If you do take fish oil for Acne or Psoriasis taking an aspirin with it might help even more!
http://www.nature.co...l/050307-8.htmlPublished online: 8 March 2005; | doi:10.1038/news050307-8
Secret of fish oil's healthy effects revealed
Charlotte Schubert
Synthetic version could one day treat range of inflammatory diseases.
Fish oil's reputation as a panacea has expanded in recent years, with
studies showing benefits in ailments ranging from asthma to heart
disease. How it works has has been a mystery, but a new study now
helps to provide the answer, and suggests that aspirin could boost the
beneficial effect even further.
Many of the diseases helped by fish oils have one thing in common:
chronic inflammation, in which immune cells and molecular mediators
flood tissues and can create damage. This can lead, for example, to
the hardening of the arteries that spurs heart attacks and strokes.
"We know that this fish oil suppresses inflammation," says Stephen
Prescott, director of the Huntsman Cancer Institute at the University
of Utah in Salt Lake City, and an expert on lipids and inflammation.
"The question is how does it do it? People have looked for more than
20 years."
Oily work
Charles Serhan at Harvard Medical School in Boston and colleagues
became intrigued by the problem in 1999, after seeing a study showing
that fish oil protects against cardiovascular disease.
Subjects in that study had consumed a gram of fish oil each day. "They
smelled like mackerel," said Serhan. But he noticed that almost all of
the subjects were also taking aspirin to prevent strokes and heart
attacks. Might the two substances be working together?
Subsequent research by Serhan and his colleagues has suggested that
they do. Their work in human cells and in mice showed that omega-3
fatty acids in the fish oil are converted into lipids that seem to
suppress inflammation. Aspirin speeds up that conversion.
The researchers have now pinned down the effect even further by
focusing on one of the lipids, called resolvin E1. First they found
that healthy human volunteers fed both aspirin and fish oil had
resolvin E1 in their bloodstream. Then they created a synthetic form
of the lipid and tested its properties.
The lipid inhibited the migration of particular human immune cells and
dramatically reduced inflammation on the skin of rabbits. Serhan and
his team believe that resolvin E1 works in the body to tone down
inflammation, and report their results in The Journal of Experimental
Medicine1.
"This is a really attractive and interesting hypothesis at this
stage," says Prescott. Raymond DuBois, a lipid researcher at
Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, echoes that
sentiment, calling the work "a great move forward".
Scaled up
Serhan is now working to prove that resolvin E1 does actually help to
treat disease. His unpublished data so far show that the synthetic
version works in a mouse model of periodontal gum disease. Such
disease is driven by inflammation, which weakens the gums and causes
teeth to fall out. Resolvin E1 counteracts the process, he says.
Serhan now aims to scale up and modify the manufacture of synthetic
resolvin E1 so that it can be made cheaply in bulk, and he hopes to
start human trials soon.
It's a powerful substance, comments Prescott. "All you need to do is
make a little bit, and bang, you have an effect."
But resolvin E1 is "just the tip of the iceberg", Serhan adds. His
group is also looking at the other lipids that derive from fish oil.
He suspects that each one has a part to play in orchestrating the
inflammatory response. Understanding how they work could lead to the
development of a range of new drugs to counteract inflammation, he
predicts.
References
Arita, et al. J. Exp.l Med. 201, 713 - 722 (2005).
and
http://www.ncbi.nlm....t_uids=15726828 Resolvins, docosatrienes, and neuroprotectins, novel omega-3-derived
mediators, and their endogenous aspirin-triggered epimers.
Serhan CN, Arita M, Hong S, Gotlinger K.
Center for Experimental Therapeutics and Reperfusion Injury, Department
of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's
Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
cnser...@zeus.bwh.harvard.edu
The molecular basis for the beneficial impact of essential omega-3
(n-3) FA remains of interest. Recently, we identified novel mediators
generated from eicosapentaenoic acid (EPA) and docosahexaenoic acid
(DHA) that displayed potent bioactions identified first in resolving
inflammatory exudates and in tissues enriched with DHA. The trivial
names resolvin (resolution phase interaction products) and
docosatrienes were introduced for the bioactive compounds from these
novel series since they possess potent anti-inflammatory and
immunoregulatory actions. Compounds derived from EPA carrying potent
biological actions (i.e., 1-10 nM range) are designated E series and
denoted resolvins of the E series (resolvin E1 or RvE1), and those
biosynthesized from the precursor DHA are denoted resolvins of the D
series (resolvin D1 or RvD1). The number 1 designates the bioactive
compounds in this family (#1-4). Bioactive members from DHA-containing
conjugated triene structures or docosatrienes (DT) that possess
immunoregulatory and neuroprotective actions were termed
neuroprotectins. Aspirin treatment initiates a related epimeric series
by triggering endogenous formation of the 17R-D series resolvins and
docosatrienes. These epimers are denoted as aspirin-triggered (AT)-RvD
and DT, and possess potent anti-inflammatory actions in vivo
essentially equivalent to their 17S series pathway products. These
include five distinct series: (i) 18R resolvins from EPA (i.e., RvE1);
(ii) 17R series (AT) resolvins from DHA (RvD1 through RvD4); (iii) 17S
series resolvins from DHA (RvD1 through RvD4), (iv) DT from DHA; and
(v) their AT form 17R series DT. In this article, we provide an
overview of the formation and actions of these newly uncovered pathways
and products.
