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Press ignores bias in study of multivitamins and prostate cancer
Permanent link to this article: http://www.kurzweilai.net/meme/frame.html?main=/articles/art0706.html
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Press ignores bias in study of multivitamins and prostate cancer
In a recent paper reporting on the National Cancer Institute study of multivitamin use and the risk of prostate cancer, the NCI authors cited several possible bias factors. An analysis by Ray Kurzweil and Terry Grossman shows why the study’s biases should be considered before drawing conclusions.
Published on KurzweilAI.net May 25, 2007.
Analysis of the report published in the JNCI (Journal
of the National Cancer Institute): Multivitamin Use and Risk
of Prostate Cancer in the National Institutes of Health–AARP
Diet and Health Study
We have carefully reviewed the recent study on prostate cancer and multivitamin use. This large study involved nearly 300,000 men and examined the correlation between supplementation and advanced prostate cancer.
After a thoughtful analysis of the study data, we observed the following:
- A related increase was found only in cases of advanced or fatal prostate cancer.
- This effect was not seen in early stage prostate cancer.
- Men who take more supplements tend to be individuals who seek more aggressive medical care and, thus, are more likely to be diagnosed. Similar "detection bias" was seen in the Health Professionals Follow-Up Study and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial studies. This detection bias was noted by the researchers.
- Early cancer detection may motivate an individual to begin vitamin therapy. This was also noted by the researchers.
- Men with advanced prostate cancer are more likely to have developed symptoms prior to diagnosis and, therefore, begin a program of heavier supplementation.
- The fact that advanced prostate cancer was more commonly diagnosed in heavy supplement users with a family history of the disease may also be due to the fact that men with a family history of prostate cancer are, in fact, more likely to both develop prostate cancer and to take supplements in an effort to avoid it. This was also noted by the researchers.
- Individuals diagnosed with early stage cancer are more likely to develop advanced or fatal cancer than the average person.
To put the results of this study in perspective, for every 10,000 men who took larger doses of supplements for 10 years there were 7 to 8 extra cases of fatal prostate cancer. This is less than 1 fatal case per 1,200–1,500 men per year. This is before taking into consideration the bias factors mentioned above. In light of the bias factors, it would not be correct, in our view, to conclude that supplements are necessarily the cause of the few extra cases of advanced prostate cancer.
Prostate cancer is found in the following groups of men who supplement in higher amounts:
- Men who test for prostate cancer more frequently
- Men with symptoms of advanced disease
- Men with a positive family history
The above factors are associated with an increased rate of detection of advanced prostate cancer that is not related to supplement use, but simply found in the same group of men who tend to supplement in greater amounts. This explains the apparent correlation between higher doses of supplements and advanced cancer. Keep in mind that correlations are not clear indicators of cause and effect.
The following are quotes from the article in the Journal of the National Cancer Institute (see first reference below) that discuss the bias factors indicated above:
"The increased risk of localized prostate cancer with heavy multivitamin use among men concomitantly using a vitamin E, selenium, or Folate supplement could be due to detection bias if supplement users were more likely to undergo PSA screening.... Indeed this interpretation is supported by the Health Professional Follow-up Study, which showed that current smokers were more likely to undergo screening for prostate cancer than nonsmokers."
"... the observed relationship between multivitamin use and advanced prostate cancer in our study may have been due to increased multivitamin use among men with early symptoms related to prostate cancer because the association with advanced prostate cancer disappeared when those diagnosed in the initial years of follow-up were excluded."
"The increased risk of advanced prostate cancer and prostate cancer
mortality with heavy use of multivitamins among men with a positive
family history of prostate cancer could be due to men with a positive
family history taking additional, unspecified supplements as part
of a 'prostate health' package to prevent the future development
of prostate cancer. A recent survey found that 50% of men
at high risk for prostate cancer (defined by African American ethnicity,
positive family history, or positive BRCA1 gene mutation) took one
or more supplements to prevent prostate cancer, and more than 25%
took three of more agents concomitantly."
