Does Vitamin D Supplementation Reduce Cancer Deaths?

Why Are Vitamin D Studies So Confusing?

Author: Dr. Stephen Chaney

 

Does vitamin D supplementation reduce cancer deaths?

vitamin d supplementationWhen I was in graduate school (which was just a few decades ago), vitamin D was thought to be important for healthy bones and teeth, and that was about it. Its role in calcium metabolism was well established, but we knew little else about its role(s) in the body. In fact, we were taught we knew all we needed to know about vitamin D.

Shortly after I graduated, it was discovered that almost every cell in our body had vitamin D receptors, and vitamin D research exploded. A few years ago, vitamin D appeared to be almost magic. Studies suggested that it:

  • Strengthened the immune system.
  • Prevented autoimmune diseases like type 1 diabetes and multiple sclerosis.
  • Reduced the risk of cancer and heart disease.
  • Helped regulate insulin levels and aided in type 2 diabetes management.
  • Supported the health of our lungs, brain, and nervous system.

Those were the headlines that you saw in the news and still see in Dr. Strangelove’s health blogs.

However, when these early studies were followed by a series of double-blind, placebo controlled clinical trials, the only benefit that was consistently validated was the strengthening of our immune system.

That has led to a series of headlines and posts in medical blogs saying things like: “Vitamin D supplements are worthless” and “You should stop taking your vitamin D supplements.”

“What is a person to believe? Why is it so confusing?”

In this week’s issue of “Health Tips From the Professor” I discuss a recent study confirming that vitamin D reduces cancer deaths. But before I do that, I will cover what I call “Vitamin D Metabolism 101” to put this week’s topic into context. Later in the article, I will discuss why vitamin D studies are so confusing.

Vitamin D Metabolism 101

 

There are two things you need to know about vitamin D metabolism to understand today’s article:

  • vitamin d supplementation 101Vitamin D occurs in two forms, D3 and D2. Vitamin D3 is the form of vitamin D that our body makes when sunlight hits our skin. Vitamin D2 is a structurally similar analog derived from yeast. For years we thought that vitamin D3 and D2 were equivalent. Vitamin D2 was less expensive, so it was one most often used in supplements.
  • Vitamin D is inactive. It needs to be activated by the body. It is first converted to 25-hydroxyvitamin D, which is the most abundant form of vitamin D in the bloodstream. It is then taken up by our cells and converted to 1,25-dihydroxyvitamin D, which is the active form. There are two things you need to know about this.
    • Since 25-hydroxyvitamin D is found in the blood, it is used as a marker to determine the vitamin D status in the body.
    • Recent studies suggest that vitamin D3 is more readily activated than vitamin D2, so it has become the preferred choice for supplementation. The result of this recent conversion from D2 to D3 means that older studies on vitamin D supplementation were primarily done with D2 while newer studies were primarily done with D3.

 

How Was The Study Done?

scientific studyThis study (Y Zhang et al, BMJ, 366:I4673, 2019  ) was a meta-analysis of 52 clinical trials with 75,454 participants looking at the relationship between vitamin D supplementation cancer deaths, heart disease deaths, and deaths due to any cause.

All the clinical trials were intervention studies in which vitamin D supplementation was compared to either a placebo or no treatment. All participants were adults over the age of 18 and without any pre-existing health conditions. The meta-analysis excluded studies if:

  • Any participants had pre-existing health conditions.
  • Any participants were pregnant or lactating women.
  • Calcium was included along with vitamin D unless both the treatment and placebo groups were given the same amount of calcium.

 

Does Vitamin D Supplementation Reduce Cancer Deaths?

