40 replies to this topic

[niner]

It is interesting, though, that Johanna Budwig lived to be 95 years old and followed a high Flax seed oil and cottage cheese diet which she developed for cancer patients.

It's not the omega 3-ness that's the problem, it's the high degree of unsaturation in EPA (5 double bonds) and DHA (6 double bonds) The susceptibility to oxidation goes up exponentially with each added double bond. Flax seed oil isn't highly unsaturated. It has 2 or 3 double bonds, I forget which.

[niner]

I took around 5g/day of EPA + DHA not 5g total fish oil volume but 5g of both EPA+DHA, back in 2006, will I be able to reverse any damage that may have caused through taking Vitamin E? I read that it addresses lipid peroxidation.

Vitamin E won't make any difference now. If it's been a number of years since high dose EPA/DHA, your membranes have probably returned to a more normal degree of unsaturation.

[zorba990]

Niner and Zorba,

Thanks so much for that info. I haven't stared 'massive' doses of DHA yet, that is just my current dosage. I will probably start taking about 30 g of fish oil as soon as I get my 500 mL bottle of it.

Thanks,

Ben

I thought Poliquin's assertion that paleo man ate copious amounts of brain tissue was interesting, but imagine cracking open the skull was a lot harder than drinking blood or eating some cooked or raw flesh. Probably more likely game, grassed meats had naturally higher Omega-3's, like this : www.northstarbison.com

You could be OK with 30 grams fish oil/day if you are careful to avoid rancid fish oil. Some folks worry about Omega3's as a cause of malondialdehyde and high levels of lipid peroxide , my personal experience has been to the contrary. In 2009 when I last took the Metametrix ION test, my result for lipid peroxides was very low despite the fact that I was taking 4 grams of omega3 a day. I attribute the test result to my care to avoid rancid fish oil. I use a 16 oz bottle of Nature's answer fish oil(rosemary oil protected). I taste all the fish oil I take, and know for certain it is not rancid. In addition, rosemary is an excellent anti-oxidant, and when I discovered how powerful it is (in the same range as BHT), I added 500 mg of rosemary extract to my supplements.

The concern is not really about the fish oil being rancid, but rather that high consumption of it causes the omega-3's to take up residence in the cell and mitochondrial membranes making those membranes and thus the integrity of the cell more likely to be oxidized (and malfunction and/or die presumably). At this point I am tending to agree with that hypothesis and I think that high dose fish oil is not a good idea. It is interesting, though, that Johanna Budwig lived to be 95 years old and followed a high Flax seed oil and cottage cheese diet which she developed for cancer patients.
http://www.budwigcen...g-biography.php

I took around 5g/day of EPA + DHA not 5g total fish oil volume but 5g of both EPA+DHA, back in 2006, will I be able to reverse any damage that may have caused through taking Vitamin E? I read that it addresses lipid peroxidation.

Why would Vitamin E be a problem? I've taken what most consider to be massive doses for decades.

[zorba990]

Niner and Zorba,

Thanks so much for that info. I haven't stared 'massive' doses of DHA yet, that is just my current dosage. I will probably start taking about 30 g of fish oil as soon as I get my 500 mL bottle of it.

Thanks,

Ben

I thought Poliquin's assertion that paleo man ate copious amounts of brain tissue was interesting, but imagine cracking open the skull was a lot harder than drinking blood or eating some cooked or raw flesh. Probably more likely game, grassed meats had naturally higher Omega-3's, like this : www.northstarbison.com

You could be OK with 30 grams fish oil/day if you are careful to avoid rancid fish oil. Some folks worry about Omega3's as a cause of malondialdehyde and high levels of lipid peroxide , my personal experience has been to the contrary. In 2009 when I last took the Metametrix ION test, my result for lipid peroxides was very low despite the fact that I was taking 4 grams of omega3 a day. I attribute the test result to my care to avoid rancid fish oil. I use a 16 oz bottle of Nature's answer fish oil(rosemary oil protected). I taste all the fish oil I take, and know for certain it is not rancid. In addition, rosemary is an excellent anti-oxidant, and when I discovered how powerful it is (in the same range as BHT), I added 500 mg of rosemary extract to my supplements.

