Non-prescription molecules:
http://www.lef.org/featured-articles...rt_060707.html
Is There a Conspiracy to Destroy Vitamin Supplements?
by Steven Joyal, M.D. and William Faloon
For the past three decades, the Life Extension Foundation has warned
about an insidious relationship that exists between the federal
government and pharmaceutical industry. Our position has been that
this alliance represents a conspiracy that is largely responsible for
the many problems faced by our health care system today.
On May 16, 2007, an agency of the federal government published a
report that linked the use of multivitamin supplements with an
increased risk of aggressive prostate cancer. The media made headline
news stories out of this government-funded report, which has the
unfortunate consequence of dissuading uninformed Americans from taking
their vitamins. This benefits the pharmaceutical industry as vitamin
deficiencies make aging humans more vulnerable to diseases that
require lots of expensive prescription drugs to treat.
Even a cursory analysis of this government study reveals flaws so
egregious that the findings have no meaning whatsoever. This article
provides a meticulous rebuttal to this defective study. I want to
point out in this introduc*tion, however, some obvious flaws that
would indicate that this study may have been deliberately designed in
a way to cast a negative light on multivitamin supplements.
Just imagine if a study were conducted where ordinary people were
asked to remember how much
vitamin E they took each day for the past
ten years. While Life Extension members might be able to recall this,
the typical person randomly taking vitamin pills is unlikely to
accurately recall their vitamin E dose.
In this government-funded study bashing multivitamins, the researchers
had the audacity to place each subject who stated they did not know
how much vitamin E they took into the 400 IU a day category. This
means when the results where tabulated to see if multivitamin use was
associated with prostate cancer risk, men who may or may not have
taken any vitamin E were deemed to have taken 400 IU a day.
Men who reported taking even one multivitamin supplement a month were
recorded as taking a multivitamin every single day. This meant that
when the data was tabulated, those who may have taken as few as twelve
multivitamin supplements a year where considered to have taken a
multivitamin each day.
Based on the absurd design parameters established, one can clearly see
that this multi-million dollar government study was designed in a way
to make it impossible to glean any meaningful data whatsoever about
the effects of multivitamins on prostate cancer risk. As you will
learn in this article, there were so many flaws in this study that it
should have been rejected for publication in any peer-reviewed
scientific journal. Since it was published in a journal controlled by
the federal government, however, it made it into the scientific arena
and as a result into the mainstream media.
Life Extension has identified defects in previous studies that seek to
discredit the value of dietary supplements. As you will read, this
particular government-funded study may perhaps be the most error-
ridden report on dietary supplements ever published.
An epidemiology study published in the Journal of the National Cancer
Institute (JNCI) on May 16, 2007, has been heralded by many in the
mainstream media as proof that multivitamin use is linked with certain
aspects of prostate cancer and that specific nutritional supplements
are associated with an increased risk of advanced prostate cancer.1
Although this study was observational in nature, that did not stop the
headline-hungry mainstream media from misrepresenting the results and
conclusions of this study. As lead study author Michael F. Leitzmann,
MD, from the National Cancer Institute was quoted as saying:
"This was an observational study, and so no conclusions can be drawn
about cause and effect. For this reason, we must be cautious in giving
any firm advice based on the results of this study."2
A questionnaire-based observational study that did not test for
causality
This recent population-based analysis used questionnaires and prostate
cancer patient recall/memory as a basis of data collection.
Questionnaire-based information collection is limited in accuracy to
the memory recall of the study subjects. The majority of people cannot
recall what they ate for breakfast one week ago, or which shirt they
wore to work two weeks ago, or how many gallons of gas they purchased
during their last trip to the gas station, never mind specific doses
and frequency of use of a myriad of dietary supplements months or
years ago.
Data dredging, also known as data mining, involves using mathematical
techniques to sift through large amounts of historical information to
try and patch together associations between bits and pieces of data.
These types of techniques look for associations, not causal
relationships. Contrast this emphasis on testing for associations
versus the use of direct-intervention studies. Direct-intervention
studies evaluate the direct effect of an intervention in a population
over time thus, direct-intervention studies assess for cause and
effect relationships.
