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Prostate Cancer Update: 3 areas where evidence has changed

Do you know more today than you did a year ago? Hopefully the answer is yes.  Prostate cancer researchers are learning more all the time, too.  Some choices that once seemed to have potential to reduce risk of prostate cancer, based on research available at the time, are no longer recommended in light of today’s stronger research. At best, they appear ineffective for most men, and at worst, show potential for posing risk of their own.research resuts show new findings on nutrition and men's risk of prostate cancer

It’s national Prostate Cancer Awareness Month.  Let’s look at three areas in which steps once identified as potentially protective are no longer advised for most men.

Selenium

Selenium is a mineral that the body uses as part of a powerful antioxidant system in our body.  Antioxidants seem to be important to reduce risk of prostate and other cancers, because they neutralize “free radicals” that can otherwise damage cells and start the disease process.

At one time, some studies suggested that since low selenium levels in the body might increase risk of prostate cancer, selenium supplements might be an easy way to reduce risk of this common cancer.  Then came the results of the SELECT trial, the largest prostate cancer prevention trial ever conducted, and its 2011 update.  Its conclusions: selenium supplements do not lower prostate cancer incidence, and some data hints that they could pose some increase in risk of diabetes.

This summer, a summary and analysis was published of 12 studies that, instead of looking at selenium consumption looked at measures of selenium status of the body – blood levels and toenail levels, a good marker of selenium status over an extended period. This analysis suggests that selenium may have the potential to be protective against prostate cancer, but only when body levels are in a particular range.

Here’s our best understanding of selenium and prostate cancer risk for now:fish supplies selenium to reduce cancer risk

  • Blood selenium concentrations in a healthy range (135 to 170 ng/mL) are linked with 15–25% lower risk of prostate cancer compared with very low blood levels.  Selenium levels may have even bigger impact on development of advanced prostate cancer.
  • The SELECT trial, which showed no risk reduction from selenium supplements, involved men who on average started the study with blood selenium already in the healthy range identified above.  With 200-microgram (mcg) selenium supplements, their blood levels rose to an average of 250 ng/mL. It’s quite possible that the lack of benefit was because there was no protection beyond the 170 ng/mL level.
  • Other studies suggest that cancer risk may increase at highest blood levels of selenium. Men in the Nutritional Prevention of Cancer Trial who began with healthy levels showed no benefit, and even  a slight trend for increased prostate cancer risk when given selenium supplements.
  • Don’t automatically assume that your selenium level is low just because you don’t eat as healthfully as you think you should.  We get small amounts of selenium from a variety of foods. Studies show that U.S. blood levels tend to be higher than levels in Europe and other countries. According to one analysis published earlier this year, most Americans’ blood levels fall within the range linked by the latest analysis to lower prostate cancer risk.
  • Researchers are looking at whether some chemical forms of selenium supplements might be more protective than others, a key question. Meanwhile, though, regardless of form, unless you have blood tests or a medical condition that shows your body is low on selenium, based on survey data, most American men should not assume that selenium supplements would reduce their risk of prostate cancer.

Vitamin E

The other component of the SELECT trial involved supplements of 400 IU vitamin E, either alone or given with selenium supplements.  This level of vitamin E supplementation at one time was recommended to reduce risk of heart disease.  Since then, based on further studies showing no benefits, the American Heart Association and American Diabetes Association both now specifically advise against use of vitamin E supplements.

As for prostate cancer, the SELECT trial was stopped early because of data suggesting a possible increase in prostate cancer linked to vitamin E supplements, and researchers continued to follow the men’s health.

Here’s our best understanding about vitamin E and prostate cancer today:nuts are good sources of vitamin E

  • Updated SELECT study data show that, after an average of 7 years (including  5.5 years on supplements), there were 17 percent more cases of prostate cancer in men taking vitamin E than in men taking placebo (inactive pills). In the Physicians Health Study II, 400 IU vitamin E taken every other day for about 8 years did not show increased prostate cancer risk, but it also showed no protection.
  • Neither of these two large studies show any difference in total cancer incidence or overall death rates among the men taking vitamin E supplements.
  • Vitamin E in food comes in several different forms, although supplements in these and other studies generally supply the form of vitamin E known as alpha-tocopherol, which is the form dietary recommendations focus on as essential. Very high levels of alpha-tocopherol might upset the normal balance in the body among these forms, and seems to reduce blood levels of one called gamma-tocopherol.  Some research suggests that gamma-tocopherol may also provide anti-cancer, health-protective effects.  It’s possible that supplements providing a balanced mixture of tocopherols would provide protection rather than risk, but we do not have studies on this yet.
  • Meanwhile, try focusing on healthful foods that supply a mixture of vitamin E forms as part of a balanced, predominantly plant-based diet. Vegetable oils, including olive oil and canola oil, are major U.S. dietary sources of vitamin E, especially as alpha-tocopherol.  Almonds and sunflower seeds are among the foods most concentrated in alpha-tocopherol, although hazelnuts and peanuts also supply some.  Dark leafy green vegetables, including cooked spinach, provide important amounts of alpha-tocopherol, too. Gamma-tocopherol is actually the major form of vitamin E in the American diet. Especially concentrated sources include walnuts, pecans, pistachios and pumpkin seeds.