The concern is not really about the fish oil being rancid, but rather that high consumption of it causes the omega-3's to take up residence in the cell and mitochondrial membranes making those membranes and thus the integrity of the cell more likely to be oxidized (and malfunction and/or die presumably). At this point I am tending to agree with that hypothesis and I think that high dose fish oil is not a good idea. It is interesting, though, that Johanna Budwig lived to be 95 years old and followed a high Flax seed oil and cottage cheese diet which she developed for cancer patients.
http://www.budwigcen...g-biography.php

Looking at this article, http://www.benbest.c.../CoEnzymeQ.html
maybe Vitamin E is an effective enough mitochondrial memrane antioxidant after all and taking massive amounts would protect from mitochondrial membrane oxidation as well:

Vitamin E is actually more effective as a mitochondrial membrane anti-oxidant than is CoEnzyme Q because Vitamin E neutralizes lipid peroxyl radicals far more readily and because Vitamin E is less hydrophobic, allowing it to more freely move throughout the mitochondrial membrane

Bit I still don't think it is worth it to take high dose fish oil.

Background on Vitamin E:
http://www.doctoryou...com/angina.html


1) Vitamin E has an oxygen-sparing effect on the heart, enabling the heart can do more work on less oxygen. The benefit for recovering heart attack patients is considerable. 1200 to 2000 IU daily relieves angina very well.
2) Vitamin E moderately prolongs prothrombin clotting time, and has a limited Coumadin/warfarin effect. This is the reason behind the Shutes' using vitamin E for thrombophlebitis and related conditions. Their dose? about 1000 to 2000 IU daily.
3) Vitamin E dilates and promotes collateral circulation and benefits diabetes patients or anyone threatened with gangrene. Dose: tailored to patient; about 800 IU or more.
4) Vitamin E strengthens and regulates heartbeat like digitalis (foxglove) and its derivatives at a dose adjusted between 800 to 3000 IU daily.
5) Vitamin E reduces scarring when frequently applied topically to burns or sites of lacerations or surgical incisions along with a daily oral dose of 800 IU.
6) Vitamin E helps gradually break down clots at a maintained dose of between 800 IU and 3,000 IU.
7) Vitamin E is vastly safer than drugs, as doses of up to 56,000 IU per day fail to harm adult humans. Gradual dosage increase is advised, and patients with congestive heart failure, rheumatic hearts or high blood pressure need careful medical supervision

[niner]

I took around 5g/day of EPA + DHA not 5g total fish oil volume but 5g of both EPA+DHA, back in 2006, will I be able to reverse any damage that may have caused through taking Vitamin E? I read that it addresses lipid peroxidation.

Why would Vitamin E be a problem? I've taken what most consider to be massive doses for decades.

I think what he means is could he take E now to fix damage that happened a long time ago. I don't think that would work.

[Hebbeh]

I found this study using 2.5 grams and 1.25 grams of EPA/DHA (7 grams and 3.5 grams regular fish oil) for 4 months interesting. It demonstrated a 15% reduction in oxidative stress and lengthing of telomeres compared to placebo....I've found other studies indicationg EPA/DHA lipid peroxidation may be over rated..of course adequate vitamin E and accompanying antioxidants is certainly wise and prudent.

http://www.scienceda...21001140957.htm

Omega-3 Supplements May Slow a Biological Effect of Aging


ScienceDaily (Oct. 1, 2012) — Taking enough omega-3 fatty acid supplements to change the balance of oils in the diet could slow a key biological process linked to aging, new research suggests.

The study showed that most overweight but healthy middle-aged and older adults who took omega-3 supplements for four months altered a ratio of their fatty acid consumption in a way that helped preserve tiny segments of DNA in their white blood cells.

