MiFR: Flax, not Fish?
mik...@my-deja.com
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
fluidity..."
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
oxidizability.
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
monounsaturates.
While welcoming ANYONE's comments, I'd especially like to hear from
Aubrey.
-Michael
(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
<sjoh...@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:
99306787
Sent via Deja.com http://www.deja.com/
Before you buy.
mik...@my-deja.com
mik...@my-deja.com
--
On Fri, 24 Mar 2000 14:07:29 Michael J Rae wrote:
>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! >
Another possible objection which I'd like to address is the benefits of
DHA/EPA for CV health. It is widely believed that fish oils are superior
to ALA for this purpose, because of the eicosanoid thing again. But if
we compare the best-controlled trial of fish oil (GISSI (1)) to the
best-controlled trial whose greatest SINGLE dietary change was a
dramatic increase of ALA and oleic over saturated fats (2), the latter
would appear to have slashed CV death much more dramatically (like
sevenfold!) -- and also possibly reduced cancer death (3). More veggies
undeniably played a role in this, natch.
>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.
>
Having TRIPLE-checked it, I actually find that Simopuolos is simply
inconsistent. Her popular book, as I'd originally posted, suggests 1g of
DHA/EPA; her review paper (4) has the figure above.
>Conclusion: flax, not fish, and perhaps less total EFAs in favor of
monounsaturates.
YIKES! If we take Simo's more extreme reccomendation of 1g EPA/DHA + 2g
ALA OR EQUIVALENT (calculating 1g DHA~10g ALA), this suggests a flax
equivalent of ~12g daily; if we take the more conservative approach,
it's more like 3.7-4.6 g (1g ALA -[0.3/0.4 g dha] + 10 [0.3/0.4]). Half
a tablespoon of flax oil nearly covers this. I've been consuming ~2 T
flax oil daily, PLUS one n3 egg (0.4g n3, largely long-chain) several
days a week, for two years now!
Another note: Jo Robinson posted (0) around its publication date. Ed
actually suggested taking in less DHA at the time. I, by contrast, had
spent the last several months reading Simopoulos, Sears, and Udo
Erasmus' _Fats that Heal, Fats that Kill_, and digging up primary
research, and had eicosanoid metabolism on the brain, accompanied by
little understanding of MiFR (standard (non-Aubrey) version) and zero
understanding of the evolution of aging, and blew it off, suggesting it
could all be explained by high d5d and resulting series II eicosanoids.
Oh, well: live and learn. Two years out of a century isn't all THAT big
a mistake. I hope.
-Michael
(0) 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
>
(1) [No authors listed], "Dietary supplementation with n-3
polyunsaturated fatty acids and vitamin E after myocardial infarction:
results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio
della Sopravvivenza nell'Infarto miocardico." Lancet. 1999 Aug
7;354(9177): 447-55. PMID: 10465168; UI: 99392837
(2) de Lorgeril et al "Mediterranean alpha-linolenic acid-rich diet in
secondary prevention of coronary heart disease." Lancet. 1994 Jun
11;343(8911):1454-9. PMID: 7911176; UI: 94260784
(3) de Lorgeril et al, "Mediterranean dietary pattern in a randomized
trial: prolonged survival and possible reduced cancer rate." Arch Intern
Med. 1998 Jun 8;158(11):1181-7. PMID: 9625397; UI: 98287079
(4) Simopoulos, "Omega-3 fatty acids in health and disease and in growth
and development." Am J Clin Nutr. 1991 Sep;54(3):438-63. Review. PMID:
1908631; UI: 91344899
Aubrey de Grey
Michael Rae wrote:
> [J Lipid Res 39:1989-94] 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
> ...
> 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!
Very possibly. However, many processes that could impinge on this may
vary with chain structure: the removal of oxidised chains by PLA2, for
example. I would not expect the situation to obey simple rules.
> 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
> oxidizability.
Actually it says "increases exponentially", which is even worse. But
this is in fact a rare slip-up by Barja, whose work I rate very highly
and have followed eagerly for some years. Interestingly he gives a
relationship closer to the accepted one in the materials and methods of
the same paper. namely that fatty acids with one double bond are
virtually unoxidisable (1/40 as much as those with two), those with
three are twice as oxidisable as those with two, those with four are
four times as oxidisable as those with two, ... five ... six, .... six
... eight. This is very close to a simple relationship that has a
nice theoretical underpinning in the chemistry, namely that those with
n double bonds are (n-1) times as oxidisable as those with two. The
underpinning is that the hydrogen atoms which are easiest to rip off
(oxidise) are those attached to bisallylic carbons, i.e. the ones that
are joined by single bonds in both directions:
H H H H H
---C===C---C---C===C---
H
^
these. A monounsaturated chain obviously has no such carbons.
See Cosgrove et al, Lipids 1987; 22:299-304. This linear (as opposed to
exponential) relationship does not translate into quite such bad news for
DHA and its ilk.
> (1) de Grey (2000), "The non-correlation between maximum lifespan and
> antioxidant enzyme levels among homeotherms: implications for retarding
> human aging." In press.
The precise reference is now available: J. Anti-Aging Med. 3(1):25-36.
Aubrey de Grey
Randall Parker
I wonder whether any of the large population studies have found PUFA
consumption correlated with any diseases.
It'd be handy to have a mono/poly ratio for various nuts and oils.
