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 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.     

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.     

Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes

Recent evidence suggests that vitamin D intakes above current recommendations may be associated with better health outcomes. However, optimal serum concentrations of 25-hydroxyvitamin D [25(OH)D] have not been defined. This review summarizes evidence from studies that evaluated thresholds for serum 25(OH)D concentrations in relation to bone mineral density (BMD), lower-extremity function, dental health, and risk of falls, fractures, and colorectal cancer. For all endpoints, the most advantageous serum concentrations of 25(OH)D begin at 75 nmol/L (30 ng/mL), and the best are between 90 and 100 nmol/L (36-40 ng/mL). In most persons, these concentrations could not be reached with the currently recommended intakes of 200 and 600 IU vitamin D/d for younger and older adults, respectively. A comparison of vitamin D intakes with achieved serum concentrations of 25(OH)D for the purpose of estimating optimal intakes led us to suggest that, for bone health in younger adults and all studied outcomes in older adults, an increase in the currently recommended intake of vitamin D is warranted. An intake for all adults of > or =1000 IU (25 microg) [corrected] vitamin D (cholecalciferol)/d is needed to bring vitamin D concentrations in no less than 50% of the population up to 75 nmol/L. The implications of higher doses for the entire adult population should be addressed in future studies.     

Critique of the considerations for establishing the tolerable upper intake level for vitamin D: critical need for revision upwards

The tolerable upper intake level (UL) for vitamin D is 50 mcg/d (2000 iu/d) in North America and in Europe. In the United Kingdom a guidance level exists for vitamin D, 25 mcg/d (1000 iu/d), defined as the dose "of vitamins and minerals that potentially susceptible individuals could take daily on a life-long basis, without medical supervision in reasonable safety." Exposure of skin to sunshine can safely provide an adult with vitamin D in an amount equivalent to an oral dose of 250 mcg/d. The incremental consumption of 1 mcg/d of vitamin D3 raises serum 25-hydroxyvitamin D [25(OH)D ] by approximately 1 nmol/L (0.4 microg/L). Published reports suggest toxicity may occur with 25(OH)D concentrations beyond 500 nmol/L (200 microg/L). Older adults are advised to maintain serum 25(OH)D concentrations >75 nmol/L. The preceding numbers indicate that vitamin D3 intake at the UL raises 25(OH)D by approximately 50 nmol/L and that this may be more desirable than harmful. The past decade has produced separate North American, European, and U.K. reports that address UL or guidance-level values for vitamin D. Despite similar well-defined models for risk assessment, each report has failed to adapt its message to new evidence of no adverse effects at higher doses. Inappropriately low UL values, or guidance values, for vitamin D have hindered objective clinical research on vitamin D nutrition, they have hindered our understanding of its role in disease prevention, and restricted the amount of vitamin D in multivitamins and foods to doses too low to benefit public health.     

Optimal vitamin D status and serum parathyroid hormone concentrations in African American women

BACKGROUND: Optimal vitamin D status for the prevention of osteoporosis has been inferred from examinations of the serum 25-hydroxyvitamin D [25(OH)D] concentration below which there is an increase in serum parathyroid hormone (PTH). OBJECTIVE: The objectives of the study were to ascertain whether a threshold for serum 25(OH)D exists below which serum PTH increases and whether persons with 25(OH)D above this threshold have lower rates of bone loss than do persons with 25(OH)D below the threshold. DESIGN: The relation of serum 25(OH)D to serum PTH was analyzed in 208 African American women studied longitudinally for 3 y. These healthy women in midlife were randomly assigned to receive placebo or 800 IU vitamin D3/d; after 2 y, the vitamin D3 supplementation was increased to 2000 IU/d. Both groups received calcium supplements to ensure an adequate calcium intake. A systematic literature review found a wide range of threshold values in part due to varied calcium intake. RESULTS: A Loess plot suggested a breakpoint between 40 and 50 nmol/L for serum 25(OH)D. A line-line model was fitted to the data, and it showed a spline knot at 44 nmol/L. A heuristic approach verified that PTH does not decline as rapidly when the serum concentration of 25(OH)D is >40 nmol/L as when it is <40 nmol/L. We found no significant difference in rates of bone loss between persons with 25(OH)D concentrations above and below 40 nmol/L. CONCLUSION: Although a threshold for 25(OH)D can be identified, we suggest that it should not be used to recommend optimal vitamin D status.     