These segments, called telomeres, are known to shorten over time in many types of cells as a consequence of aging. In the study, lengthening of telomeres in immune system cells was more prevalent in people who substantially improved the ratio of omega-3s to other fatty acids in their diet.

Omega-3 supplementation also reduced oxidative stress, caused by excessive free radicals in the blood, by about 15 percent compared to effects seen in the placebo group. "The telomere finding is provocative in that it suggests the possibility that a nutritional supplement might actually make a difference in aging," said Jan Kiecolt-Glaser, professor of psychiatry and psychology at Ohio State and lead author of the study.

In another recent publication from this study, Kiecolt-Glaser and colleagues reported that omega-3 fatty acid supplements lowered inflammation in this same group of adults.
"Inflammation in particular is at the heart of so many health problems. Anything that reduces inflammation has a lot of potentially good spinoffs among older adults," she said.
Study participants took either 2.5 grams or 1.25 grams of active omega-3 polyunsaturated fatty acids, which are considered "good fats" that, when consumed in proper quantities, are associated with a variety of health benefits. Participants on the placebo took pills containing a mix of oils representing a typical American's daily intake.
The researchers say this combination of effects suggests that omega-3 supplements could represent a rare single nutritional intervention that has potential to lower the risk for a host of diseases associated with aging, such as coronary heart disease, Type 2 diabetes, arthritis and Alzheimer's disease.

The study is published online and scheduled for later print publication in the journal Brain, Behavior, and Immunity.

Participants received either the placebo or one of the two different doses of omega-3 fatty acids. The supplements were calibrated to contain a ratio of the two cold-water fish oil fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), of seven to one. Previous research has suggested that EPA has more anti-inflammatory properties than DHA.

In the case of fatty acids, omega-3 supplementation alone doesn't tell the whole story of how this dietary change can affect health, explained Martha Belury, professor of human nutrition at Ohio State and a co-author of the study. Also important is the ratio of omega-6 fatty acids to omega-3 fatty acids that are present in a person's blood.
Omega-6 fatty acids come from vegetable oils, and since the 1960s, research has suggested that these oils, too, can help protect the cardiovascular system. However, the typical American diet tends to be heavy on omega-6 fatty acids and comparatively low in omega-3s that are naturally found in cold-water fish such as salmon and tuna. While the ratio of omega-6 to omega-3 fatty acids averages about 15-to-1, researchers tend to agree that for maximum benefit, this ratio should be lowered to 4-to-1, or even 2-to-1.
The long chains -- or bigger molecules -- that make up EPA and DHA fatty acids are believed to be the secret to their effectiveness, Belury said.
Both groups of participants who took omega-3 supplements showed, on average, lengthening of telomeres compared to overall telomere effects in the placebo group, but the relationship could have been attributed to chance. However, when the researchers analyzed the participants' omega-6 to omega-3 ratio in relationship to telomere lengthening, a lower ratio was clearly associated with lengthened telomeres.

"The idea we were looking at with the ratio of omega-6 to omega-3 fatty acids was an increase in the denominator to make the ratio smaller. In the United States, we need to focus on the omega-3 part because we don't get enough of those," Belury said.

The researchers also measured levels of compounds called F2-isoprostanes to determine levels of oxidative stress, which is linked to a number of conditions that include heart disease and neurodegenerative disorders. Both omega-3 groups together showed an average overall 15 percent reduction in oxidative stress compared to effects seen in the placebo group.

When the scientists revisited their earlier inflammation findings, they also found that decreases in an inflammatory marker in the blood called interleukin-6 (IL-6) were associated with telomere lengthening. In their earlier paper on omega-3s and inflammation, they reported that omega-3 supplements lowered IL-6 by 10 to 12 percent, depending on the dose. By comparison, those taking a placebo saw an overall 36 percent increase in IL-6 by the end of the study.

"This finding strongly suggests that inflammation is what's driving the changes in the telomeres," Kiecolt-Glaser said.

Telomeres are a hot topic in science, and their tendency to shorten is associated with such age-related problems as heart disease and early mortality. These short fragments of DNA act as caps at the end of chromosomes, and can be likened to the protective plastic at the end of a shoelace.

