a quick question. My understanding is that Omega 3 fatty acids have
some anticoagulant effects, I have always put down their protection against
CHD to this factor. Is this your understanding of how they work? Or is there
some other mechanism of action at work.
Malcolm, Sceptics and others:
I attach the pdf of the Lancet (Singh et al. Indo-Mediterranean trial
Effect of an Indo-Mediterranean diet on progression of coronary
artery disease in high risk patients (Indo-Mediterranean Diet Heart Study):
a randomised single-blind trial. LANCET • Vol 360 • November 9, 2002)
my own "omega-3 for dummies" view:
C18:3-n3 ALA plant based; mother of longer n-3's and the most
anti-arrhythmic of the fatty acids [gate-control]; C20:5-n3 EPA; fish;
mother of n-3 based eicosanoids; plus control functions in nerves/brain/DNA;
C22:6-n3 DHA; fish; work horse of cell wall fat based machinery [retina,
nerve, brain]. The latter 2 [or just EPA] would have the most anticoagulant
effects; all are different --and Western diet's gross excess intake of
omega-6 family [mainly linoleic] hi-jacks our cell wall machinery. EPA
might be the most "COX inhibitor"-like of the 3 n-3's. All n-3 and
n-6 has to be eaten since we cannot make them from scratch. True
vitamins [F3 and F6 in my book]. We're therefore vitamin OVERdosing on F6,
and absolutely AND relatively UNDERdosing on F3.
I'd propose that the ONLY fat/cholesterol-related heart studies ever to show
all-cause benefit are high omega-3 intake or omega-3 enrichment trials, ALA,
EPA and DHA having different and additional effects. Enjoy
P.S. That Indo-Med. trial, control: 0.8g/d ALA, intervention 1.8g/d, i.e.
close to the ISSFAL recommended 1%en and close to the Lyon study amounts, as
per Stephen Cunnane and my letter in Feb. 2003 AJCN.
This is another study conducted in the wrong context as it is comparing one
unnatural diet against another. Half a century ago,
CHD was rare in India. It was only after the West told them that their diet
was 'unhealthy' and the Prudent Diet introduced them to polyunsaturated
vegetable oils that CHD took off in that country. A
population comparison was reported in 1967. Dr S L Malhotra, Chief Medical
Officer for the Western Railway system had reason to question the Prudent
Diet. (Malhotra S L. Serum lipids, dietary factors and ischemic heart
J Clin Nutr. 1967; 20: 462-75.) He
reported that in Madras, in the south of India, the population was
vegetarian, living mainly on rice. Although they had a relatively high-fat
diet, it was mainly of peanut oil. As vegetarians, there was practically no
animal fat in their diet. In effect they were living on the Prudent Diet
more strictly than were the Americans. Malhotra compared these Madrassis
with a population who lived in the north near Udaipur. Their religion
allowed them to eat meat and their fat intake was almost entirely from
animal sources and highly saturated. They cooked in ghee (clarified butter)
and had what was probably the highest butterfat consumption in the
world. Present-day 'wisdom' would predict that the
vegetarian Madrassis would have the lower rate of heart disease but the
opposite was true. Malhotra found that the Madrassis who adhered so well to
the precepts of the Prudent Diet had fifteen times the death rate from heart
attacks compared to the northern Indians even though those in the north ate
nine times as much fat - and that fat was saturated animal fat. Twenty years
later the Lancet noted an increase in heart-attack deaths amongst the
northern Indians. By this time the northerners diet had also been made 'healthier'
by the replacement of the traditional ghee in their diets with margarine and
refined vegetable oils. ((No authors listed) Ghee, cholesterol, and heart
disease. Lancet. 1987; 2 (8568):1144-5.)
would seem sensible that the Indians should forget about omega-this or
omega-that and go back to eating the natural saturated animal fat diets they
are genetically adapted to.
really need to get back to thinking in terms of eating proper food --real
food -- natural food.
Barry, a brief response.
Indo-Mediterranean trial in question was in 2/3rds northern Indian
vegetarians [150 km E of Delhi, 700 km N-E of Udaipur], not low animal fat
/high glycemic index /low micronutrient southern Madras Indians. The
trial doubled the fruit/veggie intake, a step in your direction, which would
have increased micronutrient intakes, likely reducing homocysteine as a
starter. Apart form that, the major intervention was the doubling of omega-3
intake to nearly 2g/d and here we differ. Let me propose to you that ANY
society where omega-3 intake falls below 2g/d [and certainly at current
linoleic intakes] there is a problem with heart disease, cancer et al.
Avoid omega-3 at one's peril. One MUST be aware of "omega-this or
omega-that" since at the current excess of linoleate n-6 and the
breeding out or the hydrogenating away of n-3, from Crisco via TenderFlake
to "vegetable ghee", there IS a problem [just as sure as scurvy,
pellagra and rickets are deficiency diseases]. Hydrogenation, the
omega-3 killer, was introduced into N. America [Procter & Gamble's first
Crisco cookbook] in 1912, the year Herrick got himself 6 pages in JAMA
describing as many heart attacks, a classic paper. We are ~7 billion people
with ~1/3rd living on $1/day. Food choices are limited. For some, mustard
seed oil [a brassica/cruciferous plant like rapeseed/canola] and unrefined
palm oil are options. Eddie [I cc Berry since I don't have Ram Singh's
e-mail- author of great magnesium and CoQ10 stuff.]
P.S. Here's a precursor to this study, fish oil OR mustard oil OR placebo
post AMI for 1 year [total n=~350]:
On the topic of ghee, remember that heated butter contains high
concentrations of cholesterol oxides, which are highly angiotoxic, causing
early arterial intimal plaques within 24 hours of administration to animals.
Highly purified preparations of cholesterol containing no cholesterol
oxides produce no evidence of arterial plaques when administered to animals.
