by Craig Weatherby
Four years ago, a team at Children’s Hospital Boston published a mouse study showing that omega-3 DHA from fish oil retards a leading cause of blindness called retinopathy.
A follow-up study from the same researchers reveals exactly how omega-3s provide protection against retinopathy (Sapieha P et al 2011).
The results also provide reassurance that widely used non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin and ibuprofen don’t blunt omega-3 DHA’s apparent preventive powers.
Retinopathy is caused by a proliferation of tortuous, leaky blood vessels in the retina, and it counts as a leading cause of blindness.
Study finds omega-3 DHA rebuffs retinopathy in mice
Vascular overgrowth in the retina affects 4.1 million Americans with diabetes—a number expected to double over the next 15 years—and many premature infants.
Another 7 million-plus Americans have age-related macular degeneration (AMD), whose blinding “wet” form is typically caused by the same kind of abnormal blood vessel growth.
“The ability to prevent these ‘neovascular’ eye diseases with omega-3 fatty acids could provide tremendous cost savings,” said Children’s Hospital ophthalmologist Lois Smith, MD, PhD, senior investigator on the study (CHB 2011).
“The cost of omega-3 supplementation is about $10 a month, versus up to $4,000 a month for anti-VEGF therapy,” she noted, referring to drugs such as Macugen and Lucentis used in AMD and diabetic retinopathy. “Our new findings give us new information on how omega-3s work that makes them an even more promising option.”
Boston team pinpoints one source of DHA’s anti-blindness effect
In the new study, the Boston group detected a new protective mechanism—namely, a direct effect on blood vessel growth (Sapieha P et al. 2011).
Amazingly enough, omega-3 DHA selectively promoted the growth of healthy blood vessels and inhibited the growth of abnormal vessels.
In addition, Smith and colleagues isolated both the DHA metabolite (4-HDHA) that exerts these beneficial effects and the enzyme that produces it, called 5-lipoxygenase or 5-LOX.
They showed that the COX enzymes involved in inflammation-related pain are not involved in omega-3 breakdown… which suggests that the aspirin and other NSAIDs taken by millions of Americans daily should not interfere with omega-3 DHA’s eye benefits.
"This is important for people with diabetes, who often take aspirin to prevent heart disease, and also for elderly people with AMD who have a propensity for heart disease," says Smith (CHB 2011).
(An asthma drug called zileuton does interfere with 5-LOX and could negate the benefits of omega-3 DHA.)
Finally, the study demonstrated that 5-LOX acts by activating the PPAR-gamma receptor, the same receptor targeted by “glitazone” drugs such as Avandia, taken by diabetics to increase their sensitivity to insulin.
Since these drugs also increase the risk for heart disease—the FDA nearly banned Avandia in 2010—boosting omega-3 intake might be a safer way to improve insulin sensitivity.
Findings add to the risks of America’s gross “omega-imbalance”
The retinas of mice and men alike are packed with omega-3 fatty acids, which are lacking in the average American’s diet.
Americans’ diets tend to be extremely high in omega-6 fatty acids, compared with typical human diets prior to the industrial and agricultural revolutions of the 1800s.
(To read about research regarding the ill effects of this “omega-imbalance”, see the “Omega-3 / Omega-6 Balance” section of our news archive.)
For example, in Dr. Smith's previous study, mice fed diets rich in omega-3s had nearly 50 percent less damaging vessel growth in the retina than mice fed omega-6-rich diets.
The results of that 2007 study also showed that the omega-3-rich diet decreased pro-inflammatory cellular “messaging” in the eye.
Smith plans to continue seeking beneficial ways in which omega-3s might help deter retinopathy, while looking for the most harmful omega 6 metabolites.
“We found the good guys, now we'll look for the bad ones,” says Smith. “If we find the pathways, maybe we can selectively block the bad [omega-6] metabolites.” (CHB 2011)
Clinical trials underway to test DHA in people
Smith works closely with scientists at the National Eye Institute who are conducting an ongoing trial of omega-3 supplements in patients with AMD, known as AREDS2, which will end in 2013.
An earlier “retrospective” study, called AREDS1, linked higher self-reported intake of fish to a lower likelihood of developing AMD.
In addition, Smith is collaborating with a group in Sweden that’s conducting a clinical trial of omega-3s in premature infants, who are often deficient in omega-3.
That study will measure infants' blood levels of omega-3 products and follow the infants to see if they develop retinopathy. If results are promising Smith will seek FDA approval to conduct a clinical trial in premature infants at Children’s Hospital.
For our coverage of prior research on the role of omega-3s in eye health, see the “Omega-3s & Eye Health” section of our news archive.
Children's Hospital Boston (CHB). Omega 3's – more evidence for their benefit. Feb. 9, 2011. Accessed at http://www.eurekalert.org/pub_releases/2011-02/chb-o3020411.php
Children's Hospital Boston (CHB). Can blindness be prevented through diet? Increasing omega-3 intake in mice reduces damaging vessel growth in the eye. June 24, 2007. Accessed at http://www.childrenshospital.org/newsroom/Site1339/mainpageS1339P1sublevel309.html
Sapieha P et al. 5-Lipoxygenase Metabolite 4-HDHA Is a Mediator of the Antiangiogenic Effect of ω-3 Polyunsaturated Fatty Acids. Sci Transl Med 9 February 2011: Vol. 3, Issue 69, p. 69ra12. DOI: 10.1126/scitranslmed.3001571