A new paper from Bischoff-Ferrari, et al., published last week, studied 200 home-dwelling men and women, over the age of 70, in Zurich, Switzerland. The purpose of the study was to assess whether vitamin D prevented falls in the elderly. The participants were divided into three groups which received monthly doses of vitamin D: 24,000 IU; 60,000 IU; or 24,000 IU of vitamin D3 plus 300 μg of calcifediol (25-Hydroxy vitamin D3). 
Bischoff-Ferrari stated in her discussion, "the physiology behind a possible detrimental effect of a high monthly bolus dose of vitamin D on muscle function and falls remains unclear and needs further investigation." Also, her final conclusion was not that vitamin D would not help seniors, but that high monthly bolus dosing was not the right approach. Instead, she proposes a new study using daily dosing.

In Defense of Vitamin D

While the paper from University Hospital Zurich has received a lot of press, the results of that trial do not surprise us at GrassrootsHealth as it might have several years ago. More information is now known about the importance of daily dosing versus monthly dosing than was known at the time the study took place. In order to prevent falls, you need strong muscles in addition to strong bones. For vitamin D to be effective in aiding muscle strength, stability and for general disease prevention you need to take it daily - not monthly.

In an effort to help evaluate research, what constitutes an effective study and what constitutes an ineffective study, Drs. Bruce Hollis and Robert Heaney joined together for a presentation which we will share with you.

Daily vs. Monthly Dosing

Bruce Hollis, PhD, of the Medical University of South Carolina has researched vitamin D and its effects on both the endocrine (skeletal) and autocrine (disease reduction and immune control) systems. He has found that that while 25(OH)D, the vitamin D metabolite that is measured in the blood as a marker of vitamin D status and is important for the endocrine system, has a half-life of 3-4 weeks, vitamin D3 has a half-life of only 24 hours. This distinction is important because it is the vitamin D3 delivered directly to the tissues of the body through the autocrine system that allows those tissues to convert the vitamin D3 to its active form as needed to help regulate cellular functions.  In order to achieve positive results for muscle strength or preventive health - you need to keep vitamin D in your autocrine system - you need to take it daily.

Please watch this webinar if you would like more detail. Hollis thoroughly explains how vitamin D supplementation is processed by both the endocrine and autocrine systems. He reviews clinical trials that have had success or failure and correlates their results with their dosing strategy. After watching this webinar you will understand why the high monthly doses did not help the elderly in the Zurich study.

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Read summary of webinar in past newsletter

Effective vs. Ineffective Clinical Trials

Robert Heaney, MD, has spent much of his career doing research on vitamin D and other nutrients. He recently published a paper with Guidelines for nutrients (see sidebar). In order to have an effective vitamin D study you need:

1. An understanding of how dosing affects the physiological systems - for vitamin D this means daily dosing for any non-skeletal body function studies.
2. Basal nutrient status must be determined and used as an inclusion criterion - this means that when designing vitamin D studies you need to start with deficient people (< 20 ng/ml) to show a positive result.
3. The change in intake must be large enough to change nutrient status meaningfully - meaning for vitamin D they should aim for large daily doses in at least one group.
4. Change in status must be quantified - for vitamin D studies to be valid the difference in 25(OH)D from the baseline level to the final level as a result of treatment must be measured.
5. Change in nutrient status, not change in intake, must be the independent variable in the hypothesis - for vitamin D this means analyzing the study results based on the change in measured 25(OH)D levels rather than just assigned dosage groups.
6. Co-nutrient status must be optimized - i.e. for vitamin D studies subjects also need adequate Calcium, Magnesium and protein consumption.
7. An understanding of the nutrient response curve to be able to define the appropriate amount of the nutrient that reduces risk - for a valid study you need to test over the range of the curve where you expect response changes, for vitamin D this is typically somewhere between 10 ng/ml - 60 ng/ml.

Below is an analysis of the Zurich study using the criteria Robert Heaney defines in his paper, Guidelines for optimizing design and analysis of clinical studies of nutrient effects.

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If you want to understand this information further we recommend you watch this presentation from our last seminar, Design Components of Interventions/Studies of Vitamin D.

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