Faculty Bibliography

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.

CONTEXT: Black women have lower 25-hydroxyvitamin D [25(OH)D] and higher PTH than white women. Recent evidence implicates PTH in adverse cardiovascular outcomes. OBJECTIVE: The objective of the study was to determine whether PTH increases at lower 25(OH)D levels (the threshold) in black compared with white women. DESIGN: Healthy black and white women, aged 20-80 yr were recruited to participate in a cross-sectional study of body-composition in black and white women. Measurement of serum 25(OH)D and PTH were carried out. SETTING: The study was a convenience sample recruited from a community setting. PATIENTS: Healthy black and white women were recruited by advertising and a direct mail campaign in a comparative study of body composition. Age ranged from 20-to 80 yr. There were 148 black and 129 white premenopausal participants and 87 black and 139 white postmenopausal participants. MAIN OUTCOME: The main outcome was to determine whether the threshold for 25(OH)D/PTH differs in black and white women. RESULTS: A threshold of 37 nmol/liter (95% confidence interval 35-40) was found for black and 59 nmol/liter (95% confidence interval 56-63) for white women. These two values were significantly different (P < 0.001). CONCLUSIONS: Black women have an increase in serum PTH at a lower 25(OH)D level than white women. Negative health outcomes of higher PTH should be investigated in black women.

BACKGROUND: Vitamin D sufficiency may be determined by the serum concentration of 25-hydroxyvitamin D [25(OH)D] that results in maximal intestinal calcium absorption efficiency. However, some investigators questioned whether 25(OH)D concentrations above the concentrations associated with rickets or osteomalacia influence calcium absorption. OBJECTIVE: We determined whether calcium absorption efficiency is related to serum 25(OH)D or serum 1,25-dihydroxyvitamin D [1,25(OH)(2)D] concentrations. DESIGN: We measured calcium absorption efficiency in 492 black and white healthy women (age range: 20-80 y) by the single-isotope method with (45)Ca. Serum 25(OH)D concentrations were measured by a radioreceptor assay. Other relevant measurements included concentrations of serum 1,25(OH)(2)D, serum parathyroid hormone, serum creatinine, and serum estradiol, calcium intake, and bone mineral density. RESULTS: There was no relation between serum 25(OH)D concentrations and calcium absorption efficiency. In development of a multivariate model, the 4 major determinants of calcium absorption efficiency were menopausal status, calcium intake, and serum estradiol and serum 1,25(OH)(2)D concentrations. There was an interaction between serum 25(OH)D and 1,25(OH)(2)D concentrations on calcium absorption efficiency. The relation between calcium absorption and 1,25(OH)(2)D was positive, and this relation was stronger for lower concentrations of 25(OH)D than for higher concentrations of 25(OH)D. CONCLUSION: The relation of serum 25(OH)D to calcium absorption is not useful as an indicator of vitamin D sufficiency.

BACKGROUND: Adequate calcium and vitamin D are needed to maintain calcium balance. OBJECTIVE: Our objective was to examine the influence of calcium intake and vitamin D exposure separately and their interaction on biomarkers of calcium sufficiency. DESIGN: Healthy men and women, age 20-80 yr, were randomly allocated to four groups: 1) double placebo, 2) calcium (1200 mg daily) plus placebo, 3) vitamin D(3) (100 microg) plus placebo, and 4) vitamin D(3) and calcium. Fasting serum and urine as well as serum and urine 2 h after a calcium load (600 mg of calcium carbonate) were obtained at baseline and 3 months. RESULTS: Ninety-nine participants were randomized; 78 completed the study. Baseline demographics, protein intake and laboratory studies did not differ among the four groups. Study medication compliance was 90%. Fasting bone turnover markers declined after 3 months only in the two groups given calcium supplements and increased in the vitamin D(3) plus placebo calcium group. The calcium load resulted in a decrease in PTH and in bone turnover markers that did not differ among groups. Urinary calcium excretion increased in the combined group. Mean serum 25-hydroxyvitamin D increased from a baseline of 67 (18 sd) nmol/liter to 111 (30 sd) nmol/liter after vitamin D supplementation. CONCLUSION: Increased habitual calcium intake lowered markers of bone turnover. Acute ingestion of a calcium load lowered PTH and bone turnover markers. Additional intake of 100 microg/d vitamin D(3) did not lower PTH or markers of bone turnover.

