Vitamin D and cancer: The difference between cranks and mainstream science

Despite the diatribes that appear here on a regular basis bemoaning the unscientific and sometimes dangerous claims made for so-called "alternative medicine" modalities, I'll be among the first to admit that in some cases it's not always clear what is "alternative" about some therapies. Indeed, there seems to be an intentional effort to "rebrand" some aspects of conventional medicine as being "alternative." Because these methods have a scientific rationale and at least some evidence that they work, by successfully marketing them as "alternative," woo-meisters can then point to them as effective and, by implication, try to claim that the real woo, such as homeopathy, must be effective. Perhaps the prime example of conventional medical interventions that have been coopted by "alternative" medical practitioners is nutritional supplementation.

However, in coopting the tools of the evil and hated "allopaths," it's not enough just to suggest what "allopathy" says about nutritional supplements. For one thing, such claims would be far too modest. For another thing, they'd be far too boring. No, alties have to distinguish themselves from "allopaths"; otherwise they'd too similar. This is where they descend into crankery. What they do is to take what are usually relatively modest or uncertain findings of conventional science and then blow up the claims far beyond what is supported by science, a distortion that can sometimes get as outlandish as claims that megadoses of vitamin C will cure cancer. Usually, these claims are accompanied by paranoid ramblings about how (pick three or more) big pharma, the NIH, the CDC, the AMA, the FDA, and the Illuminati are "suppressing" information about the benefits of these supplements, because supposedly big pharma can't patent them or make money about them. (I'm only half-kidding about the Illuminati, by the way, and never mind that big pharma is moving into the supplement business in a big way lately.)

In looking over the overheated and overblown claims of one particularly rabid woo-meister, namely Mike Adams of NewsTarget, I've learned of the latest and greatest favored supplement, Vitamin D. Given the amazing claims that Mike Adams makes on a routine basis for this vitamin and inspired by a recent news article about a study casting doubt upon whether vitamin D prevents cancer, I thought I'd take a look at (1) the peer-reviewed article upon which Adams bases this claim and (2) a more recent peer-reviewed article.

First, let's look at the sorts of things that Mike Adams claims:

Exciting new research conducted at the Creighton University School of Medicine in Nebraska has revealed that supplementing with vitamin D and calcium can reduce your risk of cancer by an astonishing 77 percent. This includes breast cancer, colon cancer, skin cancer and other forms of cancer. This research provides strong new evidence that vitamin D is the single most effective medicine against cancer, far outpacing the benefits of any cancer drug known to modern science.

The study involved 1,179 healthy women from rural Nebraska. One group of women was given calcium (around 1500 mg daily) and vitamin D (1100 IU daily) while another group was given placebo. Over four year, the group receiving the calcium and vitamin D supplements showed a 60 percent decrease in cancers. Considering just the last three years of the study reveals an impressive 77 percent reduction in cancer due to supplementation. (The full press release of this study is included below. It provides more details about the findings.)

Note that these astonishing effects were achieved on what many nutritionists consider to be a low dose of vitamin D. Exposure to sunlight, which creates even more vitamin D in the body, was not tested or considered, and the quality of the calcium supplements was likely not as high as it could have been (it was probably calcium carbonate and not high-grade calcium malate, aspartate or similar forms). What does all this mean? It means that if you take high-quality calcium supplements and get lots of natural sunlight exposure or take premium vitamin D supplements (such as those made from fish oil), you could easily have a greater reduction than the 77 percent reduction recorded in this study.

Notice how Adams is already making some unwarranted assumptions from this one study. For one thing, he seems to assume that "premium vitamin D supplements" given at a higher dose could produce a greater than 77% reduction in cancer incidence. Even if the results of this one study were replicated and found to be true, it's highly unlikely that it would make one whit of difference whether the vitamin D used was "premium" or not. For another thing, just because the dose given apparently resulted in a 77% reduction in cancer incidence does not mean that a higher dose would produce even more of a reduction. It might, or it might not. The dose-response curve may be biphasic, in which certain doses decrease the risk, while others increase it. Or the curve may reach a plateau. It's impossible to know without more studies. In fact, given that the study to which Adams refers is definitely an outlier in that it finds a far greater risk reduction among more cancers than previous studies of vitamin D and cancer means that it should be viewed with some skepticism and, more importantly, that it definitely needs to be repeated and verified. It's certainly not unreasonable to infer that vitamin D may have cancer preventative properties; indeed, the observation that sparked this hypothesis and several studies is the observation that sun exposure is negatively correlated with cancer rates. Given that sun exposure results in vitamin D production, the obvious first explanation to examine was that vitamin D is somehow involved.

