Vitamin D and Cancer Risk Archives - Health Tips From The Professor

Does Vitamin D Supplementation Reduce Cancer Deaths?

October 22, 2019 by Dr. Steve Chaney

Why Are Vitamin D Studies So Confusing?

Author: Dr. Stephen Chaney

Does vitamin D supplementation reduce cancer deaths?

When 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 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?

This 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 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?

[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.

- They 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?

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.

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.

The Truth About Vitamin D

December 11, 2018 by Dr. Steve Chaney

Does Vitamin D Reduce Risk Of Heart Disease & Cancer?

Author: Dr. Stephen Chaney

You have every right to be confused. One day you are told that vitamin D reduces your risk of heart disease and cancer. The next day you are told vitamin D makes has no effect on those diseases. You are told vitamin D is a waste of money. What should you believe? What is the truth about vitamin D?

In mid-November a major clinical study called VITAL was published. It examined the effect of vitamin D and omega-3s on heart disease and cancer risk. Last week I wrote about the omega-3 portion of the study. This week I will cover the vitamin D portion of the study.

Once again, if you rely on the media for your information on supplementation, you are probably confused. Headlines ranged from “Vitamin D Is Ineffective For Preventing Cancer And Heart Disease to “Vitamin D Lowers Odds Of Cancer Death.” What is the truth?

The problem is that reporters aren’t scientists. They don’t know how to interpret clinical studies. What they report is filtered through their personal biases. That is why I take the time to carefully evaluate the clinical studies, so I can provide you with accurate information. Let me sort through the dueling headlines and give you the truth about vitamin D, cancer, and heart disease.

How Was The Study Designed?

The VITAL study (JE Manson et al, New England Journal of Medicine, DOI: 10.1056/NEJMoa1811403) enrolled 25,871 healthy adults (average age = 67) in the United States. The study participants were 50% female, 50% male, and 20% African American. None of the participants had preexisting cancer or heart disease. The characteristics of the study group were typical of the American population at that age, namely:

The average BMI was 28, which means that most of the participants were significantly overweight.
7% of them had diabetes.

Study participants were given questionnaires on enrollment to assess clinical and lifestyle factors including dietary intake. Blood samples were taken from about 65% of the participants to determine 25-hydroxyvitamin D levels (a measure of vitamin D status) at baseline and at the end of the first year. The participants were given either 2,000 IU of vitamin D/day or a placebo and followed for an average of 5.3 years.

There were two important characteristics of the participants in this study that may have influenced the outcome.

The average 25-hydroxyvitamin D level of participants at the beginning of the study was 31 ng/ml (78 nmol/L). The NIH considers 20-50 ng/ml (50-125 nmol/L) to be the optimal level of 25-hydroxyvitamin D for most physiological functions. This means that study participants started in the middle of the optimal range with respect to vitamin D status.

[Note: The NIH defines the 20-50 ng/ml range as “adequate.” However, I know many of my readers like to aim beyond adequate to reach what they consider to be “optimal.” In the case of vitamin D, that might not be a good idea. The NIH considers anything above 50 ng/ml as associated “with potentially adverse effects.” For that reason, I will refer to the 20-50 ng/ml range as optimal for this article. I wouldn’t want to encourage my readers to be aiming for above 50 ng/ml.]

Only 12.7% of participants had 25-hydroxyvitamin D levels below 20 ng/ml, which the NIH considers to be inadequate. The results with this group were not statistically different from the study participants with optimal vitamin D status, but it is not clear that there were enough people in this subgroup for a statistically valid comparison with participants starting with an optimal vitamin D status.
At the end of the first year, 25-hydroxyvitamin D levels in the treatment group increased to 42 ng/ml (105 nmol/L), which is near the upper end of the optimal range. Thus, for most of the participants, the study was evaluating whether there was a benefit of increasing vitamin D status from the middle to the upper end of the optimal range.
The study allowed subjects to continue taking supplements that contained up to 800 IU of vitamin D. While the authors tried to correct for this statistically, it is a confounding variable.

Does Vitamin D Reduce The Risk Of Cancer?

You may remember from last week that omega-3s were more effective for reducing heart disease risk than for reducing cancer risk. What is the truth about vitamin D and cancer risk? The results are reversed for vitamin D, so I will discuss cancer first.

The study reported that vitamin D supplementation did not reduce a diagnosis of invasive cancer of any type, breast cancer, prostate cancer, or colon cancer during the 5.3-year time-period of this study. This was the result that was reported in the abstract and was what lazy journalists, who never read past the abstract, reported.