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Mind·X Discussion About This Article:
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Prostate Cancer
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Like many others, I have become suspect whenever I read a report that a natural approach to health and healing has no value or a negative effect. Re the increase in deaths from prostate cancer for those men using vitamin therapy I say this:
In 1995, I was diagnosed with prostate cancer at age 52. My urologist wanted to operate (a prostatectomy). I refused and began a study of the disease and then went on to start a PhD Program in Natural Health. Using mind-body methods, stress-reduction, sleep, excercise, herbs, and vitamins, I am now in what they call "remission". 12 years later, my readings are completely normal. I have never had any traditional interventions such as surgery, radiation, hormone therapy, etc. Had I listened to my urologist, I would most likely be impotent and somewhat incontinent for the last 12 years. Instead, I am completely functional.
Remember that skepticism is the chastity belt of the mind. Our FDA, AMA, and medical-pharmaceutical complex has their own agenda, and it is not primarily in our best interest. Always think for yourself!
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Re: Prostate Cancer
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My father's oncologist phoned me to concede that my protocol worked and therefore the projected hormone thereby would not be necessary. I not only halted the progression of the PSA velocity, but substantially lowered the PSA count into the safety zone. Composing the protocol was a real molecular challenge, stimulating my mastery of associative thinking to the maximum. As the Jackson Memorial Hospital ( another third-world nest of incompetents) lost my father's medical records, I had to mathematically project all variables and correlate them with a myriad of carcinoma pathways and projected alternative pathways that take form when each variant is blocked. This also necessitated finding the correct molecular counter-action to PGE-2, a tumor promoting hormone-like element activated by the enzyme COX-2. This, in turn, involved finding a synergistic combination of herbal pharmacopoeia in the correct proportion and sufficient strength to inhibit COX-2 and promote healthy cell growth and division.
In conjunction with this, it was necessary to identify a substance that could inhibit the AP1 (activator protein), which the much lauded antioxidants do not touch. I think so many simple-minded homeopathic practitioners and nutritionists fail in their quest to cure cancer because they do not understand that antioxidants, while beneficial, are insufficient. The AP-1 can only be inhibited by an non-antioxidant pathway, namely, by obstructing signal-transduction via protein phosphorylation and thereby reducing cancer cell activity. After searching international databases and conducting my own experiments, I was able to identify the correct natural substances -- again formulate a synergistic molecular configuration that would apply to all projected pathway modifications. Fortunately, I found that the same substances could perform the next task of inhibiting the signal-transduction of the PKC (protein kinase C) and PTC (protein tyrosine kinases).
On another level, I needed to find a way to activate the beneficial p53 gene via an estrogen-independent action. This is very important, as it increases apoptosis (carcinoma cell death).
There are other areas I had to address, such as inhibiting basic fibroblast growth factor (bFGF), a growth signal promoting angiogenesis which creates blood vessel proliferation for cancer cells. Simultaneously, it was necessary to promote healthy cell division, which needed to be conducted via four specific mechanisms. An extract (PEITC, an isothiocynaate precursor) from rosemary, broccoli, and watercress achieved this beautifully, enhancing liver metabolism of estrdiiol and estrone while mitigating the growth of DNA adducts.
There was much more involved in halting my father's dangerous PSA velocity and lowering it into the safely zone without the usual radiation or hormone treatment. But as it gets even more complex, I will spare you further details.
I was inspired in this endeavor by Szilard, the Hungarian genius who is rightly considered the father of the hydrogen bomb. When he was diagnosed with advanced cancer and told by the medical establishment he had only six months to live, he set his own biochemistry lab and cured himself (though his formulae have been lost). He collaborated with Einstein (whom Szilard taught much in physics), in writing a letter to Roosevelt encouraging the development of the H-bomb; and later futilely petitioned Truman not to use it against civilian populations. He had a debate over the later petition before Congress with neurotic genius physicist Teller (whom the character Dr. Strangelove was based). The heated exchange with Teller, a tormented hyper-intellect with a prosthetic foot who was also a key figure in the development of the H-bomb ( and later conceived the SDI, an idea embraced by Reagan) generated more luminescence than that assembly was ever exposed to, though I doubt it remotely understood the arguments of either scientist.
