Serum vitamin D concentration and prostate cancer risk: a nested case-control study.

Abstract

BACKGROUND: Epidemiological studies have yielded inconsistent associations between vitamin D status and prostate cancer risk, and few studies have evaluated whether the associations vary by disease aggressiveness. We investigated the association between vitamin D status, as determined by serum 25-hydroxyvitamin D [25(OH)D] level, and risk of prostate cancer in a case-control study nested within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.

METHODS: The study included 749 case patients with incident prostate cancer who were diagnosed 1-8 years after blood draw and 781 control subjects who were frequency matched by age at cohort entry, time since initial screening, and calendar year of cohort entry. All study participants were selected from the trial screening arm (which includes annual standardized prostate cancer screening). Conditional logistic regression was used to estimate adjusted odds ratios (ORs) with 95% confidence intervals (CIs) by quintile of season-standardized serum 25(OH)D concentration. Statistical tests were two-sided.

RESULTS: No statistically significant trend in overall prostate cancer risk was observed with increasing season-standardized serum 25(OH)D level. However, serum 25(OH)D concentrations greater than the lowest quintile (Q1) were associated with increased risk of aggressive (Gleason sum > or = 7 or clinical stage III or IV) disease (in a model adjusting for matching factors, study center, and history of diabetes, ORs for Q2 vs Q1 = 1.20, 95% CI = 0.80 to 1.81, for Q3 vs Q1 =1.96, 95% CI = 1.34 to 2.87, for Q4 vs Q1 = 1.61, 95% CI = 1.09 to 2.38, and for Q5 vs Q1 = 1.37, 95% CI = 0.92 to 2.05; P(trend) = .05). The rates of aggressive prostate cancer for increasing quintiles of serum 25(OH)D were 406, 479, 780, 633, and 544 per 100 000 person-years. In exploratory analyses, these associations with aggressive disease were consistent across subgroups defined by age, family history of prostate cancer, diabetes, body mass index, vigorous physical activity, calcium intake, study center, season of blood collection, and assay batch.

CONCLUSION: 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.

ANOTHER STUDY

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"In an interview with Renal & Urology News, Dr. Albanes speculated about how higher 25-hydroxyvitamin D levels could increase PCa risk. One possibility is that higher levels of this form of vitamin D displaces the more bioactive hormonal form (1,25-dihydroxyvitamin D) from the primary vitamin D transport molecule in blood (vitamin D binding protein), so it is less available to prostate cells, he said.

In addition, vitamin D stimulates insulin receptors and promotes insulin synthesis, and studies have linked elevated insulin levels with a higher risk of PCa as well as pancreatic cancer. Therefore, higher vitamin D levels could promote cell proliferation and tumor growth in both organs through hyperinsulinemia. The strong association between higher vitamin D levels and aggressive disease would be consistent with a stimulatory effect on tumor growth, he noted.

Clinicians should “not to act on the assumption that more vitamins and megavitamin doses are necessarily always going to be beneficial,” Dr. Albanes said. They should monitor the research and base their use of vitamin D supplements in men on currently available evidence. For now, he said, doctors should be cautious in recommending high-dose vitamin D supplementation to men. ref   The chart below appears in this article.

(article conclusion) Collectively, Dr. Klein explained, the data suggest a U-shaped dose-response curve with the use of micronutrients. Among individuals with deficiencies, adding micronutrients may be helpful in preventing specific conditions, but in those who are replete (already have sufficient levels), adding micronutrients can result in harmful supraphysiologic levels. Micronutrients are not beneficial for people in between."  end of copy

Analysis: There are always possible drawbacks in every study. For this one, a high percentage of smokers and very low vitamin D levels to begin with could have compromised results, BUT there is a general trend growing mentioned by the Doctors interviewed that appears to fit for the action of vitamin D on prostate cancer risk. The precautionary principle should be at work here. ref <Check out the other nutrient associations; calcium, Vitamin E, total cholesterol, as well as vitamin D.

