Chapter 10

Furthering Science’s Knowledge of Vitamin D

In This Chapter

Understanding how research studies work

Finding out about a comprehensive study

Our understanding of the nonbone roles for vitamin D is in its infancy. Researchers have a great deal to learn about what vitamin D does and doesn’t do, how much of it is necessary for all its functions, and how best to take it. As you read this, studies are ongoing to answer all these questions and more.

In this chapter, I explain how researchers conduct studies to figure out how vitamin D affects our bodies. Then I tell you about one of the largest vitamin D studies ever undertaken. I predict that the results of that study will be analyzed for decades after the study ends.

After you read this chapter, I think you’ll be impressed by the amount of work it takes to research vitamin D and health. If you’ve read any magazines, newspapers, or blogs recently about vitamin D, you know that there’s some serious disagreement about what is the optimal amount of vitamin D needed to protect all aspects of health. Researchers are taking this idea very, very seriously. Many studies include vitamin D levels higher than the current recommendations, so in a few short years we’ll have clear answers to a lot of questions about vitamin D and health. But that’s the way science works — it’s the ultimate put-up-or-shut-up world. When you have the scientific evidence, you win the argument!

You may ask, “What’s the point of doing all these studies if it turns out that vitamin D isn’t all it’s cracked up to be?” The famous inventor Thomas Alva Edison had the answer to that. Someone once remarked on the huge number of failures Edison had encountered in his search for a new storage battery: He conducted 50,000 experiments before he achieved results. “Results?” said the inventor. “Why, I’ve gotten a lot of results. I know 50,000 things that won’t work.”

Seeing the Importance of Research Studies

Through the mechanism of research studies, scientists determine the way the body works and how external factors such as diet, exercise, toxins, or drugs affect our health.

In Chapter 2, I told you how an expert committee formed by the Institute of Medicine set new dietary requirements for vitamin D based upon what we know about the effect of vitamin D on bone. These new recommendations were announced in November 2010 and formally published in early 2011. The committee members felt that there wasn’t enough information from nonbone issues like diabetes, cancer, or autoimmune diseases for them to reliably set a vitamin D intake requirement to prevent those diseases. These studies still need to be done.

Also, remember that there are specific requirements for different age groups, from babies to adults, and for pregnant and lactating women. Researchers will have to do studies on each of these groups for every important health outcome to get the information we need to set requirements. And it’s a longer road than you might think — the expert panel felt that this information was missing in certain age groups for bone, too. Because of this, the research panel’s conclusions related to protecting bone in some age groups can be considered the “best guess” based on the currently available evidence. Future research may determine whether the panel’s recommendations need to be revised upward or downward.

How research studies work

There is a common misconception about the purpose of research. Many people think that scientists do research studies to prove something is true. In actuality, the goal of research is to challenge ideas and to try to prove that something is wrong. By doing it this way, an idea has to survive the test of time. That’s also why when an idea hasn’t been fully challenged, scientists don’t fully accept it.

So how does this apply to vitamin D?

Scientists first come up with an idea worth challenging, such as “an increase of vitamin D is the reason people who live closer to the equator are protected from diseases like colon cancer.” It’s an interesting idea and it makes sense based on what we know about the capability of skin to make vitamin D when exposed to UVB light. But an idea isn’t proof — the relationship between location and disease is too indirect. For example, people who live closer to the equator eat differently than people in colder climates; they may be more active; or they might be different based on one of a hundred other reasons.

So next they ask, “Do serum 25-hydroxyvitamin D or vitamin D intake levels associate with colon cancer risk?” This idea gets people closer to a real relationship, but this still isn’t enough. Higher 25-hydroxyvitamin D levels may just be a marker for more outdoor activity, and exercise is protective against a number of chronic diseases. Also, a standard needs to be set for when to measure serum vitamin D levels to make a good relationship between vitamin D and colon cancer. If you just look at people who have colon cancer and then find that they have low vitamin D levels, does that mean low vitamin D status causes colon cancer? Or that colon cancer lowers vitamin D status?

These examples show just a few problems with these types of studies, and there are many others.

The types of population-based associations that I’ve been describing sometimes can seem stronger if there’s a good reason to think that vitamin D will affect the tissue or disease in question. For example, in 1980 when Frank and Cedric Garland first proposed that high vitamin D status could prevent colon cancer, it didn’t fit into the idea of vitamin D affecting bone health, so it wasn’t embraced as an idea; however, researchers did basic cell culture studies and found that calcitriol (active vitamin D) could stop the growth of cancer cells and encourage them to die. After that, they did studies in animals to see what effect calcitriol or complete vitamin D deficiency could do to the development of colon cancer. This is useful proof of principle that there may be a mechanistic reason for protection. But they still have to translate this type of information into humans — as humans, we don’t consume calcitriol, but rather regular vitamin D that has to be metabolized to turn into 25-hydroxyvitamin D and then into calcitriol. And people are rarely severely vitamin D deficient, so we need to know if more relevant levels of vitamin D status are helpful against colon cancer.

