Okay, so a summary of the metabolites of Mead acid (so far):
COX metabolites[1] [2] [3]:
Mead acid was oxygenated by platelet lipoxygenase to:
12-hydroxy-5,8,10-icosatrienoic acid [12-OH-20:3(5,8,10)]
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.
Mead acid was found to be metabolized by the cyclooxygenase enzyme system of ram seminal vesicle microsomes in a calcium-dependent manner:
13-hydroxy-5,8,11-icosatrienoate (the major product)
11-hydroxy-5,8,12-icosatrienoate
9-hydroxy-5,7,11-icosatrienoate
and two isomeric 8,11-dihydroxy-5,9,12-icosatrienoates.
Prostaglandin H synthase-1 gave a 13-hydroxy-5,8,11-icosatrienoate to 11-hydroxy-5,8,12-icosatrienoate ratio of 5:1
Prostaglandin H synthase-2 gave a ratio of 3:2
5-LOX metabolites[4] [5]
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.
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.
LTB4 production is also strongly inhibited.
P450 epoxygenase metabolites[6]
Incubation of 5,8,11-[1-14C]eicosatrienoic acid with prostaglandin endoperoxide synthase of ram vesicular gland microsomes led to formation of:
(11R)-hydroxy-5,8,12-eicosatrienoic acid
8,9,11-trihydroxy-5,12-eicosadienoic acid (two diastereoisomers)
8,9-epoxy-11-hydroxy-5,12-eicosadienoic acid.
Oxygenation of 5,8,11-eicosatrienoic acid by cytochrome P450 from liver microsomes of cynomolgus monkeys and phenobarbital-treated rats was also investigated. The metabolites formed included:
19- and 20- hydroxyeicosatrienoic acid
8,9- and 11,12-dihydroxyeicosadienoic acids
(12R)-hydroxy-5,8,10-hydroxyeicosatrienoic acid.
So, it seems as PGE like substances can be formed, HETEs and leukotrienes. Questions are if LTB4 and LTB3 are needed in the proportions you have them when not in a Mead Acid productive state (much dietary PUFAs).
Mead acid (a polyunsaturated fatty acid)
-
overkees
- Posts: 598
- https://cutt.ly/meble-kuchenne-wroclaw
- Joined: Fri 05 Aug 2011 14:20
Re: Mead acid (a polyunsaturated fatty acid)
Alright, a summary I made of alot of mead acid research to get a good overview. Be aware of the fact that alot of the researchers automatically speak of a essential fatty acid deficiency (EFAD) if there is an appearance of Mead Acid (MA). Please be critical when reviewing the researches I post below and keep these kind of things in mind.
MA metabolites
COX metabolites[x] [x] [x]:
Mead acid was oxygenated by platelet lipoxygenase to:
12-hydroxy-5,8,10-icosatrienoic acid [12-OH-20:3(5,8,10)]
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.
Mead acid was found to be metabolized by the cyclooxygenase enzyme system of ram seminal vesicle microsomes in a calcium-dependent manner:
13-hydroxy-5,8,11-icosatrienoate (the major product)
11-hydroxy-5,8,12-icosatrienoate
9-hydroxy-5,7,11-icosatrienoate
and two isomeric 8,11-dihydroxy-5,9,12-icosatrienoates.
Prostaglandin H synthase-1 gave a 13-hydroxy-5,8,11-icosatrienoate to 11-hydroxy-5,8,12-icosatrienoate ratio of 5:1
Prostaglandin H synthase-2 gave a ratio of 3:2
5-LOX metabolites[x] [x]
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.
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.
LTB4 production is also strongly inhibited.
P450 epoxygenase metabolites[6]
Incubation of 5,8,11-[1-14C]eicosatrienoic acid with prostaglandin endoperoxide synthase of ram vesicular gland microsomes led to formation of:
(11R)-hydroxy-5,8,12-eicosatrienoic acid
8,9,11-trihydroxy-5,12-eicosadienoic acid (two diastereoisomers)
8,9-epoxy-11-hydroxy-5,12-eicosadienoic acid.
