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| From:  taka00381 (Original Message) | Sent: 2/28/2007 1:59 AM |
Hans,
can we open this new thread gathering scientific information about the Mead acid? I think it is important to demonstrate that the Mead acid can substitute for all the AA/EPA/GLA functions the "experts" feel to be essential for healthy life. It's amazing to see that Mead acid is the main component of membranes in young, growing and healthy tissues ... I will start with some abstracts:
Lipids. 1995 Oct;30(10):949-53.
Differences in fatty acid composition of immature and mature articular cartilage in humans and sheep.
Cleland KA, James MJ, Neumann MA, Gibson RA, Cleland LG.
Rheumatology Unit, Royal Adelaide Hospital, Australia.
Chondrocytes are imbedded in an avascular, highly charged extracellular matrix which could form a barrier to the transfer of dietary essential fatty acids (EFA) to chondrocytes. A study was designed to assess the composition of immature and mature joint cartilage with respect to essential and nonessential fatty acids relevant to EFA deficiency. Cartilage and muscle samples were obtained from human fetus, infant and adult cadavers, and from fetal and mature sheep. Lipid extracts were prepared and the fatty acid composition determined. In human and sheep joint cartilage, linoleic acid (LA; 18:2n-6) content was lower, and n-9 eicosatrienoic acid (ETrA; 20:3n-9) and arachidonic acid (AA; 20:4n-6) were higher in fetuses compared to mature subjects. An intermediate pattern was seen in infant cartilage. n-3 Fatty acids tended to be higher in fetal than in mature cartilage in humans and in sheep. In human muscle (and in other noncartilaginous comparison tissues), similar differences between fetuses and adults were seen in LA and AA, but not in ETrA. In fetal sheep muscle, very low LA, reduced AA and raised ETrA levels compared to mature sheep muscle were seen. However, although the pattern is characteristic of EFA deficiency, the abundance of n-6 EFA in liver and spleen of human fetuses and of n-3 EFA in liver and spleen of fetal sheep suggests that placental transfer of EFA is not likely to be limiting. During fetal development, the metabolism of fatty acids is distinctive and differs between the species. ETrA appears to be a readily measurable component of some tissues at certain stages of development when its presence in tissues does not indicate EFA deficiency.
FASEB J. 1991 Mar 1;5(3):344-53.
Unique fatty acid composition of normal cartilage: discovery of high levels of n-9 eicosatrienoic acid and low levels of n-6 polyunsaturated fatty acids.
Adkisson HD 4th, Risener FS Jr, Zarrinkar PP, Walla MD, Christie WW, Wuthier RE.
Department of Chemistry, University of South Carolina, Columbia 29208.
We report here the finding that normal, young cartilages, in distinction from all other tissues examined, have unusually high levels of n-9 eicosatrienoic (20:3 cis-delta 5,8,11) acid and low levels of n-6 polyunsaturated fatty acids (n-6 PUFA). This pattern is identical to that found in tissues of animals subjected to prolonged depletion of nutritionally essential n-6 polyunsaturated fatty acids (EFA). This apparent deficiency is consistently observed in cartilage of all species so far studied (young chicken, fetal calf, newborn pig, rabbit, and human), even though levels of n-6 PUFA in blood and all other tissues is normal. The n-9 20:3 acid is particularly abundant in phosphatidylethanolamine, phosphatidylinositol, and the free fatty acid fractions from the young cartilage. Several factors appear to contribute to the reduction in n-6 PUFA and the appearance of high levels of the n-9 20:3 acid in cartilage: 1) limited access to nutritional sources of EFA due to the impermeability and avascularity of cartilage, 2) rapid metabolism of n-6 PUFA to prostanoids by chondrocytes, and 3) a unique fatty acid metabolism by cartilage. Evidence is presented that each of these factors contributes. Previously, EFA deficiency has been shown to greatly suppress the inflammatory response of leukocytes and rejection of tissues transplanted into allogeneic recipients. Because eicosanoids, which are derived from EFA, have been implicated in the inflammatory responses associated with arthritic disease, reduction of n-6 PUFA and accumulation of the n-9 20:3 acid in cartilage may be important for maintaining normal cartilage structure.