The results of the study were:

  • vitamin d supplementation reduce cancer deathsVitamin D supplementation reduced cancer deaths by 16%. This difference was statistically significant. And:
    • This effect was only seen with vitamin D3 supplementation, not with vitamin D2 supplementation.
    • The reduction in cancer deaths by vitamin D was only seen in clinical trials that lasted more than 3 years but was not seen in shorter clinical trials.
  • Vitamin D supplementation did not reduce heart disease deaths. However:
    • Weaknesses in the clinical trials included in this meta-analysis made it virtually impossible to determine whether vitamin D supplementation influenced heart disease deaths or not.
  • Vitamin D supplementation did not significantly reduce death from all causes. However:
    • Death from all causes was significantly less in studies using vitamin D3 than in studies in studies using vitamin D2.
    • Death from all causes was significantly lower in clinical trials with a longer duration.

 

Why Are Vitamin D Studies So Confusing?

strengths weaknesses[Note: This section is a bit technical, so if you aren’t really interested in why vitamin D studies are confusing, you can just skip this section.]

To understand why vitamin D studies are so confusing, it is important to look at vitamin D research from a historical perspective.

Vitamin D research, like most nutrition research, starts with association studies. Association studies have suggested that vitamin D deficiency significantly increases the risk of heart disease and cancer and slightly increased the risk of death from any cause. However, association studies have their strengths and weaknesses. For example:

Strengths:

  • Association studies can follow large groups of people for a long time.
  • Association studies are particularly good at identifying the long-term effects of nutritional patterns (such as vitamin D deficiency) on health outcomes.

Weaknesses:

  • Association studies cannot prove cause and effect, so they are usually followed by intervention studies, such as the ones included in this meta-analysis.

However, intervention studies and this meta-analysis also have their own strengths and weaknesses.

Strengths: The strengths of this meta-analysis are the sample size (52 clinical trials, 75,454 participants) and the rigorous criteria for inclusion of studies in the meta-analysis.

Weaknesses: There are three kinds of weaknesses associated with this study.

  • Weaknesses of Meta-Analysis Studies: A meta-analysis increases statistical power by combining multiple studies. However, these studies do have weaknesses. For example:
    • The strength of the meta-analysis is only as good as the strength of the individual studies that go into it. This is the “garbage in – garbage out” phenomenon.
    • The individual studies use different amounts of vitamin D for different lengths of time. So, this meta-analysis is unable to tell you how much supplemental vitamin D would be required to lower your cancer risk.
  • Weaknesses of Intervention Studies: Double-blind, placebo-controlled intervention studies are considered the “gold standard” for evidence-based medicine. However, they also have their own weaknesses.
    • thumbs down symbolThey are usually small. This limits their statistical power to see small effects.
    • They are usually short.
      • This is a problem for studies looking at disease outcomes because most major diseases like heart disease or cancer develop over decades. Intervention studies like the ones included in this meta-analysis are simply too short to determine whether vitamin D supplementation could prevent those diseases.
      • It is also a problem for heart disease deaths because they often occur a decade or more after diagnosis. Thus, it is not surprising that the intervention studies included in this meta-analysis have failed to confirm an association between vitamin D and heart disease deaths.
      • However, most cancer deaths occur within the first 2-5 years after diagnosis. So, it is not surprising that intervention studies lasting 3 years or more have been able to confirm an association between vitamin D and cancer deaths.
  • Weaknesses of Studies With Popular Supplements: Once the benefits of certain nutrients show up in the headlines, people start taking those supplements. This has become a big problem for studies with vitamin D and omega-3 fatty acids. For example:
    • > 75% of Americans take a multivitamin with vitamin D, and an additional 18% of adults over 50 also take a vitamin D supplement.
    • In this meta-analysis more than half of the participants had a baseline 25-hydroxyvitamin D level of > 50 nmol/L, which the NIH considers to be adequate, prior to supplementation.
  • That means most of these studies were not asking whether correcting a vitamin D deficiency reduced the risk of death. They were asking whether giving a vitamin D supplement to someone whose vitamin D status was already adequate had any additional benefit. In this context:
    • Previous association studies have suggested that a 25-hydroxyvitamin D level of 50 nmol/L is enough to reduce heart disease deaths. Since most of the participants in the clinical trials included in this study started with this level prior to supplementation, it is not surprising that this study found no benefit of vitamin D supplementation on heart disease deaths.
    • However, previous association studies have suggested that a 25-hydroxyvitamin D level of 75 nmol/L or greater is required to reduce cancer deaths. Thus, it is not surprising that this and other studies have been able to show that vitamin D supplementation reduces cancer deaths.