A systematic review and meta-regression analysis of the vitamin D intake-serum 25-hydroxyvitamin D relationship to inform European recommendations

The present study used a systematic review approach to identify relevant randomised control trials (RCT) with vitamin D and then apply meta-regression to explore the most appropriate model of the vitamin D intake-serum 25-hydroxyvitamin D (25(OH)D) relationship to underpin setting reference intake values. Methods included an updated structured search on Ovid MEDLINE; rigorous inclusion/exclusion criteria; data extraction; and meta-regression (using different model constructs). In particular, priority was given to data from winter-based RCT performed at latitudes >49·5°N (n 12). A combined weighted linear model meta-regression analyses of natural log (Ln) total vitamin D intake (i.e. diet and supplemental vitamin D) v. achieved serum 25(OH)D in winter (that used by the North American Dietary Reference Intake Committee) produced a curvilinear relationship (mean (95 % lower CI) serum 25(OH)D (nmol/l) = 9·2 (8·5) Ln (total vitamin D)). Use of non-transformed total vitamin D intake data (maximum 1400 IU/d; 35 μg/d) provided for a more linear relationship (mean serum 25(OH)D (nmol/l) = 0·044 × (total vitamin D)+33·035). Although inputting an intake of 600 IU/d (i.e. the RDA) into the 95 % lower CI curvilinear and linear models predicted a serum 25(OH)D of 54·4 and 55·2 nmol/l, respectively, the total vitamin D intake that would achieve 50 (and 40) nmol/l serum 25(OH)D was 359 (111) and 480 (260) IU/d, respectively. Inclusion of 95 % range in the model to account for inter-individual variability increased the predicted intake of vitamin D needed to maintain serum 25(OH)D ≥ 50 nmol/l to 930 IU/d. The model used to describe the vitamin D intake-status relationship needs to be considered carefully when setting new reference intake values in the Europe.     

Vitamin D intake is low and hypovitaminosis D common in healthy 9- to 15-year-old Finnish girls.

OBJECTIVES: To study the prevalence of hypovitaminosis D, the effect of vitamin D supplementation on serum 25-hydroxyvitamin D [S-25(OH)D], and the intakes of vitamin D and calcium in Finnish 9- to 15-year-old athletic and nonathletic girls. DESIGN: 1-year follow-up study (February 1997-March 1998) with three months of vitamin D supplementation (10 microg/d) from October to January. SETTING: Turku University Central Hospital, Finland. SUBJECTS: 191 female volunteers aged 9-15 y (131 athletes and 60 controls). METHODS: Vitamin D and calcium intakes were estimated by a four-day food recording and a semi-quantitative food frequency questionnaire (FFQ). S-25(OH)D was followed by radioimmunoassay (RIA). RESULTS: At baseline the mean S-25(OH)D concentration was 33.9 nmol/l among all girls. In winter severe hypovitaminosis D (S-25(OH)D < 20 nmol/l) occurred in 13.4% of the participants and in 67.7% S-25(OH)D was below 37.5 nmol/l. By the next summer the mean S-25(OH)D concentration was 62.9 nmol/l and in 1.6% of the subjects it was below 37.5 nmol/l. The prevalence of severe hypovitaminosis D was not significantly reduced by three months of vitamin D (10 microg/d) supplementation. At baseline, the mean intake of vitamin D was 2.9 microg/d by food recording and 4.3 microg/d by FFQ. The mean calcium intake was 1256 mg/d and 1580 mg/d, respectively. The intakes of vitamin D and calcium remained unchanged during the follow-up period. The athletes consumed more calcium than nonathletic controls, whereas the intake of vitamin D was quite similar among both groups. The vitamin D intake by FFQ correlated with the S-25(OH)D concentration in wintertime (r = 0.28, P < 0.01). CONCLUSION: Hypovitaminosis D is fairly common in growing Finnish girls in the wintertime, and three months of vitamin D supplementation with 10 microg/d was insufficient in preventing hypovitaminosis D. The daily dietary vitamin D intake was insufficient (< 5 microg/d) in the majority of participants, while the calcium intake was usually sufficient.     

