164 replies to this topic

[Shepard]

I would be surprised to find any study to find w-3s increasing oxidative stress, especially in metabolically deranged states where AA concentration in the membrane is high. I was speaking of what happens in general cases of polyunsaturate autoxidation. The question is once you're low-carbed, with a proper balance of PUFA in cellular membranes, should you restrict dietary PUFAs? That answer is probably going to remain theoretical for a long time.

[DukeNukem]

I would be surprised to find any study to find w-3s increasing oxidative stress, especially in metabolically deranged states where AA concentration in the membrane is high. I was speaking of what happens in general cases of polyunsaturate autoxidation. The question is once you're low-carbed, with a proper balance of PUFA in cellular membranes, should you restrict dietary PUFAs? That answer is probably going to remain theoretical for a long time.

I agree. My current stance is that by restricting grains and processed vegetable oils (soy oil, corn oil, peanut oil, canola oil, and other oils with higher than 10% PUFA) you can also reduce fish oil. Because fish oil, in abundance, may by pro-inflammatory, I'd like to take only the amount needed for positive benefit and no more. It's still unknown what that amount is, or what the ratio is (n-3 to n-6), but some of the evidence in this thread suggests that when n-6 is low, n-3 can be low, too. I'm getting my blood work result on Tuesday, and I'll be keenly interested in my CRP level, for example.

Edited by DukeNukem, 18 January 2009 - 04:49 AM.

[niner]

This is one of the studies that david mentioned. That's a pretty big increase in serum malondialdehyde by the low-E oil. The generic fish oil that I take contains "natural tocopherols", but it doesn't say how much. I get some E in my multi, but only every other day and not at the same time as the fish oil. I don't know what to make of this.

J Nutr. 1991 Feb;121(2):165-9.
The effects of fish oil on triglycerides, cholesterol, fibrinogen and malondialdehyde in humans supplemented with vitamin E.
Haglund O, Luostarinen R, Wallin R, Wibell L, Saldeen T.

Department of Forensic Medicine, University of Uppsala, Sweden.

The effects of fish oils supplemented with 0.3 IU/g and 1.5 IU/g of vitamin E were compared in a double-blind, cross-over study. Twelve healthy volunteers were given 30 mL/day of either oil for 3 wk. Intake of the vitamin E-rich fish oil resulted in a marked decrease in serum triglycerides (48%) and in fibrinogen (11%). After administration of the low vitamin E-containing oil there was a considerably smaller reduction of serum triglycerides and no significant reduction of fibrinogen. Both oils caused an increase in high density lipoprotein cholesterol and a decrease in the atherogenic index, but neither oil altered the total cholesterol level. Serum vitamin E was decreased by 9% and plasma malondialdehyde was increased by 122% after intake of the low vitamin E-containing oil, but both remained normal after intake of the other oil. The effect of vitamin E may be due to inhibition of fatty acid peroxidation with less formation of malondialdehyde and a larger amount of active (n-3) fatty acids in their sites of action in the liver, resulting in a greater decrease in the synthesis of triglycerides and fibrinogen.

PMID: 1995786

[david ellis]

This is one of the studies that david mentioned. That's a pretty big increase in serum malondialdehyde by the low-E oil. The generic fish oil that I take contains "natural tocopherols", but it doesn't say how much. I get some E in my multi, but only every other day and not at the same time as the fish oil. I don't know what to make of this.

I don't know what to make of it either. I didn't worry as much because I supplement Vit E daily. First, the other studies didn't show an increase. So this study is an outlier. It would be good to know if the test subjects were supplementing with Vit E. Maybe higher malondialdehyde only happens to people deficient in serum Vitamin E.

edit note:
Maybe the study was to find out what happens when you compare protected fish oil with unprotected fish oil. Regular level of anti-oxidant protection compared with 5 times weaker?

We now have some excellent insight into what happens when you take fish oil that is not fresh.

Edited by david ellis, 18 January 2009 - 02:50 PM.

[david ellis]

That answer is probably going to remain theoretical for a long time.

Theoretical is good to hear because I supplement at 3.9 epa/dha grams a day. Nobody has evidence of what the upper limit per day should be. The malondialdehyde studies certainly suggest that significant amounts are beneficial, and the peroxidation is not linear. I would worry about losing fish oil benefits more than increased peroxidation. I failed to find a study that used large amounts of fish oil so we could have an idea of where that line is. I have the feeling that with millions of evolutionary years as hunter gatherers that the line will be much higher than my current intake. Hunter gatherers ate brains and bone marrow, excellent sources of EPA/DHA.