Let's move on to the study so trumpeted by Adams, though. The specific study, Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial, did indeed come from Creighton University and did indeed study 1,179 women age 55 and older in Nebraska. The strength of the study was primarily that it was randomized and double-blinded. That's good. Even so, it had significant weaknesses. Perhaps the most significant weakness is that cancer was a secondary outcome of this study, not its primary endpoint. The study was designed to determine whether vitamin D plus calcium supplementation was superior to calcium supplementation alone in presenting osteoporosis. It's always problematic to look at secondary endpoints like this. In this case, the experimental groups included calcium and vitamin D placebos, calcium supplementation plus vitamin D placebo, and calcium supplementation plus vitamin D supplementation. There was no vitamin D alone group. Another weakness in the study is that it only covered four years, enough time for osteoporosis but probably not enough time for a good look at cancer.

However, the most glaring weakness of the study is the small number of cancers that were observed. There were only 50 cancers of all types, not including skin cancer, which they excluded for unclear reasons. This included, for example, a total, divided among all groups, of 19 breast cancers, 3 colon cancers, 7 lung cancers, 10 lymphatic cancers, 3 uterine cancers, and 8 other cancers. The raw numbers showed 20 cancers in the placebo group, 17 in the calcium supplementation alone group, and 13 in the vitamin D plus calcium group, for a risk reduction of 58%. Then the investigators did something that seems somewhat reasonable on the surface. They excluded cancers developed in the first year of the study, using the rationale that such tumors were probably present before the study started. In actuality, for common cancers like breast and colon cancer, tumors diagnosed at four years were probably there at the beginning of the study, given that the atypia to in situ to invasive cancer sequence takes several years. Be that as it may, when these patients were excluded from the analysis, there were 18 cancers in the placebo group, 15 in the calcium supplementation alone group, and 8 in the vitamin D plus calcium group, for a risk reduction of the magical 77% that Mike Adams trumpets every chance he gets on NewsTarget, even going so far as to accuse "allopathic medicine" of racism and "enslaving black women" because it doesn't recommend vitamin D supplementation for all black women, who tend to have lower levels of vitamin D metabolites.

What finally prompted me to write about the above study, however, is a new study just released this week and published in the Journal of the National Cancer Institute, which I became aware of through Dr. Len's Cancer Blog. The study is entitled Prospective Study of Serum Vitamin D and Cancer Mortality in the United States, was performed by researchers at the Division of Cancer Epidemiology and Genetics at the National Cancer Institute. It, too, has its strengths and weakness, but its strengths relative to the Creighton University study include (1) a much larger study population; (2) measuring cancer mortality, which is important; and (3) the study was prospective, with cancer as a primary endpoint. Its main weakness, relative to the previous study, was that it was correlative, rather than interventional. Even so, it's worth looking at, particularly since it also included both men and women over a wider age range.

Basically, there were 16,818 people in the study, from whom researchers took blood samples to measure baseline vitamin D levels. These people were part of the Third National Health and Nutritional Examination Survey (NHANES III). Over the course of the study, 536 people died of cancer, nearly 11 times the number of cancer deaths examined in the Creighton University study. The investigators found that total cancer mortality was unrelated to baseline vitamin D status in the whole study population and in subgroups including men, women, non-Hispanic whites, non-Hispanic blacks, and Mexican-Americans. Other factors were monitored, including smoking, educational levels, and physical activity, and higher levels of vitamin D were measured in men, whites and more highly educated people. In contrast, women, African and Mexican Americans, and less educated participants had lower levels of vitamin D in their blood tests. Finally, those who were more overweight and obese had lower blood levels of vitamin D than those who were thinner, a finding consistent with multiple other studies.

Investigators then looked at whether vitamin D levels correlated with mortality from specific cancers. What they found is that, for all cancers examined save one, there was no correlation. The one tumor for which there was a significant inverse correlation between vitamin D levels and cancer mortality was colorectal cancer, where a 25(OH)D (the active form of vitamin D measured) level higher than 80 nmol/L or higher was associated with a 72% risk reduction. This result is consistent with some previous studies There was also a suggestion of a similar inverse relation between vitamin D levels and breast cancer mortality, but the numbers were too small to confirm it.

