[ZucchiniFlower]

This is disturbing...

Heavy multivitamin use may be linked to advanced prostate cancer


While regular multivitamin use is not linked with early or localized prostate cancer, taking too many multivitamins may be associated with an increased risk for advanced or fatal prostate cancers, according to a study in the May 16 issue of the Journal of the National Cancer Institute.

Millions of Americans take multivitamins because of a belief in their potential health benefits, even though there is limited scientific evidence that they prevent chronic disease. Researchers have wondered what impact multivitamin use might have on cancer risk.

Karla Lawson, Ph.D., of the National Cancer Institute in Bethesda, Md., and colleagues followed 295,344 men enrolled in the National Institutes of Health-AARP Diet and Health Study to determine the association between multivitamin use and prostate cancer risk. After five years of follow-up, 10,241 men were diagnosed with prostate cancer, including 8,765 with localized cancers and 1,476 with advanced cancers.

The researchers found no association between multivitamin use and the risk of localized prostate cancer. But they did find an increased risk of advanced and fatal prostate cancer among men who used multivitamins more than seven times a week, compared with men who did not use multivitamins. The association was strongest in men with a family history of prostate cancer and men who also took selenium, beta-carotene, or zinc supplements.

“Because multivitamin supplements consist of a combination of several vitamins and men using high levels of multivitamins were also more likely to take a variety of individual supplements, we were unable to identify or quantify individual components responsible for the associations that we observed,” the authors write.

In an accompanying editorial, Goran Bjelakovic, M.D., of the University of Nis in Serbia, and Christian Gluud, M.D., of Copenhagen University Hospital in Denmark, discuss the positive and negative health effects of antioxidant supplements. “Lawson [and colleagues] add to the growing evidence that questions the beneficial value of antioxidant vitamin pills in generally well-nourished populations and underscore the possibility that antioxidant supplements could have unintended consequences for our health,” the authors write.

[reverett123]

...if the study was adjusted to take into account the length of time the supplements had been taken. That is, did they differentiate between the guy who had taken such for ten years before diagnosis and the guy who took none until he got scared by symptoms and started taking them by the handful?

[ZucchiniFlower]

It was a very large study:

http://jnci.oxfordjournals.org/cgi/c...e2=tf_ipsecsha

Multivitamin Use and Risk of Prostate Cancer in the National Institutes of Health–AARP Diet and Health Study
Karla A. Lawson, Margaret E. Wright, Amy Subar, Traci Mouw, Albert Hollenbeck, Arthur Schatzkin, Michael F. Leitzmann

Background: Multivitamin supplements are used by millions of Americans because of their potential health benefits, but the relationship between multivitamin use and prostate cancer is unclear.

Methods: We prospectively investigated the association between multivitamin use and risk of prostate cancer (localized, advanced, and fatal) in 295344 men enrolled in the National Institutes of Health (NIH)–AARP Diet and Health Study who were cancer free at enrollment in 1995 and 1996. During 5 years of follow-up, 10241 participants were diagnosed with incident prostate cancer, including 8765 localized and 1476 advanced cancers. In a separate mortality analysis with 6 years of follow-up, 179 cases of fatal prostate cancer were ascertained. Multivitamin use was assessed at baseline as part of a self-administered, mailed food-frequency questionnaire. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated by use of Cox proportional hazards regression, adjusted for established or suspected prostate cancer risk factors.

Results: No association was observed between multivitamin use and risk of localized prostate cancer. However, we found an increased risk of advanced and fatal prostate cancers (RR = 1.32, 95% CI = 1.04 to 1.67 and RR = 1.98, 95% CI = 1.07 to 3.66, respectively) among men reporting excessive use of multivitamins (more than seven times per week) when compared with never users. The incidence rates per 100000 person-years for advanced and fatal prostate cancers for those who took a multivitamin more than seven times per week were 143.8 and 18.9, respectively, compared with 113.4 and 11.4 in never users. The positive associations with excessive multivitamin use were strongest in men with a family history of prostate cancer or who took individual micronutrient supplements, including selenium, beta-carotene, or zinc.

Conclusion: These results suggest that regular multivitamin use is not associated with the risk of early or localized prostate cancer. The possibility that men taking high levels of multivitamins along with other supplements have increased risk of advanced and fatal prostate cancers is of concern and merits further evaluation.