Oxygenation of 5,8,11-eicosatrienoic acid by cytochrome P450 from liver microsomes of cynomolgus monkeys and phenobarbital-treated rats was also investigated. The metabolites formed included:
19- and 20- hydroxyeicosatrienoic acid
8,9- and 11,12-dihydroxyeicosadienoic acids
(12R)-hydroxy-5,8,10-hydroxyeicosatrienoic acid.
MA conversion
MA was converted by mouse mastocytoma cells to slow reacting substances: LTC3, 11-trans-LTC3, LTD3 and 11-trans-LTD3. The biological effects were approximately the same as of leukotrienes derived from arachidonic. [x]
MA readily converts, via the 5-lypoxygenase-leukotrienepathway to LTA3. [x]
MA and its effects on leukotrienes
MA significantly reduced LTB4 by inhibition of leuotriene A hydrolase by a lypoxygenase metabolite. [x]
MA doesn’t inhibit other products of 5-lipoxygenase metabolism, like (5-HETE) and the all-trans isomers of LTB4. In comparison, EPA inhibits the all-trans isomers too. [x]
Dietary MA can accumulate in leucocytes and suppress inflammatory eicosanoid synthetsis (LTB4). [x]
EFA-deficients macrophages produced markedly less LTC4 and LTB4 than controls. They did synthesize LTC3. The effects on leukotriene production, postraglandin and thromboxane production were only minimally affected by EFA deficiency.
EFA-deficient macrophages exhibited a marked reduction in receptor-mediated pinocytosis. Phagocytosis was unaffected. [x]
MA is naturally present, independent of diet, in some tissues. MA is also associated with young tissues.
In rats, the milk of EFAD mothers fed a fat free or hydrogenated fat diet contained about 3% n-6 and 1.7% n-3. In the plasma of the suckling pups, the proportions of n-6 and n-3 increased to about 20% and 3-5% respectively, 1 week after birth. After weaning to the same diets as the mothers (fat free or hydrogenated fats only) the n-3 and n-6 fatty acids rapidly decreased and endogenous n-9 (MA) appeared.
“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.”
[x]
MA : AA ratio is much higher in (especially the young) cartilages compared to other tissues, even if there are sufficient dietary EFAs available. [x] [x]
The phospholipids of umbillical arterial tissue contained fewer fatty acids of the n-6 family and more of the n-9 family than umbilical venous tissue.
Mead acid was 5 times higher in the efferent than in afferent cord vessels.
In neonatal plasma and blood cells it was twice as high as compared with maternal levels.
[x]
The effects on MA incorporation by n-3s and n-6s
Cellular MA is lower in rats fed a higher level of LA. [x]
The data showed that 0.5x LA or 10x AA, but not 1x AA, could quickly replete AA, accompanied by the synthesis of AA-derived eicosanoids and restoration of edema. These results suggest that in humans consumption of the average daily amount of AA without concurrent ingestion of LA would not alleviate an EFAD state. [x]
In rats MA in plasma and tissue phospholipids is in proportion to the amount of dietary MA. Addition of LA reduced the amount of MA incorporation.
Rats remained apparently healthy with high levels of dietary MA, and a histological survey of major organs revealed no abnormality. [x]
The essential fatty acid deficient state can be induced rapidly
There occurred no biochemical symptoms of essential fatty acid deficiency in a 10-14 days feeding containing only amino acids. LA decreased greatly and measured plasma MA increased. [x]
A fat free diet for 2 weeks reduces LA content in cholesterol esters 5 times, in phospholipids 7 times and in triglycerides 6 times. MA, (“normally”) undetectable, also started appearing[x]
EFAD rats had less damage than controls when exposed to several toxins.
Essential fatty acid deficient rats are significantly more reistant to the lethal effects of S. enteritidis endotoxin.
EFAD rats also manifested less severe alterations of hepatic and lysosomal integrity and became less hypoglycemic.