So thanks shepard.

[Sillewater]

I'm wondering if anybody has seen the papers that Peter talks about over at HyperLipid

Enhanced free radical scavenging and decreased lipid peroxidation in the rat fetal brain after treatment with ethyl docosahexaenoate.

Green P, Glozman S, Weiner L, Yavin E.
Department of Neurobiology, Weizmann Institute of Science, Rehovet, Israel.
In order to explore possible mechanisms to explain previously observed decreases in fetal brain lipid peroxidation (LPO) following intraamniotic administration of ethyl docosahexaenoate (Et-DHA) to near term fetuses, the hydroxyl radical trapping capacity of Et-DHA treated fetal brain preparations was compared to control ethyl oleate injected fetuses by electron spin resonance using 5,5'-dimethyl-1-pyrroline N-oxide (DMPO) probe. Lipid extracts from control brains showed little hydroxyl radical scavenging activity, whereas those from the Et-DHA injected animals exhibited an almost 70% decrease in the amount of DMPO-OH adducts. A marked decrease (58%) in LPO formation was noticed in the Et-DHA treated animals compared to controls. The Et-DHA treatment related trapping capacity resided in the phospholipid fraction of the lipid extract, which was enriched in both docosahexaenoic acid and aminophospholipid contents. The decreased LPO production, as well as increased production of prostaglandin E(2) and nitric oxide by the fetal brain following Et-DHA administration, could be mimicked by a synthetic quinone possessing both hydroxyl radical producing and LPO propagation inhibiting properties. The data are consistent with the possibility that the neuroprotective effect of Et-DHA might be due to possible free radical scavenging ability of the brain tissue and interference with LPO propagation.

Intraamniotic ethyl docosahexaenoate administration protects fetal rat brain from ischemic stress.

Glozman S, Green P, Yavin E.
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
Studies were conducted on the prenatal rat given a single intraamniotic injection of ethyl docosahexaenoate (Et-DHA; 9.6-12 mmol per fetus) or subjected to an n-3 fatty acid-deficient diet to assess the role of docosahexaenoate on oxidative stress during episodes of ischemia. A time-dependent decrease in the ability of brain slices from animals treated with Et-DHA to produce thiobarbituric acid-reactive substance (TBARS), most pronounced after 1 day (from 58.1 +/- 4.22 to 15.9 +/- 1.6 nmol/mg of DNA), was noticed on stimulation with Fe2+. Brain slices from fetuses treated for 1 day with Et-DHA and those from untreated fetuses produced TBARS levels of 46.7 +/- 6.5 and 114.8 +/- 10.8 nmol/mg of DNA, respectively, after a 20-min occlusion of the fetal-maternal circulation at embryonic day 20, suggesting a protective effect of Et-DHA. The protective effect of a single dose of Et-DHA in utero remained high up to 3 days after injection (p < 0.001) and was long-lasting, yet not significant, up to 3 days following birth. In agreement with a reduction in TBARS production by slices, the endogenous levels of TBARS in brains of Et-DHA-treated animals were lower than in the controls. Et-DHA-injected fetuses exhibited significantly higher levels of esterified DHA than the noninjected controls. n-3-deficient diet given to dams for 2 weeks before birth did not affect the levels of TBARS production in control fetal brain slices but abolished the increase caused by ischemia. Et-DHA administration for 24 h to n-3-deficient fetuses reduced the amount of TBARS produced by the fetal brain slices from 49.1 +/- 8.5 to 31.7 +/- 4.1 nmol/mg of DNA. A protective effect from oxidative damage after postischemic oxidative stress in fetal brain following DHA supplements is suggested, whereas the effect of n-3 fatty acid deficiency in this regard is more ambiguous.

He goes over the papers here: DHA in rats

For now I'm reducing my fish oil intake to every other day, but the fish oil I consume has mixed tocopherols in it, and every other day I take FamilE with my fish oil.

[rwac]

For now I'm reducing my fish oil intake to every other day, but the fish oil I consume has mixed tocopherols in it, and every other day I take FamilE with my fish oil.

What fish oil would that be ?