In the report by Marc S. Jacobsen in Lancet of September 19, 1987, pages
656-658, ghee was found to contain about 12.3% of all sterols in the form of
cholesterol oxides, primarily 7-hydroxycholesterol, 25-hydroxy cholesterol,
20-alpha-hydroxy cholesterol, 25-hydroxy cholesterol epoxide, and traces of
cholestanetriol. Jacobsen attributed the high morbidity and mortality
from coronary heart disease of Asian Indians in the London area to
consumption of ghee containing these angiotoxic oxysterols.
and other skeptics!
Jacobsen is probably right when he speculates that oxidized cholesterol may
induce vascular changes in animals, while purified cholesterol does not. But
is it relevant? I mean, is there any other evidence that oxidized
cholesterol is a villain? The salient counter-argument against Jacobsen, is,
as I see it, that the vascular changes produced by feeding animals with
excessive amounts of lipids and oxidized cholesterol (and many other things)
has nothing to do with atherosclerosis. This has been demonstrated most
convincingly by William Stehbens, see for instance Prog Cardiovasc
Dis. 1986 Sep-Oct;29(2):107-28.
Barry's note on Malhotra's work (AJCN 20:462,1967) brings back memories.
I commented on it (AJCN 27:1202,1974) in relation to Trowell's concepts on
dietary fiber. In Udaipur 22 of 28 men had vegetable fibers in their
feces in contrast to 6 of 28 in Madras (p<0.00006). After relating
this to Morris's bank men and pointing out that the lipid hypothesis is
supported by international, epidemiologic studies, I summarized more than a
dozen studies done in single countries showing no relationship between
dietary fat and either IHD mortality or cholesterol concentration ( many
more, similar studies are cited in my later papers on the THINCS site.
My suggestion---that if everyone in the Western world eats too much of
the wrong fat, fat is not of epidemiologic interest---deserves repeating.
Something else in this diet (or something missing from it) causes heart
attacks. The lipid hypothesis has outlived its usefulness.
Golly ghee whiz. Ghee only causes CHD in the UK but not in India. Must be
response: let's all agree that non-oxidized cholesterol is vital and that
oxidized/degraded cholesterol [including
that found in butter derived ghee] is not beneficial for health [there is a
resemblance to rancid > polyunsaturates, also hormone(-like) precursors].
IF, like here, in Indiathe "M.I. epidemic" is less than
100 years old, the traditional uses before that of ghee, or butter,
are not particularly deleterious. That > brings me back to things
like B vitamin and omega-3 deficiencies. >
To Malcolm, nice play of words...
but it's not the climate of India, ghee may also be a marker of class >
status/wealth [my interpretation of RB Singh] which is positively associated
to type 2 DM, CVD, etc. [and if one
can avoid either ghee or trans fat "vegetable ghee", those seem
wise choices.] e.
I do not agree. The case is open until you present the evidence against the
assumed villain, oxidized/degraded cholesterol. Don't judge by hearsay or
to my understanding of fatty acids turning into ("per")oxidized
hormones [C20's] by specific COX and other
-genases I can see why rancid fats [pre-peroxidized fats] can have
deleterious effect in our control mechanisms
if they get sucked into [fit in] the enzymes present.
Similarly, cholesterol on its way to our steroid hormones also
undergo specific changes and I would think that
pre-peroxidized cholesterol can generate damaged hormone-like
molecules [and our macrophages appear to feast on them for a reason].
There must be sound logic behind the report that all cholesterol in the
brain is synthesized in situ, the brain taking no chances with damaged
cholesterol. Considering there
are no known benefits of oxidized cholesterol and since mankind is the only
[recent] species consuming the
stuff, I can see reasons to avoid it, being atherosclerotic or not.
Trans fats in common oils also
have no know nutritional benefit and some demonstrated harm. Same kind
of thinking suggests avoidance.
is something fascinating about science. One gets such a wholesale return of
conjecture for such a trifling investment of fact."
any of these studies accounted for the concomitant consumption of types and
amounts of carbohydrates?
Kilmer, eaters of ghee in India, half a century ago, didn't suffer from
cardiovascular disease. As Asian Indians in London do, then some other agent
may be at work. I propose Malcolm's "emigration" as a likely
contender. The Rosetan, Irish Brothers, Japanese and Tokelau immigrant
studies lend weight to this being a cause. I don't put much store by dietary
studies on animals, by the way, particularly as far as fats are concerned. I
am not convinced that lab rats'
or rabbits' metabolic responses are necessarily the same as ours in similar
and Uffe, et al
I agree with Uffe that the possible angiotoxic effects of
cholesterol oxides in human atherogenesis require extensive investigation of
the concentration of these compounds in human diets along with assessment of
their effects, if any, on morbidity and mortality from coronary heart
disease. Very few studies have been published on the effects of
cholesterol oxides in human arteriosclerosis. The ultrastructural features
of the vascular lesions induced by cholesterol oxides in animals include
intimal craters, blebs, with apoptosis of intimal cells, edema, necrosis of
smooth muscle cells, and other evidence of intimal damage. These
changes are a long way from the advanced atherosclerotic plaques observed in
humandisease. To me this field is a promising one for future research.
The possible relation of dietary cholesterol oxides to the pathogenesis of
human arteriosclerosis remains to be established by future investigation in
this area, in my opinion.
anyone know if cholesterol oxide reductase enzymes have been discovered?
Eric, No I don't think so and in secondary prevention I've seen little re
Uffe: sorry you did not like my conjecture, fascinating though it is.
to our American friends about the space shuttle - sad day indeed.
all. The Langsjoens pointed me to another publication by Ram Singh et
al [c.c'd], in Lancet Jan. 4 2003 that I attach as a PDF [Prevention of
coronary artery disease: the south Asian paradox; a comment].