J Biol Chem. 1983 Nov 10;258(21):12797-800.
Products derived from 5,8,11-eicosatrienoic acid by the 5-lipoxygenase-leukotriene pathway.
Jakschik BA, Morrison AR, Sprecher H.
Analysis of products derived from 5,8,11-eicosatrienoic acid via the 5-lipoxygenase-leukotriene pathway showed that this fatty acid is readily converted to leukotriene (LT)A3. When 10,000 X g supernatant from rat basophilic leukemia cell homogenates was incubated with 30 microM fatty acid, 5,8,11-eicosatrienoic acid produced 6.2 +/- 1.1 nmol of LTA3 and arachidonic acid 15.5 +/- 1.9 nmol of LTA4 (n = 4). However, only insignificant amounts of LTB3 were formed (0.15 +/- 0.04 nmol of LTB3 and 4.2 +/- 0.4 nmol of LTB4, n = 4). These data indicate that the LTA-hydrolase requires not only the three double bonds of the triene but also the double bond at C-14 to efficiently convert LTA to LTB. These findings have significant implications for essential fatty acid deficiency.
J Biol Chem. 1984 Oct 10;259(19):11784-9.
Leukotriene B formation by neutrophils from essential fatty acid-deficient rats.
Stenson WF, Prescott SM, Sprecher H.
Analysis of neutrophil phospholipids from rats fed an essential fatty acid-deficient diet revealed a 33% reduction in arachidonate and a 90% reduction in linoleate compared to neutrophil phospholipids of rats fed a normal diet. The neutrophil phospholipids from rats fed the essential fatty acid-deficient diet also contained significant amounts of 5,8,11-eicosatrienoate, a fatty acid not found in the neutrophils of rats fed a normal diet. Analysis of the production of leukotrienes of the B series by ionophore-stimulated neutrophils from rats fed an essential fatty acid-deficient diet revealed a 87% reduction in leukotriene B4 compared to neutrophils from rats fed a normal diet even though the arachidonate content was reduced by only 34%. Essential fatty acid-deficient neutrophils converted endogenous 5,8,11-eicosatrienoic acid to leukotriene A3 and its nonenzymatic degradation products, but little or no leukotriene B3 was formed. Neutrophils from rats fed a normal diet incubated with ionophore and exogenous 5,8,11-eicosatrienoate also produced leukotriene A3 and its nonenzymatic degradation products but little or no leukotriene B3. Exogenous 5,8,11-eicosatrienoate incubated with ionophore-stimulated normal neutrophils caused a dose-dependent inhibition of leukotriene A hydrolase resulting in diminished production of leukotriene B4 from endogenous arachidonate. Assays of leukotriene A hydrolase in the 10,000 X g supernatant fraction of a homogenate of RBL-1 cells revealed that a lipoxygenase metabolite of 5,8,11-eicosatrienoate rather than 5,8,11-eicosatrienoate itself is the inhibitor of leukotriene A hydrolase. Thus the finding that leukotriene B4 production by neutrophils from essential fatty acid-deficient rats is diminished out of proportion to the decrease in arachidonate content appears to be due to inhibition of leukotriene A hydrolase by a lipoxygenase metabolite. |
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In this new study the "experts" are saying that normal pregnancy is not normal because the Mead acid appears. This EFAD hysteria is going to cause some serious damage in long term because they are going to feed the mothers extra PUFAs. I would guess there is a link between high n-3/n-6 PUFA content in the milk and breast cancer ...