This suggests a deleterious role for AA and its conversion to TxA2 in the pathogenesis of endotoxic shock. [x]
“The results showing that EFAD rats are resistant to endotoxin-induced increases in HCT and vascular permeability raise the possibility that this may, in part, be a result of preferential LTC3 production that is less potent than LTC4.” [x]
In EFAD rats the second phase of LPS (an endotoxin) induced hypotension was strongly reduced. Platelet-activating factor (PAF) levels in stomach and duodenum were also reduced and correlated to diminished damage. [x]
AA metabolites contribute to oleic acid-induced pulmonary permeability. In EFAD rats this wasn’t the case. [x]
“In intact rats raised on the EFAD diet, CVF-induced lung injury was attenuated. When blood and excised lungs from rats raised on the normal diet were used, CVF caused pulmonary vascular constriction and acute lung injury.” [x]
EFAD prevents the interstitial cellular infiltrate and the renal ischemia associated with experimental nephrosis. [x]
“Thus, EFAD confers complete protection against the histopathologic and functional sequelae of immune-initiated injury in the glomerulus. The data suggest that the initial wave of complement-induced neutrophil infiltration (with resultant proteinuria) is not sufficient to perpetuate injury into the more destructive chronic phases.” [x]
“The injury to the colon was more evident in control rats compared with EFAD rats. Besides colonic tissue of control rats showed a highly significant increase of PGE2, LTB4 and PAF, compared with levels in EFAD rats.” [x]
EFAD might be highly protective in diabetes in humans
EFAD prevents diabetes in nonebese diabetic mice.
Essential fatty acid deficiency thus prevents the insulitis and resultant diabetes in low-dose streptozotocin-treated CD-1 mice, suggesting a central role for macrophages and lipid mediators in this autoimmunity model.
Misc.
Tissues that were ‘deficient’ in essential fatty acids are could be transplanted without immunosuppresion[x]
Celiac disease is characterized by chronic inflammation of the small intestinal mucosa. MA level in the mucosa was incraesed, with an increased ratio of MA : AA, this abnormallity was not reflected in serum values. [x]
Essential fatty acid deficiency seems to diminish the development of experimental metastases in the lungs. [x]
In experimentally induced bowel lesions MA may have both prophylactic and therapeutic effects. [x]
EFAD rats have a 87% reduction of edema. [x]
On injury, the MA group had less inflammation than EPA. [x]
Rat mast cells were cultured in the medium containting PA, AA, MA or EPA and the high affinity IgE receptor (FcepsilonRI)-mediated mast cell activation was examined,
In AA supplemented cells, beta-hexosamidase, TNF-alpha release, calcium influx (Ca2+)and some protein tyrosine phophorylations including Syk and linker for activation of T cells (LAT) were enhanced, whereas, in MA or PA supplemented cells they were not changed.
In AA or EPA supplemented cells, intracellular production of ROS that is required for the tyrosine phosphorylation of LAT and Ca2+ influx were enhanced when compared with the others.
MA might therefore be very helpful to alleviate allergies. [x]
The OXE receptor optimally activated with 5-oxo-ETE, 5-oxo-18:2 and 5-oxo-20:3. The last can be formed under EFAD conditions. [x]
MA metabolites
COX metabolites[x] [x] [x]:
Mead acid was oxygenated by platelet lipoxygenase to:
12-hydroxy-5,8,10-icosatrienoic acid [12-OH-20:3(5,8,10)]
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.
Mead acid was found to be metabolized by the cyclooxygenase enzyme system of ram seminal vesicle microsomes in a calcium-dependent manner:
13-hydroxy-5,8,11-icosatrienoate (the major product)
11-hydroxy-5,8,12-icosatrienoate
9-hydroxy-5,7,11-icosatrienoate
and two isomeric 8,11-dihydroxy-5,9,12-icosatrienoates.
Prostaglandin H synthase-1 gave a 13-hydroxy-5,8,11-icosatrienoate to 11-hydroxy-5,8,12-icosatrienoate ratio of 5:1
Prostaglandin H synthase-2 gave a ratio of 3:2
5-LOX metabolites[x] [x]
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.
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.
LTB4 production is also strongly inhibited.
P450 epoxygenase metabolites[6]
Incubation of 5,8,11-[1-14C]eicosatrienoic acid with prostaglandin endoperoxide synthase of ram vesicular gland microsomes led to formation of:
(11R)-hydroxy-5,8,12-eicosatrienoic acid
8,9,11-trihydroxy-5,12-eicosadienoic acid (two diastereoisomers)
8,9-epoxy-11-hydroxy-5,12-eicosadienoic acid.
