8 replies to this topic

[niner]

One of my favorite things in science is discovering that something I believe is wrong. It's like figuring out that you had the wrong word in a crossword puzzle or the wrong piece in a jigsaw puzzle- it leads to greater progress. In the Fish Oil ethyl ester vs TG thread, Hebbeh brought the following paper to our attention. I think it deserves its own thread, as I'd like to bring the collective brain power of this community to this question: Is oxidized fish oil ok to consume? Are PUFAs and HUFAs harmless? This paper suggests that at least oxidized fish oil is not as bad as we might have thought, according to short term (7 week) measures. Long term effects remain an open question. Anything wrong with this picture?

British Journal of Nutrition , FirstView Articles : pp 1-12
DOI: 10.1017/S0007114511005484 (About DOI) Published online: 2011

Oxidised fish oil does not influence established markers of oxidative stress in healthy human subjects: a randomised controlled trial

Inger Ottestada1a2, Gjermund Vogta3, Kjetil Retterstøla4, Mari C. Myhrstada1, John-Erik Haugena3, Astrid Nilssona3, Gitte Ravn-Harena5, Berit Nordvia6, Kirsti W. Brønnera6, Lene F. Andersena2, Kirsten B. Holvena2 and Stine M. Ulvena1 c1

Intake of fish oil reduces the risk of CHD and CHD deaths. Marine n-3 fatty acids (FA) are susceptible to oxidation, but to our knowledge, the health effects of intake of oxidised fish oil have not previously been investigated in human subjects. The aim of the present study was to investigate markers of oxidative stress, lipid peroxidation and inflammation, and the level of plasma n-3 FA after intake of oxidised fish oil. In a double-blinded randomised controlled study, healthy subjects (aged 18–50 years, n 54) were assigned into one of three groups receiving capsules containing either 8 g/d of fish oil (1·6 g/d EPA+DHA; n 17), 8 g/d of oxidised fish oil (1·6 g/d EPA+DHA; n 18) or 8 g/d of high-oleic sunflower oil (n 19). Fasting blood and morning spot urine samples were collected at weeks 0, 3 and 7. No significant changes between the different groups were observed with regard to urinary 8-iso-PGF2α; plasma levels of 4-hydroxy-2-hexenal, 4-hydroxy-2-nonenal and α-tocopherol; serum high sensitive C-reactive protein; or activity of antioxidant enzymes in erythrocytes. A significant increase in plasma level of EPA+DHA was observed in both fish oil groups, but no significant difference was observed between the fish oil groups. No changes in a variety of in vivo markers of oxidative stress, lipid peroxidation or inflammation were observed after daily intake of oxidised fish oil for 3 or 7 weeks, indicating that intake of oxidised fish oil may not have unfavourable short-term effects in healthy human subjects.

(Accepted September 08 2011)

Here are a couple points that are brought up in the discussion section of the paper:

-Subjects were healthy & young. Would results be different otherwise?

-8-iso-PGF2a when measured in 24hr urine shows opposite results in other studies. This paper used a one-time spot urine collection, and might have missed the effect.

-Was there a problem with their use of 4-HHE as a marker of n-3 lipid oxidation? There was no correlation between plasma n-3 lipids and 4-HHE before the intervention. A previous study shows the expected effect on 4-HHE from n-3 supplementation.

So... are you ready to start swigging rancid oil?

[John2009]

I still want my fish oil as fresh as I can get it. The Eskimos get their fish as fresh as possible and they are the main model that started the fish oil craze.

The fact that these were healthy young subjects does make a difference in my view, because if someone is dealing with an illness, their system and their production of anti-oxidants may be overladed and/or maxed out. There is probably a big difference in the way a healthy person responds to pro-oxidants as compared to a person coping with an illness. There are many variables that could affect oxidation within the body, smoking, diet, stress (even traffic while driving to the study), and exposure to things in the persons work or home environment. You almost have to put people in the same living environment and on the same diet while doing a study like this just to try to control for some of the variables.

