All:
--

Saul Lubkin wrote [in several posts, here collated]:

> I was, in fact, considering switching [from EPA/DHA to ALA] -- until i
>asked ny GP/nuritionist!
>
>She thought that falx il is a definite plus; indicated (as I've noted)
>that not everyone can convert ALA to EPA/DHA

>>My GP claims, in fact, that some people have difficulty with that conversion
--
>>and definitely need EPA/DHA directly -- that it depends on the individual.

>as my GP asserts, "it's fine if yur body can make the conversion from ALA
>to longer chain -- but some people can't.

This appears to be your key concern: the belief that the metabolism of ALA to
EPA/DHA is dramatically lower, or zero, in some segement of the population.
However, thus far, there has been absolutely no evidence dug up to justify this
fear -- & certainly none that you, personally, are a victim of this putative
disorder.

The abstract posted by Dean (1) does indicate (based on studies (plural) in
humans) that there is some interindividual variability, but not enough to
justify being concerned about it, as he elegantly demonstrated.

It is clear, as (1) notes, that metabolism of ALA -->DHA does vary; however, it
is also clear that, contrary to Saul's understanding of his GP's belief, the
degree to which this variation happens is quite limited, & ANYONE who isn't
suffering from some quite obvious, advanced metabolic disorders (ie. not
something subtle that one might miss) can get more than adequate n3 from 1 T
flax oil/ day. This post presents evidence for this statement.

>Knowing my GP/nutritionist, i don't take her recommendations
>lightly --
>truthfully, neither do I take yours lightly. I finally found a
>refernce
>to the "10% conversion" of ALA to longer chain -- an excellent
>general
>reference, "The Omega Diet". BUT, it gives no confirming sources.

True. However, the book is written by Artemis Simopoulos, who has virtually
built an academic career on n3 in health & disease, & who has a fairly extensive
peer-reviewed bibliography on the topic, several volume editorships to her
credit, etc. Her blanket, unreferenced statement of a 10% conversion ratio is
not proper evidence, I agree -- but it is MASSIVELY better evidence than a
blanket statement to the contrary by a GP, however otherwise nutritionally
astute.

>Also, the post from Sear's organization is vaguely consistent with my GP's
>claim. (I certainly hope that Sears isn't her source!)

He may very well be. Sears is, at least, a biochemist, and a peer-reviewed
published scientist: on this point, he's certainly more of an authority than a
GP. But, in any case, he would be a much poorer source on n3 metabolism than
Simo -- & certainly, neither Sears' nor your GP's flat statement is proper
evidence.

Ie., if you're going to make an argumetn from authority, pick an actual
AUTHORITY on the subject!

In any case, the above is quite moot, as Simo's source is at last revealed in
(7) (discussed in more detail below): it's (8). Per (7), this study in humans
found that "keeping the amount of dietary LA constant, 3.7 g ALA appears to have
biological effects similar to those of 0.3 g [EPA/DHA] with conversion of 11 g
ALA to 1 g [EPA/DHA]."

The study, as summarized, also indicates that higher n6 can interfere with n3
metabolism (as was also found in rodents): "Dietary amounts of LA as well as the
ratio of LA to ALA appear to be important for the metabolism of ALA to[EPA/DHA].
Indu and Ghafoorunissa [ie. (8)] ... showed that ... a ratio of 4 (15 g LA:3.7 g
ALA) is appropriate for conversion." NB she is not saying that a lower LA:ALA
won't work, but that a HIGHER ratio is inhibitory: "conversion of deuterated ALA
to longer-chain metabolites was reduced ... when dietary intake of LA was
increased..." "Relatively large reserves of LA in body fat, ... would tend to
slow down the formation of long-chain n3 fatty acids from ALA."

This latter comment is of particular interest. It suggests that the longer one
is on a higher n3:n6 diet, the more efficient the metabolism of ALA will become,
as overall cellular reserves change. (To clarify this point: eicosanoids are
not, as one might imagine, made from precursors floating around in one's
cytoplasm, but from snipping the fatty acyl chains out of membrane phospholipids
usin phospholipase A2. Long-term dietary changes will be reflected in membrane
PL. Thus, the REAL n3:n6 ratio is the one in your cellular PL, not in your
day-to-day diet).