In short, these weaknesses in intervention studies have made it virtually impossible to determine whether vitamin D supplementation influences heart disease deaths. Unfortunately, a meta-analysis like this one is only as good as the intervention studies that go into it. This is the “garbage in – garbage out” phenomenon.

However, those weaknesses did not apply to cancer deaths. This and other studies make a strong case that vitamin D supplementation does reduce cancer deaths.

 

What Does This Study Mean For You?

what does vitamin d supplementation mean for youAssociation studies have suggested that vitamin D deficiency significantly increases the risk of heart disease and cancer and slightly increased the risk of death from any cause.

  • This study confirms vitamin D supplementation significantly decreases cancer deaths as predicted from association studies. This observation is strengthened by two other major clinical studies in recent months that have come to the same conclusion. I reported on one of them in a recent issue of “Health Tips From The Professor.”
  • This study does not indicate an optimal dosage, but the recent VITAL study) reported that 2,000 IU of vitamin D/day was effective at reducing the risk of cancer deaths.
  • The authors of this study concluded that vitamin D supplementation has no effect on heart disease deaths. However:
  • It would be more accurate to say that weaknesses in the design of the intervention trials included in their study made it virtually impossible to determine whether vitamin D supplementation influenced heart disease deaths.
  • To adequately assess whether vitamin D reduced heart disease deaths one would need to start with a population that was deficient in vitamin D and supplement with vitamin D for 5 years or more. That kind of study has not been performed.
  • The data on whether vitamin D reduces the risk of dying from any cause is less clear.
  • This study reported that vitamin D supplementation decreased the risk of death from any cause by a non-significant 2%.
  • Two other recent meta-analyses reported that vitamin D supplementation did have a significant effect on the risk of dying from any cause. However, the risk reduction was 3% in one study and 4% in the other study.
  • Clearly, vitamin D supplementation is not going to help you live to 100.

 

The Bottom Line

 

Previous association studies have suggested that vitamin D deficiency significantly increases the risk of heart disease and cancer and slightly increased the risk of death from any cause.

A recent meta-analysis of 52 clinical trials with 75,454 participants tested those predictions by looking at the effect of vitamin D supplementation on cancer deaths, heart disease deaths, and deaths due to any cause. All the clinical trials were intervention studies in which vitamin D supplementation was compared to either a placebo or no treatment. All participants were adults over the age of 18 and without any pre-existing health conditions.

The results of this meta-analysis were:

  • Vitamin D supplementation reduced cancer deaths by 16%. This difference was statistically significant. And:
  • This effect was only seen with vitamin D3 supplementation, not with vitamin D2 supplementation.
  • The effect of vitamin D supplementation on cancer deaths is strengthened by two other major clinical studies in recent months that have come to the same conclusion.
  • This study did not indicate an optimal dosage, but the recent VITAL study reported that 2,000 IU of vitamin D/day was effective at reducing the risk of cancer deaths.
  • Vitamin D supplementation did not reduce heart disease deaths. However:
  • Weaknesses in the clinical trials included in this meta-analysis made it virtually impossible to determine whether vitamin D supplementation influenced heart disease deaths or not.
  • Vitamin D supplementation did not significantly reduce death from all causes. However:
  • Death from all causes was significantly less in studies using vitamin D3 than in studies using vitamin D2.
  • Death from all causes was significantly lower in clinical trials with a longer duration.

For more details on the study and what it means for you, read the article above. Also, if you would like to understand why there is so much confusion about vitamin D’s health benefits, it is also discussed in the article above.

