health strategy to increase vitamin D intakes and circulating 25-hydroxyvitamin D [25(OH)D] concentrations. We updated a previous systematic review to evaluate current evidence from randomized controlled intervention studies in community-dwelling adults of the effect of fortified foods on 25(OH)D concentrations. Ovid MEDLINE, PubMed, CINAHL, Embase, and Cochrane Central Register of Controlled Trials were searched for randomized controlled intervention studies with vitamin D-fortified foods in free-living adults and data on circulating 25(OH)D. Two reviewers independently screened 441 papers for eligibility and extracted the relevant data. A meta-analysis of the absolute mean change in circulating 25(OH)D concentrations was conducted using a random effects model. Sixteen studies from 15 publications were included, of which 14 showed a significant effect of fortified foods on 25(OH)D concentrations. Heterogeneity was high (P = <0.0001, I(2) = 89%) and was partly explained by dose, latitude (range, 3-60°), and baseline 25(OH)D (range, 24.0-83.6 nmol/L). When combined in a random effects analysis (n = 1513; 767 treated, 746 controls), a mean individual intake of ~11 μg/d (440 IU/d) from fortified foods (range, 3-25 μg/d) increased 25(OH)D by 19.4 nmol/L (95% CI: 13.9, 24.9), corresponding to a 1.2 nmol/L (95% CI: 0.72, 1.68) increase in 25(OH)D for each 1 μg ingested. Vitamin D food fortification increases circulating 25(OH)D concentrations in community-dwelling adults. Safe and effective food-based strategies could increase 25(OH)D across the population distribution and prevent vitamin D deficiency with potential benefit for public health.     

Vitamin D-fortified milk achieves the targeted serum 25-hydroxyvitamin D concentration without affecting that of parathyroid hormone in New Zealand toddlers

For young children, the level of vitamin D required to ensure that most achieve targeted serum 25-hydroxyvitamin D [25(OH)D] ≥50 nmol/L has not been studied. We aimed to investigate the effect of vitamin D-fortified milk on serum 25(OH)D and parathyroid hormone (PTH) concentrations and to examine the dose-response relationship between vitamin D intake from study milks and serum 25(OH)D concentrations in healthy toddlers aged 12-20 mo living in Dunedin, New Zealand (latitude 46°S). Data from a 20-wk, partially blinded, randomized trial that investigated the effect of providing red meat or fortified toddler milk on the iron, zinc, iodine, and vitamin D status in young New Zealand children (n = 181; mean age 17 mo) were used. Adherence to the intervention was assessed by 7-d weighed diaries at wk 2, 7, 11, 15, and 19. Serum 25(OH)D concentration was measured at baseline and wk 20. Mean vitamin D intake provided by fortified milk was 3.7 μg/d (range, 0-10.4 μg/d). After 20 wk, serum 25(OH)D concentrations but not PTH were significantly different in the milk groups. The prevalence of having a serum 25(OH)D <50 nmol/L remained relatively unchanged at 43% in the meat group, whereas it significantly decreased to between 11 and 15% in those consuming fortified study milk. In New Zealand, vitamin D intake in young children is minimal. Our findings indicate that habitual consumption of vitamin D-fortified milk providing a mean intake of nearly 4 μg/d was effective in achieving adequate year-round serum 25(OH)D for most children.     

Effects of vitamin D fortified milk on vitamin D status in Mongolian school age children

Mongolians are at high risk for vitamin D deficiency because of their residence at northern latitude, reduced exposure to UV-B rays during the winter months, and a low availability of vitamin-D fortified foods. We performed a pilot study in May 2005 to estimate the prevalence of hypovitaminosis D in Mongolian school age children and to determine the feasibility of conducting a longer and larger trial with fortified milk and vitamin D supplements. In a group of 46 Mongolian children (22 girls and 24 boys) aged 9-11 years, 76% (35) had levels of 25-hydroxyvitamin D (25(OH)D) below 50 nmol/L (20 ng/mL) and 32% had levels below 37 nmol/L (15 ng/mL). After a month of consuming 710 ml of vitamin D-fortified (total 300 IU or 7.5 microg) milk daily, only 3 of the children were below 50 nmol/L (20 ng/mL) and none below 37 nmol/L (15 ng/mL). These results reveal prevalent and serious 25(OH)D deficiency among Mongolian prepubertal school age children that appears to be ameliorated by a month of consuming approximately 7.5 microg of vitamin D3 in fortified milk.     

