Vitamin D Supplements for Reducing Cancer Mortality

It all started with a famous study entitled “Do sunlight and vitamin D reduce the likelihood of colon cancer?” that was published in 1980. Johns Hopkins University researchers were trying to figure out why states like New Mexico and Arizona have only about half the colon cancer rates of states like New York, New Hampshire, and Vermont. Could it be because New Mexicans and Arizonans get so much more sun? The researchers proposed that perhaps vitamin D, known as the sunshine vitamin, is a protective factor against colon cancer. Since then, sun exposure has also been associated with lower rates of 14 other types of cancer.

As I discuss in my video Do Vitamin D Supplements Reduce the Risk of Dying from Cancer?, vitamin D may also affect cancer survival. Higher blood levels of vitamin D were associated with lower mortality of patients with colorectal cancer. How much lower? Nearly half the mortality. And, the higher the vitamin D levels, the lower the death rate appeared to fall. This may explain why the survival rate from colon cancer may depend in part “on the season of diagnosis.” The risk of rapid death is lowest if you’re diagnosed in the fall after you’ve spent the summer building up your vitamin D stores. Other risk factors could be seasonal, too. For example, perhaps people are taking advantage of the fall harvest and eating healthier, which might explain lower risk in the autumn. Additionally, “[a]lcohol intake is a risk factor and may be highest in the winter season…” What about physical activity? In the summer, we may be more likely to be outside running around, not only getting more sun, but also getting more exercise, which may itself be protective.

These kinds of studies just provide circumstantial evidence. Establishing a cause-and-effect relationship between colon cancer and vitamin D deficiency using observational studies is challenging because of confounding factors, such as exercise habits—so-called lurking variables. For example, there may be a tight correlation between ice cream sales and drowning deaths, but that doesn’t mean ice cream causes drowning. A more likely explanation is that there is a lurking third variable, like hot weather in summertime, that explains why drowning deaths are highest when ice cream consumption is also at its highest.

This actually happened with hormone replacement therapy. Women taking drugs like Premarin appeared to have 50 percent less risk of heart disease, so doctors prescribed it to women by the millions. But, if we dig a little deeper into the data, we find that, indeed, women taking estrogen had 50 percent lower risk of dying from heart disease, but they also had a 50 percent lower risk of dying from accidents and homicide, so it probably wasn’t the drug. The only way to know for sure is to put it to the test in a randomized, clinical trial, where half the women are given the drug and we see what happens. A decade later, such a study was done. Instead of having a 50 percent drop in risk, within a year of being given the hormone pills, heart attack and death rates shot up 50 percent. In retrospect, the lurking variable was likely socioeconomic class. Poor women are less likely to be prescribed hormone replacement therapy and more likely to be murdered and die of heart disease. Because of the lurking variable, a drug we now know to be dangerous had initially appeared to be protective.

Besides lurking variables, there’s also the possibility of reverse causation. Perhaps low vitamin D levels didn’t worsen the cancer. Instead, maybe the cancer worsened the vitamin D levels. This may be unlikely, since tumors don’t appear to directly affect vitamin D levels, but cancer treatment might. Even simple knee surgery can cause vitamin D levels to drop dramatically within hours, thought to be due simply to the inflammatory insult of cutting into someone. So, maybe that could help explain the link between lower vitamin D and lower survival. And, cancer patients may be spending less time running around the beach. So, yes: Higher vitamin D levels are associated with improved survival in colorectal cancer, and the same has been found for breast cancer. In fact, there is about double the risk of breast cancer recurrence and death in women with the lowest vitamin D levels. What’s more, higher vitamin D levels are associated with longer survival with ovarian cancer, as well as having better outcomes for other cancers like lymphoma. But, the bottom-line, as we learned with hormone replacement, is that we have to put it to the test. There weren’t a lot of randomized controlled trials on vitamin D supplements and cancer, however…until now.

We now have a few randomized controlled trials, and vitamin D supplements do indeed appear to reduce the risk of dying from cancer! What dose? Researchers suggest getting blood levels up to at least about 75 nanomoles per liter. These levels are not reached by as many as three-quarters of women with breast cancer nor achieved by a striking 97 percent of colon cancer patients .

Getting up to these kinds of levels—75 or, perhaps even better, 100 nanomoles—might require about 2000 to 4000 IU of vitamin D a day, levels of intake for which there appear to be no credible evidence of harm. Regardless of what the exact level is, the findings of these kinds of studies may have a profound influence on future cancer treatment.


What about just getting sun instead? Be sure to check out my six-part video series:

It’s better, of course, to prevent colon cancer in the first place. See, for example:

For more on that extraordinary story about Premarin and hormone replacement therapy, see How Did Doctors Not Know About the Risks of Hormone Therapy?

In health,
Michael Greger, M.D.