Oxygenation of 5,8,11-eicosatrienoic acid by cytochrome P450 from liver microsomes of cynomolgus monkeys and phenobarbital-treated rats was also investigated. The metabolites formed included:
19- and 20- hydroxyeicosatrienoic acid
8,9- and 11,12-dihydroxyeicosadienoic acids
(12R)-hydroxy-5,8,10-hydroxyeicosatrienoic acid.
MA conversion
MA was converted by mouse mastocytoma cells to slow reacting substances: LTC3, 11-trans-LTC3, LTD3 and 11-trans-LTD3. The biological effects were approximately the same as of leukotrienes derived from arachidonic. [x]
MA readily converts, via the 5-lypoxygenase-leukotrienepathway to LTA3. [x]
MA and its effects on leukotrienes
MA significantly reduced LTB4 by inhibition of leuotriene A hydrolase by a lypoxygenase metabolite. [x]
MA doesn’t inhibit other products of 5-lipoxygenase metabolism, like (5-HETE) and the all-trans isomers of LTB4. In comparison, EPA inhibits the all-trans isomers too. [x]
Dietary MA can accumulate in leucocytes and suppress inflammatory eicosanoid synthetsis (LTB4). [x]
EFA-deficients macrophages produced markedly less LTC4 and LTB4 than controls. They did synthesize LTC3. The effects on leukotriene production, postraglandin and thromboxane production were only minimally affected by EFA deficiency.
EFA-deficient macrophages exhibited a marked reduction in receptor-mediated pinocytosis. Phagocytosis was unaffected. [x]
MA is naturally present, independent of diet, in some tissues. MA is also associated with young tissues.
In rats, the milk of EFAD mothers fed a fat free or hydrogenated fat diet contained about 3% n-6 and 1.7% n-3. In the plasma of the suckling pups, the proportions of n-6 and n-3 increased to about 20% and 3-5% respectively, 1 week after birth. After weaning to the same diets as the mothers (fat free or hydrogenated fats only) the n-3 and n-6 fatty acids rapidly decreased and endogenous n-9 (MA) appeared.
“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.”
[x]
MA : AA ratio is much higher in (especially the young) cartilages compared to other tissues, even if there are sufficient dietary EFAs available. [x] [x]
The phospholipids of umbillical arterial tissue contained fewer fatty acids of the n-6 family and more of the n-9 family than umbilical venous tissue.
Mead acid was 5 times higher in the efferent than in afferent cord vessels.
In neonatal plasma and blood cells it was twice as high as compared with maternal levels.
[x]
The effects on MA incorporation by n-3s and n-6s
Cellular MA is lower in rats fed a higher level of LA. [x]
The data showed that 0.5x LA or 10x AA, but not 1x AA, could quickly replete AA, accompanied by the synthesis of AA-derived eicosanoids and restoration of edema. These results suggest that in humans consumption of the average daily amount of AA without concurrent ingestion of LA would not alleviate an EFAD state. [x]
In rats MA in plasma and tissue phospholipids is in proportion to the amount of dietary MA. Addition of LA reduced the amount of MA incorporation.
Rats remained apparently healthy with high levels of dietary MA, and a histological survey of major organs revealed no abnormality. [x]
The essential fatty acid deficient state can be induced rapidly
There occurred no biochemical symptoms of essential fatty acid deficiency in a 10-14 days feeding containing only amino acids. LA decreased greatly and measured plasma MA increased. [x]
A fat free diet for 2 weeks reduces LA content in cholesterol esters 5 times, in phospholipids 7 times and in triglycerides 6 times. MA, (“normally”) undetectable, also started appearing[x]
EFAD rats had less damage than controls when exposed to several toxins.
Essential fatty acid deficient rats are significantly more reistant to the lethal effects of S. enteritidis endotoxin.
EFAD rats also manifested less severe alterations of hepatic and lysosomal integrity and became less hypoglycemic.
