Re: [DIYbio] Re: Antioxidant supplements are bad for you

"The trials appeared to have enough statistical similarity that they
could be combined."

ALARM ALARM ALARM

I discard most "metastudies" if they can't immediately convince me
they're not a fishing expedition. Do they have an entire paper chapter
devoted to "all the studies we didn't incorporate"?

When presented with a corpus of research data that you propose a
"metastudy" of, if you want a certain answer you can trivially (and
crucially *unconsciously*) choose just the studies that, by
statistically irrelevant chance variance, will present the answer you
want when considered in aggregate.

This method is used by unscrupulous drug manufacturers all the time; as
they are not required (yet) to release *all* of their trials for
assessment by the FDA etc., they instead release the fraction of their
trials that support their assertion of benefit, and withhold the others.

Say you want to prove your coin flip can cure cancer. Trivial; just
release the trial data where flipping heads lead to better patient
outcomes, and disregard the rest. Same for a "meta-analysis" of studies
examining coinflips which all get different results; you can
deliberately or inadvertently (due to confirmation bias) disqualify
studies that disagree with your hypothesis and get *great, solid*
statistical answers that support it.

On 22/02/14 00:43, David Murphy wrote:
>> What are the excipients
>
> this is the sort of criticism which could be applied to every trial ever
> for anything and leaves me thinking of a certain episode of "yes minister"
>

> *Sir* *Humphrey*: In stage two you go on to discredit the information
> you're not publishing.
> *Jim* *Hacker*: How, if you're not publishing it?
> *Sir* *Humphrey*: It's much easier if it's not published. You do it by

> press leaks. Say it leaves some important questions unanswered, that much
> of the evidence is inconclusive, that the figures are open to other
> interpretations, that certain findings are contradictory and that some of
> the main conclusions have been questioned.

> *Jim* *Hacker*: Suppose they haven't?
> *Sir* *Humphrey*: Then question them. Then they have.
> *Jim* *Hacker*: But to make accusations like that you'd have to go through

> it with a fine-toothed comb.

> *Sir* *Humphrey*: Nonsense - you can say all that without reading it. There

> are always some questions unanswered.

> *Jim* *Hacker*: Such as?
> *Sir* *Humphrey*: The ones that weren't asked.

>
> Lets just jump straight to the Cochrane Review
>
> http://summaries.cochrane.org/CD007176/antioxidant-supplements-for-prevention-of-mortality-in-healthy-participants-and-patients-with-various-diseases
>

> The present systematic review included *78 randomised clinical trials*. In

> total, 296,707 participants were randomised to antioxidant supplements
> (beta-carotene, vitamin A, vitamin C, vitamin E, and selenium) versus
> placebo or no intervention. Twenty-six trials included 215,900 healthy
> participants. Fifty-two trials included 80,807 participants with various
> diseases in a stable phase (including gastrointestinal, cardiovascular,
> neurological, ocular, dermatological, rheumatoid, renal, endocrinological,
> or unspecified diseases). A total of 21,484 of 183,749 participants (11.7%)
> randomised to antioxidant supplements and 11,479 of 112,958 participants
> (10.2%) randomised to placebo or no intervention died. The trials appeared
> to have enough statistical similarity that they could be combined. When all
> of the trials were combined, antioxidants may or may not have increased
> mortality depending on which statistical combination method was employed;
> the analysis that is typically used when similarity is present demonstrated
> that antioxidant use did slightly increase mortality (that is, the patients
> consuming the antioxidants were 1.03 times as likely to die as were the
> controls). When analyses were done to identify factors that were associated
> with this finding, the two factors identified were better methodology to
> prevent bias from being a factor in the trial (trials with 'low risk of
> bias') and the use of vitamin A. In fact, when the trials with low risks of
> bias were considered separately, the increased mortality was even more
> pronounced (1.04 times as likely to die as were the controls). The
> potential damage from vitamin A disappeared when only the low risks of bias
> trials were considered.

> *The increased risk of mortality was associated with beta-carotene and

> possibly vitamin E and vitamin A, but was not associated with the use of
> vitamin C or selenium. The current evidence does not support the use of
> antioxidant supplements in the general population or in patients with

> various diseases.*

>
>
> On Fri, Feb 21, 2014 at 4:01 PM, Jonathan BISSON
> <bjonnh-diybio@bjonnh.net>wrote:
>
>> David Murphy <murphy.david@gmail.com> writes:
>>
>>>> Really ? Do you have sources about that ?
>>>
>> http://www.goodreads.com/quotes/735647-two-large-trials-of-antioxidants-were-set-up-after-peto-s
>>> Two groups of people at high risk of lung cancer were studied: smokers,
>> and
>>> people who had been exposed to asbestos at work. Half were given
>> 3-carotene
>>> and vitamin A, while the other half got placebo. Eighteen thousand
>>> participants were due to be recruited throughout its course, and the
>>> intention was that they would be followed up for an average of six years;
>>> but in fact the trial was terminated early, because it was considered
>>> unethical to continue it. Why? The people having the antioxidant tablets
>>> were 46 per cent more likely to die from lung cancer, and 17 per cent
>> more
>>> likely to die of any cause,* than the people taking placebo pills.
>>>
>>> http://www.ncbi.nlm.nih.gov/pubmed/15572756
>>> The Beta-Carotene and Retinol Efficacy Trial (CARET) tested the effect of
>>> daily beta-carotene (30 mg) and retinyl palmitate (25,000 IU) on the
>>> incidence of lung cancer, other cancers, and death in 18,314 participants
>>> who were at high risk for lung cancer because of a history of smoking or
>>> asbestos exposure. CARET was stopped ahead of schedule in January 1996
>>> because participants who were randomly assigned to receive the active
>>> intervention were found to have a 28% increase in incidence of lung
>> cancer,
>>> a 17% increase in incidence of death and a higher rate of cardiovascular
>>> disease mortality compared with participants in the placebo group.
>>>
>>>
>> All of that is interesting but:
>> They are taking tablets so:
>> - What are the excipients
>> - What is the purity of the "antioxydants". Working in a phytochemistry
>> lab that is concerned by this question, I can tell you that the 99.9%
>> purity advertised is almost NEVER the case. And when you have a 95%

>> purity on 30mg of something, it's still 1.5mg of ... something ... which we
>> may hope it's water... Well it's not just that... And I don't talk about

>> mixtures of compounds advertised as a single compound because the
>> analytical technique used can't discriminate between them. It's like,

>> hey here is a nice mattress... Oh and I have 0.01% bed bugs inside it, but
>> it's nothing .01% tsss...

>> - What about the matrix effect ? Taking a pure compound from a dry
>> tablet is not the same matrix as taking it from food. The pH is not the
>> same, the sugar/lipids content is not the same (modifying

>> absorption/release in the gut... hey wait a minute...). And what about the

>> effect of the tablet on smokers ? You have all the previous elements,
>> someone smokes, where are the compounds and excipients ? still in his
>> mouth, in his gut ?
>>
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