Dose response to vitamin d supplementation in postmenopausal women: a randomized trial.

Ann Intern Med. 2012 Mar 20;156(6):425-37.
Gallagher JC jcg at creighton.edu, Sai A, Templin T 2nd, Smith L.
Bone Metabolism Unit, Creighton University School of Medicine, and College of Public Health, University of Nebraska Medical Center, Omaha, Nebraska.

Background: Serum 25-hydroxyvitamin D (25-[OH]D) is considered the best biomarker of clinical vitamin D status.

Objective: 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-[OH]D 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).

Design: Randomized, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00472823)

Setting: Creighton University Medical Center, Omaha, Nebraska.

Participants: 163 healthy postmenopausal white women with vitamin D insufficiency enrolled in the winter or spring of 2007 to 2008 and followed for 1 year.

Intervention: 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.

Measurements: The primary outcomes were 25-(OH)D and PTH levels at 6 and 12 months.

Results: 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.

Limitation: Findings may not be generalizable to other age groups or persons with substantial comorbid conditions.

Conclusion: 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.

Obese had less response to the same vitamin D dose (perhaps just due to extra weight)

Primary Funding Source: National Institute on Aging.

PMID: 22431675
PDF of study is attached at bottom of this page
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Clips from listing for this Clinical Trial

Vitamin D Supplementation in Older Women (VIDOS)

Purpose

The purpose of this study is to examine the effects of several doses of vitamin D on hormones related to bone, calcium absorption, bone density and muscle strength.
Condition Intervention
Osteoporosis

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Determination of RDA for Vitamin D in Caucasian and African American Women {not reported on here}

Detailed Description:

The prevalence of osteoporosis is high in the United States, with about 10 million people over the age of 50 already having the disease and another 34 million at risk for developing it. Development of low-cost and effective strategies is important for preventing osteoporosis and reducing osteoporotic fractures. A simple inexpensive strategy to prevent osteoporosis is adequate nutrition with calcium and vitamin D. Serum 25OHD (25-hydroxyvitamin D) is now accepted as the objective measure of vitamin D nutrition. There is a growing understanding that serum 25OHD concentrations of at least 30-32 ng/ml are needed for optimal bone health at which serum parathyroid hormone (PTH) concentrations reach a minimum.

There are no systematic prospective dose response studies aimed at determining the optimum amount of vitamin D intake required to maintain optimum serum 25OHD levels in the population which will help in determining the estimated average requirement (EAR) and recommended dietary requirement (RDA) for vitamin D. More work to determine the RDA for vitamin D has been recommended by the Panel on Calcium and Related Nutrients of the Food and Nutrition Board. This study is aimed at filling the information gap by concentrating on the high risk group of postmenopausal women. We are testing the theory that increasing serum 25OHD to a level greater than 30 ng/ml will reduce serum PTH in the high risk group of vitamin D insufficient postmenopausal women with an adequate intake of calcium. We also believe that the dose of vitamin D that will achieve this level is approximately 4400 IU per day, which is well above the suggested adequate intake of 400-600 ID recommended for the elderly.

In a one year double blind, randomized prospective clinical trial, we will examine the dose response effect of supplementation with different doses of vitamin D3 (400, 800, 1600, 2400, 3200, 4000, 4800IU/day) on the primary outcomes of serum 25OHD and PTH in 160 postmenopausal Caucasian and 160 African American women {we assume will be reported on later} who have inadequate vitamin D levels in winter. We expect that the results from this study will add useful and important information about the RDA for vitamin D for postmenopausal women who are more susceptible to osteoporosis. The results from this study will also help in designing future clinical trials to study the effect of vitamin D, for example in preventing fractures, falls, cancer.

The main objective of the current proposal is to study the effect of increasing doses of vitamin D3 in the high risk group of postmenopausal Caucasian and African American women with hypovitaminosis D (serum 25OHD <20 ng/ml) in winter in presence of sufficient calcium intake, in order to determine the Estimated Average Requirement (EAR) that covers 50% and the Recommended Daily allowance (RDA) covers 97.5% of population for vitamin D. We will use a serum 25OHD concentration equal >30 ng/ml and normalization of serum PTH as indicators of adequacy. We expect that the results from this proposal will add important information helpful in designing future larger clinical trials to determine the recommended dietary allowance (RDA) for vitamin D in other ethnic groups and designing clinical trials on the effect of vitamin D on falls and fractures.

