Re: Re: Dietary omega-3 pufas (and some effects of the essential fatty acids)

[Guest guest]

Thanks, ,

I just hafta believe the human is far more complex than a rat in terms of hormonal pathways which are ill defined in the human. I also believe type 2 is caused by overeating.

We know that eating less and losing weight, IF we are overweight, will lower BP, and can cure type 2. It also has a large effect improving lipids in overweight people.

We also have pretty good idea what levels of LA and ALA we might need - very low (Harvard nurses study).

Everything else is a question of energy and what happens to excess unstable PUFA fatty acids. I don't doubt they effect the mitochondria.

We also know that CRONies experience lower BP and type 2, and better lipids, in general.

So why would I have to hypothesize or extrapolate from a rat model?

Regards.

[ ] Re: Dietary omega-3 pufas (and some effects of the essential fatty acids)

The "essentiality" status of LA and LNA has been much debated in the last few decades: with good reason as it has been long known that animals fed EFA deficient diets don't die of EFA deficiency but usually suffer from defiencies in other nutrients brought about by an otherwise poor diet. Such diets deficient in FA that have been considered essential (though with little and very obsolete scientific evidence)have surprising effects, such as the prevention of diabetes:(This study is somewhat old but still deserves attention when you consider the rather dramatic results of a rather straightforward protocol)J Exp Med. 1990 Mar 1;171(3):729-43. Prevention of diabetes in the BB rat by essential fatty acid deficiency. Relationship between physiological and biochemical changes.Lefkowith J, Schreiner G, Cormier J, Handler ES, Driscoll HK, Greiner D, Mordes JP, Rossini AA.Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.Essential fatty acid (EFA) deficiency exerts a striking protective effect in several animal models of autoimmune disease. We now report that EFA deprivation prevents diabetes in the BB rat, an animal model of human insulin-dependent diabetes mellitus. In diabetes-prone (DP)-BB rats, the incidences of spontaneous diabetes and insulitis (the pathological substrate of autoimmune diabetes) were greatly reduced by EFA deficiency. This beneficial effect of the deficiency state was also seen in diabetes-resistant (DR)-BB rats that, after treatment with antibody to eliminate RT6+ T cells, would otherwise have become diabetic. The susceptibility of EFA-deprived DP-BB rats to spontaneous diabetes was restored when they were given dietary supplements of linoleate at 70 d of age (during the usual period of susceptibility), but not when they were repleted beginning at 120 d (after the peak incidence of diabetes). EFA deficiency did lead to growth retardation, but calorically restricted control rats demonstrated that the protective effect of the deficiency state was not a function of decreased weight. To examine the relationship between the biochemical changes of EFA deficiency and its physiological effects in this system, we compared the fatty acid changes that occurred in EFA-deficient animals that did and did not develop diabetes. Nondiabetic animals had significantly lower levels of (n-6) fatty acids (i.e., linoleate and arachidonate) and higher levels of oleate, an (n-9) fatty acid, than did diabetic animals. Levels of 20:3(n-9), the fatty acid that uniquely characterizes EFA deficiency, were similar in both groups, however. Among diabetic EFA-deficient rats, the age at onset of diabetes was found to correlate inversely with the level of (n-6) fatty acids, the least depleted animals becoming diabetic earliest, whereas there was no correlation with levels of 20:3(n-9). Among animals repleted with linoleate beginning at 70 d, restoration of susceptibility to diabetes correlated with normalization of the level of arachidonate. In summary, EFA deprivation reduced the frequency of diabetes in both DP and RT6-depleted DR-BB rats. This protective effect was strongly associated with depletion of (n-6) fatty acids, particularly arachidonate, but not with accumulation of the abnormal 20:3(n-9). Conjecturally, arachidonate and/or a metabolite may play a key role in mediating inflammatory injury in this animal model of autoimmune diabetes.PMID: 2307932 [PubMed - indexed for MEDLINE] Very recent study on the adverse effects of PUFA on mitochondria, which, of course, would have negative consequences on energy production:The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 61:107-114 (2006)© 2006 The Gerontological Society of America Age-Related Mitochondrial DNA Deletion in Rat Liver Depends on Dietary Fat Unsaturation José L. Quiles, Julio J. Ochoa, M. Carmen -Tortosa, Jesús R. Huertas and José Mataix Institute of Nutrition and Food Technology, Departments of 1 Physiology 2 Biochemistry and Molecular Biology, University of Granada, Spain. We fed male Wistar rats lifelong on virgin olive (rich in the monounsaturated oleic acid) or sunflower (rich in the polyunsaturated