Omega-3s from fish oxidize quickly when exposed to air, but are safe in the body, where they appear to blunt oxidation 10/06/2008
Fanciful factoids like this one, found on a Web site selling dietary supplements, appear all too frequently:
"Many people take fish oil supplements daily. However, research has shown that this can actually cause more free radicals to be released.”
Recently, we reported on a review of the medical literature, which exploded the myth that fish oil presents a bleeding risk because of its abundant omega-3s. (See "Can Fish Oil Cause Bleeding Risks?”.)
Today, we'll tackle another baseless fear.
Birth of a myth
There is no evidence that taking omega-3 fish oil creates significant amounts of free radicals in the body.
Yet this myth, born from unexamined assumptions, keeps getting repeated by careless commentators.
This misunderstanding stems from the fact that omega-3s are highly unsaturated fats, and as such will oxidize quickly when exposed to air.
Indeed, the susceptibility of a fatty acid to oxidation outside the body is largely dependent on its degree of un-saturation. (Lard, which is very high in fully saturated fats, resist rancidity for weeks or months at room temperature.)
However, animal and test tube studies suggest that highly unsaturated fats—including omega-3s—are not susceptible to oxidation inside the body.
Before reviewing the evidence that omega-3s do not create free radicals—and may actually act as free-radical suppressing antioxidants in the body—we should start with some basic facts:Oxidation is a chemical reaction in which the double bond on a fatty acid molecule reacts with oxygen to produce a variety of chemical byproducts, including the unstable oxygen compounds called free radicals.
- If created (or ingested) in numbers that overwhelm the body's internal "antioxidant network” (and any food-borne antioxidants), free radicals will damage cells.
- Oxidation of fats and other compounds in human cells damages DNA and causes inflammation, cancer, cardiovascular disease, senility, and overall aging.
- Oxidation destroys the nutritional value of omega-3 and omega-6 unsaturated fats, and results in the off-flavors associated with rancidity.
As we've said, unsaturated fats are susceptible to oxidation outside the body, but appear far less susceptible to oxidation in a living cell or body.
A recent research paper affirms this dichotomy and suggests that omega-3s may actually help suppress the formation of free radicals in the body.
Let's review that test tube study… and the results of three clinical trials, which support the safety and value of dietary omega-3s from fish and fish oil with regard to free radicals.
Omega-3s as antioxidants
Earlier this year, French researchers at the University of Pierre and Marie Curie published the results of a study in human arterial cells (Richard D et al. 2008).
|Our Salmon Oil's
bright orange antioxidant
Makers of fish oil supplements invariably add some vitamin E to control free radicals present in the oil when it is encapsulated.
If a fish oil was processed carefully, there should be few, but left unchecked, free radicals will gradually create more of themselves over time.
We add the carotene-class antioxidant pigment called astaxanthin to our Sockeye Oil, which wild sockeye absorb from the zooplankton they eat.
The astaxanthin in our Sockeye Salmon Oil is up to 100 times more powerful than vitamin E, which is used in most standard fish oils.
Fish oils are routinely tested for levels of oxidation, and our unrefined Salmon Oil just passed a regular, independent oxidation test with flying colors, coming in well under the industry standard. (See "What is the peroxide value of your Salmon Oil?” on our FAQ page.)
They probably chose to study the effects of omega-3s in arterial cells because they're where cardiovascular disease starts… and can be slowed or prevented.
In particular, the French team tested human aortic endothelial cells, taken from the lining of the largest artery in the human body.
The researchers exposed the artery cells to different fatty acids—including omega-3s, omega-6s, and saturated fats—and looked for the effects that each type of fat would have on creation of free radicals.
They also measured the effects that each fat had on creation of the two types of free radicals: oxygen- and nitrogen-based
Compared with exposing cells to saturated, monounsaturated, or omega 6 polyunsaturated fatty acids, exposing the artery cells to omega-3s resulted in creation of fewer oxygen radicals and fewer nitrogen radicals.
The antioxidant effects of omega-3s were greatest on oxygen radicals, which, compared with nitrogen radicals, wreak much greater havoc in the body.
Based on these results, the French scientists proposed that omega-3s act as indirect antioxidant agents in vascular endothelial cells, "hence diminishing inflammation and, in turn, the risk of atherosclerosis and cardiovascular disease.”
In other words, instead of creating free radicals and increasing oxidation in the body, their experiment indicates that omega-3s are strong allies against oxidation of artery cells.
Dietary fish oil does not need an antioxidant clean-up crew
As we said at the outset, many sources assert—based on the exceptional vulnerability of omega-3s to oxidation outside the body—that it is necessary to take antioxidants along with omega-3 fish oil.
These misguided folks presume that omega-3s get oxidized easily in the body, which certainly would create free radicals.
But the outcomes of two studies at Oregon State University—both led by Rosemary C. Wander, Ph.D.—demonstrated that people who consume omega-3s do not show significantly increased levels of free radicals.
And, significantly, this was true whether or not people took vitamin E—an antioxidant with special ability to protect fats—at the same time.
In one clinical trial, 46 postmenopausal women were divided into groups. Some took fish oil alone, and some took fish oil along with varying amounts (100 to 400 mg) of vitamin E (Wander RC, Du SH 2000).
