January-February 2020


What your patient is taking and its effect on the eye
Nutraceuticals: Benefits to ocular health and importance of product selection

by Vanessa Caceres Contributing Writer

“I tell patients that not all omega-3s are the same.”

—Cynthia Matossian, MD

Ophthalmologists normally focus on medication when treating patients with ocular surface disease, age-related macular degeneration, and other conditions or pathologies. However, nutraceuticals are also considered by some physicians.
Omega-3 fatty acids in particular come out strong in the discussion about nutraceutical use within ophthalmology.

The scoop on omega-3s

Omega-3 fatty acids have been both touted and debated in the literature for a variety of health benefits.
Research on omega-3s and dry eye has found that re-esterified omega-3 supplementation can lead to a statistically significant improvement in multiple endpoints including tear osmolarity, omega-3 index levels, tear breakup time, symptom scores, and matrix metalloproteinase-9 inflammation, said Alice Epitropoulos, MD, who was lead author of a study on the topic.1
The buzz over omega-3s for dry eye led to a “real world” randomized clinical trial known as the Dry Eye Assessment and Management (DREAM) Study. This study was published in 2018 and compared patients randomly assigned to receive supplements containing 3,000 mg of omega-3 for a year vs. those getting a placebo of olive oil.2 Patients in the omega-3 and the placebo arms experienced improvements in the Ocular Surface Disease Index score and in conjunctival and corneal staining, however, researchers did not find a statistically significant difference in those receiving omega-3 supplementation with those who received the placebo.
Nevertheless, these results have not discouraged anterior segment surgeons who recommend omega-3 supplement use. If anything, they found it supported what they already follow. “Both olive oil and omega-3 fatty acids worked,” said John Sheppard, MD. “That’s encouraging because we’re always hearing how the Mediterranean diet is good for the eyes.” The Mediterranean diet encourages fish and olive oil, in addition to vegetables and whole grains.
Although there is not a clear-cut omega-3 dosing recommendation for the general public, the American Heart Association recommends patients with documented heart disease consume 1,000 combined milligrams of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) daily, preferably from food. EPA and DHA are two types of omega-3 fatty acids. Registered dietitians generally advise consuming fatty fish for omega-3s but say that a supplement may be used if that is not possible.

There is a caveat

The ophthalmologists interviewed for this story said omega-3 fatty acid supplementation processed in a specific way has the most benefits for ocular health, with fewer side effects.
“I tell patients that not all omega-3s are the same,” said Cynthia Matossian, MD, who was a coauthor of the study led by Dr. Epitropoulos. When fish are caught for omega-3 processing, their oil is squeezed out, but that oil also contains heavy metals, such as mercury. Most processors of omega-3 supplements take the oil and add alcohol to process it, Dr. Matossian said. Then, they extract heavy metals through a processing called ethyl ester.
“Most cheaper versions of omega-3 let the product cool to room temperature and then they encapsulate it,” Dr. Matossian said. However, the gastrointestinal (GI) tract does not recognize this version as fish as it’s been chemically altered. “As a result, absorption is not as good. The omega sits around in the gut and leads to fish burps, embarrassing gas, and stomach issues. A lot of people discontinue it because of GI effects,” she said.
A process called re-esterification extracts the heavy metals but then converts the product back to a triglyceride fish form, so the body recognizes the omega-3 as salmon or tuna. It helps absorption and reduces GI issues, Dr. Matossian said.
Brands mentioned by the physicians interviewed for this article include DE3 Dry Eye Omega Benefits (Physician Recommended Nutriceuticals), HydroEye (Science Based Health), and Ultimate Omega (Nordic Naturals).
The drawback with the re-esterification process for a more absorbable product is the additional cost. If patients can afford the more expensive brands, they should use them, the physicians said. If that’s not possible, they should still take a closer look at how the omega-3 they select is processed. Dr. Sheppard has patients who use omega-3 nutraceuticals from some multilevel marketing companies that appear to be better quality than less expensive generic versions. “At least they’re taking something that’s supposedly pharmaceutical-grade as well as mercury-free,” he said.

Dosing, side effects

As for dosing, Henry Perry, MD, finds that less is more. Less frequent dosing can help address budget concerns, so patients uncomfortable with a higher price can still buy a high-quality product but not use it as often. Less frequent dosing also helps with patient adherence.
“You can take as few as two pills three times a week, and that still gives a benefit for dry eye, skin, joints, and the entire body,” he said. In more severe patients, Dr. Perry will recommend two pills twice a day, every day. For patients who eat three or more fish meals a week, Dr. Perry recommends twice-a-week supplementation dosing.
It may take a couple of months for patients to see the benefits of omega-3 fatty acids, Dr. Sheppard said.
Finding the right dosing balance is important because patients may have to take supplements indefinitely.
Side effects of omega-3 fatty acid supplementation include a fishy taste, nausea, upset stomach, and loose stools. These effects are more common with omega-3 in the ethyl ester form vs. the re-esterified form, Dr. Epitropoulos said. If someone has a rare, severe allergy to fish oil, Dr. Sheppard will prescribe flaxseed oil, a reasonably highly bioavailable plant-based omega-3 source. “When combined with a gamma linolenic acid preparation, like black currant seed oil or primrose oil, omega-3 polyunsaturated fatty acids including flaxseed oil can be very effective,”3 he said. “This combination is the strategy utilized in HydroEye.”
Omega-3 fatty acid supplementation is often used along with other medication-based or non-medication-based therapies. In patients specifically aiming to avoid medications, Dr. Sheppard will advise the use of punctal plugs and lid scrubs with hypochlorous acid.
Dr. Sheppard also addresses other common sense health advice with dry eye or MGD patients, including eating a healthier, anti-inflammatory diet. “It’s incumbent upon the provider to pay attention to the whole patient including supplementation, nutrition, and general health,” he said.

