Chronic and acute hypervitaminosis A are associated with suboptimal anthropometric measurements in a cohort of South African preschool children.

BACKGROUND: Excessive vitamin A (VA) can cause bone resorption and impair growth. Government-mandated VA supplementation (VAS) and adequate intake through dietary fortification and liver consumption led to excessive VA in South African children. OBJECTIVES: We evaluated the relation between VAS and underlying hypervitaminosis A assessed by retinol isotope dilution (RID) with measures of growth and bone turnover in this cohort. METHODS: Primary outcomes in these children (n = 94, 36-60 mo) were anthropometric measurements [height-for-age (HAZ), weight-for-age (WAZ), and weight-for-height (WHZ) z scores], serum bone turnover markers [C-terminal telopeptide of type I collagen (CTX) and N-terminal propeptide of type I procollagen (P1NP)], and inflammation defined as C-reactive protein (CRP; ≥5 mg/L) and/or α1-acid glycoprotein (AGP; ≥1 g/L). VA status was previously measured by RID-estimated total body VA stores (TBSs) and total liver VA reserves (TLRs), and serum retinol and carotenoid concentrations, before and 4 wk after children were administered 200,000 IU VAS. Serum 25-hydroxyvitamin D3 was measured by ultra-performance LC. RESULTS: In this largely hypervitaminotic A cohort, HAZ, WAZ, and WHZ were negatively associated with increasing TLRs, where TLRs predicted 6-10% of the variation before VAS (P < 0.05), increasing to 14-19% 4 wk after VAS (P < 0.01). Bone resorption decreased after VAS (P < 0.0001), whereas formation was unaffected. Neither CTX nor P1NP were correlated with TLRs at either time. Serum carotenoids were low. One child at each time point was vitamin D deficient (<50 nmol/L). CRP and AGP were not associated with growth measurements. CONCLUSIONS: Excessive TLRs due to dietary VA intake and VAS are associated with lower anthropometric measures and bone resorption decreased after supplementation. VA supplementation programs should monitor VA status with biomarkers sensitive to TLRs to avoid causing negative consequences in children with hypervitaminosis A. This trial is registered at clinicaltrials.gov as NCT02915731.

Comparison of vitamin D metabolites in wild and captive baboons.

Vitamin D adequacy is essential for multiple physiologic processes. With limited exposure to sunlight for vitamin D3 synthesis, captive primates are supplemented with vitamin D3 (cholecalciferol). Vitamin D metabolite data from wild primates living indigenously could suggest optimum levels. The purpose of this study was to: 1) to explore whether baboons, a speciose genus whose members have significant exposed skin, coat color variation and wide geographical distribution, mirrors the skin pigmentation-vitamin D relationship found in humans; 2) compare vitamin D metabolite levels in wild and captive members of the same or similar baboon species; and 3) apply a recently developed method currently used in humans for measuring multiple vitamin D metabolites as a panel to explore if/how these metabolites can inform us on vitamin D sufficiency. Serum samples from males of three baboon species in the wild: Papio anubis (olive baboon, dark exposed skin), P. cynocephalus (yellow baboon, brown exposed skin), and P. hamadryas (hamadryas baboon, pink exposed skin), were compared with vitamin D supplemented captive olive baboons with sun exposure. Liquid chromatography/tandem mass spectrometry (LC/MS/MS) measured vitamin D and its main metabolites. Cholecalciferol, 25 hydroxyvitamin D2&3 (25(OH)D2&3 ), and 24,25 dihydroxyvitamin D2&3 (24,25(OH)2 D2&3 ), showed significant differences by species. The levels of cholecalciferol due to supplements in the captive olive baboons did not convert to higher 25(OH)D3 while the wild olive baboons exhibited the lowest levels for both cholecalciferol and 25(OH)D3 . Further metabolic conversion of 25(OH)D3 to 24,25(OH)2 D3 indicated that all baboons had more similar conversion ratios and these were within the same range found for humans that are depicted as having adequate vitamin D levels. This study provided evidence that exposed skin color does influence vitamin D3 levels, with lower levels in darker skinned species, but these differences are eliminated in the downstream metabolite conversion indicating strong regulatory control.

Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline.

OBJECTIVE: The objective was to provide guidelines to clinicians for the evaluation, treatment, and prevention of vitamin D deficiency with an emphasis on the care of patients who are at risk for deficiency. PARTICIPANTS: The Task Force was composed of a Chair, six additional experts, and a methodologist. The Task Force received no corporate funding or remuneration. CONSENSUS PROCESS: Consensus was guided by systematic reviews of evidence and discussions during several conference calls and e-mail communications. The draft prepared by the Task Force was reviewed successively by The Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Core Committee, and cosponsoring associations, and it was posted on The Endocrine Society web site for member review. At each stage of review, the Task Force received written comments and incorporated needed changes. CONCLUSIONS: Considering that vitamin D deficiency is very common in all age groups and that few foods contain vitamin D, the Task Force recommended supplementation at suggested daily intake and tolerable upper limit levels, depending on age and clinical circumstances. The Task Force also suggested the measurement of serum 25-hydroxyvitamin D level by a reliable assay as the initial diagnostic test in patients at risk for deficiency. Treatment with either vitamin D(2) or vitamin D(3) was recommended for deficient patients. At the present time, there is not sufficient evidence to recommend screening individuals who are not at risk for deficiency or to prescribe vitamin D to attain the noncalcemic benefit for cardiovascular protection.

Fracture risks for women in long-term care: high prevalence of calcaneal osteoporosis and hypovitaminosis D.

STUDY OBJECTIVES: To determine the prevalence of osteoporosis as assessed by peripheral bone mineral density (BMD) in women living in a nursing home, to determine how many women with low BMD had received a diagnosis of osteoporosis, to assess the prevalence of vitamin D deficiency, and to seek reasons for vitamin D deficiency. DESIGN: Measurement of calcaneal BMD and serum 25-hydroxyvitamin D. SETTING: Skilled nursing facility. PATIENTS: Forty-nine women aged 68-100 years. MEASUREMENTS AND MAIN RESULTS: Bilateral calcaneal BMD was measured by dual-energy x-ray absorptiometry and serum 25-hydroxyvitamin D by radioimmunoassay. Medical records were reviewed to assess osteoporosis risk factors, previous documentation of osteoporosis or malabsorption, and supplemental vitamin D intake. Fifty-nine percent of the 39 women with calcaneal BMD measurements (95% confidence interval [CI] 44-74%) exhibited calcaneal osteoporosis (T score < -2.5). Sixty percent (95% CI 46-74%) had 25-hydroxyvitamin D levels of 20 ng/ml or less, which is associated with secondary hyperparathyroidism; only 4% of women had levels above 30 ng/ml, recently recommended as optimal. Vitamin D status was suboptimal even in most women taking multivitamins. Osteoporosis was documented in the records of 17% of 23 women with calcaneal osteoporosis. CONCLUSION: Osteoporosis was prevalent but poorly documented in women living in the nursing home. Peripheral BMD measurements have the potential to improve the recognition and management of osteoporosis in women in long-term care facilities. The high prevalence of vitamin D deficiency, even in those taking multivitamins, indicates that practical new approaches for vitamin D repletion in this population are urgently needed.

A high phylloquinone intake is required to achieve maximal osteocalcin gamma-carboxylation.

