Serum 25-hydroxyvitamin D (25-OHD) is considered the best biomarker of clinical vitamin D status.
To determine the effect of increasing oral doses of vitamin D(3) on serum 25-(OH)D and serum ...parathyroid hormone (PTH) levels in postmenopausal white women with vitamin D insufficiency (defined as a 25-OHD level ≤50 nmol/L) in the presence of adequate calcium intake. These results can be used as a guide to estimate the Recommended Dietary Allowance (RDA) (defined as meeting the needs of 97.5% of the population) for vitamin D(3).
Randomized, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00472823)
Creighton University Medical Center, Omaha, Nebraska.
163 healthy postmenopausal white women with vitamin D insufficiency enrolled in the winter or spring of 2007 to 2008 and followed for 1 year.
Participants were randomly assigned to receive placebo or vitamin D(3), 400, 800, 1600, 2400, 3200, 4000, or 4800 IU once daily. Daily calcium supplements were provided to increase the total daily calcium intake to 1200 to 1400 mg.
The primary outcomes were 25-(OH)D and PTH levels at 6 and 12 months.
The mean baseline 25-(OH)D level was 39 nmol/L. The dose response was curvilinear and tended to plateau at approximately 112 nmol/L in patients receiving more than 3200 IU/d of vitamin D(3). The RDA of vitamin D(3) to achieve a 25-(OH)D level greater than 50 nmol/L was 800 IU/d. A mixed-effects model predicted that 600 IU of vitamin D(3) daily could also meet this goal. Compared with participants with a normal body mass index (<25 kg/m(2)), obese women (≥30 kg/m(2)) had a 25-(OH)D level that was 17.8 nmol/L lower. Parathyroid hormone levels at 12 months decreased with an increasing dose of vitamin D(3) (P = 0.012). Depending on the criteria used, hypercalcemia occurred in 2.8% to 9.0% and hypercalciuria in 12.0% to 33.0% of participants; events were unrelated to dose.
Findings may not be generalizable to other age groups or persons with substantial comorbid conditions.
A vitamin D(3) dosage of 800 IU/d increased serum 25-(OH)D levels to greater than 50 nmol/L in 97.5% of women; however, a model predicted the same response with a vitamin D(3) dosage of 600 IU/d. These results can be used as a guide for the RDA of vitamin D(3), but prospective trials are needed to confirm the clinical significance of these results.
National Institute on Aging.
Vitamin D and aging Gallagher, J Christopher
Endocrinology and metabolism clinics of North America,
06/2013, Volume:
42, Issue:
2
Journal Article
Peer reviewed
Open access
Age-related changes affect vitamin D metabolism and increase the requirement for vitamin D in the elderly. Also there is an age related decrease in calcium absorption and a higher calcium intake is ...needed. Increasing calcium from dietary sources may be better than supplements, and requires increasing the intake of dairy products or other and calcium-fortified foods. Evidence suggests that vitamin D and calcium nutrition can be improved in the elderly by increasing the vitamin D intake to 800 IU daily together with a total calcium intake of 1000 mg daily. This combination is a simple, inexpensive strategy that can reduce fractures in institutionalized individuals by 30%.
•One year double blind trial, 7 daily oral doses of vitamin D or placebo, on incidence Fallers.•Faller rate was a U shaped curve, maximum decrease on doses 1600–3200 IU or serum 25OHD of ...32–38ng/ml.•High vitamin D dose 4000–4800 IU increases Faller incidence in those with previous Fall history.
Falls are a serious health problem in the aging population. Because low levels of vitamin D have been associated with increased fall rates, many trials have been performed with vitamin D; two meta-analyses showed either a small effect or no effect of vitamin D on falls. We conducted a study of the effect of vitamin D on serum 25 hydroxyvitamin D (25OHD) and data on falls was collected as a secondary outcome. In a 12-month double blind randomized placebo trial, elderly women, mean age 66 years, were randomized to one of seven daily oral doses of vitamin D or placebo. The main inclusion criterion for study was a baseline serum 25OHD<20ng/ml (50nmol/L). A history of falls was collected at baseline and fall events were collected every 3 months. Results showed that the effect of vitamin D on falls followed a U-shaped curve whether analyzed by dose or serum 25OHD levels. There was no decrease in falls on low vitamin D doses 400, 800 IU, a significant decrease on medium doses 1600, 2400,3200 IU (p=0.020) and no decrease on high doses 4000, 4800 IU compared to placebo (p=0.55). When compared to 12-month serum 25OHD quintiles, the faller rate was 60% in the lowest quintile <25ng/ml (<50nmol/L), 21% in the low middle quintile 32–38ng/ml (80–95nmo/L), 72% in the high middle quintile 38–46ng/ml (95–115nmo/L) and 45% in the highest quintile 46–66ng/ml (115–165nmol/L). In the subgroup with a fall history, fall rates were 68% on low dose, 27% on medium doses and 100% on higher doses. Fall rates on high doses were increased compared to medium doses (Odds Ratio 5.6.95% CI: 2.1–14.8). In summary, the maximum decrease in falls corresponds to a 12- month serum 25OHD of 32–38ng/ml (80–95nmol/L) and faller rates increase as serum 25OHD exceed 40–45ng/ml (100–112.5nmol/L). The Tolerable upper limit (TUL) recently increased in 2010 from 2000 to 4000 IU/day may need to be reduced in elderly women especially in those with a fall history.
