cron-web.org

[A1CR]

[posted on behalf of Dean and MR; 2001-08-21]

Dean wrote:
>
> As promised, here is a link to an easy to read synopsis of MR's
> hypothesis about fish oil and aging, composed by the sorely missed CRON-sherm:
>
> http://groups.yahoo.com/group/crsociety/message/2990
>
> with this follow-up from MR:
>
> http://groups.yahoo.com/group/crsociety/message/2994


Dean, thank you for posting this, and also for previously taking the
trouble to summarize the DHA-Accelerated Aging hypothesis. At the risk
of being perceived to be an ingrate, however, I must object to both summaries.

As I note in my reply to CRON-sherm's presentation of the hypothesis, both
your & his summaries invoke theoretical concerns (Aubrey de Grey's
brilliant MiFRA) which are not, per se, evidential and are not actually
part of my hypothesis (tho' you're welcome to make them part of yours
). MiFRA provides a pretty good explanation for the reasons BEHIND the
observed data, but my conclusion -- that one should get one's n3 (&6,
BTW) from EFAs per se, rather than long-chain metabolites (EPA, DHA, AA,
etc) -- is dependent on the EMPIRICAL DATA THEMSELVES, &in no way on an
explanation as to WHY these data may be.

(This, also, against CRONie1's recent comments about "anyone who thinks
they understand the MECHANISM of aging," etc. Saul, as I've pointed out
repeatedly, to you, personally, in the past, in discussing these issues,
I make no such claim. Mechanism is not asserted. Likewise: CR,
empirically, increases max LS. Why? Damned if I know -- though, again,
MiFRA provides a pretty solid explanation. But the DATA are unarguable).

Bringing up MiFRA IN THE MIDST of the presentation of the argument thus
muddles two seperate issues -- "mixes the planes."

So when will I get off of my lazy ass and present my version of the
hypothesis in a rigorous fashion? Good question . In the interim, here
is a brief summary, with an assembly of relevant links to
previously-posted data:

he by now well-established facts which constitute essence of the
argument:

------------------------------------------------------------------
1.Across species, double bond content in the mt inner membrane (MIM) --
and esp DHA content -- is inversely correlated with max LS.

PMID 9788245

PMID 11432462

[enter the PMIDs above here to see Abstracts: http://www.cron-web.org/PubMed-search.php]

http://groups.yahoo.com/group/crsociety/message/2980

This effect is particularly impressive in comparing outliers, such as
birds, which -- becase of their size &high metabolic rate -- would
otherwise be predicted to have short LSs (rodents, of similar size &
slower metabolic rates, live ~3 yrs; canaries can live > 10 times this long):

PMID 10337442

PMID 10100156

PMID 66736

[enter the PMIDs above here to see Abstracts: http://www.cron-web.org/PubMed-search.php]

-------------------------------------------------------------
2. Within a species, double bond content in MIM increases with aging.

http://groups.google.com/groups [rest of URL unknown?]


(And de Grey's confirming reply, which nixes my self-imposed caveat):

http://groups.google.com/groups [rest of URL unknown?]

--------------------------------------------------------------

3. CR, the only anti-aging therapy per se (only therapy which extends max
LS), retards (2).

(Some examples are present in the first post under point (2), above:
refs. (1) and (3)).

------------------------------------------------------------------

4. Feeding all animals yet tested longer-chain PUFA, such as DHA,
increases DHA content in MIM.

http://groups.google.com/groups? [rest of URL unknown?]


-------------------------------------------------------------------

5. Specifically, in rodents, feeding fish oil both increases MIM DHA
content, AND increases the actual peroxidation of the MIM.

http://groups.yahoo.com/group/crsociety/message/2905

Dean's posting of the results is neater:

http://www.egroups.com/message/crscience/7

----------------------------------------------------

6. CR opposes the incorporation of dietary EPA/DHA into MIM.

http://groups.google.com/groups [rest of URL unknown?]

(To understand how these abstracts show this, NB that CL=cardiolipin
(diphosphatidylglycerol), a phospholipid only found exclusively (or,
some would claim, just OVERWHELMINGLY) in MIM), &MIM contain PL
exclusively (no TGs):

http://groups.google.com/groups [rest of URL unknown?]

-----------------------------------------

Inductive conclusion, from the above &a few other tidbits: eating DHA
will lead to more DHA in MIM; more DHA in MIM and correlates with aging
within and across species, and is actively opposed by normal organisms
-- an effect upregulated in CR. Eating DHA causes effects which parallel
the 'normal' aging process and which oppose known effects of CR, the
only proven anti-aging intervention in mammals.

So don't eat DHA.

-----------------------------------

Of interest, it's also been found that even TISSUE LCPUFA levels are
inveresely related to species max LS:

PMID 10687923

... and that CR further opposes even TISSUE LCPUFA, endogenously or from
the diet:

PMID 10954013
PMID 11485162

Is this evidence that mt inner membranes are not, per se, the issue? Or
are tissue levels just an indiscriminate side-target of an anti-LCPUFA
mechanism whose primary target is MIM? I don't claim to know, tho' I
suspect the latter. Either way: more LCPUFA are clearly not a good idea.