Dr. G. Heath King |
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Re: Press ignores bias in study of multivitamins and prostate cancer
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Both the Ray Terry's critique to the NCI paper as well as the [admittedly small N of 6] responders comments, points out some fascinating points as what has become, in my opinion, the "nutraceutical industrial complex", growing rapidly, and producing fabulous wealth for many, with little to know evidence in support of efficacy, safety, pharmaodynamics, purity—and frequently many well designed studies showing no to harmful effects v. placebo.
Namely:
1. Points are well taken by study design issues. This was a longitudinal study design not a blinded randomized control trial, so confounding variables are always an issue.
2. Most importantly, the criticism was leveled at the NCI paper suggesting a slight bias towards more deaths with supplementation, and as pointed out the numbers [of additional deaths] were small anyways. An issue that, with all do respect, "nutraceutical" proponents often fall down on in their “zeal”, is seemingly being unable to see the flip side of their arguments. For example, Ray and Terry’s criticism is to knock down this small, possible not meaningful, increase in death with supplementation in prostate cancer, however, put in a different light, it also supports the point that AT BEST, supplementation is no better than placebo [sugar pills] in this [and so many other] cases.
3. Furthermore, at least studies are being done, and increasingly so, to look at the role of alternative medicine--be it nutraceuticals, acupuncture etc. Of course medicine has held itself to the high bar of peer reviewed manuscripts for decades, and the ability for other investigators to reproduce other's result independently is still a corner stone of science. What is ASTONISHING to me is the ability for people, many who have little disposal income and are frequently have no health insurance, to blindly put their face in the trust of completely unproven "treatments" from the "nutraceutical industrial complex". This isn't about whether something is "natural--so must be good or at least cause no harm"; [try out a handful of Chinese herbs and sign yourself up for a liver transplant], v. “it's made in test tubes so isn't organic"; [one of the top 5 breakthroughs in medicine is the discovery of penicillin, a natural mold accidentally found growing in Alexander Flemming's petri dish]. For the record, I am no apologist for the “medical industrial complex” and clearly Big Pharma needs a PR makeover, and justifiably so, in many instances, but net-net they have benefited humanity far greater than the new breed of "entrepreneurs" safe from FDA scrutiny [for now] that can make fortunes over night, frequently praying on the less well off and naive with their multi-level marketing distributor business models [Amway, Quixtar, Market America, etc].
3. On a more "macro" front, this post points to how it is human nature to seek information sources that match their own biases. So 20 years ago, it was picking up the New York Times or the Wall Street Journal, for example, if one leaned "left" or "right" respectively. Now, with thousands of blogs, sometimes by people who have established themselves reputably in other fields, sometimes by complete unknown loose cannons, people can find exactly what the want to hear/see online, further supporting their biases. I see this as the "dark" flip side of the Web, and likely to only worsen.
These issues and more will be discussed in the Journal of Pharmacology and Therapeutics, in October’s issue, in the Editorial section’s Macroscopy column.
Respectively,
Mark HT Ridinger, MD
Editor-at-Large
Clinical Pharmacology and Therapeutics
Nature Publishing Group
www.nature.com/cpt
American Society for Clinical Pharmacology and Therapeutics
528 North Washington Street
Alexandria, VA 22314
v: 703.836.6981
f: 703.836.5223
www.ascpt.org
ridinger_cpt@ascpt.org
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Re: Press ignores bias in study of multivitamins and prostate cancer
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Responding to Mark HT Ridinger, MD, Editor-at-Large, Clinical Pharmacology and Therapeutics
I found your post, 5/26/07, extremely well thought out and written. I am a devotee of nutritional supplementation, but not an extremist, and certainly not one who rejects useful drugs and medical practices. Most nutrient supplemental usage in the United States is based on zero evidence of benefit and the buyer should be very much aware and wary. Most buyers, most of the time, are wasting their money. On the other hand, there is not the financial incentive or backing for the kind of thorough research with nutricuticals that there is with pharmaceuticals – so my assessment of research based indications of benefit are less rigorous. Every time there are strong (but not definitive) indications of benefit for nutricuticals, the rush is not to test them scientifically, but to create a knock-off patentable drug that is financially lucrative. That is then further compromised by the lack of full reporting of all outcomes and potential liabilities associated with the pharmaceuticals. In the long run, pharmaceutical drugs are about the 6th leading cause of death in the United States, whereas nutricuticals aren’t even on the radar screen, partially because we cannot yet tailor drugs to individual biochemistries. You may counter that they are more deadly, but also far more effective at saving lives – but that is impossible to test for lack of reliable data to contrast.