Pharmacokinetics of High-Dose Weekly Oral Vitamin D3 Supplementation during the Third Trimester of Pregnancy in Dhaka,Bangladesh

A pharmacokinetic study was conducted to assess the biochemical dose-response and tolerability of high-dose prenatal vitamin D3 supplementation in Dhaka, Bangladesh (23°N). Pregnant women at 27–30 weeks gestation (n = 28) were randomized to 70,000 IU once + 35,000 IU/week vitamin D3 (group PH: pregnant, higher dose) or 14,000 IU/week vitamin D3 (PL: pregnant, lower dose) until delivery. A group of non-pregnant women (n = 16) was similarly administered 70,000 IU once + 35,000 IU/week for 10 weeks (NH: non-pregnant, higher-dose). Rise (∆) in serum 25-hydroxyvitamin D concentration ([25(OH)D]) above baseline was the primary pharmacokinetic outcome. Baseline mean [25(OH)D] were similar in PH and PL (35 nmol/L vs. 31 nmol/L, p = 0.34). A dose-response effect was observed: ∆[25(OH)D] at modeled steady-state was 19 nmol/L (95% CI, 1 to 37) higher in PH vs. PL (p = 0.044). ∆[25(OH)D] at modeled steady-state was lower in PH versus NH but the difference was not significant (−15 nmol/L, 95% CI −34 to 5; p = 0.13). In PH, 100% attained [25(OH)D] ≥ 50 nmol/L and 90% attained [25(OH)D] ≥ 80 nmol/L; in PL, 89% attained [25(OH)D] ≥ 50 nmol/L but 56% attained [25(OH)D] ≥ 80 nmol/L. Cord [25(OH)D] (n = 23) was slightly higher in PH versus PL (117 nmol/L vs. 98 nmol/L; p = 0.07). Vitamin D3 was well tolerated; there were no supplement-related serious adverse clinical events or hypercalcemia. In summary, a regimen of an initial dose of 70,000 IU and 35,000 IU/week vitamin D3 in the third trimester of pregnancy was non-hypercalcemic and attained [25(OH)D] ≥ 80 nmol/L in virtually all mothers and newborns. Further research is required to establish the safety of high-dose vitamin D3 in pregnancy and to determine if supplement-induced [25(OH)D] elevations lead to maternal-infant health benefits.     

Vitamin D status in adolescents and young adults with HIV infection

BACKGROUND: Vitamin D status affects immune function and thus may affect the progress of HIV infection. OBJECTIVES: Our goals were to assess vitamin D intake and status in subjects with HIV infection and in matched control subjects and to determine whether HIV infection was associated with vitamin D insufficiency. DESIGN: Plasma 25-hydroxyvitamin D [25(OH)D] concentrations and vitamin D intake were measured in a cross-sectional study of members of the Reaching for Excellence in Adolescent Health (REACH) cohort. RESULTS: The subjects were aged 14-23 y; 74% were female, and 72% were black. Mean (+/-SE) vitamin D intake from food was 30% greater (P = 0.023) in HIV-positive subjects (295 +/- 18 IU/d; n = 237) than in HIV-negative subjects (227 +/- 26 IU/d; n = 121). The prevalence of vitamin D supplement use was 29% (104 of 358 subjects) and did not differ significantly by HIV status (P = 0.87). Mean plasma 25(OH)D did not differ significantly (P = 0.62) between the HIV-positive (20.3 +/- 1.1 nmol/L; n = 238) and HIV-negative (19.3 +/- 1.7 nmol/L; n = 121) subjects, nor was HIV status a significant predictor of plasma 25(OH)D when multiple regression analysis was used to adjust for other variables. The prevalence of vitamin D insufficiency [plasma 25(OH)D < or = 37.5 nmol/L] in the subjects was 87% (312 of 359 subjects). CONCLUSIONS: HIV infection did not influence vitamin D status. The prevalence of vitamin D insufficiency in both HIV-positive and HIV-negative REACH subjects was high, perhaps because these disadvantaged, largely urban youth have limited sun exposure.     