[ZucchiniFlower]

editorial:

EDITORIALS
Surviving Antioxidant Supplements
Goran Bjelakovic, Christian Gluud

Affiliations of authors: Department of Internal Medicine–Gastroenterology and Hepatology, Medical Faculty, University of Nis, Nis, Serbia (GB); The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Center for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark (GB, CG)

Correspondence to: Goran Bjelakovic, MD, Dr Med Sci, Department of Internal Medicine–Gastroenterology and Hepatology, Medical Faculty, University of Nis, Blvd Dr Zorana Djindjica 81, 18000 Nis, Serbia (e-mail: goranb@junis.ni.ac.yu) or Christian Gluud, MD, Dr Med Sci, The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Center for Clinical Intervention Research, Dept 33.44, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark (e-mail: cgluud@ctu.rh.dk).

An association between healthy diet and good health has been noted since Hippocrates (460–377 BC)—and in fact long before (1). Our diet provides numerous vitamins and trace elements that are essential to good health. Observational studies have shown that there is a positive association between a healthy diet, especially high intake of fruits and vegetables, and delayed aging, reduced risk of cancer, and reduced risk of cardiovascular diseases (2,3). Fruits and vegetables contain numerous micronutrients, including beta-carotene (a precursor of vitamin A), vitamin C, vitamin E, and selenium. These organic components have antioxidant potential and are defined as essential micronutrients (4). Because our body cannot synthesize them, they must be consumed.

In spite of intensive research, it is still not clear exactly which specific dietary constituents of fruits and vegetables might be beneficial. Antioxidant vitamins and elements have attracted most attention in this regard. It is assumed that antioxidants may prevent oxidative damage to cellular components, a potentially important function given that oxidative stress might play a role in aging and the pathogenesis of number of diseases, including cardiovascular diseases and cancer, the leading causes of death in high-income countries (5).

Hypotheses as to the role played by oxidative stress in human disease have stimulated interest in the preventive potential of antioxidant supplements. Worldwide, institutions have been created to study antioxidants, and many resources have been allocated to this area. Consumption of antioxidant supplements in high-income countries has become widespread—it is estimated that about one-third of adults in high-income countries consume antioxidant supplements (6). A large number of primary or secondary prevention randomized trials have been conducted to assess the benefits and harms of antioxidant supplements versus placebo or no intervention. Systematic reviews and meta-analyses of these randomized trials have not demonstrated that beta-carotene, vitamin A, and vitamin E in the administered dosages lead to decreased mortality, and some analyses have suggested the possibility of increased mortality (7–11). As to vitamin C and selenium, the verdict is still out (11).

There are several possible explanations for the potential negative effect of antioxidant supplements. Reactive oxygen species in moderate concentrations are essential mediators of reactions by which the body gets rid of unwanted cells. Thus, if administration of antioxidant supplements decreases free radicals, it may interfere with essential defensive mechanisms for ridding the organism of damaged cells, including those that are precancerous and cancerous (12). Thus, antioxidant supplements may actually cause some harm (7–11,13). Our diets typically contain safe levels of vitamins, but high-level antioxidant supplements could potentially upset an important physiologic balance (7–11,13).

The amounts of antioxidants that may afford protection are not known and may differ among individuals. People exposed to increased oxidative stress may have elevated antioxidant requirements. Furthermore, antioxidants could be beneficial in people with innate or acquired high baseline levels of reactive oxygen species but be harmful in people with lower innate levels (12). It is important to keep in mind that antioxidant supplements are synthetic and possess prooxidant properties as well (14). These factors could explain a possible increase in the risk of cancer (8,9,13) and cardiovascular diseases (7). Meta-analyses of randomized clinical trials have not shown that antioxidant supplements reduce cancer incidence (8,9,13,15).

In this issue of the journal, Lawson et al. (16) report the results of a prospective observational study. They investigated the association between multivitamin use and prostate cancer risk in 295344 men enrolled in the National Institutes of Health (NIH)–AARP Diet and Health Study (16). The men were clinically cancer free at enrollment. The authors found that use of multivitamins more than seven times per week, when compared with never use, was associated with a doubling in the risk of fatal prostate cancer (relative risk = 1.98, 95% confidence interval = 1.07 to 3.66). The study of Lawson et al. (16) is observational, and therefore confounding by indication and other confounding cannot be excluded. But the sample studied is very large, which reduces random errors, and the study seems well conducted. The results are in accord with the results of systematic reviews and meta-analyses of randomized clinical trials (7–11,13). The findings lend further credence to the possibility of harm associated with increased use of supplements, including increased rates of cancer (8,9,13,15) and cardiovascular mortality (7).