25-Hydroxyvitamin D and vitamin D in human milk: effects of supplementation and season

Breast-milk 25-hydroxyvitamin D (25-[OH]D) and vitamin D were measured in mothers supplemented with 2000 or 1000 IU (50 or 25 micrograms) of vitamin D/d or with no supplementation. Fore- and hindmilk samples were collected at two stages of lactation (8 and 15 or 20 wk after delivery) and at different seasons. Season affected the levels of 25-(OH)D and vitamin D. The 25-(OH)D levels were higher in hind- than in foremilk. Supplementation had no effect on vitamin D levels. Milk 25-(OH)D levels of mothers receiving either 1000 or 2000 IU (25 or 50 micrograms) vitamin D/d were significantly higher than those of unsupplemented mothers in February and April. In theory, supplementation with 2000 IU (50 micrograms) vitamin D should have increased the calculated antirachitic activity of the milk in winter to the levels of unsupplemented mothers in September; however, responses varied widely among individuals.     

Effects of ergocalciferol supplementation on the concentration of vitamin D and its metabolites in human milk

The effect of maternal ergocalciferol (vitamin D2) supplementation on the concentrations of vitamin D, 25-hydroxyvitamin D (25-OH-D), 24R,25-dihydroxyvitamin D [24,25-(OH)2D], and 1 alpha,25-dihydroxyvitamin D [1,25-(OH)2D] in their milk was studied. Vitamin D2, D3, 25-OH-D2 and 25-OH-D3 were simultaneously determined by high performance liquid chromatography, and the determination of 24,25-(OH)2D and 1,25-(OH)2D was performed by competitive protein binding assay and radioreceptor assay, respectively, after separation of the D2 and D3 compounds. After healthy lactating mothers had received a daily oral dose of vitamin D2 (1,200 IU/d) for 4 wk, the concentrations of vitamin D2, D3 and the metabolites were determined in their plasma and milk. Although the plasma levels of 25-OH-D2 were significantly increased, the increase in milk was relatively small. On the other hand, the increase of vitamin D2 levels in milk was greater than that of 25-OH-D2 in milk after supplementation. The levels of 1,25-(OH)2D in milk was lower after 5 wk of lactation than after 1 wk of lactation, regardless of maternal vitamin D2 supplementation. When total antirachitic activities in milk were calculated, only a very slight increase was observed as a result of supplementation.     

Efficacy and safety of vitamin D3 intake exceeding the lowest observed adverse effect level

BACKGROUND: The Food and Nutrition Board of the National Academy of Sciences states that 95 microg vitamin D/d is the lowest observed adverse effect level (LOAEL). OBJECTIVE: Our objective was to assess the efficacy and safety of prolonged vitamin D3 intakes of 25 and 100 microg (1000 and 4000 IU)/d. Efficacy was based on the lowest serum 25-hydroxyvitamin D [25(OH)D] concentration achieved by subjects taking vitamin D3; potential toxicity was monitored by measuring serum calcium concentrations and by calculating urinary calcium-creatinine ratios. DESIGN: Healthy men and women (n = 61) aged 41 +/- 9 y (mean +/- SD) were randomly assigned to receive either 25 or 100 microg vitamin D3/d for 2-5 mo, starting between January and February. Serum 25(OH)D was measured by radioimmunoassay. RESULTS: Baseline serum 25(OH)D was 40.7 +/- 15.4 nmol/L (mean +/- SD). From 3 mo on, serum 25(OH)D plateaued at 68.7 +/- 16.9 nmol/L in the 25-microg/d group and at 96.4 +/- 14.6 nmol/L in the 100-microg/d group. Summertime serum 25(OH)D concentrations in 25 comparable subjects not taking vitamin D3 were 46.7 +/- 17.8 nmol/L. The minimum and maximum plateau serum 25(OH)D concentrations in subjects taking 25 and 100 microg vitamin D3/d were 40 and 100 nmol/L and 69 and 125 nmol/L, respectively. Serum calcium and urinary calcium excretion did not change significantly at either dosage during the study. CONCLUSIONS: The 100-microg/d dosage of vitamin D3 effectively increased 25(OH)D to high-normal concentrations in practically all adults and serum 25(OH)D remained within the physiologic range; therefore, we consider 100 microg vitamin D3/d to be a safe intake.     