[Jacovis]

Would taking the Algatrium branded DHA product be any different? - it is marketed as boosting antioxidant activity in the body...

http://www.nutraingr...s-North-America
New high bioavailability DHA reaches North America
By Lorraine Heller, 14-May-2009

A concentrated DHA ingredient that claims to closely resemble DHA found in human breast milk has been launched on the North American market, following a distribution agreement between Spanish firm Brudy and New Jersey-based Xsto Solutions.
The structural similarities between Algatrium branded docosahexaenoic acid (DHA) omega-3 and the DHA found and utilized in the human body mean that it is more bioavailable and bioactive than other alternatives on the market, claim the companies.

Algatrium, which is derived from fish oil, is made using a technology that Brudy first started working on ten years ago. This uses natural enzymes to concentrate DHA in the second position on the triglyceride molecule, which is the structural form found in human breast milk.

Triglycerides, which are the lipid forms that omega-3 DHA and EPA are found in, are made up of glycerol molecules with three fatty acids linking to them.

DHA from fish or algae is generally found in the first or third positions on the triglyceride backbone. When it is consumed, the body converts and stores most of it in tissue in the second position.

“In the case of Algatrium, we are enzymatically doing (outside the body) what our body would normally do internally be rearranging and concentrating the DHA molecule from the one and three position on the triglyceride backbone to the number two position,” explained Brudy and Xsto.

According to the companies, this allows for a higher bioavailability and bioactivity of the ingredient compared to some other sources of DHA.

Although Brudy’s technology can be applied to omega-3 from algae or vegetal sources, the firm says that fish is currently the “optimal” source of raw material.

Antioxidant benefits

Another major property of the Algatrium ingredient is that it can boost antioxidant activity in the body, explained Brudy.

By increasing intracellular concentration of the antioxidant glutathione, the company claims its ingredient can help cells in the human body increase their antioxidant activity by 300 percent.

This antioxidant activity is supported by six in vitro trials and two human trials, said Xsto.

The Algatrium studies used cycling athletes in strenuous workouts to create metabolic stress, oxidative stress and possible DNA damage, explained Dan Murray, VP of business development at Xsto. Some of the findings included decreased DNA damage, decreased oxidative damage, and an increase in total plasma anti-oxidant capacity.

Alagtrium will be marketed for both its antioxidant benefits and the heart and cognitive benefits associated with DHA in general.

“Brudy focuses on the anti-oxidant benefit above all else (…) While Xsto agrees the product has significant anti-oxidant benefit, we feel this is not communicating the full value of the product. It is, after all, DHA and deserves to carry all the claims and benefits of DHA products. However, with its enhanced bioavailability, it can claim all the regular benefits plus the more potent anti-oxidant claim researched as well,” Murray told NutraIngredients-USA.com.

“As the Brudy process is more expensive than normal processing, we will be priced at a premium to regular sources of DHA. We will need to clearly distinguish ourselves from ‘regular’ DHA.”

To watch a short video with Brudy’s director general Francisco Gassó and Xsto’s VP of business development Dan Murray, click here .

[nameless]

Interesting site at HyperLipid, thanks for posting a link.

A couple of fishy questions:

If DHA causes some pro-oxidant effects in the body, how much E must be consumed at the same time to mitigate this? And for that matter, how much DHA could potentially cause a problem?

Would taking an EPA-only fish oil have similar oxidation concerns too?

And does EPA suppress the immune system or modulate it? I was never clear on that issue, or what doses are considered acceptable before the immune system could be affected.

And does krill oil bypass all of these potential fish problems?

[Sillewater]

For now I'm reducing my fish oil intake to every other day, but the fish oil I consume has mixed tocopherols in it, and every other day I take FamilE with my fish oil.

What fish oil would that be ?

I'm taking this one right now:
Natural Factors, RxOmega-3 Factors Pharmaceutical Grade

But I used to take one that was high in DHA and low in EPA:
NSI DHA EFA from Fish Oil

I took the one high in DHA because I was wondering if there would be any cognitive effects. For me there was none, except it may have made me feel a bit more lethargic than usual. I'll be taking the Natural Factors one soon and see if there is a difference. But what I'm worried about most is whether its slowly unextending my life, so for now I'll stick to a low dose of EPA/DHA and try and keep my omega 6 low.

[david ellis]

That answer is probably going to remain theoretical for a long time.