 

These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure or prevent any disease.

Are Vitamin D Supplements Worthless?

Are We Asking The Right Question?

Author: Dr. Stephen Chaney

 

are vitamin d supplements worthlessWe have been told that vitamin D is a miraculous “must have” vitamin. We have been told it’s not just important for healthy bones. It’s also important for a strong immune system, heart health, protection from cancer, and many other health benefits. We have been told that we should get our 25-hydroxy vitamin D levels tested and supplement with extra vitamin D if they are low.

Now, the latest headlines are saying all of that is wrong. They are telling us vitamin D supplements do not improve bone density or protect against falls and bone fractures. They are telling us to forget all the other claimed benefits of vitamin D. Those claims have been disproved. Forget about the 25-hydroxy vitamin D tests. They are a waste of money.

What is the truth? Why is it so confusing? Are vitamin D supplements worthless?  Let me guide you through the claims and counterclaims so you can discover the truth for yourself.

How Did Vitamin D Become So Popular?

are vitamin d supplements worthless popularLet’s start with a brief history of vitamin D. It all started with the industrial revolution in Northern Europe. Suddenly, children and adults in the large cities were spending the bulk of their waking hours in dark factories rather than outdoors on the farm. They were already living in northern latitudes where sunlight was weak during the winter months. To make matters worse pollution from the factories was creating a haze that blocked the sunlight.

That lead directly to the discovery that sunlight was crucial to our body’s ability to synthesize vitamin D and that vitamin D was essential for building strong bones. The solution to the public health crisis of rickets and osteomalacia was to fortify dairy products with vitamin D. The almost universal adaptation of vitamin D fortification virtually eliminated rickets and osteomalacia except in association with certain rare diseases. The two important lessons learned from this experience were:

  • Vitamin D is essential for healthy bone formation.
  • Vitamin D supplementation improves bone health for individuals who are deficient in vitamin D

As we discuss the latest findings, we need to keep in mind that these fundamental principles have not changed.

In the late 20th century our understanding of vitamin D took another leap with the discovery that vitamin D receptors were not restricted to bone cells. Almost every cell in our body contained vitamin D receptors. That lead to studies showing that people with low vitamin D intakes were more likely to experience heart disease, cancer, some autoimmune diseases, and infectious diseases such as flu than people with high vitamin D intakes.

The final leap in our understanding of vitamin D took place when the medical profession started routinely testing blood levels of 25-hydroxy vitamin D. That is when we discovered that some people who appeared to have adequate intake of vitamin D and/or adequate exposure to sunlight had low blood levels of 25-hydroxy vitamin D. Furthermore, follow-up studies showed that low 25-hydroxyvitamin D levels correlated with an increased risk of heart disease, cancer, and infectious disease. The important lessons learned from these experiments were:

  • Vitamin D deficiency is associated with increased risk of multiple diseases.
  • 25-hydroxy vitamin D tests are the best way to measure vitamin D deficiency.

Once again, these fundamental principles have not changed.

What Did The Study Show?

are vitamin d supplements worthless studyThe study (MJ Bolland et al, Lancet Diabetes Endocrinology 2018) behind the headlines was a meta-analysis of 81 randomized, placebo-controlled studies with a total of 53,537 subjects that looked at the effect of vitamin D supplementation in elderly populations on bone mineral density, bone fractures, and falls.

The meta-analysis only included studies in which vitamin D intake was the sole variable. In many cases the subjects were not taking a calcium supplement. If they were taking a calcium supplement, both the vitamin D group and placebo group were taking the same amount of calcium.

 

The results were unequivocal. In this study vitamin D supplementation had no effect on bone mineral density, bone fractures, or falls in elderly populations. The authors concluded “There is little justification to use vitamin D supplements to maintain or improve musculoskeletal health.”

 

Is this conclusion justified? Let’s put the findings of this study into a broader perspective.