linoleic acid) oil-based diets. At 6 and 24 months, liver mitochondria were analyzed for a mitochondrial DNA (mtDNA) deletion, reactive oxygen species, antioxidants, and ultrastructural alterations. An aging-related increase in the relative amount of the deletion was observed for both dietary groups, being higher in animals fed sunflower oil. Oxidative stress was lower in virgin olive oil-fed animals. Aging led to higher superoxide dismutase, catalase, and glutathione peroxidase activities and increased -tocopherol and coenzyme Q. Mitochondria from aged animals fed sunflower oil exhibited a lower number of cristae and a higher circularity. Results suggest that the age-related increase of the relative amount of deleted mtDNA depends on fat unsaturation. Moreover, the studied mtDNA deletion was correlated with mitochondrial oxidative stress and ultrastructural alterations. Conversely, would a deficiency in PUFA (less unsaturation, more saturation)lead to increased energy state? Better mitochondria function? More linking PUFA to DNA unstability:(The FASEB Journal. 1999;13:2138-2142.)© 1999 FASEB The effect of increased intakes of polyunsaturated fatty acids and vitamin E on DNA damage in human lymphocytes A. McE. JENKINSON1, A. R. COLLINS, S. J. DUTHIE, K. W. J. WAHLE and G. G. DUTHIE Rowett Research Institute, Bucksburn, Aberdeen, Scotland, U.K. AB21 9SB The effect of increasing dietary intakes of polyunsaturated fatty acids (PUFAs) and vitamin E on indices of oxidative DNA damage was investigated. Twenty-one healthy male, nonsmokers aged 28.9 ± 1.3 years participated in a free-living, split plot/change over trial in which half the volunteers consumed diets containing 5% PUFA as food energy for 4 wk and, after a 10 wk washout period, consumed a 15% PUFA diet for another 4 wk. The other volunteers followed an identical protocol, except that they consumed the 15% PUFA diet first. The diets were provided to volunteers either with or without an additional 80 mg d-tocopherol acetate/day; otherwise total fat, carbohydrates, protein, and basal vitamin E contents remained unchanged. DNA damage induced by 200 µM H2O2 in lymphocytes from volunteers as well as endogenous DNA damage in the form of oxidized pyrimidines, measured by alkaline single-cell gel electrophoresis (the comet assay), significantly decreased after consumption of the 5% PUFA diet (P<0.001 and P=0.01, respectively), but significantly increased after consumption of the 15% PUFA diet when -tocopherol levels were in the range of 5–7 mg/day (P=0.008 and P=0.03, respectively). These changes were abolished by an additional 80 mg d-tocopherol/day. This study indicates that increasing dietary levels of PUFA to 15% may adversely affect some indices of DNA stability. However, increasing the dietary intake of vitamin E by 80 mg/day ameliorates the damaging effects of PUFA.—on, A. McE., , A. R., Duthie, S. J., Wahle, K. W. J., Duthie, G. G. The effect of increased intakes of polyunsaturated fatty acids and vitamin E on DNA damage in human lymphocytes. Prsumamably, less intake of PUFA would decrease need for vitamin E.The following (perhaps)establishes implication of PUFA in etiology of skin cancer:Exp Dermatol. 2005 Mar;14(3):194-201. Polyunsaturated fatty acids partially reproduce the role of melanocytes in the epidermal melanin unit.Cario-Andre M, Briganti S, Picardo M, Nikaido O, de Verneuil H, Taieb A.INSERM E0217, Universite Victor Segalen Bordeaux II, 146 rue Leo Saignat, 33076 Bordeaux cedex, France.The incidence rate of melanoma is higher in fair-skinned than in dark-skinned individuals. In negroid skin there is more eumelanin which is present in all skin layers and fewer polyunsaturated fatty acids (PUFA) than in caucasoid skin. The western diet, which is rich in omega-6 polyunsaturated fatty acids, is associated with more proneness to cancer including cutaneous melanoma. To study the respective influence of omega-6 PUFA and low phototype melanocytes on redox status -basal and following UV irradiation-, we used epidermal reconstructs. The addition of polyunsaturated fatty acids as well as the presence of low phototype melanocytes affected basal status similarly except for catalase activity, which decreased significantly in polyunsaturated fatty acid-supplemented reconstructs. Following UV, polyunsaturated fatty acids and low phototype melanocytes increased lipid and protein oxidative damage without affecting direct DNA damage. However, polyunsaturated fatty acids increased epidermal apoptosis whereas low phototype melanocytes decreased it. Since our data suggest that an omega-6 PUFA rich-diet may increase oxidative damage in melanocytes without inducing apoptosis, the long-term net outcome could be cumulated mutations and an increased risk of skin cancer, especially melanoma.PMID: 15740592 [PubMed - indexed for MEDLINE] Regards, >> My problem, after reading all the posts and articles, is I still don't know what to do about poly's, so I'll continue getting the essential fatty acids and ignore the excess fat idea.> > Regards.>