The optimal measure of vitamin D status is unknown.
To directly measure circulating free 25-hydroxyvitamin D 25(OH)D concentrations and relationships to total 25(OH)D in a clinically diverse sample ...of humans.
Cross-sectional analysis.
Seven academic sites.
A total of 1661 adults: healthy (n = 279), prediabetic (n = 479), outpatients (n = 714), cirrhotic (n = 90), pregnant (n = 20), nursing home resident (n = 79).
Merge research data on circulating free 25(OH)D (directly-measured immunoassay), total 25(OH)D (liquid chromatography/tandem mass spectrometry), D-binding protein DBP; by radial (polyclonal) immunodiffusion assay, albumin, creatinine, intact parathyroid hormone, and DBP haplotype.
Distribution of free 25(OH)D (ANOVA with Bonferroni correction for post hoc comparisons) and relationships between free and total 25(OH)D (mixed-effects modeling incorporating clinical condition, DBP haplotype with sex, race, estimated glomerular filtration rate (eGFR), body mass index (BMI), and other covariates).
Free 25(OH)D was 4.7 ± 1.8 pg/mL (mean ± SD) in healthy persons and 4.3 ± 1.9 pg/mL in outpatients, with levels of 0.5 to 8.1 pg/mL and 0.9 to 8.1 pg/mL encompassing 95% of healthy persons and outpatients, respectively. Free 25(OH)D was higher in patients with cirrhosis (7.1 ± 3.0 pg/mL; P < 0.0033) and nursing home residents (7.9 ± 2.1 pg/mL; P < 0.0033) than in other groups and differed between whites and blacks (P < 0.0033) and between DBP haplotypes (P < 0.0001). Mixed-effects modeling of relationships between free and total 25(OH)D identified clinical conditions (patients with cirrhosis > nursing home residents > patients with prediabetes > outpatients > pregnant women) and BMI (lesser effect) as covariates affecting relationships but not eGFR, sex, race, or DBP haplotype.
Total 25(OH)D, health condition, race, and DBP haplotype affected free 25(OH)D, but only health conditions and BMI affected relationships between total and free 25(OH)D. Clinical importance of free 25(OH)D needs to be established in studies assessing outcomes.
To review the data on the effect of early menopause on bone. Do women undergoing early menopause develop lower bone mineral density at an earlier age and do they have a higher incidence of ...osteoporotic fractures? Is there a difference on bone between women who undergo early natural menopause compared to women who have early menopause after oophorectomy?
The earlier in life that menopause occurs, the lower the bone density will be later in life. Low bone density is associated with a higher fracture rate, and several studies show a relationship between early menopause, oophorectomy, and an increase in osteoporotic fractures.
Early menopause is a risk factor for osteoporosis. Women with an early menopause should have bone density testing performed within 10 years of menopause so that osteopenia or osteoporosis will be diagnosed early and appropriate anti-resorptive therapy initiated.
This article summarizes the new 2011 report on dietary requirements for calcium and vitamin D from the Institute of Medicine (IOM). An IOM Committee charged with determining the population needs for ...these nutrients in North America conducted a comprehensive review of the evidence for both skeletal and extraskeletal outcomes. The Committee concluded that available scientific evidence supports a key role of calcium and vitamin D in skeletal health, consistent with a cause-and-effect relationship and providing a sound basis for determination of intake requirements. For extraskeletal outcomes, including cancer, cardiovascular disease, diabetes, and autoimmune disorders, the evidence was inconsistent, inconclusive as to causality, and insufficient to inform nutritional requirements. Randomized clinical trial evidence for extraskeletal outcomes was limited and generally uninformative. Based on bone health, Recommended Dietary Allowances (RDAs; covering requirements of ≥97.5% of the population) for calcium range from 700 to 1300 mg/d for life-stage groups at least 1 yr of age. For vitamin D, RDAs of 600 IU/d for ages 1–70 yr and 800 IU/d for ages 71 yr and older, corresponding to a serum 25-hydroxyvitamin D level of at least 20 ng/ml (50 nmol/liter), meet the requirements of at least 97.5% of the population. RDAs for vitamin D were derived based on conditions of minimal sun exposure due to wide variability in vitamin D synthesis from ultraviolet light and the risks of skin cancer. Higher values were not consistently associated with greater benefit, and for some outcomes U-shaped associations were observed, with risks at both low and high levels. The Committee concluded that the prevalence of vitamin D inadequacy in North America has been overestimated. Urgent research and clinical priorities were identified, including reassessment of laboratory ranges for 25-hydroxyvitamin D, to avoid problems of both undertreatment and overtreatment.
There is an urgent clinical and public health need for consensus cut-points for serum 25OHD inadequacy to avoid problems of both under- and overtreatment.
▸ There was an inverse and independent relationship between serum 25OHD and body fat mass at baseline. ▸ There was no treatment effect of vitamin D or calcitriol on fat mass in randomized trials. ▸ ...The response to vitamin D treatment varies according to body weight and those with normal or low BMI should use smaller doses of vitamin D.
Obese people are known to have lower serum 25OHD levels compared to non-obese people. It is not known whether it is due to storage of vitamin D in fat, inadequate input from sunlight, diet or other unknown factors. We examined the relationship at study baseline of serum 25OHD, PTH, 1,25(OH)2D with body composition measurements using dual energy X-ray absorptiometry. The results showed a significant inverse relation between total body fat mass and serum 25OHD (p<0.0001) and serum 1,25(OH2)D (p=034) and an independent positive correlation between serum PTH and total body fat mass (p<0.0001). In a randomized controlled study of seven doses of vitamin D (400–4800IU/d) the increase in serum 25OHD levels was compared in women with a normal body mass index to obese women. The response to the low doses of vitamin D (400–800IU/d) was significantly less than that of the medium (1600–2400IU/d) and high doses groups (3200–4800IU) (p<0.0001) in all BMI categories. The increase in serum 25OHD in the medium and high dose groups was not significantly different with increasing level of obesity. But thinner women with a normal BMI (<25kg/m2) showed a much higher response to vitamin D at any dose level compared to other BMI groups. There was no significant change in total body fat mass after treatment with vitamin D or calcitriol in our randomized trials. In summary, the response to vitamin D is dependent on body weight. Women with BMI <25kg/m2 develop much higher levels of serum 25OHD after vitamin D supplementation compared to those with BMI of >25kg/m2. The differences in serum 25OHD levels between normal and obese women may be due to differences in volume dilution. After vitamin D supplementation, all obese women reach adequate levels of serum 25OHD but normal women (BMI<25kg/m2) reach much higher levels of 25OHD and in this group smaller doses of vitamin D used should be used.
This article is part of a Special Issue entitled ‘Vitamin D Workshop’.
Context:
Serum 25-hydroxyvitamin D (25OHD) is lower in women with darker skin color. Is it due to lower skin production, lower absorption, or different metabolism of vitamin D?
Objectives:
The ...objective of the study was to measure the effect of vitamin D3 on serum 25OHD and serum PTH in older African American women with vitamin D insufficiency and the serum 25OHD 20 ng/mL or less (<50 nmol/L). The results can be used to estimate the Recommended Dietary Allowance (RDA).
Design and Setting:
This was a randomized, double-blind placebo trial at Creighton University Medical Center and Indiana University Medical Center.
Participants:
Participants were 110 healthy older African American women.
Interventions:
The intervention consisted of participants randomly assigned to placebo, vitamin D3 400, 800, 1600, 2400, 3200, 4000, or 4800 IU daily; calcium supplements were given to maintain total calcium intake of 1200–1400 mg/d.
Main Outcome Measurements:
Change in serum 25OHD and serum PTH levels at 12 months was measured.
Results:
Mean baseline serum 25OHD was 13 ng/mL (33 nmol/L). On 4800 IU, serum 25OHD averaged 50 ng/mL (125 nmol/L) compared with 47 ng/mL (117 nmol/L) in Caucasian women. Serum PTH at 12 months decreased significantly (P = .008) when related to serum 25OHD but not dose. Hypercalcemia occurred in 7% and hypercalciuria in 15%. Events were unrelated to vitamin D dose.
Conclusion:
Vitamin D3 800 IU increased serum 25OHD greater than 20 ng/mL (>50 nmol/L) in 97.5% of the African American women just as it did in the Caucasian women, and therefore, the RDA is the same for both groups. Because absorption and metabolism of oral vitamin D absorption is similar in both groups, lower levels of serum 25OHD in African Americans must be due to lower production of vitamin D in skin.
In early 2011, a committee convened by the Institute of Medicine issued a report on the Dietary Reference Intakes for calcium and vitamin D. The Endocrine Society Task Force in July 2011 published a ...guideline for the evaluation, treatment, and prevention of vitamin D deficiency. Although these reports are intended for different purposes, the disagreements concerning the nature of the available data and the resulting conclusions have caused confusion for clinicians, researchers, and the public. In this commentary, members of the Institute of Medicine committee respond to aspects of The Endocrine Society guideline that are not well supported and in need of reconsideration. These concerns focus on target serum 25-hydroxyvitamin D levels, the definition of vitamin D deficiency, and the question of who constitutes a population at risk vs. the general population.
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