Barry, a brief response. The Indo-Mediterranean trial in question was
in 2/3rds northern Indian vegetarians [150 km E of Delhi, 700 km N-E of
Udaipur], not low animal fat /high glycemic index /low micronutrient
southern Madras Indians. The trial doubled the fruit/veggie intake, a
step in your direction, which would have increased micronutrient intakes,
likely reducing homocysteine as a starter.Apart form that, the major
intervention was the doubling of omega-3 intake to nearly 2g/d and here we
differ.Let me propose to you that ANY society where omega-3 intake falls
below 2g/d [and certainly at currentlinoleic intakes] there is a problem
with heart disease, cancer et al. Avoid omega-3 at one's peril.
One MUST be aware of "omega-this or omega-that" since at the
current excess of linoleate n-6 and the breeding out or the hydrogenating
away of n-3, from Crisco via TenderFlake to "vegetable ghee",
there IS a problem [just as sure as scurvy, pellagra and rickets are
Hydrogenation, the omega-3 killer, was introduced into N. America [Procter
& Gamble's first Crisco cookbook] in 1912, the year Herrick got himself
6 pages in JAMA describing as many heart attacks, a classic paper. We are ~7
billion people with ~1/3rd living on $1/day. Food choices are limited. For
some, mustard seed oil [a brassica/cruciferous plant like rapeseed/canola]
and unrefined palm oil are options.
cc Berry since I don't have Ram Singh's e-mail- author of great magnesium
and CoQ10 stuff.]
Here's a precursor to this study, fish oil OR mustard oil OR placebo post
AMI for 1 year [total n=~350]: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9310278&dopt=Abstract
Uffe et al.
Re: Low cholesterol hazards with respect to emotional disorders (depression,
suicide, violent behavior, etc.) I have attached in PDF format an article in
the current issue of Psychosomatic Medicine that follows up on a previous
report that cholesterol levels were lower in cocaine addicts. This
could result from many factors, but for what it's worth, this study showed
that cholesterol was significantly lower in addicts who had been detoxified
but subsequently relapsed compared to others who had not.
Paul, thank you for the pdf. The authors, Buydens/Branchey, speculate
that low cholesterol in their high risk group may stem from poor nutrition [homocysteine
status determination would have been interesting to pin-point this] or from
high omega-6 vs. low omega-3 intake [adipose and/or red blood cell fatty
acid analysis would pin-point this]. This brings me back to by proposal to
the group last week and to which nobody reacted which was that degenerative
disease increases when omega-3 consumption falls below 2g/d [1%energy].
For some, this may also include decreasing linoleic acid, allowing
cholesterol to raise somewhat, and for some it means that "long chain"
C20 and C22 omega-3 acids [EPA and DHA from fish] should be included [ISSFAL
proposes 0.3%en from long chain n-3 in addition to 1%en from "short
chain" C18 n-3]. In the U.S., for example, long chain n-3 mean
intake is at about 1/4 of this level and at 1/2 for short chain.
of the most senior fat people in the world, David Horrobin, has come up with
what I would call a "unifying theory of degenerative disease"
where he has EPA as the underlying king-pin molecule. This is in a new
book of which I don't have the title [and probably could not afford the
price] but of which I could fax some pages from a print proof chapter.
Here is one piece of writing by Horrobin:
conjecture, sorry Uffe.
Not related but interesting, here's an association [like a rooster and
sunrise or rush-hour traffic and 8 a.m.] between congestive heart failure
Enjoy! [Horrobin and Buydens/Branchey c.c'd -non members of http://www.thincs.org
P.S. More on fatty acids in point 1. of http://www.health-heart.org/comments.htm
to all, I guess I got distracted by our own little blurb (Cunnane/Vos)
in Feb. 2003 AJCN but here is a great study from the same AJCN issue
regarding omega-3 in elderly and ischemic heart disease [especially the
fatal type]. All 3 forms of omega-3 showed up as protective [RR, fatal 0.3
DHA+EPA p=0.01; RR 0.48 ALA 18:3; p=0.04 and INTERESTINGLY, linoleic, the
cholesterol lowering omega-6, increased RR to 2.4; p=0.03].
The authors, RN Lemaitre et al, like us, also refer to the Yam/Berry Israeli
paradox: high n-6 polyunsaturate with low saturates positively associated
with high CHD+, and they refer to Singh's first omega-3 enrichment study.
Table 2 illustrates clearly that linolenic 18:3 does NOT store well; Cunnane
showed that >90% gets quickly metabolized and only a small fraction is
otherwise utilized, as feed stock for eicosanoids and cholesterol. Linoleic
was present in plasma at 125x linolenic n-3 which points to the need to
regularly consume alpha-linolenic [it's the best ntiarrhythmic in my - not
universally agreed to - interpretation]. Table 2 also shows that DHA/EPA
do get conserved well in plasma.
I doubt their final paragraph that high DHA/EPA consumers would consume
generally less linoleic, not likely in the U.S.- everybody gets too much.
Here's the Medline abstract: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12540389&dopt=Abstract
and Alice Ottoboni
Thanks very much for your stimulating comments and links to excellent
paperson the subject . We are amazed at your ability to stay up to
date on the relevant literature.
Underlying much of this problem seems to be a huge dose of pseudo science
that has been used to promote the almost universal use of the so-called
heart-healthy polyunsaturated vegetable seed oils. In the long run,
the adverse impact on human health will probably be larger than that caused
by cigarette smoking.
The current omega-3/omega-6 dietary situation might be described as a very
large scale experiment, using humans as the test animals, aimed at eliciting
the effects of a diet that is overabundant in one essential fatty acid and
almost totally lacking in the other essential fatty acid. We are now
beginning to see the results.