[Guest guest]

LA as an EFA was determined in human tests. EFAD occurred in parenteral feeding and when they added n6 the deficiency went away.

If you eat too little oil you will get dusty arms. I've done that.

The idea of ALA importance came about because it was thought the ALA was needed for the EPA pathway. Eicosanoids result from both the AA and EPA pathways and we saw a lot of that in Sear's books.

BUT the EPA does not regulate the bad ole AA pathway, just the contrary, the AA metabolite, eicosa tetray noic acid, regulates both the AA and EPA pathways. (my post 7-12-05, 2:05PM, "The brains of .." referring to:

http://www.nutrition.org/cgi/content/abstract/130/6/1561?ijkey=0a16f307d73c95495a2bb7decb577f03cb2c1df6 & keytype2=tf_ipsecsha)

So there are eicosanoids from EPA, maybe. The paths are effected by verapamil, indomethiacin, aspirin, et al NSAIDS/medications.

I vote for using EPA/DHA supps. And I forget the ALA, other than the 2 gms in walnuts.

They have to do more than claim an association of say flax oil and cancer. They have to show a reasonable biochem connection.

And I've found no reasonable support for a ratio of n6:n3.

And I wouldn't gulp any fat/oil because I think the low fat idea has been quite accepted by many people who don't bother to comment.

I can't get to PMID: 2307932 PDF - my browser crashes. There are, I'm guessing some hormones that haven't been identified, that somehow regulate type 2, at least in the rat.

But not all overweight humans get type 2, right? Probably everyone eats some LA.

Should be some follow on insulin biochem article if that strategy is real.

Can a human that eats no LA get obese?

Regards.

[ ] Re: Dietary omega-3 pufas (and some effects of the essential fatty acids)

I agree too, JW. Yet the concept of EFA essentiality in humans was established as a result of experiments done on rats (Burr), which seemed acceptable at the time and is still cited today as there is still not much else to cite. So why would'nt more recent work showing the contrary be less acceptable to us? Overeating means excesses of all kinds of foods, including PUFA. Because the authors of the diabetic rat study posted found that the onset of diabetes as well as insulitis was not just retarded but prevented alltogether in all cases (see free PDF), it is conceivable that too much of these could represent the trigger for diabetes even in humans and that may not be the limit of their potential for endocrine disruption. Remember that PUFA represent a burden that accumulates with age and its effects could very likely be the same as aging in general. What we don't know for sure despite some strongly held positions for and against, is whether n-3 fatty acids also contribute to that burden. It seems more prudent to lower n-6 intake than gulping down quarts of flax seed oil. This morning I read somewhere the foolish notion that such oils are non-toxic in any quantity and thus recommended liberal intake...Kind Regards,> >> > My problem, after reading all the posts and articles, is I still > don't know what to do about poly's, so I'll continue getting the > essential fatty acids and ignore the excess fat idea.> > > > Regards.> >>

[Guest guest]

Off hand, I wouldn't know how to safely implement a low LA diet. I think if you did for too long you wouldn't remember what you did wrong. AA is a respectable part of the brain.

Mitos do die, maybe due to many things, respiration is one theory of aging.

Aubrey de Grey's Mitochondrial Free Radical Aging (MiFRA) theory?

Regards

[ ] Re: Dietary omega-3 pufas (and some effects of the essential fatty acids)

My argument is can one get too little of LA? Can such deficienciesreally occur outside the lab? LA is found in so many foods as to bealmost unavoidable unless you're only eating the special casein dietdesigned to produce EFA deficiency. It seems that the supposed effectsof LA deficiency were a little later on recognized as B6 deficiency.One major clue, it seems, that one is deficient in LA ishypermetabolism. Absence of mitochondrial/respiratory defect was earlyon observed as an effect of EFA deficiency. With higher metabolismdeficiencies are quick to manifest themselves, as nutrients are usedup more quickly, so sufficient nutrient intake is critical.J Nutr. 1984 Feb;114(2):255-62. The effect of essential fatty acid deficiency on basal respirationand function of liver mitochondria in rats. J, Patzelt J, Schafer H, Elmadfa I.Rats were fed a diet poor (0.05%) in essential fatty acids (EFA)with hydrogenated coconut oil as fat component, or a control dietcontaining 4% of the total energy intake in the form of linoleic acid.Effects of dietary EFA deficiency were investigated during a period of2-30 weeks. Growth retardation becomes significant after 4 weeks ofdeficiency and attains about 25% when the deficiency is maintained forlonger than 12 weeks. Respiration, body weight and age ofEFA-deficient rats and controls are in a nonlinear relationship. Basalrespiration in relation to the body weight is significantly increasedby EFA deficiency; it is unchanged when related to total animals underthe employed experimental conditions. Oxidative phosphorylation inisolated liver mitochondria is unaffected by EFA deficiency, i.e., theincreased metabolic rate of EFA-deficient rats, related to the bodyweight, cannot be explained from impaired functional integrity of theinner mitochondrial membrane. Respiratory chain enzyme activities inmitochondria from heart and skeletal muscle and specific amounts ofmitochondria in these tissues are unchanged by EFA deficiency.PMID: 6693988 [PubMed - indexed for MEDLINE]We know from the recent study I posted here that the cristae whichform the inner mitochondrial membrane are progressively damaged bydietary intake of LA:© 2006 The Gerontological Society of AmericaAge-Related Mitochondrial DNA Deletion in Rat Liver Depends on DietaryFat UnsaturationJosé L. Quiles, Julio J. Ochoa, M. Carmen -Tortosa, Jesús R.Huertas and José MataixWe fed male Wistar rats lifelong on virgin olive (rich in themonounsaturated oleic acid) or sunflower (rich in the polyunsaturatedlinoleic acid) oil-based diets...Mitochondria from aged animals fedsunflower oil exhibited a lower number of cristae and a highercircularity.Hence damaged cellular respiration? What do you think?Regards, >> LA as an EFA was determined in human tests. EFAD occurred inparenteral feeding and when they added n6 the deficiency went away.> If you eat too little oil you will get dusty arms. I've done that. > > The idea of ALA importance came about because it was thought the ALAwas needed for the EPA pathway. Eicosanoids result from both the AAand EPA pathways and we saw a lot of that in Sear's books. > BUT the EPA does not regulate the bad ole AA pathway, just thecontrary, the AA metabolite, eicosa tetray noic acid, regulates boththe AA and EPA pathways. (my post 7-12-05, 2:05PM, "The brains of .."referring to: >http://www.nutrition.org/cgi/content/abstract/130/6/1561?ijkey=0a16f307d73c95495a2bb7decb577f03cb2c1df6 & keytype2=tf_ipsecsha)> > So there are eicosanoids from EPA, maybe. The paths are effected byverapamil, indomethiacin, aspirin, et al NSAIDS/medications. > > I vote for using EPA/DHA supps. And I forget the ALA, other than the2 gms in walnuts. > > They have to do more than claim an association of say flax oil andcancer. They have to show a reasonable biochem connection. > > And I've found no reasonable support for a ratio of n6:n3.> > And I wouldn't gulp any fat/oil because I think the low fat idea hasbeen quite accepted by many people who don't bother to comment. > > I can't get to PMID: 2307932 PDF - my browser crashes. There are,I'm guessing some hormones that haven't been identified, that somehowregulate type 2, at least in the rat. > But not all overweight humans get type 2, right? Probably everyoneeats some LA.> > Should be some follow on insulin biochem article if that strategy isreal.> > Can a human that eats no LA get obese?> > Regards. > > >

..

[Guest guest]

At least, not well understood. There are many such items.