This suggests a deleterious role for AA and its conversion to TxA2 in the pathogenesis of endotoxic shock. [x]
“The results showing that EFAD rats are resistant to endotoxin-induced increases in HCT and vascular permeability raise the possibility that this may, in part, be a result of preferential LTC3 production that is less potent than LTC4.” [x]
In EFAD rats the second phase of LPS (an endotoxin) induced hypotension was strongly reduced. Platelet-activating factor (PAF) levels in stomach and duodenum were also reduced and correlated to diminished damage. [x]
AA metabolites contribute to oleic acid-induced pulmonary permeability. In EFAD rats this wasn’t the case. [x]
“In intact rats raised on the EFAD diet, CVF-induced lung injury was attenuated. When blood and excised lungs from rats raised on the normal diet were used, CVF caused pulmonary vascular constriction and acute lung injury.” [x]
EFAD prevents the interstitial cellular infiltrate and the renal ischemia associated with experimental nephrosis. [x]
“Thus, EFAD confers complete protection against the histopathologic and functional sequelae of immune-initiated injury in the glomerulus. The data suggest that the initial wave of complement-induced neutrophil infiltration (with resultant proteinuria) is not sufficient to perpetuate injury into the more destructive chronic phases.” [x]
“The injury to the colon was more evident in control rats compared with EFAD rats. Besides colonic tissue of control rats showed a highly significant increase of PGE2, LTB4 and PAF, compared with levels in EFAD rats.” [x]
EFAD might be highly protective in diabetes in humans
EFAD prevents diabetes in nonebese diabetic mice.
Essential fatty acid deficiency thus prevents the insulitis and resultant diabetes in low-dose streptozotocin-treated CD-1 mice, suggesting a central role for macrophages and lipid mediators in this autoimmunity model.
Misc.
Tissues that were ‘deficient’ in essential fatty acids are could be transplanted without immunosuppresion[x]
Celiac disease is characterized by chronic inflammation of the small intestinal mucosa. MA level in the mucosa was incraesed, with an increased ratio of MA : AA, this abnormallity was not reflected in serum values. [x]
Essential fatty acid deficiency seems to diminish the development of experimental metastases in the lungs. [x]
In experimentally induced bowel lesions MA may have both prophylactic and therapeutic effects. [x]
EFAD rats have a 87% reduction of edema. [x]
On injury, the MA group had less inflammation than EPA. [x]
Rat mast cells were cultured in the medium containting PA, AA, MA or EPA and the high affinity IgE receptor (FcepsilonRI)-mediated mast cell activation was examined,
In AA supplemented cells, beta-hexosamidase, TNF-alpha release, calcium influx (Ca2+)and some protein tyrosine phophorylations including Syk and linker for activation of T cells (LAT) were enhanced, whereas, in MA or PA supplemented cells they were not changed.
In AA or EPA supplemented cells, intracellular production of ROS that is required for the tyrosine phosphorylation of LAT and Ca2+ influx were enhanced when compared with the others.
MA might therefore be very helpful to alleviate allergies. [x]
The OXE receptor optimally activated with 5-oxo-ETE, 5-oxo-18:2 and 5-oxo-20:3. The last can be formed under EFAD conditions. [x]
Re: Mead acid (a polyunsaturated fatty acid)
Good work; nice overview.
Levels of various essential nutrients (eg iron) are lowered in various diseases (and appetite suppressed), as being protective.
That does not make these nutrients less essential.
Given the overwhelming scientific evidence, there is no doubt about the benefits of essential fatty acids.
And as with every nutrient, its essentiality is conditional and too much is harmful.
But again, the info about mead acid is very much appreciated.
Levels of various essential nutrients (eg iron) are lowered in various diseases (and appetite suppressed), as being protective.
That does not make these nutrients less essential.
Given the overwhelming scientific evidence, there is no doubt about the benefits of essential fatty acids.
And as with every nutrient, its essentiality is conditional and too much is harmful.
But again, the info about mead acid is very much appreciated.
Re: Mead acid (a polyunsaturated fatty acid)
What about eating mead acid? It seems to be most concentrated in cartilage:
http://www.ncbi.nlm.nih.gov/pubmed/2001795
Could eating cartilage give mead acid
?
Just speculating.
Edit:
Plain laboratory analysis shows that unadulterated dry shark cartilage powder is approximately 41 % ash, 39 % protein, 12 % carbohydrates, 7 % water, less than 1 % fiber and less than 0.3 % fat.
So fat content is really low.
http://www.ncbi.nlm.nih.gov/pubmed/2001795
Could eating cartilage give mead acid
? Just speculating.