In <8bj3lk$41n$1...@nnrp1.deja.com>, swami mik...@my-deja.com mikalra@my-
deja.com verbally radiated thusly:
> All:
> --
>
> On Fri, 24 Mar 2000 14:07:29 Michael J Rae wrote:
>
> >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! >
>
mik...@my-deja.com
In article <8bji5q$2t7$1...@pegasus.csx.cam.ac.uk>,
ag...@mole.bio.cam.ac.uk (Aubrey de Grey) wrote:
>
> Michael Rae wrote:
>
> > [J Lipid Res 39:1989-94] 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
> > ...
> > 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!
>
> Very possibly. However, many processes that could impinge on this may
> vary with chain structure: the removal of oxidised chains by PLA2, for
> example. I would not expect the situation to obey simple rules.
>
Do you mean that the findings of McMurchie et al (Lipids 1986
May;21(5):315-23), that
"Elevation of dietary linoleic acid led to an increase in membrane
linoleic acid and a marked decrease in membrane arachidonic acid, such
that the membranes from animals fed the sunflowerseed oil diet exhibited
the lowest proportion of arachidonic acid. In this latter respect, the
response of the marmoset monkey to dietary lipid supplementation differs
markedly from the rat."
... might not apply to the n3s because of THEIR chain structure? I do
know that the desaturases show a higher affinity for n3 than n6; does
this enter into it?
> > 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
> > oxidizability.
>
> Actually it says "increases exponentially", which is even worse.
Sir, I quoted directly from the text :) ! Seriously: he says "power
function" in one place and "exponentially" elsewhere.
-Michael
CGG
Just read a book by Jeannette Ewin PhD ("a medical journalist trained
in human biology") called "The Fats We Need to Eat", Thorsons, London
1995.
Referring to red blood cell fluidity and flexibility she says:
"Although the omega-3 essential fatty acids may have as many - or more
- double bonds as those classified as omega-6 series, they are unable
to reverse the effects of essential fatty acid deficiency on cell
membranes."
Is this true, or do we have more recent knowledge that contradicts it?
Chris G
Michael Sherman
CGG <chris@N_O_S_P_A_Msoluna.demon.co.uk> wrote:
> "Although the omega-3 essential fatty acids may have as many - or more
> - double bonds as those classified as omega-6 series, they are unable
> to reverse the effects of essential fatty acid deficiency on cell
> membranes."
>
> Is this true, or do we have more recent knowledge that contradicts it?
Sure it's true. Both omega-6 and omega-3 polyunsaturated fats
are essential for humans. They are not interconvertible and
we can't synthesize them. They must be obtained from diet.
The reason you hear more about omega-3's is that omega-6's
are much more plentiful in typical diets and most people
consume them to excess.
sherm
Aubrey de Grey
Michael Rae wrote:
> > > 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!
> >
> > Very possibly. However, many processes that could impinge on this may
> > vary with chain structure: the removal of oxidised chains by PLA2, for
> > example. I would not expect the situation to obey simple rules.
>
> Do you mean that the findings of McMurchie et al (Lipids 1986
> May;21(5):315-23), that
>
> "Elevation of dietary linoleic acid led to an increase in membrane
> linoleic acid and a marked decrease in membrane arachidonic acid, such
> that the membranes from animals fed the sunflowerseed oil diet exhibited
> the lowest proportion of arachidonic acid. In this latter respect, the
> response of the marmoset monkey to dietary lipid supplementation differs
> markedly from the rat."
>
> ... might not apply to the n3s because of THEIR chain structure? I do
> know that the desaturases show a higher affinity for n3 than n6; does
> this enter into it?
No, I would expect dietary linolenic acid to displace docosahexaecoic
acid in the same way. All I meant was that the turnover of oxidised
lipids is a complex process which is hard to generalise about.
Aubrey de Grey
mik...@my-deja.com
In article <8c5il7$77o$1...@pegasus.csx.cam.ac.uk>,
ag...@mole.bio.cam.ac.uk (Aubrey de Grey) wrote:
>
> Michael Rae wrote:
>
> > > > 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!
> > >
Sorry: that wasn't what I meant to ask. I would expect LA to displace
DHA; I meant to ask whether you thought that, since McMurchie reported
that feeding higher LA lowered AA (I presume because of the AA content
in the alternate diet (sheep fat)), replacing DHA with alpha-linolenic
acid as an n3 source might not be expected to similarly result in less
MIM DHA and more ALA. I understand that you believe that removal of
OXIDIZED lipids might vary by chain structure; what about INCORPORATION,
(or removal (eg. by phospholipase A2 -- or is this active in MIM?)) of
non-oxidized lipids?
Thanks for being there, Aubrey!
Aubrey de Grey
Michael Rae wrote:
> > No, I would expect dietary linolenic acid to displace docosahexaecoic
> > acid in the same way. All I meant was that the turnover of oxidised
> > lipids is a complex process which is hard to generalise about.
>
> Sorry: that wasn't what I meant to ask. I would expect LA to displace
> DHA; I meant to ask whether you thought that, since McMurchie reported
> that feeding higher LA lowered AA (I presume because of the AA content
> in the alternate diet (sheep fat)), replacing DHA with alpha-linolenic
> acid as an n3 source might not be expected to similarly result in less
> MIM DHA and more ALA.
Um, yes, that's what I thought you asked -- and my answer is/was "yes".
I said linolenic (ie ALA) would displace docosahexaecoic (DHA) just as
linoleic (LA) displaces arachidonic (AA).
> I understand that you believe that removal of
> OXIDIZED lipids might vary by chain structure; what about INCORPORATION,
> (or removal (eg. by phospholipase A2 -- or is this active in MIM?)) of
> non-oxidized lipids?
Sure, that might vary too. I'm not aware of any detailed studies on
the subject.
Aubrey de Grey