Lawson et al. (16) add to the growing evidence that questions the beneficial value of antioxidant vitamin pills in generally well-nourished populations (16) and underscore the possibility that antioxidant supplements could have unintended consequences for our health. There are still many gaps in our knowledge of the mechanisms of bioavailability, biotransformation, and action of antioxidant supplements. How much fruit and vegetables do we have to eat to obtain an optimal amount of these nutrients? Why is it not possible to take a vitamin pill to obtain the same effect as a balanced diet? Antioxidant supplements in pills are synthetic, factory processed, and may not be safe compared with their naturally occurring counterparts (17–21). a possible explanation for the negative effects of antioxidant supplementation observed in trials is that the studies were conducted in middle- and high-income countries among populations already well saturated with vitamins and trace elements (11). The American diet provides 120% of the recommended dietary allowances for beta-carotene, vitamin A, and vitamin C, and dietary vitamin E deficiency has never been reported in the United States (17–21). Whether oxidative stress is a primary cause of chronic diseases and the aging process itself or merely a secondary phenomenon is another question that deserves debate and scrutiny (22).

Results of ongoing clinical trials and further studies will be required to extend our knowledge of the impact of antioxidant supplements on health. Is oxidative stress the cause of disease or rather a consequence? Is it wise to artificially modulate the delicate balance between oxidative stress and antioxidants in our cells? Ideally, we should have more data to address these questions.

One way to extend our knowledge about the effects of supplemental vitamins on health would be to test for benefits and harms of supplements before they come to the market. This would entail fair testing of all commercial ingested products with claimed health benefits, as we intend to do with pharmaceutical drugs (23,24). What happens in a petri dish or in preclinical assays may not happen in people (http://www.jameslindlibrary.org; http://www.cochrane.org). Public investment in independent clinical research will be needed to adequately test hypotheses generated in the laboratory.

[ZucchiniFlower]

Assessment of Supplement Use

The baseline questionnaire asked participants about the frequencies with which they used three types of multivitamins ("stress-tab type", "therapeutic or theragran type", and "one-a-day type") during the preceding 12 months. For each type of multivitamin, participants were asked to report frequency of use as never, less than one time per week, one to three times per week, four to six times per week, or every day. Each frequency category was assigned a single value (never = 0, less than one time per week = 0.5, one to three times per week = 2, four to six times per week = 5, and every day = 7). Multivitamin use was defined as the sum of the values obtained for each type of multivitamin and was categorized as never use, casual use (between zero and six times per week), consistent use (seven times/wk), or heavy use (more than seven times per week). Thus, a participant who reported using a stress-tab type one to three times per week and a one-a-day type four to six times per week was considered to have been consuming multivitamins seven times/wk. Participants were also queried regarding dose and frequency of use of single supplements including vitamin A, beta-carotene, vitamin C, vitamin E, and calcium. Daily dose for vitamin E supplement intake was calculated as dose x daily frequency (frequency of use options were the same as multivitamins, and dose options were <100, 100–250, 300–500, ≥600 IU, or unknown). Each category of dose was assigned as 100, 200, 400, and 800 IU, and for those answering "unknown", a value of 400 IU was assigned. For those taking a multivitamin, daily dose of supplemental vitamin E was assumed to be 30 IU. Use of iron, zinc, selenium, and folic acid was assessed by asking participants whether or not they used each of these individual supplements more than once per month in the past 12 months (yes or no).

***They also had questions about diet. Full article:

http://jnci.oxfordjournals.org/cgi/c...7a92e7153#SEC2

[reverett123]

I have come to believe in two guiding principles where my supplements are concerned. First and foremost is moderation in all things. The second is that the closer to nature the better.

It does seem to be an interesting study. At least they had a large sample to work with. But something about it makes me uneasy. Anti-oxidants have been studied out the wazoo and there have been hints that have reinforced my moderation credo. I guess I would like to see more reconcilliation with other studies. Selenium, for instance, has been shown repeatedly as being a big help for prostate problems. Just the opposite here. Maybe my unease comes from the "broad brush" approach taken.

Then there is my distrust of any study which hints that the FDA really ought to tell me what to take.

I am drifting toward a belief that adaptogens combined with good nutrition, exercise, and rest may be more sensible than simply extending the mindset of "better living through chemistry" that single ingredient synthesis represents. Ashwagandha anyone?