FINALLY, A Positive STUDY FOR VITAMIN D REDUCING PROSTATE CANCER SIGNS  

In men already with prostate cancer, the non-aggressive form, Vitamin D given at 4000 IUs over one year reduced the measurements of prostate cancer. Here is the study reference.  ref

While this looks to be in contrast with the above studies, there may be different aspects to Vitamin D actions at low, moderate, or very high intakes, especially at each stage of a disease process. The top two studies looked at future prostate cancer risk from different current vitamin D levels. This last study, just looked at men after they had prostate cancer and how vitamin D levels at this stage influenced the progression of the disease.

55% of subjects taking vitamin D benefited while 34% exhibited increases. This could very well be a situation where certain men might be responsive to vitamin D while others are not.

SiDEBAR: This is a known fact. Higher blood levels of the free or ionized form of calcium versus the calcium bound to protein is a marker for the aggressive form of Prostate Cancer. ref  Free calcium levels are increased with greater vitamin D intake. Even though overall calcium blood levels are under strict genetic controls, they do vary some. This is counter to the information some Nutritionist are giving for the effects of vitamin D on cancers.

There are least three concepts at play here. First, vitamin D may have unique influences on different types of cancer. Second, vitamin D intake levels might have opposite influences at different cancer stages.  A prevention action before cancer development, acceleration at early cancer growth, and later at mega-doses, it might slow progression of mature cancers. And third, either cancer cells or vitamin D influence other body processes or functions that relate to cancer growth, like glucose/insulin levels. ref  Remember, cancer cells develop the ability to speed up the destruction and elimination of the hormone form of vitamin D and also possibly reduce the building up of the storage form of vitamin D as well.

The vitamin criteria developed here considers these aspects in establishing recommendations using the precautionary principle, but medical attention and monitoring direction is paramount. There is room for greater clarification from research.

FYT: Men on Vitamin D and Testosterone

There may be an association between vitamin D levels and testosterone levels.The highest testosterone levels are found at a vitamin D reading between 34-38 ng/mL (85-95 nmol/L). Both below and above this range of vitamin D, total testosterone slowly fails. Below falls faster than above. article

But, treatment to raise testosterone with vitamin D does not always show positive results. Some are neutral. It may be that both have to be low to exhibit an increase in testosterone after optimizing vitamin D level, not too low but not too high either. Could this subtle changes in testosterone impact prostate conditions?

CAUTION for Men on Vitamin K2 concerning Prostate Cancer Connection

This is very new and still in preliminary stage of development. Osteocalcin participates in normal prostate cell growth. The two forms of osteocalcin, unOC for uncarboxylated osteocalcin, and cOC for vitamin K activated carboxylated osteocalcin appear to have opposite effects on prostate cancer growth. ref The unOC form inhibits while the cOC form stimulates prostate cancer cell growth individually in a test tube study. This at first appears to be counter intuitive since it is the cOC form that is needed to build bone but the non-bone forming unOC is the one tht stops prostate cancer growth in the study. This begins to make sense with the knowledge that prostate cancer first spreads to bones. Prostate cancer cells hijack the bone building mechanics for this process. Thus, nature knew it would be best to use the non bone builiding Osteocalcin form unOC to stop or limit prostate cancer growth and not use the cOC form as it potentially helps prostate cancer spread to the bones.

More will be forthcoming on this critical issue shortly. But the precautionary approach is of course to not take or limit vitamin K if prostate cancer is present, or a history exists in blood relatives. ref

Doctors have been testing for cOC amounts for some time as a marker for bone building. Thus, for healthy individuals, it might be prudent to take small amounts of K2 as MK7 to maintain a balance between the two forms of osteocalcin. Using diet as basis for food sources of K2 and testing for blood levels, probably only need to add 45 up to 120 mcg. Probably OK to rotate every other day or even third day after a 14 day build up. Remember, vitamin K2 also has functions in other areas such as cardiovascular disease and blood sugar control so these also need to be maintained.

FYI: Vitamins A, D, and E plus Beta Carotene have some associations with prostate cancer here. More soon!