Folate and Folic Acid

This may be yet another case in which both too much and too little of a nutrient pose prostate cancer risk.  Folate is a B vitamin, and folic acid is the form found in fortified foods and supplements.  At first, folate’s role in DNA production and repair seemed the likely reason that studies linked low levels – either in the blood or in the diet – with increased risk of cancer.

More recently, research is also looking at other ways folate may interact with DNA to turn on and turn off expression of genes, like tumor suppressor genes, that influence cancer risk.  Both too much and too little folate seem to have negative results in this regard.

Folate and folic acid help decrease risk of birth defects when women consume enough before and during pregnancy.  Since Americans have tended to eat low amounts of foods naturally concentrated in folate – like dark green vegetables and dried beans – folate fortification of grain products was begun to decrease birth defects.  Since fortification began, lack of folate or folic acid has become far less common in the U.S.

Today’s take-home message about folate and folic acid:

Broccoli, dark green leafy vegetables and dried beans supply folate

AICR’s Not-so-Boring Broccoli shows how delicious this folate-rich green vegetable can be

  • Studies of people with colon polyps (benign tumors that are the starting point for most colon cancer) show that timing may change folate’s role in cancer.  Some evidence suggests that it may be protective before cancer cells form.  But once early cell damage has begun, very large amounts of folic acid could aid tumor development.  Trials link high-dose folic acid supplements to increased development of advanced colon polyps;  risk is reduced only for those who start with low blood levels of folate.
  • This is a concern for prostate cancer, since like colon cancer’s development from polyps, it can quietly develop over many years. A meta-analysis of six randomized controlled trials showed a 24 percent increase in prostate cancer risk for men receiving folic acid compared to controls.
  • Some people may benefit from increased amounts of folate or folic acid.  For example, some medications, like the diabetes medication, metformin, may increase needs. People taking methotrexate, either in high doses to treat cancer, or in low doses for conditions like rheumatoid arthritis, should be sure to talk with their doctor about the level of folate/folic acid consumption that is right for them. Since high doses of folic acid can interfere with high-dose methotrexate, cancer survivors should stay tuned for ongoing research on this topic.
  • Current recommendations from the Institute of Medicine call for adults to get no more than 1000 micrograms (mcg) of folic acid per day.  This is a large amount, but with the many cereals, drinks and bars fortified with folic acid today, it is not hard to accumulate high levels if you use multiple such products regularly, especially if you also take a multi-vitamin or other supplement that contains folic acid.
  • Naturally-occurring folate in foods affects body levels differently than the same amount of folic acid from fortified foods and supplements, because a much larger proportion of folic acid is absorbed. Recommended upper limits of folic acid consumption do not apply to folate.  Abundant use of vegetables, citrus fruit, beans and other natural sources of folate also brings a host of other nutrients and natural plant compounds that seem to promote good health, so including plenty in a balanced plant-based diet is the optimal way to meet folate needs when possible.

So what’s a man to do that is supported by research?  Prostate cancer is a complex disease, and unfortunately, this is an area with far more questions than answers.  Based on what we know right now, start with basic healthy choices that promote lower overall cancer risk as the foundation: reach and maintain a healthy weight, get some physical activity daily, and eat a balanced, predominantly plant-based diet that avoids excess red and processed meat.  All three of the nutrients discussed above may play a role in reducing prostate cancer risk; the key is getting enough, without going overboard in hopes that more is better.

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References

Klein, EA et al.  Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT).  JAMA, 2011.  306(14):1549-56.

Hurst, R et al. Selenium and prostate cancer: systematic review and meta-analysis.  Am J Clin Nutr, 2012.  96 (1): 111-122.

Rayman. MP. Selenium and human health. Lancet, 2012.  379: 1256–68.

Gaziano JM et al. Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians’ Health Study II randomized controlled trial. JAMA., 2009. 301(1):52-62

Wien, TN et al. Cancer risk with folic acid supplements: a systematic review and meta-analysis. BMJ Open, 2012 Jan 12.  2(1):e000653.

 

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