BACKGROUND: Dietary vitamin K is usually inadequate to maximize serum osteocalcin gamma-carboxylation. Phylloquinone supplementation increases osteocalcin gamma-carboxylation; however, the amount required to maximize carboxylation is not known. OBJECTIVE: This study assessed the ability of various doses of phylloquinone (vitamin K(1)) to facilitate osteocalcin gamma-carboxylation. DESIGN: Healthy adults aged 19-36 y participated in 2 substudies. In an initial dose-finding study (substudy A), 6 women and 4 men received a placebo daily for 1 wk and then phylloquinone daily for 3 wk: 500, 1000, and 2000 micro g during weeks 2, 3, and 4, respectively. Osteocalcin and undercarboxylated osteocalcin were measured at baseline and after each week of supplementation. Subsequently, to further delineate the gamma-carboxylation response of osteocalcin to various doses of vitamin K, 58 women and 42 men were randomly assigned to receive placebo or phylloquinone supplementation (250, 375, 500, and 1000 micro g/d) for 2 wk (substudy B). The percentage of undercarboxylated osteocalcin (%ucOC) was measured at baseline and weeks 1 and 2. RESULTS: In substudy A, %ucOC decreased with phylloquinone supplementation (P < 0.0001); a greater reduction was observed with 1000 and 2000 micro g than with 500 micro g (P < 0.05). In substudy B, %ucOC decreased in all supplemented groups by week 1 (P for the trend < 0.0001), which was sustained through week 2. Phylloquinone supplementation decreased %ucOC dose-dependently; %ucOC was significantly different between the 250- micro g and the placebo groups and between the 1000- and 500- micro g groups but not between the 250-, 375-, and 500- micro g groups. CONCLUSION: A daily phylloquinone intake of approximately 1000 micro g is required to maximally gamma-carboxylate circulating osteocalcin.

Short-term vitamin A supplementation does not affect bone turnover in men.

Limited data in humans and animals indicate that excess vitamin A stimulates bone resorption and inhibits bone formation, effects that over time might lead to bone loss and fracture. Thus, it is possible that vitamin A supplementation is a currently unrecognized risk factor for the development of osteoporosis. To further evaluate this possibility, a prospective, randomized, single-blind study of vitamin A supplementation was conducted in 80 healthy men age 18-58 y. One half received 7576 microg (25,000 IU) of retinol palmitate daily with their evening meal; the others took a placebo. Blood was collected from fasting subjects and serum prepared at baseline and after 2, 4 and 6 wk of supplementation. Serum bone specific alkaline phosphatase (BSAP) and N-Telopeptide of type 1 collagen (NTx) were measured at all time points. Serum osteocalcin (Oc) was measured at baseline and after 6 wk of supplementation. BSAP, NTx and Oc did not differ between the supplemented and placebo-treated groups over the course of the study. In conclusion, short-term vitamin A supplementation at this dosage in healthy men does not alter serum markers of skeletal turnover. Thus, it is unlikely that short-term administration of vitamin A would contribute to the development of osteoporosis. Whether long-term vitamin A supplementation might have adverse skeletal effects remains to be determined.

Pharmacy-based bone mass measurement to assess osteoporosis risk.

OBJECTIVE: To evaluate elderly women's knowledge of their skeletal status, assess adequacy of calcium intake, determine the prevalence of low bone density, and determine whether peripheral bone density testing led to medical interventions in a group of rural, elderly Wisconsin women recruited in community pharmacies. DESIGN: Recruiting notices were posted in each pharmacy, and eligible women were enrolled in the order in which they volunteered. Each completed a fracture-risk questionnaire. Calcaneal bone density was measured within the following 6 weeks, using peripheral dual-energy X-ray absorptiometry. Mail surveys were used to assess interventions subsequent to the womens' study participation. SETTING: The study was conducted at 5 community pharmacies in rural Wisconsin. RESULTS: Of 133 women, 20% had calcaneal osteoporosis, defined as a T score < or =2.5 (calcaneal bone density <2.5 SDs below the young reference database). Thirty percent of women met National Osteoporosis Foundation (NOF) treatment criteria based on heel bone density and NOF-designated risk factors. Of those meeting treatment criteria, 75% were unaware of their low bone mass. Half of the women received <1200 mg/d of calcium, the recommended dose for osteoporosis prevention. Those who were taking a calcium supplement were much more likely to receive the recommended amount. Women who had discussed bone density test results with their physicians were more likely to receive central dual energy X-ray absorptiometry (DXA) measurements and/or start antiresorptive therapy than women who did not. CONCLUSIONS: Rural, elderly Wisconsin women are at substantial risk for osteoporosis, based on calcaneal bone density, but most are unaware of their risk. Compounding this risk is low calcium intake. Community screening of rural, elderly women by peripheral bone density measurement can lead to medical interventions in such individuals.