PS: If you haven’t yet, you can subscribe to my free videos here and watch my live, year-in-review presentations:

Why Did Doctors Keep Prescribing Cancer?

We’ve known about the role of estrogen in breast cancer going back to the 1800s, when surgical removal of the ovaries seemed to help in some cases. Ovaries were said to send out “mysterious” influences to the rest of the body, which were identified as estrogen in 1923. The medical profession jumped on this discovery and started injecting menopausal women by the thousands, and it was said that “[t]he ‘shot’ gives a ‘respectable’ hook on which to hang the visit to the doctor…” Soon, there were pills and patches, and medical journals like the Journal of the American Medical Association regaled doctors with ads I feature in my video How Did Doctors Not Know About the Risks of Hormone Therapy? on how they can “help the women to happiness by simply prescribing estrogen” and, “[w]hen women outlive their ovaries…,” there is Premarin.

As far back as the 1940s, concerns were raised that this practice might cause breast cancer, noting it would have been nice to figure this out before we started dosing women en masse. But breast cancer risk didn’t seem to matter as much, because heart disease was the number-one killer of women, reviews concluded, and because women taking hormones appeared to have lower heart attack rates, which would outweigh any additional breast cancer. However, women taking estrogen tended to be of a higher socioeconomic class, exercised more, and engaged in other healthy lifestyle changes like consuming more dietary fiber and getting their cholesterol checked. So, maybe that’s why women taking estrogen appeared to be protected from heart disease. Perhaps it had nothing to do with the drugs themselves. Despite the medical profession’s “enthusiasm for estrogen replacement therapy,” only a randomized clinical trial could really resolve this question. We would need to divide women into two groups, with half getting the hormones and half getting a placebo, and follow them out for a few years. There was no such study…until the 1990s, when the Women’s Health Initiative study was designed.

Wait a second. Why did it take the bulk of a century to decide to definitively study the safety of something prescribed to millions of women? Perhaps because there had never been a female director of the National Institutes of Health until then. “Just three weeks after being named NIH Director in 1991, [Bernadine Healy] went before Congress to announce, ‘We need a moon walk for women.’ That ‘moon walk’ took the form of the Women’s Health Initiative, the most definitive, far-reaching clinical trial of women’s health ever undertaken in the United States.”

The bombshell landed in summer 2002. There was so much more invasive breast cancer in the hormone users that they were forced to stop the study prematurely. What about heart disease? Wasn’t that supposed to balance things out? The women didn’t just have more breast cancer—they had more heart attacks, more strokes, and more blood clots to their lungs.

The news that women treated with hormone replacement therapy “experienced higher rates of breast cancer, cardiovascular disease, and overall harm has rocked women and physicians across the country.” Estrogen started out as the most prescribed drug in America before the study, but, after, the number of prescriptions dropped immediately and, within a year, so did the incidence of breast cancer in the United States.

The most important question about this story is why were we all so surprised? There had been “decades of repeated warnings” about the risks of cancer. In fact, the reason breast cancer patients had so much trouble suing the pharmaceutical company was that “the drugs have contained warning labels for decades.” And, with that disclosure, surely any reasonable physician would have included it in their risk and benefit discussions with their patients, right? It’s like the warning labels on packs of cigarettes. If you get lung cancer now, you should have known better. And, so, if you were on hormone replacement therapy and got breast cancer, don’t blame the drug company. They warned you about the risks, right there in the fine print.

Why didn’t more doctors warn their patients? Even after the study came out, millions of prescriptions continued to be dispensed. That’s a lot of cancer in our patients we caused, wrote one doctor. “How long will it take us to discard the financial gains, to admit that we are harming many of our patients, and to start changing our prescription habits?”

“Why did this practice continue in the face of mounting evidence of harm?” Well, it is a multibillion-dollar industry. “Despite an overwhelming amount of evidence to the contrary, many physicians still believe that estrogenic hormones have overall health benefits,” a “non-evidence-based perception [that] may be the result of decades of carefully orchestrated corporate influence on medical literature.” Indeed, “[d]ozens of ghostwritten reviews and commentaries published in medical journals and supplements were used to promote unproven benefits and downplay harms of menopausal hormone therapy…” PR companies were paid to write the articles that were then passed off as having been written by some expert.

What now? “Gynecologists must switch allegiance from eminence-based to evidence-based medicine.” In other words, they must consider what the science says and not just what some so-called expert says. It’s been said that the “current culture of gynecology encourages the dissemination of health advice based on advertising rather than science.”

“Women were placed in the way of harm by their physicians, who acted as unsuspecting patsies for the pharmaceutical companies.” If we really wanted to prevent heart attacks in women, simple lifestyle behaviors can eliminate more than 90 percent of heart attack risk. So, instead of being Big Pharma’s pawns, “recommending a healthful diet, increased exercise, and smoking cessation would truly benefit women’s health.”