"If that plastic comes off, the shoelace unravels and it doesn't work anymore," said study co-author Ron Glaser, professor of molecular virology, immunology and medical genetics and director of the Institute for Behavioral Medicine Research (IBMR) at Ohio State. "In the same way, every time a cell divides, it loses a little bit of its DNA at the ends, and over time, that can cause significant problems."

Kiecolt-Glaser noted that this population was disease-free and reported very little stress. The study included 106 adults, average age 51 years, who were either overweight or obese and lived sedentary lives. The researchers excluded people taking medications to control mood, cholesterol and blood pressure as well as vegetarians, patients with diabetes, smokers, those routinely taking fish oil, people who got more than two hours of vigorous exercise each week and those whose body mass index was either below 22.5 or above 40.

"People who are less healthy than this group, and especially those who experience chronic stress, may gain even more benefits from omega-3 supplementation," she said.
Co-authors of the study include Elissa Epel, Jue Lin and Elizabeth Blackburn of the University of California, San Francisco; Rebecca Andridge and Beom Seuk Hwang of Ohio State's College of Public Health; and William Malarkey of the IBMR.

This work was supported in part by grants from the National Institutes of Health.

Journal Reference:

• Janice K. Kiecolt-Glaser, Martha A. Belury, Rebecca Andridge, William B. Malarkey, Beom Seuk Hwang, Ronald Glaser. Omega-3 supplementation lowers inflammation in healthy middle-aged and older adults: A randomized controlled trial. Brain, Behavior, and Immunity, 2012; 26 (6): 988 DOI: 10.1016/j.bbi.2012.05.011

[david ellis]

Looking at this article, http://www.benbest.c.../CoEnzymeQ.html
maybe Vitamin E is an effective enough mitochondrial memrane antioxidant after all and taking massive amounts would protect from mitochondrial membrane oxidation as well:

Vitamin E is actually more effective as a mitochondrial membrane anti-oxidant than is CoEnzyme Q because Vitamin E neutralizes lipid peroxyl radicals far more readily and because Vitamin E is less hydrophobic, allowing it to more freely move throughout the mitochondrial membrane

Bit I still don't think it is worth it to take high dose fish oil.

Background on Vitamin E:
http://www.doctoryou...com/angina.html


1) Vitamin E has an oxygen-sparing effect on the heart, enabling the heart can do more work on less oxygen. The benefit for recovering heart attack patients is considerable. 1200 to 2000 IU daily relieves angina very well.
2) Vitamin E moderately prolongs prothrombin clotting time, and has a limited Coumadin/warfarin effect. This is the reason behind the Shutes' using vitamin E for thrombophlebitis and related conditions. Their dose? about 1000 to 2000 IU daily.
3) Vitamin E dilates and promotes collateral circulation and benefits diabetes patients or anyone threatened with gangrene. Dose: tailored to patient; about 800 IU or more.
4) Vitamin E strengthens and regulates heartbeat like digitalis (foxglove) and its derivatives at a dose adjusted between 800 to 3000 IU daily.
5) Vitamin E reduces scarring when frequently applied topically to burns or sites of lacerations or surgical incisions along with a daily oral dose of 800 IU.
6) Vitamin E helps gradually break down clots at a maintained dose of between 800 IU and 3,000 IU.
7) Vitamin E is vastly safer than drugs, as doses of up to 56,000 IU per day fail to harm adult humans. Gradual dosage increase is advised, and patients with congestive heart failure, rheumatic hearts or high blood pressure need careful medical supervision

Zorba- I am just saying what I experienced. And it wasn't what everyone was afraid would happen. My lipids were less oxidized than normal. And it had nothing to do with Vitamin E. Rosemary oil was the antioxidant used to protect the fish oil. The explanation of the danger is too simple. It is true that Omega3's easily oxidize. But it is also true that Omega3's are necessary for a superior membrane. Especially in the brain. Messaging and metabolism are much faster and better with a highly permeable membrane. There is a balance that evolution has made. The danger of oxidation has and the advantages of a permeable membrane have been brought into balance by enough glutathione, glutathione conjugates, and SOD to pay the cost of easier oxidation. I don't know when the amount of Omega3 becomes dangerous. I do know when I supplemented 4 grams/day, I was safe.