A look at the structure that supports this pseudo-scientific house of cards
seems to reveal a complex combination of advertising, carefully cultivated
influence on governments, nutritional scientists who, for the most part, are
uninformed, a focus on diagnosis and treatment by the medical community, and
an extremely gullible general public.
I see that my Mark Twain-quotation can be misunderstood. I love conjectures
and hopefully we will see more of them in our discussions. What I oppose is
the transformation of conjectures to "established facts" as long
as there is no hard evidence.
However, the interesting paper sent by Paul about cholesterol and cocaine
addiction appears as a strong piece of evidence that low cholesterol is bad
for the brain.
By the way - isn't a heart attack a common cause of death in cocaine addicts?
Multivites might be theoretically useful in preventing atherosclerosis but
it seems that the epidemiology does not support this view, at least as
suggested by the enclosed reference.
et al Vitamin Supplement Use in a Low-Risk Population of US Male
Physicians and Subsequent Cardiovascular Mortality.
Archives of Internal Medicine. 162(13):1472-1476, July 8,
Conclusions: In this large cohort of apparently healthy US male
physicians, self-selected supplementation with vitamin E, vitamin
C, or multivitamins was not associated with a significant decrease in
total CVD or CHD mortality. Data from ongoing large randomized trials will be necessary to definitely establish small
potential benefits of vitamin supplements on subsequent
Let's get biochemical for a moment or two. (Please correct my biochemistry
where it goes wrong)
Omega-3 means a double bond, three along from the CH3 end of the fat
molecule. Omega-6, means a double bond six along from the CH3 end of the fat
molecule. Fat is used for energy, and so omega sixes and omega threes are
all destined to be chopped up and burnt.
Either fat enzymes cannot cleave a double bond (wherever it may be), or they
can. If they can, why does it matter where the double bond sits? What is the
process whereby omega 3 to 6 ratio matters.
When I see a theory, I like to start at the end, namely the biological
process. What biological process can anyone point to that shows exactly what
Omega 3's do that Omega 6's don't - or vice versa - that ends up causing an
atherosclerotic plaque. Either I missed this, or it doesn't exist.
On a related note, a chemist friend of mine just laughs when I start trying
to explain fat biochemistry to him. As he says, double bonds are basically
quantum states, they don't exist as concrete double bonds like a suspension
bridge. They energy states jump, the electrons constantly shift. The double
bond could be almost anywhere on the chain at any time, it just has a
tendency to be around carbon atoms three and four. We talk about Omega 3 as
if it was a concrete entity, but it's not.
I'm sorry, but I find all of this discussion around 3 and 6 tends to exist
in a kind of self-referential bubble. My own belief is that it doesn't
matter at all. The only reason, as I understand it, why anyone got
interested in Omega 3 is because it was the only ad-hoc hypothesis the lipid
hypothesis fanatics could find to explain away the low rate of CHD in Innuit
Indians. (I could, of course, be mistaken on this).
In short, where is the biological pathway that links Omega 3s and 6s, and
their ratios, to CHD.
Can anyone answer a question for me. Is there any proof that the lipoprotein
remnents found in plaque come from LDL. Or is it just assumed that LDL is
the culprit. I can't find any information on this specific area.
There is some confusing literature on how trace elements affect desaturases
and elongases. More experiments are needed to clarify things. It
seems worth studying.
It is true that heart attack is a frequent cause of death among
cocaine addicts. The drug causes arterial spasm and localized areas of
myocardial necrosis. If the myocardial ischemia involves conduction
bundles, dysrhythmias, including ventricular fibrillation or asystole, can
occur, causing sudden death. In long term cocaine addicts, the
myocardium characteristically contains areas of fibrosis that results from
healing of the areas of acute myocardial necrosis.
Paul, re Hcy reducing carotid plaque as per your ref: Hackam DG, Peterson
JC, Spence JD.; Am J Hypertens 2000 Jan;13(1 Pt 1):105-10,
, I've had a link to this study from my site [point 11. in http://www.health-heart.org/comments.htm
-homocysteine] for some time now.
The study suggests the higher the Hcy, the faster plaque growth and the more
Hcy is reduced, the greater the plaque reduction [dose response - if human
carotid plaque is a good model for sclerosis elsewhere]. The cost of
such intervention is minuscule -and, personally, a day without high B
multivitamin is unthinkable.
Combine this with the G. Schnyder's work in NEJM and JAMA: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11757505&dopt=Abstract
[as per attached graph from http://www.health-heart.org
] and we have pretty hard data that reducing homocysteine, or separate B
vitamin effects, are protective before or after interventions.
Paul, This is your original study:
and this is a Dec. 2002 study in Stroke from the same group: Spence JD,
Hackam DG : "plaque area as tool":
I did a little math with these 2 studies:
Mean quartile plaque surface in mm2 : 5.5, 28, 82 and 400 mm2 Relative Risk
[combined end points] : 1 1.9, 2.5, 3.5 [2.5yr;
n=420/group: stroke+MI+ vasc. death]
Hcy reduction in 2x50 patients [older study]:Hcy >14 : 21 mm2 baseline;
after B vitamin therapy, reduction [-] 5 mm2/year Hcy <14 : 13 mm2
baseline; after B vitamin therapy, reduction [-] 2.4 mm2/year
Some patients  in the recent study had 2 measurements: regressed:
28%: 9.4% endpoints [5 year combined, adjusted endpoint]
progressed: 63%: 15.7% ,,no change: 16%:
Ergo: plaque size IS important and high dose B vitamins can "eat way"
relatively large %% of plaque/year [if you're not starting with 400 mm2 in
the first place.