Prospective study on food fortification with vitamin D among adolescent females in Finland: minor effects

Vitamin D insufficiency is common particularly during winter time. After the recommendation by the Ministry of Social Affairs and Health, Finnish fluid milks and margarines have been fortified with vitamin D since February 2003. The aims of the present study were to examine the impact of vitamin D fortification of food supplies on serum 25-hydroxyvitamin D (S-25(OH)D) concentrations and on daily dietary vitamin D intake among adolescent females. One hundred and forty-two girls of Caucasian ethnicity aged 12-18 years completed semi-quantitative FFQ from which the dietary vitamin D and Ca intakes were calculated. S-25(OH)D was measured by radioimmunoassay. The study was performed from February-March 2000 to February-March 2004, one year after the initiation of fortification. The mean dietary intake of vitamin D was < 7.5 microg in 91.5 % of the adolescent girls in 2000 and 83.8 % in 2004. The midwinter mean S-25(OH)D concentration did not change significantly during the follow-up period (48.3 v. 48.1 nmol/l, NS). The proportion of participants who had S-25(OH)D concentration < 50 nmol/l was 60.6 % in 2000 and 65.5 % in 2004. Only 7.0 % of the participants had an adequate S-25(OH)D ( >or= 75 nmol/l) level in 2000 or 4 years later. The vitamin D fortification of fluid milks and margarines was inadequate to prevent vitamin D insufficiency. There are numerous adolescent girls and women who are not reached by the current fortification policy. Therefore new innovative and feasible ways of improving vitamin D nutrition are urged.     

Effect of calcium fortified milk supplementation with or without vitamin K on biochemical markers of bone turnover in premenopausal women

OBJECTIVE: We compared the effect of supplementation with a fortified skimmed milk product (high calcium skim milk) with or without added phylloquinone (vitamin K(1)) on markers of bone formation and resorption in premenopausal women. METHODS: Eighty-two women 20 to 35 y of age were randomly allocated to three groups. Two groups received two daily servings of high calcium skim milk (1000 mg/d of extra calcium) with or without added phylloquinone (80 microg/d) for 16 wk, and a third control group received no supplementation. Bone density was assessed at baseline and the bone markers, total osteocalcin, type I N-terminal procollagen peptide, and cross-linked C-telopeptide of type I collagen were measured at baseline and at weeks 2, 12, and 16. Serum phylloquinone and undercarboxylated osteocalcin were measured in the control and vitamin K-supplemented groups at weeks 0 and 16. RESULTS: Baseline values for age, body mass index, and bone density did not differ across groups. In vitamin K-supplemented women, mean serum phylloquinone concentrations increased from 0.27 to 0.76 microg/L (P < 0.05) and undercarboxylated osteocalcin concentrations decreased from 9.68 to 4.46 microg/L (P < 0.05) over 16 wk. Plasma cross-linked C-telopeptide of type I collagen, total osteocalcin, and type I N-terminal procollagen peptide levels decreased significantly in both supplemented groups compared with the control group over 16 wk (cross-linked C-telopeptide of type I collagen >30%, total osteocalcin and type I N-terminal procollagen peptide >15%). CONCLUSION: Fortified milk supplementation in premenopausal women reduced bone turnover significantly. Phylloquinone fortification substantially improved vitamin K status but had no demonstrable additive effect on bone turnover in this short-term study.     

