Dr. Ron’s Research Review – February 2, 2011

This week’s research review contains information on vitamin D.

Recognition and management of vitamin D deficiency (Bordelon, Ghetu et al. 2009)

What Have We Learned About Vitamin D Dosing? (Pizzorno 2010)

Vitamin D: criteria for safety and efficacy (Heaney 2008)

Serum vitamin D levels and severe asthma exacerbations in the Childhood Asthma Management Program study (Brehm, Schuemann et al. 2010)

Vitamin D2 (ergocalciferol) was the first synthetic form and is the basis for ALL Prescription Vitamin D.

Vitamin D3 Is More Potent Than Vitamin D2 in Humans (Heaney, Recker et al. 2010)

Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D (Holick, Biancuzzo et al. 2008)

Determining vitamin D status - The most valid method was HPLC-APCI-MS. (Snellman, Melhus et al. 2010)

        

Dr. Ron
Abstracts

Recognition and management of vitamin D deficiency

         (Bordelon, Ghetu et al. 2009) Download

Vitamin D deficiency affects persons of all ages. Common manifestations of vitamin D deficiency are symmetric low back pain, proximal muscle weakness, muscle aches, and throbbing bone pain elicited with pressure over the sternum or tibia. A 25-hydroxyvitamin D level should be obtained in patients with suspected vitamin D deficiency. Deficiency is defined as a serum 25-hydroxyvitamin D level of less than 20 ng per mL (50 nmol per L), and insufficiency is defined as a serum 25-hydroxyvitamin D level of 20 to 30 ng per mL (50 to 75 nmol per L). The goal of treatment is to normalize vitamin D levels to relieve symptoms and decrease the risk of fractures, falls, and other adverse health outcomes. To prevent vitamin D deficiency, the American Academy of Pediatrics recommends that infants and children receive at least 400 IU per day from diet and supplements. Evidence shows that vitamin D supplementation of at least 700 to 800 IU per day reduces fracture and fall rates in adults. In persons with vitamin D deficiency, treatment may include oral ergocalciferol (vitamin D2) at 50,000 IU per week for eight weeks. After vitamin D levels normalize, experts recommend maintenance dosages of cholecalciferol (vitamin D3) at 800 to 1,000 IU per day from dietary and supplemental sources.

What Have We Learned About Vitamin D Dosing?

            (Pizzorno 2010) Download

Serum vitamin D levels and severe asthma exacerbations in the Childhood Asthma Management Program study

            (Brehm, Schuemann et al. 2010) Download

BACKGROUND: Asthma exacerbations, most often caused by respiratory tract infections, are the leading causes of asthma morbidity and comprise a significant proportion of asthma-related costs. Vitamin D status might play a role in preventing asthma exacerbations. OBJECTIVES: We sought to assess the relationship between serum vitamin D levels and subsequent severe asthma exacerbations. METHODS: We measured 25-hydroxyvitamin D levels in sera collected from 1024 children with mild-to-moderate persistent asthma at the time of enrollment in a multicenter clinical trial of children randomized to receive budesonide, nedocromil, or placebo (as-needed beta-agonists): the Childhood Asthma Management Program. Using multivariable modeling, we examined the relationship between baseline vitamin D levels and the odds of any hospitalization or emergency department visit over the 4 years of the trial. RESULTS: Thirty-five percent of all subjects were vitamin D insufficient, as defined by a level of 30 ng/mL or less 25-hydroxyvitamin D. Mean vitamin D levels were lowest in African American subjects and highest in white subjects. After adjusting for age, sex, body mass index, income, and treatment group, insufficient vitamin D status was associated with a higher odds of any hospitalization or emergency department visit (odds ratio, 1.5; 95% CI, 1.1-1.9; P = .01). CONCLUSION: Vitamin D insufficiency is common in this population of North American children with mild-to-moderate persistent asthma and is associated with higher odds of severe exacerbation over a 4-year period.

Vitamin D3 Is More Potent Than Vitamin D2 in Humans

            (Heaney, Recker et al. 2010) Download

Background: Current unitage for the calciferols suggests that equimolar quantities of vitamins D2 (D2) and D3 (D3) are biologically equivalent. Published studies yield mixed results. Objective: The aim of the study was to compare the potencies of D2 and D3. Design: The trial used a single-blind, randomized design in 33 healthy adults. Calciferols were dosed at 50,000 IU/wk for 12 wk. Principal outcome variables were area under the curve for incremental total 25-hydroxyvitamin D [25(OH)D] and change in calciferol content of sc fat. Results: Incremental mean (SD) 25(OH)D area under the curve at 12 wk was 1366 ng . d/ml (516) for the D2-treated group and 2136 (606) for the D3 (P < 0.001). Mean (SD) steady-state 25(OH)D increments showed similar differences: 24 ng/ml for D2 (10.3) and 45 ng/ml (16.2) for D3 (P <0.001). Subcutaneous fat content of D2 rose by 50 mug/kg in the D2-treated group, and D3 content rose by 104 mug/kg in the D3-treated group. Total calciferol in fat rose by only 33 ng/kg in the D2-treated, whereas it rose by 104 mug/kg in the D3-treated group. Extrapolating to total body fat D3, storage amounted to just 17% of the administered dose. Conclusion: D3 is approximately 87% more potent in raising and maintaining serum 25(OH)D concentrations and produces 2- to 3-fold greater storage of vitamin D than does equimolar D2. For neither was there evidence of sequestration in fat, as had been postulated for doses in this range. Given its greater potency and lower cost, D3 should be the preferred treatment option when correcting vitamin D deficiency.

Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D

            (Holick, Biancuzzo et al. 2008) Download

CONTEXT: Two reports suggested that vitamin D2 is less effective than vitamin D3 in maintaining vitamin D status. OBJECTIVE: Our objective was to determine whether vitamin D2 was less effective than vitamin D3 in maintaining serum 25-hydroxyvitamin D levels or increased the catabolism of 25-hydroxyvitamin D3. SUBJECTS AND DESIGN: This was a randomized, placebo-controlled, double-blinded study of healthy adults ages 18-84 yr who received placebo, 1000 IU vitamin D3, 1000 IU vitamin D2, or 500 IU vitamin D2 plus 500 IU vitamin D3 daily for 11 wk at the end of the winter. RESULTS: Sixty percent of the healthy adults were vitamin D deficient at the start of the study. The circulating levels of 25-hydroxyvitamin D (mean+/-sd) increased to the same extent in the groups that received 1000 IU daily as vitamin D2 (baseline 16.9+/-10.5 ng/ml; 11 wk 26.8+/-9.6 ng/ml), vitamin D3 (baseline 19.6+/-11.1 ng/ml; 11 wk 28.9+/-11.0 ng/ml), or a combination of 500 IU vitamin D2 and 500 IU vitamin D3 (baseline 20.2+/-10.4 ng/ml; 11 wk 28.4+/-7.7 ng/ml). The 25-hydroxyvitamin D3 levels did not change in the group that received 1000 IU vitamin D2 daily. The 1000 IU dose of vitamin D2 or vitamin D3 did not raise 25-hydroxyvitamin D levels in vitamin D-deficient subjects above 30 ng/ml. CONCLUSION: A 1000 IU dose of vitamin D2 daily was as effective as 1000 IU vitamin D3 in maintaining serum 25-hydroxyvitamin D levels and did not negatively influence serum 25-hydroxyvitamin D3 levels. Therefore, vitamin D2 is equally as effective as vitamin D3 in maintaining 25-hydroxyvitamin D status.

Determining vitamin D status: a comparison between commercially available assays

(Snellman, Melhus et al. 2010) Download

BACKGROUND: Vitamin D is not only important for bone health but can also affect the development of several non-bone diseases. The definition of vitamin D insufficiency by serum levels of 25-hydroxyvitamin D depends on the clinical outcome but might also be a consequence of analytical methods used for the definition. Although numerous 25-hydroxyvitamin D assays are available, their comparability is uncertain. We therefore aim to investigate the precision, accuracy and clinical consequences of differences in performance between three common commercially available assays. METHODOLOGY/PRINCIPAL FINDINGS: Serum 25-hydroxyvitamin D levels from 204 twins from the Swedish Twin Registry were determined with high-pressure liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (HPLC-APCI-MS), a radioimmunoassay (RIA) and a chemiluminescent immunoassay (CLIA). High inter-assay disagreement was found. Mean 25-hydroxyvitamin D levels were highest for the HPLC-APCI-MS technique (85 nmol/L, 95% CI 81-89), intermediate for RIA (70 nmol/L, 95% CI 66-74) and lowest with CLIA (60 nmol/L, 95% CI 56-64). Using a 50-nmol/L cut-off, 8% of the subjects were insufficient using HPLC-APCI-MS, 22% with RIA and 43% by CLIA. Because of the heritable component of 25-hydroxyvitamin D status, the accuracy of each method could indirectly be assessed by comparison of within-twin pair correlations. The strongest correlation was found for HPLC-APCI-MS (r = 0.7), intermediate for RIA (r = 0.5) and lowest for CLIA (r = 0.4). Regression analyses between the methods revealed a non-uniform variance (p<0.0001) depending on level of 25-hydroxyvitamin D. CONCLUSIONS/SIGNIFICANCE: There are substantial inter-assay differences in performance. The most valid method was HPLC-APCI-MS. Calibration between 25-hydroxyvitamin D assays is intricate.


References

Bordelon, P., M. V. Ghetu, et al. (2009). "Recognition and management of vitamin D deficiency." Am Fam Physician 80(8): 841-6.

Brehm, J. M., B. Schuemann, et al. (2010). "Serum vitamin D levels and severe asthma exacerbations in the Childhood Asthma Management Program study." J Allergy Clin Immunol 126(1): 52-8 e5.

Heaney, R. P. (2008). "Vitamin D: criteria for safety and efficacy." Nutr Rev 66(10 Suppl 2): S178-81.

Heaney, R. P., R. R. Recker, et al. (2010). "Vitamin D3 Is More Potent Than Vitamin D2 in Humans." J Clin Endocrinol Metab.

Holick, M. F., R. M. Biancuzzo, et al. (2008). "Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D." J Clin Endocrinol Metab 93(3): 677-81.

Pizzorno, J. (2010). "What Have We Learned About Vitamin D Dosing?" Integrative Medicine 9(1).

Snellman, G., H. Melhus, et al. (2010). "Determining vitamin D status: a comparison between commercially available assays." PLoS One 5(7): e11555.