Just some happy conjecture -
I'll forward the full studies if ever I get pdf versions. Enjoy
I appreciate your thorough and erudite comments and offer the following
1. Plaque size is a notoriously unreliable measure of severity of coronary
artery disease progression, particularly when the measurements are not done
2. Epidemiology is always suspect because it is not prospective nor
randomised and there is always the risk of bias due to self selection of
groups. However a negative result has more meaning than a positive one
i.e., the measured variable such as vitamin intake is demonstrively free
from self selection if the result is negative.
epidemiology: these are the people [mainly Harvard] that have us believe
"polyunsaturates" are beneficial based on <15yr. studies like
this one. Yet, these studies have not looked at food patterns over the
last 90 years when low or no omega-3 foods and long shelf life low nutrient
foods were unleashed. Kilmer's theory of heart disease, i.e. low B
vitamin = high Hcy, and the massive drop in rates since multi's were added
to breakfast cereals [think B6, folacin]. It ain't faster ambulances,
finer drugs or sharper scalpels that dropped disease rates.
The Nurses/Health Professionals studies BOTH suggested RR 0.6 for vitamin E
supplementation... The Harvard Medical School Guide to Healthy Eating
[Walter Willett's 2001 book] has a proposed food pyramid with "Multiple
Vitamins for Most" [hardcover, page 17]. However, this pyramid
still has in its base corn, sunflower, soy and "other vegetable oils
-which is why I disagree with W.W., not splitting out omega-3 from omega-6.
The latter demonstrates the difficulty of epidemiological confounders: think
"total cholesterol" and not considering the various types and
their varying contents. The study below, I believe, does not give data
about the type and contents of the multi's used.
It is true there are no massive studies comparing multivitamins with placebo
--and it would be unethical as well as unprofitable to do such long trials
in high risk groups; therefore we must thank the Hcy link for having
generated such interest [with clearly defined doses of vitamins] and hard
endpoints [restenosis] as well as suggestive studies like plaque size and
reduction [plaque size full text study attached in PDF; I don't have the PDF
of the vitamin intervention vs plaque size study].
Spending $0.15/day on a high dose multi -before you become a Guido Schnyder
restenosis subject- seems a wise move. A seatbelt may never save your
life but I would not drive without one.
VITAMIN C: http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=1591317&form=6&db=m&Dopt=b
From my website
re C: Canadian Medical Association Journal of Sept. 23 1972. During
102 days (3.4 months) in winter, 407 about 25 year old Canadians took 1 g/day
+ 3 g/day during the first 3 days of any illness. An identical group
of 411 on taste and look-alike dummy pills had 40% more people seeking
medical help (56 vs. 40), 58% more doctors visits [94 vs. 60] and a "similar[ly]"
increased prescription drug use. Statistically, many of the benefits
were important, such as the 99.9% probable decrease in days of disability.
[no abstract available]
Epidemiology may not be without its flaws. But death rates in countries are
pretty powerful objective indicators of underlying disease rates. To my
mind, if you are going to present a hypothesis regarding any causal factor
then you must attempt to relate it, not just to USA figures on CHD, but
figures from around the World.
So, for example, how does the intake of vitamins relate to CHD rates in
Lithuania (currently the country with the highest rate of CHD in the world).
How does the intake of vitamins relate to the death rates from CHD in Japan,
presently and over time.
Malcolm, I could not agree more and as I look at things, the confounder of
most studies lies in the micronutrients [folic acid, B6 becoming ever more
evident]. The population studied is in one area on Ontario and as such
valid. The new laboratory you mentioned, Lithuania, has 4x more heart
disease than countries to its West and has been well studied [but to my
knowledge, not in B vitamins]. Here are 3 abstracts:
Ultrasound [interesting indicator/predictor as per the Canadian work]:
Lower cholesterol, fatty acid study [a dead-end, red herring approach, but
Carotenoids, lower fat soluble antioxidants [indicator of micronutrient
intake but itself reddish herring]:
The latter study might be indicative for lower B vitamin [=low grade
degraded foods] intakes. No Hcy study done I believe in this
population [nothing in Medline].
studies you refer to, not least the vocabulary. Anders G. Olsson,
co-author of all three papers, has been one of the staunchest
proponents of the cholesterol paradigm in Sweden since many years and I
have had several tough discussions with him in Läkartidningen, the Journal
of the Swedish Medical Association. I was therefore curious to learn how the
authors might have explained away the fact that tC and LDL-C was
significantly higher in the Swedish cohort than in the Lituanina (5.1 vs
5.49, and 3.3 vs. 3.68, respectively) although CHD was four times higher in
Lithuania. The final comment did not surprise me: "The high
mortality from coronary heart disease in Lithuania is not caused by
traditional risk factors alone (!)."
curious statement in the abstract from the ultrasound study is also the
following: "In a linear regression model of the pooled
material, after adjustment for city was made, smoking, systolic blood
pressure, low density lipoprotein cholesterol and beta-carotene (inversely)
significantly contributed to a high total ultrasound score (r2 =
0.32)." Let alone that they cannot know anything
about what did "contribute" to the high score, they can only
measure statistical associations, but this is of course unnecessary to point
out in this forum, but if Chol was significantly higher in Lithuania and if
they also had more atherosclerosis, how could LDL-C "contribute to
a high score"? As I have not access to the full paper (please send
it, Eddie!) I guess that also LDL-C, just as beta-carotene, was
inversely asociated with the score. Or is it an effect of adjustment for
city? Do they mean that in the individual cities LDL-C correlated, but not
totally??? Why adjust for city?
never said if LDL contributed for or against a high score. 'Include me out.'
Lithuanians score high on Vital Exhaustion (VE) and depression and they all
hate their work vs. Sweden. I shall try to dig out the paper.
They also have lots of insulin resistance
Uffe et al.
In case you missed this. What will they conclude if this does not
correlate with decreased coronary morbidity and mortality? (see below)
Stanford researcher studies newly discovered 'good' cholesterol gene.