PMID: 15726828
and one more:
http://www.jbc.org/c...ll/278/17/14677Chemical mediators and autacoids such as local acting lipid mediators derived from arachidonic acid are well established regulators of key events of interest in host defense, coagulation, inflammation, and cancer (1). The tight control of the enzymes that regulate conversion of unesterified arachidonic acid to key classes of mediators, including prostaglandins, thromboxane, leukotrienes, and lipoxins highlights the importance of arachidonic acid as an essential fatty acid and precursor of these potent bioactive eicosanoids (2). The potential for dysregulation of each of the individual classes of eicosanoids has been suspect as important molecular events associated with several human diseases, including, inflammatory diseases, atherosclerosis, cardiovascular disorders, Alzheimer's disease, and cancer. The control in physiologic systems of these lipid mediators is an ongoing area of intense investigation, because early results indicated that deficiency disease can be initiated by exclusion of fat from the diet (3), and arachidonic acid was also uncovered as the precursor to prostanoids that play key roles in the regulation of parturition and renal function (4, 5).
Results from recent studies indicate that arachidonic acid is not the only fatty acid precursor that is transformed to potent bioactive mediators in inflammation and resolution (6, 7). Both DHA1 and eicosapentaenoic acid (EPA), the well-known omega -3 fatty acids present in fish oils, appear to be effective as dietary supplements in the treatment of a wide range of human disorders (8-11). For example, omega -3 fatty acid supplementation is reported to have a beneficial impact in treating asthma, atherosclerosis, cancer, and cardiovascular disorders (for a recent review, see Ref. 12). Of interest, the lack of omega -3 fatty acid consumption has also been shown to correlate with mental depression (13). Several clinical trials aimed at testing the therapeutic value of omega -3 supplementation have convincingly established that omega -3 fatty acids can display beneficial actions reducing the incidence and the severity of disease (14). In many of these, aspirin therapy was also used in conjunction, although apparently unintentionally, along with the omega -3 supplementation (i.e. see Refs. 14 and 15). Recent results evaluating the impact of aspirin in the transformation of omega -3 in inflammatory exudates in vivo, namely acute inflammation and spontaneous resolution, demonstrate that DHA and EPA are each converted via independent pathways to potent bioactive local mediators. These new di- and tri-hydroxy-containing compounds derived from omega -3 fatty acids were termed "resolvins," because they are (a) formed within the resolution phase of acute inflammatory response, at least in part, as cell-cell interactions products, (b) "stop" neutrophil entry to sites of inflammation, and © reduce exudates (7). These findings, together with earlier results (16-21), suggest that omega -3 fatty acids, in addition to arachidonic acid, an n-6 fatty acid (2, 4), can serve as precursors for potent bioactive molecules with distinct functions (22). Hence, it is likely that the resolvins and related compounds identified might represent the active products responsible, at least in part, for the many reported beneficial responses obtained in clinical studies with patients given high doses of omega -3 supplementation (see Refs. 6 and 7 and references within).
Another aspect for the many years of sustained interest in DHA lies in the fact that the brain is lipid-rich and that DHA is highly enriched in the membranes of brain synapses and in the retina (16). DHA declines in brain neurons with age and may result in loss in mental function (20). Also, it is now clear that DHA is required for fetal brain development and is held to be critical in the newborn for appropriate development and intelligence (23). Hence, from these and many other recent studies (24), it is now apparent that, in humans, DHA serves a critical role in both physiologic and pathophysiologic responses. Our recent finding that aspirin therapy can lead to the biosynthesis of unique series of 17R resolvins generated from DHA led us to question whether the significant roles reported for DHA in the many biological systems noted above were related to DHA conversion to potent local bioactive mediators. The reason for this line of thinking is that in most experimental systems, where the actions of either DHA or EPA were assessed either clinically or in animal models, the concentrations required to evoke beneficial actions are usually in the high microgram to high milligram range. In this context, it is difficult to envision direct and specific molecular actions responsible for the many beneficial outcomes from in vivo studies. Thus, with the coordinates (physical and biologic properties) in hand for the new aspirin-triggered 17R series resolvins obtained using lipidomics and bioassays (see Ref. 7), we determined in the present experiments whether DHA is converted to bioactive mediators de novo. The present results indicate that (a) DHA is a precursor to a potent family of bioactive docosanoids that include novel docosatrienes as well as the 17S epimer resolvin series generated in human blood cells, mouse brain, and by human glial cells; (b) these compounds display potent actions on leukocyte trafficking as well as on glial cell functions down-regulating cytokines expression. Hence, our present results indicate that DHA is a precursor in novel biosynthetic pathways to previously unrecognized potent molecules.
.
