Vitamin D supplements may increase prostate cancer risk (at least among Finnish smokers)


Proving the point that (at least in prostate cancer) if you look carefully enough you can always find a study that supports your particular point of view, a new report from researchers at the National Institutes of Health and partner organizations has now demonstrated that, “High blood levels of vitamin D may increase a man’s risk of prostate cancer.”

The new study by Albanes et al., published on line in the journal Cancer Biomarkers, Epidemiology & Prevention, and also discussed in depth in an article on Renal & Urology News, is based on an analysis of serum levels of 25-hydroxy vitamin D in 2,000 Finnish men, of between 50 and 69 years of age, who were participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (the so-called ATBC study).

We know that vitamin D compounds can be shown to inhibit the development of prostate tumors in experimental and animal models (some of the time). However, there has never been any clear epidemiological or clinical evidence that vitamin D compounds can either prevent or delay the progression of prostate cancer. Despite this lack of any specific evidence of the impact of vitamin D on prostate cancer, many men — and many prostate cancer patients — do in fact take supplementary quantities of vitamin D on the well-established grounds that vitamin D can prevent other progressive forms of disorder and that therefore it “can’t hurt.” Unfortunately, that assumption may be misguided (at least for some).

Albanes et al. carried out a retrospective “nested-case control” study in which they matched 1,000 men in the ATBC study who were diagnosed with prostate cancer (the “cases”) to another 1,000 participants in the ATBC study who did not have a prostate cancer diagnosis (the “controls”). Matching was based on the patients’ ages, their blood collection dates, and other factors.

Here is what they found:

  • On average, overall, serum 25-hydroxy vitamin D levels were 3 percent higher in the cases than they were in the controls, but this difference was not statistically significant (P = 0.19).
  • When cases and controls were categorized in to five groups (“quintiles”) based on their season-specific levels of serum 25-hydroxy vitamin D, their overall risk (OR) for prostate cancer went up from a baseline based on the season-specific level of serum 25-hydroxy vitamin D … from 1.00 (the baseline reference of the lowest quintile)  to 1.29, 1.34, 1.26, and 1.56, respectively.
  • These findings appeared stronger among groups of men who
    • Had aggressive forms of prostate cancer
    • Took more physical activity
    • Had higher serum total cholesterol  levels
    • Had higher α-tocopherol levels
    • Had higher daily intakes of total calcium
    • Had higher daily intakes of vitamin D
    • Had received α-tocopherol supplements as part of the ATBC study

The authors conclude that their study indicates that “men with higher vitamin D blood levels may be at increased risk of developing prostate cancer,” leading to the implication that “Greater caution is warranted with respect to recommendations for high-dose vitamin D supplementation and higher population target blood levels” of 25-hydroxy vitamin D.

The article in Renal & Urology News includes some interesting comments by Eric Klein of the Cleveland Clinic.

In the first place, Klein agrees with the authors’ caution about high doses of vitamin D supplements, adding, ” This suggestion is in line with many other studies showing that for healthy individuals who eat a normal diet, adding micronutrients adds no benefit and may be harmful.” He goes on to propose that there may be a U-shaped (or a “reverse bell-shaped”) dose-response curve associated with the use of micronutrients. What he means by this is that adding micronutrients may be helpful in preventing specific conditions for people who have very low levels of such micronutrients, but for those people who have normally high micronutrient levels, adding more of them may well be harmful.  For the people with relatively normal blood levels of micronutrients there is no real benefit to supplementation, but nor will there be any great risk either.

Now there is two definite flies in the ointment of the ATBC study … (1) This study was carried out exclusively in white males who were still active smokers. (2) The study population for the ATBC trial all lived at a relatively high northern latitude (above 60ºN). It is generally true that people living at higher northern latitudes have lower serum levels of vitamin D than those living closer to the Equator to begin with, and so the degree to which the data from this study is relevant to non-whites, to non-smokers, and to men living at lower latitudes is therefore completely unknown.