Serum 25(OH)D response to vitamin D3 supplementation: A meta-regression analysis

ObjectiveThe aim of this study was to review factors that influence serum 25(OH)D when patients are given vitamin D supplements.MethodsFrom a comprehensive search of all randomized controlled clinical trials with vitamin D₃ supplementation available on PubMed up to November 2011, we selected 33 with 43 treatment arms that included at least 30 adult participants. The achieved pooled mean difference (PMD) and 95% confidence intervals (CIs) were calculated using the random-effects models. Meta-regression and subgroup analyses were performed for prespecified factors, including dose, duration, baseline serum 25(OH)D, and age.ResultsWith a mean baseline serum 25(OH)D of 50.4 nmol/L, PMD was 37 nmol/L (95% CI, 33–41) with significant heterogeneity among studies. Dose (slope: 0.006; P < 0.001), trial duration (slope: 0.21; P < 0.001), baseline serum 25(OH)D (slope: −0.19; P < 0.001), and age (slope: 0.42; P < 0.001) independently influenced vitamin D response. Similar results were found in studies with a mean baseline serum 25(OH)D <50 nmol/L. In subgroup analyses, the PMD was higher with doses ≥800 IU/d (39.3 nmol/L) after 6 to 12 mo (41.7 nmol/L), with baseline 25(OH)D <50 nmol/L (39.6 nmol/L), and in adults aged >80 y (40.5 nmol/L).ConclusionThis meta regression indicates that a higher increase in serum levels of 25(OH)D in adults is found with a dose of ≥800 IU/d, after at least 6 to 12 mo, and even when baseline 25(OH)D is low and in adults >80 y.     

How much vitamin D3 do the elderly need?

BACKGROUND: Vitamin D insufficiency poses a problem in many parts of the world, the elderly being an especially vulnerable group. This insufficiency results from an inadequate amount of sunshine and a low dietary intake of vitamin D. Typically, insufficiency is accompanied with high intact parathyroid hormone, (S-iPTH) concentrations. AIMS OF THE STUDY: We studied how serum 25-hydroxy vitamin D (S-25-OHD) concentrations respond to different doses of vitamin D3 supplementation. Secondly to determine the smallest efficient dose to maintain serum 25-OHD concentration above the insufficiency level. We also studied which dose would be efficient in decreasing S-iPTH concentration in these subjects. SUBJECTS AND METHODS: Forty-nine 65- to 85-year-old women participated. The women were randomly assigned into one of four groups receiving 0 (placebo), 5, 10 or 20 microg of vitamin D3 daily for 12 weeks. Fasting morning blood was drawn at the beginning of the study, and thereafter every second week. Calciotropic variables were assessed from serum and urine samples. RESULTS: The S-25-OHD concentration increased significantly (p < 0.001) in all supplemented groups [5 microg: by 10.9 (8.5) nmol/L, 10 microg: by 14.4 (6.9) nmol/L, 20 microg: by 23.7 (11.9) nmol/L], whereas it decreased in the placebo group by 8.3 (13.2) nmol/L. Equilibrium in S-25-OHD concentration was reached in all groups after 6 weeks of supplementation at 57.7 (8.9) nmol/L, 59.9 (8.9) nmol/L and 70.9 (8.9) nmol/L in the groups with increasing vitamin D supplementation. The dose-response to supplementation decreased with increasing vitamin D status at baseline, r = -0.513, p = 0.002. S-iPTH tended to decrease in those with highest dose response to supplementation. CONCLUSIONS: A clear dose response was noted in S-25-OHD to different doses of vitamin D3. The recommended dietary intake of 15 microg is adequate to maintain the S-25-OHD concentration around 40-55 nmol/L during winter, but if the optimal S-25-OHD is higher than that even higher vitamin D intakes are needed. Interestingly, subjects with lower vitamin D status at baseline responded more efficiently to supplementation than those with more adequate status.     