Safety of vitamin D3 in adults with multiple sclerosis

BACKGROUND: Vitamin D3 may have therapeutic potential in several diseases, including multiple sclerosis. High doses of vitamin D(3) may be required for therapeutic efficacy, and yet tolerability--in the present context, defined as the serum concentration of 25-hydroxyvitamin D [25(OH)D] that does not cause hypercalcemia--remains poorly characterized. OBJECTIVE: The objective of the study was to characterize the calcemic response to specific serum 25(OH)D concentrations. DESIGN: In a 28-wk protocol, 12 patients in an active phase of multiple sclerosis were given 1200 mg elemental Ca/d along with progressively increasing doses of vitamin D3: from 700 to 7000 microg/wk (from 28 000 to 280 000 IU/wk). RESULTS: Mean (+/- SD) serum concentrations of 25(OH)D initially were 78 +/- 35 nmol/L and rose to 386 +/- 157 nmol/L (P < 0.001). Serum calcium concentrations and the urinary ratio of calcium to creatinine neither increased in mean values nor exceeded reference values for any participant (2.1-2.6 mmol/L and <1.0, respectively). Liver enzymes, serum creatinine, electrolytes, serum protein, and parathyroid hormone did not change according to Bonferroni repeated-measures statistics, although parathyroid hormone did decline significantly according to the paired t test. Disease progression and activity were not affected, but the number of gadolinium-enhancing lesions per patient (assessed with a nuclear magnetic brain scan) decreased from the initial mean of 1.75 to the end-of-study mean of 0.83 (P = 0.03). CONCLUSIONS: Patients' serum 25(OH)D concentrations reached twice the top of the physiologic range without eliciting hypercalcemia or hypercalciuria. The data support the feasibility of pharmacologic doses of vitamin D3 for clinical research, and they provide objective evidence that vitamin D intake beyond the current upper limit is safe by a large margin.     

Determinants of vitamin D status in patients with hip fracture and in elderly control subjects

The factors that influence vitamin D status were investigated in 125 patients with hip fracture and in 74 elderly control subjects. The serum concentrations of 25-hydroxyvitamin D [25(OH)D] varied with sunshine score and were paralleled by serum 1,25-dihydroxyvitamin D [1,25(OH)2D]. The control subjects showed a higher sunshine score and higher serum 24(OH)D levels than the patients with hip fracture. Dietary vitamin D intake was similar in both groups (mean 115 IU/d). A positive correlation between vitamin D intake and serum 25(OH)D was observed in the patients with low sunshine exposure. It appeared from this relation that dietary vitamin D intake should be approximately 300 IU/d to maintain an adequate serum (25(OH)D concentration. Vitamin D status was very poor in patients who were institutionalized before hip fracture. Multiple regression analysis on serum 25(OH)D confirmed the primary role of sunshine exposure as determinant of vitamin D status. The principal determinants of serum 1,25(OH)2D were serum 25(OH)D, serum creatinine, and serum phosphate.     

Associations of diet, supplement use, and ultraviolet B radiation exposure with vitamin D status in Swedish women during winter

BACKGROUND: Vitamin D is produced endogenously after sun exposure but can also be obtained from natural food sources, food fortification, and dietary supplements. OBJECTIVE: We aimed to determine the vitamin D status of women (61-86 y old) living in central Sweden (latitude 60 degrees ) during winter and its relation with vitamin D intake and exposure to ultraviolet B radiation. DESIGN: In a cross-sectional study, we assessed the vitamin D status (serum 25-hydroxyvitamin D [25(OH)D]) of 116 women by using an enzyme immunoassay. The women completed questionnaires covering food habits, use of dietary supplements, and sun-related behavior. RESULTS: In a multiple linear regression model, the main determinants of serum 25(OH)D concentrations (x +/- SD: 69 +/- 23 mmol/L) were dietary vitamin D (6.0 +/- 1.8 mug/d), travel to a sunny location during winter within the previous 6 mo (26%), and the use of dietary supplements (16%). There was no association between serum 25(OH)D status during the winter and age, time spent outdoors, the use of sunscreen, or skin type. Serum 25(OH)D concentrations increased by 25.5 nmol/L with 2-3 servings (130 g/wk) fatty fish/wk, by 6.2 nmol/L with the daily intake of 300 g vitamin D-fortified reduced-fat dairy products, by 11.0 nmol/L with regular use of vitamin D supplements, and by 14.5 nmol/L with a sun vacation during winter. Among nonsupplement users without a wintertime sun vacation, 2-3 servings fatty fish/wk increased serum vitamin D concentrations by 45%. CONCLUSION: Fatty fish, vitamin D-fortified reduced-fat dairy products, regular supplement use, and taking a sun vacation are important predictors for serum concentrations of 25(OH)D during winter at a latitude of 60 degrees .     