In addition to the op cit review (1), (2-5 [on which I'm sure the (1) is at
least partly drawing]) are direct experiments on real human cases of ALA
deficiency and the amount of various EFAs req'd to cure it: the amount of pure
ALA does vary, but is finite & quite low. The discussion in (4), reviewing new
data & previous experiments, indicates that "In adults, [ALA] requirement is
~0.2% of energy when [EPA/DHA] contribute 0.08% of energy, increasing to >0.3%
... when [EPA/DHA] are reduced to 0.03% of energy."

(5) went further than this: in their patient, as much as 0.54% of energy as ALA
was required to fully reverse her symptoms; however, a greater req'mt for n3 is
to be expected in a growing child of 6, & as (4) notes, children have previously
been found to need significantly more n6 than adults, too. Indeed, (4) goes on
to note that this amount is almost exactly what is found in human breast milk, &
similar to previusly-reported data in primates.

At this "high" level, an adult would need 1.5 g ALA/day, assuming an AL 2500 Cal
diet. Or, to go by her bodyweight, she needed 44 mg/kg; in a 70 kg adult, this
is a whopping 3g.

BTW, This study may give the best evidence for wide individual variation: but in
the opposite direction to the one you're worried about. They found that EPA/DHA
was only about 2X as good as ALA, per gram, at restoring the child's
phospholipid EPA/DHA to normal. This same conversion rate is given in
(4). I tend to expect that this is not so much a matter of freakishly-efficient
conversion as the well-known effect in which EFA deficiency (the state of all
the subjects of these experiments) revs up desaturase activity; in any case, it
is certainly evidence against any issue of a failure to convert.

(8a), the bible of nutritional orthodoxy, came to the similar numbers as (4),
tho' suggesting that ALA needs, if EPA/DHA is negligible, are as high as 1% of
Calories (say 2.8g). They make no mention of a subpopulation with dramatically
low ALA metabolism.

It does note that premature infants often have low desaturase activity
(presumably as their bodies are still designed to be in the womb, where the
mother's blood DHA would cross the placenta). This, however, is actually
evidence FOR the adequate desaturation in the normally-born, as the associated
secondary n3 deficiency signs of preemies do not appear in the bulk of the
population.

(6) is a major review on n3 in health & disease. It mentions 3 groups which
might have low desaturation. These examples again prove the point tha, while n3
metabolism may vary, it does not do so to a degree as to make ALA
unmetabolizable.

One group Simo (6) cites (12), with which readers of the Albatross will already
be familiar, is type I diabetics. As insulin is req'd for d5d activity, IDDM
patients fail to metabolize GLA to AA unless they get their insulin shots (13).
NB that NIDDM patients have the OPPOSITE problem (14, 15): too much desaturase.
This, from insulin resistance, seems a much more likely population-wide issue.

Another group she (6) cites (10) as possibly having low desaturase activity is
hypertensives. But more recently, (10a) found the REVERSE: 'C20:4/C18:2,
C20:5/C18:3, and C22:6/ C20:5 ratios were significantly higher in essential
hypertensive patients than control subjects.'

The latter makes more sense, as hypertension is most commonly associated
w/hyperinsulinemia (see above). I note that (10) just says EFA n6 was high in
hypertensives, which could just be overfeed of n6; & that LCPUFA didn't go UP
after EFA loading: but if LCPUFA were already q. high (as they would be if
desaturase activity were high), & esp if (as one would expect) LC n6 was
overbalanced, this is what one would tend to expect; whereas (10a) looked at
initial levels of BOTH LCPUFA & EFAS, & found the RATIO higher in hypertensives.

OTOH, (10b) found that high-salt diets, which can create 'artificial' (largely
non-genetic), readily-reversible hypertension does decrease n6 desaturation.
This might explain (10). The point would remain the same: the problem wouldn't
be 'hypertensives don't metabolize EFA,' but 'high-salt diets inhibit EFA
metabolism.' (10b) also found spontaneous hypertension to decrease desaturase
activiyt -- in a rodent model.