[niner]

Kiecolt-Glaser noted that this population was disease-free and reported very little stress. The study included 106 adults, average age 51 years, who were either overweight or obese and lived sedentary lives. The researchers excluded people taking medications to control mood, cholesterol and blood pressure as well as vegetarians, patients with diabetes, smokers, those routinely taking fish oil, people who got more than two hours of vigorous exercise each week and those whose body mass index was either below 22.5 or above 40.

"People who are less healthy than this group, and especially those who experience chronic stress, may gain even more benefits from omega-3 supplementation," she said.
Co-authors of the study include Elissa Epel, Jue Lin and Elizabeth Blackburn of the University of California, San Francisco; Rebecca Andridge and Beom Seuk Hwang of Ohio State's College of Public Health; and William Malarkey of the IBMR.

Well, this is weird. It says that Elizabeth Blackburn and her co-workers are co-authors, but they aren't on the paper. Here's the abstract from pubmed:

Brain Behav Immun. 2012 Aug;26(6):988-95. Epub 2012 May 26.
Omega-3 supplementation lowers inflammation in healthy middle-aged and older adults: a randomized controlled trial.

Kiecolt-Glaser JK, Belury MA, Andridge R, Malarkey WB, Hwang BS, Glaser R.


Institute for Behavioral Medicine Research, Ohio State University College of Medicine, OH 43210, USA. Janice.Kiecolt-Glaser@osumc.edu


Observational studies have linked lower levels of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) with inflammation and depression. This study was designed to determine whether n-3 supplementation would decrease serum cytokine production and depressive symptoms in 138 healthy middle-aged and older adults (average age=51.04, SD=7.76) who were sedentary and overweight (average BMI=30.59, SD=4.50). This three-arm randomized, placebo-controlled, double-blind 4-month trial compared responses to (1) 2.5 g/d n-3 PUFAs, or (2) 1.25 g/d n-3 PUFAs, or (3) placebo capsules that mirrored the proportions of fatty acids in the typical American diet. Serum interleukin-6 decreased by 10% and 12% in our low and high dose n-3 groups, respectively, compared to a 36% increase in the placebo group. Similarly, low and high dose n-3 groups showed modest 0.2% and -2.3% changes in serum tumor necrosis factor alpha, compared to a 12% increase in the control group. Depressive symptoms were quite low at baseline and did not change significantly in response to supplementation. Our data suggest that n-3 PUFAs can reduce inflammation in overweight, sedentary middle-aged and older adults, and thus could have broad health benefits. These data provide a window into the ways in which the n-3 PUFAs may impact disease initiation, progression, and resolution. ClinicalTrials.gov identifier: NCT00385723.
PMID: 22640930 PMCID: PMC3398219 [Available on 2013/8/1]

Nothing about telomeres here, either. Is there a second paper? At any rate, they selected only fat couch potatoes. Vegetarians, thin people, and people who exercised were excluded, along with a lot of other exclusion criteria. These were people who had crappy carb and PUFA-laden diets and higher than average levels of inflammation. Getting their omega 3/6 ratio straightened out would be expected to reduce inflammation, which in turn would reduce oxidative stress. Telomeric DNA is particularly susceptible to oxidative damage, and there have been a host of papers connecting telomere length to stress and various conditions that all revolve around inflammation and oxidative stress. However, I'm not so sure that these results would translate to a healthy person with a good diet. If you are not suffering from oxidative stress or an omega-6 overload, you might see less of the positive outcome and more of the negative consequences. Getting your membranes loaded up with HUFAs is the gift that keeps on giving- they'll gradually get peroxidized, then break down to gnarly reactive compounds that float off and attack other biomolecules. At the same time, they'll also be gradually leaving the membrane if your diet changes to a less highly unsaturated version, so things can get better. Other weirdness: Why would the placebo group have a 36% increase in IL-6?