Edit:
Plain laboratory analysis shows that unadulterated dry shark cartilage powder is approximately 41 % ash, 39 % protein, 12 % carbohydrates, 7 % water, less than 1 % fiber and less than 0.3 % fat.
So fat content is really low.
Mead acid vs EPA, DHA, AA
The 10-fold increase in mead acid in essential fatty acid deficiency, may simply represent malnutrition.
Why do EPA, DHA or AA suppress mead acid production? Mayer, K et al Dahlin M Ling PR et al
Maybe simply because the body prefers these fatty acids over mead acid,
which likely has less functionality in comparison.
"Mead acid has been associated with an essential fatty acid deficit leading to male infertility"
"ELOVL2 was decreased, an essential enzyme for the formation of very-long PUFA, indispensable for spermatogenesis in testis". Casado ME et al
"testicular membrane phospholipids are high in DHA, as DHA is essential in proper delivery of membrane proteins" Roqueta-Rivera M et al
"Seminal plasma EPA and DHA concentrations positively correlate with seminal plasma SOD-like and catalase-like activity, which positively correlate with sperm count, sperm motility, and sperm morphology" Safarinejad MR
"DHA supplementation fully restores fertility and spermatogenesis" Roqueta-Rivera M et al
"DHA supplemenation shifts serum phospholipid fatty acids to a less pro-inflammatory profile"
(more DHA elevates DHA and EPA, and downregulates mead acid, DGLA and AA) van Biervliet S et al
"Linoleic acid, the major n-6/n-3 FA ratios, Mead acid and the EFA deficiency index in early breast milk were negatively associated with development up to 18 months of age. DHA and AA, respectively, in infants' plasma phospholipids was positively, but the AA/DHA ratio negatively, associated with development from 6 to 18 months of age". Sabel KG et al
"Docosahexaenoic acid (DHA) and arachidonic acid (AA) are important for neurodevelopment
Mead acid was negatively and n-6 fatty acids were weakly positively associated to the BSID mental developmental index". van Goor SA et al
Why do EPA, DHA or AA suppress mead acid production? Mayer, K et al Dahlin M Ling PR et al
Maybe simply because the body prefers these fatty acids over mead acid,
which likely has less functionality in comparison.
"Mead acid has been associated with an essential fatty acid deficit leading to male infertility"
"ELOVL2 was decreased, an essential enzyme for the formation of very-long PUFA, indispensable for spermatogenesis in testis". Casado ME et al
"testicular membrane phospholipids are high in DHA, as DHA is essential in proper delivery of membrane proteins" Roqueta-Rivera M et al
"Seminal plasma EPA and DHA concentrations positively correlate with seminal plasma SOD-like and catalase-like activity, which positively correlate with sperm count, sperm motility, and sperm morphology" Safarinejad MR
"DHA supplementation fully restores fertility and spermatogenesis" Roqueta-Rivera M et al
"DHA supplemenation shifts serum phospholipid fatty acids to a less pro-inflammatory profile"
(more DHA elevates DHA and EPA, and downregulates mead acid, DGLA and AA) van Biervliet S et al
"Linoleic acid, the major n-6/n-3 FA ratios, Mead acid and the EFA deficiency index in early breast milk were negatively associated with development up to 18 months of age. DHA and AA, respectively, in infants' plasma phospholipids was positively, but the AA/DHA ratio negatively, associated with development from 6 to 18 months of age". Sabel KG et al
"Docosahexaenoic acid (DHA) and arachidonic acid (AA) are important for neurodevelopment
Mead acid was negatively and n-6 fatty acids were weakly positively associated to the BSID mental developmental index". van Goor SA et al
Re: Mead acid vs EPA, DHA, AA
Mead acid is, as I have demonstrated before, not the sign of an essential fatty acid deficiency. These kind of quotes mean nothing. Mead acid is produced even when there are no signs of an essential fatty acid deficiency. It is also naturally alot higher in cartilage. If this quote would mean anything then people naturally have EFAD in their cartilage? These kind of claims can lead to false conclusions. The preassumption that MA indicates EFAD is not true.RRM wrote: "Mead acid has been associated with an essential fatty acid deficit leading to male infertility"
What I find interesting is that, since a diet will never be deficient in essential fatty acids so that is a silly thing to research, mead acid might have been produced next to the dietary PUFAs we get through our evolution. This is what we should investigate. We were never able to get our hands on so much PUFAs as we do now, look at indigineous pacific islanders that do not consume more than 2% PUFAs (and they do eat lots of fish) of their daily calories (like I showed in the topic of Kasper's thoughts) They might naturally produce mead acid.. We should also take into account that food always was scarce during our evolution, so that the production of Mead acid might have been even more likely to be produced. I would find it very interesting to know when mead acid production begins. And how much DHA and EPA you can take to keep on producing it. It is very hard to find good research on this.