All this might explain why later reviews ((8a), & (7), which is Simo's own later
publication) make no mention of hypertensives as at risk for low desaturase
activity.

(11), again according to (6), apparently shows that desaturase activity is
reduced with aging. Be that as it may, total LCPUFA actually ACCUMULATE with
aging, as has been noted in the broader 'MiFRAA' debate, making this of little
relevance; & again, later reviews make no mention of such an effect.

(7, 7a) are also such reviews, & are especially valuable, as they are part of a
symposium on vegetarian nutrition, & thus look more closely at the issue of a
large population with (until the recent (~1995) advent of DHA supplements from
marine algae & of n3 eggs) no dietary EPA/DHA available to them.

(7a), in particular, is on pregnant & lactating vegetarians, who obvioulsy have
a higher need for n3 than the bulk of the population. No mention is made of any
issue of a subpopulation with a failure to metabolize ALA, tho' the issue of low
intake of n3 as a whole, and high n6, is repeatedly raised.

From (7): "ALA, the precursor of n3 fatty acids, can be converted to long-chain
n3 PUFAs and can therefore be substituted for fish oils." Then the data op cit
on the 10:1 conversion. A blanket statement that ALA works just fine; no
caveats.

From (7a): "LCPUFAs [EPA/DHA] are generally absent from plant foods, thus it is
important find out how essential fatty acid requirements are met by vegetarians.
A developing fetus obtains LCPUFAs via selective uptake from its mother's plasma
and LCPUFAs are present in the breast milk of vegetarians."

"There is no evidence that the capacity to synthesize LCPUFAs is limited in
vegetarians."

"However, there are greater proportions of [AA] and lower proportions of
[EPA/DHA] in vegetarians compared with omnivores. This difference is probably a
consequence of the selection of foods by vegetarians with high amounts of" LA

"in rats fed adequate intakes of [ALA], it is possible to decrease the
proportion of DHA in fetal brain with high intakes of" LA.

"Because the proportion of AA in the blood and tissue lipids of vegetarians and
vegans is similar to or greater than that of omnivores, the implication is that
vegans and vegetarians do not require AA in their diets because they can
synthesize adequate amounts from linoleic acid."

As noted previously, the same enzymes which desaturate LA do the same job on
ALA; hence, this could be rephrased, "the implication is that vegans and
vegetarians do not require EPA/DHA in their diets because they can synthesize
adequate amounts from alpha-linoleNic acid."

Surely somewhere along the line it would have been noticed if vegetarians were
suffering the massive retinal & brain damage, dermatitis, etc. seen in the n3
deficiency cases in (2-5). Vegans, in particular, had absolutely no EPA in their
diet until 1995 (trace quantitites would exist for ovolactos). As Simo notes
somewhere in her popular book, vegetarians' total n3 is often undetectable --
yet they don't seem to be deficient, per se, as a population.

>-- and that you need the
>latter [EPA/DHA],
>both for circulatory/heart benefits

As indicated in the post to which you're responding, the evidence appears pretty
clear that ALA is in fact SUPERIOR to EPA/DHA for cardiovascular benefits.
Several points, here. Re: this, you say:

>I'm afraid the Lyon heart study isn't much use on this -- the subjects
>using ALA oils were allowed to -- envouraged to -- among other things eat
>fish. So the study gives zilch, for information, on conversion of ALA to
>long chain.

But:

(a) the fact that the Lyon study patients were ENCOURAGED to eat more fish is
not relevant: what's relevant is whether they DID. In this large cohort, there
were no significant differences in fish intake between intervention subjects &
controls (p= 0.16). The text specifically notes, "After 52 weeks, there were
higher concentrations of [EPA] ... in the experimental groupu.. [which were]
probably related to [ALA] because intake of fish was not significantly
increased..."

(b) in the post to which you're responding:

http://www.egroups.com/message/crsociety/3070

... 2 massive epidemiological investigations are cited which came to the same
results: a small increase in dietary ALA led to dramatic slashing of CVD
mortality. The epidemiology on fish, again reviewed in this post, is much less
impressive.