Background. The role of vitamin D in the body's ability to fight influenza and URI's may be dependent on regulation of specific cytokines that participate in the host inflammatory response. The aim of this study was to test the hypothesis that vitamin D can influence intracellular signaling to regulate the production of cytokines. Subjects and Methods. This study was a 3-month prospective placebo-controlled trial of vitamin D3 supplementation in ambulatory adults [Li-Ng et al., 2009]. 162 volunteers were randomized to receive either 50 mug/d (2000 IU) of vitamin D3 or matching placebo. 25(OH)D and the levels of 10 different cytokines (IL-2, 4, 5, 6, 8, 10, 13, GM-CSF, IFN-gamma, TNF-alpha) were measured in the serum of participants at baseline and the final visit. There were 6 drop-outs from the active vitamin D group and 8 from the placebo group. Results. In the active vitamin D group, we found a significant median percent decline in levels of GM-CSF (-62.9%, P < .0001), IFN-gamma (-38.9%, P < .0001), IL-4 (-50.8%, P = .001), IL-8 (-48.4%, P < .0001), and IL-10 (-70.4%, P < .0001). In the placebo group, there were significant declines for GM-CSF (-53.2%, P = .0007) and IFN-gamma (-34.4%, P = .0011). For each cytokine, there was no significant difference in the rate of decline between the two groups. 25(OH)D levels increased in the active vitamin D group from a mean of 64.3 +/- 25.4 nmol/L to 88.5 +/- 23.2 nmol/L. Conclusions. The present study did not show that vitamin D3 supplementation changed circulating cytokine levels among healthy adults.

BACKGROUND/AIMS: Growth hormone (GH) deficiency in pediatric patients results in short stature and osteopenia. We postulated that the GH and parathyroid hormone (PTH) combination would result in improvement in bone growth and bone formation. METHODS: Forty hypophysectomized female rats at age 8 weeks were divided into hypophysectomy (HX), HX + PTH (62.5 microg/kg, s.c. daily), HX + GH (3.33 mg/kg, s.c. daily), and HX + PTH + GH for a 4-week study. RESULTS: GH increased body weight, bone growth, bone mineral content (BMC) and bone mineral density (BMD), whereas PTH increased BMC and BMD without a significant effect on bone size. GH increased both periosteal and endocortical bone formation and cortical size, while PTH increased only endocortical bone formation. GH mitigated the trabecular bone loss by increasing bone formation, while PTH increased bone mass by increasing bone formation and suppressing osteoclast number per bone area. The result of combined intervention shows an increase in trabecular, periosteal and endocortical bone formation and suppression of bone resorption resulting in a synergistic effect on increasing trabecular and cortical bone volume and BMD. CONCLUSION: The combination treatment of PTH and GH increases bone growth, bone formation, decreases bone resorption and has a synergistic effect on increasing bone density and bone mass.

Vitamin D has been shown to be an important immune system regulator. Vitamin D insufficiency during winter may cause increased susceptibility to upper respiratory tract infections (URIs). To determine whether vitamin D supplementation during the winter season prevents or decreases URI symptoms, 162 adults were randomized to receive 50 microg vitamin D3 (2000 IU) daily or matching placebo for 12 weeks. A bi-weekly questionnaire was used to record the incidence and severity of URI symptoms. There was no difference in the incidence of URIs between the vitamin D and placebo groups (48 URIs vs. 50 URIs, respectively, P=0.57). There was no difference in the duration or severity of URI symptoms between the vitamin D and placebo groups [5.4+/-4.8 days vs. 5.3+/-3.1 days, respectively, P=0.86 (95% CI for the difference in duration -1.8 to 2.1)]. The mean 25-hydroxyvitamin D level at baseline was similar in both groups (64.3+/-25.4 nmol/l in the vitamin D group; 63.0+/-25.8 nmol/l in the placebo group; n.s.). After 12 weeks, 25-hydroxyvitamin D levels increased significantly to 88.5+/-23.2 nmol/l in the vitamin D group, whereas there was no change in vitamin D levels in the placebo group. There was no benefit of vitamin D3 supplementation in decreasing the incidence or severity of symptomatic URIs during winter. Further studies are needed to determine the role of vitamin D in infection.

Growth hormone (GH) deficiency in children causes severe growth retardation, vitamin D deficiency, and osteopenia. We investigated whether alfacalcidol (1OHD) alone or in combination with GH can improve bone formation. Forty hypophysectomized female rats (HX) at the age of 8 wk were divided into HX, HX + 1OHD (oral 0.25 microg/kg daily), HX+GH (0.666 mg/0.2 mL SC daily) and HX+GH + 1OHD groups for a 4-wk study. Results showed that GH increased body weight, bone area, bone mineral content (BMC), and bone mineral density (BMD), whereas 1OHD only increased BMC and BMD. In cortical bone, GH increased both periosteal and endocortical bone formation resulting in a significant increase in cortical size and area in percentage, whereas 1OHD suppressed endocortical erosion surface per bone surface (ES/BS) without a significant effect on bone formation rate per bone surface (BFR/BS). In trabecular bone, GH mitigated the bone loss by increasing BFR/BS, whereas the 1OHD effect was by suppression of trabecular bone turnover in the HX rats. The combination of GH and 1OHD had no additive effect on increasing trabecular bone mass. In conclusion, GH activates new bone formation and increases bone turnover whereas 1OHD suppresses bone turnover. The combination intervention does not seem to provide any additive benefit.