The whole Premarin debacle speaks to the importance of putting purported therapies to the test (see, for example, Do Vitamin D Supplements Help with Diabetes, Weight Loss, and Blood Pressure?), as well as to the power of Big Pharma (Eliminating Conflicts of Interest in Medical Research), medical community collusion (American Medical Association Complicity with Big Tobacco), and my most series on mammograms.

What about Plant-Based Bioidentical Hormones and Soy Phytoestrogens for Menopause Hot Flashes? Check out the videos to find out.

In general, patients (and doctors) tend to wildly overestimate the efficacy of pills and procedures. See Why Prevention Is Worth a Ton of Cure and The Actual Benefit of Diet vs. Drugs.

Medical care, in general, may be the third leading cause of death in the United States. See How Doctors Responded to Being Named a Leading Killer.

In health,
Michael Greger, M.D.

PS: If you haven’t yet, you can subscribe to my free videos here and watch my live, year-in-review presentations:

The Effects of the Hops Phytoestrogen in Beer on Breast Cancer Risk

Hops have been used for centuries as a flavoring agent in beer, but “[o]ver the years, a recurring suggestion has been that hops”—and therefore beer—may be estrogenic, thanks to a potent phytoestrogen in hops called 8-PN, also known as hopein. Might beer drinking affect our hormones? I discuss this in my video What Are the Effects of the Hops Phytoestrogen in Beer?.

Even just the alcohol in beer can reduce testosterone levels in men, so when beer was tested as a source of estrogens, the alcohol was first removed. Researchers tested the equivalent of one can of beer every day for a month on the hormone levels of postmenopausal women, so as to not confound the results with her own estrogens, and they found significant alterations of hormonal levels during the beer month and then a return to baseline a week afterwards. But does this have any clinical effects, whether good or bad?

A cross-sectional study of about 1,700 women found that beer drinkers appear to have better bone density, perhaps because of the pro-estrogenic effects. They don’t recommend women start drinking beer for bone health, but suggest it may have beneficial bone effects for women who already drink.

What about helping with hot flashes? About half of postmenopausal and premenopausal women in the United States suffer from hot flashes, whereas the prevalence in Japan may be ten times lower, presumed to be because of their soy consumption. What about hops? There have been a few studies showing potential benefit, leading to a 2013 review suggesting that “hop extract may be somewhat effective in treating menopausal discomforts especially against hot flushes,” but that was before a study reported extraordinary results with about a half teaspoon of dried hop flowers. In the placebo group, the women started out having 23 hot flashes a week and continued to have 23 hot flashes a week throughout the three-month study. In the hops group, the women started out even worse with about 29 hot flashes a week, but then got down to 19 at the end of the first month, then 9, and finally just 1 hot flash a week. And similar findings were reported for all the other menopausal symptoms measured.

Animal estrogens work, too. Millions of women used to be on horse hormones—Premarin, from pregnant mares’ urine. That drug also took care of hot flashes, as well as  curtailed osteoporosis, but caused a pesky little side effect called breast cancer. Thankfully, when this was realized and millions of women stopped taking it, breast cancer rates fell in countries around the world.

The question, then, is: Are the estrogens in hops more like the breast cancer-promoting horse estrogens or the breast cancer-preventing soy estrogens? The key to understanding the health-protective potential of soy phytoestrogens is understanding the difference between the two types of estrogen receptors, alpha receptors and beta receptors. Unlike animal estrogen, the soy phytoestrogens bind preferentially to the beta receptors, and in breast tissue, they’re like yin and yang with the alpha receptors signaling breast cell proliferation. This explains why horse hormones increase breast cancer risk, whereas the beta receptors, where the soy binds, oppose that proliferative impact. So, do the hops phytoestrogens prefer beta, too? No. 8-PN is a selective estrogen receptor alpha promoter. “Surprisingly and in clear contrast to genistein [the soy], 8-PN is a much weaker” binder of beta than of alpha. So, that explains why hops is such a common ingredient in so-called breast enhancing supplements—that is, because it acts more like estrogen estrogen. Given the breast cancer concerns, use of such products should be discouraged, but just drinking beer could provide the exposure to the hops estrogen, which could help explain why beer may be more carcinogenic to the breast than some other forms of alcohol.


A phytoestrogen in beer? For more on the background of this issue, see The Most Potent Phytoestrogen Is in Beer.

Other videos on phytoestrogen include:

To learn more about dietary effects on testosterone, see:

What about “natural” hormones for menopause? See my video Plant-Based Bioidentical Hormones.

For more on the risks of alcohol in terms of breast cancer risk, see Breast Cancer and Alcohol: How Much Is Safe? and Breast Cancer Risk: Red Wine vs. White Wine.

In health,
Michael Greger, M.D.

PS: If you haven’t yet, you can subscribe to my free videos here and watch my live, year-in-review presentations: