News on C-rective Protein and LDL, with notes by S. Harris
Steve Harris
Ostler once remarked that the doctor who understands syphilis understands
medicine. The closest we can come to such a statement in today's world might
be that the doctor who understands the _inflammatory response_ understands
medicine. Inflammation is responsible for the classical signs of disease in
the ancient Galenic view (rubor, calor, tumor, dolor = redness, head,
swelling, pain), and very often inflammation is partly responsible for the
fifth sign of disease that historically was added in the middle ages:
dysfunction. Treatments which affect inflammation, such as application of
heat and cold, were (and are) strangely powerful in general medical care. As
are foods and drugs that modulate the process: the story of aspirin is
familiar, but other antiinflammatories have had a long history as "nostrums"
simply because they affect symptoms of so many diseases positively. For
example, the body oil of the Chinese water snake, which is 20% EPA (an n-3
fatty acid also common in fish) was long sold as a cure for rheumatism and
aches and pains anywhere. Thus the pejorative "snake oil." But the stuff
probably worked like aspirin, because today we know that (in general) the
3-series prostaglandins made from n-3 fatty acids are not as inflammatory as
the more common ordinary kinds. Fish oil is good for arthritis, and so is
snake oil. Take that, quackbusters.
Inflammation is a two-edged sword, and so is the suppression of it. Modern
medical care consumes vast amounts of anti-inflammatories, with such gusto
and with so many negative consequences, that these drugs are probably
responsible for the majority of serious outpatient drug reactions. The
modern doctor spends time thinking about inflammation and its direct and
indirect consequences every day.
Inflammation causes symptoms, but as regards the actual pathogeneisis of
some disease, inflammation is beginning to look like it often has a role
here also. To be sure, inflammation helps healing, and helps with bacterial
infection, but our inflammatory responses are built to deal with small
bacterial infections and small wounds. Here is where the two edges of the
sword come in: in the case of gross systemic infections (septic shock),
large traumas, ischemic/reperfusion injury, and the like, the inflammatory
response may well be inappropriate, since evolution didn't design us to
survive these anyway. For example: inflammation after brain ischemia is now
known to cause some of the damage of post-resuscitation syndrome, and we
have recently discovered that it can be partly blocked by application of low
temperatures, in just the same way that immediately putting a burned finger
or a twisted ankle in cold water helps to limit the damage for these
tissues. Cooling the brain is the first resuscitation treatment which has
actually worked in a clinical trial, and there is much more to come.
Another example: the inflammatory response to the degeneration of old age
may also in many cases be inappropriate, since the problem there is not an
injury which is capable of being fully healed. Think of degenerative
arthritis and the chicken-and-egg role which aging and chronic inflammation
play. More on this later.
Most recently, both atherosclerosis and Alzheimer's disease have been
prospectively associated with chronically elevated levels of inflammation in
the body (as measured by by the inflammatory mediator C-reactive protein
(CRP) levels) long before the disease pathologies manifested themselves
(scientists checked stored blood from people who developed the diseases
years later). Is CRP merely a confounder (ie, marker variable)--- or is it a
player? From the independent and powerful association CRP and
atherosclerosis, which we've yet to control for by using any other risk
factor for atherosclerosis, we suspect it's a player. CRP is as good a
predictor of heart disease as LDL cholesterol levels, but independent of
them. Of course, in the absence of prospective interventive trials, we don't
know for sure if CRP is a causal agent in atherosclerosis, but we do have
some mechanistic evidence to tie CRP causally into the general process. We
do know that CRP causes macrophages to take up LDL cholesterol (a key step
in atherogenesis), and in the news today it has been reported that CRP
actually binds to oxidized LDL, and thus may trigger off the immune system
inside vessels by that mechanism (news report appended).
There is of course by now an inflammatory theory of aging (see below-it's
one of dozens of "theories" of aging that are now out there seeking
support). It's known that many markers of systemic inflammation go up in
aging, and also from simply being obese (IL-6 and TNF levels). It's also
known that dietary restriction (DR) in animals (which retards aging) blocks
this rise in these two mediators. So the "inflammatory theory of aging" is
in some ways Dr. Roy Walford's old autoimmune theory of aging, now picked up
and dusted off a little for the modern world. As for the newer mediator CRP,
it isn't known (so far as I can tell) what happens to CRP levels in animals
on DR, but in humans there is epidemiologic and direct experimental data
that the fatter you are, the higher your CRP is, and that losing weight
causes it to drop (see abstract appended). It is quite probable that there's
a direct connection between obesity and CRP, and from there it's possible
that obesity connects to who-knows what problems associated with aging.
An example of where this might occur: we know that obesity is certainly
associated directly and causally with some inflammatory problems which are
age-related. It has recently been shown that Labrador dogs gets less
age-associated osteoporosis, as well as live longer, if they are
calorie-restricted. Also, we know that obesity is an independent risk factor
for not only osteoarthritis of the knees, but also the HANDS in humans.
Unless these obese people are walking on their knuckles, that means
osteoarthritis is at least partly a metabolic problem, and has nothing to do
with stresses and loads.
It is known also that IL6 induces the liver to make CRP, and the heavy
modulation of IL6 by energy restriction has long been known in animals. CRP
also makes macrophages make nitric oxide and a lot of other inflammatory and
perhaps nasty chemicals. Statin drugs themselves are modest
antiinflammatories, and also anticarcinogens in many systems. It would not
be surprising if statin drugs were better at correcting inflammation in
obese people, but so far as I can tell, this has not been specifically
tested (there's an idea for somebody).
Perhaps CRP will prove to be a causal factor in both atherosclerosis AND
some other degenerative processes of aging in humans. We're naturally
interested in what causes CRP levels to drop in humans. Weight loss does, at
least if we believe epidemiologic trials plus one small prospective weight
loss trial (see below). The "statin" drug atorvastatin/Lipitor does (see
abstract), and the drop of 0.8 in the study is significant in light of the
fact that CRP levels below 1 are considered "low" risk, and above 2
"moderate risk." Also the combination of niacin and lovastatin decreases
CRP in a dose-dependent manner (not clear if the niacin is helping, but
probably). Statins are presently the only class of drugs which has been
proven to extend life in a subset of humans (people with coronary risk
factors) who are even reasonable proximate stand-ins for the average person.
I know of no life-span studies of statins on rodents, perhaps because nobody
thought to do them, since rodents don't get atherosclerosis and coronary
disease. But with the new connection of inflammation, CRP, statins, and
aging, it may be a better idea to test statins on rodents in a full-on life
span study, than we had thought. Hmmm. You read it here first.
One last comment of interest on a trifle: Some years ago I had the chance to
go through data from the China Health Study, a gigantic study of
prospective lab tests and later disease and death in some hundreds of
thousands of Chinese. One of the fascinating effects noted is that there is
no effect of LDL levels on heart disease at the cholesterol levels common in
rural China (cholesterol about 125 mg/dl), but there is a marked effect of
very low cholesterol levels (less than 90 or so) on death by infectious
disease-primarily pneumonia. Very low levels of LDL are bad. I had assumed
that they were merely a marker for malnutrition, which in turn subjected
people to higher risk of infections. But perhaps not. In the interview
below, one of the factors reported to contribute to the research was the
fact that "Recently, the Witztum team found that many mouse antibodies that
are specific to oxidized LDL are identical to "T15" type natural antibodies
that have been extensively studied for 30 years by immunologists for their
recognition of S. pneumoniae, the most common cause of pneumonia. T15 also
binds to phosphocholine present on pathogens and provides a protective
immune defense against those pathogens." So there you are: if you have a lot
of oxidized LDL perhaps this causes your levels of antibodies to this rise,
and these protect you, in turn, from strep pneumonia. This feeds a bit into
my long suspicion that the systems which protects you from infection may
well be the ones that later cause degeneration and aging, and there is only
a limited amount that can be done with them in the real and dirty world.
Most calorie restriction experiments, remember, have been done in
semi-isolated laboratories.
Steve Harris, MD
News and abstracts:
The following news release and any accompanying images can be accessed on
the web at: http://health.ucsd.edu/news/2002/09_09_Chang.html
Contact: Sue Pondrom (619) 543-6163 spon...@ucsd.edu at SCSD
News Date: September 9, 2002
Team Identifies Potential Role of CRP In Development of Atherosclerosis
Another piece of the complex puzzle of how inflammation is involved in heart
attacks and strokes has been discovered by researchers at the University of
California, San Diego (UCSD) School of Medicine.
Their findings demonstrate that C-reactive protein (CRP) binds to oxidized
low density lipoprotein (LDL), implicating the interaction of CRP and
oxidized LDL as a potential trigger for the cascade of events leading to
atherosclerosis. This form of artery disease is characterized by the buildup
of fatty deposits and chronic inflammation along the artery wall, eventually
leading to heart attack. Published in the online edition of Proceedings of
the National Academy of Sciences (PNAS) the week of Sept. 9, 2002, the study
by the UCSD researchers pinpoints how CRP attaches itself to oxidized LDL,
the so-called "bad cholesterol" that accumulates in the artery wall and
generates atherosclerotic plaques. LDL is the major cholesterol carrying
particles. When they enter the artery wall from the circulation, they are
believed to be modified by oxidation. It is this "oxidized LDL" that is
thought to be the culprit leading to inflammation and cholesterol
accumulation. "Our study points out that CRP is not merely a marker of
future cardiovascular events, as most people believe, but it actually binds
to oxidized LDL and apoptotic or dying cells, giving it a potential role in
development or modulation of atherosclerosis, as well as in other
inflammatory disease," said Mi-Kyung Chang, M.D., an assistant project
scientist and the first author of the paper in PNAS. In the new studies, the
UCSD team showed that CRP binds to oxidized LDL through the recognition of
phosphocholine, a part of an oxidized molecule on the surface that is
exposed when LDL undergoes oxidation.
Noting that there is an accumulation of dead and dying cells (apoptotic
cells) in atherosclerotic lesions and that these cells are under increased
oxidative stress, the UCSD researchers also determined that CRP binds to
these cells in a similar manner as it recognizes oxidized LDL. CRP is
conventionally regarded as a first-line defense of the immune system against
invading pathogens and confers protection to humans by removing pathogens.
Recently, CRP has been reported as a useful marker for predicting future
atherosclerotic cardiovascular events, but the basis for this correlation
remains unclear.
Although scientists still do not understand all the steps in the development
of atherosclerosis, it is known that oxidized LDL in the artery wall are
taken up (engulfed) by macrophages, scavenger cells that have been drawn to
the site by oxidized LDL. When they become engorged with the oxidized LDL,
the macrophages become "foam cells," the hallmark of atherosclerotic
plaques. It is possible that CRP may bind to oxidized LDL and further
enhance the uptake into cells.The paper's senior author, Joseph Witztum,
M.D., professor of medicine, added that cholesterol is still a key player in
coronary heart disease. He said that CRP may be working in its "correct
role" as part of the immune response to the toxic oxidized LDL and may help
promote its clearance. "If you have low levels of LDL, and thus, low levels
of oxidized LDL, then CRP may be of benefit," Witztum said. "However, when
there is an overwhelming accumulation of LDL, and thus oxidized LDL, in its
attempt to help clear the toxic particle, the CRP may actually make things
worse. It may cause more oxidized LDL to be taken up into macrophage
scavenger cells, which in turn cause cholesterol accumulation a sort of
'Trojan horse'." For the past 20 years, the Witztum lab at UCSD, in
collaboration with UCSD professor of medicine Daniel Steinberg, M.D., Ph.D.,
has pioneered the role of oxidized LDL as a major contributing factor for
the development of atherosclerosis. In particular, the Witztum lab has been
studying immunological response to oxidized LDL and its impact on
development and modulation of atherosclerosis. Recently, the Witztum team
found that many mouse antibodies that are specific to oxidized LDL are
identical to "T15" type natural antibodies that have been extensively
studied for 30 years by immunologists for their recognition of S.
pneumoniae, the most common cause of pneumonia. T15 also binds to
phosphocholine present on pathogens and provides a protective immune defense
against those pathogens.As both T15 antibody and CRP recognize the same
molecule, phosphocholine, Chang reasoned that CRP might bind to oxidized
LDL, but not native LDL that does not expose phosphocholine. Indeed, Chang
and colleagues showed that CRP does bind to oxidized LDL as well as
apoptotic cells through the recognition of phosphocholine. Therefore, CRP is
now a novel immune response to oxidized LDL, along with macrophages and T15
antibodies, through the recognition of the same phosphocholine molecule,
which is also present on many infectious pathogens. Studies are now underway
to determine whether CRP is protective, or could actually cause harm.
The UCSD research was funded by the National Institutes of Health. In
addition to Chang and Witztum, additional authors were Christoph J. Binder,
Ph.D., post doctoral fellow, and Michael Torzewski, M.D., visiting scholar,
UCSD Department of Medicine.
ABSTRACTS OF INTEREST
J Nutr Biochem 2002 Jun;13(6):316-321
C-reactive protein and coronary artery disease: influence of obesity,
caloric
restriction and weight loss.
Heilbronn LK, Clifton PM.
CSIRO Health Sciences and Nutrition, Adelaide, SA 5000, Australia
C reactive protein (CRP) values in blood are a good indicator of the
likelihood
of acute coronary and cerebral events in both healthy subjects and patients
with
coronary artery disease. This indicates that atherosclerotic lesions rich in
inflammatory cells and cytokines are more likely to produce acute events
either
through vasospasm and/or thrombosis and also can be readily detected through
elevations in CRP when measured using a high sensitivity assay (hsCRP).
However
the arterial wall is only one potential source of cytokines which induce CRP
production. Fat cells also produce cytokines, in particular IL-6 which
induces
the synthesis of CRP by the liver. Obesity, especially abdominal obesity, is
associated with elevations of hsCRP. This may be of pathogenic significance
as
CRP stimulates the uptake of LDL by macrophages, induces complement
activation
which may cause cellular damage in the artery, and enhances monocyte
production
of tissue factor, thus enhancing the risk of thrombosis. Caloric restriction
and
weight loss lowers IL-6 and CRP levels and may beneficially suppress an
immune
response. Whether particular dietary macronutrients or micronutrients alter
IL-6
or CRP is unknown but this issue is clearly becoming more important.
PMID: 12088796 [PubMed - as supplied by publisher]
Circulation 2002 Feb 5;105(5):564-9
Comment in:
Circulation. 2002 Feb 5;105(5):E9071-2.
Weight loss reduces C-reactive protein levels in obese postmenopausal women.
Tchernof A, Nolan A, Sites CK, Ades PA, Poehlman ET.
Department of Medicine, College of Medicine, University of Vermont,
Burlington.
BACKGROUND: C-reactive protein (CRP) has been proposed as an independent
risk
factor for cardiovascular disease and has been positively associated with
body
weight and body fatness. We examined the hypothesis that weight loss would
reduce plasma CRP levels in obese postmenopausal women. METHODS AND RESULTS:
In
a sample of 61 obese (body mass index, 35.6 +/- 5.0 kg/m(2)), postmenopausal
women (age, 56.4 +/- 5.2 years), we found that plasma CRP levels were
positively
associated with dual x-ray absorptiometry-measured total body fatness
(r=0.36,
P<0.005) and CT-measured intra-abdominal body fat area (r=0.30, P<0.02).
Significant correlations were also found between plasma CRP and triglyceride
levels (r=0.33, P<0.009) and glucose disposal measured by the
hyperinsulinemic-euglycemic clamp technique (r=-0.29, P<0.03). Twenty-five
of
the 61 women tested at baseline completed a weight loss protocol. The
average
weight loss was 14.5 +/- 6.2 kg (-15.6%, P<0.0001), with losses of 10.4 +/-
5.4
kg fat mass (-25.0%, P<0.0001) and 2.8 +/- 1.4 kg fat-free mass (-6.0%,
P<0.0001). Visceral and subcutaneous fat areas were reduced by -36.4% and
-23.7%, respectively (P<0.0001). Plasma CRP levels were significantly
reduced by
weight loss: average -32.3%, from 3.06 (+0.69, -1.29) to 1.63 (+0.70, -0.75)
microgram/mL (P<0.0001, medians and interquartile differences). Changes in
body
weight and in total body fat mass were both positively associated with
plasma
CRP level reductions. CONCLUSIONS: Adiposity was a significant predictor of
plasma CRP in postmenopausal women on a cross-sectional basis. Moreover,
caloric
restriction-induced weight loss decreased plasma CRP levels. Weight loss may
represent an important intervention to reduce CRP levels, which may mediate
part
of its cardioprotective effects in obese postmenopausal women.
Publication Types:
Clinical Trial
PMID: 11827920 [PubMed - indexed for MEDLINE]
Clin Chem 2002 Jun;48(6 Pt 1):877-83
Effect of atorvastatin and fish oil on plasma high-sensitivity C-reactive
protein concentrations in individuals with visceral obesity.
Chan DC, Watts GF, Barrett PH, Beilin LJ, Mori TA.
University Department of Medicine, University of Western Australia and the
Western Australia Institute for Medical Research, Royal Perth Hospital,
Perth, Western Australia WA 6847, Australia.
BACKGROUND: Chronic low-grade inflammation may contribute to the increased
risk of atherosclerosis in visceral obesity. Statin and fish oil have been
reported to have antiinflammatory effects. We studied whether dyslipidemic,
obese individuals have increased plasma high-sensitivity C-reactive protein
(hs-CRP) concentrations and whether treatment with atorvastatin and fish oil
lowered plasma hs-CRP concentrations. METHODS: We compared plasma hs-CRP,
interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)
concentrations in 48 obese individuals with the concentrations in 10 lean
normolipidemic men. The obese individuals were then randomized to treatment
with atorvastatin (40 mg/day), fish oil (4 g/day), atorvastatin plus fish
oil, or matching placebo for 6 weeks. RESULTS: Compared with controls, obese
individuals had increased hs-CRP [geometric mean, 2.19 mg/L (95% confidence
interval, 2.15-3.15 mg/L) vs 0.49 mg/L (0.30- 0.93 mg/L); P <0.001] and IL-6
[351 pg/L (318-449 pg/L) vs 251 pg/L (211-305 pg/L); P <0.01]. Atorvastatin
treatment had a significant main effect of decreasing plasma hs-CRP (-0.87
mg/L; 95% confidence interval, -0.10 to -1.60 mg/L; P <0.01) and IL-6 (-70
pg/L; 10 to -140 pg/L; P <0.01), but this was not seen with fish oil. The
reductions in hs-CRP with atorvastatin were not significantly correlated to
changes in plasma lipids, IL-6, insulin resistance, or cholesterogenesis.
Plasma TNF-alpha concentrations in obese individuals, however, were neither
statistically different from concentrations in the lean controls nor altered
with atorvastatin or fish oil treatment. CONCLUSIONS: This study shows that
visceral obesity is associated with increased plasma hs-CRP and IL-6 and,
hence, a low-grade chronic inflammatory state and that treatment with
atorvastatin or atorvastatin with fish oil, but not fish oil alone, reverses
this abnormality.
Publication Types: Clinical Trial Randomized Controlled Trial
PMID: 12029003 [PubMed - indexed for MEDLINE]
---------
Ann N Y Acad Sci 2001 Apr;928:327-35
The inflammation hypothesis of aging: molecular modulation by calorie
restriction.
Chung HY, Kim HJ, Kim JW, Yu BP.
Department of Pharmacy, College of Pharmacy, Research Institute of Genetic
Engineering, Pusan National University, Korea. hyj...@hyowon.pusan.ac.kr
Current evidence strongly indicates that reactive oxygen species (ROS) and
reactive nitrogen species (RNS) are widely implicated in the inflammatory
process. However, mechanistic information is not readily available on the
extent
to which ROS/RNS contributes to the proinflammatory states of the aging
process.
The involvement of the underlying inflammation during the aging process and
the
molecular delineation of anti-inflammatory action of calorie restriction
(CR) is
described. Age-related upregulations of NF-kappaB, IL-beta, IL-6, TNFalpha,
cyclooxygenase-2, and inducible NO synthase are all attenuated by CR. The
suppression of the NF-kappaB activation was accomplished by blocking the
dissociation of inhibitory IkappaBalpha and IkappaBbeta by CR. These
findings
provide underlying molecular insights into the anti-inflammatory action of
CR in
relation to the aging process. Based on these and other available data, it
is
suggested that the "Inflammation Hypothesis of Aging" supports the molecular
basis of the inflammatory process as a plausible cause of the aging process.
Publication Types:
Review
Review, Tutorial
PMID: 11795524 [PubMed - indexed for MEDLINE]
Mech Ageing Dev 1997 Feb;93(1-3):87-94
Calorie restriction inhibits the age-related dysregulation of the cytokines
TNF-alpha and IL-6 in C3B10RF1 mice.
Spaulding CC, Walford RL, Effros RB.
Department of Pathology and Laboratory medicine, University of California
School
of Medicine, Los Angeles 90095-1732, USA.
TNF-alpha and IL-6 are generally increased in the sera of aged humans and
mice.
The dysregulation of these cytokines may be critical in autoreactivity and
immune dysfunction. In earlier studies we demonstrated that production of
TNF-alpha and IL-6 following in vitro stimulation of peritoneal macrophages
by
LPS was reduced in old compared to young mice, and that dietary caloric
restriction (CR) had no effect on the induction of TNF-alpha in this system.
In
the present study we examined the effects of age and calorie restriction on
the
constitutive production of both TNF-alpha and IL-6. Serum levels of both
cytokines were significantly higher in old versus young mice. However, in
old
mice subjected to long term CR the serum levels were comparable to those of
young mice. The potential involvement of normalization of TNF-alpha and IL-6
levels in the life extension effect of CR are discussed.
PMID: 9089573 [PubMed - indexed for MEDLINE]
--
I welcome email from any being clever enough to fix my address. It's open
book. A prize to the first spambot that passes my Turing test.
galya
Well done, thank you for your efforts and sharing your thoughts(a
keeper post for sure)!!!
Some more about statins:
Article #1 reports about the first study to suggest that statins
(in-vitro)suppress T-cells activation.
Article #2 is the most recent one on the subject… still only talking
about the "scientific rationale for suggesting the use of statins as
novel immunosuppressors, not only in organ transplantation but in
numerous other pathologies as well." :-(
Article # 3 suggests that Lovastatin reduces risk of cancer.
Isn't it time to sell them OTC with Co-Q10 (you mentioned Co-Q10
recently)?
Any comments?
Thank you again,
Galya
SOURCE: Nature Medicine 2000;6:1311-1312, 1399-1402.
Cholesterol-Lowering Drugs Affect Immune System
A popular class of cholesterol-lowering drugs, known as statins,
appears to suppress certain immune system cells and may be useful for
treating transplant patients, researchers report. In a study of
laboratory-grown cells, statin drugs suppressed the activation of
helper T-cells, which are a component of the body's complex immune
system that helps fight off infection and also contributes to
inflammation. ``This unexpected effect provides a scientific rationale
for using statins as immunosuppressors, not only in organ
transplantation, but in numerous other (conditions) as well,''
according to lead author Dr. Brenda Kwak, of the Foundation for
Medical Research in Geneva, Switzerland, and colleagues. Their study
included the drugs atorvastatin (Lipitor), lovastatin (Mevacor) and
pravastatin (Pravachol). The results are published in the December
issue of Nature Medicine. The concentrations of the drugs were very
similar to doses used in patients, Dr. Wulf Palinski of the University
of California, San Diego, explained in an article accompanying the
study. ``Although the benefit of taking these drugs--the lowering of
cholesterol--is well documented, how the statins worked was not well
established. The current study suggests a biological mechanism for how
these drugs work,'' Palinski told Reuters Health. ``However, one
should use caution when results obtained from tissue cultures in the
lab are related to humans,'' he added. ``The statins may prove to be
another drug that can help those who undergo organ transplants,'' he
noted. The immune systems of organ transplant patients often reject
the foreign tissue of the new organ and these patients usually have to
take immune-suppressing drugs for the rest of their lives.
Traditionally, statins are prescribed to reduce the levels of fats in
the blood, such as cholesterol and triglycerides. When such blood-fats
are elevated, it can lead to narrowing of the arteries, which in turn
can lead to heart attack or stroke.
Transpl Immunol 2002 May;9(2-4):197-200
Statins as immunomodulators.
Mach F.
Department of Medicine, University Hospital Geneva, Foundation for
Medical Research, Switzerland. ma...@cmu.unige.ch
HMG-CoA reductase inhibitors, or statins, are effective lipid lowering
agents, extensively used in medical practice. Statins have never been
shown to be involved in the immune response, although few clinical
reports have suggested a better outcome of cardiac transplantation in
patients under pravastatin therapy. Major histocompatibility complex
class II (MHC-II) molecules are directly involved in the activation of
T lymphocytes and in the control of the immune response. Whereas only
a limited number of specialized cell types express MHC-II
constitutively, numerous other cells become MHC-II positive upon
induction by interferon gamma (IFN-gamma). We and others recently
demonstrated that statins act as direct inhibitors of induction of
MHC-II expression by IFN-gamma and thus as repressors of
MHC-II-mediated T cell activation. This effect was observed in several
cell types, including primary human endothelial cells and macrophages.
Interestingly, this inhibition is specific for inducible MHC-II
expression and does not concern either constitutive expression of
MHC-II or expression of MHC-I. In repressing induction of MHC-II, and
subsequent T lymphocyte activation, statins therefore behave as a
novel type of immunomodulator. This unexpected effect provides a
scientific rationale for suggesting the use of statins as novel
immunosuppressors, not only in organ transplantation but in numerous
other pathologies as well.
PMID: 12180830 [PubMed - in process]
Cholesterol drug reduces risk of cancer
Researchers said on Tuesday they had figured out how a popular
cholesterol?lowering drug can reduce the risk of cancer and said the
mechanism might be used to design drugs that can prevent cancer.
Several studies have indicated that people who take lovastatin, sold
by Merck and Co. under the name Mevacor, have a lower risk of cancer,
especially colon cancer. "This is one instance where we have actually
found a good side?effect for a drug,'' Khandan Keyomarsi, a biochemist
at the State University of New York at Albany, said in a telephone
interview. Keyomarsi and colleagues set out to discover the mechanism
and found the drug helps destroy cancerous cells. They said that this
action is independent of the drug's cholesterol?lowering effects.
"Lovastatin, when people take it, they take it in the prodrug form,''
Keyomarsi said in a telephone interview.
That means the drug is inactive at least against the intended target
until it is converted to the active form by the liver. However,
lovastatin's prodrug form has an unintended but beneficial effect.
"What we have found is that the prodrug form of lovastatin inhibits
another pathway in the cell and that pathway is what is responsible
for the cancer?preventative effects,'' Keyomarsi said. Lovastatin is
designed to help stop the liver from making cholesterol. What
Keyomarsi's team found was that the prodrug form interferes with what
is known as the proteasome pathway in cells, which acts like a kind of
garbage disposal. "The proteasome pathway is a pathway that degrades
proteins or destroys proteins,'' she said. Among the proteins it gets
rid of are cyclin?dependent kinase inhibitors (CKI) p21 and p27."
Steve Harris
>Steve,
>Well done, thank you for your efforts and sharing your thoughts(a
>keeper post for sure)!!!
>Some more about statins:
>Article #1 reports about the first study to suggest that statins
>(in-vitro)suppress T-cells activation.
>Article #2 is the most recent one on the subject… still only talking
>about the "scientific rationale for suggesting the use of statins as
>novel immunosuppressors, not only in organ transplantation but in
>numerous other pathologies as well." :-(
>Article # 3 suggests that Lovastatin reduces risk of cancer.
>
>Isn't it time to sell them OTC with Co-Q10 (you mentioned Co-Q10
>recently)?
>Any comments?
COMMENT:
Yes, they should be OTC, and in some sense are already. You can buy red rice
yeast pills OTC now. These have natural lovastatin (called "mevinolin" as a
natural product, in amounts sufficient to significantly lower cholesterol if
you take a couple of grams a day of extract. This yeast which makes the
statin also provides the red coloring for a lot of Chinese dishes (the red
of a Peking Duck!) and it's where the statins were discovered originally.
Heck, if it weren't for AIDS and a few other problems where people need all
the helper T-cell activity they can get, I'd be suggesting that statins be
added, in fat Western cultures, to cholesterol raising foods! They certainly
have the potential to be a major weapon in our obese sat and trans fat
intoxicated, bloated society. Alas, trans fats practically just about ARE
everywhere in every processed food and anything with milk fat, and your tax
dollars support the sales of the big saturated fat killers (your fed income
tax pays for the those beef and whole milk commercials on TV). And you pay
again when medicare pays for bypasses, but not for statins. Dumb, dumb,
dumb, *criminally* dumb federal policy. Statins are the closest thing to a
life-extension drug pill ever invented, but they are $100 a month, and only
a small fraction of people who could be befitting from them, are taking
them.
I'm personally also incensed about the fibrate drugs (Tricor/ fenofibrate
and the older Lopid/gemfibrozil), which may be keeping needy people from
getting a statin, by fixing numbers instead of the disease. These drugs
*suck* as a class-- they may lower chance of an MI by a small amount, but
nothing like what is suggested by their cholesterol effect, and they haven't
been shown to increase life span-- probably because what they give in
decreased cholesterol, they take away in cancer risk. Indeed, there is
reasonable evidence that they CAUSE GI cancer. Yech. But many a dollar
which should be spent on statins is wasted here. Similar comments apply to
cholesterol-lowering bile acid binding agents (cholestyramine and
colestipol). Niacin is a much better second-line drug.
I'll drink menhaden
Oil and take a statin
Pill or two.
And add an aspirin to
The brew.
You can't be half-assed
Avoiding bypass
Surgery
It fries your brain, you see--
Suddenly.
[Again, appologies to Larry Hart]
Steve Harris, MD
Doug Brooks
> galya wrote in message <160201d6.0209...@posting.google.com>...
>
>>Steve,
>>Well done, thank you for your efforts and sharing your thoughts(a
>>keeper post for sure)!!!
Ditto
>>Some more about statins:
>>Article #1 reports about the first study to suggest that statins
>>(in-vitro)suppress T-cells activation.
>>Article #2 is the most recent one on the subject… still only talking
>>about the "scientific rationale for suggesting the use of statins as
>>novel immunosuppressors, not only in organ transplantation but in
>>numerous other pathologies as well." :-(
>>Article # 3 suggests that Lovastatin reduces risk of cancer.
>>
>>Isn't it time to sell them OTC with Co-Q10 (you mentioned Co-Q10
>>recently)?
>>Any comments?
>
>
>
> COMMENT:
>
> Yes, they should be OTC, and in some sense are already. You can buy red rice
> yeast pills OTC now. These have natural lovastatin (called "mevinolin" as a
> natural product, in amounts sufficient to significantly lower cholesterol if
> you take a couple of grams a day of extract. This yeast which makes the
> statin also provides the red coloring for a lot of Chinese dishes (the red
> of a Peking Duck!) and it's where the statins were discovered originally.
What's the deal with Red Yeast Rice, anyway? I thought the FDA banned
it, but I notice online there seem to be a few people selling it.
> Heck, if it weren't for AIDS and a few other problems where people need all
> the helper T-cell activity they can get, I'd be suggesting that statins be
> added, in fat Western cultures, to cholesterol raising foods!
You're the doc, but this whole immune suppression thing doesn't sound
too good to me. As life extensionists, aren't we trying to improve our
immune systems?
Paul Chefurka
>What's the deal with Red Yeast Rice, anyway? I thought the FDA banned
>it, but I notice online there seem to be a few people selling it.
The American FDA banned imports of red yeast rice in 1998. The ban was
overturned in 1999 by a federal court judge in Utah, who declared it to be
a supplement and not a drug.
Paul
John@getstev.com Sir John
Cholestron at any vitamin store.
"Steve Harris" <sbha...@ix.RETICULATEDOBJECTcom.com> wrote in message
news:sW7h9.1226$E53.1...@newsread2.prod.itd.earthlink.net...
> galya wrote in message <160201d6.0209...@posting.google.com>...
> >Steve,
> >Well done, thank you for your efforts and sharing your thoughts(a
> >keeper post for sure)!!!
> >Some more about statins:
> >Article #1 reports about the first study to suggest that statins
> >(in-vitro)suppress T-cells activation.
> >Article #2 is the most recent one on the subject. still only talking
Tom Matthews (Paul Wakfer)
> galya wrote in message <160201d6.0209...@posting.google.com>...
>>Isn't it time to sell them OTC with Co-Q10 (you mentioned Co-Q10
>>recently)?
>>Any comments?
>>
>
>
> COMMENT:
>
> Yes, they should be OTC, and in some sense are already. You can buy red rice
> yeast pills OTC now. These have natural lovastatin (called "mevinolin" as a
> natural product, in amounts sufficient to significantly lower cholesterol if
> you take a couple of grams a day of extract. This yeast which makes the
> statin also provides the red coloring for a lot of Chinese dishes (the red
> of a Peking Duck!) and it's where the statins were discovered originally.
> Heck, if it weren't for AIDS and a few other problems where people need all
> the helper T-cell activity they can get, I'd be suggesting that statins be
> added, in fat Western cultures, to cholesterol raising foods! They certainly
> have the potential to be a major weapon in our obese sat and trans fat
> intoxicated, bloated society. Alas, trans fats practically just about ARE
> everywhere in every processed food and anything with milk fat, and your tax
> dollars support the sales of the big saturated fat killers (your fed income
> tax pays for the those beef and whole milk commercials on TV). And you pay
> again when medicare pays for bypasses, but not for statins. Dumb, dumb,
> dumb, *criminally* dumb federal policy. Statins are the closest thing to a
> life-extension drug pill ever invented, but they are $100 a month, and only
> a small fraction of people who could be befitting from them, are taking
> them.
I have not considered taking statins mostly because I appear to be accomplishing
without doing so all the benefits which they appear to have. However, I also
have reservations about the use of any therapy which has insufficient history of
long-term usage that there is good evidence that its use will not be life
shortening (for healthy people already successfully using a multitude of other
therapies to avoid the negatives which statins help), even though such a therapy
may be acutely and mid-term beneficial for morbidity and mortality. Thus, at
this time, I see statin use as a "second best" approach to other therapies (such
as CR) which are harder for some people to follow.
I would appreciate receiving comments on this latter concern and viewpoint.
--Tom Matthews (Paul Wakfer)
MoreLife for the rational - http://morelife.org
Reality based tools for More Life in quantity & quality
Dr. Dickie
I tend to go with you. So far I have been able to reduce my cholesterol levels to
acceptable 120 total with very good HDL/LDL values (don't remember them right off)
by means of diet and exercise. So, I see no reason to take statins. As long as I
can maintain around this level (two years so far), I see no reason to dose myself
with something that does not have good long term studies to back up safety.
I assume that there has been no good long term studies yet.
Still, nice to know that it is there if I need a fall back position.
--
Dr. Dickie
Skepticult member in good standing #394-00596-438
Poking kooks with a pointy stick
------------------------------------------------------
"The important thing is not to stop questioning.
Curiosity has its own reason for existing."
A. Einstein
John 'the Man'
rambled on about "Re: News on C-rective Protein and LDL, with notes
by S. Harris."
Our champion De-Medicalizing in sci.med.nutrition retorts, thusly ...
>I tend to go with you. So far I have been able to reduce my cholesterol levels to
>acceptable 120 total with very good HDL/LDL values (don't remember them right off)
>by means of diet and exercise. So, I see no reason to take statins. As long as I
>can maintain around this level (two years so far), I see no reason to dose myself
>with something that does not have good long term studies to back up safety.
>I assume that there has been no good long term studies yet.
>Still, nice to know that it is there if I need a fall back position.
Well, it is no surprise to me that our conventional and square Steve
Harris supports the regular use of statins.
Statins should be used on a temporary basis in order to get your TC
down, NOW.
--
John Gohde,
Achieving good Health is an Art, NOT a Science!
http://NaturalHealthPerspective.com/
The ONLY Frauds in Health are those who couldn't care less about
prevention. Beware of anybody who brags about eating a lousy diet,
eating crispbread, being overweight, or about smoking!
Tim Tyler
: Yes, they should be OTC, and in some sense are already. You can buy red rice
: yeast pills OTC now. These have natural lovastatin (called "mevinolin" as a
: natural product, in amounts sufficient to significantly lower cholesterol if
: you take a couple of grams a day of extract. This yeast which makes the
: statin also provides the red coloring for a lot of Chinese dishes (the red
: of a Peking Duck!) and it's where the statins were discovered originally.
: Heck, if it weren't for AIDS and a few other problems where people need all
: the helper T-cell activity they can get, I'd be suggesting that statins be
: added, in fat Western cultures, to cholesterol raising foods! They certainly
: have the potential to be a major weapon in our obese sat and trans fat
: intoxicated, bloated society.
Some pretty negative articles about Statins:
http://www.mercola.com/article/statins.htm
--
__________
|im |yler http://timtyler.org/ t...@tt1.org
Steve Boshkov
depletion. Thus, as one experienced cardiologist has recently
summarized his views:
http://www.redflagsweekly.com/features/2002_july08.html. Langsjoen has
devoted a good deal of research to Co Q 10 and obviously knows a great
deal about heart disease. A Medline search will disclose a large
number of his papers. It will be noted that his view of the statin
benefit is that it is "slight" in any event. Of course, you can always
take more Co Q 10, but it seems to me that anything which impairs the
flow of a vital bodily nutrient must be suspect and the problems it
causes cannot automatically be supposed to be fixed in this manner.
Much the same view of the benefit is held by Ravnskov, who also raises
the cancer spectre as well in this letter to the BMJ:
http://bmj.com/cgi/content/full/324/7340/789#art. For a fuller
exposition, see: http://www.ravnskov.nu/myth6.htm. Tom, I'm with you
on this one, at least until the dust settles more favorably.
"Tom Matthews (Paul Wakfer)" <t...@morelife.org> wrote in message news:<3D85D362...@morelife.org>...
Martin
Min: .4 mg/day
Max: .8mg/day
I've been on 10mg/day for several years now; it has always been my
understanding that 10mg was a minimal dose.
galya
Tom (Paul),
Wile I applaud your approach and practice I think that it's more like
a life-long maintenance-type and not an available option anymore for
the many who need an aggressive therapy that statin drugs offer.
Regards,
Galya
K
"Dr. Dickie" <dr_d...@chembench.com> wrote
> I tend to go with you. So far I have been able to reduce my
cholesterol levels to
> acceptable 120 total with very good HDL/LDL values (don't remember
them right off)
> by means of diet and exercise. So, I see no reason to take statins.
As long as I
> can maintain around this level (two years so far), I see no reason to
dose myself
> with something that does not have good long term studies to back up
safety.
> I assume that there has been no good long term studies yet.
> Still, nice to know that it is there if I need a fall back position.
> --
Hi,
What's your diet?
Kosta
Tom Matthews (Paul Wakfer)
> Tom Matthews (Paul Wakfer),
> Tom (Paul),
> Wile I applaud your approach and practice I think that it's more like
> a life-long maintenance-type and not an available option anymore for
> the many who need an aggressive therapy that statin drugs offer.
I agree with this, but my whole approach is preventative instead of waiting
until aggressive (read potentially dangerous) therapies are necessary.
In addition, even the person who requires the "aggressive therapy that statin
drugs offer" can and should aim for just such a "life-long maintenance-type"
approach which should in time allow him to reduce/eliminate the aggressiveness
of the therapies that he previously needed (to keep him alive and able to get to
the point where he no longer needs them).
Dr. Dickie
I eat a cup of berries (blue, cherries, etc.--whatever is in season) along
with a cup of "All bran" cereal and a little bit of "Grape nuts". One cup
no-fat milk and cup of V-8 juice for breakfast (5:30 am). A an apple and
some celery for snack (9:30am). For lunch two sandwiches of tuna and salmon
(total of about 4-6 oz--with a little no-fat mayo and chopped celery) on
whole wheat bread (looked a long time for low carb-high fiber--Nature's Own
was the best I could find--50 calories a slice). Along with two cups of cut
carrots and an pear.
For afternoon snack, another apple and some celery if I am really hungry
(2-3 pm).
For dinner, a spinach and lettuce salad with Roma tomato, 2 tbs. of no-fat
salad dressing. 2 cups of cooked legumes (spiced with garlic and Louisiana
hot sauce), then 1/2 cup of peas, 1 1/2 cup of broccoli, and 1 1/2 cup
cauliflower. Finally, a couple of strawberries for dessert (frozen)(5:50
pm).
I have much the same thing day in day out. I don't mind a similar diet
everyday. I eat different fruit when I want, different legumes every few
days. Occasionally I will go out to dinner with a friend or my wife and I
try to eat right. At night I snack some times on almonds or no-fat
saltines.
I also run 7-10 miles three days a week, on the other three days I
stairstep for 20 minutes then lift weights for 45 minutes. Every afternoon
I walk on the treadmill or ride my bike for 35-40 minutes. And on my one
day of rest, I get up at 4:00 am and walk on the treadmill for 30 minutes.
I am diabetic (t-2)and do not want to have to take drugs, so I must
exercise everyday (twice a day is better). SO far (two years), no drugs and
my blood glucose level is normal. Triglycerides are 55, and resting heart
rate is 55, blood pressure is 110/70.
That is from cholesterol of 270, triglycerides of 350, RHR of 75, and blood
pressure slightly elevated two years ago. I was also 100 lbs heavier.
Fortunately, I have exercised most of my life. Not as often or as regular
as I do now, but for most of my life I tried to do the minimum 20 minutes,
3 times a week). The minimum sucks. The minimum should be 45-1 hour 5-7
days a week (I was glad to see minimum brought up to more realistic
standards recently). Of course, when you can't get most Americans to do 20
minutes three times a week, what difference does it make if you up the
standard?
That has to be much more than you ever wanted to know about my life.
Dr. Dickie
> In article <3D8707B7...@chembench.com>,
> Dr. Dickie <dr_d...@chembench.com> wrote:
>
> >I eat a cup of berries (blue, cherries, etc.--whatever is in season) along
> >with a cup of "All bran" cereal and a little bit of "Grape nuts". One cup
> >no-fat milk and cup of V-8 juice for breakfast (5:30 am). A an apple and
> >some celery for snack (9:30am). For lunch two sandwiches of tuna and salmon
> >(total of about 4-6 oz--with a little no-fat mayo and chopped celery) on
> >whole wheat bread (looked a long time for low carb-high fiber--Nature's Own
> >was the best I could find--50 calories a slice). Along with two cups of cut
> >carrots and an pear.
> >For afternoon snack, another apple and some celery if I am really hungry
> >(2-3 pm).
> >For dinner, a spinach and lettuce salad with Roma tomato, 2 tbs. of no-fat
> >salad dressing. 2 cups of cooked legumes (spiced with garlic and Louisiana
> >hot sauce), then 1/2 cup of peas, 1 1/2 cup of broccoli, and 1 1/2 cup
> >cauliflower. Finally, a couple of strawberries for dessert (frozen)(5:50
> >pm).
>
> What's the total amount of protein in all that?
>
> Marcus
Don't have the numbers in front of me, but I get about twice the RDA for
protein. Mostly from legumes and salmon. However, with all the exercise...
wuzzy
-barely breathe over wave of work to do-
but my impression from a nutrient standpoint is that C-reactive
protein mostly reflects disease status.
In particular, it is more likely that CRP *causes* a decrease in
serum Vitamin E than a change in Vitamin E will do anything to CRP.
Nevertheless I'm sure many ppl supplement with Vitamin E and other
antioxidants during infections etc.. even URI (upp resp inf=common
cold) decreases serum vitamin e acutely.
Matti Narkia
<sbha...@ix.RETICULATEDOBJECTcom.com> wrote:
>This week's news on C-reactive protein and LDL, with notes by S. Harris.
>
>Ostler once remarked that the doctor who understands syphilis understands
>medicine. The closest we can come to such a statement in today's world might
>be that the doctor who understands the _inflammatory response_ understands
>medicine. Inflammation is responsible for the classical signs of disease in
>the ancient Galenic view (rubor, calor, tumor, dolor = redness, head,
>swelling, pain), and very often inflammation is partly responsible for the
>fifth sign of disease that historically was added in the middle ages:
>dysfunction. Treatments which affect inflammation, such as application of
>heat and cold, were (and are) strangely powerful in general medical care. As
>are foods and drugs that modulate the process: the story of aspirin is
>familiar, but other antiinflammatories have had a long history as "nostrums"
>simply because they affect symptoms of so many diseases positively. For
>example, the body oil of the Chinese water snake, which is 20% EPA (an n-3
>fatty acid also common in fish) was long sold as a cure for rheumatism and
>aches and pains anywhere. Thus the pejorative "snake oil." But the stuff
>probably worked like aspirin, because today we know that (in general) the
>3-series prostaglandins made from n-3 fatty acids are not as inflammatory as
>the more common ordinary kinds. Fish oil is good for arthritis, and so is
>snake oil. Take that, quackbusters.
>
So as Dr. Steve Harris, MD, so eloquently puts it:
"Fish oil is good for arthritis, and so is snake oil. Take that,
quackbusters."
I rest my case.
Matti Narkia
> This week's news on C-reactive protein and LDL, with notes by S. Harris.
>
> Ostler once remarked that the doctor who understands syphilis understands
> medicine. The closest we can come to such a statement in today's world might
> be that the doctor who understands the _inflammatory response_ understands
> medicine. Inflammation is responsible for the classical signs of disease in
> the ancient Galenic view (rubor, calor, tumor, dolor = redness, head,
> swelling, pain), and very often inflammation is partly responsible for the
> fifth sign of disease that historically was added in the middle ages:
> dysfunction. Treatments which affect inflammation, such as application of
> heat and cold, were (and are) strangely powerful in general medical care. As
> are foods and drugs that modulate the process: the story of aspirin is
> familiar, but other antiinflammatories have had a long history as "nostrums"
> simply because they affect symptoms of so many diseases positively. For
> example, the body oil of the Chinese water snake, which is 20% EPA (an n-3
> fatty acid also common in fish) was long sold as a cure for rheumatism and
> aches and pains anywhere. Thus the pejorative "snake oil." But the stuff
> probably worked like aspirin, because today we know that (in general) the
> 3-series prostaglandins made from n-3 fatty acids are not as inflammatory as
> the more common ordinary kinds. Fish oil is good for arthritis, and so is
> snake oil. Take that, quackbusters.
>
"Fish oil is good for arthritis, and so is snake oil. Take that,
quackbusters."
I rest my case.
--
Matti Narkia
Dr. Andrew B. Chung, MD/PhD
Ask folks who have arthritis whether either relieves their pain. They are the
jury.
--
Dr. Andrew B. Chung, MD/PhD
Atlanta Cardiologist
http://www.heartmdphd.com
Matti Narkia
<and...@heartmdphd.com> wrote:
>Matti Narkia wrote:
>>
>Ask folks who have arthritis whether either relieves their pain. They are the
>jury.
I have asked. Fish oil does seem to help often those people who have the
patience to continue its use the required 3 months or and who take at least the
recommended quantity.
I even looked into alt.support.arthritis newsgroup. Here's a message from
there:
http://groups.google.com/groups?selm=7fbe7h%24qq1%241%40ultra.sonic.net&output=gplain
From: "Liz G." <pio...@neteze.com>
Subject: Re: Fish...and Fish oil
Date: 1999/04/17
Message-ID: <7fbe7h$qq1$1...@ultra.sonic.net>#1/1
References: <21886-37...@newsd-293.iap.bryant.webtv.net>
<19990417173614...@ng34.aol.com>
X-MimeOLE: Produced By Microsoft MimeOLE V4.72.3110.3
Organization: Sonic,Santa Rosa CA,http://www.sonic.net
Newsgroups: alt.support.arthritis
I tried fish oil on my doctor's recommendation and still use
it. I would recommend fish oil concentrates, not cod liver
oil as it gives you the omega 3's without so high a
concentration of vit A & D. It is sometimes marketed as EPA
(from the name of the fatty acid). I use Salmon Oil. I
personally think it is better than the flax as flax contains
other fatty acids as well. I also take GLA in the form of
borage oil, also on my doc's approval. I did not find that
the effect was very dramatic but it gave a gradual
improvement, now I hardly take any nsaids at all. When I
stopped taking the fish oil for awhile, the pain increased
and then improved again when I restarted. I am also taking
tetracycline so don't know exactly how much of the benefit is
from either one, only that I felt more pain when not on the
fish oil. Good for the heart too and I read an article not
long ago that indicated fish oils may help with depression as
well. I'll post it also, it is called "Prozac of the Deep" if
you're interested. Hope this helps. LizG
Links for a couple of other messages with excerpts:
http://groups.google.com/groups?selm=3D34A5D6.DABB110F%40earthlink.net
"Carol, I use fish oil also with good results. And feverfew also helps.
Just be careful with the brand that you buy because some don't have
diddly in them. CQ 10 is helpful. Good luck and I'll be praying for you.
donnah"
http://groups.google.com/groups?selm=20020719090326.01198.00000204%40mb-dd.aol.com
"I am a fanatic about fish oil and RA. Last night I made home made smoked
salmon burgers! I love salmon because it is medicine for RA! I great deals
on smoked salmon on ebay.Ken Mc"
http://groups.google.com/groups?selm=Ginger09-809EFE.07342017032000%40news.sowega.net
"In the past I have taken Fish Oil (Omega-3) with good
results. But I stopped taking them because in order to get
the amount the Arthritis Foundation recommends (3,000 mg per
day) I had to take 10 caplets a day (each had 300 mg). So I
have two questions:
1) Can anyone recommend, FROM PERSONAL EXPERIENCE, a brand of
fish oil caplets that has more than 300 mg of the Omega-3 per
caplet? I'd like to have to take only 5 caplets at the most
per day if possible, and even less than that would be great.
Also if you could tell me where you can get this brand (and
please give me the exact name of the product, not just the
brand name) as well, that would be great.
2) Those of you who do take Fish oil for your Omega-3s, how
much do you take? Do you follow the AF recommendation of
3,000 mg per day or have you found an amount that works as
well as that?
3) I know some people use Flax seed oil or another oil (which
name escapes me) instead of Fish Oil to get their Omega-3s.
Do you feel that this is better to take and easier to take
(example, 4 pils of Flax seed oil vs 10 pills of fish oil to
get the same amount of Omega-3s)? What do you use it as
opposed to Fish Oil?
Thanks in advance."
Someone even posted this study abtract there:
http://groups.google.com/groups?selm=7rh6vm%24o0v%241%40ultra.sonic.net
Pierre L
I thought I might just point out that you can't just willy-nilly start
taking large quantities of fish oil. Best to check with your doctor. Fish
oil is very concentrated EPA and DHA. These are fatty acids that the fish
has already produced (unlike flax oil, which has the necessary building
block fatty acids to make EPA and DHA, but your own body has to actually
make them). EPA and DHA are thought to be the fatty acids that actually have
the anti-inflammatory effects some people and studies claim. Because of the
concentrated form, fish oil has been known to add to the anti-coagulation
effect of aspirin and other drugs. So, if you're on coumadin or something,
it might not be a good idea to take large amounts of fish oil. It's also
probably not a great idea to take this if you happen to have high blood
pressure that isn't under good control (despite claims that fish oil lowers
blood pressure).
Pierre
Matti Narkia
>By the way, since fish oil is not a prescription drug (maybe it should be),
>I thought I might just point out that you can't just willy-nilly start
>taking large quantities of fish oil. Best to check with your doctor. Fish
>oil is very concentrated EPA and DHA. These are fatty acids that the fish
>has already produced (unlike flax oil, which has the necessary building
>block fatty acids to make EPA and DHA, but your own body has to actually
>make them).
To put things in a perspective: my favorite can (small, 120 g) of sardines has
about 2.25 g of omega-3 fatty acids, i.e EPA+DHA in it. Sometimes I eat two
cans daily and therefore get 4.5 grams EPA+DHA from sardines alone. Now how
does that compare with the dose recommended for arthritis? Am I living
dangerously by eating one or two cans of sardines daily? ;-).
BTW, fish does not produce EPA or DHA. Unlike us, it lacks the enzymes required
for that. Instead it gets its EPA and DHA by eating algae who produce them.
Our capability to convert linoleic acid to EPA is rather limited and conversion
is slow. Moreover the conversion is vulnerable and can be disturbed by various
factors. Advancing age, nutritional deficiencies or diseases could limit the
availability of the required enzymes.
>EPA and DHA are thought to be the fatty acids that actually have
>the anti-inflammatory effects some people and studies claim. Because of the
>concentrated form, fish oil has been known to add to the anti-coagulation
>effect of aspirin and other drugs. So, if you're on coumadin or something,
>it might not be a good idea to take large amounts of fish oil. It's also
>probably not a great idea to take this if you happen to have high blood
>pressure that isn't under good control (despite claims that fish oil lowers
>blood pressure).
>Pierre
>
I agree that it's good to take notice about these things and be careful. Still,
one shouldn't overexaggerate the anti-coagulation effect of fish oil. Surgeons
customarily ask the patients to stop aspirin before operations, but they are
not worried about fish oil, ginkgo biloba, garlic etc.. I myself was a few
years ago six months on anti-coagulant warfarin (coumadin) and continued taking
6-7 g of EPA+DHA daily from food and supplements. And not only that, I needed
about 3 times the standard dose of warfarin! When you take warfarin the most
important thing is not to make any major changes in your diet or supplement
program while you are on it. Your warfarin dose will be adjusted to your
standard diet and life style. That's the advice I got from my doctors :-).
Dr. Andrew B. Chung, MD/PhD
Matti Narkia wrote:
> On Thu, 26 Sep 2002 10:19:55 -0400, "Dr. Andrew B. Chung, MD/PhD"
> <and...@heartmdphd.com> wrote:
>
> >Matti Narkia wrote:
> >>
> >Ask folks who have arthritis whether either relieves their pain. They are the
> >jury.
>
> I have asked. Fish oil does seem to help often those people who have the
> patience to continue its use the required 3 months or and who take at least the
> recommended quantity.
Such folks are rare (though they may be quite commonplace on an ALT newsgroup).
--
Dr. Andrew B. Chung, MD/PhD
Atlanta Cardiologist
http://www.heartmdphd.com
Matti Narkia
> I have asked. Fish oil does seem to help often those people who have the
>> patience to continue its use the required 3 months or and who take at least the
>> recommended quantity.
>
>Such folks are rare (though they may be quite commonplace on an ALT newsgroup).
In your clinic? I wouldn't be surprised. If you're instead implying something
general, you're simply lying, because you have no other reasonably reliable way
of knowing that than randomized controlled clinical trials, and they don't
support your claim.
Dr. Andrew B. Chung, MD/PhD
Matti Narkia wrote:
> On Thu, 26 Sep 2002 12:53:26 -0400, "Dr. Andrew B. Chung, MD/PhD"
> <and...@heartmdphd.com> wrote:
> >
> >Matti Narkia wrote:
> >´
> > I have asked. Fish oil does seem to help often those people who have the
> >> patience to continue its use the required 3 months or and who take at least the
> >> recommended quantity.
> >
> >Such folks are rare (though they may be quite commonplace on an ALT newsgroup).
>
> In your clinic? I wouldn't be surprised.
Actually, you should be surprised because many of my patients are seeking alternative
approaches. My ethnic background is asian so culturally I am probably inclined to be
more open-minded about this topic than most. Folks who are crippled by their
arthritis typically are not willing to wait three months for fish oil to possibly
work.
--
Dr. Andrew B. Chung, MD/PhD
Atlanta Cardiologist
http://www.heartmdphd.com
Don Kirkman
<eu46pu4d4d7pusvo3...@4ax.com>:
>>Matti Narkia wrote:
>http://groups.google.com/groups?selm=7fbe7h%24qq1%241%40ultra.sonic.net&output=gplain
I have been reading alt.support.arthritis regularly for about five or
six years. LizG is a respected and reasonable person and a good
reporter of her experiences, but she is one of a few among the several
hundred active group participants who have reported using or receiving
help from fish oil.
However reliable and well intentioned, anecdotes don't substitute for
science.
--
Don
don...@covad.net
Matti Narkia
<s0m6pu0je8tce5t9s...@4ax.com> Don Kirkman <don...@covad.net>
wrote:
>
>However reliable and well intentioned, anecdotes don't substitute for
>science.
And that's excatly the reason I provided the scientical information, i.e.
the double blind trials about the use of fish oil and GLA in arthritis
first, and anecdotes only afterwards, when user experiences were requested
fby DR. Chung (IMHO they don't add anything to scientical information
provided first, but for some peculiar reason Dr. Chung seems to value user
experiences over the results of double blind trials :-) :-); it was a small
trouble so I didn't mind providing a couple of anecdotes as well).
See the previously provided Medline references in the thread "Results of
Heart Health?"
--
Matti Narkia
Matti Narkia
<3D93668E...@heartmdphd.com> "Dr. Andrew B. Chung, MD/PhD"
<and...@heartmdphd.com> wrote:
>
>Matti Narkia wrote:
>
>> On Thu, 26 Sep 2002 12:53:26 -0400, "Dr. Andrew B. Chung, MD/PhD"
>> <and...@heartmdphd.com> wrote:
>> >
>> >Such folks are rare (though they may be quite commonplace on an ALT newsgroup).
>>
>> In your clinic? I wouldn't be surprised.
>
>Actually, you should be surprised because many of my patients are seeking alternative
>approaches. My ethnic background is asian so culturally I am probably inclined to be
>more open-minded about this topic than most. Folks who are crippled by their
>arthritis typically are not willing to wait three months for fish oil to possibly
>work.
Now doc, do you intentionally twist your logic, or is it that you cannot
think straight? If your patients are crippled by their arthritis they
continue taking whatever medication will make they feel less crippled, don't
they? If after three months use of fish oil they don't seem to be able to
reduce the medication without the worsening of the symptoms, fine, perhaps
fish oil is not for them. They could still eat fatty fish though, that's
good for most people. But if, on the other hand, they can reduce the
medication, they may reduce their risk of getting kidney or other organ
damage. No need to be more crippled for three months while waiting for fish
oil to work.
Another matter is that some people do get kidney damage from the long term
use of NSAIDs. Then they may be forced to stop NSAIDs and try something
else, fish oil, for example, and hope it works. If it does, the kidney
damage would have been avoidable with the earlier use of fish oil. So
according to my logic it's wise to try fish oil as early as possible. What
you have to lose? Unnecessary payment for three month's supply of fish oil,
if it doesn't work. That's negligible compared with the benefits, if it does
work.
--
Matti Narkia
Matti Narkia
<n4s6puotq3of1b8fe...@4ax.com> Matti Narkia
<mn...@despammed.com> wrote:
That's in the newsgroup sci.med.cardiology only (if you're reading this from
sci.med).
--
Matti Narkia
Steve Harris
<3D93668E...@heartmdphd.com>...
>Actually, you should be surprised because many of my patients are seeking
alternative
>approaches. My ethnic background is asian so culturally I am probably
inclined to be
>more open-minded about this topic than most. Folks who are crippled by
their
>arthritis typically are not willing to wait three months for fish oil to
possibly
>work.
>
>--
>Dr. Andrew B. Chung, MD/PhD
>Atlanta Cardiologist
>http://www.heartmdphd.com
COMMENT
But your other patients I'm sure have other reasons to be changing their
n-3/n-6/sat ratios. If you've reading the NEJM you know that now there is
some prelimary mechnistic data that n-3 fatty acids are antiarrythmic. Fish
eating has long been associated with less risk of sudden cardiac death
epidemiologically, and this may be part of the reason. IOW, people may have
other reasons besides triglyceride lowering and less CHD, to have less
cardiac mortality as a result of a high fish (3x/week) diet.
SBH
--
I welcome email from any being clever enough to fix my address. It's open
book. A prize to the first spambot that passes my Turing test.
Dr. Andrew B. Chung, MD/PhD
> Dr. Andrew B. Chung, MD/PhD wrote in message
> <3D93668E...@heartmdphd.com>...
>
> >Actually, you should be surprised because many of my patients are seeking
> alternative
> >approaches. My ethnic background is asian so culturally I am probably
> inclined to be
> >more open-minded about this topic than most. Folks who are crippled by
> their
> >arthritis typically are not willing to wait three months for fish oil to
> possibly
> >work.
> >
> >--
> >Dr. Andrew B. Chung, MD/PhD
> >Atlanta Cardiologist
> >http://www.heartmdphd.com
>
> COMMENT
>
> But your other patients I'm sure have other reasons to be changing their
> n-3/n-6/sat ratios. If you've reading the NEJM you know that now there is
> some prelimary mechnistic data that n-3 fatty acids are antiarrythmic. Fish
> eating has long been associated with less risk of sudden cardiac death
> epidemiologically, and this may be part of the reason. IOW, people may have
> other reasons besides triglyceride lowering and less CHD, to have less
> cardiac mortality as a result of a high fish (3x/week) diet.
I do encourage my patients to shift their protein anf fat intake toward fish
for the reasons you describe. However, if there is substrate for SCD, I
arrange for an AICD implantation rather than rely on the promise of higher
n-3/n-6/sat ratios.
Matti Narkia
<9su6pu496pb9d6rpn...@4ax.com> Matti Narkia
<mn...@despammed.com> wrote:
On second thought I repost the most relevant references here, too:
Fish Oil
--------
Calder PC.
Polyunsaturated fatty acids, inflammation, and immunity.
Lipids. 2001 Sep;36(9):1007-24. Review.
PMID: 11724453 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11724453&dopt=Abstract
Joel M Kremer
n-3 Fatty acid supplements in rheumatoid arthritis
American Journal of Clinical Nutrition, Vol. 71, No. 1, 349S-351s, January
2000
http://www.ajcn.org/cgi/content/full/71/1/349S
Michael J James, Robert A Gibson, and Leslie G Cleland
Dietary polyunsaturated fatty acids and inflammatory mediator production
Am J Clin Nutr 2000 71: 343-348
http://www.ajcn.org/cgi/content/full/71/1/343S
James MJ, Cleland LG.
Dietary n-3 fatty acids and therapy for rheumatoid arthritis.
Semin Arthritis Rheum. 1997 Oct;27(2):85-97. Review.
PMID: 9355207 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9355207&dopt=Abstract
Kremer JM, Jubiz W, Michalek A, Rynes RI, Bartholomew LE, Bigaouette J,
Timchalk M, Beeler D, Lininger L.
Fish-oil fatty acid supplementation in active rheumatoid arthritis. A
double-blinded, controlled, crossover study.
Ann Intern Med. 1987 Apr;106(4):497-503.
PMID: 3030173 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3030173&dopt=Abstract
van der Tempel H, Tulleken JE, Limburg PC, Muskiet FA, van Rijswijk MH.
Effects of fish oil supplementation in rheumatoid arthritis.
Ann Rheum Dis. 1990 Feb;49(2):76-80.
PMID: 2138449 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2138449&dopt=Abstract
Astorga G, Cubillos A, Masson L, Silva JJ.
[Active rheumatoid arthritis: effect of dietary supplementation with omega-3
oils. A controlled double-blind trial]
Rev Med Chil. 1991 Mar;119(3):267-72. Spanish.
PMID: 1842119 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1842119&dopt=Abstract
Nielsen GL, Faarvang KL, Thomsen BS, Teglbjaerg KL, Jensen LT, Hansen TM,
Lervang HH, Schmidt EB, Dyerberg J, Ernst E.
The effects of dietary supplementation with n-3 polyunsaturated fatty acids
in patients with rheumatoid arthritis: a randomized, double blind trial.
Eur J Clin Invest. 1992 Oct;22(10):687-91.
PMID: 1459173 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1459173&dopt=Abstract
Kjeldsen-Kragh J, Lund JA, Riise T, Finnanger B, Haaland K, Finstad R,
Mikkelsen K, Forre O.
Dietary omega-3 fatty acid supplementation and naproxen treatment in
patients with rheumatoid arthritis.
J Rheumatol. 1992 Oct;19(10):1531-6.
PMID: 1464864 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1464864&dopt=Abstract
Lee TH, Arm JP, Horton CE, Crea AE, Mencia-Huerta JM, Spur BW.
Effects of dietary fish oil lipids on allergic and inflammatory diseases.
Allergy Proc. 1991 Sep-Oct;12(5):299-303.
PMID: 1959766 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1959766&dopt=Abstract
Jaya T. Venkatraman and Wei-chia Chu
Effects of Dietary omega-3 and omega-6 Lipids and Vitamin E on Serum
Cytokines, Lipid Mediators and Anti-DNA Antibodies in a Mouse Model for
Rheumatoid>Arthritis
Journal of the American College of Nutrition, Vol. 18, No. 6, 602-613 (1999)
http://www.jacn.org/cgi/content/full/18/6/602
GLA
---
Jill JF Belch and Alexander Hill
Evening primrose oil and borage oil in rheumatologic conditions
Am J Clin Nutr 2000 71: 352-356
http://www.ajcn.org/cgi/content/full/71/1/352S
Zurier RB, Rossetti RG, Jacobson EW, DeMarco DM, Liu NY, Temming JE,
White BM, Laposata M.
gamma-Linolenic acid treatment of rheumatoid arthritis. A randomized,
placebo-controlled trial.
Arthritis Rheum. 1996 Nov;39(11):1808-17.
PMID: 8912502 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8912502&dopt=Abstract
Rothman D, DeLuca P, Zurier RB.
Botanical lipids: effects on inflammation, immune responses, and rheumatoid
arthritis.
Semin Arthritis Rheum. 1995 Oct;25(2):87-96. Review.
PMID: 8578315 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8578315&dopt=Abstract
Leventhal LJ, Boyce EG, Zurier RB.
Treatment of rheumatoid arthritis with blackcurrant seed oil.
Br J Rheumatol. 1994 Sep;33(9):847-52.
PMID: 8081671 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8081671&dopt=Abstract
Leventhal LJ, Boyce EG, Zurier RB.
Treatment of rheumatoid arthritis with gammalinolenic acid.
Ann Intern Med. 1993 Nov 1;119(9):867-73.
PMID: 8214997 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8214997&dopt=Abstract
Belch JJ, Ansell D, Madhok R, O'Dowd A, Sturrock RD.
Effects of altering dietary essential fatty acids on requirements for
non-steroidal anti-inflammatory drugs in patients with rheumatoid arthritis:
a double blind placebo controlled study.
Ann Rheum Dis. 1988 Feb;47(2):96-104.
PMID: 2833184 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2833184&dopt=Abstract
Johnson MM, Swan DD, Surette ME, Stegner J, Chilton T, Fonteh AN,
Chilton FH.
Dietary supplementation with gamma-linolenic acid alters fatty acid content
and eicosanoid production in healthy humans.
J Nutr. 1997 Aug;127(8):1435-44.
PMID: 9237935 [PubMed - indexed for MEDLINE]
http://www.nutrition.org/cgi/content/full/127/8/1435
Tate G, Mandell BF, Laposata M, Ohliger D, Baker DG, Schumacher HR,
Zurier RB.
Suppression of acute and chronic inflammation by dietary gamma linolenic
acid.
J Rheumatol. 1989 Jun;16(6):729-34.
PMID: 2550629 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2550629&dopt=Abstract
Furse RK, Rossetti RG, Seiler CM, Zurier RB.
Oral administration of gammalinolenic acid, an unsaturated fatty acid with
anti-inflammatory properties, modulates interleukin-1beta production by
human monocytes.
J Clin Immunol. 2002 Mar;22(2):83-91.
PMID: 11998897 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11998897&dopt=Abstract
Kaku S, Ohkura K, Yunoki S, Nonaka M, Tachibana H, Sugano M, Yamada K.
Dietary gamma-linolenic acid dose-dependently modifies fatty acid
composition and immune parameters in rats.
Prostaglandins Leukot Essent Fatty Acids. 2001 Oct;65(4):205-10.
PMID: 11728173 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11728173&dopt=Abstract
Furse RK, Rossetti RG, Zurier RB.
Gammalinolenic acid, an unsaturated fatty acid with anti-inflammatory
properties, blocks amplification of IL-1 beta production by human monocytes.
J Immunol. 2001 Jul 1;167(1):490-6.
PMID: 11418687 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11418687&dopt=Abstract
Tate GA, Mandell BF, Karmali RA, Laposata M, Baker DG, Schumacher HR
Jr, Zurier RB.
Suppression of monosodium urate crystal-induced acute inflammation by diets
enriched with gamma-linolenic acid and eicosapentaenoic acid.
Arthritis Rheum. 1988 Dec;31(12):1543-51.
PMID: 2848532 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2848532&dopt=Abstract
Barham JB, Edens MB, Fonteh AN, Johnson MM, Easter L, Chilton FH.
Addition of eicosapentaenoic acid to gamma-linolenic acid-supplemented diets
prevents serum arachidonic acid accumulation in humans.
J Nutr. 2000 Aug;130(8):1925-31.
PMID: 10917903 [PubMed - indexed for MEDLINE]
http://www.nutrition.org/cgi/content/full/130/8/1925
Fan YY, Chapkin RS. R
Importance of dietary gamma-linolenic acid in human health and nutrition.
J Nutr. 1998 Sep;128(9):1411-4. Review.
PMID: 9732298 [PubMed - indexed for MEDLINE]
http://www.nutrition.org/cgi/content/full/128/9/1411
--
Matti Narkia
Dr. Andrew B. Chung, MD/PhD
> Thu, 26 Sep 2002 15:57:02 -0400 in article
> <3D93668E...@heartmdphd.com> "Dr. Andrew B. Chung, MD/PhD"
> <and...@heartmdphd.com> wrote:
>
> >
> >Matti Narkia wrote:
> >
> >> On Thu, 26 Sep 2002 12:53:26 -0400, "Dr. Andrew B. Chung, MD/PhD"
> >> <and...@heartmdphd.com> wrote:
> >> >
> >> >Such folks are rare (though they may be quite commonplace on an ALT newsgroup).
> >>
> >> In your clinic? I wouldn't be surprised.
> >
> >Actually, you should be surprised because many of my patients are seeking alternative
> >approaches. My ethnic background is asian so culturally I am probably inclined to be
> >more open-minded about this topic than most. Folks who are crippled by their
> >arthritis typically are not willing to wait three months for fish oil to possibly
> >work.
>
> Now doc, do you intentionally twist your logic, or is it that you cannot
> think straight?
Pain is a simple concept. When folks have it, they generally want immediate relief. Does
fish oil capsules provide immediate relief?
Didn't think so.
--
Dr. Andrew B. Chung, MD/PhD
Atlanta Cardiologist
http://www.heartmdphd.com
Matti Narkia
<3D938662...@heartmdphd.com> "Dr. Andrew B. Chung, MD/PhD"
<and...@heartmdphd.com> wrote:
>Matti Narkia wrote:
>
>> Thu, 26 Sep 2002 15:57:02 -0400 in article
>> <3D93668E...@heartmdphd.com> "Dr. Andrew B. Chung, MD/PhD"
>> <and...@heartmdphd.com> wrote:
>>
>> >
>> >Matti Narkia wrote:
>> >
>> >> On Thu, 26 Sep 2002 12:53:26 -0400, "Dr. Andrew B. Chung, MD/PhD"
>> >> <and...@heartmdphd.com> wrote:
>> >> >
>> >> >Such folks are rare (though they may be quite commonplace on an ALT newsgroup).
>> >>
>> >> In your clinic? I wouldn't be surprised.
>> >
>> >Actually, you should be surprised because many of my patients are seeking alternative
>> >approaches. My ethnic background is asian so culturally I am probably inclined to be
>> >more open-minded about this topic than most. Folks who are crippled by their
>> >arthritis typically are not willing to wait three months for fish oil to possibly
>> >work.
>>
>> Now doc, do you intentionally twist your logic, or is it that you cannot
>> think straight?
>
>Pain is a simple concept. When folks have it, they generally want immediate relief. Does
>fish oil capsules provide immediate relief?
>
You're having a bad day again or you're intentionally trying to confuse the
matter. Reread what I wrote.
--
Matti Narkia
Steve Harris
My, either you must be "arranging for" automatic defibrilator implantation
in just about everybody who has coronary disease in your practice, or else
you must have some magical powers to tell you who is going to have a
thrombosis and who isn't.
You know full well that most sudden deaths from acute V-fib without
preceding CHF are people who hever met criteria for AICD by anybody's
reasonable standards. They get dyrhythmia due to new ischemia which is due
to some sudden thrombotic event which there is no predicting, except vaguely
with numbers far too low for anything as drastic as an implantable
defibrillator. So until you cath everybody to see who has CHD, and put an
implantable defibrillator in everybody who does, I suggest you recommend
that everybody eat fish, in the same way they wear seat belts. It's a lot
less of a pain in the chest than a zapper.
Matti Narkia
<k0b6pu8gfkodgsa30...@4ax.com> Matti Narkia
<mn...@despammed.com> wrote:
>On Thu, 26 Sep 2002 11:17:28 -0400, "Pierre L" <pier...@hotmail.com> wrote:
>
>>By the way, since fish oil is not a prescription drug (maybe it should be),
>>I thought I might just point out that you can't just willy-nilly start
>>taking large quantities of fish oil. Best to check with your doctor. Fish
>>oil is very concentrated EPA and DHA. These are fatty acids that the fish
>>has already produced (unlike flax oil, which has the necessary building
>>block fatty acids to make EPA and DHA, but your own body has to actually
>>make them).
>
[snip]
>Our capability to convert linoleic acid to EPA is rather limited and conversion
>is slow. Moreover the conversion is vulnerable and can be disturbed by various
>factors. Advancing age, nutritional deficiencies or diseases could limit the
>availability of the required enzymes.
>
A small (but annoying) lapsus linguae above: should've of course been
"alpha-linolenic acid to EPA", not "linoleic acid to EPA".
Here's the reference to a study that shows that conversion of
alpha-linolenic acid to long-chain metabolites is approximately 6% for EPA
and 3.8% for DHA. With a diet rich in omega-6 PUFA, conversion is reduced by
40 to 50%:
Gerster H.
Can adults adequately convert alpha-linolenic acid (18:3n-3) to
eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3)?
Int J Vitam Nutr Res. 1998;68(3):159-73. Review.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9637947&dopt=Abstract
Abtract:
"A diet including 2-3 portions of fatty fish per week, which
corresponds to the intake of 1.25 g EPA (20:5n-3) + DHA
(22:6n-3) per day, has been officially recommended on the
basis of epidemiological findings showing a beneficial role of
these n-3 long-chain PUFA in the prevention of cardiovascular
and inflammatory diseases. The parent fatty acid ALA
(18:3n-3), found in vegetable oils such as flaxseed or
rapeseed oil, is used by the human organism partly as a source
of energy, partly as a precursor of the metabolites, but the
degree of conversion appears to be unreliable and restricted.
More specifically, most studies in humans have shown that
whereas a certain, though restricted, conversion of high doses
of ALA to EPA occurs, conversion to DHA is severely
restricted. The use of ALA labelled with radioisotopes
suggested that with a background diet high in saturated fat
conversion to long-chain metabolites is approximately 6% for
EPA and 3.8% for DHA. With a diet rich in n-6 PUFA, conversion
is reduced by 40 to 50%. It is thus reasonable to observe an
n-6/n-3 PUFA ratio not exceeding 4-6. Restricted conversion to
DHA may be critical since evidence has been increasing that
this long-chain metabolite has an autonomous function, e.g. in
the brain, retina and spermatozoa where it is the most
prominent fatty acid. In neonates deficiency is associated
with visual impairment, abnormalities in the electroretinogram
and delayed cognitive development. In adults the potential
role of DHA in neurological function still needs to be
investigated in depth. Regarding cardiovascular risk factors
DHA has been shown to reduce triglyceride concentrations.
These findings indicate that future attention will have to
focus on the adequate provision of DHA which can reliably be
achieved only with the supply of the preformed long-chain
metabolite."
--
Matti Narkia
Dr. Andrew B. Chung, MD/PhD
Joel M Kremer
n-3 Fatty acid supplements in rheumatoid arthritis
American Journal of Clinical Nutrition, Vol. 71, No. 1, 349S-351s, January
2000
http://www.ajcn.org/cgi/content/full/71/1/349S
Michael J James, Robert A Gibson, and Leslie G Cleland
Dietary polyunsaturated fatty acids and inflammatory mediator production
Am J Clin Nutr 2000 71: 343-348
http://www.ajcn.org/cgi/content/full/71/1/343S
James MJ, Cleland LG.
Dietary n-3 fatty acids and therapy for rheumatoid arthritis.
Semin Arthritis Rheum. 1997 Oct;27(2):85-97. Review.
PMID: 9355207 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9355207&dopt=Abstract
Kremer JM, Jubiz W, Michalek A, Rynes RI, Bartholomew LE, Bigaouette J,
Timchalk M, Beeler D, Lininger L.
Fish-oil fatty acid supplementation in active rheumatoid arthritis. A
double-blinded, controlled, crossover study.
Ann Intern Med. 1987 Apr;106(4):497-503.
PMID: 3030173 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3030173&dopt=Abstract
One would have liked a decrease in sedimentation rate or rheumatoid factor with this trial in order to confidently conclude that fish oil was retarding the progression of rheumatoid arthritis. Instead, the authors were comfortable with only stating:
"fish-oil ingestion results in subjective alleviation of active rheumatoid arthritis and reduction in neutrophil leukotriene B4 production. Further studies are needed to elucidate mechanisms of action and optimal dose and duration of fish-oil supplementation."
van der Tempel H, Tulleken JE, Limburg PC, Muskiet FA, van Rijswijk MH.
Effects of fish oil supplementation in rheumatoid arthritis.
Ann Rheum Dis. 1990 Feb;49(2):76-80.
PMID: 2138449 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2138449&dopt=Abstract
"This study shows that dietary fish oil supplementation is effective in suppressing clinical symptoms of rheumatoid arthritis."
As in the earlier study, no evidence for modifying the course of rheumatoid arthritis.
Astorga G, Cubillos A, Masson L, Silva JJ.
[Active rheumatoid arthritis: effect of dietary supplementation with omega-3
oils. A controlled double-blind trial]
Rev Med Chil. 1991 Mar;119(3):267-72. Spanish.
PMID: 1842119 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1842119&dopt=Abstract
see above comments
Nielsen GL, Faarvang KL, Thomsen BS, Teglbjaerg KL, Jensen LT, Hansen TM,
Lervang HH, Schmidt EB, Dyerberg J, Ernst E.
The effects of dietary supplementation with n-3 polyunsaturated fatty acids
in patients with rheumatoid arthritis: a randomized, double blind trial.
Eur J Clin Invest. 1992 Oct;22(10):687-91.
PMID: 1459173 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1459173&dopt=Abstract
see above comments
Kjeldsen-Kragh J, Lund JA, Riise T, Finnanger B, Haaland K, Finstad R,
Mikkelsen K, Forre O.
Dietary omega-3 fatty acid supplementation and naproxen treatment in
patients with rheumatoid arthritis.
J Rheumatol. 1992 Oct;19(10):1531-6.
PMID: 1464864 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1464864&dopt=Abstract
"In Groups 1 and 3 there was a significant deterioration for most of the variables measured."
These are the groups taken off naproxen. Fish oil ameliorated but did not prevent the deterioration.
Lee TH, Arm JP, Horton CE, Crea AE, Mencia-Huerta JM, Spur BW.
Effects of dietary fish oil lipids on allergic and inflammatory diseases.
Allergy Proc. 1991 Sep-Oct;12(5):299-303.
PMID: 1959766 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1959766&dopt=Abstract
not a RCT
Ok, that's more fun than I can stand. For the folks following this thread, an important point should be made at this juncture. Rheumatoid arthritis (RA) is *not* the same as osteoarthritis (OA). OA is far more common than RA. So far there has been no evidence that fish oils can replace NSAIDs in the treatment of RA. Certainly there is evidence that fish oil can help NSAIDs work better at relieving symptoms but if you have RA, you should continue with following up with your rheumatologist for treatments proven to alter the course of your disease rather than self-medicating with fish oil.
Now, what about OA?
Fish oil has been looked in a double-blind placebo controlled trial involving 86 patients (larger than any of the studies cited for RA) and found to provide no benefit compared to placebo (olive oil).
See:
I rest my case :-)
--
Dr. Andrew B. Chung, MD/PhD
Atlanta Cardiologist
http://www.heartmdphd.com
Dr. Andrew B. Chung, MD/PhD
Magical powers are not required at all. It is not hard to determine that
someone has a scarred left ventricle thereby having "substrate" for SCD. If one
were more worried about SCD from acute thrombosis of a large coronary vessel, I
would focus more on preventing the thrombosis than preventing the arrhythmias
secondary to the thrombosis. Just a word to the wise...
Matti Narkia
<3D93A568...@heartmdphd.com> "Dr. Andrew B. Chung, MD/PhD"
<and...@heartmdphd.com> wrote:
>Matti Narkia wrote:
>>
>> On second thought I repost the most relevant references here, too:
>>
>> Fish Oil
>> --------
>>
>> Calder PC.
>> Polyunsaturated fatty acids, inflammation, and immunity.
>> Lipids. 2001 Sep;36(9):1007-24. Review.
>> PMID: 11724453 [PubMed - indexed for MEDLINE]
>> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11724453&dopt=Abstract
>>
>
>not a RCT.
>
But a good review article reviewing existing RCTs, an excerpt from the
abstract:
"... Clinical studies have reported that fish oil supplementation has
beneficial effects in rheumatoid arthritis, inflammatory bowel disease,
and among some asthmatics, supporting the idea that the n-3 PUFA in
fish oil are anti-inflammatory and immunomodulatory."
>>
>> Joel M Kremer
>> n-3 Fatty acid supplements in rheumatoid arthritis
>> American Journal of Clinical Nutrition, Vol. 71, No. 1, 349S-351s, January
>> 2000
>> http://www.ajcn.org/cgi/content/full/71/1/349S
>>
>not a RCT.
>
But a full text excellent review article reviewing, among other things the
available RCTs. Here its abstract:
"Ingestion of dietary supplements of n-3 fatty acids has been
consistently shown to reduce both the number of tender joints
on physical examination and the amount of morning stiffness in
patients with rheumatoid arthritis. In these cases,
supplements were consumed daily in addition to background
medications and the clinical benefits of the n-3 fatty acids
were not apparent until they were consumed for 12 wk. It
appears that a minimum daily dose of 3 g eicosapentaenoic and
docosahexaenoic acids is necessary to derive the expected
benefits. These doses of n-3 fatty acids are associated with
significant reductions in the release of leukotriene B4 from
stimulated neutrophils and of interleukin 1 from monocytes.
Both of these mediators of inflammation are thought to
contribute to the inflammatory events that occur in the
rheumatoid arthritis disease process. Several investigators
have reported that rheumatoid arthritis patients consuming n-3
dietary supplements were able to lower or discontinue their
background doses of nonsteroidal antiinflammatory drugs or
disease-modifying antirheumatic drugs. Because the methods
used to determine whether patients taking n-3 supplements can
discontinue taking these agents are variable, confirmatory and
definitive studies are needed to settle this issue. n-3 Fatty
acids have virtually no reported serious toxicity in the dose
range used in rheumatoid arthritis and are generally very well
tolerated."
>>
>> Michael J James, Robert A Gibson, and Leslie G Cleland
>> Dietary polyunsaturated fatty acids and inflammatory mediator production
>> Am J Clin Nutr 2000 71: 343-348
>> http://www.ajcn.org/cgi/content/full/71/1/343S
>>
>not a RCT.
>
An excellent full text article about the mechanisms of fish oil effects. An
excerpt from the abstract:
"... Regarding the proinflammatory cytokines, tumor necrosis factor and
interleukin 1ß, studies of healthy volunteers and rheumatoid arthritis
patients have shown 90% inhibition of cytokine production after dietary
supplementation with fish oil."
>>
>> James MJ, Cleland LG.
>> Dietary n-3 fatty acids and therapy for rheumatoid arthritis.
>> Semin Arthritis Rheum. 1997 Oct;27(2):85-97. Review.
>> PMID: 9355207 [PubMed - indexed for MEDLINE]
>> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9355207&dopt=Abstract
>>
>not a RCT.
>
But a good review article reviewing existing RCTs. Here an excerpt from the
abstract:
"... RESULTS: There is consistent evidence from double-blind,
placebo-controlled clinical trials that dietary n-3 fats,
supplied as fish oil, can have beneficial effects in RA. The
beneficial effects appear modest, but their size and extent
may have been moderated by common trial design factors such as
high n-6 polyunsaturated fat diets and concurrent
antiinflammatory drug use. Mechanisms for the clinical effects
of n-3 fats in RA may involve their ability to suppress
production of inflammatory mediators, including n-6
eicosanoids and proinflammatory cytokines. Suppression of n-6
eicosanoid and cytokine production will be possible using
foodstuffs that are rich in n-3 fats and poor in n-6 fats.
CONCLUSIONS: There are many overlapping biochemical effects of
n-3 fatty acids and antiinflammatory pharmaceuticals that
could explain the clinical actions of n-3 fats in RA. They
suggest that there is the potential for complementarity
between drug therapy and dietary choices that increase intake
of n-3 fats and decrease intake of n-6 fats. In particular,
there is the potential for drug-sparing effects. Future
studies with n-3 fats in RA need to address the fat
composition of the background diet and the issue of concurrent
drug use..."
>>
>> Kremer JM, Jubiz W, Michalek A, Rynes RI, Bartholomew LE, Bigaouette J,
>> Timchalk M, Beeler D, Lininger L.
>> Fish-oil fatty acid supplementation in active rheumatoid arthritis. A
>> double-blinded, controlled, crossover study.
>> Ann Intern Med. 1987 Apr;106(4):497-503.
>> PMID: 3030173 [PubMed - indexed for MEDLINE]
>> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3030173&dopt=Abstract
>
>"There were no statistically significant differences in hemoglobin level, sedimentation rate, or presence
>of rheumatoid factor..."
>
My goodness, no one has claimed that fish oil _cures_ arthritis, just that
the _symptoms_ may be recuded allowing a possible reduction in NSAID dose or
even leading to complete elimination of them some cases. The reduction in
the NSAID dose is extremely valuable in preventing the kidney damage and
other side effects of long term use of large dose of NSAIDS.
Excerpts from the abstract:
" ... Results: the following results favored fish oil placebo after
14 weeks: mean time to onset of fatigue improved by 156 minutes (95%
confidence interval, 1.2 to 311.0 minutes), and number of tender
joints decreased by 3.5 (95% Cl, -6.0 to -1.0). Other clinical
measures favored fish oil as well but did reach statistical
significance. Neutrophil leukotriene B4 production was correlated
with the decrease in number of tender joints (Spearman rank
correlation r=0.53; p less than 0.05)...
... An effect from the fish oil persisted beyond the 4-week washout
period. Conclusions: fish-oil ingestion results in subjective
alleviation of active rheumatoid arthritis and reduction in
neutrophil leukotriene B4 production ..."
>One would have liked a decrease in sedimentation rate or rheumatoid factor with this trial in order to
>confidently conclude that fish oil was retarding the progression of rheumatoid arthritis
Even NSAIDs cannot retard the progression of rheumatoid arthritis, you need
drugs like methotrexate for that. The idea is to replace the NSAIDs or
reduce their dose.
>> van der Tempel H, Tulleken JE, Limburg PC, Muskiet FA, van Rijswijk MH.
>> Effects of fish oil supplementation in rheumatoid arthritis.
>> Ann Rheum Dis. 1990 Feb;49(2):76-80.
>> PMID: 2138449 [PubMed - indexed for MEDLINE]
>> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2138449&dopt=Abstract
>
>"This study shows that dietary fish oil supplementation is effective in suppressing clinical symptoms of
>rheumatoid arthritis."
>
>As in the earlier study, no evidence for modifying the course of rheumatoid arthritis.
>
I repeat that the intention is to replace the NSAIDs or reduce their dose.
Clearly that seems possible if the study shows that "that dietary fish oil
supplementation is effective in suppressing clinical symptoms of
rheumatoid arthritis", as it does.
>>
>>
>> Astorga G, Cubillos A, Masson L, Silva JJ.
>> [Active rheumatoid arthritis: effect of dietary supplementation with omega-3
>> oils. A controlled double-blind trial]
>> Rev Med Chil. 1991 Mar;119(3):267-72. Spanish.
>> PMID: 1842119 [PubMed - indexed for MEDLINE]
>> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1842119&dopt=Abstract
>
>see above comments
>
Ditto.
>>
>>
>> Nielsen GL, Faarvang KL, Thomsen BS, Teglbjaerg KL, Jensen LT, Hansen TM,
>> Lervang HH, Schmidt EB, Dyerberg J, Ernst E.
>> The effects of dietary supplementation with n-3 polyunsaturated fatty acids
>> in patients with rheumatoid arthritis: a randomized, double blind trial.
>> Eur J Clin Invest. 1992 Oct;22(10):687-91.
>> PMID: 1459173 [PubMed - indexed for MEDLINE]
>> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1459173&dopt=Abstract
>
>see above comments
>
Ditto.
>>
>> Kjeldsen-Kragh J, Lund JA, Riise T, Finnanger B, Haaland K, Finstad R,
>> Mikkelsen K, Forre O.
>> Dietary omega-3 fatty acid supplementation and naproxen treatment in
>> patients with rheumatoid arthritis.
>> J Rheumatol. 1992 Oct;19(10):1531-6.
>> PMID: 1464864 [PubMed - indexed for MEDLINE]
>> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1464864&dopt=Abstract
>
> "In Groups 1 and 3 there was a significant deterioration for most of the variables measured."
>
>These are the groups taken off naproxen. Fish oil ameliorated but did not prevent the deterioration.
>
See the previous comments.
>>
>>
>> Lee TH, Arm JP, Horton CE, Crea AE, Mencia-Huerta JM, Spur BW.
>> Effects of dietary fish oil lipids on allergic and inflammatory diseases.
>> Allergy Proc. 1991 Sep-Oct;12(5):299-303.
>> PMID: 1959766 [PubMed - indexed for MEDLINE]
>> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1959766&dopt=Abstract
>
>not a RCT.
>
But a review which explains the mechanisms and reviews the RCTs concluding:
"... "Clinical trials in rheumatoid arthritis, psoriasis, atopic
dermatitis, and bronchial asthma have shown beneficial effects..."
>
>Ok, that's more fun than I can stand. For the folks following this thread, an important point should be
>made at this juncture. Rheumatoid arthritis (RA) is *not* the same as osteoarthritis (OA). OA is far
>more common than RA.
I'm aware of that. In addition to fish oil, there are currently more
effective treatments for OA, such as glucosamine sulfate and chondroitin
sulfate, which have been tested in double blind trials for OA. Therefore,
for OA, the use of NSAIDs can be largely eliminated using these most modern
treatments.
>So far there has been no evidence that fish oils can replace NSAIDs in the
>treatment of RA.
I beg to disagree, clinical trials show that you can at least partially
replace NSAIDS for many patients. Every kidney saved proves that the effort
of trying fish oil for every patient is worth taking.
>Certainly there is evidence that fish oil can help NSAIDs work better at relieving
>symptoms but if you have RA, you should continue with following up with your rheumatologist for
>treatments proven to alter the course of your disease rather than self-medicating with fish oil.
>
Every patient should find a doctor who is interested in trying to save
his/her kidney by experimenting also with fish oil.
>Now, what about OA?
>
>Fish oil has been looked in a double-blind placebo controlled trial involving 86 patients (larger than
>any of the studies cited for RA) and found to provide no benefit compared to placebo (olive oil).
>
>See:
>
>http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1540019&dopt=Abstract
>
>I rest my case :-)
Don't rest too long. The above study used cod liver, not fish oil. Therefore
it doesn't even start proving anything about fish oil. You don't use aspirin
to prove something about ibuprofen, do you?
Apparently you are not aware of it, but cod liver oil and fish oil are not
the same thing. One of the differences is that cod liver oil is obviously
made from the liver, not from the flesh of fish like fish oil. One result of
this is that cod liver oil contains so large quantities of vitamins A and D,
that it cannot be used in doses sufficient to provide the required dose of
omega-3 fatty acids.
However, fortunately the above is now almost purely academic for OA, because
treatment with apparently non-toxic disease modifying agents such as
glucosamine sulphate and chondroitin sulphate seems to be a way to go.
Fish oil could still be used to further alleviate any symptoms which
possibly still may remain, and to promote general health :-).
See the full text article
Long-term effects of glucosamine sulphate on osteoarthritis progression: a
randomised, placebo-controlled clinical trial.
Jean Yves Reginster, Rita Deroisy, Lucio C Rovati, Richard L Lee, Eric
Lejeune, Olivier Bruyere, Giampaolo Giacovelli, Yves Henrotin, Jane E Dacre,
Christiane Gossett.
Lancet, Volume 357, Number 9252, 27 January 2001
http://www.thelancet.com/journal/vol357/iss9252/full/llan.357.9252.original_research.14985.1
Abstract:
"Background Treatment of osteoarthritis is usually limited to
short-term symptom control. We assessed the effects of the
specific drug glucosamine sulphate on the long-term
progression of osteoarthritis joint structure changes and
symptoms.
Methods We did a randomised, double-blind placebo controlled
trial, in which 212 patients with knee osteoarthritis were
randomly assigned 1500 mg sulphate oral glucosamine or placebo
once daily for 3 years. Weightbearing, anteroposterior
radiographs of each knee in full extension were taken at
enrolment and after 1 and 3 years. Mean joint-space width of
the medial compartment of the tibiofemoral joint was assessed
by digital image analysis, whereas minimum joint-space width--
ie, at the narrowest point--was measured by visual inspection
with a magnifying lens. Symptoms were scored by the Western
Ontario and McMaster Universities (WOMAC) osteoarthritis
index.
Findings The 106 patients on placebo had a progressive joint-
space narrowing, with a mean joint-space loss after 3 years of
-0·31 mm (95% CI -0·48 to -0·13). There was no significant
joint-space loss in the 106 patients on glucosamine sulphate:
-0·06 mm (-0·22 to 0·09). Similar results were reported with
minimum joint-space narrowing. As assessed by WOMAC scores,
symptoms worsened slightly in patients on placebo compared
with the improvement observed after treatment with glucosamine
sulphate. There were no differences in safety or reasons for
early withdrawal between the treatment and placebo groups.
Interpretation The long-term combined structure-modifying and
symptom-modifying effects of gluosamine sulphate suggest that
it could be a disease modifying agent in osteoarthritis."
See also
Tim McAlindon
Commentary
Glusoamine for osteoarthritis: dawn of a new era?
Lancet, Volume 357, Number 9252, 27 January 2001
http://www.thelancet.com/journal/vol357/iss9252/full/llan.357.9252.editorial_and_review.15027.1
... The 3-year randomised placebo-controlled trial suggests
that an oral agent, glucosamine sulphate, retards the
progression of symptomatic knee osteoarthritis. The study is
a landmark in OA research, not only for its scientific
results, but also for highlighting vexing issues in this
area...
... In fact, the results are impressive; patients assigned to
glucosamine experienced significant improvements in pain and
disability that were sustained for the 3 years of the study,
whereas the scores among the placebo group worsened.
Furthermore, adverse-event rates were not higher than those
associated with placebo. These findings are consistent with
those seen in previous symptom-based studies of
glucosamine..."
And don't forget to look at the following articles:
Glucosamine in osteoarthritis
Lancet, Volume 354, Number 9190, 06 November 1999
http://www.thelancet.com/journal/vol354/iss9190/full/llan.354.9190.correspondence.2759.1
Verbruggen G, Goemaere S, Veys EM.
Chondroitin sulfate: S/DMOAD (structure/disease modifying
anti-osteoarthritis drug) in the treatment of finger joint OA.
Osteoarthritis Cartilage. 1998 May;6 Suppl A:37-8.
PMID: 9743818 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9743818&dopt=Abstract
Mazieres B, Loyau G, Menkes CJ, Valat JP, Dreiser RL, Charlot J,
Masounabe-Puyanne A.
[Chondroitin sulfate in the treatment of gonarthrosis and coxarthrosis.
5-months result of a multicenter double-blind controlled prospective study
using placebo]
Rev Rhum Mal Osteoartic. 1992 Jul-Sep;59(7-8):466-72. French.
PMID: 1485136 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1485136&dopt=Abstract
Leeb BF, Petera P, Neumann K.
[Results of a multicenter study of chondroitin sulfate (Condrosulf) use in
arthroses of the finger, knee and hip joints]
Wien Med Wochenschr. 1996;146(24):609-14. German.
PMID: 9123947 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9123947&dopt=Abstract
Alekseeva LI, Mednikov BL, Piiavskii SA, Nasonova VA, Soldatov DG. R
[Pharmacoeconomic aspects of use of structum in osteoarthrosis]
Ter Arkh. 2001;73(11):90-2. Russian.
PMID: 11806219 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11806219&dopt=Abstract
Nasonova VA, Alekseeva LI, Arkhangel'skaia GS, Davydova AF, Karmil'tseva EA,
Kogan KM, Mazurov VI, Rebrov AP, Riabitseva OF, Shemerovskaia TG, Shmidt EI,
Iakushin SS, Soldatov DG.
[Results of the multicenter clinical trial of structum preparation in
Russia]
Ter Arkh. 2001;73(11):84-7. Russian.
PMID: 11806217 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11806217&dopt=Abstract
Alekseeva LI, Benevolenskaia LI, Nasonov EL, Chichasova NV, Kariakin AN.
[Structum (chondroitin sulfate)--a new agent for the treatment of
osteoarthrosis]
Ter Arkh. 1999;71(5):51-3. Russian.
PMID: 10399232 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10399232&dopt=Abstract
Bucsi L, Poor G. R
Efficacy and tolerability of oral chondroitin sulfate as a symptomatic
slow-acting drug for osteoarthritis (SYSADOA) in the treatment of knee
osteoarthritis.
Osteoarthritis Cartilage. 1998 May;6 Suppl A:31-6.
PMID: 9743817 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9743817&dopt=Abstract
I rest _my_ case ;-)
PS. Some new, promising agents are emerging for OA. One of them, Lyprinol
(New Zealand's green lipped mussel extract) is a natural source of
glucosamine sulphate and chondroitin sulphate, and also contains - in
addition to EPA and DHA - also another very important anti-inflammatory
fatty acid, ETA. See for example
Halpern GM.
Anti-inflammatory effects of a stabilized lipid extract of Perna canaliculus
(Lyprinol).
Allerg Immunol (Paris). 2000 Sep;32(7):272-8. Review.
PMID: 11094640 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11094640&dopt=Abstract
Shiels IA,
Lyprinol: anti-inflammatory and uterine-relaxant activities in rats, with
special reference to a model for dysmenorrhoea.
Allerg Immunol (Paris). 2000 Sep;32(7):279-83.
PMID: 11094641 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11094641&dopt=Abstract
Dugas B.
Lyprinol inhibits LTB4 production by human monocytes.
Allerg Immunol (Paris). 2000 Sep;32(7):284-9.
PMID: 11094642 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11094642&dopt=Abstract
--
Matti Narkia
Matti Narkia
<and...@heartmdphd.com> wrote:
>Pain is a simple concept. When folks have it, they generally want immediate relief. Does
>fish oil capsules provide immediate relief?
>
>Didn't think so.
As I in painful (pun not intended :-) details have explained, NSAIDs can be
provided simultaneously with fish oil to provide as much immediate relief as
possible. The dose of NSAIDs can then in due course be reduced, if fish oil
treatment is at least partially successful.
BTW, you have repeatedly implied that you treat patients as they want. Are
you a doctor or a coin operated treatment automat? Don't you think that
regardless of what patients wan,t you should advice them a) about
consequences if give you them want they want, and b) about other, possibly
better options? For example, don't you think that in this case it is your
responsibility to advice patients that there may be a possibility, which is
even supported by existing evidence, that a dietary change towards consuming
more omega-3 fats (either by taking fish oil capsules or by eating daily
sufficient amount of fatty fish) and less omega-6 fats could result in due
time result in a smaller dose of NDSAIDs than initially seems necessary, and
that this dose reduction may have a sparing effect on his/her kidney. If you
fail to inform the patient about this, I don't consider you to be doctor who
puts patient's interest first.
--
Matti Narkia
Matti Narkia
<h338pu8d6603uvj7k...@4ax.com> Matti Narkia
<mn...@despammed.com> wrote:
Moreover, as one would expect you as a cardiologist to be aware of this new
NEJM study:
Albert CM, Campos H, Stampfer MJ, Ridker PM, Manson JE, Willett WC, Ma J.
Blood levels of long-chain n-3 fatty acids and the risk of sudden death.
N Engl J Med. 2002 Apr 11;346(15):1113-8.
PMID: 11948270 [PubMed - indexed for MEDLINE]
http://content.nejm.org/cgi/content/abstract/346/15/1113
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11948270&dopt=Abstract
"... CONCLUSIONS: The n-3 fatty acids found in fish
are strongly associated with a reduced risk of sudden death
among men without evidence of prior cardiovascular disease."
This study clearly suggests that fish oil supplementation could bring even
for arthritis patient with no evidence of prior cardiovascular disease also
other benefits than sparing his kidney.
--
Matti Narkia
Dr. Andrew B. Chung, MD/PhD
Fish oil has no proven role as either a replacement for NSAIDs or as disease modifying therapy.
Brevity remains the soul of wit :-)
--
Dr. Andrew B. Chung, MD/PhD
Atlanta Cardiologist
http://www.heartmdphd.com
Dr. Andrew B. Chung, MD/PhD
> Thu, 26 Sep 2002 18:12:50 -0400 in article
> <3D938662...@heartmdphd.com> "Dr. Andrew B. Chung, MD/PhD"
> <and...@heartmdphd.com> wrote:
>
> >Pain is a simple concept. When folks have it, they generally want immediate relief. Does
> >fish oil capsules provide immediate relief?
> >
> >Didn't think so.
>
> As I in painful (pun not intended :-) details have explained, NSAIDs can be
> provided simultaneously with fish oil to provide as much immediate relief as
> possible. The dose of NSAIDs can then in due course be reduced, if fish oil
> treatment is at least partially successful.
>
> BTW, you have repeatedly implied that you treat patients as they want.
I practice evidence-based medicine.
--
Dr. Andrew B. Chung, MD/PhD
Atlanta Cardiologist
http://www.heartmdphd.com
Dr. Andrew B. Chung, MD/PhD
> Fri, 27 Sep 2002 08:09:10 GMT in article
> <h338pu8d6603uvj7k...@4ax.com> Matti Narkia
> <mn...@despammed.com> wrote:
When someone starts responding to his/her own posts, it is time to kill the thread.
--
Dr. Andrew B. Chung, MD/PhD
Atlanta Cardiologist
http://www.heartmdphd.com
Matti Narkia
<and...@heartmdphd.com> wrote:
>Matti Narkia wrote:
>
>> Fri, 27 Sep 2002 08:09:10 GMT in article
>> <h338pu8d6603uvj7k...@4ax.com> Matti Narkia
>> <mn...@despammed.com> wrote:
>
>When someone starts responding to his/her own posts, it is time to kill the thread.
When someone starts commenting meta-contents and formalities _instead_ of the
presented facts, even _repeatedly_, I suggest that the commentor sticks to his
proposed line of action to save us from meta-meta-.. comments which otherwise
obviously would follow :-) :-)
Matti Narkia
<and...@heartmdphd.com> wrote:
>The bottomline is that the much maligned NSAIDs remain the mainstay of relieving symptoms for both RA and OA.
Not likely. Glucosamine sulfate and possibly also chondroitin sulfate will
probably make NSAIDs less necessary in OA in near future. The results so far
seem to be so good, that if doctors don't prescribe them, the patients will
start self-medicating, because these medicationa are also available without
prescription as nutritional supplements.
In the 3-year glucosamine sulfate trial published Lancet the rescue drugs
(NSAIDs or simple analgesics) were only needed on less than one of every 6 days
throughout the study duration.
>Fish oil has no proven role as either a replacement for NSAIDs or as disease modifying therapy.
>
Depends on the level of proof one requires. The existing evidence as symptom
reliever seems unequivocal. I'm not aware of contradicting evidence.
Don Kirkman
>On Fri, 27 Sep 2002 07:08:14 -0400, "Dr. Andrew B. Chung, MD/PhD"
><and...@heartmdphd.com> wrote:
>>The bottomline is that the much maligned NSAIDs remain the mainstay of relieving symptoms for both RA and OA.
>Not likely. Glucosamine sulfate and possibly also chondroitin sulfate will
>probably make NSAIDs less necessary in OA in near future. The results so far
>seem to be so good, that if doctors don't prescribe them, the patients will
>start self-medicating, because these medicationa are also available without
>prescription as nutritional supplements.
Actually pain control is the primary treatment for OA, since joints once
destroyed aren't apt to regenerate (and NSAIDS aren't primarily pain
killers but inflammation killers). Inflammation is secondary to the
joint damage in OA. GS/CS *apparently* slow the deterioration of
cartilage, and just possibly may cause some regeneration, but rigid
studies are needed and are getting under way. Apart from pain control
GS/CS may be the most widely used treatment for OA. There's no "also
available" about GS/CS, since they aren't prescription drugs but are
purely nutritionals
BTW, don't confuse NSAIDS with DMARDs, Disease Modifying Anti-Rheumatics
Drugs, which are the big guns in rheumatoid arthritis.
>In the 3-year glucosamine sulfate trial published Lancet the rescue drugs
>(NSAIDs or simple analgesics) were only needed on less than one of every 6 days
>throughout the study duration.
That sounds like moderate OA; you'd have a hard time convincing my
newsgroup acquaintances on canes, crutches, and wheel chairs that they
only need pain relief once a week even with GS/CS. Did Lancet speak to
the severity of their subjects' disease?
--
Don
don...@covad.net
Don Kirkman
I was rather hoping for double blind study findings from rheumatologists
instead of from nutritionists. Got any?
--
Don
don...@covad.net
Don Kirkman
[Re arthritis and fish oil]
>Now doc, do you intentionally twist your logic, or is it that you cannot
>think straight? If your patients are crippled by their arthritis they
>continue taking whatever medication will make they feel less crippled, don't
>they? If after three months use of fish oil they don't seem to be able to
>reduce the medication without the worsening of the symptoms, fine, perhaps
>fish oil is not for them. They could still eat fatty fish though, that's
>good for most people. But if, on the other hand, they can reduce the
>medication, they may reduce their risk of getting kidney or other organ
>damage. No need to be more crippled for three months while waiting for fish
>oil to work.
>Another matter is that some people do get kidney damage from the long term
>use of NSAIDs.
Liver damage seems to be the main thing rheumatologists regularly
monitor for, and I suspect this is indicated in the published
information for any of the NSAIDS or DMARDs. There are a few of these
implicated in kidney problems, of course, and in some of the arthritises
eyes, lungs, and other tissues may also be affected by the disease
and/or the medications.
The heaviest current long term use seems to be moving toward DMARDs, not
NSAIDS. Like nearly everything any of us put into our bodies, there are
implications for the liver.
> Then they may be forced to stop NSAIDs and try something
>else, fish oil, for example, and hope it works.
Actually they would be more apt to switch to a different NSAID or DMARD.
There are increasing numbers of them available, and most newer ones have
less serious side effects. Many patients have to try several before
they find one that works for their particular case--rheumatic arthritis
in particular is a very individualized disease. Some of the NSAIDs and
DMARDs seem to burn out after a few years of use, and in that case also
a switch is indicated.
>If it does, the kidney
>damage would have been avoidable with the earlier use of fish oil. So
>according to my logic it's wise to try fish oil as early as possible. What
>you have to lose? Unnecessary payment for three month's supply of fish oil,
>if it doesn't work. That's negligible compared with the benefits, if it does
>work.
Liver. I'm afraid to ask, because I see a can of worms sitting there
untouched and because this is really a *cardiology* newsgroup, but what
benefit has fish oil (read "any of the oils that have been studied") for
the kidneys over a routine good diet? Never mind.
--
Don
don...@covad.net
Don Kirkman
>>>See the previously provided Medline references in the thread "Results of
>>>Heart Health?"
>On second thought I repost the most relevant references here, too:
>Fish Oil
>--------
>Calder PC.
>Polyunsaturated fatty acids, inflammation, and immunity.
>Lipids. 2001 Sep;36(9):1007-24. Review.
>PMID: 11724453 [PubMed - indexed for MEDLINE]
>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11724453&dopt=Abstract
Review article
>Joel M Kremer
>n-3 Fatty acid supplements in rheumatoid arthritis
>American Journal of Clinical Nutrition, Vol. 71, No. 1, 349S-351s, January
>2000
>http://www.ajcn.org/cgi/content/full/71/1/349S
Review article
>Michael J James, Robert A Gibson, and Leslie G Cleland
>Dietary polyunsaturated fatty acids and inflammatory mediator production
>Am J Clin Nutr 2000 71: 343-348
>http://www.ajcn.org/cgi/content/full/71/1/343S
Review article
>James MJ, Cleland LG.
>Dietary n-3 fatty acids and therapy for rheumatoid arthritis.
>Semin Arthritis Rheum. 1997 Oct;27(2):85-97. Review.
>PMID: 9355207 [PubMed - indexed for MEDLINE]
>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9355207&dopt=Abstract
Review article
>Kremer JM, Jubiz W, Michalek A, Rynes RI, Bartholomew LE, Bigaouette J,
>Timchalk M, Beeler D, Lininger L.
>Fish-oil fatty acid supplementation in active rheumatoid arthritis. A
>double-blinded, controlled, crossover study.
>Ann Intern Med. 1987 Apr;106(4):497-503.
>PMID: 3030173 [PubMed - indexed for MEDLINE]
>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3030173&dopt=Abstract
Forty sufferers from rheumatoid arthritis; seven did not finish; no
indication of which non-finishers were in the treatment group and which
in the placebo group. Conclusions:
"Measurements and Main Results: the following results favored fish oil
placebo after 14 weeks: mean time to onset of fatigue improved by 156
minutes (95% confidence interval, 1.2 to 311.0 minutes), and number of
tender joints decreased by 3.5 (95% Cl, -6.0 to -1.0). Other clinical
measures favored fish oil as well but did reach statistical
significance. Neutrophil leukotriene B4 production was correlated with
the decrease in number of tender joints (Spearman rank correlation
r=0.53; p less than 0.05). There were no statistically significant
differences in hemoglobin level, sedimentation rate, or presence of
rheumatoid factor or in patient-reported adverse effects. An effect from
the fish oil persisted beyond the 4-week washout period. Conclusions:
fish-oil ingestion results in subjective alleviation of active
rheumatoid arthritis and reduction in neutrophil leukotriene B4
production. Further studies are needed to elucidate mechanisms of action
and optimal dose and duration of fish-oil supplementation."
Two phrases read as though they contain typos: "fish oil placebo" and
"Other clinical measures favored fish oil as well but did reach
statistical significance."
NOTE: Rheumatoid arthritis is commonly associated with 'flares' and
with temporary periods of reduced inflammation apart from medication
regimens. This is not suggested in the abstract or in any of the ones
below where rheumatoid arthritis was at issue.
>van der Tempel H, Tulleken JE, Limburg PC, Muskiet FA, van Rijswijk MH.
>Effects of fish oil supplementation in rheumatoid arthritis.
>Ann Rheum Dis. 1990 Feb;49(2):76-80.
>PMID: 2138449 [PubMed - indexed for MEDLINE]
>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2138449&dopt=Abstract
Similar to the preceding study but with 12 patients. In both studies
patients continued with their NSAIDS, some of which take weeks to show
meaningful results. This should be noted in the findings, since
depending on the timing the results could be from the NSAIDS kicking in.
>Astorga G, Cubillos A, Masson L, Silva JJ.
>[Active rheumatoid arthritis: effect of dietary supplementation with omega-3
>oils. A controlled double-blind trial]
>Rev Med Chil. 1991 Mar;119(3):267-72. Spanish.
>PMID: 1842119 [PubMed - indexed for MEDLINE]
>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1842119&dopt=Abstract
Eight treated patients, eight controls. "After 12 weeks of therapy a
significant improvement in prehensile function was detected in patients
receiving active treatment, other clinical parameters remaining
unchanged. No significant side effects were detected. A larger trial may
help define a possible therapeutic role for omega-3 fatty acids in
patients with rheumatoid arthritis."
>Nielsen GL, Faarvang KL, Thomsen BS, Teglbjaerg KL, Jensen LT, Hansen TM,
>Lervang HH, Schmidt EB, Dyerberg J, Ernst E.
>The effects of dietary supplementation with n-3 polyunsaturated fatty acids
>in patients with rheumatoid arthritis: a randomized, double blind trial.
>Eur J Clin Invest. 1992 Oct;22(10):687-91.
>PMID: 1459173 [PubMed - indexed for MEDLINE]
>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1459173&dopt=Abstract
Fifty one patients for 12 weeks; "MAIN RESULTS: Significant improvement
of morning stiffness and joint tenderness. No significant effect on the
four other assessed clinical parameters. No serious side effects.
CONCLUSIONS: Dietary supplementation with n-3 PUFA in patients with
rheumatoid arthritis improved two out of six patient reported disease
parameters. Further studies are needed to clarify the more precise role
of n-3 PUFA in the treatment of rheumatoid arthritis."
>Kjeldsen-Kragh J, Lund JA, Riise T, Finnanger B, Haaland K, Finstad R,
>Mikkelsen K, Forre O.
>Dietary omega-3 fatty acid supplementation and naproxen treatment in
>patients with rheumatoid arthritis.
>J Rheumatol. 1992 Oct;19(10):1531-6.
>PMID: 1464864 [PubMed - indexed for MEDLINE]
>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1464864&dopt=Abstract
Sixty-seven patients; those on placebo got naproxen for the first ten of
the sixteen weeks, then were tapered off to zero in three weeks; the
second group received Omega-3 oils and naproxen for the entire 16 weeks,
and the third group received Omega-3 oils but only ten weeks of full
dose naproxen the same as the first group.
One obvious question is what effect the differential use of naproxen
made in the outcomes. The logic of it boggles the mind, at least mine.
>Lee TH, Arm JP, Horton CE, Crea AE, Mencia-Huerta JM, Spur BW.
>Effects of dietary fish oil lipids on allergic and inflammatory diseases.
>Allergy Proc. 1991 Sep-Oct;12(5):299-303.
>PMID: 1959766 [PubMed - indexed for MEDLINE]
>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1959766&dopt=Abstract
This study primarily concerns allergies; the abstract concludes
"Clinical trials in rheumatoid arthritis, psoriasis, atopic dermatitis,
and bronchial asthma have shown beneficial effects. Whether the benefit
obtained clinically is sufficient to replace or significantly reduce any
clinical condition remains to be answered."
>Jaya T. Venkatraman and Wei-chia Chu
>Effects of Dietary omega-3 and omega-6 Lipids and Vitamin E on Serum
>Cytokines, Lipid Mediators and Anti-DNA Antibodies in a Mouse Model for
>Rheumatoid>Arthritis
>Journal of the American College of Nutrition, Vol. 18, No. 6, 602-613 (1999)
>http://www.jacn.org/cgi/content/full/18/6/602
Mouse study.
>GLA
>---
Of course the topic you've been pushing has been fish oil, not these
others. :-)
>Jill JF Belch and Alexander Hill
>Evening primrose oil and borage oil in rheumatologic conditions
>Am J Clin Nutr 2000 71: 352-356
>http://www.ajcn.org/cgi/content/full/71/1/352S
Review article re: essential fatty acids, not limited to fish oil.
>Zurier RB, Rossetti RG, Jacobson EW, DeMarco DM, Liu NY, Temming JE,
>White BM, Laposata M.
>gamma-Linolenic acid treatment of rheumatoid arthritis. A randomized,
>placebo-controlled trial.
>Arthritis Rheum. 1996 Nov;39(11):1808-17.
>PMID: 8912502 [PubMed - indexed for MEDLINE]
>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8912502&dopt=Abstract
12-month study, first six months double blind. "CONCLUSION: GLA at
doses used in this study is a well- tolerated and effective treatment
for active RA. GLA is available as a component of several plant seed
oils and is usually taken in far lower doses than were used in this
trial. It is not approved in the United States for the treatment of any
condition, and should not be viewed as therapy for any disease. Further
controlled studies of its [use] in RA are warranted."
The next to last sentence is significant.
>Rothman D, DeLuca P, Zurier RB.
>Botanical lipids: effects on inflammation, immune responses, and rheumatoid
>arthritis.
>Semin Arthritis Rheum. 1995 Oct;25(2):87-96. Review.
>PMID: 8578315 [PubMed - indexed for MEDLINE]
>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8578315&dopt=Abstract
Review article. "DATA SYNTHESIS: GLA treatment is associated with
clinical improvement in patients with RA, as evaluated by duration of
morning stiffness, joint pain and swelling, and ability to reduce other
medications. However, studies vary in terms of duration, GLA dose,
whether or not they were placebo controlled, and, if so, what placebo
was used, criteria for evaluation, and use of concomitant medication.
Studies done in vitro generally indicated that GLA reduces lymphocyte
activation and production of mediators of inflammation. CONCLUSIONS: A
small number of studies suggest that GLA is effective treatment for RA
patients. Further controlled studies of its use in RA seem warranted."
>Leventhal LJ, Boyce EG, Zurier RB.
>Treatment of rheumatoid arthritis with blackcurrant seed oil.
>Br J Rheumatol. 1994 Sep;33(9):847-52.
>PMID: 8081671 [PubMed - indexed for MEDLINE]
>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8081671&dopt=Abstract
Clinical trial of blackcurrant seed oil (BCSO); "Treatment with BCSO
resulted in reduction in signs and symptoms of disease activity in
patients with RA (P < 0.05). In contrast, patients given a placebo
showed no change in disease. Overall clinical responses (significant
change in four measures) were no better in the treatment group than in
the placebo group. No patients withdrew from BCSO treatment because of
adverse reactions. However, many patients withdrew because BCSO and its
placebo had to be administered in 15 large capsules daily. Nonetheless,
the study indicates that BCSO is a potentially effective treatment for
active RA. However, means must be found to reduce the size and number of
capsules taken, so that larger studies of longer duration in RA patients
can be done."
>Leventhal LJ, Boyce EG, Zurier RB.
>Treatment of rheumatoid arthritis with gammalinolenic acid.
>Ann Intern Med. 1993 Nov 1;119(9):867-73.
>PMID: 8214997 [PubMed - indexed for MEDLINE]
>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8214997&dopt=Abstract
Test of borage seed oil; "CONCLUSION: Gammalinolenic acid in doses used
in this study is a well-tolerated and effective treatment for active
rheumatoid arthritis. Gammalinolenic acid is available worldwide as a
component of evening primrose and borage seed oils. It is usually taken
in far lower doses than used in this trial. It is not approved in the
United States for the treatment of any condition and should not be
viewed as therapy for any disease. Further controlled studies of its use
in rheumatoid arthritis are warranted."
>Belch JJ, Ansell D, Madhok R, O'Dowd A, Sturrock RD.
>Effects of altering dietary essential fatty acids on requirements for
>non-steroidal anti-inflammatory drugs in patients with rheumatoid arthritis:
>a double blind placebo controlled study.
>Ann Rheum Dis. 1988 Feb;47(2):96-104.
>PMID: 2833184 [PubMed - indexed for MEDLINE]
>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2833184&dopt=Abstract
Evening primrose oil; "Results at 12 months showed a significant
subjective improvement for EPO and EPO/fish oil compared with placebo.
In addition, by 12 months the patients receiving EPO and EPO/fish oil
had significantly reduced their NSAIDs. After 3 months of placebo those
receiving active treatment had relapsed. Despite the decrease in NSAIDs,
measures of disease activity did not worsen. It is suggested that EPO
and EPO/fish oil produce a subjective improvement and allow some
patients to reduce or stop treatment with NSAIDs. There is, however, no
evidence that they act as disease modifying agents."
Disease modifying agents are what are wanted in rheumatoid arthritis.
Some patients, when symptoms lessen, may reduce or stop their use of
NSAIDS, usually to be caught soon after by what some refer to as "the
flare from hell."
>Johnson MM, Swan DD, Surette ME, Stegner J, Chilton T, Fonteh AN,
>Chilton FH.
>Dietary supplementation with gamma-linolenic acid alters fatty acid content
>and eicosanoid production in healthy humans.
>J Nutr. 1997 Aug;127(8):1435-44.
>PMID: 9237935 [PubMed - indexed for MEDLINE]
>http://www.nutrition.org/cgi/content/full/127/8/1435
Healthy volunteers.
>Tate G, Mandell BF, Laposata M, Ohliger D, Baker DG, Schumacher HR,
>Zurier RB.
>Suppression of acute and chronic inflammation by dietary gamma linolenic
>acid.
>J Rheumatol. 1989 Jun;16(6):729-34.
>PMID: 2550629 [PubMed - indexed for MEDLINE]
>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2550629&dopt=Abstract
Ah, the famous old study of induced arthritis in rats. If memory
serves, this is the one cited by the Make Money Fasters pushing, was it
CMO or was it MSM? Who knows if it's applicable to actual humans with
actual diseases?
>Furse RK, Rossetti RG, Seiler CM, Zurier RB.
>Oral administration of gammalinolenic acid, an unsaturated fatty acid with
>anti-inflammatory properties, modulates interleukin-1beta production by
>human monocytes.
>J Clin Immunol. 2002 Mar;22(2):83-91.
>PMID: 11998897 [PubMed - in process]
>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11998897&dopt=Abstract
Unless I misread the abstract this is an in vitro study combined with
some administration of gammalinolenic acid (GLA) to healthy and
arthritic volunteers, for which no protocol or numbers are given.
>Kaku S, Ohkura K, Yunoki S, Nonaka M, Tachibana H, Sugano M, Yamada K.
>Dietary gamma-linolenic acid dose-dependently modifies fatty acid
>composition and immune parameters in rats.
>Prostaglandins Leukot Essent Fatty Acids. 2001 Oct;65(4):205-10.
>PMID: 11728173 [PubMed - indexed for MEDLINE]
>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11728173&dopt=Abstract
Another gammalinolenic acid (GLA) study, with findings similar to
others.
>Furse RK, Rossetti RG, Zurier RB.
>Gammalinolenic acid, an unsaturated fatty acid with anti-inflammatory
>properties, blocks amplification of IL-1 beta production by human monocytes.
>J Immunol. 2001 Jul 1;167(1):490-6.
>PMID: 11418687 [PubMed - indexed for MEDLINE]
>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11418687&dopt=Abstract
Looks very much like the same study above by the same authors--different
journal.
>Tate GA, Mandell BF, Karmali RA, Laposata M, Baker DG, Schumacher HR
>Jr, Zurier RB.
>Suppression of monosodium urate crystal-induced acute inflammation by diets
>enriched with gamma-linolenic acid and eicosapentaenoic acid.
>Arthritis Rheum. 1988 Dec;31(12):1543-51.
>PMID: 2848532 [PubMed - indexed for MEDLINE]
>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2848532&dopt=Abstract
Rats with induced inflammation.
>Barham JB, Edens MB, Fonteh AN, Johnson MM, Easter L, Chilton FH.
>Addition of eicosapentaenoic acid to gamma-linolenic acid-supplemented diets
>prevents serum arachidonic acid accumulation in humans.
>J Nutr. 2000 Aug;130(8):1925-31.
>PMID: 10917903 [PubMed - indexed for MEDLINE]
>http://www.nutrition.org/cgi/content/full/130/8/1925
Four subjects in first protocol, 12 in second, all healthy volunteers;
no information about control groups if any. Goal was to find how to
avoid increase in certain inflammation-raising lipids resulting from
administration of GLA.
>Fan YY, Chapkin RS. R
>Importance of dietary gamma-linolenic acid in human health and nutrition.
>J Nutr. 1998 Sep;128(9):1411-4. Review.
>PMID: 9732298 [PubMed - indexed for MEDLINE]
>http://www.nutrition.org/cgi/content/full/128/9/1411
"On January 27, 1993, the United States Court of Appeals for the Seventh
Circuit ruled that -linolenic acid [GLA, 18:3(n-6)]2 containing oil is a
single food ingredient and therefore not subject to food additive
regulation. As a result of this legislation, GLA-containing oils
(primrose oil, blackcurrant seed oil and borage oil) have become
increasingly popular with retailers and are being sold as encapsulated
supplements. In view of this burgeoning interest, it is estimated that a
sustainable market for GLA-plant oils in the United States is
developing. To evaluate GLA-related nutraceuticals critically, it is
essential to elucidate the mechanisms underlying the relationship
between dietary GLA and health maintenance. This review will focus on
recent studies that address the physiologic functions and mechanisms of
action of GLA in humans and relevant disease model systems."
"Watch your wallet." (Thanks, drdoc of South Africa.)
My wrap-up based on these references:
Fish oil seems to have no more demonstrated benefits than any of the
vegetable-derived unsaturated oil used in other tests.
Some benefits were noted in some trials for sufferers of rheumatoid
arthritis:
- shorter period of morning stiffness
- subjective reduction of joint pain
However, the primary goal of arthritis treatment is to slow down the
erosion of joints. None of these trials addressed that issue, nor could
they in trials over periods of only a few weeks. Neither could they
with healthy subjects, as several trials had.
ISTM the majority of trials concluded that further testing was called
for, which is reasonable, rather than claiming they had found
significant treatment methods for immediate use. Some of the tested
medications apparently are not approved for use in the US.
I guess I'm not overwhelmed by the strength of the data. Consider me
whelmed, and now I suppose I know why so few of my acquaintances in the
arthritis newsgroups are using these treatments so far.
--
Don
don...@covad.net
Matti Narkia
<uaa9pugotb8ql6ug6...@4ax.com> Don Kirkman <don...@covad.net>
wrote:
>
>I was rather hoping for double blind study findings from rheumatologists
>instead of from nutritionists. Got any?
I'm not sure if you are familiar how medical research is financed nowadays?
I've done some personal research on that and related topics and could
provide you a few references if you wish. The bottom line is that most money
comes from the pharmaceutical companies, especially the money which goes to
drug research. Medical researchers including rheumatologists may have to
work a lot harder to get from the government a small amount of money for the
research of unpatentable natural substances such as fish oil or GLA than to
get a generous grant from pharmaceutical company for the research of its new
drug.
For nutrition researchers the situation is different. Its their job to
research nutrients, not drugs. Their work is usually financed by a
university directly, i.e. by the government. They don't expect to get
generous grants from commercial enterprises. Because money is more limited,
even the sizes of the trials have their limits, which do not usually rise to
the sizes required for FDA approval or something to that effect in various
other countries.
--
Matti Narkia
Matti Narkia
wrote:
>It seems to me I heard somewhere that Matti Narkia wrote in article
><nns6pucd2hdob764r...@4ax.com>:
>>
>>Another matter is that some people do get kidney damage from the long term
>>use of NSAIDs.
>
>Liver damage seems to be the main thing rheumatologists regularly
>monitor for, and I suspect this is indicated in the published
>information for any of the NSAIDS or DMARDs. There are a few of these
>implicated in kidney problems, of course, and in some of the arthritises
>eyes, lungs, and other tissues may also be affected by the disease
>and/or the medications.
>
I think that almost any medication could affect liver. For young people
with previously healthy kidneys the use of NSAIDs rarely affect kidneys. But
kidney function reduces with age, and for older people long term use of
large doses of NSAIDs could pose risks, especially when used in doses
required in arthritis. See
Field TS, Gurwitz JH, Glynn RJ, Salive ME, Gaziano JM, Taylor JO, Hennekens
CH. R
The renal effects of nonsteroidal anti-inflammatory drugs in older people:
findings from the Established Populations for Epidemiologic Studies of the
Elderly.
J Am Geriatr Soc. 1999 May;47(5):507-11.
PMID: 10323640 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10323640&dopt=Abstract
"CONCLUSION: Community-dwelling older people who use NSAIDs
tend to have higher levels of common laboratory markers of
renal dysfunction. This hypothesis requires further testing in
prospective cohort studies designed a priori to evaluate these
issues."
about
ANALGESICS AND YOUR KIDNEYS
National Kidney Foundation of Illinois
http://www.nkfi.org/factsheets/Analgesi.html
"What are NSAIDs? Are they safe to take?
Nonsteroidal anti-inflammatory drugs (NSAIDs) are a group of
painkillers, including drugs like ibuprofen, ketoprofen,
naproxen and indomethacin. Some of them are available over-
the-counter. This includes some forms of ibuprofen (Advil,
Motrin, Nuprin), ketoprofen (Orudis) and naproxen (Aleve).
NSAIDs are safe when taken as directed for a limited period of
time. However, patients with certain conditions such as
underlying kidney disease, heart disease, severe high blood
pressure or liver disease, and elderly patients taking
diuretics, should be discouraged from taking these drugs as
they may cause acute kidney failure and even progressive
kidney damage.
I have arthritis. What painkillers can I take that won’t hurt
my kidneys?
You should speak to your doctor about what the best choice is
for you. Your kidney function should be monitored carefully,
especially if you already have a kidney disease or are at risk
for developing kidney disease (for example, if you have
diabetes or severe high blood pressure). This would consist of
following your serum creatinine concentration (by means of a
simple blood test) at regular intervals."
Colorado HealthSite
http://www.coloradohealthsite.org/chnqna.html?Kidney%20Disease?Medications?2853
The Facts Of NSAIDs
http://arthritis.about.com/library/weekly/aa061097.htm
"Adverse effects of NSAIDs which can occur at any time include renal
(kidney) failure, hepatic (liver) dysfunction, bleeding, and gastric
(stomach) ulceration"
>> Then they may be forced to stop NSAIDs and try something
>>else, fish oil, for example, and hope it works.
>
>Actually they would be more apt to switch to a different NSAID or DMARD.
>There are increasing numbers of them available, and most newer ones have
>less serious side effects. Many patients have to try several before
>they find one that works for their particular case--rheumatic arthritis
>in particular is a very individualized disease. Some of the NSAIDs and
>DMARDs seem to burn out after a few years of use, and in that case also
>a switch is indicated.
>
>>If it does, the kidney
>>damage would have been avoidable with the earlier use of fish oil. So
>>according to my logic it's wise to try fish oil as early as possible. What
>>you have to lose? Unnecessary payment for three month's supply of fish oil,
>>if it doesn't work. That's negligible compared with the benefits, if it does
>>work.
>
>Liver.
As for NSAIDs, kidneys and liver. I know arthritic patients who have had to
go to dialysis because of irreversible kidney failure after years of high
dose NSAID use.
