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Food, Health, and Eco-news
Fish Oil Fears Prove Baseless, Again
Mouse study shows that normal oxidation of fish oil in the body is no risk, and likely a benefit 03/31/2014 By Craig Weatherby
Aging is driven in part by the gradual “rusting” (oxidation) of the molecules that make up our cells.
And the body uses its own internal “rustoleum”– called the antioxidant network – to slow that process.
Controlling oxidation requires a delicate balance, because the body uses oxidation reactions to turn foods into fuel and enable countless essential processes.
Consumption of oxidized or “rancid” fats poses a threat because these damaged fats can generate swarms of the unstable oxygen-based molecules called free radicals.
In turn, these free radicals damage molecules in our cells, which can cause problems and induce an injurious inflammation response that may become chronic and accelerate disease and aging.
Saturated fats are very resistant to oxidation, but polyunsaturated fats are very vulnerable to oxidation when exposed to air and light.
These include the omega-3 fatty acids from fish and a few plant foods (walnuts, flax seed, chia seed, and dark leafy greens), and the omega-6 fats from plants (corn, soy, safflower, sunflower, cottonseed).
The highly unsaturated “long chain” omega-3 fats found only in fish (DHA and EPA) are especially vulnerable to oxidation.
So we took it seriously when, a few years ago, some doctors began warning that supplemental fish oil is prone to oxidation in the body, with the potential to cause more harm than good.
Those anxieties were provoked by faulty leaps of logic, prompted by studies in which rodents were fed enormous amounts of seafood-source omega-3s (Song JH et al. 2000; Song JH et al. 2001; Saito M et al. 2003).
Such fears persists and keep cropping up on the Internet ... even though the available evidence indicates that supplemental (and food-borne) omega-3s do not get oxidized uncontrollably inside our bodies.
In fact, there's good evidence that normal intakes of seafood-source omega-3s produce indirect antioxidant effects that actually reduce consumers' free radical levels.
Now, evidence from a study in rodents offer more evidence that oxidation of dietary omega-3s is a normal, necessary, healthful process.
First, to put the findings in context, let's review the processes driving and underlying cardiovascular disease.
Cardiovascular disease: The key role of atherosclerosis (hardening of the arteries)
Atherosclerosis – a term that describes accumulation of arterial “plaque” – is the immediate cause, though not the root cause, of cardiovascular disease and congestive heart failure.
Arterial plaque eventually becomes inflamed and unstable and tosses off clots that cause heart attacks, stroke, and/or sudden cardiac death.
It's now clear that – with uncommon, genetics-based exceptions – dietary saturated fat and cholesterol are not the cause of cardiovascular disease or congestive heart failure in most patients.
Instead, sedentary lifestyles and the starchy, sugary American diet – which is also very high in omega-6 vegetable oils – drives the major risk factors for cardiovascular disease: chronic inflammation, high blood triglycerides, high blood levels of small, dense LDL cholesterol, and a low ratio of HDL cholesterol to total cholesterol.
Evidence that dietary omega-3s from fish fat help prevent atherosclerosis and cardiovascular disease is both voluminous and indisputable.
This is especially true disease when intake of competing omega-6 vegetable fats is not at the extremely high levels seen in the standard American diet.
The results of a new mouse study shed light on one reason why seafood-source omega-3s (DHA and EPA) appear to help prevent atherosclerosis and cardiovascular disease.
And they suggest that – far from being a problem – oxidation of omega-3s in the body yields cardiovascular benefits.
Mouse study finds cardiovascular benefits from oxidized omega-3s
A French-U.S. team that included USDA and University of California scientists just published the intriguing results of a study in rodents (Gladine C et al. 2014).
The cardiovascular system and risk factors of mice mirror our own pretty closely.
But the animals used in this study were highly prone to developing atherosclerosis, to more easily and quickly detect the effects of any changes to their diet.
The French-U.S. team set out to do three things:
  • See whether supplemental omega-3s became oxidized inside mice.
  • Identify the omega-3 metabolites (breakdown byproducts) created by oxidation.
  • Reveal whether the metabolites of oxidized omega-3s promote or prevent atherosclerosis.
For the study, atherosclerosis-prone mice received increasing doses of omega-3 DHA for 20 weeks.
Importantly, the maximum omega-3 dose the animals got roughly equaled the maximum daily intake (percent of total dietary calories) recommended for people ... not the extremely high doses used in in earlier studies, which produced problems.
After 20 weeks on DHA supplements, the researchers noted several beneficial outcomes:
  • A dose-related reduction in atherosclerosis, and in the animals' blood levels of triglycerides and cholesterol.  
  • Higher liver levels of a family of oxidation-produced DHA metabolites (F4-neuroprostanes) were linked to lower plaque levels.
  • Higher levels of omega-3-derived metabolites produced by oxidation proved a strong predictor of slower buildup of arterial plaque.
To paraphrase the authors, higher levels of oxidized omega-3s were an accurate “biomarker” for a slowing of the atherosclerosis process.
Of course, as they wrote, more research is needed to confirm this beneficial effect, and learn exactly how oxidized omega-3s might work to prevent atherosclerosis in people.
That said, this study should help ease unsubstantiated fears about the normal – and apparently beneficial – oxidation of seafood-source omega-3s in the body.
  • Egert S, Somoza V, Kannenberg F, Fobker M, Krome K, Erbersdobler HF, Wahrburg U. Influence of three rapeseed oil-rich diets, fortified with alpha-linolenic acid, eicosapentaenoic acid or docosahexaenoic acid on the composition and oxidizability of low-density lipoproteins: results of a controlled study in healthy volunteers. Eur J Clin Nutr. 2007 Mar;61(3):314-25. Epub 2006 Sep 13.
  • Gladine C, Newman JW, Durand T, Pedersen TL, Galano JM, Demougeot C, Berdeaux O, Pujos-Guillot E, Mazur A, Comte B. Lipid Profiling following Intake of the Omega 3 Fatty Acid DHA Identifies the Peroxidized Metabolites F4-Neuroprostanes as the Best Predictors of Atherosclerosis Prevention. PLoS One. 2014 Feb 18;9(2):e89393. doi: 10.1371/journal.pone.0089393. eCollection 2014.
  • Saito M, Kubo K. Relationship between tissue lipid peroxidation and peroxidizability index after alpha-linolenic, eicosapentaenoic, or docosahexaenoic acid intake in rats. Br J Nutr. 2003 Jan;89(1):19-28.
  • Song JH, Fujimoto K, Miyazawa T. Polyunsaturated (n-3) fatty acids susceptible to peroxidation are increased in plasma and tissue lipids of rats fed docosahexaenoic acid-containing oils. J Nutr. 2000 Dec;130(12):3028-33.
  • Song JH, Miyazawa T. Enhanced level of n-3 fatty acid in membrane phospholipids induces lipid peroxidation in rats fed dietary docosahexaenoic acid oil. Atherosclerosis. 2001 Mar;155(1):9-18.

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