This leads us to the final type of study, the one that really challenges the ideas that vitamin D protects against colon cancer. This is a clinical intervention trial. These aren’t easy to do, especially for a disease like colon cancer. For example, if a researcher wants to test whether raising vitamin D status prevents the development of colon cancer, he has to start the study before the people studied have already developed the disease. Because the disease takes decades to develop, that might not even be possible.

An alternative approach to prevention studies is that a researcher may want to know if raising vitamin D status alters the course of the disease in those who already have it, or makes other treatments more effective. That’s more achievable, so I use that as an example in this chapter.

In this case, the scientists have to get people with colon cancer to volunteer for the study. They need a lot of people to make sure that their study results are accurate. Then they need to find out how much vitamin D their volunteers have in their system. They do this because a study might get a different result in people with low vitamin D status versus people with high vitamin D status. After that the volunteers will get assigned to treatments. They need a control group — people who don’t get any vitamin D; then they need several doses of vitamin D. This lets the researchers determine the exact relationship between vitamin D intake or serum 25-hydroxyvitamin D and the effect on colon cancer. The best of these studies are done so that neither the volunteer nor the research team knows what treatment is given. This is called a double-blind study and is done so no one’s preconceived notions affect the outcome of the research.

Researchers then regularly obtain vitamin D levels from the subjects until the level is reached or until some predetermined date. After that, the researchers compare the groups and then break the code to determine who got which amount. In this way, they know exactly whether higher vitamin D intake can help slow colon cancer as well as exactly how much vitamin D is effective.

Participating in research studies

Studies constantly need volunteers to participate in them. Some of the studies mentioned in this chapter are closed to new subjects, but others are still recruiting, and new studies arise frequently. If you want to participate in a research study, you can find announcements for clinical studies at universities and major medical centers.

Just so you don’t get worried, the National Institutes of Health (NIH, the medical research wing of the U.S. federal government) and Health Canada to the north set rules to protect volunteers in research studies. Basically, they have to tell you everything that they know will happen during the study, and you have to willingly agree to it all. This is called informed consent. The NIH and Health Canada are so serious about protecting volunteers that if a researcher breaks the rules, his research lab can be shut down, and he could even go to jail.

If you decide to participate in a research study, you need to know a few points:

Every study has criteria for admission that you have to pass. For example, you may have to be a certain age or a certain sex, or you may need to have or not have a certain condition.

Most studies require lots of regular testing of the blood, so be prepared to be stuck with needles.

You may or may not get the treatment that they’re testing. Neither you nor the researcher performing the study will know what you’re receiving until the end of the study. (Of course, the code can be broken in case of emergencies, for example, if you’re severely ill and it’s important to know what you were receiving.)

Generally participation doesn’t involve a monetary reward. You may have your expenses reimbursed, and other medications or tests might be covered during the trial, but you won’t be paid. Your pay is the knowledge that you’re advancing science.

Where can you find information about these studies? The NIH has a website called the NIH RePORTER (http://projectreporter.nih.gov/reporter.cfm). This is a searchable database that allows you to see a brief description of any study that is supported by the NIH. Other groups might fund research on vitamin D, but the NIH is the biggest one. Later in this chapter I tell you about some of the studies that I found in the NIH RePORTER as well as others I learned about in other places.

A Big Vitamin D Study That’s Trying to Do Everything

One of the big criticisms of most clinical studies on vitamin D is that they don’t have enough people to be sure that the question has been adequately tested. For example, if a study is small and has a positive outcome, the results may not apply to a broader group of people; if the outcome is negative, it may be because the study wasn’t long enough or the effect was smaller than the study could detect. That shouldn’t be a problem after a huge study being conducted through Harvard University is completed.

The VITAL study — or Vitamin D and Omega-3 fatty acid supplementation trial — will recruit 20,000 men and women who are over 60 years old. They’ll give people one of four treatments: a placebo; 2,000 IU of vitamin D; 1 gram of omega-3 fatty acids; or the vitamin D combined with the omega-3 fatty acids. This means at least 5,000 people will get just vitamin D! This study will take at least five years, but my guess is that if they find some interesting things, they’ll follow the outcome of this study even longer.

You might wonder what outcomes they’re going to measure. A better question might be what aren’t they going to measure? Although the main study goals are to see what vitamin D does to the development of various cancers, a huge team of people is going to ask about the role of vitamin D in

Fractures

Inflammation and joint pain

Lung conditions like asthma, pneumonia, and COPD

Heart disease and stroke

Diabetes-related conditions

This is a huge, comprehensive study that’s going to tell us a lot about whether improving vitamin D intake can help prevent a large number of chronic diseases. Although this study is great, it’s not perfect. This is just older adults, so we won’t know how vitamin D affects kids, teens, or young adults. Also, there’s only one dose of vitamin D, so it won’t be perfect for setting a requirement. I mention this not to get you disappointed about the study but just to show you that even a great study that’s, well, huge, is still just one piece of the big picture scientists are trying to paint about vitamin D and health.