STANFORD, Calif. - Stanford University Medical Center researchers have found
that a recently discovered gene regulates HDL (high density lipoproteins)
cholesterol, also known as "good" cholesterol. The study,
published in the February issue of the Journal of Clinical Investigation,
could lead to new therapies for heart disease, said lead author Thomas
Quertermous, MD. "This is a significant and unexpected finding, and the
gene is going to be a real target for the prevention and treatment of heart
disease," said Quertermous, the William G.Irwin Professor and chief of
cardiovascular medicine at Stanford University School of Medicine.
"This type of thing doesn't happen every day."
cholesterol, often referred to as the "good" cholesterol, has been
proven to impact a person's risk of developing heart disease. "HDL
cholesterol is an independent predictor of one's risk," said
Quertermous. "If you have a high level of HDL cholesterol your chance
of getting heart disease is very low."Researchers know that levels of
HDL cholesterol are regulated in part by members of the lipase gene family.
Three years ago, Quertermous' team and a laboratory on the East Coast
simultaneously discovered the newest member of that family and found that
its protein was expressed in a variety of tissues. Subsequent studies showed
that the new gene - the endothelial lipase gene (LIPG) - played a role in
was a striking, if not dramatic, finding that this gene that we found in the
blood vessel walls appeared to regulate HDL cholesterol levels," said
Quertermous. Quertermous' team sought to examine the gene's exact role in
regulating HDL cholesterol level by examining genetic models with altered
levels of endothelial lipase (EL) expression. Working with mouse models, the
researchers increased EL expression in one group by inserting copies of the
human gene and decreased EL expression by knocking out the LIPG gene in
reports that the findings were striking: Altering the genes showed a clear
and significant inverse relationship between HDL cholesterol level and EL
expression. Levels of HDL cholesterol decreased by 19 percent in the first
group and increased by 57 percent in the group whose gene was knocked out.
"When we overexpressed the human gene in the mice, the HDL cholesterol
levels dropped," said Quertermous. "Conversely, when we knocked
out the gene in mice, the levels were much higher." Quertermous said
that his team lacks insight into the mechanism by which EL impacts HDL
cholesterol levels, and that this is something his team will explore. The
group will also further study mouse models, and a group of human
patients, to see if changes in HDL cholesterol levels directly correlate
with heart disease. "My hypothesis - and strong suspicion - is that if
you knock out the gene, your chance of disease development is decreased,"
said a greater understanding of this gene's role in HDL cholesterol's
formation and metabolism will help researchers regulate this risk factor.
"This becomes one of the most attractive targets available for the
development of pharmaceutical agents to modulate HDL cholesterol levels,"
Quertermous? Quertermous and
the Pit? Quertermous, half man, half biscuit?
Quertermous and the - I don't know what I've discovered, but I think I can
get twenty million dollars from a pharmaceutical company to help develop an
HDL raising agent.
Teensy, weensy problem. Has anyone the faintest idea how a high level of HDL
is supposed to protect against CHD? Perhaps, gentle reader, it is the
underlying metabolic abnormaltiy of insulin resistance causes HDL to drop.
Insulin has a role in regulating lipase expression, and people with IR
havereduced lipase expression. A shocking finding?
Is there really any point in reading studies into the supposed causes and
cures for ischaemic heart disease? It takes up a lot of time -- and where is
the benefit? If there is one thing I have a profound distrust of, it's
mucking about with genes, either in animals or plants. I really don't
believe we have the intelligence to manage it safely -- even if it were
I realise that this work does keep many scientists employed and that this
may reduce social security tax burdens of several countries. But, looking
back at the record of this disease to a time when its incidence was
somewhere between rare and non-existent, it is quite clear that a major
cause is the modern methods of food production combined with "healthy"
diet recommendations and the stress that conflicting advice puts on
If all this gene work were actually necessary to our survival, we would now
be as extinct as Neanderthal.
We (and by "we" I mean "civilised Man") have cracked the
atom; are mapping the human genome; and we (think we) know what macro- and
micro-nutrients do what in the body -- and yet we are profoundly unhealthy. Any
primitive who has not had contact with our form of civilisation not only
doesn't get fat, diabetes, heart disease, et al, they rarely if ever succumb
to infectious diseases either. In a word, they are healthy. Why don't we
just study and take a lesson from these people? It seems to me that they are
the real experts.
PS. Please excuse this outburst, but I do get feelings of frustration
Primitive man doesn't quite have such a wonderful time. I think it is
complete baloney to suggest that they don't get any infections. Malaria was
common, just to give one example. Death rates were high, and I would be
willing to bet large sums of money that the average life expectancy in the
Western World is considerably longer than in any primitive society.
I agree that we pay the price for the psychological stresses imposed by
living in such massive and highly structured societies. Also that we eat
some right old rubbish, and that we don't excerise enough anymore.
However, on the basis that we are stuck living an 'unhealthy' lifestyle, and
we are not going to return to a primitive way of life, it is surely worth
trying to unravel the truly 'bad' things i.e. the things that are really
damaging our health. Then we can change the things we need to change.
I am a cholesterol skeptic, primarily because I feel that the current health
'fascism' is not driven by reason, or facts. It is driven by rather darker
forces: the need to control, the sense that indulgence i.e. eating nice food,
should be punished. This is ignoring the commercial pressures.
In my opinion, billons of people are being manipulated, frightened and to a
great extent controlled by the diet-heart/cholesterol myth. We need to stick
to our guns and keep battling away - I think.
Barry, Malcolm and all:
understand that Sweden has some of the most reliable records of life
expectancy because of the church registration system dating back several
hundred years. The life expectancy in the 1700s was something like 39
years for women and 36 years for men. (Tongue-in cheek, was Sweden
advanced or primitive in the 1700s?) Interestinglywomen lived longer than
men then as now.
apparent paradox is that North American life expectancy has risen more or
less in parallel with the number of MacDonald fast food outlets.
for Eddie, I believe that the incidence of hemorrhagic strokes is negatively
correlated with serum cholesterol concentrations.