4 Responses

  1. As someone taking 5000 IU daily of vitamin D3, I’m thankful for this alert to evidence that is on the other side of the issue. However, in addition to concerns raised by Sitemaster, there are some other concerns.

    A primary concern is that this study is a “post hoc” analysis of a study that was designed for a different purpose. Parallel to Sitemaster’s point about being able to find evidence on either side of a prostate cancer issue if you look hard enough is the point that you can usually find an interesting association in many studies if you just keep mining the data, running calculations of associations. For example, if you run 100 tests of associations each of which has a true 1% chance of being true, you have a strong chance that at least some of them will appear to be significant.

    It would be helpful to know how many prostate cancer patients and control men fell into each quintile of serum vitamin D. Based on the fact that there was a slight (3%) and non-significant elevation in the vitamin D level for the whole group of prostate cancer patients, in contrast to that surprisingly high risk for the highest quintile vitamin D range group, it seems likely that many, if not a substantial majority, of prostate cancer patients fell into the first quintile where vitamin D levels were not elevated. If so, that would mean that there were relatively few men in the upper quintile groups, and that would suggest that the risk of prostate cancer could be affected by other factors, several of which were mentioned in the abstract and Sitemaster’s summary. For instance, it would be quite possible that a substantially disproportionate number of prostate cancer patients in the highest quintile had high alpha-tocopherol levels or were receiving alpha-tocopherol as part of the study. Based on research after conclusion of the ATBC trial, excessive alpha-tocopherol in comparison to gamma-tocopherol may increase risk of prostate cancer. Sitemaster’s report/the abstract show that there was at least some disproportion between prostate cancer patients and controls regarding alpha-tocopherol. The question is whether it was substantial.

  2. Jim: If you ask the authors for a copy of the actual paper, you might be able to find the answers to some of the questions you raise. In all truth, my personal view was that there are some many questions about the significance of this finding that I wasn’t motivated to track down the actual paper.

  3. Glad Jim commented since it saves me having to comment further. Way too much not explained to stop my daily 5600 IU of vitamin D that keeps my 25-hydroxy vitamin D within the range of 60 to 75 ng/ml recommended by Charles Myers and Stephen Strum.

  4. Talk about screening out points of view in conflict with pre-conceived notions: What about the US PLCO Screening Trial (http://jnci.oxfordjournals.org/content/100/11/796.full.pdf) which concluded, “The findings of this large prospective study do not support the hypothesis that vitamin D is associated with decreased risk of prostate cancer; indeed, higher circulating 25(OH)D concentrations may be associated with increased risk of aggressive disease.”

    Or, if we think that Finnish smokers are different, how about the following study of a multi-ethnic cohort in California and Hawaii (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834847/) that found no overall association between levels of plasma vitamin D and risk of prostate cancer, but those with the highest levels of serum vitamin D were 50% more likely to have prostate cancer.

    Those studies dealt with plasma measurements. Studies have also looked at vitamin D supplementation. In the almost 10,000 person Prostate Cancer Prevention Trial that ran in the US and Canada from 1994-2003, there was no association found between dietary or supplemental intake of vitamin D and risk of prostate cancer. A similar study to the US one, called the European Prospective Investigation into Cancer and Nutrition (EPIC) was run in Europe in 23 centers in 10 European countries and included 153,457 men. It too found no association between vitamin D intake and risk of prostyate cancer.

    In fact, I could only find one research study that showed that higher plasma vitamin D was associated with better prostate cancer prognosis. In this study (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3071841/) , those with lower serum vitamin D had more advanced prostate cancer and higher Gleason score, and it would be valid to hypothesize that the lower serum vitamin D may be a result of the cancer, or perhaps a related VDR polymorphism, rather than a cause.

    There have also been several meta-analyses, which consistently fail to show any association.

    Considering the large amount of evidence that plasma vitamin D has, at best, no association with prostate cancer, the lack of evidence that supplementation has any benefit, and the known toxicity of large intakes of vitamin D — as well as the possibility that it might increase the risk of more aggressive prostate cancer — supplemental vitamin D intake seems unwarranted to me, based on our knowledge at this time.

    – Allen

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