Vitamin D intake to attain a desired serum 25-hydroxyvitamin D concentration

BACKGROUND: Indirect evidence suggests that optimal vitamin D status is achieved with a serum 25-hydroxyvitamin D [25(OH)D] concentration >75 nmol/L. OBJECTIVE: We aimed to determine the intake of vitamin D(3) needed to raise serum 25(OH)D to >75 nmol/L. DESIGN: The design was a 6-mo, prospective, randomized, double-blinded, double-dummy, placebo-controlled study of vitamin D(3) supplementation. Serum 25(OH)D was measured by radioimmunoassay. Vitamin D(3) intake was adjusted every 2 mo by use of an algorithm based on serum 25(OH)D concentration. RESULTS: A total of 138 subjects entered the study. After 2 dose adjustments, almost all active subjects attained concentrations of 25(OH)D >75 nmol/L, and no subjects exceeded 220 nmol/L. The mean (+/-SD) slope at 9 wk [defined as 25(OH)D change/baseline dose] was 0.66 +/- 0.35 (nmol/L)/(microg/d) and did not differ statistically between blacks and whites. The mean daily dose was 86 microg (3440 IU). The use of computer simulations to obtain the most participants within the range of 75-220 nmol/L predicted an optimal daily dose of 115 microg/d (4600 IU). No hypercalcemia or hypercalciuria was observed. CONCLUSIONS: Determination of the intake required to attain serum 25(OH)D concentrations >75 nmol/L must consider the wide variability in the dose-response curve and basal 25(OH)D concentrations. Projection of the dose-response curves observed in this convenience sample onto the population of the third National Health and Nutrition Examination Survey suggests a dose of 95 microg/d (3800 IU) for those above a 25(OH)D threshold of 55 nmol/L and a dose of 125 microg/d (5000 IU) for those below that threshold.     

High risk of vitamin D deficiency in children with sickle cell disease

Vitamin D is a particularly concerning nutrient for children with homozygous SS sickle cell disease (SCD-SS) due to their increased skin melanin concentrations, reduced levels of physical activity, and poor vitamin D intake. The goal of this study was to compare the vitamin D status of children with SCD-SS to healthy African-American children living in the same geographic area. Growth, dietary intake, serum 25-hydroxyvitamin D [25(OH)D], and intact parathyroid hormone (iPTH) concentrations were measured in 61 African-American subjects with SCD-SS and 89 healthy African-American control subjects age 5 to 18 years from the Philadelphia, PA, region (latitude 39.95 degrees N). Median serum 25(OH)D concentrations were 15 ng/mL (95% confidence interval [CI]: 13, 17) in subjects with SCD-SS and 21 ng/mL (95% CI: 18, 22) in healthy control subjects (P<0.0002). Vitamin D deficiency [25(OH)D<11 mg/mL] was found in 33% of subjects with SCD-SS and 9% of healthy control subjects (P<0.001); 25% of subjects with SCD-SS and 17% of healthy control subjects had elevated iPTH [(>59 rhog/mL), P<0.05]. Ninety-three percent of subjects with SCD-SS and 90% of healthy subjects had vitamin D insufficiency [25(OH)D<30 mg/mL]. The risk of vitamin D deficiency among subjects with SCD-SS was 5.3 (95% CI: 2.5, 8.2) times greater than control subjects, adjusted for season and age. Poor vitamin D status was prevalent in children with SCD-SS and healthy African-American children living in the same geographic area. However, children with SCD-SS were at greater risk for vitamin D deficiency than healthy African-American children.     

Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety

For adults, the 5-microg (200 IU) vitamin D recommended dietary allowance may prevent osteomalacia in the absence of sunlight, but more is needed to help prevent osteoporosis and secondary hyperparathyroidism. Other benefits of vitamin D supplementation are implicated epidemiologically: prevention of some cancers, osteoarthritis progression, multiple sclerosis, and hypertension. Total-body sun exposure easily provides the equivalent of 250 microg (10000 IU) vitamin D/d, suggesting that this is a physiologic limit. Sailors in US submarines are deprived of environmentally acquired vitamin D equivalent to 20-50 microg (800-2000 IU)/d. The assembled data from many vitamin D supplementation studies reveal a curve for vitamin D dose versus serum 25-hydroxyvitamin D [25(OH)D] response that is surprisingly flat up to 250 microg (10000 IU) vitamin D/d. To ensure that serum 25(OH)D concentrations exceed 100 nmol/L, a total vitamin D supply of 100 microg (4000 IU)/d is required. Except in those with conditions causing hypersensitivity, there is no evidence of adverse effects with serum 25(OH)D concentrations <140 nmol/L, which require a total vitamin D supply of 250 microg (10000 IU)/d to attain. Published cases of vitamin D toxicity with hypercalcemia, for which the 25(OH)D concentration and vitamin D dose are known, all involve intake of > or = 1000 microg (40000 IU)/d. Because vitamin D is potentially toxic, intake of >25 microg (1000 IU)/d has been avoided even though the weight of evidence shows that the currently accepted, no observed adverse effect limit of 50 microg (2000 IU)/d is too low by at least 5-fold.     

Dose response to vitamin D supplementation among postmenopausal African American women

BACKGROUND: Reports on the dose response to vitamin D are conflicting, and most data were derived from white men and women. OBJECTIVE: The objective was to determine the response of serum 25-hydroxyvitamin D [25(OH)D] to oral vitamin D(3) supplementation in an African American population. DESIGN: Healthy black postmenopausal women (n = 208) participated in a vitamin D(3) supplementation trial for a period of 3 y. Analyses were done in the vitamin D supplementation arm (n = 104) to quantify the response in serum 25-hydroxyvitamin D concentrations at a steady state vitamin D input. The participants received 20 microg/d (800 IU) oral vitamin D(3) for the initial 2 y and 50 microg/d (2000 IU) for the third year. RESULTS: Supplementation with 20 microg/d (800 IU/d) vitamin D(3) raised the mean serum 25(OH)D concentration from a baseline of 46.9 +/- 20.6 nmol/L to 71.4 +/- 21.5 nmol/L at 3 mo. The mean (+/-SD) concentration of serum 25(OH)D was 87.3 +/- 27.0 nmol/L 3 mo after supplementation increased to 50 microg/d (2000 IU/d). All participants achieved a serum 25(OH)D concentration >35 nmol/L, 95% achieved a concentration >50 nmol/L, but only 60% achieved a concentration >75 nmol/L. All patients had concentrations <153 nmol/L. On the basis of our findings, an algorithm for prescribing vitamin D so that patients reach optimal serum concentrations was developed. The algorithm suggests a dose of 70 microg (2800 IU/d) for those with a concentration >45 nmol/L and a dose of 100 microg (4000 IU/d) for those with a concentration <45 nmol/L. CONCLUSIONS: Supplementation with 50 microg/d (2000 IU/d) oral vitamin D(3) is sufficient to raise serum 25-hydroxyvitamin D concentrations to >50 nmol/L in almost all postmenopausal African American women. However, higher doses were needed to achieve concentrations >75 nmol/L in many women in this population.     

Vitamin D fortification as public health policy: significant improvement in vitamin D status in young Finnish men

BACKGROUND: Vitamin D insufficiency is common in northern countries during wintertime. In Finland, after the recommendation by the Ministry of Social Affairs and Health, vitamin D has been added to liquid milk products and margarines from February 2003. OBJECTIVE: We determined the effects of national policy on vitamin D fortification on vitamin D status among young Finnish men. DESIGN: A comparison before and after intervention with study population of 196 young Finnish men (18-28 years) was carried out. Serum 25-hydroxyvitamin D3 (25-OHD3) concentrations were determined with the OCTEIA enzymeimmunoassay by IDS (Immunodiagnostic Systems Limited, Bolden, UK) in January 2003 (n = 96) and in January 2004 (n = 100), nearly 1 year after national vitamin D fortification had started. RESULTS: The mean serum 25-OHD3 concentrations during the wintertime increased by 50% after implementation of the vitamin D fortification of dairy products. Correspondingly, the prevalence of vitamin D insufficiency (serum 25-OHD3 < 40 nmol/l) was decreased by 50% from 78% in January 2003 to 35% in January 2004. CONCLUSIONS: Our results demonstrate that national vitamin D fortification substantially improved the vitamin D status of young Finnish men. Still, a third remained vitamin D insufficient.     