So what do we have when we take this study and a bunch of other studies? If I have to guess what future studies will likely find, I'd guess that vitamin D will likely be found to be protective against some cancers, including most likely colorectal cancer and possibly breast cancer (although probably not as protective as Mike Adams asserts constantly) and not against others. I would also guess that there may be unforeseen conclusions. For example, any molecule as biologically active as vitamin D may very well increase the risk of some cancers. The full range of effects is not likely to be known until many patients have been followed many years. Moreover, vitamin D supplementation is not without potential complications, as toxicity, albeit uncommon, can result when supplementation is too vigorous. However, when you ramp up a preventative intervention to millions and millions of otherwise healthy people, uncommon adverse reactions suddenly become more of a concern, as does the possibility that there will be other risks that have not yet been characterized.

Of course, I'm being far too even-handed, nuanced, and cautious for a crank like Mike Adams, who imagines all sorts of intransigence and conspiracies to suppress this knowledge in this hilariously over-the-top screed:

Each day that the American Cancer Society, the AMA, the FDA and others in conventional medicine refuse to acknowledge the benefits of vitamin D supplements for preventing cancer, they lose yet more credibility and slip one step closer towards global humiliation and irrelevance. It is difficult to imagine how anyone from conventional medicine can show up at a health event and say, with a straight face, that they're doing everything they can to fight cancer when in reality they are willfully ignoring a prevention medicine that really works: Vitamin D. It's simple, safe and virtually free, and it has no negative side effects, requires no patent royalties, and is available right now to everyone.

If there were ever a cancer prevention strategy to get behind, this is it! The people in the cancer industry, if they had any sense, should be leaping out of their chairs, fumbling over each other in a mad rush to the press conference podium to announce their support for vitamin D. And yet what do we hear in the United States? Complete apathy. It's as if these people somehow believe that a vitamin manufactured by the human body itself has no role in human nutrition. The depth of blind ignorance at work here is mind boggling. Someone should actually start a psychological study of the people in the cancer industry to figure out how their minds can work that way. It should be called, "The Madness of Crowds and the Illusion of Cancer Treatments in Western Medicine."

And:

The American Cancer Society, however, seems stuck in the nutritional dogma of the 1950's and continues to claim that only drugs, radiation and surgery can treat cancer, and that nutritional supplements have no role to play whatsoever in cancer prevention. This view is so out of date that it belongs in a museum of medicine, not on the agenda of an advanced nation. (Stating that vitamin D has no useful role in preventing cancer is as hopelessly outdated as claiming the Earth is flat.)

This is the sort of rant that makes me wonder if Mike Adams can ever turn it down from 11.In real life, is he like the old Saturday Night Live character who could not modulate his voice and always spoke loudly? But what is the American Cancer Society's real position? Why not listen to Dr. Len Lichtenstein, the Deputy Chief Medical Officer for the national office of the American Cancer Society:

Since vitamin D has come into the spotlight, I have transitioned from being a skeptic to believing there may in fact be a role of vitamin D in reducing the risks of a variety of cancers. The evidence has been inferential, but I can't ignore the weight of that evidence suggesting that such a relationship exists.

But the American Cancer Society has resisted the temptation to draw the conclusion that we currently know enough to make a general recommendation to the more than 300 million people in this country (and throughout the world) that they should markedly and routinely increase their vitamin D intake.

[...]

We have consistently called for more research into this topic. This is especially important given our past experience with other vitamins, such as vitamin C and beta-carotene, where well-qualified experts touted the benefit of those vitamins in reducing cancer risk.

When the studies were actually done, we discovered that the vitamins had either no effect or, for some people, may have actually increased their risk of cancer.

The ACS has also called for more vitamin D research.

The difference in positions between the ACS and Mike Adams on the matter of vitamin D is an excellent example of the difference between science and cranks. Science, when done properly, does not jump to conclusions. It takes into account confounding factors and recognizes the limitations of its findings. It does not leap to generalize health recommendations based on a single study and recognizes that any health intervention will involve a careful balancing of benefits versus risks. It does not cherry pick data to support a pet conclusion. Sure, scientists sometimes fail in this ideal, sometimes spectacularly. No human is able to perform to the ideal without fail. However, science has mechanisms that are very good at eventually correcting such errors. Cranks like Mike Adams, on the other hand, will often fixate on one area, take existing science, and then either to twist it beyond all recognition or to go far beyond what the current state of knowledge justifies. Whether their belief comes from seeing a study or two or whether it existed prior to good evidence, they will seldom be swayed from it by uncertainties in existing data or even massive amounts of contradictory evidence. Not for them is the weighing of risks versus benefits. To a crank like Adams, iterventions are either all good (vitamin D) or unalloyed evil (any sort of chemotherapy).

And anyone who disagrees with them must be part of the "establishment" or "conspiracy."