Supplements for other purposes

Patients with other eye diseases and conditions can benefit from certain nutraceuticals.
Age-related macular degeneration, for example, has published evidence showing that a combination of vitamins/antioxidants, omega- 3s, and zinc (known as the AREDS 2 formula) can help slow the progression of disease.
Dr. Perry said he favors Eye Omega Advantage (Physician Recommended Nutriceuticals) because it has the omega-3 fatty acids and lutein and zeaxanthin, both touted to help macular health. It also contains vitamin D. “It’s for dry eye, but I also use it for macular health,” he said.
Although not as well-known, there is a growing market for nutraceuticals for optic nerve disease, Dr. Sheppard said. One product he’ll recommend is Optic Nerve Formula (Science Based Health), which contains omega-3s, antioxidants, ginkgo biloba, and other nutrients. Another supplement product for glaucoma is GlaucoCetin (Guardion Health Sciences), which contains curcumin, ginkgo biloba, grape seed extract, and other ingredients.
Patients with glaucoma also can benefit from omega-3 supplementation due to the toxic effect of most IOP-lowering medications on their ocular surface, Dr. Matossian said. Dr Epitropoulos said that diabetic patients may benefit from a supplement known as Nuretin (Physician Recommended Nutriceuticals), which provides EPA and DHA in a 1:5 ratio to reduce the risk of diabetic retinopathy.

Side effects from other nutraceuticals

Patients may use nutraceuticals for other health conditions and find, inadvertently, that the products affect the eyes. One example is saw palmetto, used by some for urologic or prostate health. Saw palmetto has led to intraoperative floppy iris syndrome in some patients. Dr. Matossian asks patients before cataract surgery if they have used this supplement. If they have, she will have a pupil expansion device available during surgery, in case it’s needed.
Additionally, some nutraceuticals used by the general population may inadvertently be anticataract due to their ingredients, which include flavonoids, carotenoids, and ascorbic acids There are no medications or supplements that have been shown in the peer-reviewed literature to prevent cataracts, Dr. Epitropoulos, said, however there are reports suggesting that including certain naturally occurring foods and nutraceuticals may have a therapeutic effect in slowing or preventing cataract formation.4

At a glance

• Nutraceuticals can play a role in bettering ocular health.
• Omega-3 fatty acids processed in a way to produce a higher-quality product can help patients with MGD and dry eye.
• If recommended dosing of omega-3 fatty acids is too expensive or cumbersome for patients, less frequent dosing still provides benefits.
• Nutraceuticals taken for other, non-ocular health benefits can have inadvertent effects on the eyes.

About the doctors

Alice Epitropoulos, MD

Clinical assistant professor
The Ohio State University
Wexner Medical Center
Columbus, Ohio

Cynthia Matossian, MD
Medical director and founder
Matossian Eye Associates
Doylestown, Pennsylvania
Hopewell, New Jersey

Henry Perry, MD
Senior founding partner
Ophthalmic Consultants
of Long Island
Rockville Centre, New York

John Sheppard, MD
Virginia Eye Consultants
Norfolk, Virginia


1. Epitropoulos AT, et al. Effect of oral re-esterified omega-3 nutrition supplementation on dry eyes. Cornea. 2016;35:1185–1191.
2. The Dry Eye Assessment and Management Research Study Group. n-3 fatty acid supplementation for the treatment of dry eye disease. N Engl J Med. 2018;378:1681–1690.
3. Sheppard JD, et al. Long-term supplementation with n-6 and n-3 PUFAs improves moderate-to-severe keratoconjunctivitis sicca: A randomized double-blind clinical trial. Cornea. 2013;32:1297–304.
4. Amandeep K. et al. Nutraceuticals in prevention of cataract – an evidence-based approach. Saudi J Ophthalmol. 2017;31:30–37.

Relevant disclosures

Epitropoulos: Physician Recommended Nutriceuticals
Matossian: Physician Recommended Nutriceuticals
Perry: Physician Recommended Nutriceuticals
Sheppard: Science Based Health


: eyesmd33@gmail.com
Matossian: cmatossian@matossianeye.com
Perry: hankcornea@gmail.com
Sheppard: jsheppard@vec2020.com

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