The same research also concludes that: "However, there was no significant clinical improvement and no change in the inflammation as measured by erythrocyte sedimentation rate and IgG". This less pro-inflammatory profile is defined as that omega 3s are less inflammatory than AA. We've already seen that Mead acid is even less pro-inflammatory than omega 3. So that this research has little to no meaning.RRM wrote:"DHA supplemenation shifts serum phospholipid fatty acids to a less pro-inflammatory profile"
(more DHA elevates DHA and EPA, and downregulates mead acid, DGLA and AA) van Biervliet S et al
The last to articles you post are about very very very small percentages of mead acid. 0.20 to 0.50% wt. What I can see in the full report of the second article (the first one has so little results about Mead acid that I can't find out how it was possible to make the claims about mead acid). It seems to be highest at around 0.40%wt and then decreases again. The effects of the other fatty acids are simply too high to make a statement about mead acid. Don't you agree?RRM wrote:"Linoleic acid, the major n-6/n-3 FA ratios, Mead acid and the EFA deficiency index in early breast milk were negatively associated with development up to 18 months of age. DHA and AA, respectively, in infants' plasma phospholipids was positively, but the AA/DHA ratio negatively, associated with development from 6 to 18 months of age". Sabel KG et al
Also in that article:
"The full significance of Mead acid at the time around birth is not known and functions other than only being a marker of imbalance in the EFA status have recently been suggested [40]." They refer to this
Where we can read the effect mead acid has on osteoblast activity. It is suggested in the article that mead acid can prevent calcification of the fetal cartilages. And that this is the reason it is so high there. They also speculate that mead acid supplementation might stop or delay progression of ossification. Why would it be that high is my question? Are cartilages and especially the fetal cartilages so prone to calcification??
Re: Mead acid (a polyunsaturated fatty acid)
Good response, overkees.
You are mixing things up a little bit here.
"Mead acid being associated with..." does not refer to the absolute term mead acid (its existence in ...),
but its relative presence; the accumulation of mead acid.
Its not that when mead acid is present in the body at all, there is an EFAD.
The more essential fatty acid levels go down, the more mead acid goes up,
so that yes, mead acid is associated to EFAD assuming that these fatty acids actually are essential.
But the studies that he quotes, are not just about 'protein energy malnutrition' (PEM); low insulin levels, protein and zinc deficiency
but also about "a marked decrease of polyunsaturated FA with low LA and severely reduced linoleic acid metabolites, incl. AA". Koletzko B et al
and that in PEM there is evidence of essential fatty acid deficiency (EFAD),
"with notably skin changes, impaired resistance to infections, impaired growth rate and disturbed development
which may at least partly be explained by essential fatty acid deficiency (EFAD)
PEM may induce EFAD, due to low EFA intake, poor lipid digestion, absorption, transport, desaturation and increased EFA beta-oxidation and peroxidation.
EFAD may perpetuate itself by decreasing lipid absorption and transport, and aggravate PEM by impairing nutrient absorption and dietary calorie utilisation".Smit EN et al
These studies actually back up the accepted claim that mead acid is a marker for essential fatty acid deficiency.
What Kasper sees as 'protein energy malnutrition', here actually includes mild to full blown EFAD, associated with elevated mead acid.
It is likely that in chronic malnutrition, both protein and EFA deficiencies occur,
sharing the same symptoms: Fatty livers and similar skin lesions (in kwashiorkor and EFAD) Bouziane M et al
"increased lipid peroxidation and impaired PUFA metabolism in protein-energy malnutrition (PEM)" Squali Houssaïni FZ
"LC-PUFA improves intestinal repair in severe protein-energy malnutrition" Gil A et al
You should also ask yourself: why does the body prefer other PUFAs over mead acid?