[Hebbeh]

Well, this is weird. It says that Elizabeth Blackburn and her co-workers are co-authors, but they aren't on the paper.

Nothing about telomeres here, either. Is there a second paper?

Some quotes from the article infer a second paper possibly. And yes, they were fat couch potatoes...because that is why these type of studies are done..

In another recent publication from this study, Kiecolt-Glaser and colleagues reported that omega-3 fatty acid supplements lowered inflammation in this same group of adults.

In their earlier paper on omega-3s and inflammation, they reported that omega-3 supplements lowered IL-6 by 10 to 12 percent, depending on the dose

[Hebbeh]

I don't think it's necessarily clear cut.......

http://www.efsa.euro...al/pub/2815.htm

Supplemental intakes of EPA and DHA consumed either alone or in combination at doses up to about 5 g/day for up to 16 weeks do not induce changes in lipid peroxidation which might raise concern in relation to cardiovascular disease (CVD) risk as long as the oxidative stability of these n-3 LCPUFA is guaranteed.

http://www.theheart....icle/1229499.do

EPA inhibited lipid hydroperoxide (LOOH) formation by 42% and 54% in vesicles with normal and elevated cholesterol levels, respectively. DHA, on the other hand, inhibited LOOH by 28% in vesicles with elevated cholesterol levels only.

More Fatties..........
http://www.ncbi.nlm....pubmed/20540666

The omega-3 fatty acids EPA and DHA decrease plasma F(2)-isoprostanes: Results from two placebo-controlled interventions.

Mas E, Woodman RJ, Burke V, Puddey IB, Beilin LJ, Durand T, Mori TA.

Source

University of Western Australia, Perth, WA, Australia. emilie.mas@uwa.edu.au

Abstract

Omega-3 (omega3) fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), protect against cardiovascular disease. Despite these benefits, concern remains that omega3 fatty acids may increase lipid peroxidation. It has previously been shown that urinary F(2)-isoprostanes (F(2)-IsoPs) were reduced following omega3 fatty acid supplementation in humans. It is now determined whether EPA or DHA supplementation affects plasma F(2)-IsoPs. In two 6-week placebo-controlled interventions, Study A: overweight, dyslipidaemic men; and Study B: treated-hypertensive Type 2 diabetic, patients were randomized to 4 g daily EPA, DHA. Post-intervention plasma F(2)-IsoPs were significantly reduced by EPA (24% in Study A, 19% in Study B) and by DHA (14% in Study A, 23% in Study B) relative to the olive oil group. The fall in plasma F(2)-IsoPs was not altered in analyses that corrected for changes in plasma arachidonic acid, which was reduced with EPA and DHA supplementation. Neither F(3)- nor F(4)-IsoPs were observed in plasma in both studies. These results show that in humans, EPA and DHA reduce in vivo oxidant stress as measured in human plasma and urine.

PMID: 20540666 [PubMed - indexed for MEDLINE]

This study indicates SOD2 is upregulated in response to Omega-3's to deal with any increased oxidation.....in rats anyway...

http://www.ncbi.nlm....pubmed/22062949

Int J Biochem Cell Biol. 2012 Jan;44(1):123-31. Epub 2011 Oct 30.
Omega-3 fatty acids enhance mitochondrial superoxide dismutase activity in rat organs during post-natal development.

Garrel C, Alessandri JM, Guesnet P, Al-Gubory KH.

Source

Unité de Biochimie Hormonale et Nutritionnelle, Département de Biologie-Toxicologie-pharmacologie, Centre Hospitalier Universitaire de Grenoble, Grenoble, France.