It seems that, while malaria was common in Europeans in Africa, that was not
the case with the indigenous populations.
Malaria only spread to human populations following the introduction of
agriculture in Africa.1 Malaria kills more people, even today, than any
other infectious disease, and, consequently, is a potent agent of natural
selection and human evolution. There is evidence that some African societies
developed biocultural systems to produce and consume food that reduced the
threat of malaria.2
Sally Fallon's writes in "Out of Africa: What Dr Price and Burkitt
discovered in their studies of Saharan tribes":
'Throughout his studies of isolated populations on native diets, Price was
continually struck by the contrast of native sturdiness and good health with
the degeneration found in the local white populace, living off the "displacing
foods of modern commerce" such as sugar, white flour, canned foods and
condensed milk. Nowhere was the contrast more evident than in Africa. In
addition to their susceptibility to chronic diseases such as cancer, heart
disease, intestinal problems, appendicitis, gall and kidney stones and
endocrinological dysfunction, the Whites also showed little resistance to
infectious diseases carried by mosquitoes, lice and flies. "In all the
districts, it was recognized and expected that the foreigners must plan to
spend a portion of every few years or every year outside that environment if
they would keep well. Children born in that country to Europeans were
generally expected to spend several of their growing years in Europe or
America if they would build even relatively normal bodies."3 By
contrast, the native Africans exhibited a very high tolerance to
infectiousdisease including malaria carried by mosquitos, typhus and fevers
transmitted by lice and sleeping sickness borne by the tsetse fly.'
1. Livingstone, F. B. Anthropological Implications of Sickle Cell Gene
Distribution in West Africa." American Anthropologist 1958; 60:533-62.
2. Jackson, F. L. . Two Evolutionary Models for the Interactions of Dietary
Organic Cyanogens, Hemoglobins, and Falciparum Malaria. American Journal of
Human Biology 1990; 2: 521-32. 3. Price, Weston A, DDS, Nutrition and
Physical Degeneration, The Price-Pottenger Nutrition Foundation, San Diego,
CA, p 130
I imagine that deaths caused by accidents and predation were common, but it
seems that we introduced the concept of catching diseases. Incidentally up
to the middle of the 20th century at least, the Masai were renowned for
their good health and longevity. They eat only blood and milk. I have no
data but I suspect they didn't get regular vaccination against endemic
The impact of oxidised LDL on both endothelial damage and blood
coagulability is well recognised, which all fits nicely within the concept
that atherosclerotic plaques develop as a consequence of two inter-related
damage to the endothelium. A combination of bio-mechanical stress, plus 'toxic'
substances in the blood including: hyperglycaemia, hyperuricaemia,
hyperhomocysteinamia, high levels of insulin, stress hormones, etc. etc.
clot formation over the damaged area. Stimuated by high fibrinogen levels,
stress, oxidised LDL, reduced NO synthesis by the endothelium etc.
role of LDL in all of this is probably quite complex. Firstly, when a clot
starts to form, platelets release free-radicals that oxidise LDL, oxidised
LDL both acts as a pro-coagulant agent, it also forms part of the lipid
surface upon which clots are formed. LDL, or perhaps Lp(a) is then
incorportated into the clot matrix. Lp(a), when incorporated makes the clot
very difficult to destroy, as the apolipoprotein (a) molecule is chemically
identical to plasminogen (but is not activated by plasminogen activator).
of this fits, in part with Linus Pauling's work. He demonstrated that only
animals that cannot manumfacture Vitamin C have the LDL molecule,
lipoprotein (a), and the function of lipoprotein (a) is to plug gaps in the
blood vessel walls that develop in situations of vitamin C deficiency.
it makes sense that endothelial damage, through release of free radicals
will attract, then oxidise LDL, and incorporate this lipoprotein into the
clot matrix, as this is one way that the body 'repairs' damaged endothelium.
It also makes sense that vitamin C has an effect on this process.
I part company with Linus Pauling is that I do not believe that massive
doses of vitamin C will prevent CHD.
it all does make sense once you stop trying to find THE factor for CHD, or
THE process that causes CHD to develop. There are, maybe, fifty things that
can damage the endothelium. If twenty are present, the endothelium is
damaged - and there may be no overalp with the other thirty factors. There
are maybe another fifty things that can increase blood coagulabiltiy. Again,
once you reach a critical mass of pro-coagulant factors, you will form
underlying process in plaque development is always the same, but the factors
that cause the process are not necessarily the same. Just as you may scratch
your hand with a knife, a stone, a pair of scissors, so you may damage the
endothelium with a high blood pressure, or hyperglycaemia, or
hyperhomocysteinaemia. Once you have damaged the endothelium clots will
form, and depending on a number of factors the clot will either be small,
and easy to clear away, or very big and difficult to remove.
hell with Occam's razor. CHD does not have a single, simple answer. It has
lots of different answers that are all correct(ish). Apart from raised
cholesterol level of course.
Uffe et al.
I happen to think that good-LDL is good until you corrupt it with
ox-cholesterol [may be] or Hcy while HDL is generally a good thing nomatter
what you do to it. Interestingly, the 3 things that raise HDL are
blood flow promoting actions: niacin [the flush kind], exercise [the flush
kind] and alcohol [the flush kind].Coincidence ? [Balz Frei once said:
running from bar-to-bar raises HDL --and incidentally, that avoids drinking
I'll try and get a copy of the Lithuania study, but as said, the authors are
looking at the wrong risk factors and fail to explain the factor 4
difference [and then there are the traditional Laps with high T-chol. and
low cardio disease].
