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

[Guest guest]

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,

--- In , " jwwright " <jwwright@...>

wrote:

>

> 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]

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]

My argument is can one get too little of LA? Can such deficiencies

really occur outside the lab? LA is found in so many foods as to be

almost unavoidable unless you're only eating the special casein diet

designed to produce EFA deficiency. It seems that the supposed effects

of LA deficiency were a little later on recognized as B6 deficiency.

One major clue, it seems, that one is deficient in LA is

hypermetabolism. Absence of mitochondrial/respiratory defect was early

on observed as an effect of EFA deficiency. With higher metabolism

deficiencies are quick to manifest themselves, as nutrients are used

up 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 respiration

and 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 diet

containing 4% of the total energy intake in the form of linoleic acid.

Effects of dietary EFA deficiency were investigated during a period of

2-30 weeks. Growth retardation becomes significant after 4 weeks of

deficiency and attains about 25% when the deficiency is maintained for

longer than 12 weeks. Respiration, body weight and age of

EFA-deficient rats and controls are in a nonlinear relationship. Basal

respiration in relation to the body weight is significantly increased

by EFA deficiency; it is unchanged when related to total animals under

the employed experimental conditions. Oxidative phosphorylation in

isolated liver mitochondria is unaffected by EFA deficiency, i.e., the

increased metabolic rate of EFA-deficient rats, related to the body

weight, cannot be explained from impaired functional integrity of the

inner mitochondrial membrane. Respiratory chain enzyme activities in

mitochondria from heart and skeletal muscle and specific amounts of

mitochondria 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 which

form the inner mitochondrial membrane are progressively damaged by

dietary intake of LA:

© 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

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...Mitochondria from aged animals fed

sunflower oil exhibited a lower number of cristae and a higher

circularity.

Hence damaged cellular respiration? What do you think?

Regards,

>

> 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=0a16f307d73c95495\

a2bb7decb577f03cb2c1df6 & 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.

>

>

>

[Guest guest]

,

" Can one get too little of LA? Can such deficiencies really occur

outside the lab? " -- The answer is yes. In the last year, I know of

at least two CRONers who had very high cholesterol levels because

their diets were very low in LA (omega-6) fatty acids. In one case,

almonds and olive oil were the main sources of dietary fat which, when

combined with caloric restriction, did not provide enough LA to

normalize blood cholesterol. Almonds and olive oil contain mostly

monounsaturated fatty acids which are useful for energy, but they do

not counter the cholesterolemic effects of the saturated fats

(palmitic acid) created by de novo synthesis of fatty acids from

carbohydrate metabolism. Low fat diets which are relatively high in

carbohydrates tend to increase cholesterol. Reference [1] shows how

LA, and polyunsturated fats in general, lower cholesterol.

Optimum Nutrition is not an easy thing to accomplish. There are many

variables.

Tony

[1] Mensink RP, Katan MB, Effect of dietary fatty acids on serum

lipids and lipoproteins: A meta-analysis of 27 trials. Arterioscler

Thromb 12: 911–919, 1992.

>

> My argument is can one get too little of LA? Can such deficiencies

> really occur outside the lab? LA is found in so many foods as to be

> almost unavoidable unless you're only eating the special casein diet

> designed to produce EFA deficiency. It seems that the supposed effects

> of LA deficiency were a little later on recognized as B6 deficiency.

> One major clue, it seems, that one is deficient in LA is

> hypermetabolism. Absence of mitochondrial/respiratory defect was early

> on observed as an effect of EFA deficiency. With higher metabolism

> deficiencies are quick to manifest themselves, as nutrients are used

> up 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 respiration

> and 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 diet

> containing 4% of the total energy intake in the form of linoleic acid.

> Effects of dietary EFA deficiency were investigated during a period of

> 2-30 weeks. Growth retardation becomes significant after 4 weeks of

> deficiency and attains about 25% when the deficiency is maintained for

> longer than 12 weeks. Respiration, body weight and age of

> EFA-deficient rats and controls are in a nonlinear relationship. Basal

> respiration in relation to the body weight is significantly increased

> by EFA deficiency; it is unchanged when related to total animals under

> the employed experimental conditions. Oxidative phosphorylation in

> isolated liver mitochondria is unaffected by EFA deficiency, i.e., the

> increased metabolic rate of EFA-deficient rats, related to the body

> weight, cannot be explained from impaired functional integrity of the

> inner mitochondrial membrane. Respiratory chain enzyme activities in

> mitochondria from heart and skeletal muscle and specific amounts of

> mitochondria in these tissues are unchanged by EFA deficiency.

>

> PMID: 6693988 [PubMed - indexed for MEDLINE]

[Guest guest]

Another nutrition science paradox then?

When you call something essential the implication is that the body

can't produce it, that it must obtain it through diet and that there

are no toxic side effects, at least at low doses. This does not seem

to be the case with linoleate. Mitochondrial toxicity is manifest at

low doses according to paper posted yesterday. When LA deficiency is

provoked in animals the contrary situation occurs: Muscle, heart and

liver mitochondria are healthy and function very vigorously without

any sign of oxidative or DNA damage according to the older paper also

posted. Thus, the more recent findings strongly seem to confirm the

earlier research. So there is evidence to support the theoretical

assumption that oxidative damage to mitochondria causes the

respiration defects which result in low energy and impaired tissue

maintenance.

The authors of the diabetic EFA deficient rat study reported that it

takes 27 weeks from the time the rat is still young to cause a

complete 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 not

take 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 symptoms

manifest themselves, why is a linoleate deficiency assumed when the

symptons disapear when linoleate is taken and no other fats? What if

olive oil (less than 7g LA per 100g)were taken instead of soy oil?

Would'nt that cure the deficiency? I know some here have experimented

with fat free diets. Any ideas? Could something else be involved or is

it 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=0a16f307d73c95495\

a2bb7decb577f03cb2c1df6 & 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.

> >

> >

> >

>

>

> .

>