Early Human Development, pp. 239-248, 2008
Biochemical EFA status of mothers and their neonates after normal pregnancy
Al, M.D.M.a , Hornstra, G.a , van der Schouw, Y.T.a , Bulstra-Ramakers, M.T.E.W.b , Huisjes, H.J.b
a Department of Human Biology, State University Limburg, Maastricht, Netherlands
b Department of Obstetrics and Gynaecology, State University Groningen, Groningen, Netherlands
The essential fatty acid (EFA) status of neonates was compared with that of their mothers by determining the fatty acid compositions of phospholipids (PL), isolated from umbilical arterial and venous tissue, blood cells (BC) and plasma, from maternal venous plasma and BC, and from non-infarcted placental tissue. The PL of umbilical arterial tissue (efferent fetal vessels) contained fewer fatty acids of the (n-6) family and more of the (n-9) family than umbilical venous tissue (afferent fetal vessel). The relative amounts of (n-6) and (n-03) fatty acids were less in arterial than in venous plasma. Mead acid, 20:3(n-9), the presence of which indicates a poor EFA status, was 5 times higher in the efferent than in afferent cord vessels. In neonatal plasma and BC it was twice as high as compared with maternal levels. In general, the fatty acid composition of the placenta PL showed a comparable pattern as neonatal venous plasma PL. These findings demonstrate that the biochemical EFA status of neonates after a normal pregnancy is not optimal. The significant correlations between neonatal and maternal EFAs indicate that the neonatal EFA status depends on the EFA content of the maternal diet. |
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The Journal of Nutritional Biochemistry
Volume 3, Issue 11, November 1992, Pages 562-579
Biochemical and nutritional aspects of eicosanoids
Vishwanath M. Sardesai
Wayne State University School of Medicine, Detroit, MI, USA
The eicosanoids are derived from 20-carbon polyunsaturated fatty acids e.g., dihomogamma linolenic, arachidonic, eicosapentaenoic, and Mead acid, which are present as components of cell membrane phospholipids. Activation of phospholipases causes release of these fatty acids that can be metabolized either via the cyclooxygenase pathway to produce the prostanoids—prostaglandins, thromboxanes, and prostacyclins—or via the lipoxygenase pathway to form leukotrienes and lipoxins. These fatty acids can also be oxidized by the cytochrome P-450 system giving rise to several metabolites including epoxyeicosatrienoic acids. Eicosanoids are highly active substances with diverse biological actions. Because arachidonic acid is the most common fatty acid present in tissue lipids, the eicosanoids derived from it predominate in human tissues. Some of the eicosanoids formed from arachidonic acid such as thromboxane A2 and leukotrienes have deleterious effects, while those derived from other polyunsaturated fatty acids are generally less potent or have beneficial actions. The steroidal anti-inflammatory agents, such as cortisone, block the release of precursor fatty acids and thus the formation of all eicosanoids. Non-steroidal anti-inflammatory agents such as aspirin inhibit cyclooxygenase and prevent the production of prostanoids. It is possible to modulate the precursor fatty acid component in cell membrane phospholipids by dietary means, which in turn can alter the types of eicosanoids formed endogenously. Some food constituents such as vitamin C, vitamin E, garlic, onion, ginger, and alcohol can affect the production of eicosanoids. The dietary manipulation may serve as a long-term strategy to favorably modify the endogenous eicosanoid production. |
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And some more on Mead acid:
Suppression of allergies patent - http://tinyurl.com/2lxb9x
Biochim Biophys Acta. 2005 Dec 30;1738(1-3):19-28. Epub 2005
Effects of arachidonic acid analogs on FcepsilonRI-mediated activation of mast cells.
Nakano N, Nakao A, Uchida T, Shirasaka N, Yoshizumi H, Okumura K, Tsuboi R, Ogawa H.