Fortunately, we may not have to wait around for the time and money to have longitudinal outcome studies that are the current gold standard for efficacy since biochips can in a very short time tell us what effects any substance has on protein production in varying tissues, pharmaceutical or nutricuticals. I would love to see the playing field equaled out and to have both forms of ingestible substances pass through the same gauntlet of proof, but as long as the financial incentives are so lopsided that is not going to happen, so I and others, like Ray and Terry, will have to depend on molecular, chemical, and cellular insights and hunches, along with large demographic studies and very small controlled studies to guide our decisions as to what will most likely be useful. Having a father and brother (both deceased) who had prostate cancer, I take the full array of nutrients that may be protective and have done so for the last 15 years. Interestingly enough, the substances recommended have changed and expanded significantly from just taking Saw Palmetto extract 15 years ago. It’s still a crap shoot, with no guarantees, but our bets are influenced by progressively improving ideas about what causes prostate cancer (and a host of other diseases) and what may work to block, or reverse such diseases. My bias is toward weaker, less powerful, logical, long-term interventions with nutricuticals as opposed to stronger, more powerful, short-term interventions with far riskier pharmaceuticals – except, of course, when I happen to need a specific drug for a specific purpose – then I thank God for the pharmaceutical industry. In all likelihood, a judicious use of both, guided by much more open, unbiased research and an increasing understanding of biochemistry, is probably the best answer.
Ken Johnson, MS, LPC
Ken_barbara@yahoo.com
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Re: Press ignores bias in study of multivitamins and prostate cancer
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APOLOGIES--HIT "SEND" BEFORE PROOFED, PLEASE REFER TO THIS RELATIVELY TYPO FREE VERSION IF INTERESTED.
Both Ray and Terry's critique to the NCI paper as well as the [admittedly small N of 6] responder’s comments, points out some fascinating points as what has become, in my opinion, the "nutraceutical industrial complex", growing rapidly, and producing fabulous wealth for many, with little to no evidence in support of efficacy, safety, pharmaodynamics, purity—and frequently in the face of many well designed studies showing no to harmful effects v. placebo.
Namely:
1. Points are well taken by study design issues. This was a longitudinal study design not a blinded randomized control trial, so confounding variables are always an issue.
2. Most importantly, the criticism was leveled at the NCI paper suggesting a slight bias towards more deaths with supplementation, and as pointed out the numbers [of additional deaths] were small anyways [although if those extra deaths were one of your loved ones, you may feel different…]. An issue that, with all do respect, "nutraceutical" proponents often fall down on in their “zeal”, is seemingly being unable to see the flip side of their arguments. For example, Ray and Terry’s criticism is to knock down this small, possible not meaningful, increase in death with supplementation in prostate cancer, however, put in a different light, it also supports the point that AT BEST, supplementation is no better than placebo [sugar pills] in this [and so many other] cases.
