Over the last decade, vitamin D has become a popular topic in healthcare without many definitive answers for items such as what are the benefits of vitamin D, optimal levels desired, or how best to treat and prevent vitamin D deficiency. There is strong evidence to support the use of vitamin D in bone health with a 25-hydroxyvitamin D (25(OH)D) level of > 50nmol/L or >20ng/mL associated with fracture efficacy; however the association between vitamin D and non-skeletal outcomes, such as cancer, autoimmune disease, infectious disease, diabetes, cardiovascular disease and quality of life, has conflicting and limited evidence. The Endocrine Society has developed guidelines for the evaluation, treatment, and prevention of vitamin D deficiency; however, some of its findings conflict with the Institute of Medicine (IOM) recommendations on vitamin D. One of the major discrepancies between the two guidelines include target 25(OH)D levels. The IOM states that levels of 50nmol/L or 20 ng/mL is needed for bone health, while the Endocrine Society defines vitamin D deficiency and insufficiency as <50nmol/L or 20ng/mL and 21-74 nmol/L or 21-29ng/mL, respectively, providing a higher target value for management of ≥75nmol/L or 30ng/mL.1,2
Based on the IOM’s recommendations for 25(OH)D levels, Gallagher and colleagues performed the VIDOS (Vitamin D Supplementation in Older Subjects) trial. This was a one-year randomized, prospective, placebo-controlled trial involving 163 healthy, white, postmenopausal women aged 57-90 years who were at least 7 years postmenopausal with vitamin D insufficiency (defined as <50nmol/L or 20ng/mL). The primary objective was to study the effect of increasing doses of vitamin D3 on serum 25(OH)D and serum parathyroid hormone (PTH) in the presence of sufficient calcium intake (1,200-1,400mg/day) either through diet or calcium citrate supplements at 6 and 12 months. Another goal of the study was to determine the Recommended Dietary Allowance (RDA) and Estimated Average Requirement (EAR) for vitamin D. The exclusion criteria for this study included various and substantial comorbid conditions, history of cancer, active or history of kidney stones, 25(OH)D levels <13nmol/L (5.2ng/mL), previous hip fracture, T-score < -3 at spine or hip, use of fluoride, PTH, PTH derivatives, calcitonin or estrogen, and current use of drugs interfering with vitamin D metabolism. Study participants were assigned to receive one of 7 vitamin D3 doses (400, 800, 1600, 2400, 3200, 4000 or 4800 IU/d) or placebo for one year. Serum 25(OH)D and PTH levels were measured at baseline, 6 months, and 12 months.3
The average age and BMI was 67±7.3 years and 30.2±5.7, respectively. The quadratic-dose response curve started to plateau at approximately 112 nmol/L (44.8ng/mL) in patients receiving 3200 IU/d indicating no additional dose response on the 6 and 12 month curves. The authors found that the RDA in which 97.5% of persons achieved a 25(OH)D level >50nmol/L (20ng/mL) was a dosage of vitamin D3 between 400IU and 800IU/d and the EAR in which 50% of persons achieved 25(OH)D levels of 50nmol/L (20ng/mL) was 400 IU/d. Additionally, to reach a 25(OH)D level of >75nmol/L (30ng/ml) the RDA was 1600IU/day and the EAR was between 800 and 1600IU/d. Various covariates were analyzed and BMI was the only covariate found to be significant. After 12 months 25(OH)D levels were higher in normal weight women than overweight women by 12.2nmol/L (4.9ng/mL, P=0.003) and in obese women by 17.7nmol/L (7.1ng/mL, P<0.001) with no significant difference between the overweight and obese groups (P=0.089). A total of 11 serious adverse events occurred in 11 patients with none being attributed to vitamin D treatment. There were 16 occurrences of hypercalcemia (≥10.3mg/dL) and 48 occurrences of hypercalciuria (≥300mg/d) which returned to normal after repeated testing except for two participants who had to discontinue calcium supplements and one who had to discontinue calcium and vitamin D treatment.3
This was the first randomized, controlled, dose-response study of vitamin D3 in older white women. When interpreting the results, they ...