Atopy (Allergy) Research Center, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Polyunsaturated fatty acids (PUFAs) such as arachidonic acid (AA) have been shown to modulate a number of inflammatory disorders. Mast cells play a critical role in the initiation and maintenance of inflammatory responses. However, the effects of PUFAs on mast cell functions have not been fully addressed. We here-in examined the effects of PUFAs on the high affinity IgE receptor (FcepsilonRI)-mediated mast cell activation using RBL-2H3 cells, a rat mast cell line, that were cultured in the medium containing palmitic acid (PA), AA, or the AA analogs mead acid (MA) and eicosapentaenoic acid (EPA). In AA-supplemented cells, the FcepsilonRI-mediated beta-hexosamidase and TNF-alpha release, calcium (Ca(2+)) influx, and some protein tyrosine phosphorylations including Syk and linker for activation of T cells (LAT) were enhanced, whereas, in MA- or PA-supplemented cells, they were not changed when compared with cells cultured in control medium. In EPA-supplemented cells, the enhancements of beta-hexosamidase release and protein tyrosine phosphorylations were observed. Furthermore, in AA- or EPA-supplemented cells, FcepsilonRI-mediated intracellular production of reactive oxygen species (ROS) that is required for the tyrosine phosphorylation of LAT and Ca(2+) influx were enhanced when compared with the other cells. Thus, preincubation of AA or EPA augmented FcepsilonRI-mediated degranulation in mast cells by affecting early events of FcepsilonRI signal transduction, which might be associated with the change of fatty acid composition of the cell membrane and enhanced production of ROS. The results suggest that some PUFAs can modulate FcepsilonRI-mediated mast cell activation and might affect FcepsilonRI/mast cell-mediated inflammation, such as allergic reaction.
PMID: 16403671
Biochim Biophys Acta. 1995 Oct 26;1259(1):82-8.
Studies on the metabolism of [1-14C]5.8.11-eicosatrienoic (Mead) acid in rat hepatocytes.
Retterstøl K, Woldseth B, Christophersen BO.
Institute of Clinical Biochemistry, University of Oslo, Rikshospitalet, Norway.
The oxidation, esterification and formation of chain elongated and desaturated products of [1-14C]5,8,11-eicosatrienoic (Mead) acid was studied. Liver cells from essentially fatty acid deficient (EFAD) and control rats were used. The metabolism of [1-14C]20:4, n-6 and [1-14C]20:5, n-3 were studied under the same experimental conditions. More 20:3, n-9 than 20:4, n-6 and 20:5, n-3 was oxidised both in EFAD and control cells. 20:3, n-9 was elongated to [14C]22:3, n-9 in both cell types and significant amounts of [14C]22:4, n-9 were formed in EFAD cells. Less 20:3, n-9 was esterified in phospholipids and more in triacylglycerol than observed with 20:4, n-6 and 20:5, n-3 in both cell types. 20:3, n-9 was mainly esterified in phosphatidylcholine and little was esterified in phosphatidylethanolamine compared to 20:4, n-6 and 20:5, n-3. In comparison, 20:3, n-9 was rather efficiently esterified in phosphatidylinositol as 18:0-20:3. [14C]22:4, n-9 formed from 20:3, n-9 in EFAD hepatocytes was esterified in triacylglycerol, not in phospholipids, unlike [14C]22:5, n-6 and [14C]22:6, n-3 which were mainly esterified in phospholipids.
PMID: 7492619
Here we are getting a PGE2-like activity from Mead acid!
FEBS Lett. 1985 Feb 11;181(1):53-6.
Prostaglandin E2-like activity of 20:3n-9 platelet lipoxygenase end-product.
Lagarde M, Burtin M, Rigaud M, Sprecher H, Dechavanne M, Renaud S.
5,8,11-Icosatrienoic acid (20:3n-9), a fatty acid associated with platelet hyperactivity, was oxygenated by platelet lipoxygenase. The end-product of this pathway was purified by high-performance liquid chromatography (HPLC) and characterized as 12-hydroxy-5,8,10-icosatrienoic acid [12-OH-20:3(5,8,10)] by capillary gas-liquid mass spectrometry. When tested upon platelet aggregation, 12-OH-20:3(5,8,10) exhibited a biphasic effect. At low concentrations (below 5 X 10(-7) M) it potentiated aggregation but inhibited it at higher levels, a pattern similar to that obtained with prostaglandin E2. However, since the amounts of 12-OH-20:3(5,8,10) generated under thrombin stimulation are in the range of concentrations with potentiating effects, it seems that the 12-OH derivative is responsible for the hyperaggrebility of 20:3n-9-rich platelets.
PMID: 3918886
Toxicol Appl Pharmacol. 1993 May;120(1):72-9.
Essential fatty acid deficiency in cultured human keratinocytes attenuates toxicity due to lipid peroxidation.
Wey HE, Pyron L, Woolery M.
