Post by Swamp Gas on Nov 17, 2008 22:57:26 GMT -5
www.antiaging.com/vitamin_e_heart_cancer.html#Researcher%20Dr.%20Eva%20Lonn%20told%20the%20G&M%20that%20Vitamin%20E%20supplements%20dont%20protect%20against%20heart%20attack%20or%20stroke
Effects of Long Term Vitamin E Supplementation on Cardiovascular Events and Cancer
The Reporting
Here we go again. The reader is referred to our previous analyses of Vitamin E papers and more specifically to excellent discussions of statistical analysis. You are being misled -- yet once again.
The paper that was released this week in JAMA concluded "that daily administration of 400 IU of natural source vitamin E for median of 7.0 years had no clear impact on fatal and nonfatal cancers, major cardiovascular event or death. We observed an increase in the risk of heart failure."
And here is an example of what you will be reading. A rationalist, scientific deduction ... or an imprecise and prejudicial mind? You decide:
Researcher Dr. Eva Lonn told the G&M that "Vitamin E supplements don't protect against heart attack or stroke", and no evidence was found to "support a protective effect against cancer."
"Stop taking them. Throw them in the garbage," said Lonn.
Let us take the liberty of looking at the facts of the study itself.
The Set-up
At the outset the use of the term "natural source vitamin E" is confusing. It turns out that the study is referring the specific organization, the "Natural Source Vitamin E Association" of Washington, DC, which seems to be a bit shrouded in mystery. No public references to the company can be found.
The authors state in the methodology section that the source used was RRR-alpha-tocopheryl acetate. Sorry, that is not exactly natural Vitamin E. That is Vitamin E from a natural source that has been chemically altered. Somewhere between synthetic vitamin E and full alpha-tocopherol. So let us not be lead to believe that this is a food quality natural vitamin E. And, as we frequently suggest and observe, all natural vitamins should be taken as full complement mixtures. So that the preferred source of vitamin E would contain the alpha, beta, gamma and delta tocopherols. Mixed tocopherols. This is decidedly not the case. Déjà vu of the now infamous Finnish beta carotene study.
Now, when the authors conclude that there was no effect on cancer it contradicts the study’s own statistics. No puzzle here.
JAMA vol 293, No p.1342
Let us just for the moment, suspend all the exceptionally arcane and capricious methods of internal statistical analysis. Just look at the above charts and see if you can discern widely divergent or meaningful differences between the two curves on the left for cancer and the two curves on the right for heart failures. In fact, there is just about as much "benefit" in cancer protection as there is "risk" from developing heart problems. You can't really have it both ways. Or there is no difference.
Incidence and relative risk of the site specific cancers:
Absolute Difference Relative Difference
Prostate 116 (2.4) 119 (2.5) 0.14% -11%
Lung 69 (1.4) 96 (2.0) 0.23% -27.6%
Oral and pharyngeal 9 (0.2) 18 (0.4) 0.10% -85%
Colorectal 69 (1.4) 57 (1.2) .25% 27.9%
Breast 25 (0.5) 29 (0.6) .10% -36.8%
Melanoma 15 (0.3) 18 (0.4) 0.06% -30.8%
So why do they conclude and lead the press to say that there was no evidence of any effect on cancers? And why the statement above that increase in heart disease was so significant as to cause us to just throw all these vitamins away?
One is constantly referred back to the misleading use of relative risks and relative change vs absolute change.
In table 5 we see the results of 3 large randomized trials and the effect on lung cancer At 50 mg (low dose) no change. At 600mg slight increase in lung cancer. But in the current study at 400 IU a rather significant decrease in lung cancer. This finding is "discarded" through a series of clever inductions and statistical manipulations. Looking at all three studies spanning 60,000 patients, a very slight improvement in outcomes.
We turn to the major outcome of the trial which is increase in cardiovascular events. Look at these graphs.
JAMA vol 293, No p.1345
A difference is seen but it is ever so slight. The figures you will hear quoted in the press would be increase in heart attacks of 6%. But the absolute change is only 1.2%. Almost … insignificant. Not what you are hearing. You are hearing an absolutist and alarmist conclusion that the study shows you should not be taking vitamin E and that is has been proven to be harmful. And the echo machine quickly is reflected in every major news and magazine source within 24 hours.
The risk ratio for hospitalization for heart failure is quoted as a 21% increase. But the absolute figure is only 0.9%. Almost insignificant. You can see by the graph from above that at 5 years the difference is almost negligible. We refer you back, yet once again, to Gerd Giggerenzer's superb treatise, Calculated Risks on the constant misuse of medical statistics.
This is what you are hearing. Look at what is in the study. The reader is also referred to an excellent paper by Kassirer and Angell in the NEJM in 1994 in an attempt to place all research papers in proper perspective.