I think all we can do is try to compile all of the good, well done, relevant in-vivo studies on the oxidation issue in one place and then try to go through it and see what the overall body of evidence suggests.

At the same time, we should compile all the good in-vivo data on health, longevity, and fish oil, irrespective of the oxidation issue and see what the overall body of evidence suggests. The reason I say this is because at the end of the day, it's not whether fish oil is a pro-oxidant or not, it's whether fish oil is healthy to consume and whether it affects healthspan, mean lifespan, or maximum lifespan.

[Sillewater]

Redox Rep. 2000;5(1):45-6.

Effect of omega 3 fatty acids on oxidative stress in humans: GC-MS measurement of urinary F2-isoprostane excretion.

Mori TA, Puddey IB, Burke V, Croft KD, Dunstan DW, Rivera JH, Beilin LJ.

I was always under the impression fish oil decreased or had a neutral effect on measurable oxidative stress. It definitely seems that our bodies antioxidant network is able to cope with the increase in oxidizability of lipids in our membranes at a systemic level (also considering the fact that in vivo oxygen tension is quite low). For example in (1) when the mitochondria of monocytes from diabetics were taken and stimulated by PMA the relative increase in the accumulating fluorescent oxidative product increased quite a bit however in baseline measurement there was not a large difference [Edit: chart didn't work out sorry]

It seems to me that only large assaults beyond the capabilities of the antioxidant system of the body will have a measurable effect in terms of urinary isoprostanes (2). Also besides that fact, isoprostanes are a result from metabolism of HUFAs (well HUFAs with 3 contiguous methylene double bonds that are interrupted. From my reading the 8-iso-PGF2a is generated from arachidonic acid, thus if n-3's decrease n-6's presence in membrane, this marker would go long. EPA is peroxidized to F3-isoprostanes and DHA is converted to F4-isoprostanes. I've only read a couple of papers on this issue, so this may be totally off. Besides oxidative stress, the isoprostane pathway may form products that are damaging to mitochondria itself (3). 8-iso-PGF2a is measured because there are commercial products that measure it, however if you measure F3-isoprostanes for EPA you indeed see more of it then arachidonic acid produced PGF2a (5):

Oxidation of EPA in vitro yielded a series of compounds that were structurally established to be F3-IsoPs using a number of chemical and mass spectrometric approaches. The amounts formed were extremely large (up to 8.7 + 1.0 microg/mg EPA) and greater than levels of F2-IsoPs generated from arachidonic acid. We then examined the formation of F3-IsoPs in vivo in mice. Levels of F3-IsoPs in tissues such as heart are virtually undetectable at baseline, but supplementation of animals with EPA markedly increases quantities up to 27.4 + 5.6 ng/g of heart. Interestingly, EPA supplementation also markedly reduced levels of pro-inflammatory arachidonate-derived F2-IsoPs by up to 64% (p < 0.05).

This would explain the decrease in measured urinary isoprostanes in various studies supplementing fish oil. Thus oxidation probably is still happening at the mitochondrial level and consuming rancid/oxidized fatty acids probably isn't a good idea for now, as long as you believe the whole unsaturation mitochondrial idea.

Nb. (4) is an interesting study targeting mitochondria with MitoE and urinary isoprostanes PGF2a decreased. Indeed all the isoprostanes probably decreased (whether this is beneficial or not I do not know, just look at the naked mole rats, and this may be outdated but increase TBARS with CR).

Here is one where supplementation increased isoprostane levels, again measuring only PGF2a. Too many antioxidants become pro-oxidant again? If the subjects had less PUFAs in the membrane, peroxidation products may have been less?

Free Radic Biol Med. 2001 Sep 15;31(6):745-53.Supplementation with vitamin C and N-acetyl-cysteine increases oxidative stress in humans after an acute muscle injury induced by eccentric exercise.Childs A, Jacobs C, Kaminski T, Halliwell B, Leeuwenburgh C.

References

01. Diabetes Metab Res Rev. 2004 Sep-Oct;20(5):399-404.Increasing of oxidative stress from mitochondria in type 2 diabetic patients.Nakanishi S, Suzuki G, Kusunoki Y, Yamane K, Egusa G, Kohno N.
02. Cancer Epidemiol Biomarkers Prev. 2010 Jun;19(6):1506-10. Epub 2010 May 25.Urinary biomarkers of oxidative status in a clinical model of oxidative assault.Il'yasova D, Spasojevic I, Wang F, Tolun AA, Base K, Young SP, Marcom PK, Marks J, Mixon G, DiGiulio R, Millington DS.
03. Free Radic Biol Med. 2010 Aug 15;49(4):567-79. Epub 2010 Jun 2.Reactive gamma-ketoaldehydes formed via the isoprostane pathway disrupt mitochondrial respiration and calcium homeostasis.Stavrovskaya IG, Baranov SV, Guo X, Davies SS, Roberts LJ 2nd, Kristal BS.
04. Br J Nutr. 2011 Jul;106(1):87-95. Epub 2011 Feb 16.Effect of a mitochondria-targeted vitamin E derivative on mitochondrial alteration and systemic oxidative stress in mice.Mao G, Kraus GA, Kim I, Spurlock ME, Bailey TB, Beitz DC.
05. J Biol Chem. 2006 May 19;281(20):14092-9. Epub 2006 Mar 28.Formation of F-ring isoprostane-like compounds (F3-isoprostanes) in vivo from eicosapentaenoic acid.Gao L, Yin H, Milne GL, Porter NA, Morrow JD.

Edited by Sillewater, 13 December 2011 - 07:21 AM.

[hivemind]

People eat grilled fish. It's hilarious how strict people are about nutritional supplements compared to the food they eat.

They worry about mercury in their fish oil supplement and they they go and eat a can of tuna.

Edited by hivemind, 13 December 2011 - 07:43 AM.

[Adaptogen]

I just unwrapped my few month old bottle of nature's answer liquid fish oil and it was covered in a very thick sticky coating of fish oil. It opened pretty easily, like it might not have been sealed, but it smells/tastes fine, and it looks like nothing is missing from this bottle? I emailed swanson and they said they have sent me another...

Do you guys think I should use up this bottle anyway?

[hivemind]

it's clearly toxic, don't buy this
why not take hydrogen peroxide instead if you want free radicals

Hydrogen peroxide makes your teeth look nice and white. Not planning on eating it though...

Edited by hivemind, 30 January 2013 - 01:16 PM.

[niner]

I just unwrapped my few month old bottle of nature's answer liquid fish oil and it was covered in a very thick sticky coating of fish oil. It opened pretty easily, like it might not have been sealed, but it smells/tastes fine, and it looks like nothing is missing from this bottle? I emailed swanson and they said they have sent me another...

Do you guys think I should use up this bottle anyway?

It sounds like some leaked out, unless there was a spill from a different bottle that didn't get cleaned up, or something like that. I don't know how bad it has to get before it actually smells or tastes bad. Since they're replacing it, personally, I think I'd toss it. It's up to you though. It won't kill you...

[NeuroNootropic]

So what's the conclusion here? Is regular Fish Oil beneficial or the opposite? There are too many antagonizing articles on the Internet about it.

[Bron]

I agree it should have its own thread. I need to let it digest a bit more. I don't really know what else to say other than I have been petrified of oxidized fish oil for years...

I love these forums. Thanks niner and Hebbeh.

Definitely not going to start swigging rancid fish oil, but I think maybe I can stop worrying about the trip from halfway around the world my fish oil takes in the mail. And maybe I don't have to buy such an expensive fish oil with loads of anti-oxidants in it.

Edited by Bron, 02 March 2013 - 04:20 AM.