Whether we look at controlled trials or epidemiology, the evidence in this post
shows that ALA is the superior n3 source for CVD issues -- and since this is
ultimately because of the PROCESS (again, only secondarily the endproduct [ie.
EPA/DHA] -- see below) of desaturation, the ability of the population at large
to properly metabolize ALA is confirmed.

>[one also needs EPA/DHA] to prevent too much of the w6
>eiconsoids being made, instead of w3's,

Again, as I indicated in the post to which you are here responding, this isn't
true when thus phrased. Leaving aside the non-involvement of DHA in eicosanoid
synthesis, different n3s prevent the formation of series 2 eicosanoids in
different ways. EPA can, to some extent, inhibit d5d by product inhibition;
however, the EPA precursor (ALA metabolite), 20:4n3, can also do so, & more
potently, by direct competitive inhibition with the enzyme's activity on DGLA
(AA's n6 precursor when acted on by d5d).

EPA per se is not REQUIRED for any of this, tho' as an added bonus, the
occupation of d5d by 20:4n3 yields some EPA, which can then do the same
product-inhibition bit as exogenous EPA. This "double whammy" doubtless plays
into the evident long-term superiority of ALA in this regard.

In this connection, (16) notes that "Inclusion of n3 fats in the diet can
suppress the production of both TNF-a and IL-1b. ... [EPA/DHA] results in
decreased monocyte synthesis of TNF-a, IL-1b, or both in healthy subjects ...
and in patients with rheumatoid arthritis ...

"An alternate approach to elevating cellular EPA concentrations is to increase
intake of ALA ... flaxseed oil ... was used by healthy male volunteers in their
domestic food preparation [(17) -- similar to the Lyon trial, NB], *leukocyte
EPA concentrations were increased* and both IL-1b and TNF-a production were
suppressed by <30% after 4 wk..."

From (17): "Fish-oil supplementation (9 g/d [NB a massive dose]) continued for a
further 4 wk [more time]; TNF alpha and IL-1 beta
synthesis were inhibited by 74% and 80%, respectively... Cytokine production
decreased as cellular EPA increased to approximately 1% of total fatty acids."

"Further increases in EPA content did not
result in further decreases in cytokine production."

"The results indicate that vegetable oils rich in n--3 fatty acids inhibit TNF
alpha and IL-1 beta synthesis."

No note of some subpopulation of nonresponders.

>What I'd really like to know is: Is there some use or even need og the
>body for ALA, that isn't done as well or better than longer chain (for the
>same number of calories)?

As an aside, this issue is actually neither here nor there. If the question
were, "should we restrict ALA or cut it out of the diet?," it woud, of course,
be relevant, but since that's not under discussion & as a good CR diet will
inevitably include SOME ALA, I don't see that it's ultimately material.

Be that as it may: (7) indicates that LA "and ALA ... and their long-chain
derivatives are important components of animal and plant cell membranes." IIRC,
the same statement is made somewhere in (2-5), but I'll be darned if I can find
it now.

If this is so, then "for the same # of Cal" is also quite irrelevant: you can't
substitute EPA for ALA, no matter how many Calories you consume.

And, even if not: again, not an objection for those trying to get higher fat
content in our diets. Indeed, inasmuch as flax has less n6 than olive oil,
almonds, etc, we're better off in this regard even ignoring the n3 content. &
since, as noted above, these "extra," easily-counterbalanced Calories clearly
(per controlled experiments & large-scale epidemiology) do a better job of
saving your life, & MAY (per my pet hypothesis -- which, BTW, has now been fully
endorsed [!] by Aubrey) also prevent accelerated aging, I'd say this is about as
much of an objection as (say) the fact that there's more Calories in turnip
greens than in iceberg lettuce.

>What if [conversion is] 0%?
>Why are you sure that it isn't zero -- or neglidgleable -- for, perhaps even a
>substantial fraction of humity? Is there any eveidence on this?