“Not surprisingly, the existence of all these contradictory reports has not escaped the attention of the media. When the recent study of the effects of vitamin E and beta carotene was published, many of the major newspapers and newsmagazines carried stories complaining about the problem. Ellen Goodman, a popular syndicated columnist, seemed to feel betrayed. She spoke of "planned obsolescence" in research, as though the problem were a conspiracy by scientists to confuse the public 15.” ...
“In our view the problem is not in the research but in the way it is interpreted for the public. In addition, the public itself must bear some responsibility for its unrealistic expectations. (Why should every scientific study reported in the media be a "win" for them?)”
“There are many ways the media could improve the way they interpret science to the public. In our view the most important would be to pay closer attention to the following caveats. First, an association between two events is not the same as a cause and effect. ... Second, demonstrating one link in a postulated chain of events does not mean that the whole chain is proved. ... Third, probabilities are not the same as certainties. ... And fourth, the way a scientific result is framed can greatly affect its impact. For example, the results of the GUSTO trial could be framed in three ways.”
-- NEJM: 1994: v331:189-190
What do we make of the "the latest" study? The Council on Responsible Nutrition (CRN) has already issued an initial public statement worthy of your time.
Interpretations
We are puzzled at even these slight differences but can offer some possible mechanisms or shortcomings.
1. This is neither a rational nor a “real world” array of anti-oxidants -- vitamin C, vitamin E (mixed tocopherols and tocotrienols) and co-factors such as alpha lipoic acid and preformed glutathione or its precursors such as NAC (n-acetyl cysteine).
2. The study uses an esterified vitamin E and not a full complement of truly natural, mixed tocopherols. We rather doubt the use of these in experimental design will ever be carried out.
3. The study is supported, in part, by large pharmaceutical interests and remains suspect. In fact, if you look at the frequency and intensity of the negative reporting on Vitamin E in the last few widely reported studies, you will begin to see a pattern. This is an orchestrated plan. The candid comments by the chief researchers, after the studies are released, bespeak the hidden agenda. Watch for the SELECT trials.
4. Deep in the discussion, the authors even postulate that there is a possibility that a displacement of gamma tocopherol disrupting the natural balance of antioxidant systems and a reduction in HDL. This confounds the study and supports our contention further that a true mix of vitamin C, mixed tocopherols, alpha lipoic acid and glutathione support factors would more properly simulate the true redox reactions in a natural system. It also slyly refutes their initial supposition and contention that alpha tocopheryl is the active form of Vitamin E. In reality, none of our patients take only one anti-oxidant. Reductio ad absurdum.
5. From the National Cancer Institute comes this more sober assessment and caveat:
Effects of Long Term Vitamin E Supplementation on Cardiovascular Events and Cancer
The Reporting
Here we go again. The reader is referred to our previous analyses of Vitamin E papers and more specifically to excellent discussions of statistical analysis. You are being misled -- yet once again.
The paper that was released this week in JAMA concluded "that daily administration of 400 IU of natural source vitamin E for median of 7.0 years had no clear impact on fatal and nonfatal cancers, major cardiovascular event or death. We observed an increase in the risk of heart failure."
And here is an example of what you will be reading. A rationalist, scientific deduction ... or an imprecise and prejudicial mind? You decide:
Researcher Dr. Eva Lonn told the G&M that "Vitamin E supplements don't protect against heart attack or stroke", and no evidence was found to "support a protective effect against cancer."
"Stop taking them. Throw them in the garbage," said Lonn.
Let us take the liberty of looking at the facts of the study itself.
The Set-up
At the outset the use of the term "natural source vitamin E" is confusing. It turns out that the study is referring the specific organization, the "Natural Source Vitamin E Association" of Washington, DC, which seems to be a bit shrouded in mystery. No public references to the company can be found.
The authors state in the methodology section that the source used was RRR-alpha-tocopheryl acetate. Sorry, that is not exactly natural Vitamin E. That is Vitamin E from a natural source that has been chemically altered. Somewhere between synthetic vitamin E and full alpha-tocopherol. So let us not be lead to believe that this is a food quality natural vitamin E. And, as we frequently suggest and observe, all natural vitamins should be taken as full complement mixtures. So that the preferred source of vitamin E would contain the alpha, beta, gamma and delta tocopherols. Mixed tocopherols. This is decidedly not the case. Déjà vu of the now infamous Finnish beta carotene study.
Now, when the authors conclude that there was no effect on cancer it contradicts the study’s own statistics. No puzzle here.
JAMA vol 293, No p.1342
Let us just for the moment, suspend all the exceptionally arcane and capricious methods of internal statistical analysis. Just look at the above charts and see if you can discern widely divergent or meaningful differences between the two curves on the left for cancer and the two curves on the right for heart failures. In fact, there is just about as much "benefit" in cancer protection as there is "risk" from developing heart problems. You can't really have it both ways. Or there is no difference.