That CBC program was about $800US full body scans [X ray dose ~300 regular
x-rays] to find "warts" that people wind up with in our free
hospital system, jumping ahead of actually ill people. Making
patients. The leukocyte / inflammation link needs more work and that Arfors/Frei
Circ. article [great SEM pictures] is worth reading!
are two interesting papers (Lehr
HA, Arfors KE Curr Opin Hematol
1994;1:92-9; Lehr, Balz Frei, Olofsson, Carew, Arfors. Circulation.
1995;91:1525-1532) about leucocyte function, relevant to our discussion
about oxidized cholesterol, co-authored and sent to me by our new member
Karl Arfors. In particular, I was impressed by figure 2 in the paper. Karl
will try to get the full paper of the abstract.
good science gives rise to more questions than answers. Evidently, oxidized
cholesterol makes leucocytes adhere to the walls of the aorta, the
arterioles and the postcapillary venules and this adherence can be prevented
by vit C. But is this the start of atherosclerosis? And if it is, why are
the venes protected but not the arteries? And does it matter to eat oxidized
cholesterol? Aren´t oxized cholesterol and other oxidative agents
taken care of during their passage through the capillaries of the intestine
and the liver before they reach the arterial system? And if not, why aren´t
vena porta and vena hepatica atherosclerotic? Also, if free radicals from
tobacco smoke and other exhausts and chemicals get access via the pulmonary
capillaries, why aren´t the pulmonary veins atherosclerotic?
Stehbens may probably tell us that it is because arteries are exposed to
higher pressure and flow, and there is much evidence to support that view,
but how come that no raised lesions were seen in the arteries of the
Masai warriors, who according to George Mann were exposed to strenous
exercise most of the day? And how come, that the only treatment in the
numerous angiographic trials that has exhibited dose-response is exercise?
As I see
it we have many interesting hypotheses around us, but none of them are able
to explain all the features of atherosclerosis.
Uffe et al.
happen to think that good-LDL is good until you corrupt it with
ox-cholesterol [may be] or Hcy while HDL is generally a good thing nomatter
what you do to it. Interestingly, the 3 things that raise HDL are
blood flow promoting actions: niacin [the flush kind], exercise [the flush
kind] and alcohol [the flush kind].
Coincidence ? [Balz Frei once said: running from bar-to-bar raises HDL
--and incidentally, that avoids
drinking and driving.]
I'll try and get a copy of the Lithuania study, but as said, the authors are
looking at the wrong risk factors and fail to explain the factor 4
difference [and then there are the traditional Laps with high T-chol. and
low cardio disease].
The leukocyte / inflammation link needs more work and that Arfors/Frei Circ.
article [great SEM pictures] is worth reading!
Malcolm et al
with you that the most likely mechanism is close to the one you have
proposed, involving many cooperating factors, hereditary or environmental,
just as is the case with many other diseases, in particular the infectious
ones. But there is a great problem with your incorporation of oxidised
LDL in the chain of events. First, what do you mean by "well recognised".
Isn't the role of cholesterol and animal fat "well recognised"
also? Such statements trigger my inner scepticist. As far as I know, the
mentioned effects of oxidised cholesterol have been demonstrated in
test tubes or laboratory animals only. Lots of assumed pathogenetic
mechanisms have been shown in test tubes and laboratory animals, but when
the hypotheses created by these experiments are confronted with the
real world they have very often been effectively falsified. For instance, if
cholesterol is oxidised during the formation of a clot, the risk should
increase if there is much cholesterol to be oxidised, but you know how it
is! Also, Malhotra´s findings (see Barrys recent letter, or my book, Myth
#1) are very, very difficult to explain if you think oxidised cholesterol is
I must be getting unclear in my ramblings. When I say well recognised, I
mean, well-recognised by me.
though, I think you misunderstand what I am trying to
are in vitro experminents that demonstrate something that very few people
are aware of. Namely that when platelets start to aggregate they release
free radicals. These free radicals oxidise LDL (I presume that they only
oxidise the LDL that is in the vicinity, and that the total amount of LDL
has no bearing on the amount of LDL that gets oxidised.) Oxidised LDL acts
as a thrombus promoting agent.
or not this is exactly true, it is well recognised, by more than just me,
that lipoproteins become part of any thrombus that is formed. Also that
lipoproteins are independent clotting agents, and provide the lipid surfaces
upon which clots form. So there is an interlinking between LDL, thrombus
formation and atherogenesis that is strong, fits the facts and makes sense
from a biological perspective.
does NOT mean that LDL causes CHD. It does NOT mean that oxidised LDL causes
CHD. All it means is that LDL probably does play a part in the mechanism of
clot formation over damaged endothelium.
hope that is clearer and doesnt' raise the skeptic within.
Fred and Alice
I am convinced that change in diet is usually all that is required. Here is
a lovely example of serendipitous 'cholesterol profile' normalising. It's
the way Kwasniewski, Lutz and I have been preaching for decades. The
abstract I have written below asks a question. The answer is: Yes!
"Multiple food allergies required a group of seven patients with
elevated serum cholesterol levels to follow a diet in which most of the
calories came from beef fat. Their diets contained no sucrose, milk, or
grains. They were given nutritional supplements. This is the only group of
people in recent times to follow such a diet. During the study, the
patients' triglyceride levels decreased from an average of 113 mg/dl to an
average of 74 mg/dl; at the same time, their serum cholesterol levels fell
from an average of 263 mg/dl to an average of 189 mg/dl. At the beginning of
the study, six of the patients had an average high-density lipoprotein
percentage of 21%. At the end of the study, the average had risen to 32%.
These findings raise an interesting question: are elevated serum cholesterol
levels caused in part not by eating animal fat (an extremely "old food"),
but by some factor in grains, sucrose, or milk ("new foods") that
interferes with cholesterol metabolism?"
(Newbold HL. Reducing the serum cholesterol level with a diet high in animal
fat. South Med J 1988;81:61-3)