Vitamin D status in a rural postmenopausal female population

BACKGROUND: Inadequate vitamin D nutritional status is increasingly recognized as common in North American and European populations, but the extent of the shortfall and the parameters of the distribution for populations of interest remain uncertain. PURPOSE: To report the distribution of values for serum 25-hydroxyvitamin D [25(OH)D] in a population of rural postmenopausal women, together with quantification of factors related to vitamin D status. SETTING: Nine largely agrarian counties in eastern Nebraska (approximately 41 degrees N). PARTICIPANTS: A population-based sample of 1,179 women 55 years of age and older recruited into a four-year trial of calcium and vitamin D supplementation. METHODS: Baseline biochemical, dietary, and anthropometric measurements obtained on entry into trial. RESULTS: Serum 25(OH)D concentration at baseline varied cyclically with season, with the solar cycle explaining 2.9% of the total variance (P < 0.001). Mean seasonally adjusted 25(OH)D concentration was 71.1 nmol/L. Serum 25(OH)D also exhibited the expected inverse curvilinear relationship with serum parathyroid hormone (PTH), with the inflection point of the curve located at approximately 80 nmol/L. Supplements containing vitamin D were regularly taken by 59% of the cohort (median dose: 200 IU/d). Nevertheless, approximately 4% of all women had values below the laboratory reference range and more than two-thirds fell below 80 nmol/L. Seasonally adjusted serum 25(OH)D concentration was positively correlated with the size of daily vitamin D supplement dose, and negatively with age, weight, and body mass index (P < 0.01 for all). In stepwise multiple linear regression models, weight, age, and supplement dose were independently correlated with seasonally adjusted serum 25(OH)D, and together explained 19% of the total variance of adjusted 25(OH)D concentration. Women taking supplements had only one-sixth the chance of having a 25(OH)D value below the reference limit of the assay, compared to women who did not use supplements. CONCLUSIONS: Approximately two-thirds of this rural population fell below 80 nmol/L, a value considered to be the lower end of the optimal range. Based on the slope of 25(OH)D on supplement dose observed in these women, it would require an additional vitamin D input of nearly 2000 IU/d to reach the goal of an RDA for vitamin D, i.e., to bring 97.5% of the cohort to levels of 80 nmol/L or higher.     

冬季早期婴儿维生素D营养状况观察

目的 观察早期婴儿维生素D营养状况,为合理地补充维生素D提供依据。方法 以我国北方地区冬季出生的72例婴儿为研究对象,自生后15 d起口服维生素D补充剂,满月起逐月询问生活史和体检。于出生及4月龄时分别采集脐血和静脉血,测定血清25-(OH)D、钙、磷和碱性磷酸酶浓度。结果 脐血25-(OH)D平均水平(21.91±5.75)nmol/L,72例(100.0%)维生素D缺乏;婴儿4月龄时血清25-(OH)D平均水平(108.12±45.30)nmol/L,10例(13.9%)维生素D缺乏。血清25-(OH)D平均水平在每日摄入维生素D 200 U~组升至(112.37±37.98)nmol/L,在400 U~组升至(133.97±34.93)nmol/L。但维生素D不足和缺乏者在每日摄入维生素D 200 U~组6例(23.1%),400 U~组仅2例(7.1%)。新生儿及婴儿血钙、磷、碱性磷酸酶水平均正常。结论 北方地区冬季新生儿普遍存在维生素D缺乏,生后尽早补充可以显著改善维生素D营养状况。每日补充200 U维生素D可显著提高早期婴儿血清25-(OH)D水平;若要达到维生素D营养充足,至少补充400 U维生素D。     

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.     

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.     

Effects of vitamin D supplementation on 25-hydroxyvitamin D, high-density lipoprotein cholesterol, and other cardiovascular disease risk markers in subjects with elevated waist circumference

The objective of the present trial was to assess the effects of vitamin D supplementation on serum 25-hydroxyvitamin D [25(OH)D] and high-density lipoprotein cholesterol (HDL-C) in subjects with high waist circumference. Subjects were randomly assigned a daily multivitamin and mineral (MVM) supplement or a MVM supplement plus vitamin D 1,200 IU/day (MVM+D) for 8 weeks. There was a significant difference in mean change for 25(OH)D between the MVM and MVM+D treatment groups ( - 1.2 ± 2.5 nmol/l vs. 11.7 ± 3.0 nmol/l, respectively; P = 0.003). Vitamin D 1,200 IU/day did not increase 25(OH)D to a desirable level ( ≥ 75 nmol/l) in 61% of participants. There were no significant changes in cardiovascular disease risk markers. Thus, vitamin D supplementation with 1,200 IU/day was insufficient to achieve desirable serum 25(OH)D in most participants and did not affect cardiovascular disease risk markers.     