Diabetes is only one thing to consider. There is AMD, arthritis, joint cartilage, perhaps MS, as well as CVD, cancer, HTN, stroke, dementia. AA is a large part of the brain fat - DHA another.

Type 2, IMO we can handle with CR.

Just HTN is an enormous task. I'm told that one observer has > 500 diff equations describing HTN. NO human can comprehend that. These charts we see in 2-d are just 2 variables, and we strain to "see" the 3rd, 4th, 5th, and 6th dimensions. There are 9 dimensions of stress (at least).

A good question, still not completely answered, is how much protein do we need on CR, at minimum calories. I think I know how much "I" need, but what's the general equation? Will the amount change at age? Will it vary with the diseases, I incur? That's just a simple 2 more dimensions.

Same thing for fatty acids. I think I need about 11 LA and 2 ALA, but I have no idea what others need - wouldn't begin to guess. It must vary due to climate.

That puts me at > 60% carbs, most days.

I just don't see how a rat model helps me a lot, until it includes about 500 dimensions, and the rat weighs 150#.

Regards.

[ ] Re: Dietary omega-3 pufas (and some effects of the essential fatty acids)

Another nutrition science paradox then?When you call something essential the implication is that the bodycan't produce it, that it must obtain it through diet and that thereare no toxic side effects, at least at low doses. This does not seemto be the case with linoleate. Mitochondrial toxicity is manifest atlow doses according to paper posted yesterday. When LA deficiency isprovoked in animals the contrary situation occurs: Muscle, heart andliver mitochondria are healthy and function very vigorously withoutany sign of oxidative or DNA damage according to the older paper alsoposted. Thus, the more recent findings strongly seem to confirm theearlier research. So there is evidence to support the theoreticalassumption that oxidative damage to mitochondria causes therespiration defects which result in low energy and impaired tissuemaintenance. The authors of the diabetic EFA deficient rat study reported that ittakes 27 weeks from the time the rat is still young to cause acomplete arachidonate deficiency. In adult humans who knows? 4 years?6 years? from the time one stops intake how long before "symptons"present themselves? When the rats were "repleted" with EFA it did nottake long before diabetes set in. Here's the PDF for the diabetic rat study:http://www.jem.org/cgi/reprint/171/3/729 When fats are completly restricted in a diet and deficiency symptomsmanifest themselves, why is a linoleate deficiency assumed when thesymptons disapear when linoleate is taken and no other fats? What ifolive oil (less than 7g LA per 100g)were taken instead of soy oil?Would'nt that cure the deficiency? I know some here have experimentedwith fat free diets. Any ideas? Could something else be involved or isit just another case of hormesis?> >> > LA as an EFA was determined in human tests. EFAD occurred in> parenteral feeding and when they added n6 the deficiency went away.> > If you eat too little oil you will get dusty arms. I've done that. > > > > The idea of ALA importance came about because it was thought the ALA> was needed for the EPA pathway. Eicosanoids result from both the AA> and EPA pathways and we saw a lot of that in Sear's books. > > BUT the EPA does not regulate the bad ole AA pathway, just the> contrary, the AA metabolite, eicosa tetray noic acid, regulates both> the AA and EPA pathways. (my post 7-12-05, 2:05PM, "The brains of .."> referring to: > >> http://www.nutrition.org/cgi/content/abstract/130/6/1561?ijkey=0a16f307d73c95495a2bb7decb577f03cb2c1df6 & keytype2=tf_ipsecsha)> > > > So there are eicosanoids from EPA, maybe. The paths are effected by> verapamil, indomethiacin, aspirin, et al NSAIDS/medications. > > > > I vote for using EPA/DHA supps. And I forget the ALA, other than the> 2 gms in walnuts. > > > > They have to do more than claim an association of say flax oil and> cancer. They have to show a reasonable biochem connection. > > > > And I've found no reasonable support for a ratio of n6:n3.> > > > And I wouldn't gulp any fat/oil because I think the low fat idea has> been quite accepted by many people who don't bother to comment. > > > > I can't get to PMID: 2307932 PDF - my browser crashes. There are,> I'm guessing some hormones that haven't been identified, that somehow> regulate type 2, at least in the rat. > > But not all overweight humans get type 2, right? Probably everyone> eats some LA.> > > > Should be some follow on insulin biochem article if that strategy is> real.> > > > Can a human that eats no LA get obese?> > > > Regards. > >

..