>I'm afraid to ask, because I see a can of worms sitting there
>untouched and because this is really a *cardiology* newsgroup, but what
>benefit has fish oil (read "any of the oils that have been studied") for
>the kidneys over a routine good diet? Never mind.
IMHO the key words in your comment are "a routine good diet". What i
s your conception about it and how many people in your opinion are willing
or able to follow it?
You probably are aware about the very pro-inflammatory nature of the common
dietary practices in the western world. What makes it pro-inflammatory? A
disproportional ratio of precursors for mediators of inflammatory response
to precursor for mediators of anti-inflammatory response.
Mediators of inflammation (such as prostaglandins E2 (PGE2) and 4-series
leukotrienes) are catalyzed from the omega-6 fatty acid arachidonic acid
(AA) by inflammatory enzymes cyclooxygenase-2 (COX-2) and 5-lipoxygenase
(5-LOX). COX-2 catalyzes PGE2 and 5-LOX the leukotrienes. Most
anti-inflammatory response mediators are produced from omega-3 pathway, for
example prostaglandin E3 and series-5 leukotrienes from EPA in fish oil.
EPA also competes with AA from COX-2 and 5-LOX enzymes and even inhibits
enzyme delta-5-desaturase, which is needed in the production of AA from its
omega-6 precursors. So in addition to serving as substrate for
anti-inflammatory mediators, EPA (and some other omega-3 fatty acids) in
more than one way also restricts the production of pro-inflammatory
mediators.
You'll find the detailed explanations of the mechanisms involved in
inflammatory and anti-inflmmatory responses from the references I provided.
The bottom line is that omega-6 fatty acids - with the exception of GLA -
are pro-inflammatory, and omega-3 fatty acids anti-inflammatory.
To answer your question, in most cases fish oil probably has not much
benefit over a routine good diet, provided that people know what is required
from a good anti-inflammatory diet, and are willing and able to follow it.
If any of these conditions is not fulfilled, use of fish oil is an easy way
out, but is still admittedly perhaps only partially effective, if omega-6
intake remains high.
In a good anti-inflammatory diet we should first exclude all visible omega-6
fatty acids. This includes practically all commercial oils. Only cooking
oils we use in our family are extra virgin olive oil, which does not
tolerate very high temperatures (which you shouldn't use in cooking anyway),
and almond oil, which does tolerate rather high temperatures. These oils are
both very high in monounsaturated (mostly omega-9) fatty acids (which are
stable and neutral (no known effect on inflammation)) and low in omega-6 and
omega-3 fatty acids. Low in omega-3, because omega-3 fatty acids, especially
alpha-linolenic acid, can form toxic, even carcinogenic compounds when
heated.
To further restrict omega-6s, we perhaps should quit using margarine and
switch to butter. Or, better still, not to use either of them. We may also
have to restrict the use of grain products, which are a major source of
omega-6 fatty acids. This includes bread, cakes, biscuits etc.. We may have
to restrict the consumption of the meat from grain-fed animals, because
their meat has relatively high omega-6 content. Meat from grass-fed animals
(naturally mostly game) has lower omega-6 and higher omega-3 content, so it
would be better choice if available.
In a good anti-inflammatory diet omega-3 fatty acids come from fatty fish.
Alpha-linolenic acid available from plant sources has more limited
anti-inflammatory effect, because its slow and restricted conversion to EPA,
the main precursor for anti-inflammatory mediators.
As you see from above, achieving a good anti-inflammatory omega-6/omega-3
ratio is not as easy in the modern world, as it was in paleolithic time.
To compensate for what we cannot do, we could reduce omega-6 as much as we
can, and then take some fish oil to further improve the ratio.
--
Matti Narkia
Matti Narkia
wrote:
>
>>Jaya T. Venkatraman and Wei-chia Chu
>>Effects of Dietary omega-3 and omega-6 Lipids and Vitamin E on Serum
>>Cytokines, Lipid Mediators and Anti-DNA Antibodies in a Mouse Model for
>>Rheumatoid>Arthritis
>>Journal of the American College of Nutrition, Vol. 18, No. 6, 602-613 (1999)
>>http://www.jacn.org/cgi/content/full/18/6/602
>
>Mouse study.
>
Fish Oil and Vitamin E Reduce Levels of Pro-Inflammatory Proteins in
Rheumatoid Arthritis, UB Study Shows
Paper named best scientific paper of year by American College of Nutrition
October 31, 2000
http://www.buffalo.edu/news/fast-execute.cgi/article-page.html?article=49210009
Fish oil, vitamin E help arthritis symptoms
Nutritional supplements shown to be promising therapies for symptoms of
disease
UB, Reporter, University at Buffalo, THURSDAY, November 2, 2000
http://www.buffalo.edu/reporter/vol32/vol32n11/n1.html
>>GLA
>>---
>
>Of course the topic you've been pushing has been fish oil, not these
>others. :-)
>
Actually, I'm not been pushing either of them. I just happened in a
discussion to present a remark about anti-inflammatory nature of both of
these oils, and was challenged to produce some evidence about fish oil.
In my remark I did not specifically mention arthritis, but evidence was for
some reason asked especially for arthritis.
>>Jill JF Belch and Alexander Hill
>>Evening primrose oil and borage oil in rheumatologic conditions
>>Am J Clin Nutr 2000 71: 352-356
>>http://www.ajcn.org/cgi/content/full/71/1/352S
>
>Review article re: essential fatty acids, not limited to fish oil.
>
Not really, it's a review article limited to two GLA containing oils,
evening primrose oil and borage oil. As I mentioned above, my original
remark was about fish oil _and_ GLA. This reference and those who follow it
are about GLA part, not about fish oil.
>>Zurier RB, Rossetti RG, Jacobson EW, DeMarco DM, Liu NY, Temming JE,
>>White BM, Laposata M.
>>gamma-Linolenic acid treatment of rheumatoid arthritis. A randomized,
>>placebo-controlled trial.
>>Arthritis Rheum. 1996 Nov;39(11):1808-17.
>>PMID: 8912502 [PubMed - indexed for MEDLINE]
>>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8912502&dopt=Abstract
>
>12-month study, first six months double blind. "CONCLUSION: GLA at
>doses used in this study is a well- tolerated and effective treatment
>for active RA. GLA is available as a component of several plant seed
>oils and is usually taken in far lower doses than were used in this
>trial. It is not approved in the United States for the treatment of any
>condition, and should not be viewed as therapy for any disease. Further
>controlled studies of its [use] in RA are warranted."
>
>The next to last sentence is significant.
>
On the contrary, it has nothing to do with the science. Don't confuse
science with local regulations, politics or ways the market economy works.
In my country there are no restrictions for GLA's use as a therapy, but it's
not officially approved for any treatment. This is the case for most natural
unpatentable substances, because there is no incentive for commercial
enterprises to finance their large scale trials required for official
approval.
>
>>Furse RK, Rossetti RG, Seiler CM, Zurier RB.
>>Oral administration of gammalinolenic acid, an unsaturated fatty acid with
>>anti-inflammatory properties, modulates interleukin-1beta production by
>>human monocytes.
>>J Clin Immunol. 2002 Mar;22(2):83-91.
>>PMID: 11998897 [PubMed - in process]
>>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11998897&dopt=Abstract
>
>Unless I misread the abstract this is an in vitro study combined with
>some administration of gammalinolenic acid (GLA) to healthy and
>arthritic volunteers, for which no protocol or numbers are given.
>
Double blind trials are only tiny part of medical science, which are needed
for further validation of earlier results - and eventually also for the
approval of a drug. I'm personally also interested in the mechanisms of
action.
.>
>>Barham JB, Edens MB, Fonteh AN, Johnson MM, Easter L, Chilton FH.
>>Addition of eicosapentaenoic acid to gamma-linolenic acid-supplemented diets
>>prevents serum arachidonic acid accumulation in humans.
>>J Nutr. 2000 Aug;130(8):1925-31.
>>PMID: 10917903 [PubMed - indexed for MEDLINE]
>>http://www.nutrition.org/cgi/content/full/130/8/1925
>
>Four subjects in first protocol, 12 in second, all healthy volunteers;
>no information about control groups if any. Goal was to find how to
>avoid increase in certain inflammation-raising lipids resulting from
>administration of GLA.
>
This is IMHO a very important study describing the interaction between EPA
and GLA.
Omega-6 fatty acid arachidonic acid (AA) is a substrate for mediators of
inflammation (such as prostaglandin E2 and 4-series leukotrienes). GLA is
the only anti-inflammatory omega-6 series fatty acid, but as the picture
Figure 1. Metabolism of gamma-linolenic acid
http://www.nutrition.org/cgi/content/full/128/9/1411/F1
shows it is also a precursor of pro-inflammatory omega-6 fatty acid AA.
Therefore a question arises that will the GLA supplementation increase AA
levels so much that AA's pro-inflammatory effects would exceed GLA's
anti-inflmmatory effects? The above study shows that simultaneous use of EPA
(in fish oil) with GLA prevents the rise in AA level (because EP inhibits
enzyme delta-5-saturase needed in AA synthesis, see
http://www.nutrition.org/cgi/content/full/130/8/1925/F7 )
This is not a study about efficacy of either GLA or EPA. It just shows that
if you use GLA, it may be advantageous (mechanistically assessed) using
simultaneously also EPA (in fish oil). I someone wanted to test this
combination as drug, he would have to do a double blind trial. But
information provided by this study may have a certain value for people
planning to use GLA as a nutritional supplement.
>My wrap-up based on these references:
>
>Fish oil seems to have no more demonstrated benefits than any of the
>vegetable-derived unsaturated oil used in other tests.
>
The effective substance in these vegetable-derived unsaturated oils is GLA.
Only few vegetable oils contain so high percentage of GLA that they could be
regarded potentially therapeutically useful. Evening primrose oil,
blackcurrant oil and borage oils are the only ones which come to my mind
right know.
The anti-inflmmatory mechanisms of fish oil and GLA are different, but the
subjectively observed results could be similar and of similar efficacy.
>Some benefits were noted in some trials for sufferers of rheumatoid
>arthritis:
>- shorter period of morning stiffness
>- subjective reduction of joint pain
Indeed.
>However, the primary goal of arthritis treatment is to slow down the
>erosion of joints. None of these trials addressed that issue, nor could
>they in trials over periods of only a few weeks. Neither could they
>with healthy subjects, as several trials had.
>
They could and should not address that issue, because they can IMHO only be
regarded as symptom relievers. Even so, their use is justified, if it enable
at least to reduce doses of such medications, which are known to be
associated with risk of harmful side effect in very long term use.
IMHO the main function of fish oil is to correct the inflammatory nature of
omega-6/omega-3 ratio in modern diets to less inflammatory direction.
GLA has two separate anti-inflammatory mechanisms
( http://www.nutrition.org/cgi/content/full/128/9/1411/F1 ):
it serves as substrate for 1-series anti-inflmmatory prostaglandins and
indirectly, via its metabolite 15-HETrE, inhibits inflammatory
5-lipoxygenase enzyme. Enzyme delta-6-desaturase is need in the synthesis of
GLA from essential omega-6 fatty acid linoleic acid (LA). Aging and disease
can reduce the availability of this enzyme and therefore cause GLA
deficiency.
>ISTM the majority of trials concluded that further testing was called
>for, which is reasonable, rather than claiming they had found
>significant treatment methods for immediate use. Some of the tested
>medications apparently are not approved for use in the US.
>
The significance of this research is that the mechanisms by which fats in
food affect the inflammation have been clarified. Interested individuals can
use this knowledge to modify their diet to less inflammatory direction.
If diet modification is too difficult does not quit reach desired results,
supplements such as fish oil could be tried. If the insufficiency of
delta-6-desaturase enzyme is the problem, GLA supplements may be needed.
>I guess I'm not overwhelmed by the strength of the data. Consider me
>whelmed, and now I suppose I know why so few of my acquaintances in the
>arthritis newsgroups are using these treatments so far.
You must be aware that the financial resource available for the research of
natural unpatentable substances such as nutrients cannot in the market
economy compete with investments available for patented drugs.
I'm surprise, if more of the people you know arthritis newsgroups are
neither modifying their diet towards less inflammatory direction nor using
anti-inflammatory supplements, especially because Liz G. seemed to have had
good results with fish oil and GLA. Perhaps not everyone has the patience to
carry on for 3 months before any results can be expected. Good be to some
extent cultural matter as well. Here in Finland quite a many arthritis
patients use fish oil and/or GLA in addition to their medication.
--
Matti Narkia
Pierre L
"Matti Narkia" <mn...@despammed.com> wrote in message
news:f2kapukq2srann9v7...@4ax.com...
> Fri, 27 Sep 2002 16:48:56 -0700 in article
> <uaa9pugotb8ql6ug6...@4ax.com> Don Kirkman
<don...@covad.net>
> wrote:
> >
> >I was rather hoping for double blind study findings from rheumatologists
> >instead of from nutritionists. Got any?
>
> I'm not sure if you are familiar how medical research is financed
nowadays?
> I've done some personal research on that and related topics and could
> provide you a few references if you wish. The bottom line is that most
money
> comes from the pharmaceutical companies, especially the money which goes
to
> drug research. Medical researchers including rheumatologists may have to
> work a lot harder to get from the government a small amount of money for
the
> research of unpatentable natural substances such as fish oil or GLA than
to
> get a generous grant from pharmaceutical company for the research of its
new
> drug.
>
>
> --
> Matti Narkia
If that's the case, then even research and clinical trials involving fish
oil are suspect, because they use very specific formulations of fish oil
such as MaxEPA and Omecor provided by specific companies that make these
(who have just as much financial interest in the outcome as do
pharmaceutical companies in other trials and research.
It's also a "buyer beware" situation with fish oil, as with most
supplements, as reported for example at:
http://consumerlabs.com/results/omega3.asp
..which found the amounts of EPA/DHA not in accordance with what is stated
on the label with many brands of fish oil.
Pierre
Don Kirkman
>Fri, 27 Sep 2002 16:48:56 -0700 in article
><uaa9pugotb8ql6ug6...@4ax.com> Don Kirkman <don...@covad.net>
>wrote:
>>I was rather hoping for double blind study findings from rheumatologists
>>instead of from nutritionists. Got any?
>I'm not sure if you are familiar how medical research is financed nowadays?
Yes, I am.
>I've done some personal research on that and related topics and could
>provide you a few references if you wish. The bottom line is that most money
>comes from the pharmaceutical companies, especially the money which goes to
>drug research. Medical researchers including rheumatologists may have to
>work a lot harder to get from the government a small amount of money for the
>research of unpatentable natural substances such as fish oil or GLA than to
>get a generous grant from pharmaceutical company for the research of its new
>drug.
This is a valid point, but what proportion of the revenue from
nutritionals is being spent on scientifically valid research on their
safety and efficacy? Where are *those* revenue dollars going? How
would those companies' profits be affected if they financed rigid double
blind studies?
>For nutrition researchers the situation is different. Its their job to
>research nutrients, not drugs. Their work is usually financed by a
>university directly, i.e. by the government. They don't expect to get
>generous grants from commercial enterprises. Because money is more limited,
>even the sizes of the trials have their limits, which do not usually rise to
>the sizes required for FDA approval or something to that effect in various
>other countries.
Aren't nutritional studies subject to input from marketers of
nutritionals fully as much as medical studies are to input from
pharmaceutical companies--and with less rigid scrutiny of the
connections?
--
Don
don...@covad.net
Don Kirkman
>Fri, 27 Sep 2002 16:48:56 -0700 in article
><rea9pu0fhv0t6a6c0...@4ax.com> Don Kirkman <don...@covad.net>
>wrote:
>>>Jaya T. Venkatraman and Wei-chia Chu
>>>Effects of Dietary omega-3 and omega-6 Lipids and Vitamin E on Serum
>>>Cytokines, Lipid Mediators and Anti-DNA Antibodies in a Mouse Model for
>>>Rheumatoid>Arthritis
>>>Journal of the American College of Nutrition, Vol. 18, No. 6, 602-613 (1999)
>>>http://www.jacn.org/cgi/content/full/18/6/602
>>Mouse study.
>Buffalo University seems to be proud of it ;-) :
Of course; mouse studies may be very high quality work, but they aren't
directly applicable to human medical issues.
>>>GLA
>>>---
>>Of course the topic you've been pushing has been fish oil, not these
>>others. :-)
>Actually, I'm not been pushing either of them. I just happened in a
>discussion to present a remark about anti-inflammatory nature of both of
>these oils, and was challenged to produce some evidence about fish oil.
>In my remark I did not specifically mention arthritis, but evidence was for
>some reason asked especially for arthritis.
>>>Jill JF Belch and Alexander Hill
>>>Evening primrose oil and borage oil in rheumatologic conditions
>>>Am J Clin Nutr 2000 71: 352-356
>>>http://www.ajcn.org/cgi/content/full/71/1/352S
>>Review article re: essential fatty acids, not limited to fish oil.
>Not really, it's a review article limited to two GLA containing oils,
>evening primrose oil and borage oil. As I mentioned above, my original
>remark was about fish oil _and_ GLA. This reference and those who follow it
>are about GLA part, not about fish oil.
I think that's what I said; it IS a review article.
>>>Zurier RB, Rossetti RG, Jacobson EW, DeMarco DM, Liu NY, Temming JE,
>>>White BM, Laposata M.
>>>gamma-Linolenic acid treatment of rheumatoid arthritis. A randomized,
>>>placebo-controlled trial.
>>>Arthritis Rheum. 1996 Nov;39(11):1808-17.
>>>PMID: 8912502 [PubMed - indexed for MEDLINE]
>>>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8912502&dopt=Abstract
>>12-month study, first six months double blind. "CONCLUSION: GLA at
>>doses used in this study is a well- tolerated and effective treatment
>>for active RA. GLA is available as a component of several plant seed
>>oils and is usually taken in far lower doses than were used in this
>>trial. It is not approved in the United States for the treatment of any
>>condition, and should not be viewed as therapy for any disease. Further
>>controlled studies of its [use] in RA are warranted."
>>The next to last sentence is significant.
>On the contrary, it has nothing to do with the science. Don't confuse
>science with local regulations, politics or ways the market economy works.
>In my country there are no restrictions for GLA's use as a therapy, but it's
>not officially approved for any treatment. This is the case for most natural
>unpatentable substances, because there is no incentive for commercial
>enterprises to finance their large scale trials required for official
>approval.
So the US is not the only country not approving this as medical
treatment, right? This throws it into the nutritional camp.
>>>Furse RK, Rossetti RG, Seiler CM, Zurier RB.
>>>Oral administration of gammalinolenic acid, an unsaturated fatty acid with
>>>anti-inflammatory properties, modulates interleukin-1beta production by
>>>human monocytes.
>>>J Clin Immunol. 2002 Mar;22(2):83-91.
>>>PMID: 11998897 [PubMed - in process]
>>>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11998897&dopt=Abstract
>>Unless I misread the abstract this is an in vitro study combined with
>>some administration of gammalinolenic acid (GLA) to healthy and
>>arthritic volunteers, for which no protocol or numbers are given.
>Double blind trials are only tiny part of medical science, which are needed
>for further validation of earlier results - and eventually also for the
>approval of a drug. I'm personally also interested in the mechanisms of
>action.
The mechanisms of an action a nice theoretical stuff, but many
medications are effective even with unknown mechanisms. Does it work
and is it safe? Double blind studies.
>>>Barham JB, Edens MB, Fonteh AN, Johnson MM, Easter L, Chilton FH.
>>>Addition of eicosapentaenoic acid to gamma-linolenic acid-supplemented diets
>>>prevents serum arachidonic acid accumulation in humans.
>>>J Nutr. 2000 Aug;130(8):1925-31.
>>>PMID: 10917903 [PubMed - indexed for MEDLINE]
>>>http://www.nutrition.org/cgi/content/full/130/8/1925
>>Four subjects in first protocol, 12 in second, all healthy volunteers;
>>no information about control groups if any. Goal was to find how to
>>avoid increase in certain inflammation-raising lipids resulting from
>>administration of GLA.
>This is IMHO a very important study describing the interaction between EPA
>and GLA.
But healthy volunteers aren't surrogates for rheumatics, twelve subjects
is a very small _n_, and a control group is lacking.
[...]
>This is not a study about efficacy of either GLA or EPA. It just shows that
>if you use GLA, it may be advantageous (mechanistically assessed) using
>simultaneously also EPA (in fish oil). I someone wanted to test this
>combination as drug, he would have to do a double blind trial. But
>information provided by this study may have a certain value for people
>planning to use GLA as a nutritional supplement.
It "may be advantageous" but this is precisely where rigid scientific
testing needs to begin.
>>My wrap-up based on these references:
>>Fish oil seems to have no more demonstrated benefits than any of the
>>vegetable-derived unsaturated oil used in other tests.
>>
>The effective substance in these vegetable-derived unsaturated oils is GLA.
>Only few vegetable oils contain so high percentage of GLA that they could be
>regarded potentially therapeutically useful. Evening primrose oil,
>blackcurrant oil and borage oils are the only ones which come to my mind
>right know.
Aren't they the ones that were in the tests?
>The anti-inflmmatory mechanisms of fish oil and GLA are different, but the
>subjectively observed results could be similar and of similar efficacy.
"Could be" and "similar" are fairly loose criteria for scientific
medicine.
>>Some benefits were noted in some trials for sufferers of rheumatoid
>>arthritis:
>>- shorter period of morning stiffness
>>- subjective reduction of joint pain
>Indeed.
Indeed. Meanwhile what's happening to the joints?
>>However, the primary goal of arthritis treatment is to slow down the
>>erosion of joints. None of these trials addressed that issue, nor could
>>they in trials over periods of only a few weeks. Neither could they
>>with healthy subjects, as several trials had.
>They could and should not address that issue, because they can IMHO only be
>regarded as symptom relievers. Even so, their use is justified, if it enable
>at least to reduce doses of such medications, which are known to be
>associated with risk of harmful side effect in very long term use.