An example of data dredging/data mining would be to look at different
groups of patient characteristics (for example, patients who recall
consuming five alcoholic drinks per week, patients who remember eating
more than 10 servings of vegetables a week, patients who attend
religious services at least 25 times per year, etc.) in an insurance
company's HMO database to see which set of characteristics was more
associated with the development of lung cancer. On the other hand, an
example of a direct-intervention study would be to give a group of
patients a particular drug, and then study how many lung cancers were
prevented by this drug over time.
The recent questionnaire-based observational study employed the use of
data dredging/data-mining techniques, and did not study the direct
intervention of supplements on prostate cancer risk.
Better-quality human clinical studies show a protective effect
Fortunately, there are a wealth of other prostate cancer prevention
studies that use rigorous and well-defined design criteria. The
following studies suggest significant benefits from selenium and other
antioxidant supplements, such as beta-carotene and the gamma-
tocopherol fraction of vitamin E:
A 1996 study from the Nutritional Prevention of Cancer Study Group
showed that patients treated with 200 mcg of selenium had a
significant 50% reduction in total cancer mortality, a 37% reduction
in total cancer incidence, and a reduction in the risk of lung,
colorectal, and prostate cancers.3
A 1998 double-blind, placebo-controlled trial showed that 200 mcg of
selenium significantly decreased the risk of prostate cancer by 63%
over an average of 4.5 years of treatment and an average follow-up of
6.5 years. Furthermore, there were significant health benefits for
total cancer mortality and the incidence of total lung and colorectal
cancer.4
The SU.VI.MAX trial was composed of 5,141 men followed over eight
years, and it evaluated antioxidant vitamin and mineral
supplementation and prostate cancer prevention. Among aging men with a
normal PSA count, there was a marked, statistically significant 48%
reduction in the rate of prostate cancer for men receiving the
antioxidant supplements.5
The Physicians' Health Study, a randomized, double-blind, placebo-
controlled trial, examined dietary supplementation in the primary
prevention of cancer among 22,071 US male physicians ages 40-84. Men
experienced a significant 32% reduction in the risk of prostate
carcinoma with 50 mg of beta-carotene supplementation.6
The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC)
demonstrated a 32% reduction in prostate cancer risk in response to
daily vitamin E supplementation. Also, participants with higher
circulat*ing concentrations of the important gamma-tocopherol form of
vitamin E had lower prostate cancer risk.7
In addition, high levels of serum selenium have been associated with a
29% decreased risk of prostate cancer (comparing highest to lowest
quartiles for serum selenium), and analysis of serum selenium levels
indicates a reduced risk of prostate cancer with selenium levels above
concentrations of 0.135 mcg/mL (median value), with additional benefit
for selenium among men with low serum alpha-tocopherol concentrations.
8
Moreover, a recent study also demonstrated that higher serum selenium
may be associated with reduced prostate cancer risks in men who
reported a high intake of vitamin E, as well as in multivitamin users.
9
Dose-collection techniques raise accuracy concerns
The recent JNCI questionnaire-based study used arbitrary dose
assignment for unknown dosing of vitamin E, as well as other low-
stringency criteria for other multivitamins.
Taken verbatim from the questionnaire-based observational study:
"Each category of (vitamin E) 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" and "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)."
If a man used iron, selenium, or folate supplements once per month in
the past 12 months, how can this be reliable for ascertaining dose or
compliance? If a man could not remember a specific dose of vitamin E
used, then how is any dose accuracy possible if men are arbitrarily
assigned a dose of 400 IU of vitamin E?
Life Extension has long reported the importance of the gamma-
tocopherol fraction of vitamin E and the suboptimal benefits of using
only alpha-tocopherol supplementation, yet this questionnaire-based
study made no attempt to record gamma-tocopherol dosing.
Amazingly, despite these inherent dosing inaccuracies, the mainstream
media was quite content to argue that supplements such as vitamin E
and selenium are linked with advanced prostate cancer risk.
The overall analysis showed no evidence of a trend for increased risk
of prostate cancer in any category of multivitamin frequency
The primary analysis in this questionnaire-based study did not show
evidence of risk of prostate cancer (Table 2 copied directly from the
study-below), yet this fact was not reported by the headline-hungry
main*stream media. Rather, the media chose to emphasize convoluted
subgroup analyses to sensationalize contrived statistical
associations.
In none of the categories in Table 2 (below) from the study, including
advanced prostate cancer, were any of the p-values (probability
values) for trends across categories significant:
Study design bias against multi-vitamins
Most, if not all, epidemiological studies are subject to bias of one
sort or another. It is important to assess the probable impact of bias
on outcomes. There are several forms of bias in this questionnaire-
based study that affected the observed associations.
In this study, a family history of prostate cancer was associated with
supplement use, and prostate cancer PSA screening was most frequent
among heavy users of multivitamins, consistent with other survey data
showing that men who used supplements were more likely to have PSA
examinations than nonusers. Therefore, there is increased prostate
cancer detection among this subpopulation of men who are heavy
supplement users and who are more likely to seek health care tests
owing to a positive family history of prostate cancer. This is a form
of detection or diagnosis bias.
As the authors accurately said (but the mainstream media did not
report):
"...it is possible that the positive association with heavy use of
multivitamins along with certain supplements was spurious..." and "...the
increased risk of localized prostate cancer among men with heavy
multivitamin use and concomitant use of a selenium or folate
supplement in our study may be due to similar diagnostic bias..."
In fact, when excluding men diagnosed with prostate cancer within the
initial two years of the study period, the relative risk of advanced
prostate cancer with heavy multivitamin use no longer existed.
Men with a family history of prostate cancer are also more likely to
consume dietary supplements for prostate health, further confounding
the interpretation of the overall data analysis in this questionnaire-
based study. Family history of prostate cancer is itself a recognized
risk factor for prostate cancer development.
Lack of biological plausibility
Even assuming that the results from this flawed, questionnaire-based
study are accurate, there remains the question of biologic
plausibility. In other words, is there a plausible mechanism that can
explain why or how these study results could occur?
Vitamin E, beta-carotene, and vitamin C are micronutrient antioxidants
that protect cells from oxidative damage involved in prostate
carcinogenesis. For example, in a separate trial, supplemental vitamin
E was associated with a decreased risk of prostate cancer among
smokers, and supplemental beta-carotene was associated with a
decreased risk of prostate cancer among men with low baseline plasma
beta-carotene levels, while beta-carotene intake at a dose level of at
least 2000 mcg/day was associated with a 48% decrease in prostate
cancer risk in men with low (below the median of 4,129 mcg/ day)
dietary beta-carotene intake.10
Although selenium and alpha-tocopherol (the major form of vitamin E in
supplements) appear to have protective effects against prostate
cancer, little attention has been paid by scientific researchers to
gamma-tocopherol. A case in point is a study that examined the
associations of alpha-tocopherol, gamma-tocopherol, and selenium with
incident prostate cancer. The results showed that the risk of prostate
cancer declined with increasing concentrations of alpha-tocopherol.
For gamma-tocopherol, men in the highest fifth of the distribution had
a powerful five-fold reduction in the risk of developing prostate
cancer than men in the lowest fifth of the distribution. Statistically
significant pro*tective associations for high levels of selenium and
alpha-tocopherol were observed only when gamma-tocopherol
concentrations were high.11 The men participating in the study
claiming that multivitamins increased aggressive prostate caner risk
were not obtaining any gamma tocopherol in supplement form.
Cancer industry profits require lots of cancer victims
The "cancer industry" is gigantic. Like any other business, profits
are dependent on consistent and predictable volume. The American
Cancer Society predicts that 1,444,920 people will be diagnosed with
cancer in the United States in year 2007.
Those involved in the "cancer industry" have a huge financial stake in
1,444,920 Americans contracting cancer this year. A substantial body
of research, however, indicates that these cancer rates could be
sharply reduced. For example, very strong evidence indicates that
higher-potency vitamin D supplements could cut the rate in which
people contract cancer by 50% or more. Yet the federal government
makes it illegal for those who sell vitamin D supplements to make a
cancer claim on the label of their product, thereby denying this
knowledge to the majority of Americans.