Theoretical is good to hear because I supplement at 3.9 epa/dha grams a day. Nobody has evidence of what the upper limit per day should be. The malondialdehyde studies certainly suggest that significant amounts are beneficial, and the peroxidation is not linear. I would worry about losing fish oil benefits more than increased peroxidation. I failed to find a study that used large amounts of fish oil so we could have an idea of where that line is. I have the feeling that with millions of evolutionary years as hunter gatherers that the line will be much higher than my current intake. Hunter gatherers ate brains and bone marrow, excellent sources of EPA/DHA.

So thanks shepard.

I was worried about this because I supplement at a relatively high level of at 3.9 grams of EPA/DHA /day. So I had my lipid peroxides measured by a Metametrix lipid peroxide test. I just missed the bottom quintile(that's good-i.e. low peroxides) of the reference range, and was in the bottom third of the Metametrix recommended range. The test measures membrane oxidative damage done by oxygen free radials to the polyunsaturated fatty acid component of cell membranes. The test reflects whole-body free radical activity. I am not an expert, it seems I shouldn't worry about taking fish oil, is there another way to look at this?

Most of the criticism of fish oil comes from Caloric Restriction folks. They are in a little bit of a bind because their peroxidation levels measured by ION tests is relatively high. Their explanation is that their peroxidation within the cell is low, and higher in the blood because of the higher level of repair activity going on. Maybe that is part of the story why they are advising others to cut down on their fish oil.

[kilgoretrout]

What about the studies that show lower levels of cardio diseases and stroke in populations that consume lots of fish oil? These were very large cohorts; observational studies.

[Sillewater]

That answer is probably going to remain theoretical for a long time.

Theoretical is good to hear because I supplement at 3.9 epa/dha grams a day. Nobody has evidence of what the upper limit per day should be. The malondialdehyde studies certainly suggest that significant amounts are beneficial, and the peroxidation is not linear. I would worry about losing fish oil benefits more than increased peroxidation. I failed to find a study that used large amounts of fish oil so we could have an idea of where that line is. I have the feeling that with millions of evolutionary years as hunter gatherers that the line will be much higher than my current intake. Hunter gatherers ate brains and bone marrow, excellent sources of EPA/DHA.

So thanks shepard.

I was worried about this because I supplement at a relatively high level of at 3.9 grams of EPA/DHA /day. So I had my lipid peroxides measured by a Metametrix lipid peroxide test. I just missed the bottom quintile(that's good-i.e. low peroxides) of the reference range, and was in the bottom third of the Metametrix recommended range. The test measures membrane oxidative damage done by oxygen free radials to the polyunsaturated fatty acid component of cell membranes. The test reflects whole-body free radical activity. I am not an expert, it seems I shouldn't worry about taking fish oil, is there another way to look at this?

Most of the criticism of fish oil comes from Caloric Restriction folks. They are in a little bit of a bind because their peroxidation levels measured by ION tests is relatively high. Their explanation is that their peroxidation within the cell is low, and higher in the blood because of the higher level of repair activity going on. Maybe that is part of the story why they are advising others to cut down on their fish oil.

Thanks for posting that test, because it takes a load of my shoulders. This is just speculation, but if incorporating DHA into our brains helped us get bigger and better brains, then our bodies should have developed mechanisms to deal with the increased oxidation. And even though hunter gatherers may have consumed high amounts of EPA/DHA doesn't mean that it promotes longevity, but it could suggest that we have by now developed protective mechanisms. So after reading the papers posted at HyperLipid, I thought it would be okay and if anything more stable than EPA.

Since your test was done when you had taken both EPA/DHA, maybe high DHA would have a different result. Did you also take any other antioxidants at the time such as Vitamin E, astaxanthin, or such? Did you also have a baseline measurement?

[david ellis]

Since your test was done when you had taken both EPA/DHA, maybe high DHA would have a different result. Did you also take any other antioxidants at the time such as Vitamin E, astaxanthin, or such? Did you also have a baseline measurement?

Yes, I take natural Vitamin E, astaxanthin, melatonin, and about 2 grams of C. The test measures general lipid peroxidation, nothing specific about EPA/DHA. The lipid peroxidation, a TBARS test, was part of an ION test battery from Metametrix. ION stands for Individual Optimized Nutrition. The ION test is my baseline.

[Sillewater]

Found these over at M&M

Omega-3: Healthy No Matter What?
Benefits of Oxidized Fish Oil??, Better at PPARa Activation
More on oxidized EPA

So what to make of these.