Centers for Disease Control, National Institute for Occupational Safety and Health, Division of Biomedical and Behavioral Science, Cellular Toxicology Section, Cincinnati, Ohio 45226.
Human keratinocytes are commonly grown in culture with a serum-free medium. Under these conditions, keratinocytes become essential fatty acid deficient (EFAD), as determined by gas chromatographic analysis of cell phospholipid fatty acid composition. Exposure of EFAD keratinocytes for 2 hr to concentrations of t-butyl hydroperoxide (tBHP) up to 2 mM did not result in toxicity assessed by lactate dehydrogenase (LDH) release and only a small indication of lipid peroxidation assessed by the release of thiobarbituric acid-reactive substances (TBARS). Addition of 10 microM linoleic acid (LA) to serum-free medium alleviated the EFAD condition by increasing the phospholipid content of LA and its elongation and desaturation products, arachidonic acid and docosatetraenoic acid. Exposure of LA-supplemented keratinocytes to tBHP resulted in significant LDH (at 1 and 2 mM tBHP) and TBARS (tBHP concentration dependent) release. TBARS release was also significantly elevated in unexposed LA-supplemented keratinocytes (basal release). Co-supplementation with the antioxidant, alpha-tocopherol succinate (TS) prevented tBHP (1 mM)-induced LDH release in LA-supplemented cultures. TS supplementation also attenuated the effect of tBHP on TBARS release, but when compared to TS-supplemented EFAD cultures, LA supplementation still led to increased tBHP-induced TBARS release. Keratinocyte cultures are potentially useful as an alternative to animals in toxicology research and testing. It is important, however, that the cell model provide a response to toxic insult similar to that experienced in vivo. Our results suggest that fatty acid and antioxidant nutrition of cultured keratinocytes are important parameters in mediating the toxic effects of lipid peroxidation.
PMID: 8511784
Most of the Mead acid biochemistry studies have been done by the Sprecher group and can be searched in Medline by:
"Sprecher H"[Author] Mead |
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| It still amazes me that this one mistake, that is, the claim that having AA in your cells is "essential," rather than a recipe for disaster, is so obvious, yet so difficult to straighten out. |
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J Nutr Sci Vitaminol (Tokyo). 1993 Jun;39(3):243-52.
Growth and essential fatty acid levels of plasma and liver of suckling rats from mothers fed on fat-free or various fat diets.
Iritani N, Matsumura Y, Fukuda H.
Tezukayama Gakuin College, Sakai, Japan.
The milk fatty acid compositions of mothers fed on a fat-free or various fat diets, and the effects on growth and fatty acid compositions of their pups were studied. Even the milk of essential fatty acid-deficient mothers fed on a fat-free or hydrogenated fat diet contained about 3 and 1.7%, n-6 and n-3 fatty acids, respectively. In the plasma of the suckling pups, however, the proportions of n-6 and n-3 fatty acids rapidly increased to about 20 and 3-5%, respectively, at 1 week after birth. In particular, the PUFAs markedly increased in the liver PC and PE, and the high levels were maintained until weaning. Although the PUFA compositions of suckling pups were influenced with those of maternal diet, small amounts of n-6 and n-3 fatty acids were usually maintained in the plasma and liver. After weaning to the same diets (without PUFAs) as the mothers, however, the n-3 and n-6 fatty acids rapidly decreased and endogenous n-9 eicosatrienoic acid appeared. On the other hand, the growth during suckling was not significantly different among the litters of mothers fed on diets with or without n-3 or n-6 fatty acids. After the weaning, however, the growth was improved in the following order: corn oil, perilla oil > fish oil > fat-free, hydrogenated fat diet group. n-3 fatty acids appeared to be used partially as substitutes for n-6. However, the essentiality was not clear, as the n-3 fatty acids always coexisted with the n-6. Thus, it appeared that small amounts of n-3 and n-6 fatty acids in milk were supplied to the suckling animals regardless of maternal diet and supported growth.
PMID: 8229316
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Taken from another thread - yet another study showing that Mead acid is present in healthy cartilage while Omega-3s destroy the cartilage (personally tested :-():
Lipids. 1994 Sep;29(9):619-25.
Dietary lipids modify the fatty acid composition of cartilage, isolated chondrocytes and matrix vesicles.
Xu H, Watkins BA, Adkisson HD.
Department of Food Science, Purdue University, West Lafayette, Indiana 47907.
The effects of dietary lipids on the fatty acid composition of hyaline cartilage, epiphyseal chondrocytes (EC) and matrix vesicles (MV) were evaluated in chicks. A basal semipurified diet was fed to chicks containing one of the following lipid sources at 70 g/kg: soybean oil, butter+corn oil, margarine+corn oil or menhaden oil+corn oil (MEC). Articular and epiphyseal growth cartilage were isolated from the proximal tibiotarsus; EC and MV were subsequently released by trypsin (EC 3.4.21.4) and collagenase (EC 3.4.24.3) digestion followed by ultracentrifugation. The fatty acid composition of polar lipids in chick epiphyseal cartilage at three and six weeks, as well as articular cartilage, EC and MV at eight weeks of age revealed the presence of high levels of saturated and monounsaturated fatty acids (up to 85.5%) but low levels of n-6 polyunsaturated fatty acids (PUFA) (2.6-10.2%). Mead acid (20:3n-9, > 3%) was also present in cartilage, EC and MV lipids, and was unaffected by the dietary lipid treatments. Total n-3 PUFA concentrations were the highest in cartilage, EC and MV of chicks consuming MEC. Feeding MEC lowered the levels of 20:4n-6 in cartilage, but increased 20:5n-3 levels. The data are consistent with those reported previously which showed that cartilage tissues are low in n-6 PUFA and that they contain 20:3n-9. We furthermore demonstrated that the PUFA composition of cartilage can be modified by dietary lipids.
PMID: 7815896 |
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This looks like certain NSAIDs can also block the inflammatory mediators made from the Mead acid:
Agents Actions Suppl. 1977 ;2 :77-83 PMID: 272845
Effects of anti-inflammatory drugs on the carrageenin-induced hind paw inflammation of rats deprived of endogenous precursors of prostaglandins.
I L Bonta, H Bult
The carrageenin-induced paw oedema was used to study anti-inflammatory drugs in normal rats and in those deprived of endogenous precursors of prostaglandins. The latter condition was achieved by permanently keeping the rats on essential fatty acid deficient (EFAD) food. Indomethacin inhibited the carrageenin-oedema in normal rats, but failed to further suppress the poorly developed delayed phase of the carrageenin-induced inflammation in EFAD rats. In contrast, aspirin exhibited equal inhibition of the carrageenin oedema in both normal and EFAD rats. The anti-inflammatory effect of dexamethasone was also indentical in both normal and EFAD rats. Since in EFAD rats the inflammatory role of an increased output of prostaglandins is of negligible importance, the results with aspirin and dexamethasone shed some doubt on such views, that suppression of the release of prostaglandins alone explains the acute anti-inflammatory effects of these drugs. The inflammatory response of EFAD rats is a model situation appearing to be useful in studying anti-inflammatory mechanisms which, under normal conditions, might be masked by interference with the release of prostaglandins.
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Prostaglandins & other lipid mediators
2003, vol. 71, no3-4, pp. 177-188
Effects of eicosatrienoic acid (20:3 n-9, Mead's acid) on some promalignant-related properties of three human cancer cell lines
HEYD V. L. ; EYNARD A. R.
The essential fatty acid deficiency (EFAD) is a metabolic condition related to cancer development. We studied the effect of eicosapentaenoic acid (EPA, 20:5 n-3) and eicosatrienoic acid (ETA, 20:3 n-9), an essential fattyacid (EFA) and non-EFA respectively, on tumour cells parameters linked to tumour progression and metastases. Human tumour cell lines (T-24 from urothelium, MCF-7 from breast and HRT-18 from colon) were used. EPA showed an anti-proliferative effect on the three lines. ETA showed the following effects: in T-24, the lipid peroxidation was decreased and E-cadherin was undetectable; in MCF-7, increased E-cadherin expression enhanced the lipid peroxidation and decreased cell proliferation; on HRT-18, the E-cadherin expression and lipid peroxidation diminished, whereas cell proliferation was increased. In conclusion, EFA (20:5 n-3) exhibited beneficial effects, whereas unusual ETA showed an opposite effect on some tumour parameters. The possible riskiness of EFA-deprivation, along with the potential of EFA as natural nutrapeutic products for human tumour prevention and treatment, makes EFA worthy of further consideration.
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Cannot get the full text but this study just seems to confirm that Omega-3s are more suitable for cancer chemotherapy than Mead acid which wouldn't kill cells through lipid peroxidation ... |
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EPA not any better than AA in alergic reactions but Mead acid makes a difference!
Biochim Biophys Acta. 2005 Dec 30;1738(1-3):19-28. Epub 2005 Dec 19.
Effects of arachidonic acid analogs on FcepsilonRI-mediated activation of mast cells.
Nakano N, Nakao A, Uchida T, Shirasaka N, Yoshizumi H, Okumura K, Tsuboi R, Ogawa H.
Atopy (Allergy) Research Center, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Polyunsaturated fatty acids (PUFAs) such as arachidonic acid (AA) have been shown to modulate a number of inflammatory disorders. Mast cells play a critical role in the initiation and maintenance of inflammatory responses. However, the effects of PUFAs on mast cell functions have not been fully addressed. We here-in examined the effects of PUFAs on the high affinity IgE receptor (FcepsilonRI)-mediated mast cell activation using RBL-2H3 cells, a rat mast cell line, that were cultured in the medium containing palmitic acid (PA), AA, or the AA analogs mead acid (MA) and eicosapentaenoic acid (EPA). In AA-supplemented cells, the FcepsilonRI-mediated beta-hexosamidase and TNF-alpha release, calcium (Ca(2+)) influx, and some protein tyrosine phosphorylations including Syk and linker for activation of T cells (LAT) were enhanced, whereas, in MA- or PA-supplemented cells, they were not changed when compared with cells cultured in control medium. In EPA-supplemented cells, the enhancements of beta-hexosamidase release and protein tyrosine phosphorylations were observed. Furthermore, in AA- or EPA-supplemented cells, FcepsilonRI-mediated intracellular production of reactive oxygen species (ROS) that is required for the tyrosine phosphorylation of LAT and Ca(2+) influx were enhanced when compared with the other cells. Thus, preincubation of AA or EPA augmented FcepsilonRI-mediated degranulation in mast cells by affecting early events of FcepsilonRI signal transduction, which might be associated with the change of fatty acid composition of the cell membrane and enhanced production of ROS. The results suggest that some PUFAs can modulate FcepsilonRI-mediated mast cell activation and might affect FcepsilonRI/mast cell-mediated inflammation, such as allergic reaction.
PMID: 16403671
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Most of the newer Mead acid studies are mostly in the patent literature. One example is here:
http://www.freepatentsonline.com/EP0635266.html
results are excellent for inhibiting the LTB4 production, therefore the Mead acid supplements may be usefull during the 2-year course of removing AA from the body ... |
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Mead acid metabolite is a potent activator of the 5-oxo-ETE receptor:
http://jpet.aspetjournals.org/cgi/reprint/jpet.107.134908v1.pdf
finally someone is looking into the natural PUFA's biological activities. |
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And another patent on the use of Mead acid to prevent cartilage degeneration:
QUOTE: omega-9 unsaturated fatty acids are known to be localized in cartilage tissues and its contents decrease with aging (FASEB J., 5,344-353, 1991), and believed to be important for maintenance of functions of chondrocytes. Furthermore, 5,8,11-eicosatrienoic acid has been confirmed to have an anti-inflammatory effect on the rat models of carrageenan-induced edema, but its pharmaceutical actions in arthropathy is little known.
Thus, in order to resolve the above problems, the inventors have carried out studies on various unsaturated fatty acids and consequently found that 5,8,11-eicosatrienoic acid has an action of inhibiting cartilage degeneration and that hence it is very useful for prevention or treatment of diseases caused by abnormalities in cartilage tissues, and we have completed the present invention.
UNQUOTE.
SOURCE: http://www.freepatentsonline.com/6765020.html |
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More evidence that Mead acid is not just a "passive filler" but has specific biological activities:
Journal of Pharmacology And Experimental Therapeutics
DOI: 10.1124/jpet.107.134908
Structural Requirements for Activation of the 5-Oxo-6E,8Z, 11Z,14Z-eicosatetraenoic Acid (5-Oxo-ETE) Receptor: Identification of a Mead Acid Metabolite with Potent Agonist Activity
The 5-lipoxygenase product 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-oxo-ETE) is a potent chemoattractant for neutrophils and eosinophils, and its actions are mediated by the oxoeicosanoid (OXE) receptor, a member of the G protein-coupled receptor family. To define the requirements for activation of the OXE receptor, we have synthesized a series of 5-oxo-6E,8Z-dienoic acids with chain lengths between 12 and 20 carbons, as well as a series of 20-carbon 5-oxo fatty acids, either fully saturated or containing between one and five double bonds. The effects of these compounds on neutrophils (calcium mobilization, CD11b expression, and cell migration) and eosinophils (actin polymerization) were compared with those of 5-oxo-ETE. The C12 and C14 analogs were without appreciable activity, whereas the C16 5-oxo-dienoic acid was a weak partial agonist. In contrast, the corresponding C18 analog (5-oxo-18:2) was nearly as potent as 5-oxo-ETE. Among the C20 analogs, the fully saturated compound had virtually no activity, whereas 5-oxo-6E-eicosenoic acid had only weak agonist activity. In contrast, 5-oxo-6E,8Z,11Z-eicosatrienoic acid (5-oxo-20:3) and its 8-trans isomer were approximately equipotent with 5-oxo-ETE in activating granulocytes. Because of the potent effects of 5-oxo-20:3, we investigated its formation from Mead acid (5Z,8Z,11Z-eicosatrienoic acid), which accumulates in dietary essential fatty acid deficiency, by neutrophils. The main Mead acid metabolite identified was 5-hydroxy-6,8,11-eicosatrienoic acid, followed by 5-oxo-20:3 and two 6-trans isomers of leukotriene B3. We conclude that optimal activation of the OXE receptor is achieved with 5-oxo-ETE, 5-oxo-18:2, and 5-oxo-20:3, and that the latter compound could potentially be formed under conditions of essential fatty acid deficiency.
SOURCE: http://jpet.aspetjournals.org/cgi/content/abstract/325/2/698 |
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| Just to be clear, I've pointed out that experiments have shown you don't get LTB4 from Mead acid (LTB4 is very dangerous stuff), but mostly LTA3. Now the "EFA" advocates say your body can't perform basic and necessary functions (such as blood clotting) with Mead acid in your cells. If this were true, at the very least, omega 6s would indeed be essential (omega 3s hinder blood clotting). However, I have found that my cuts heal at least as quickly (often seems more quickly) and the scab is rubbery, not like a hard plastic, as was the case when I had arachidonic acid in my cells. Thus, it's an issue of maximum effectiveness without any unhealthy developments, and only Mead acid delivers this combination (omega 3s seem to be worse in every way, and are only "good" in that they can counteract the excessive qualities of AA derivatives like LTB4 (by not allowing as much LTB4 to be produced in the first place, it seems). |
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This is interesting, there is more Mead acid in the Cystic fibrosis patients:
QUOTE: Although platelet AA and docosahexaenoic acid (DHA) content is normal in CF platelets, another fatty acid, Mead acid (20:3 n-9), is present in excess (47). Interestingly, when Mead acid is metabolized by platelet 12-lipoxygenase an end product is generated with PGE2-like activity, which enhances platelet aggregation (50, 51). Thus, an intrinsic fatty acid abnormality is present in CF platelets and, through the metabolism of Mead acid, may contribute to the observed increase in CF platelet activation. However, whether or not this platelet fatty acid abnormality can explain CF platelet activation has been questioned. UNQUOTE
SOURCE:
http://ajrccm.atsjournals.org/cgi/content/full/173/5/483 |
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