Iif a person really had a ZERO desaturation rate, s/he would be quite dead.
Basic cellular maintenance functions via COX-1 would grind to a halt, unless
large AA supplements were taken; brains would not develop, retinas would be
nonfunctional, etc etc. While a person might just HAPPENED to have gotten all
the EPA/DHA & AA s/he needed, thru'out hir life, from the diet, such does not
hold for GLA. (Yes, this includes oatmeal: rolled oats' GLA content is quite
negligible).

> the same enzymes which make the series 2 eicos are involved in making the
series 3 (and have, in fat, a higher affinity for the latter). Hence, if you cut
your rate of generation of EPA from ALA in half because you have unusually low
desaturase activity, you SIMULTANEOUSLY cut your generation of AA from LA in
half. Hence, in fact, conversion rate per se is virtually a non-issue from this
POV.
>
>SAUL:
>
>I'm certainly not competent on this. BUT, this assumes that the individual who
>has trouble converting ALA to longer chain, has the same trouble with the LA
>conversion -- if there is a (maybe commom?) mutation that modifies the enzyme,
>the nefarious stuff might conceivably work fine on the w6's but not the w3's!

But aside from all the evidence above that this doesn't happen, & the fact that
this scenario is not itself founded on anything but sheer, unadulterated
speculation -- aside, I say, from all of this, to my limited biochemical
understanding, it's also nearly impossible. LA & ALA are identical except for
the rpesence of a single double bond at the third carbon from the methyl group
in ALA, which slightly bends the molecule. The desaturase enzyme works by
"counting" from the acid group. To reduce affinity selectively, I can see
speculating (based on the extant GREATER affinity); to eliminate it selectively
in the opposite direction, I can't. Speculation, in any case: hard data, above,
says not so.

>>> The only question is, how much? At the very generous 8g I suggest/day,
>>
>>Again, we're assuming that we know minimum conversertion levels for everybody.
>
>Again: no, we're not. We're just assuming they're not off by astounding degrees
in a very small % of the poppulation of which some individual on CR happens to
belong.
>
>SAUL:
>If there are such people, how do you know it's rare?

Because people dropping dead of the kind of symptoms seen in (2-5) is just not
happening. These people were mostly on TPN and getting NO n3: hence their
problems. In the population at large, it just isn't occurring. (7, 7a) again.

Again: suppose this putative subpopulation existed. Why should one assume that
one is in such a group? Such subpopulations could just as easily (& on the same
evidence, ie. sheer speculation) exist for any number of biochemical processes,
as eg. the formaiton of various biologically active coenzymes from their
biologically inactive vitamin substrates. Should we all begin supplementing NADH
in addition to making sure we are getting enough B3, just in case we happen to
belong to such a supoopulation?

Ditto for CoA for B5; PLP for B6; methylcobalamin & adenosylcobalamin for B12
(NB these people do exist -- & they have very definite, non-vague symptoms, & if
homozygous die in early childhood); methyltetrahydrofolate for folic acid; & so
on down the line. There is genuinely no end to this kind of speculation. Why
should one even begin it?

>I'd consider switching from fish oil to falx, if
>
>(1) The question that I brought up -- that was brought up by my GP -- was
>wrong.

All posted evidence is that it is. With all due respect, I take it you will now
either (a) present evidence tht your GP is right, OUTSIDE of her flat statement,
or (b) stop arguing on the subject.
>
>(2) There was some (non-Michael's-pet-theory) reason for making the
>switch.

This creates a closed system: give me a reason to do X, but don't present
evidence supporting your thesis.

But, of course, the above data on ALA vs. EPA in CVD (& cancer, NB) is such
evidence. So I've got you coming or going ;).

> There is a differnce between a pesticide in minute quantities, and an
> anti-nutrient that a plant has developed, usually over thousands of years
> of evolution, to combat being eaten by animals... The plant's may be more
> insidious. A plant that has no relative that our paleo ancestors ate is
> particularly suspect. Flax is far worse than soy by this criterion.