Incidence and relative risk of the site specific cancers:
Absolute Difference Relative Difference
Prostate 116 (2.4) 119 (2.5) 0.14% -11%
Lung 69 (1.4) 96 (2.0) 0.23% -27.6%
Oral and pharyngeal 9 (0.2) 18 (0.4) 0.10% -85%
Colorectal 69 (1.4) 57 (1.2) .25% 27.9%
Breast 25 (0.5) 29 (0.6) .10% -36.8%
Melanoma 15 (0.3) 18 (0.4) 0.06% -30.8%
So why do they conclude and lead the press to say that there was no evidence of any effect on cancers? And why the statement above that increase in heart disease was so significant as to cause us to just throw all these vitamins away?
One is constantly referred back to the misleading use of relative risks and relative change vs absolute change.
In table 5 we see the results of 3 large randomized trials and the effect on lung cancer At 50 mg (low dose) no change. At 600mg slight increase in lung cancer. But in the current study at 400 IU a rather significant decrease in lung cancer. This finding is "discarded" through a series of clever inductions and statistical manipulations. Looking at all three studies spanning 60,000 patients, a very slight improvement in outcomes.
We turn to the major outcome of the trial which is increase in cardiovascular events. Look at these graphs.
JAMA vol 293, No p.1345
A difference is seen but it is ever so slight. The figures you will hear quoted in the press would be increase in heart attacks of 6%. But the absolute change is only 1.2%. Almost … insignificant. Not what you are hearing. You are hearing an absolutist and alarmist conclusion that the study shows you should not be taking vitamin E and that is has been proven to be harmful. And the echo machine quickly is reflected in every major news and magazine source within 24 hours.
The risk ratio for hospitalization for heart failure is quoted as a 21% increase. But the absolute figure is only 0.9%. Almost insignificant. You can see by the graph from above that at 5 years the difference is almost negligible. We refer you back, yet once again, to Gerd Giggerenzer's superb treatise, Calculated Risks on the constant misuse of medical statistics.
This is what you are hearing. Look at what is in the study. The reader is also referred to an excellent paper by Kassirer and Angell in the NEJM in 1994 in an attempt to place all research papers in proper perspective.
“Not surprisingly, the existence of all these contradictory reports has not escaped the attention of the media. When the recent study of the effects of vitamin E and beta carotene was published, many of the major newspapers and newsmagazines carried stories complaining about the problem. Ellen Goodman, a popular syndicated columnist, seemed to feel betrayed. She spoke of "planned obsolescence" in research, as though the problem were a conspiracy by scientists to confuse the public 15.” ...
“In our view the problem is not in the research but in the way it is interpreted for the public. In addition, the public itself must bear some responsibility for its unrealistic expectations. (Why should every scientific study reported in the media be a "win" for them?)”
“There are many ways the media could improve the way they interpret science to the public. In our view the most important would be to pay closer attention to the following caveats. First, an association between two events is not the same as a cause and effect. ... Second, demonstrating one link in a postulated chain of events does not mean that the whole chain is proved. ... Third, probabilities are not the same as certainties. ... And fourth, the way a scientific result is framed can greatly affect its impact. For example, the results of the GUSTO trial could be framed in three ways.”
-- NEJM: 1994: v331:189-190
What do we make of the "the latest" study? The Council on Responsible Nutrition (CRN) has already issued an initial public statement worthy of your time.
Interpretations
We are puzzled at even these slight differences but can offer some possible mechanisms or shortcomings.
1. This is neither a rational nor a “real world” array of anti-oxidants -- vitamin C, vitamin E (mixed tocopherols and tocotrienols) and co-factors such as alpha lipoic acid and preformed glutathione or its precursors such as NAC (n-acetyl cysteine).
2. The study uses an esterified vitamin E and not a full complement of truly natural, mixed tocopherols. We rather doubt the use of these in experimental design will ever be carried out.
3. The study is supported, in part, by large pharmaceutical interests and remains suspect. In fact, if you look at the frequency and intensity of the negative reporting on Vitamin E in the last few widely reported studies, you will begin to see a pattern. This is an orchestrated plan. The candid comments by the chief researchers, after the studies are released, bespeak the hidden agenda. Watch for the SELECT trials.
4. Deep in the discussion, the authors even postulate that there is a possibility that a displacement of gamma tocopherol disrupting the natural balance of antioxidant systems and a reduction in HDL. This confounds the study and supports our contention further that a true mix of vitamin C, mixed tocopherols, alpha lipoic acid and glutathione support factors would more properly simulate the true redox reactions in a natural system. It also slyly refutes their initial supposition and contention that alpha tocopheryl is the active form of Vitamin E. In reality, none of our patients take only one anti-oxidant. Reductio ad absurdum.
5. From the National Cancer Institute comes this more sober assessment and caveat: