MiFR: Flax, not Fish?

mikalra at my-deja.com mikalra at my-deja.com
Fri Mar 24 17:15:32 EST 2000


A little while ago, Sherm wrote:

 > To move off theory for a moment, do you think that this implies
 > a danger for humans who intentionally increase their dietary
 > consumption of unsaturated fats, especially the trendy w3 polys?
 > Are these likely to find their way into mitochondrial membranes
 > or is the composition of these membranes fixed for a species?

The concern here is that n3s hve more double-bonds than other lipids, so
that more n3s in the mitochondrial inner membrane (MIM) means more
susceptibility to oxidation, which not only disrupts the functioning of
the membrane, but may lead to damage to mitochondrial DNA because of the
physical attachment of mtDNA to the MIM (1), initiating a process which
Aubrey believes initiates the aging process [plug: buy his book (2)!].
Indeed, as MiFR predicts, the total number of highly oxidizable double
bonds in mitochondrial membranes (and thus their peroxidizability) is
inversely correlated to species max LS (3).

Aubrey "the man" de Grey replied:

<< I think there would be such an effect, yes.  However, it it vital to
bear in mind that
 the effect would be on the relative amounts of the various
polyunsaturated fatty
 acids, rather than on the proportion of saturated to unsaturated.
There was a
 study in 1986 (McMurchie et al, Lipids 21:315) which showed that the
former is
 indeed altered by diet but the latter is not.  This is no big surprise
when one
 bears in mind that one side chain of a typical phospholipid is
saturated and the
 other unsaturated.>>

So far, so good. We NEED n3, but probably shouldn't overdo it.  But
there is another implication here, methinks. (3) notes that the
difference in mitochondrial membrane peroxidizability "is not due to a
low content of unsaturated fatty acids in longevous animals, but mainly
to a redistribution between kinds of the polyunsaturated n-3 fatty acids
series, shifting from the highly unsaturated docosahexaenoic acid (r =
-0.89, P < 0.003) to the less unsaturated linolenic acid ... This
redistribution pattern strongly suggests the presence of a
constitutively low delta6-desaturase activity in longevous animals."
Actually, it could just as easily be caused by a low d*5* desaturase,
but their data don't give relative amounts of SDA or ETA to EPA, so we
don't know; but, in any case, it would appear taht part of longer max LS
is having an EFA desaturation pattern which favors more ALA and less DHA
in mt membranes, since virtually all of these animals n3s come in as ALA
(they're vegetarian), so dietary DHA doesn't confound their genetic
control over degree of fatty acid desaturation.

But when we take in DHA (or, to a lesser extent, EPA) we are jumping
over the rate-limiting desaturase steps, and buggering this evolutionary
advantage. The conclusion would seem to be that, contrary to most
nutritionists' guidelines, we best guard our health by getting as much
of our n3 as ALA as possible, and as little DHA, because while the
latter may have health benefits in the medium-term via eicosanoid
metabolism, it may actually accelerate the aging process!

"But," you say, "we need DHA to maintain membrane fluidity." But
according to (3), "Whereas strong increases in lipid fluidity are
observed after introduction of the first double bonds to a saturated
fatty acid, progressively smaller effects are observed after the
introduction of additional double bonds... This is so because when a
double bond is added near the center of the fatty acid chain (first
double bond added) the impact on the fluidity through the kink ... of
the fatty acyl chain is much larger than  wehen it is added nearer to
the extremes (subsequent double bods added). Thus [more ALA and less
DHA] may allow a decrease in the double bond content of mitochondrial
membranes [and thus oxidizability] without greatly changing membrane

Further, (3) says that PUFAs' oxidative sensitivity "increases as a
POWER FUNCTION of the number of double bonds PER FATTY ACID MOLECULE."
So while an extra double bond or two may be of little extra  BENEFIT in
terms of membrane fluidity, it adds a great deal to membrane

Finally, it would appear (4) that the place where we would be most
concerned about not getting "enough"  DHA into the CELLULAR membranes --
the brain -- is insensitive to dietary EFA type, maintaining a fairly
constant levels of DHA no matter which n3 is administered; but in  heart
and liver tissue, where we are also very much concerned about MIM
oxidation but (AFAIK) much less concerned about getting DNA in CELLULAR
membranes, "dietary ALA had little effect on tissue DHA proportions
although the proportion of AA was slightly depressed at the highest
dietary ALA intake [which latter is a good thing, from both an
eicosanoid metabolism and a membrane peroxidizability POV], but dietary
DHA and AA supplements led to large increases (up to 10-fold [!]) in the
proportions of these PUFA."

I should also add that, having double-cheked it, my recent post on n3s
exaggerated the reccomendations of Simopoulos and the Canadian
government: the former suggests 1g n3, including 3-400 mg as EPA or DHA,
while the latter gives varying reccomendations by age and weight, but
looks to average ~1.5 g daily total n3 intake.

Conclusion: flax, not fish, and perhaps less total EFAs in favor of

While welcoming ANYONE's comments, I'd especially like to hear from


(1) De Grey (2000), "The non-correlation between maximum lifespan and
antioxidant enzyme levels among homeotherms: implications for retardig
human aging." In press.

(2) Title:    The Mitochondrial Free Radical Theory of Aging
Author:    Aubrey D.N.J. de Grey
Price:    $89.00 (212pp, hardback) + $5 shipping
Publisher: Landes Bioscience, 810 South Church Street Georgetown, TX,
USA  tel: +1 512 863 7762, fax: +1 512 863 0081 (email Sara
Johnson,Sales Manager, Landes Biosciences
<sjohnson at landesbioscience.com>).
ISBN:      1-57059-564-X .

(3) Pamplona et al (1998), "Mitochondrial membrane peroxidizability
index is inversely related to maximum life span in mammals." J Lipid
Res. 1998 Oct;39(10):1989-94. PMID: 9788245; UI: 99002294

(4)Abedin et al (1999), "The effects of dietary alpha-linolenic acid
compared with docosahexaenoic acid on brain, retina, liver, and heart in
the guinea pig." Lipids. 1999 May;34(5):475-82. PMID: 10380119; UI:

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