These studies seem to reflect the whole spirit of the times right now.
Everything is so corporately run.  If you read Thomas Kuhn, one can
see the paradigm for science is to now back up pharmacueticals.
Linus Pauling lived, very active,  to his 90's.  We will see the
real life results of people who are pro-supplements.

Studies also came down on mega-dosing vitamin C.  What were wrong
with all those studies that were done in the pre-Reagan era?  

Still, it makes you have a more balanced view.  
--
Robert Pearson
http://www.rspearson.com/
ParaMind Brainstorming Software http://www.paramind.net

Yes, this analysis clearly points out what is WRONG with this very old
story about vitamin E.

"This is an unfortunate misdirection of science in an attempt to make
something out of nothing for the sake of headlines," comments John
Hathcock, Ph.D., vice president, scientific and international affairs,
CRN.
...
A meta-analysis on vitamin E and all-cause mortality ... tries to
draw conclusions for the whole population based on a combination of
studies of people who were already at grave risk with existing
diseases including cancer, heart disease, Alzheimer's, Parkinson's and
kidney failure ... stating "the generalizability of the findings to
healthy adults is uncertain. ...Yet they go on to make sweeping
generalizations about the use of vitamin E and all-cause mortality for
the whole population, although they provide no evidence that these
kinds of effects would occur in healthy populations.

Dr. Hathcock added, "In reviewing the totality of evidence on vitamin
E, including all clinical trial data and several large observational
studies, CRN agrees with the Institute of Medicine in finding vitamin
E supplements safe at levels of at least up to 1,000 mg (1,600 I) for
normal, healthy adults. This meta-analysis provides no convincing
evidence to the contrary."

Yes Mark 'the Toad' this is clearly another fraudulent use of science
in an attempt to make something out of nothing for the sake of
headlines.  Thus, study actually got Dr. Mercola going on the
anti-vitamin E bandwagon. :(

I would classify this study as another pathetic attempt to making
sweeping generalizations about healthy populations from studies of
gravely sick and dying individuals.

Vitamin E is a preventative rather than a quick fix magical potion.
Once you get heart disease, Mark ... don't expect vitamin E to bail
you out.

Just thought that you might want to know.
--
john gohde
http://gnu-dictionary.naturalhealthperspective.com/

Sample size was more strongly correlated than Vitamin E dosage.

From Figure 2, I was able to do my own ciphering. :)

There were 19 studies that had a total of 135,967 test subjects.  Of
these 12,506 or 9.2% died (6,232 [9.17%] took vitamin E and 6,272
[9.22%] were controls).

So, from these totally neutral results this study concluded that
Vitamin E caused deaths and showed a dosage dependent trend.  Ha, ...
Hah, Ha!  Where?  I surely do NOT see it from the data.

There was only one study with dramatically positive results which had
430 subjects in each group. And, there were only 3 dramatically
negative studies (149 in one group, 211 in another study, and with 600
subects in a group in the third study).  However, there were an
average of subjects per study group of  3,578 for all 19 studies.

Ha, ... Hah, Ha!  

Therefore, I can easily conclude from the data that the subject sample
size showed a stronger correlation to the death rate than the dosage
rate of Vitamin E did.

Further, when looking at the studies with over 3,500 test subjects per
study group there WERE only 5 studies worth looking at. Two were
favorable, two were neutral, and only one was negative.   That one
study alone (MRC/BHF HPS 2002), at a dosage of 660 IU's day, accounts
for the entire 5% negative death rate.  Gee, I wonder if that study
was bogus?  Ha, ... Hah, Ha!

Therefore I concur, that the meta-analysis combined 19 individual
studies, eighteen of which showed no statistically significant
increase in mortality, squeezing out an overall finding of no
increased risk.
--
john gohde
http://gnu-dictionary.naturalhealthperspective.com/

MRC/BHF Heart Protection Study of antioxidant vitamin supplementation
in 20,536 high-risk individuals: a randomised placebo-controlled
trial. Lancet. 2002;360:23-33. [PMID: 12114037].[Medline]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=1
2114037&dopt=Abstract

"METHODS: 20,536 UK adults (aged 40-80) with coronary disease, other
occlusive arterial disease, or diabetes were randomly allocated to
receive antioxidant vitamin supplementation (600 mg vitamin E, 250 mg
vitamin C, and 20 mg beta-carotene daily) or matching placebo.
Intention-to-treat comparisons of outcome were conducted between all
vitamin-allocated and all placebo-allocated participants. An average
of 83% of participants in each treatment group remained compliant
during the scheduled 5-year treatment period. Allocation to this
vitamin regimen approximately doubled the plasma concentration of
alpha-tocopherol, increased that of vitamin C by one-third, and
quadrupled that of beta-carotene. Primary outcomes were major coronary
events (for overall analyses) and fatal or non-fatal vascular events
(for subcategory analyses), with subsidiary assessments of cancer and
of other major morbidity. FINDINGS: There were no significant
differences in all-cause mortality (1446 [14.1%] vitamin-allocated vs
1389 [13.5%] placebo-allocated), or in deaths due to vascular (878
[8.6%] vs 840 [8.2%]) or non-vascular (568 [5.5%] vs 549 [5.3%])
causes. Nor were there any significant differences in the numbers of
participants having non-fatal myocardial infarction or coronary death
(1063 [10.4%] vs 1047 [10.2%]), non-fatal or fatal stroke (511 [5.0%]
vs 518 [5.0%]), or coronary or non-coronary revascularisation (1058
[10.3%] vs 1086 [10.6%]). For the first occurrence of any of these
"major vascular events", there were no material differences either
overall (2306 [22.5%] vs 2312 [22.5%]; event rate ratio 1.00 [95% CI
0.94-1.06]) or in any of the various subcategories considered. There
were no significant effects on cancer incidence or on hospitalisation
for any other non-vascular cause. INTERPRETATION: Among the high-risk
individuals that were studied, these antioxidant vitamins appeared to
be safe. But, although this regimen increased blood vitamin
concentrations substantially, it did not produce any significant
reductions in the 5-year mortality from, or incidence of, any type of
vascular disease, cancer, or other major outcome."

Ha, ... Hah, Ha!  

Funny how Lancet interprets their findings differently.

There were no significant differences in all-cause mortality.Lancet
says high dosage Vitamin E is safe, but not effective.
--
john gohde
http://gnu-dictionary.naturalhealthperspective.com/

I suspect that the water solubilized forms would
have better bioavailability ........lets reword that...
the water solubilized forms would get into the
blood stream whereas other forms might
be somewhat more likely to pass all the way thru
the gut.

I doubt there is any risk from vitamin E provided
the the user is using rrr-alpha tocopherol and
plus mixed tocopherols OR tocotrienols.
Many of these studies used racemic tocopherol.
A vitamin E supplement taker does well to
take vitamin C, flavonoids, alpha lipoic acid
to regenerate the free radical form into the
antioxidant form. Further the user should
maintain a good vitamin K status. At a minimum
400 mcg per day and preferably a milligram or more.
I take a vitamin K supplement with my vitamin E.
And my vitamin E isn't what the EU bureaucrats
call vitamin E as I take mixed tocopherols that
is high gamma and I also take some palm
derived tocotrienols. And I also take some
tocopheryl succinate.

If you knew what the recommended daily amount was actually representing, it may not
seem so absurd. I'll use the terms from the US, because I'm more familiar with them.

The core determination is the EAR, the Estimated Average Requirement. That's the
50th percentile of overt deficiency risk, based on the seven-day averaged intake of
a nutrient. At the EAR, there are equal numbers of individuals showing overt
deficiency symptoms, and equal numbers not. The RDA is two standard deviations above
the EAR. By definition, that captures all individuals up to the 97.5th percentile.
At the RDA of intake, 1 in 40 *healthy and normal* subjects is still exhibiting
overt deficiency symptoms.

For a visual representation, see the graph at:
http://books.nap.edu/books/0309071836/html/24.html#pagetop

Usually, the overt deficiency symptoms are with respect to one particular and
defined symptom or symptom cluster. In the case of B12, that is blood counts, and
the deficiency state is defined pernicious anemia. The problem is that not all
people deficient in B12 have pernicious anemia. Moreover, as circulating B12
concentrations do not reflect tissue stores, even serum concentration assessment
does not clarify if B12 deficiency exists. Additionally, restricting thinking to
pernicious anemia alone does not address the other functions of vitamin B12 in the
body (e.g. as a scavenger of peroxynitrite).

Now, back to that "idiotic" 100,000% of RDA. If you look at the table at:
http://books.nap.edu/books/0309065542/html/310.html#pagetop, you'll see that
high-dose crystalline B12 is absorbed at about 1% of intake (by passive diffusion,
rather than via the saturable uptake pump which requires intrinsic factor).
Immediately, we're down to each tablet supplying 1,000% of RDA, or 10 times the 5
microgram recommended daily intake. Given that normal food intake leads to about a
50% uptake, we're looking at about a 20-fold increase in B12 uptake, above the RDA.

Vitamin B12 is stored in tissues, unlike any other B-vitamin. Circulating levels of
B12 are buffered by tissue stores. It has been estimated that the tissue stores
might hold about a 3 year supply of B12. The only way to replenish those tissues is
to exceed the RDA (the floating average mean requirement) by a substantial amount,
over a substantial period of time. There is no Upper Limit or toxic threshold to
consider for B12. The limiting factor is physiological, as plasma binding proteins
are saturable. Excess unbound B12 is excreted in urine.

Who might benefit from such high doses of B12? Apart from those deficient in
intrinsic factor, anyone with hypochlorhydria (low stomach acid) or achlorhydria (no
stomach acid), whether idosyncratic or iatrogenic. Anyone taking a proton pump
inhibitor or other acid-reducing medication is living on borrowed time, as
sufficient stomach acid is a requirement for the extraction of B12 from food.
Vegetarians of all sorts are at substantial risk. It is an indirect mechanism, but
B12 is essential for the production of stomach acid in the first place. Being
deficient in B12 can be a cause of poor B12 uptake, locking in the deficiency state.
By the time symptoms show up, you're well into a systemic depletion of B12, which
may show neurological signs or GERD (for example), rather than the classic
pernicious anemia.

By no means am I advocating huge intakes of vitamins, absent some indication of
health problems. However, RDAs are based on overt deficiency states in *normal
healthy* people. There is (generally) a huge separation between RDA and Upper Limit
of intake. Somewhere in the broad expanse, I believe there is another conceptual
position (not defined in the conventional paradigm) which I call Optimal Intake.
Just because some people get what they need from diet alone (half of all people at
EAR are no longer exhibiting overt deficiency) does not mean that all people can do
so. There are many acquired or lifespan-related reasons for needing supplemental
intake.

"I wonder how humans existed before vitamin tablets, maybe they used placebos,
actually thinking about it - they did."

Almost right. You missed a letter. They died.

Lar