"Justified, *if* it enable . . . to reduce doses;" that's the "if" that
hasn't been answered. In fact in some of the studies the NSAIDS were
part of the protocol, and nothing is known about the long term results
of either method of treatment. Only long-term controlled studies can
tell us.
>IMHO the main function of fish oil is to correct the inflammatory nature of
>omega-6/omega-3 ratio in modern diets to less inflammatory direction.
Mechanisms aside, how about just adding more fish to the diet?
>>ISTM the majority of trials concluded that further testing was called
>>for, which is reasonable, rather than claiming they had found
>>significant treatment methods for immediate use. Some of the tested
>>medications apparently are not approved for use in the US.
>The significance of this research is that the mechanisms by which fats in
>food affect the inflammation have been clarified. Interested individuals can
>use this knowledge to modify their diet to less inflammatory direction.
>If diet modification is too difficult does not quit reach desired results,
>supplements such as fish oil could be tried. If the insufficiency of
>delta-6-desaturase enzyme is the problem, GLA supplements may be needed.
The significance of knowing the mechanisms is that we can do strong
reliable research looking for effectiveness and safety.
>>I guess I'm not overwhelmed by the strength of the data. Consider me
>>whelmed, and now I suppose I know why so few of my acquaintances in the
>>arthritis newsgroups are using these treatments so far.
>You must be aware that the financial resource available for the research of
>natural unpatentable substances such as nutrients cannot in the market
>economy compete with investments available for patented drugs.
I've answered this elsewhere, but if the nutritional companies cared to
feed their profits back into rigorous studies as the pharmaceutical
companies do perhaps we could all be satisfied.
>I'm surprise, if more of the people you know arthritis newsgroups are
>neither modifying their diet towards less inflammatory direction nor using
>anti-inflammatory supplements, especially because Liz G. seemed to have had
>good results with fish oil and GLA. Perhaps not everyone has the patience to
>carry on for 3 months before any results can be expected. Good be to some
>extent cultural matter as well. Here in Finland quite a many arthritis
>patients use fish oil and/or GLA in addition to their medication.
Those folks are pretty smart cookies, and although many of them use
supplements they work with their doctors, stick with their medications,
and don't suffer marketers of nutritionals gladly. They know when
something helps and when it doesn't.
--
Don
don...@covad.net
Don Kirkman
>Fri, 27 Sep 2002 16:48:56 -0700 in article
><72l9pu4l9hhabaru1...@4ax.com> Don Kirkman <don...@covad.net>
>wrote:
>>It seems to me I heard somewhere that Matti Narkia wrote in article
>><nns6pucd2hdob764r...@4ax.com>:
>>>Another matter is that some people do get kidney damage from the long term
>>>use of NSAIDs.
>>Liver damage seems to be the main thing rheumatologists regularly
>>monitor for, and I suspect this is indicated in the published
>>information for any of the NSAIDS or DMARDs. There are a few of these
>>implicated in kidney problems, of course, and in some of the arthritises
>>eyes, lungs, and other tissues may also be affected by the disease
>>and/or the medications.
>I think that almost any medication could affect liver. For young people
>with previously healthy kidneys the use of NSAIDs rarely affect kidneys. But
>kidney function reduces with age, and for older people long term use of
>large doses of NSAIDs could pose risks, especially when used in doses
>required in arthritis. See
Stipulated that your citations refer to kidney problems *in older
"geriatric" patients*; arthritis may begin in childhood or at any other
age.
[...]
>>>If it does, the kidney
>>>damage would have been avoidable with the earlier use of fish oil. So
>>>according to my logic it's wise to try fish oil as early as possible. What
>>>you have to lose? Unnecessary payment for three month's supply of fish oil,
>>>if it doesn't work. That's negligible compared with the benefits, if it does
>>>work.
>>Liver.
>As for NSAIDs, kidneys and liver. I know arthritic patients who have had to
>go to dialysis because of irreversible kidney failure after years of high
>dose NSAID use.
The liver risk seems to be the major factor and the main concern of
rheumatologists.
>>I'm afraid to ask, because I see a can of worms sitting there
>>untouched and because this is really a *cardiology* newsgroup, but what
>>benefit has fish oil (read "any of the oils that have been studied") for
>>the kidneys over a routine good diet? Never mind.
>IMHO the key words in your comment are "a routine good diet". What i
>s your conception about it and how many people in your opinion are willing
>or able to follow it?
>You probably are aware about the very pro-inflammatory nature of the common
>dietary practices in the western world. What makes it pro-inflammatory? A
>disproportional ratio of precursors for mediators of inflammatory response
>to precursor for mediators of anti-inflammatory response.
[...]
>To answer your question, in most cases fish oil probably has not much
>benefit over a routine good diet, provided that people know what is required
>from a good anti-inflammatory diet, and are willing and able to follow it.
>If any of these conditions is not fulfilled, use of fish oil is an easy way
>out, but is still admittedly perhaps only partially effective, if omega-6
>intake remains high.
But there's little profit in a "routine good diet," I suppose. :-)
>As you see from above, achieving a good anti-inflammatory omega-6/omega-3
>ratio is not as easy in the modern world, as it was in paleolithic time.
>To compensate for what we cannot do, we could reduce omega-6 as much as we
>can, and then take some fish oil to further improve the ratio.
How little we really know about the paleolithic diet, but we have some
lovely speculations.
--
Don
don...@covad.net
Matti Narkia
<8p7cpuoagq3rn733t...@4ax.com> Don Kirkman <don...@covad.net>
wrote:
>It seems to me I heard somewhere that Matti Narkia wrote in article
><6nlapucqlvdrsb30g...@4ax.com>:
>
>>I think that almost any medication could affect liver. For young people
>>with previously healthy kidneys the use of NSAIDs rarely affect kidneys. But
>>kidney function reduces with age, and for older people long term use of
>>large doses of NSAIDs could pose risks, especially when used in doses
>>required in arthritis. See
>
>Stipulated that your citations refer to kidney problems *in older
>"geriatric" patients*; arthritis may begin in childhood or at any other
>age.
>
I guess you didn't read the text from the page
Colorado HealthSite
http://www.coloradohealthsite.org/chnqna.html?Kidney%20Disease?Medications?2853
"Question: I have been reading your other question answered on
NSAIDS and kidney disease, and would like to know if you can
please tell me why NSAIDS are potentially dangerous to people
suffering Kidney Disease?
Answer: NSAIDS or non-steroidal antiinflammatory drugs have a
number of potential side effects on kidneys. One of the more
common side effects is due to the role NSAIDS may have in
blood flow to the glomeruli which are the filtering units of
the kidney. In normal settings, there is not much of an effect
but in conditions wherein the kidney is very dependent on
blood flow such as heart failure, liver disease, dehydration
and other conditions this could be significant enough to cause
kidney failure. In someone with existing kidney disease this
can be further exacerbated.
Another potential effect of NSAIDS on the kidneys is the
development of "acute interstitial nephritis" which is similar
to the kidneys having an allergic reaction to the drug causing
kidney damage. This would sometimes present with a rash and
fever associated with worsening of kidney function but could
also be "silent" with no overt symptoms other than the kidney
failure. Stopping the drug usually leads to resolution of the
condition but sometimes steroids may be necessary.
Another condition that is associated with NSAIDS is the
"nephrotic syndrome" which is manifested by large amounts of
protein in the urine with or without worsening of kidney
function. Again, this almost always resolves with stopping the
drug.
The long term use of NSAIDS has also been associated chronic
kidney damage. Kidney function gradually begins to deteriorate
over a long period of time. This has been seen with the use of
NSAIDS for several months to years. It is important to
remember that a majority of patients taking NSAIDS do not
develop kidney problems and that the above mentioned
conditions are potential side effects that need to be
monitored for closely. Dennis Roy Imperio, M.D., Private
Practice, Sarasota, Florida May 2001"
>
>The liver risk seems to be the major factor and the main concern of
>rheumatologists.
>
I guess that to some extent it depends on the drug. As the quote above
shows, there is also reason to worry about kidneys. Still, whether liver or
kidney is more vulnerable to a particular drug is not an issue here. The
issue is that the drugs may have dangerous side effects and their risks may
be reduced if doses of the drugs could be reduced.
>>To answer your question, in most cases fish oil probably has not much
>>benefit over a routine good diet, provided that people know what is required
>>from a good anti-inflammatory diet, and are willing and able to follow it.
>>If any of these conditions is not fulfilled, use of fish oil is an easy way
>>out, but is still admittedly perhaps only partially effective, if omega-6
>>intake remains high.
>
>But there's little profit in a "routine good diet," I suppose. :-)
>
What's your point? Where do you live? In a communist country or a in a
market economy? Do yo work free or do you get paid? Do you get your food
free? How about your house? Free, too? Especially, do you get your "routine
good diet" free? And even if _you_ do, _someone_ has to pay for it. There is
no such thing as a free lunch, remember?
>>As you see from above, achieving a good anti-inflammatory omega-6/omega-3
>>ratio is not as easy in the modern world, as it was in paleolithic time.
>>To compensate for what we cannot do, we could reduce omega-6 as much as we
>>can, and then take some fish oil to further improve the ratio.
>
>How little we really know about the paleolithic diet, but we have some
>lovely speculations.
You have an odd way of picking single irrelevant words from the text you
comment. I don't care what we know about the paleolithic diet, it's not
relevant for the matter at hand. We have a fairly good understanding how
food affects inflammatory reactions. Polyunsaturated fats play a major part
in it. We know how to shift the diet towards more anti-inflammatory
direction. From what I've read, the paleolithic diet could've been
anti-inflammatory, because food items rich in omega-6 were not available.
If it wasn't anti-inflammatory, it doesn't matter. We know what foods are
anti-inflammatory and what are pro-inflammatory, we don't have to stick any
particular label in the diet based on using this knowledge, and especially
we don't need the knowledge about the composition of the paleolithic diet to
do that.
--
Matti Narkia
Don Kirkman
>Sat, 28 Sep 2002 15:40:12 -0700 in article
><8p7cpuoagq3rn733t...@4ax.com> Don Kirkman <don...@covad.net>
>wrote:
>>It seems to me I heard somewhere that Matti Narkia wrote in article
>><6nlapucqlvdrsb30g...@4ax.com>:
>>>I think that almost any medication could affect liver. For young people
>>>with previously healthy kidneys the use of NSAIDs rarely affect kidneys. But
>>>kidney function reduces with age, and for older people long term use of
>>>large doses of NSAIDs could pose risks, especially when used in doses
>>>required in arthritis. See
>>Stipulated that your citations refer to kidney problems *in older
>>"geriatric" patients*; arthritis may begin in childhood or at any other
>>age.
>I guess you didn't read the text from the page
>Colorado HealthSite
>http://www.coloradohealthsite.org/chnqna.html?Kidney%20Disease?Medications?2853
> "Question: I have been reading your other question answered on
> NSAIDS and kidney disease, and would like to know if you can
> please tell me why NSAIDS are potentially dangerous to people
> suffering Kidney Disease?
IOW, *pre-existing kidney disease.* not as a result of the NSAIDs.
> Answer: NSAIDS or non-steroidal antiinflammatory drugs have a
> number of potential side effects on kidneys. One of the more
> common side effects is due to the role NSAIDS may have in
> blood flow to the glomeruli which are the filtering units of
> the kidney. In normal settings, there is not much of an effect
^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
> but in conditions wherein the kidney is very dependent on
> blood flow such as heart failure, liver disease, dehydration
> and other conditions this could be significant enough to cause
> kidney failure. In someone with existing kidney disease this
> can be further exacerbated.
[...]
> The long term use of NSAIDS has also been associated chronic
> kidney damage. Kidney function gradually begins to deteriorate
> over a long period of time. This has been seen with the use of
> NSAIDS for several months to years. It is important to
^^^^^^^^^^^^^^^^
> remember that a majority of patients taking NSAIDS do not
^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
> develop kidney problems and that the above mentioned
^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
> conditions are potential side effects that need to be
> monitored for closely. Dennis Roy Imperio, M.D., Private
> Practice, Sarasota, Florida May 2001"
>>The liver risk seems to be the major factor and the main concern of
>>rheumatologists.
>>
>I guess that to some extent it depends on the drug. As the quote above
>shows, there is also reason to worry about kidneys. Still, whether liver or
>kidney is more vulnerable to a particular drug is not an issue here. The
>issue is that the drugs may have dangerous side effects and their risks may
>be reduced if doses of the drugs could be reduced.
You were focussing on kidneys, therefore I responded about kidneys but
brought up liver function.
>>>To answer your question, in most cases fish oil probably has not much
>>>benefit over a routine good diet, provided that people know what is required
>>>from a good anti-inflammatory diet, and are willing and able to follow it.
>>>If any of these conditions is not fulfilled, use of fish oil is an easy way
>>>out, but is still admittedly perhaps only partially effective, if omega-6
>>>intake remains high.
>>But there's little profit in a "routine good diet," I suppose. :-)
>What's your point? Where do you live? In a communist country or a in a
>market economy? Do yo work free or do you get paid? Do you get your food
>free? How about your house? Free, too? Especially, do you get your "routine
>good diet" free? And even if _you_ do, _someone_ has to pay for it. There is
>no such thing as a free lunch, remember?
The point is that supplements and nutritionals are a big business world
wide, and especially in the US and Canada. They are often touted as
"natural" with the implication that they are risk-free and better than
pharmaceuticals. Patients are hurt if supplements interact with
prescribed medicines or, maybe more importantly, if patients forego
pharmaceuticals and place their trust entirely in supplements.
I don't intend to respond to any more posts in this thread. My main
points have been made:
- knowing the mechanism of a biochemical process does not per se
validate the substances involved as either effective or safe for real
people with real diseases
- contrary to much rhetoric, nutritionals are as fully involved in the
search for profits and market share as pharmaceuticals
- "natural" does not equal safe or effective
- rigid logic and rigid science should be applied equally to both
categories of treatment, nutritional and medical
--
Don
don...@covad.net
DiWitt
have RA and MS and use both fish oil and Evening Primrose oil. Only after
3-6 months of the addition of these supplements to my diet as well as
changing my diet (no red meat, no hydrogenated stuff - basically the MS Diet
at the recommendation of my neurologist) was I able for the first time in 5
years to get my RA/MS under control despite aggressive treatments with
DMARDS for both diseases. I was able to reduce my steroid level and still
maintain a low sed rate. The diet was no red meat at all for the first 6
months and then only 1-2 times a week after that initial 6 mo period. It
also encouraged eating fish like Salmon that is high in those certain oils
being discussed. I followed it exactly for almost 2 years.
Unfortunately, I got lazy. I broke a bone and developed an infection which
caused me to take lots of antibiotics which bothered my stomach. I stopped
the NSAID because of its slowing the bone growth and bothering my stomach.
I stopped the supplements for a brief time because my stomach was so bad.
That turned into 8 months. And guess what flared worse than ever? The RA.
I am now trying to get things under control again but it is harder this
time. I have been on Enbrel, a disease modifier for the RA, since about 6
mo before I started the dietary changes. Even the Enbrel is having a hard
time controlling the RA now and we are having to add another drug, Arava, to
the mix in order to settle things down. Arava is know to be tough on the
liver as well as the stomach but I do not have the pain threshold to wait
the 6 months of getting my diet back under control and the joint swelling is
indicative that real damage could be occurring. This is not something to
play with. But I am getting back on track with the dietary changes and
supplements again with the hope that I will be able to wean some of the more
dangerous drugs when things settle down. If I could give myself a kick in
the butt for slacking off that diet and letting things fall apart, believe
me, I would!
I know I am not a double blind study. I am just one person. And I know
that diseases like RA and MS have periods of flares and remissions. Call it
coincidence if you will, but the 2 years I was following the MS Diet and
taking the fish oil supplements and evening primrose oil were the best two
years I have had since my diagnoses. I wasn't cured. I wasn't even pain
free. But I was able to reduce the amount of pain medication I took. My
liver enzymes returned to normal. I was able to use NSAIDS occasionally
instead of every day. I was able to wake up and get out of bed without
assistance as the morning stiffness had lessened significantly. I had good
energy and was able to resume some household chores that had previously been
delegated to paid help or others in the family. I resumed some simple
gardening. So argue the facts of the research all you want, the bottom line
FOR ME is that these supplements as well as the change in diet improved the
quality of my life and after all, isn't that what's most important?
--
Cyberhugs,
DianeW
"Matti Narkia" <mn...@despammed.com> wrote in message
news:lq2bpuc5b5sud376k...@4ax.com...
Matti Narkia
<0jk9pus75ljbgc738...@4ax.com> Don Kirkman <don...@covad.net>
wrote:
> There's no "also
>available" about GS/CS, since they aren't prescription drugs but are
>purely nutritionals
>
Here in Finland GS is available bot as a phamaceutical grade drug from
pharmacy (I'm not sure if a prescription si required) and as a nutritional
supplement from health shop. The most significant difference is that for the
same amount of GS, the nutritional product is _a lot_ cheaper.
>
>That sounds like moderate OA; you'd have a hard time convincing my
>newsgroup acquaintances on canes, crutches, and wheel chairs that they
>only need pain relief once a week even with GS/CS. Did Lancet speak to
>the severity of their subjects' disease?
The whole article is readable on the web free of charge.
--
Matti Narkia
Matti Narkia
wrote:
>It seems to me I heard somewhere that Matti Narkia wrote in article
><lq2bpuc5b5sud376k...@4ax.com>:
>
>>Fri, 27 Sep 2002 16:48:56 -0700 in article
>><rea9pu0fhv0t6a6c0...@4ax.com> Don Kirkman <don...@covad.net>
>>wrote:
>
>Of course; mouse studies may be very high quality work, but they aren't
>directly applicable to human medical issues.
>
Not directly. That does not mean that they are without interest.
>
>>>Review article re: essential fatty acids, not limited to fish oil.
>
>>Not really, it's a review article limited to two GLA containing oils,
>>evening primrose oil and borage oil. As I mentioned above, my original
>>remark was about fish oil _and_ GLA. This reference and those who follow it
>>are about GLA part, not about fish oil.
>
>I think that's what I said; it IS a review article.
>
Ah, but that's not what you said, you said
"Review article re: essential fatty acids, not limited to fish oil."
which is incorrect, for example it does not handle essential fatty acids.
>>>The next to last sentence is significant.
>
>>On the contrary, it has nothing to do with the science. Don't confuse
>>science with local regulations, politics or ways the market economy works.
>>In my country there are no restrictions for GLA's use as a therapy, but it's
>>not officially approved for any treatment. This is the case for most natural
>>unpatentable substances, because there is no incentive for commercial
>>enterprises to finance their large scale trials required for official
>>approval.
>
>So the US is not the only country not approving this as medical
>treatment, right? This throws it into the nutritional camp.
>
What camp you've been in so far ? :-) :-)
>>Double blind trials are only tiny part of medical science, which are needed
>>for further validation of earlier results - and eventually also for the
>>approval of a drug. I'm personally also interested in the mechanisms of
>>action.
>
>The mechanisms of an action a nice theoretical stuff, but many
>medications are effective even with unknown mechanisms. Does it work
>and is it safe? Double blind studies.
>
You have a tunnel vision. Double blind visions don't just pop up from the
vacuum, there is need for many kind of studies before them and often even
after them. Do you want to ban all the other studies except for double blind
studies?
>
>>This is IMHO a very important study describing the interaction between EPA
>>and GLA.
>
>But healthy volunteers aren't surrogates for rheumatics, twelve subjects
>is a very small _n_, and a control group is lacking.
>
Tunnel vision strikes again. This study is not specific to arthritis, but
investigates interaction of GLA and EPA, especially about EPA's capability
to prevent the rise of AA levels when GLA is taken. This is basic
nutritional information, which may come useful if one is planning to take
GLA.
>
>Indeed. Meanwhile what's happening to the joints?
>
To my knowledge symptom relief is the only claim that has been presented for
these oils when used with arthritis.
>
>>IMHO the main function of fish oil is to correct the inflammatory nature of
>>omega-6/omega-3 ratio in modern diets to less inflammatory direction.
>
>Mechanisms aside, how about just adding more fish to the diet?
>
That's fine. There are. however. some practical considerations (which I've
handled in another message) which may favor the use of fish oil in addition
(or instead of) to fish.
>
>>You must be aware that the financial resource available for the research of
>>natural unpatentable substances such as nutrients cannot in the market
>>economy compete with investments available for patented drugs.
>
>I've answered this elsewhere, but if the nutritional companies cared to
>feed their profits back into rigorous studies as the pharmaceutical
>companies do perhaps we could all be satisfied.
>
You're probably aware that pharmaceutical industry has consistently had one
of the highest profit margins of all businesses. Regardless of that it has
completely failed to do for example morbidity and mortality studies for some
medications, and for many other drugs these studies have been done with much
too small patient-year material. This was the case for example for some new
blood pressure medications a few years ago, as pinpointed at that time for
example by professor Curt Furberg from Wake Forest University in North
Carolina in TV-interviews and articles.
I agree that more studies and standardization is needed for the supplements.
That is, however, difficult to achieve, if the company who invests into
research does not get a similar protection against competitors than the drug
companies get in the form of a patent. Government financed studies could be
at least partial answer.
>>I'm surprise, if more of the people you know arthritis newsgroups are
>>neither modifying their diet towards less inflammatory direction nor using
>>anti-inflammatory supplements, especially because Liz G. seemed to have had
>>good results with fish oil and GLA. Perhaps not everyone has the patience to
>>carry on for 3 months before any results can be expected. Good be to some
>>extent cultural matter as well. Here in Finland quite a many arthritis
>>patients use fish oil and/or GLA in addition to their medication.
>
>Those folks are pretty smart cookies, and although many of them use
>supplements they work with their doctors, stick with their medications,
>and don't suffer marketers of nutritionals gladly. They know when
>something helps and when it doesn't.
Exactly. According to my brief investigation in these newsgroups a majority
of those, who had tried fish oil or GLA or both for at least 3 months, have
reported positive experiences.
--
Matti Narkia