X-Message-Number: 27877
From: "Hare, Tim R" <>
Subject: RE: [CN] Antioxidant Selenium Offers No Heart-disease
Date: Fri, 28 Apr 2006 11:26:03 -0400

"Despite the documented antioxidant and chemopreventive properties of

I find this statement a bit troubling, in that selenium is a transition
metal, with no inherent REDOX bias (putting aside the lack of meaning of any
such bias within different body compartments, and associated REDOX
microenvironment).  As well, metals have a complex role as enzyme active
site components, and selenium is no exception, being associated with
GSH-peroxidase, and the transferase family of enzymes involved in xenobiotic
metabolism in the liver.  

The net of all this is that for an author to refer to selenium as an
"antioxidant" begs the question of the author's knowledge base, and the
journals peer review process.  Such gaffs only confound and misinform,
extending debunking process of "antioxidants" via confusion over terms and

As a chemopreventative, even, it's role is unclear, given that low dietary
doses (not to mention different forms with attendant differences in
bioavailability, clearance, and metabolic fate) have not been clearly
implicated as chemopreventative, and higher doses found effective are close
to the toxic dose (again, depending on form) and are clearly pharmacological
in action, rather than dietary.

The statistics may be sound, but the discussion and the conclusions are

To crow about knocking down another "antioxidant" is simply rhetoric that
misrepresents the science, and misrepresents the positions of all parties on
both sides of the issue, and helps no one.  

Timothy R. Hare 
Automated Biotechnology (952) 
Bld NW-2, 503 Louise Lane, North Wales, PA 19454 
Merck E-mail: <mailto:> 
Voice: (267) 305-3235
Mobile (267) 984-7136
FAX: (267) 305-0182 

-----Original Message-----
From: CryoNet F [mailto:] On Behalf Of Doug Skrecky
Sent: Friday, April 28, 2006 12:20 AM
To: CryoNet F
Subject: [CN] Antioxidant Selenium Offers No Heart-disease Protection

[More of the same. Free radicals do not drive atherosclerosis.]

Selenium does not protect against cardiovascular disease, despite its
documented antioxidant and chemopreventive properties, analysis of a
randomized placebo-controlled clinical trial covering 13 years has shown.

The selenium-CVD association was a secondary endpoint in the Nutritional
Prevention of Cancer Trial, which was designed primarily to determine if
selenium supplementation could prevent the recurrence of non-melanoma
skin cancer.

Results of the trial, the only large randomized clinical trial to date to
examine selenium supplementation alone in the prevention of CVD, appear
in the April 15 issue of the American Journal of Epidemiology. Saverio
Stranges, M.D., Ph.D., assistant professor of social and preventive
medicine in the School of Public Health and Health Professions, University
at Buffalo, is first author.

"Our results extend previous research based on smaller intervention
trials focusing on cardiovascular risk factors," said Stranges. "Our
findings are consistent with those from previous studies that have shown
no beneficial effect of selenium supplementation in combination with
other antioxidants on the primary prevention of cardiovascular disease."

Several antioxidants, vitamins C and E in particular, that were thought
to play a role in preventing heart disease based on observational studies
have turned out not to be protective in randomized clinical trials, and
selenium now has joined this group.

The main findings of this report focus on the 1,004 participants in the
study, conducted from 1983-96, who were free of cardiovascular disease
when they were recruited. Participants came from seven dermatology
clinics in low selenium areas of the eastern United States: Augusta and
Macon, Ga.; Columbia, S.C.; Miami, Fla.; Wilson and Greenville, N. C.; and
Newington, Conn.

Enrollees were assigned randomly to take a tablet containing 200
micrograms of selenium daily or a placebo. Information on
sociodemographics, health habits, education and body mass index also was

Participants provided blood samples at their respective clinics twice a
year and reported any new illnesses or medications. Individuals were
followed for an average of 7.6 years.

Results showed no association between selenium supplementation on any of
the endpoints studied: coronary heart disease, stroke or deaths from
cardiovascular disease, Stranges said. There also was no difference in
the endpoints based on the level of selenium at baseline. In addition,
the lack of significant association with CVD endpoints was confirmed even
in the 246 participants who had CVD at baseline. (This data does not
appear in the published manuscript.)

"These results must be interpreted cautiously," said Stranges, "because
they result from exploratory analyses, although from the largest
randomized clinical trial available that has selenium only as the
intervention. However, this report adds important information to our
knowledge on the role of selenium in cardiovascular-disease prevention,
indicating no overall benefit of supplementation by selenium alone in
prevention of cardiovascular disease."

Am J Epidemiol. 2006 Apr 15;163(8):694-9. Epub 2006 Feb 22.
Effects of selenium supplementation on cardiovascular disease incidence
and mortality: secondary analyses in a randomized clinical trial.
  Despite the documented antioxidant and chemopreventive properties of
selenium, studies of selenium intake and supplementation and
cardiovascular disease have yielded inconsistent findings. The authors
examined the effect of selenium supplementation (200 microg daily) on
cardiovascular disease incidence and mortality through the entire blinded
phase of the Nutritional Prevention of Cancer Trial (1983-1996) among
participants who were free of cardiovascular disease at baseline
(randomized to selenium: n = 504; randomized to placebo: n =
500). Selenium supplementation was not significantly associated with any
of the cardiovascular disease endpoints during 7.6 years of follow-up
(all cardiovascular disease: hazard ratio (HR) = 1.03, 95% confidence
interval (CI): 0.78, 1.37; myocardial infarction: HR = 0.94, 95%
CI: 0.61, 1.44; stroke: HR = 1.02, 95% CI: 0.63, 1.65; all cardiovascular
disease mortality: HR = 1.22, 95% CI: 0.76, 1.95). The lack of
significant association with cardiovascular disease endpoints was also
confirmed when analyses were further stratified by tertiles of baseline
plasma selenium concentrations. These findings indicate no overall effect
of selenium supplementation on the primary prevention of cardiovascular
disease in this population.

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