In our last post, we introduced the latest publication using the VITAL trial data, authored by LeBoff et al., titled “Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults.” This publication concluded that vitamin D supplementation did not reduce the risk of fracture compared to placebo among their study population, and the publicity that followed prompted many to question the usefulness of vitamin D in general.

We discussed the importance of looking at the “Totality of Evidence” when making decisions for our health based on research, as well as how to identify whether specific study criteria were met when conducting and reporting on nutrient research. Following these criteria can be essential to providing accurate and reliable study results, especially when it comes to vitamin D.

Before digging into each of the specific nutrient study criteria, a key concept to understanding their importance can be illustrated by the following nutrient response curves. Understanding this curve is important to be able to define the appropriate amount of the nutrient that reduces risk of a specific health outcome. (This concept is described in detail in the “Nutrition and Medicine Webinar” by Dr. Robert Heaney, from approximately 10:36 to 18:35.)

The way the body responds to most nutrients can be described by an ‘S’ shaped curve, or Sigmoid Response Curve.

The curve shows how a change in a nutrient’s intake or status affects a particular body system, with the x-axis representing the nutrient intake or status, and the y-axis representing the response or benefit seen within that body system. When observing the nutrient response curve, the following can be seen:

For example, consider the effect of vitamin D on bone strength:

Let’s say bones require a vitamin D level of 30 ng/ml (75 nmol/L) to reach their maximum bone strength. Any change in vitamin D status from below 30 ng/ml up to 30 ng/ml might show added benefit (increased bone strength), however, the amount of benefit seen will depend on the starting vitamin D level. If going from 12 ng/ml or lower up to 30 ng/ml, one would expect to see the greatest increase in bone strength. However, if going from 25 ng/ml up to 30 ng/ml, very minimal benefit will be seen, since most of the benefit had already been achieved at the starting level.

Most nutrients have many different functions within the body, with response curves varying by system (such as skeletal vs immune) and nutrient responses varying with basal (baseline) and achieved nutrient status, dose/intake, and system-specific sensitivity. For example, the skeletal benefits of vitamin D (to prevent rickets) are seen at much lower levels, while cancer prevention benefits are seen at much higher levels.

This next chart builds on this concept by illustrating examples of system-specific responses of a given nutrient to a given intake or dose.

Let’s imagine the curves in the chart below represent the need of vitamin D (intake/resulting serum level) to carry out specific functions within the skeletal system (curve A), during pregnancy (curve B), and within the immune system (curve C). The same change in a given intake or serum level will have varying effects in each system, as shown by each curve. When considering a specific intake or change, that same dose/change in level may produce a measurable response in one system (as illustrated by the green arrow with curve ‘A,’ representing bone strength) and a null response in another system (as illustrated by the red arrow with curve ‘C,’ representing the immune response).

The Disease Incidence Prevention (DIP) Chart was one of the first graphics created by GrassrootsHealth to illustrate this concept for vitamin D. The DIP chart summarizes the percent of disease reduction for specific conditions by achieved vitamin D level, based on data from 15 peer-reviewed, published papers. It uses a reference level of 25 ng/ml, which means that the percentage reductions are based on raising levels from 25 ng/ml to the amount showing the percentage reduction. (25 ng/ml is the average vitamin D level in the US and Canada).

This concept is further described for the top diseases known to be major causes of death, based on a review of the strongest evidence published to date, in a recent paper by Grant et al..

Now that we have a clear understanding of the concepts above, let’s take a look at a couple of the nutrient study criteria and apply them to the LeBoff paper on fracture risk and vitamin D.

Measuring vitamin D levels at the beginning of a study is essential to defining a starting point, telling the researchers how much vitamin D participants are already getting (from supplements as well as sun/UVB and food), and whether they might already be getting enough to fulfill certain needs within the body. Baseline vitamin D status should therefore be an inclusion criterion, with the study enrolling only participants with deficient vitamin D levels, or levels below a known response range for the desired outcome (typically below 20 ng/ml or 50 nmol/L for bone health).

Vitamin D levels were measured at baseline for 16,757 of the 25,871 participants (this part of this criteria was therefore only met for some of the participants). However, for those who did have a baseline vitamin D level, it was not used as part of the study inclusion criteria (criteria not met). As stated in the study abstract, “Participants were not recruited on the basis of vitamin D deficiency, low bone mass, or osteoporosis.” In fact, the average baseline vitamin D level for the participants who did have a baseline vitamin D level, including those in the placebo group, was 31 ng/ml – which is already considered sufficient for bone health (see the Zhu et al. study, which found a 39% lower risk of hip fracture and a 30% lower risk of fracture-related hospitalization for participants with vitamin D levels of at least 30 ng/ml versus below 20 ng/ml).

While baseline vitamin D level was measured for some of the participants, follow-up levels were only measured for 2,655 participants. This makes determining a change in nutrient status (and meeting Criteria #4 – covered in Part 3) impossible for a majority of the participants in the study.

Don’t ever consider a situation too late to take steps for correcting or avoiding vitamin D deficiency. Measuring your vitamin D level and calculating a supplementation amount to help reach and maintain a target level, or taking loading doses to correct deficiency faster, could possibly make all the difference in how a current disease situation progresses. Test your level now!

Create your custom home blood spot kit by adding any of the following measurements, along with your vitamin D:

Did you know that each of the above can be measured at home using a simple blood spot test? As part of our ongoing research project, you can order your home blood spot test kit to get your levels, followed by education and steps to take to help you reach your optimal target levels. Start by enrolling and ordering your kit to measure each of the above important markers, and make sure you are in a healthy range of each!

The eBook, Vitamin D & COVID-19, A Summary of Published Research, is a condensed and concise compilation of much of the published research on vitamin D and COVID-19, easy to read and share as a downloadable, printable PDF. Your purchase helps to further public knowledge and education of this invaluable research! Be sure to educate yourself on the benefits and importance of vitamin D for immune health, and take steps to ensure you and your loved ones are getting enough.

Don't get stuck with low vitamin D levels - learn more about what might affect your level and response to supplementation, and the steps to take through each season to keep levels in your target range.

Have a beautiful and HEALTHY day.

Onwards,