Mead acid must be regarded as a "substitute", proven by the fact that mead acid levels go down if sufficient other PUFAs are available.
As much as we need it, that much the body will produce it. No need for interfering here.
And as (multiple-generation-) carnivorous animals and humans cannot make mead acid,
due to great dietary PUFA intake, this proves that we only need it as a back-up for dietary PUFAs.
You have not demonstrated that.overkees wrote:Mead acid is, as I have demonstrated before, not the sign of an essential fatty acid deficiency. These kind of quotes mean nothing. Mead acid is produced even when there are no signs of an essential fatty acid deficiency. It is also naturally alot higher in cartilage. If this quote would mean anything then people naturally have EFAD in their cartilage? These kind of claims can lead to false conclusions.RRM wrote: "Mead acid has been associated with an essential fatty acid deficit leading to male infertility"
You are mixing things up a little bit here.
"Mead acid being associated with..." does not refer to the absolute term mead acid (its existence in ...),
but its relative presence; the accumulation of mead acid.
Its not that when mead acid is present in the body at all, there is an EFAD.
The more essential fatty acid levels go down, the more mead acid goes up,
so that yes, mead acid is associated to EFAD assuming that these fatty acids actually are essential.
Kasper uses 2 studies to back up this claim.Kasper previously wrote:Mead acid production is not a reliable indicator of EFA status, as the mead acid/AA ratio is also up regulated in protein energy malnutrition.
But the studies that he quotes, are not just about 'protein energy malnutrition' (PEM); low insulin levels, protein and zinc deficiency
but also about "a marked decrease of polyunsaturated FA with low LA and severely reduced linoleic acid metabolites, incl. AA". Koletzko B et al
and that in PEM there is evidence of essential fatty acid deficiency (EFAD),
"with notably skin changes, impaired resistance to infections, impaired growth rate and disturbed development
which may at least partly be explained by essential fatty acid deficiency (EFAD)
PEM may induce EFAD, due to low EFA intake, poor lipid digestion, absorption, transport, desaturation and increased EFA beta-oxidation and peroxidation.
EFAD may perpetuate itself by decreasing lipid absorption and transport, and aggravate PEM by impairing nutrient absorption and dietary calorie utilisation".Smit EN et al
These studies actually back up the accepted claim that mead acid is a marker for essential fatty acid deficiency.
What Kasper sees as 'protein energy malnutrition', here actually includes mild to full blown EFAD, associated with elevated mead acid.
It is likely that in chronic malnutrition, both protein and EFA deficiencies occur,
sharing the same symptoms: Fatty livers and similar skin lesions (in kwashiorkor and EFAD) Bouziane M et al
"increased lipid peroxidation and impaired PUFA metabolism in protein-energy malnutrition (PEM)" Squali Houssaïni FZ
"LC-PUFA improves intestinal repair in severe protein-energy malnutrition" Gil A et al
Most likely, its always there, and only very much elevated in malnutrition (PUFAs, with/without protein deficiency)overkees wrote:I would find it very interesting to know when mead acid production begins.
You should also ask yourself: why does the body prefer other PUFAs over mead acid?
Mead acid must be regarded as a "substitute", proven by the fact that mead acid levels go down if sufficient other PUFAs are available.
As much as we need it, that much the body will produce it. No need for interfering here.
And as (multiple-generation-) carnivorous animals and humans cannot make mead acid,
due to great dietary PUFA intake, this proves that we only need it as a back-up for dietary PUFAs.
Re: Mead acid
This has been very clarifying, I must admit that I am now sure that Mead Acid (aka omege3/omega 6 deficient) isn't the way to go. However, I still think in the case of chronic stress due to chronic inflammations mead acid production can be very helpfull.
We also must develop a good understanding of other factors involved in the desaturase inhibition case as this might give a good indiciation of what levels of omegas are optimal and what is not. I've got some interesting things that I will post in my research development topic relating to that.
We also must develop a good understanding of other factors involved in the desaturase inhibition case as this might give a good indiciation of what levels of omegas are optimal and what is not. I've got some interesting things that I will post in my research development topic relating to that.