Growth, bone mass, and vitamin D status of Chinese adolescent girls 3 y after withdrawal of milk supplementation

BACKGROUND: A 2-y school milk intervention trial showed that 330 mL of a dietary milk supplement (fortified with calcium alone or with both calcium and vitamin D) enhanced the growth and bone mineral accretion of Chinese girls aged 10 y at baseline. Girls who received milk fortified with both calcium and vitamin D also had better vitamin D status than did girls who received nothing or girls who received milk fortified only with calcium. OBJECTIVE: The aim was to evaluate whether these effects were sustained 3 y after supplement withdrawal. DESIGN: Anthropometric measures and dietary intake were reassessed in 501 of the 698 girls whose data had been studied at the end of the intervention. As in the intervention phase, total-body bone mineral content and bone mineral density and serum 25-hydroxyvitamin D concentrations were measured in half of these subjects. RESULTS: At follow-up, 99% of girls had reached menarche, at a mean (+/-SD) menarcheal age of 12.1 +/- 1.1 y. No significant differences in the timing of menarche were observed between the 3 groups (P = 0.6). No significant differences in the changes of total-body bone mineral content and bone mineral density since baseline were observed between the groups. The group receiving calcium-fortified milk had significantly greater gains in sitting height (0.9 +/- 0.3%; P = 0.02) than did the control group. The group that received calcium- and vitamin D-fortified milk had 17.1 +/- 6.7% lower serum 25-hydroxyvitamin D concentrations than did the control group (P = 0.04), but the difference was attenuated by additional adjustment for physical activity level (14.2 +/- 6.7%; P = 0.08). CONCLUSION: Milk supplementation during early puberty does not have long-lasting effects on bone mineral accretion.     

Bread cofortified with folic acid and vitamin B-12 improves the folate and vitamin B-12 status of healthy older people: a randomized controlled trial

BACKGROUND: Mandatory fortification of flour with folic acid has reduced the number of neural tube defects in North America. Concerns that high intakes of folic acid might mask vitamin B-12 deficiency in older persons have delayed the introduction of fortification in many European countries. Cofortification of flour with folic acid and vitamin B-12 could simultaneously improve folate and vitamin B-12 status. OBJECTIVE: The objective was to estimate the effect of the consumption of bread fortified with modest amounts of folic acid and vitamin B-12 on folate and vitamin B-12 status in healthy older persons living in the Netherlands, where folic acid fortification is not taking place. DESIGN: Men and women aged 50-75 y were randomly assigned in this 12-wk double-blind, placebo-controlled trial to consume bread fortified with 138 mug folic acid and 9.6 mug vitamin B-12 daily (n = 72) or unfortified bread (n = 70). RESULTS: The consumption of fortified bread increased serum folate concentrations by 45% (mean: 6.3 nmol/L; 95% CI: 4.5, 8.1 nmol/L) and serum vitamin B-12 concentrations by 49% (mean: 102 pmol/L; 95% CI: 82, 122 pmol/L) relative to the placebo group. Fortified bread increased erythrocyte folate concentrations by 22% and holotranscobalamin concentrations by 35%; it decreased homocysteine concentrations by 13% and methylmalonic acid concentrations by 10%. Consumption of fortified bread decreased the proportion of individuals with marginal serum vitamin B-12 concentrations (<133 pmol/L) from 8% at enrollment to 0% after 12 wk. CONCLUSION: Bread fortified with modest amounts of folic acid and vitamin B-12 will improve folate and vitamin B-12 status and a considerable proportion of vitamin B-12 deficiency in older people. This trial was registered at clinicaltrials.gov as NCT00353353.