 

Are We Asking The Right Questions?

are vitamin d supplements worthless holistic approachBefore throwing out our vitamin D supplements let’s ask whether this study is asking the right question. I have covered this topic in detail in my new book “Slaying The Supplement Myths” (https://slayingthesupplementmyths.com) with respect to similar studies that had called into question the value of calcium supplements for bone health. Let me cover the highlights here.

In my book I created the graphic on the right to put the question of who benefits from supplementation into perspective. For the purposes of this discussion, I will just focus on poor diet (or, in the case of vitamin D, poor exposure to sunlight). As I discussed above, science shows that people who are not getting enough vitamin D from diet and sunlight benefit from vitamin D supplementation. Unfortunately, vitamin D enthusiasts and some supplement companies have muddied the waters by going beyond what good science shows and suggesting or implying that everyone will benefit from vitamin D supplementation.

This is part of the problem. Once you have created a paradigm that everyone will benefit from vitamin D supplementation, that paradigm is easy to disprove. If someone already has adequate, or nearly adequate, levels of 25-hydroxy vitamin D, would we expect additional vitamin D to make a difference? Of course not, but that is exactly the question the most recent study was asking.

In discussing the limitations of their study, the authors said: “It is possible that trials of populations with low baseline 25-hydroxy vitamin D might produce different results because only 4 trials, involving 831 participants (1.6% of all participants), reported mean baseline 25-hydroxy vitamin D levels lower than 25 nmol/L (the level indicating vitamin D deficiency).

In other words, the study did not measure the effect of vitamin D supplementation for people who were vitamin D deficient. The only take-home lesson from this study is that people with adequate, or near adequate, vitamin D status do not benefit from vitamin D supplementation. That is a “no-brainer.”

 

Vitamin D And A Bone Healthy Lifestyle

are vitamin d supplements worthless garbage in outThe other glaring deficiency of this study is that it was only measuring the effect of vitamin D on bone health. They purposely excluded any other factor that might influence bone health. That was a fatal flaw because healthy bone requires a holistic approach, not individual nutrients. In my book Slaying the Supplement Myths  I refer to this as a “bone healthy lifestyle.”

The most important feature of a “bone healthy lifestyle” is this:

  • Calcium, vitamin D, and resistance (weight bearing) exercise are all essential for healthy bones.
  • However, none of them is sufficient by itself. You need all three. You need a holistic approach if you wish to build strong bones.

Simply put, that means unless you include adequate calcium and exercise there is no reason to expect vitamin D supplementation to help build strong bones. Unfortunately, none of the studies included in the recent meta-analysis took a holistic approach to bone health. Some included calcium, but many didn’t. Resistance exercise was never considered. The studies were doomed to failure.

When you include flawed studies in your meta-analysis, you have what computer programmers call “Garbage in. Garbage out.” A meta-analysis can never be stronger than the individual studies it includes.

Other features of a “bone healthy lifestyle” include:

  • We need more than calcium and vitamin D for strong bones. We need magnesium, zinc, copper, manganese, vitamin C and vitamin K. If we are deficient in any of these, calcium will not be utilized as efficiently.
  • The foods we eat are also important. Our bones serve as a buffer system to keep our bodies slightly alkaline. Every time we eat acid-forming foods a little bit of bone is dissolved to neutralize the acid. For optimal bone health we need to minimize acid-forming foods and eat more alkaline-forming foods. That means we need to avoid sodas, sweets and refined grains. We also need to minimize meats, eggs, and dairy. Instead, we should focus on fruits, vegetables, peas, beans, lentils, seeds, and nuts.
  • Beware of drugs. The list of common medications that dissolve bones is a long one. Some of the worst offenders are anti-inflammatory steroids such as cortisone and prednisone, drugs to treat depression, drugs to treat acid reflux, and excess thyroid hormone. I am not suggesting that you should avoid properly prescribed medications. I would suggest you ask your doctor or pharmacist whether the drugs you are taking adversely affect bone density. If they do, you should pay a lot more attention to the other aspects of a “bone healthy lifestyle.”

 

Are Vitamin D Supplements Worthless?

are vitamin d supplements worthless bone healthNow we can come back to the question “Are vitamin D supplements worthless?” as the recent headlines have suggested. If you phrase the question as “Does everyone benefit from vitamin D supplementation?” or “Is vitamin D supplementation alone sufficient to build strong bones?” the answer is a clear no.

However, those are the wrong questions. If you ask: “Does vitamin D supplementation benefit people who are vitamin D-deficient?” the answer is a clear yes. If you ask: “Does a holistic approach that includes resistance exercise, adequate calcium, and adequate vitamin D improve bone health?” the answer is likely to be yes as well.

What about the headlines claiming that vitamin D is also worthless for strengthening the immune system and reducing the risk of heart disease, cancer, and auto-immune diseases?  The studies on which these claims are based suffer from the same flaws. They are asking the same wrong questions.

My recommendations:

  • Have your blood levels of 25-hydroxy vitamin D tested on a regular basis. I have them tested each year when I get my physical.
  • If your blood levels of 25-hydroxy vitamin D are below 25 nmol/L (which the NIH considers deficient), you are likely to benefit from vitamin D supplementation. If they are above 50 nmol/L (which the NIH considers sufficient), vitamin D supplementation is unlikely to provide additional benefit. However, that level of vitamin D doesn’t guarantee that you will have strong bones. You also need sufficient calcium and resistance exercise.
  • If your blood levels are in the insufficient range (between 25 nmol/L and 50 nmol/L), the situation is more complicated. If you are close to 50 nmol/L, you may benefit slightly from adding a vitamin D supplement, but the benefit will be too small to show up in a clinical study such as the one that resulted in the recent headlines. My advice is to look at your diet and medication use. If they put you at risk for low bone density, my recommendation would be to add a vitamin D supplement – along with adequate calcium and resistance exercise, of course. If you are closer to 25 nmol/L, you will likely benefit from a vitamin D supplement along with adequate calcium and exercise.
  • Don’t think of vitamin D supplementation as a “magic bullet” that will solve all your ills. Instead, think of it as just one component of a holistic approach to a bone healthy lifestyle.

 

The Bottom Line

 

A recent meta-analysis concluded that vitamin D supplementation did not improve bone mineral density, reduce bone fractures, or reduce falls in the elderly. While this conclusion was definitive, the study was asking the wrong questions.

  • We know that vitamin D improves bone health for people who are vitamin D-deficient. However, only 1.6% of the people in this study were vitamin D-deficient at the beginning of the study. That means the study was really asking: “If people have adequate, or near adequate, vitamin D status, does vitamin D supplementation provide any additional benefit?”  The answer to that question is a “no-brainer.”  There is no reason to expect that additional vitamin D would provide benefit.
  • We know that while vitamin D is essential for building strong bones, it is not sufficient by itself. Strong bones require a holistic approach that includes resistance exercise, adequate calcium, and adequate vitamin D. However, this study only looked at the effect of vitamin D on bone health. Calcium and exercise were excluded from consideration. That means the study was really asking: “Is vitamin D a “magic bullet” that can build strong bones by itself?” Again, there is no reason to expect vitamin D to provide much benefit under those conditions.

My recommendations:

  • Have your blood levels of 25-hydroxy vitamin D tested on a regular basis. I have them tested each year when I get my physical.
  • If your blood levels of 25-hydroxy vitamin D are low, you are likely to benefit from vitamin D supplementation. If they are already optimal, vitamin D supplementation is unlikely to provide additional benefit.
  • Don’t think of vitamin D supplementation as a “magic bullet” that will keep your bones strong by itself. Instead, think of it as just one component of a holistic “bone healthy lifestyle.”

 

For more details and to see my detailed recommendations, read the article above.

 

These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure or prevent any disease.

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