The fish oil supplements contained relatively high doses of omega-3s… 2.5 grams of omega-3 EPA plus 1.8 grams of omega-3 DHA.
The results showed no clinically significant increase in free radicals after taking fish oil, and no difference between taking fish oil alone or with vitamin E.
As they wrote, "Although these data show a small but statistically significant increase in oxidative stress… after the consumption of EPA and DHA, the clinical relevance of this change is questionable… the results of this study indicate that there is no basis for vitamin E supplementation after consumption of EPA and DHA.”
In a second trial, 15 postmenopausal women took 15 grams (about ½ ounce) of one of three oils per day (Higdon JV et al. 2000):
- Hi-oleic sunflower oil rich in monounsaturated fats.
- Safflower oil rich in omega-6 fatty acids.
Fish oil rich in omega-3s (2.0 grams EPA and 1.4 grams DHA).
Like Dr. Wander's other study, this was a "crossover” trial, in which the subjects swapped regimens to be sure that the results were not affected by individual genetic or lifestyle differences among the women.
Blood tests showed that levels of a key marker of free radical damage associated with dangerous oxidation of LDL cholesterol (called MAD) were slightly higher after taking sunflower or safflower oil, while levels of other oxidation markers (called TBARs) were slightly higher after taking fish oil.
Dr. Wander's research fits with the French team's test tube findings, and indicates that omega-3s do not raise oxidation rates in the body.
British study affirms omega-3s' artery-protecting effects
In 2003, British researchers at the University of Southampton decided to test the hypothesis that uptake of omega-3 and omega-6 fats into advanced atherosclerotic plaques increases and decreases plaque stability, respectively.
As we've reported many times, omega-6 fats tend to promote inflammation, which destabilizes arterial plaque. When arterial plaque ruptures, it can release clots that cause heart attacks or strokes.
The British team performed a randomized, controlled clinical trial in 170 patients with dangerous plaque in the lining of their vital carotid artery (Thies F et al. 2003).
Some took omega-3-rich fish oil, others consumed sunflower oil—which is high in omega-6s—and some received placebo pills.
The volunteers were all scheduled to have plaque surgically removed from the lining of their carotid artery, which allowed the researchers to examine samples of the plaque post-surgery for three key factors that raise the risk that arterial plaque will rupture:
- Thin, unstable fibrous "caps” enclosing the plaque (as opposed to thicker, safer caps).
- Elevated levels of plaque-destabilizing inflammation.
- Higher number of macrophages (special white blood cells), which are attracted to and envelope the oxidized LDL cholesterol in plaque.
Their findings favored omega-3s:
- "Fewer plaques from patients being treated with fish oil had thin fibrous caps and signs of inflammation and more plaques had thick fibrous caps and no signs of inflammation, compared with plaques in patients in the control and sunflower oil groups.”
- "The number of macrophages in plaques from patients receiving fish oil was lower than in the other two groups.”
And their concluding remarks lend weight to the American Heart Association's advice that heart patients should take fish oil:
"Atherosclerotic plaques readily incorporate [omega-3s] from fish-oil supplementation, inducing changes that can enhance stability of atherosclerotic plaques. Stability of plaques could explain the reductions in non-fatal and fatal cardiovascular events associated with increased [omega-3] intake.”
The British team's findings also support admonitions to cut back on the omega-6 fats that dominate most vegetable oils and processed foods, which did not improve plaque stability over the short term of the study and are known to raise inflammation levels over time:
"By contrast, increased consumption of [omega-6s] does not affect [improve] carotid plaque fatty-acid composition or stability over the time course studied here.”
The bottom line is simple:
- Use olive oil instead of standard vegetable oils (corn, sunflower, safflower, cottonseed, canola, soy).
- Avoid packaged and restaurant foods, which are almost invariably loaded with standard, omega-6-rich oils.
- Make sure your diet includes ample amounts of fish-derived omega-3s.
The first and last lines are fairly easy to follow, but don't overlook the need to avoid omega-6s. Intake ratios of omega-6s to omega-3s that rise much higher than four to one are associated strongly with increased risk of cancer, heart disease, and depression.
And the average American's omega-6 to omega-3 intake ratio is more like 30 to one... ouch!
- Higdon JV, Liu J, Du SH, Morrow JD, Ames BN, Wander RC. Supplementation of postmenopausal women with fish oil rich in eicosapentaenoic acid and docosahexaenoic acid is not associated with greater in vivo lipid peroxidation compared with oils rich in oleate and linoleate as assessed by plasma malondialdehyde and F(2)-isoprostanes. Am J Clin Nutr. 2000 Sep;72(3):714-22.
- Richard D, Kefi K, Barbe U, Bausero P, Visioli F. Polyunsaturated fatty acids as antioxidants. Pharmacol Res. 2008 May 18. [Epub ahead of print]
- Thies F, Garry JM, Yaqoob P, Rerkasem K, Williams J, Shearman CP, Gallagher PJ, Calder PC, Grimble RF. Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial. Lancet. 2003 Feb 8;361(9356):477-85.
- Wander RC, Du SH. Oxidation of plasma proteins is not increased after supplementation with eicosapentaenoic and docosahexaenoic acids. Am J Clin Nutr. 2000 Sep;72(3):731-7.