Abstract

The protection of the developing organism from oxidative damage is ensured by antioxidant defense systems to cope with reactive oxygen species (ROS), which in turn can be influenced by dietary polyunsaturated fatty acids (PUFAs). PUFAs in membrane phospholipids are substrates for ROS-induced peroxidation reactions. We investigated the effects of dietary supplementation with omega-3 PUFAs on lipid peroxidation and antioxidant enzyme activities in rat cerebrum, liver and uterus. Pups born from dams fed a diet low in omega-3 PUFAs were fed at weaning a diet supplying low α-linolenic acid (ALA), adequate ALA or enriched with eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA). Malondialdehyde (MDA), a biomarker of lipid peroxidation, and the activities of superoxide dismutase 1 (SOD1), SOD2, catalase (CAT) and glutathione peroxidase (GPX) were determined in the three target organs. Compared to low ALA feeding, supplementation with adequate ALA or with EPA+DHA did not affect the cerebrum MDA content but increased MDA content in liver. Uterine MDA was increased by the EPA+DHA diet. Supplementation with adequate ALA or EPA+DHA increased SOD2 activity in the liver and uterus, while only the DHA diet increased SOD2 activity in the cerebrum. SOD1, CAT and GPX activities were not altered by ALA or EPA+DHA supplementation. Our data suggest that increased SOD2 activity in organs of the growing female rats is a critical determinant in the tolerance to oxidative stress induced by feeding a diet supplemented with omega-3 PUFAs. This is may be a specific cellular antioxidant response to ROS production within the mitochondria.
Copyright © 2011 Elsevier Ltd. All rights reserved.

PMID: 22062949 [PubMed - indexed for MEDLINE]

Edited by Hebbeh, 15 October 2012 - 03:38 AM.

[niner]

I don't think it's necessarily clear cut....... http://www.efsa.euro...al/pub/2815.htm

Supplemental intakes of EPA and DHA consumed either alone or in combination at doses up to about 5 g/day for up to 16 weeks do not induce changes in lipid peroxidation which might raise concern in relation to cardiovascular disease (CVD) risk as long as the oxidative stability of these n-3 LCPUFA is guaranteed.

This study indicates SOD2 is upregulated in response to Omega-3's to deal with any increased oxidation.....in rats anyway... http://www.ncbi.nlm....pubmed/22062949

I suspect that the EFSA has given this a pretty careful look, and maybe the 5g mark is a reasonable cutoff? Below is a paper that had guys on a little over 6g of n-3 fatty acids from fish oil, and they were clearly showing oxidative stress.

Likewise, the SOD upregulation is a classic marker of oxidative stress. There's a definite inverted U-shaped curve with fish oil, we just need to figure out the dimensions of it. Here's a few refs regarding the dark side of fish oil.

Lipids. 1997 May;32(5):535-41.
Lipid peroxidation during n-3 fatty acid and vitamin E supplementation in humans.
Allard JP, Kurian R, Aghdassi E, Muggli R, Royall D.


The purpose of this study was to investigate in healthy humans the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake, alone or in combination with dL-alpha-tocopherol acetate (vitamin E) supplements on lipid peroxidation. Eighty men were randomly assigned in a double-blind fashion to take daily for 6 wk either menhaden oil (6.26 g, n-3 fatty acids) or olive oil supplements with either vitamin E (900 IU) or its placebo. Antioxidant vitamins, phospholipid composition, malondialdehyde (MDA), and lipid peroxides were measured in the plasma at baseline and week 6. At the same time, breath alkane output was measured. Plasma alpha-tocopherol concentration increased in those receiving vitamin E (P < 0.0001). In those supplemented with n-3 fatty acids, EPA and DHA increased in plasma phospholipids (P < 0.0001) and plasma MDA and lipid peroxides increased (P < 0.001 and P < 0.05, respectively). Breath alkane output did not change significantly and vitamin E intake did not prevent the increase in lipid peroxidation during menhaden oil supplementation. The results demonstrate that supplementing the diet with n-3 fatty acids resulted in an increase in lipid peroxidation, as measured by plasma MDA release and lipid peroxide products, which was not suppressed by vitamin E supplementation.

PMID: 9168460