3. Furthermore, at least studies are being done, and increasingly so, to look at the role of alternative medicine--be it nutraceuticals, acupuncture etc. Of course medicine has held itself to the high bar of peer reviewed manuscripts for decades, and the ability for other investigators to reproduce other's result independently is still a corner stone of science. What is ASTONISHING to me is the ability for people, many who have little disposal income and are frequently without health insurance, to blindly put their faith in the trust of completely unproven "treatments" from the "nutraceutical industrial complex". This shouldn’t be about whether something is "natural--so must be good or at least cause no harm"; [try out a handful of Chinese herbs and sign yourself up for a liver transplant], v. “it's made in test tubes so isn't organic and so bad"; [one of the top 5 breakthroughs in medicine is the discovery of penicillin, a natural mold accidentally found growing in Alexander Flemming's petri dish]. For the record, I am no apologist for the “medical industrial complex” and clearly Big Pharma needs a PR makeover, and justifiably so, in many instances, but net-net they have benefited humanity far greater than the new breed of "entrepreneurs" safe from FDA scrutiny [for now] that can make fortunes over night, frequently praying on the less well off and naive with their multi-level marketing distributor business models [Amway, Quixtar, Market America, etc]. Meanwhile, bringing a new drug from the “bench” to market is ~ $1B.
3. On a more "macro"—and I find personally fascinating-- front, this post points to how it is human nature to seek information sources that match their own biases. So 20 years ago, it was picking up the New York Times or the Wall Street Journal, for example, if one leaned "left" or "right" respectively. Now, with thousands of blogs, sometimes by people who have established themselves reputably in other fields, sometimes by complete unknown loose cannons, people can find exactly what the want to hear/see online, further supporting their biases, with no peer review, standards of fact checking and due diligence etc. I see this as the "dark" flip side of the Web, and likely to only worsen.
These issues and more will be discussed in the Journal of Pharmacology and Therapeutics, in October’s issue, in the Editorial section’s Macroscopy column.
Respectively,
Mark HT Ridinger, MD
Editor-at-Large
Clinical Pharmacology and Therapeutics
Nature Publishing Group
www.nature.com/cpt
American Society for Clinical Pharmacology and Therapeutics
528 North Washington Street
Alexandria, VA 22314
v: 703.836.6981
f: 703.836.5223
www.ascpt.org
ridinger_cpt@ascpt.org
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Re: Press ignores bias in study of multivitamins and prostate cancer
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I recently responded to a friend re Prostate "study:"
1. This was not a controlled study, but rather a review of several previous studies, which basically relied on people reporting whether they took multis or not;
2. The studies referenced were old, 1995 -- knowledge/supplements have changed considerably since;
3. No mention of what the multi consisted of.
a. I'm assuming esp 10 yrs ago, most of these people took drug-store multis like Centrum. Not only is the "multi" aspect in question, but I've always thought both the quality of the ingredients & due to shelf live in drug-store chain environment, that some of the ingredients are actually detrimental.
b. I'm quite sure the 1992/1995 multi did not contains things like CoQ10, green teas, other anti-oxidants, etc.
c. Also suspect the multi contained plain old Vit E, which we now know to be actually harmful if not combined with the other elements -- Gamma E, tocotrienols, etc. [ Only taking d (and esp the dl -- the artificial form -- tocopherol might account for the increased prostate cancer by itself.]
d. Article said 12 % of the people took multis with iron. We now know that this can be very dangerous for older men.
e. Pretty sure the multi did not contain the impt items for preventing prostate: saw palmetto, pygeum, stinging nettle, etc. If these were avail 10 years ago, they certainly were not popular enough to be included in most multis.
f. If fish oils were contained, they were probably rancid after being on shelves for 2-4 years.
g. Article also mentions about possible cadmium, a known carcinogen, being mixed with the zinc. Again, no reason to trust the popular Centrum-type manufacturers.
4. No analysis was done with the food-frequency questionnaire. Many people who eat poorly think they can counteract this by also taking a multi.
5. Even the article says:
The key limitation of the study, according to the authors, is that the researchers did not know how long each participant used multi-vitamins. As the duration of multivitamin use is critical, lack of information of this sort could virtually render the results useless.
According to the authors, heavy multivitamin users were more likely to have prostate cancer screening using prostate specific antigen. This fact means that the heavy vitamin users were more than likely have some underlying conditions that are linked with higher risk of prostate cancer.
For instance, when a high count of antigen was detected, patients may be more likely advised by their physicians to take better care of their health, probably taking vitamins as one of protective measure against their conditions. This is what the foodconsumer.org scientist speculated.
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