This might be argued for flaxSEED, but not reasonably for flax OIL. The Paleo
issues are: (a) nutritinal discordance (not an objection to flax oil as part of
a broader diet); (b) the presence of substances to which, themselves, we are
unadapted. Now, many non-paleo foods do clearly contain such substances -- but
they're either proteins (trypsin inhibitors, lectins, etc) or water-soluble
components (lignans, isoflavones, antinutrient "vitamins," etc). A priori, I
can't see how an OIL is going to contain any such beasties.

I don't, in any case, think the non-Paleohood of a food should, a priori, rule
out its consumption.

> incorporting longer cahin w3's in you cellular membranes -- e.g., mt
>membranes, but others as well -- will increase their flexibility more than
>ALA -- as per Sherm's elegant diagrams some time ago -- and this is an
>advantage.

But, as has been noted again & again in the "MiRFAA" discussion, (20) notes that

"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..."

It also 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."

Indeed, the whole point of Sherm's elegant diagrams was to illustrate this exact
point.

>Ahhh! That's the real question! If Michael's theory had more clinical
>evidence -- rather than purely theoretical -- I'd agree with you (no
>personal insult meant to Michael). OTHH, Michael, justifiably, commands
>much respect on this List (from myself included). IN THE SOCIAL CONTEXT
>OF THIS LIST, therefore, it might be considered "moderate" -- by the
>popular definiton that I've noted above -- to simply conform to this
>social pressure, and give Michael's theory credence.
>

> > If [taking the opinions of others on the list is] the best that you can do.
Thinking for yourself, and weighing
> the evidence -- if one's cognition is high, and one's confidence in it --
> might be better than this conformist definition of "moderation".

I wholeheartedly agree. From the posted material at present, the scales are
loaded down on the side saying that one does't need dietary EPA/DHA, & quite
empty on the other side. Saul, with all due respect, taking your GP's opinion as
the truth -- or even worthy of consideration! -- in the absence of ANY
evidence, and in the presence of extensive evidence to the contrary previously
cited on the list (& now massively reinforced, I expect you will agree), is
hardly "thinking for oneself" or "weighing the evidence."

Without giving you TOO much shit, singling you out, or being unfair, & withfull
& sincere respect, I don't think it was appropriate to suggest that those who
accepted the idea (for which I happen to argue) that ALA can substitute
adequately for EPA/DHA were simply engaged in bowing to authority, when EVIDENCE
had been put forward to back this statement, whereas the only 'evidence' to the
contrary had been the unreferenced statements of your GP and Sears -- both of
whom, I am certainly ready to agree, are bright people.

"Social pressure" makes even less sense. How would this pressure exert itself in
a person who (eg) simply continued taking hir fish oil caps & read the arguments
without comment? Presumably, anyone who takes the trouble to post has either a
question or an opnion which s/he feels moved to express. I fail to see how the
respect (I agree, probably excessive) with which my opinions are greeted on this
list can be attributed to, or meaningfully translate into, "social pressure" --
esp in this case, where they were backed by data.

>[Unless, again, "moderation" means "conformity to the majority of posts to
>this List". i think that would make Aristotle shudder -- and Socrates
>trun over in his grave;]

Now I'm REALLY getting off-topic, but I can't resist on this one. "Socrates"
(ie. not the historical figure, who is a largely unknown Sophist, but the
fictional character used as a mouthpiece by Plato in his dialogs) was no
advocate of free enquiry except for those "properly" suited to it -- who would,
naturally, come to agree with Plato (the intellectual equivalent of Napoleon's
remark that he'd be happy to give power over to the populace, provided they
agreed to always make the decisions he wanted).

The vast majority of the population, in "Socrates'" utopia, was to fulfil their
social caste duty, leaving thinking to the mental elites, & the social harmony
was to be maintained by the creation of "noble lies." & contrary to the fictions
which have created entire academic careers, the "Socratic method" is little
more, in Plato's dialogs, than an excuse to have everyone agree with him ("Yes,
Socrates" "No, Socrates" "How could it be otherwise, Socrates?"), including when
he made abyssmal arguments thru' which a child could see (If red is not white,
then red must be UN-white, that is, black"). "Socrates," if "alive" today, would
be a promulgator of the Food Pyramid (those Egyptians were very wise, you know).
He is a poor model of intellectual independence.

-Michael

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