If cancer incidences did decline by 50%, an enormous economic upheaval
would occur throughout the "cancer industry". There is thus a huge
economic bias in keeping Americans in the dark about what they can do
to reduce their risk of contracting cancer.
The amount of vitamin D contained in the multivitamin supplements
taken by participants in the study that claimed an increased risk of
aggressive prostate cancer was small, as were the potencies of
selenium, vitamin E and other nutrients. In response to the many
favorable reports about vitamin D, we expect the makers of
multivitamins to add more vitamin D to their formulas, as it takes up
virtually no space and costs very little.
The problem is that fewer Americans are likely to take these
multivitamin supplements based on the wildly distorted stories
disseminated by the media (based on this horribly flawed government-
published study). The cancer industry's public relations machine thus
ensures a continuous flow of new patients who will require surgery,
radiation, chemotherapy, and a host of other super-expensive drugs.
Good financial news for the cancer industry, but disastrous for the
1.4 million individuals who face the nightmare of mutilating and toxic
treatments that too often fail to cure the disease.
As educated health consumers, Life Extension members learn the hard
facts as to what may or may not prevent cancer. Our fear is that the
effect of this recent questionnaire-based observational study will
both deter men from aggressive prostate health and cancer prevention
strategies, and quell future research on dietary supplementation and
prostate cancer risk.
References
1. Lawson KA, Wright ME, Subar A, et al. Multivitamin use and risk of
prostate cancer in the National Institutes of Health-AARP Diet and
Health Study. J Natl Cancer Inst. 2007 May 16;99(10):754-64.
2. Available at:
http://www.medscape.com/viewarticle/556711. Accessed
May 22, 2007.
3. Clark LC, Combs GF, Jr., Turnbull BW, et al. Effects of selenium
supplementation for cancer prevention in patients with carcinoma of
the skin. A randomized controlled trial. Nutritional Prevention of
Cancer Study Group. JAMA. 1996 Dec 25;276(24):1957-63
4. Clark LC, Dalkin B, Krongard, et al. Decreased incidence of
prostate cancer with selenium supplementation: results of a double-
blind cancer prevention trial. Br J Urol. 1998 May;81(5):730-4.
5. Meyer F, Galan P, Douville P, et al. Antioxidant vitamin and
mineral supplementation and prostate cancer prevention in the
SU.VI.MAX trial. Int J Cancer. 2005 Aug 20;116(2):182-6.
6. Cook NR, Stampfer MJ, Ma J, et al. Beta-carotene supplementation
for patients with low baseline levels and decreased risks of total and
prostate carcinoma. Cancer. 1999 Nov 1;86(9):1783-92.
7. Weinstein SJ, Wright ME, Pietinen P, et al. Serum alpha-tocopherol
and gamma-tocopherol in relation to prostate cancer risk in a
prospective study. J Natl Cancer Inst. 2005 Mar 2;97(5):396-9.
8. Vogt TM, Ziegler RG, Graubard BI, et al. Serum selenium and risk of
prostate cancer in U.S. blacks and whites. Int J Cancer. 2003 Feb
20;103(5):664-70.
9. Peters U, Foster CB, Chatterjee N, et al. Hayes RB. Serum selenium
and risk of prostate cancer-a nested case-control study. Am J Clin
Nutr. 2007;85(1):209-17.
10. Kirsh VA, Hayes RB, Mayne ST, et al. Supplemental and dietary
vitamin E, beta-carotene, and vitamin C intakes and prostate cancer
risk. J Natl Cancer Inst. 2006 Feb 15;98(4):245-54.
11. Helzlsouer KJ, Huang HY, Alberg AJ, et al. Association between
alpha-tocopherol, gamma-tocopherol, selenium, and subsequent prostate
cancer. J Natl Cancer Inst. 2000 Dec 20;92(24):2018-23.
Non-prescription molecules for Diabetes 
Linear Mode