Wintertime vitamin D insufficiency is common in young Canadian women, and their vitamin D intake does not prevent it.

OBJECTIVE: We asked whether women self-reporting the recommended consumption of vitamin D from milk and multivitamins would be less likely to have low wintertime 25-hydroxyvitamin D (25(OH)D) levels. METHODS: This cross-sectional study enlisted at least 42 young women each month (age 18-35 y, 796 women total) through one year. We measured serum 25(OH)D and administered a lifestyle and diet questionnaire. RESULTS: Over the whole year, prevalence of low 25(OH)D (<40 nmol/l) was higher in non-white, non-black subjects (25.6% of 82 women) than in the white women (14.8% of 702 white women, P<0.05). Of the 435 women tested during the winter half of the year (November-April), prevalence of low 25(OH)D was not affected by vitamin D intake: low 25(OH)D occurred in 21% of the 146 consuming no vitamin D, in 26% of the 140 reporting some vitamin D intake, up to 5 microg/day (median, 2.5 microg/day), and in 20% of the 149 women reporting vitamin D consumption over 5 microg/day (median, 10 microg/day). INTERPRETATION: The self-reported vitamin D intake from milk and/or multivitamins does not relate to prevention of low vitamin D nutritional status of young women in winter. Recommended vitamin D intakes are too small to prevent insufficiency. Vitamin D nutrition can only be assessed by measuring serum 25(OH)D concentration.     

Vitamin A Intake,Serum Vitamin D and Bone Mineral Density: Analysis of the Korea National Health and Nutrition Examination Survey (KNHANES, 2008–2011)

The association of high vitamin A intake and low bone mineral density (BMD) is still controversial. To determine the association of dietary vitamin A intake and serum 25-hydroxyvitamin D (25(OH)D) concentration with BMD, a total of 6481 subjects (2907 men and 3574 women) aged ≥50 years from the Korean National Health and Nutrition Examination Survey (2008–2011) were divided into groups according to dietary vitamin A intake (tertiles) and serum 25(OH)D (<50, 50–75, >75 nmol/L), and evaluated for BMD after adjusting for relevant variables. Mean dietary vitamin A intakes were 737 and 600 μg RE (Retinol Equivalents) in men and women, respectively. Total hip and femoral neck BMD in men and lumbar spine BMD in women were both positively correlated with dietary vitamin A intake in subjects with serum 25(OH)D >75 nmol/L. Among men with serum 25(OH)D <50 nmol/L, both the top (mean 1353 μg RE) and bottom (mean 218 μg RE) tertiles of dietary vitamin A intake had lower BMD than the middle group (mean 577 μg RE). In this population, BMD was the highest among men and women with serum 25(OH)D = 50–75 nmol/L and that there were no differences in BMD by vitamin A intake in these vitamin D adequate groups. This cross-sectional study indicates that vitamin A intake does not affect bone mineral density as long as the serum 25(OH)D concentration is maintained in the moderate level of 50–75 nmol/L.     

Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D

It has been more than 3 decades since the first assay assessing circulating 25-hydroxyvitamin D [25(OH)D] in human subjects was performed and led to the definition of "normal" nutritional vitamin D status, i.e., vitamin D sufficiency. Sampling human subjects, who appear to be free from disease, and assessing "normal" circulating 25(OH)D levels based on a Gaussian distribution of these values is now considered to be a grossly inaccurate method of identifying the normal range. Several factors contribute to the inaccuracy of this approach, including race, lifestyle habits, sunscreen usage, age, latitude, and inappropriately low dietary intake recommendations for vitamin D. The current adult recommendations for vitamin D, 200-600 IU/d, are very inadequate when one considers that a 10-15 min whole-body exposure to peak summer sun will generate and release up to 20,000 IU vitamin D-3 into the circulation. We are now able to better identify sufficient circulating 25(OH)D levels through the use of specific biomarkers that appropriately increase or decrease with changes in 25(OH)D levels; these include intact parathyroid hormone, calcium absorption, and bone mineral density. Using these functional indicators, several studies have more accurately defined vitamin D deficiency as circulating levels of 25(OH)D < or = 80 nmol or 32 microg/L. Recent studies reveal that current dietary recommendations for adults are not sufficient to maintain circulating 25(OH)D levels at or above this level, especially in pregnancy and lactation.