We hypothesize that increasing serum 25OHD to a level greater than 30 ng/ml with vitamin D supplements in 97 percent of the study subjects will reduce serum PTH and bone markers to premenopausal range. We postulate that the RDA of vitamin D that will achieve a serum 25OHD of ? 30 ng/ml in 97.5% of women during winter is approximately 4400 IU/d and the EAR dose of vitamin D is between 800-1000 IU.

The specific aims of the proposal are,

• To examine the dose response effect of vitamin D3, 400, 800, 1600, 2400, 3200, 4000, and 4800 IU /d in postmenopausal Caucasian and African American women with hypovitaminosis D (serum 25OHD equal <20 ng/ml) in winter plus an adequate calcium intake compared to a calcium control group, on serum 25OHD and PTH levels, which constitute our primary outcome measures.
• To determine the EAR and RDA for postmenopausal women by establishing the dose of vitamin D3 that will increase serum 25OHD above 30 ng/ml in 97.5% of study subjects in winter and reduce serum PTH to the normal premenopausal range.
• To study the dose response effect of vitamin D3 on calcium absorption, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) serum calcium, serum bone markers, bone mineral density (BMD) and falls (only in elderly) (the secondary outcome measures)
• To establish the long term safety of these doses relating to hypercalcemia and hypercalciuria

Progress: Caucasian enrollment completed July 2008; African American enrollment continuing

Eligibility

Ages Eligible for Study: 57 Years and older
Genders Eligible for Study: Female
Accepts Healthy Volunteers: No

Inclusion Criteria:

At least 7 years post-menopause
Serum 25OHD level 5 ng/ml to 20 ng/ml
BMI less than or equal to 40 kg/m2
Willing to discontinue multivitamins that contain vitamin D during the study

Exclusion Criteria:

Cancer (except basal cell carcinoma) or terminal illness
Previous hip fracture
Hemiplegia (paralysis of one side of the body)
Uncontrolled type I diabetes or fasting blood sugar greater than 140 mg in type II
Kidney stones more than twice in a lifetime
Chronic renal failure
Evidence of chronic liver disease, including alcoholism
Physical conditions such as severe osteoarthritis, rheumatoid arthritis, heart failure severe enough to prevent reasonable physical activity
Previous treatment with bisphosphonates (more that 3 months), PTH or PTH derivatives, (e.g. Teriparatide or Fluoride) in the last 6 months
Previous treatment within the last 6 months with calcitonin or estrogen
Chronic high dose corticosteroid therapy (more than 10 mg per day) for over 6 months and not within the last 6 months
Anticonvulsant therapy
High dose thiazide therapy (more than 37.5 mg)
24 hour urine calcium greater than 290 mg on 2 baseline tests
Serum calcium exceeding upper normal limit on 2 baseline tests
Bone Mineral Density T-score less than -3.0 for spine or hip
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See also Vitamin D Life

• Is 50 ng of vitamin D too high, just right, or not enough
• All items in category How Much Vitamin D 211 items as of March 2012
• Overview Vitamin D Dose-Response
  14,000 IU to get 50 ng, lots of graphs
• Overview How Much vitamin D
• Calcium bioavailability and how much to take
• Must balance co-factors when increasing vitamin D which has the following graphs

The amount of Calcium intake in this study (1200 to 1400 mg) was borderline or in the dangerous region reported by previous studies

Additional reasons that they did not seem to consider for having low response to vitamin D CLICK HERE for entire list

Soft drink cola - uses up Calcium which uses up vitamin D
Some drugs consume or block vitamin D
   Antiseizure, Prednisone, AIDS drugs, Orlistat, Questran, Dilatin, Phenobarbital, Rifampin, Steroids, Calcium channel blockers
   Cholestyramine, Mineral Oil, , St Johns wort
Use of polyunsaturated fats decreased bio-availablity of vitamin D
Less Magnesium in foods - Magnesium is needed to utilize vitamin D (as well as build bones)
Undergoing Chemotherapy
Have MS prevented AND treated by vitamin D, a mountain of evidence
Had a condition which Prevents Adsorption in the gut
Had Bariatric Surgery
Colon Cancer more than 10 years before
IBD UC and CD at risk of being vitamin D deficient
Have +Gluten Intolerance
Have Celiac Disease
Have HIV both prevents conversion and consumes vitamin D
Have a condition which requires more vitamin D - or time in the sun
Surgery and trauma within the past year