However, the rest of the study was more positive. For example, occurrence of invasive cancer of any type was reduced by:

23% in African-Americans.
24% in patients with a healthy body weight.

Several previous studies have suggested that vitamin D may be more effective at preventing cancer in people with a healthy body weight, but the mechanism of this effect is currently unknown.

Most previous studies have not included enough African-Americans to determine whether they respond more favorably to vitamin D supplementation. However, African-Americans have a higher risk of cancer, so this finding deserves follow-up.

In addition, when the study looked at deaths from cancer, the results were very positive. For example:

Cancer deaths during the 5.3-year study period were reduced by 17%.
The longer vitamin D supplementation was continued the more effective it became at reducing cancer deaths. For example,
When the authors excluded cancer deaths occurring during the first year of supplementation, vitamin D reduced cancer deaths by 21%.
When the authors excluded cancer deaths occurring during the first two years of supplementation, vitamin D reduced cancer deaths by 25%.

Finally, no side effects were noted in the vitamin D group.

Does Vitamin D Reduce The Risk Of Heart Disease?

The VITAL study also looked at the effect of vitamin D on heart disease risk. What is the truth about vitamin D and heart disease? The results from this study were uniformly negative. There was no effect of vitamin D supplementation on all major cardiovascular events combined, heart attack, stroke, or death from heart disease. Does that mean vitamin D has no role in reducing heart disease risk? That’s not clear.

The authors had a thought-provoking explanation for why the results were negative for heart disease, but positive for cancer. Remember that the participants in this trial started with a 25-hydroxyvitamin D level of 31 ng/ml and increased it to at least 42 ng/ml with vitamin D supplementation.

The authors stated that previous studies have suggested the 25-hydroxyvitamin D level associated with the lowest risk for heart disease is between 20 and 25 ng/ml. If that is true, most of the participants in this trial were already in the lowest possible risk for heart disease with respect to vitamin D status before the study even started. There would be no reason to expect additional vitamin D to further reduce their risk of heart disease.

In contrast, the authors said that previous studies suggest the 25-hydroxyvitamin D level associated with the lowest risk of cancer deaths is above 30 ng/ml. If that is true, it would explain why vitamin D supplementation in this study was effective at reducing cancer deaths.

However, previous placebo-controlled clinical studies have also been inconclusive with respect to vitamin D and heart disease. My recommendation would be to think of adequate vitamin D status as part of a holistic approach to reducing heart disease – one that includes a heart-healthy diet and a heart-healthy lifestyle – rather than a “magic bullet” that decreases heart disease risk by itself.

As for heart-healthy diets, I discuss the pros and cons of various diets in my book, “Slaying The Food Myths.” As I discuss in my book, the weight of scientific evidence supports primarily plant-based diets that include omega-3s as heart healthy. As an example, the Mediterranean diet is primarily plant-based and is rich in healthy oils like olive oil and omega-3s. It is associated with reduced risk of both heart disease and cancer.

What Is The Truth About Vitamin D?

There is a lot of confusion around the question of whether vitamin D reduces the risk of cancer. This study strengthened previous observation suggesting that vitamin D supplementation decreases cancer deaths. However, it is also consistent with previous studies that have failed to find an effect of vitamin D on cancer development. How can we understand this apparent discrepancy? The authors provided a logical explanation. They pointed out that:

Cancer development takes 20-30 years while this clinical study lasted only 5.3 years. That means that vitamin D supplementation only occurred at the tail end of the cancer development process. In fact, the cancer was already there in most of the patients in the study who developed cancer. It just had not been diagnosed yet. In the words of the authors: “Given the long latency for cancer development, extended follow-up is necessary to fully ascertain potential effects [of vitamin D supplementation].”
In contrast, none of the patients had been diagnosed with cancer when they entered the trial. That means that the patients were diagnosed with cancer during the 5.3-year study period. They were receiving extra vitamin D during the entire period of cancer treatment. Thus, the effect of vitamin D on reducing cancer deaths was easier to detect.

What Does This Study Mean For You?

Vitamin D Is Likely To Decrease Your Risk Of Dying From Cancer: When you combine the results of this study with what we already know about vitamin D and cancer, the results are clear. Vitamin D appears to reduce your risk of dying from cancer. More importantly, the longer you have been supplementing with vitamin D, the greater your risk reduction is likely to be.

Vitamin D May Decrease Your Risk Of Developing Cancer: Association studies suggest that optimal vitamin D status is associated with decreased cancer risk, especially colon cancer risk. However, the long time for cancer development means that we may never be able to prove this effect through double-blind, placebo-controlled clinical trials.