None of this is to say that the MiFRA issues are irrelevant, or
uninteresting -- jus tthat they're secondary, IN MY THINKING ON THE
SUBJECT, and not the same KIND of argument (correlational induction vs.
theoretical deduction). See, eg,

http://groups.yahoo.com/group/crscience/message/4

As Dean rightly notes, the issue is not WHETHER to get n3, or WHETHER to
get EPA/DHA, but HOW to get it best. More importantly, as re: recent
discussions on KIM and long-chain n3:n6: NB that KIM does NOT set
targets for LEVELS of long-chain PUFA, but for RATIOS of long-chain
n3:n6. One can meet the KIM ratios (if one wishes to -- my opinion on
KIM &t he KIM tissue targets is a subject for another day) with either
high or low ABSOLUTE LEVELS of LCPUFA in one's tissues. As Greg rightly
points out, per the KIM software (going with it for the moment: my
comments on KIM at some later date):

> You can work the numbers thus and get approx the same tissue ratios:
>
[The US working group's reccomendations are]:

> Omega 6; 6 - 7 g (~ 2 % of energy) [Here, by "omega 6," LA is clearly meant;
> AA, of course, is also "omega 6."]
> Omega 3; 2.5 g [Here, by "omega 3," ALA is clearly meant; EPA/DHA of course,
> is also "omega 3."]
> EPA + DHA; 0.65 g
>
> Omega 6 [ie., LA]: 6 - 7 g (~ 2 % of energy)
> Omega 3 [ie., ALA]: 9 g (Hello Paleo Man!!!)

This is, of course, almost exactly my long-held reccomendation of 8g
each of ALA & LA (from at least May of Y2K:

http://groups.yahoo.com/group/crsociety/message/861 )

... which is PLENTY, based on the 10:1 ALA:EPA conversion ratio &the
basal requirements documented in these posts:

http://groups.yahoo.com/group/crsociety/message/2794
http://groups.yahoo.com/group/crsociety/message/6840

Not coincidentally, these are largely the same data cited by assorted
bodies in making their reccomendations, to which reccomendations Greg
has repeatedly drawn our attention:

http://www.ajcn.org/content/vol71/issue1/images/large/017901.jpeg ; see
also CR archives post 6840, op cit).

"But I need EPA/fish DIRECTLY, for my heart!" No, you don't: ALA works better:

http://groups.yahoo.com/group/crsociety/message/3070

Specifically: the intake of ALA in the active group in the Lyon heart
trial was a mere 1.73 g/day; the upper-quinstile intake of ALA in the
Nurses' Health Study was a mere 1.36 g; that in the Health Professionals
Followup Study, just 1.5 g.

"But I need EPA/DHA DIRECTLY for my brain!" Do you mean, to avoid simple
brain deficiency or age-related cognitive decline? No, you don't:
adequate ALA preserves DHA levels in the brain nicely, &DHA
supplementation in the long term is bad for the brain, even tho' (as has
been repeated ad nauseam of late) it's helpful in the rapidly-growing
brains of infants:

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&b=PubMed&ist_uids=10380119&opt=Abstract

http://groups.yahoo.com/group/crsociety/message/8795

"But this is all based on correlation. You have no study showing that
fewer CRONies break max LS if fed DHA than if fed ALA." True. I'm
operating on the precautionary principle. A weaker standard of evidence
is required to get me to AVOID something, on the basis that it might be
BAD, than is required to get me to EMBRACE something, on the basis that
it might be GOOD. Of course, strong evidence outweighs weaker evidence
in all cases; here, however, we have no strong evidence (direct
intervention study) to trump this weaker (correlational) evidence.

Since it's clear that ALA can meet our basic needs, & that ALA yields
superior health benefits compared to EPA/DHA, it seems I'd be FOCUSSING
on getting my n3 requirements via ALA anyway; I'm just taking the extra
step of ACTIVELY AVOIDING EPA/DHA. I can see no valid reason not to, & a
pretty good case to do so. The precautionary principle demands that I do so.

"But I have bipolar disorder/schizophrenia. There are controlled trials
that suggest that EPA is helpful in these disorders, &none with ALA."
True, but the amounts required do not appear to be unreachable via ALA,
the mechanism specifically suggests that EPA, rather than DHA, is at
work, &there is no evidence as yet to suggest that failure in
desaturase enzymes is at work; rather, excess catabolic activity via
phospholipase may be at work. It's hard to call this one, but one MIGHT
try a relatively high maintenance dose of ALA once EPA supplementation
has brought EPA levels up.

"But I have an autoimmune disease. There are controlled trials that
truly MASSIVE doses of EPA/DHA are helpful in these disorders, &none
with ALA; in fact, tere is a good case to be made that ALA won't do the
trick in these disorders."

You're right. For Christ's sake, take EPA/DHA. Lupus will kill you long
before mildly accelerated aging will. But let's not extrapolate this
into people who do not have these disorders.

-MR