Holistic Is Best: When you combine the VITAL study results with what we already know about vitamin D and heart disease, it appears that supplementing with vitamin D is unlikely to reduce your risk of developing heart disease unless you are vitamin D deficient. However, a holistic approach that starts with a healthy, primarily plant-based diet and makes sure your vitamin D status is adequate is likely to be effective.

The same is likely true for cancer. While the latest study suggests that vitamin D supplementation reduces your risk of dying from cancer, those vitamin D supplements are likely to be even more effective if you also adopt a healthy diet and lifestyle.

How Much Vitamin D Do You Need? The optimal dose of vitamin D is likely to be different for each of us. One of the things we have learned in recent years is that there are significant differences in the efficiency with which we convert vitamin D from diet and/or sun exposure into the active form of vitamin D in our cells. Fortunately, the blood test for 25-hydroxyvitamin D is readily available and is widely considered to be an excellent measure of our vitamin D status.

I recommend that you have your blood level of 25-hydroxyvitamin D tested on an annual basis. Based on the best currently available data, I recommend you aim for >20 ng/ml (50 nmol/L) if you wish to minimize your risk of heart disease and >30 ng/ml (75 nmol/L) if you wish to minimize your risk of cancer. If you can achieve those levels through diet and a multivitamin supplement, that is great. If not, I would recommend adding a vitamin D supplement until those levels are achieved.

Finally, you shouldn’t think of vitamin D as a magic bullet. If you are a couch potato and eat sodas and junk food, don’t expect vitamin D to protect you from cancer and heart disease. You should think of maintaining adequate 25-hydroxyvitamin D levels as just one component of a holistic approach to healthy, disease-free living.

The Bottom Line

There is a lot of confusion around the question of whether vitamin D reduces the risk of cancer and heart disease. A major clinical study has just been published that sheds light on these important questions. It reported:

Vitamin D did not decrease the risk of developing cancer during the 5.3-year study duration. The authors pointed out that cancer takes 20-30 years to develop, which means their study was probably too short to detect an effect of vitamin D on the risk of developing cancer.
Vitamin D did decrease the risk of dying from cancer, and the longer people were supplementing with vitamin D the bigger the protective effect of vitamin D was.
Vitamin D did not decrease the risk of heart disease. However, most study participants had a level of 25-hydroxyvitamin D that was optimal for reducing the risk of heart disease at the beginning of the study. There was no reason to expect that extra vitamin D would provide additional benefit.
With respect to both cancer and heart disease the best advice is to:
- Get your 25-hydroxyvitamin D levels tested on an annual basis and supplement, if necessary, to keep your 25-hydroxyvitamin D levels in what the NIH considers to be an adequate range (20-50 ng/ml).
- We do not have good dose response data for the beneficial effects of vitamin D on heart disease and cancer. However, according to this article, previous studies suggest you may want to am for 25-hydroxyvitamin D levels above 20 ng/ml to reduce the risk of heart disease and above 30 ng/ml to reduce your risk of cancer.
- Consider vitamin D as just one component of a holistic approach to healthy, disease-free living.

For more details about the interpretation of these studies and what they mean for you, 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.

Vitamin D and Cancer Risk?

May 8, 2018 by Dr. Steve Chaney

Does Vitamin D Reduce Cancer Risk?

Author: Dr. Stephen Chaney

The relationship between vitamin D and cancer risk is controversial. Some studies suggest that vitamin D reduces cancer risk. In those studies, the risk reduction was strongest for colon cancer, lung cancer, and breast cancer. However, other studies have found no association between vitamin D status and cancer risk.

Most previous studies have been conducted in European and American populations. Very few of the studies have been done in Asian populations. So, the authors of the current study (S. Budhathoki et al, BMJ 2018; 360:k671, doi: 10.1136/bmj.k671 ) focused their attention on the Japanese population.

How Was The Study Done?

The data for this study were drawn from the much larger Japanese Public Health Center (JPHC) Study. THE JPHC Study is an ongoing study investigating the role of lifestyle and other factors on the risk of cancer and other diseases. The study began in 1990 and enrolled 140, 420 participants aged 40-59.

All participants in the JPHC study filled out a detailed food frequency questionnaire at the time of entry into the study. A subset of participants also donated blood upon entry into the study for determination of 25-hydroxyvitamin D levels (the most reliable measurement of vitamin D status). It is this subset of participants who formed the basis of the current study.

There were 33,736 participants in this study. Based on plasma 25-hydroxyvitamin D levels at entry into the study, the participants were divided into four groups of around 1000 participants.

Group 1 had a median serum 25-hydroxyvitamin D level of 36.9 nmol/L.
Group 2 had a median serum 25-hydroxyvitamin D level 48.4 nmol/L.
Group 3 had a median serum 25-hydroxyvitamin D level of 56.9 nmol/L.
Group 4 had a median serum 25-hydroxyvitamin D level of 72.6 nmol/L.

For reference, the NIH considers < 30 nmol/L to be deficient, 30 to < 50 nmol/L to be insufficient for bone and overall health, > 50 nmol/L to be sufficient, and > 150 nmol/L to be potentially associated with adverse effects. By these criteria, group 1 had insufficient serum levels of 25-hydroxyvitamin D, group 2 was borderline, and groups 3 and 4 had sufficient serum levels of 25-hydroxyvitamin D.

The participants were followed for a total of 19 years. During this time 3301 participants developed cancer. The cancer incidence in groups 2, 3 and 4 were compared to the cancer incidence in group 1 to determine the effect of vitamin D status on cancer risk.

Vitamin D and Cancer Risk

The results of the Vitamin D and cancer risk study were:

Vitamin D reduced total cancer risk by up to 25%.
Vitamin D reduced the risk of liver cancer by up to 55%.
Vitamin D reduced the risk of pre-menopausal breast cancer by up to 44%.
There was a trend towards reduction of colon, liver, and prostate cancer by vitamin D, but the results did not quite reach significance.
There were too few cases for most other cancers to assess whether vitamin D status had any effect.
Risk reduction was not linear. Except for liver cancer, risk reduction for group 4 (72.6 nmol/L) was not greater than the risk reduction for group 3 (56.9 nmol/L). The significance of this observation will be discussed below.

The authors concluded: “Our findings support the hypothesis that vitamin D may confer protection against cancer. Nevertheless, the lower risk associated with higher circulating vitamin D concentrations seemed to show a ceiling effect, which may suggest that although maintaining an optimal 25-hydroxyvitamin D concentration is important for prevention of cancer, having a concentration beyond this optimal level may provide no further benefit.”

Why Is The Association of Vitamin D And Cancer Risk So Confusing?

So why do some studies demonstrate confusing data on Vitamin D and cancer risk? The “ceiling effect” mentioned by the authors of this study may explain much of the variation in results from previous trials. As I say in my upcoming book, “Slaying The Supplement Myths” , supplementation is most likely to be effective when the subjects are deficient in that nutrient at the beginning of the study. If they are starting with adequate levels of the nutrient, supplementation is unlikely to provide additional benefit.

While that statement seems to be obvious, many previous studies have ignored the beginning nutritional status. Some have not measured 25-hydroxyvitamin D levels at the beginning of the study. Others have measured starting 25-hydroxyvitamin levels but have not considered the starting levels in interpretation of their data.

Group 1 in the current study clearly had inadequate 25-hydroxyvitamin D levels. That may be why the groups with sufficient 25-hydroxyvitamin D levels showed a reduction in risk. The low baseline 25-hydroxyvitamin D is logical because most of Japan lies north of the United States, so sun exposure is less. In addition, the authors stated that food fortification and supplementation with vitamin D is much less in Japan than the US. In contrast, the baseline 25-hydroxyvitamin D status in many US studies is significantly higher.

The authors did a thorough analysis of previous studies. In general, studies with a low baseline level of 25-hydroxyvitamin D showed a reduction in cancer risk by vitamin D. Studies with a higher baseline level of 25-hydroxyvitamin D showed no effect.

This analysis does not permit a definitive conclusion, but it clearly defines how future studies should be designed. Simply put, to reliably test whether vitamin D reduces cancer risk, the experiment must be designed in such a way that the baseline 25-hydroxyvitamin D level is in the inadequate range. Otherwise, there is no reason to expect that higher levels of 25-hydroxyvitamin D will confer any benefit.

The Bottom Line:

A recent study looked at the effect of vitamin D status (serum 25-hydroxyvitaminD levels) on cancer risk. The study reported:

Vitamin D reduced total cancer risk by up to 25%.
Vitamin D reduced the risk of liver cancer by up to 55%.
Vitamin D reduced the risk of pre-menopausal breast cancer by up to 44%.
There was a trend towards reduction of colon, liver, and prostate cancer by vitamin D, but the results did not quite reach significance.
There were too few cases for most other cancers to assess whether vitamin D status had any effect.
Risk reduction was not linear. Except for liver cancer, risk reduction for group 4 (72.6 nmol/L) was not greater than the risk reduction for group 3 (56.9 nmol/L).

The “ceiling effect” mentioned by the authors of this study may explain much of the variation in results from previous trials.

For more details, 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.