Omega 3: How much is enough & what is the best way to get them into our body?

Omega 3: How much is enough & what is the best way to get them into our body?

EyeMDs know that Omega 3 fatty acids are excreted through the meibomian glands and have been proven to improve dry eye symptoms of foreign body sensation, burning, reflex tearing, vision fluctuations, even itching.


But how much is enough?


I could not find a published report comparing different formulas and concentrations of Omega 3 in a randomized, controlled, blinded trial with normal controls. If I missed one, please let me know.


I did find, as Reference 1, below a meta-analysis of all recent papers looking at Omega 3 & dry eye. It does show a very strong correlation between Omega 3 intake and improved dry eye symptoms. But it did not really address what type of Omega 3 is best nor how much.


For now, based on the below literature search as of 10/23/2014, it appears that most patients need at least 1000mg (1.0g) of Omega 3.


There are studies showing patients improve with 4500mg (see below, though the paper- Reference 3)-is not really that clear).


For now, I have switched to the below Omega 3 as it is a teaspoon gives 1450mg EPA and 1060 DHA. Of note: I do not have any stock in any of these companies, nor any financial interest in any product noted below. 


If you see better studies than those published below, please let me know.
Sandra Cremers, MD, FACS

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References: Located at end of this article:

More information below:
From: 
http://www.eyeworld.org/article.php?sid=3385


Dry Eye & Omega 3 Acids:



by Vanessa Caceres EyeWorld Contributing Editor


How flaxseed oil may work to counteract dry eye after LASIK.

There was no change in dry-eye grading with the Kowa interferometer at three months after LASIK.
 Punctate epitheliopathy and thick lipid secretions post-LASIK.
Source: Colin C.K. Chan, M.D.



More clinical research needed, physicians say

Omega-3 acids may help alleviate some of your dry-eye patients’ symptoms. Still, the quantity of omega-3 acids that patients need for lasting benefits are under investigation.
The connection between nutrition and dry eye has only recently been spotlighted. Ophthalmologists tend to focus on clinical concerns versus nutritional treatment, physicians said.
Yet with the press that surrounds the overall nutritional value of omega-3 fatty acids—including the link between increased consumption of omega-3 acids and a lower incidence of dry eye—the latest research is hard to ignore, said Robert L. Latkany, M.D., Dry Eye Clinic, New York Eye and Ear Infirmary, New York.
The possibility of nutritional healing will intrigue patients that want to avoid medicine when possible, Dr. Latkany said. “Some patients like medicine but others want this [kind of information]. Those patients love to hear dietary suggestions,” he said.
Here is a roundup of some of research from physicians that have explored dry eye and the omega-3 connection.


Omega-3 benefits 

Much of the research thus far has focused on omega-3 versus omega-6 fatty acids and how they are linked to the incidence of dry eye. Omega-3 acids are found in walnuts and oily, cold, dark fish such as tuna and salmon. Omega-6 acids are found in meat, canola and corn oil, and margarine. Although both kinds of fats are needed to function, omega-3 acids are healthier than the omega-6 acids, said James McCulley, M.D., professor and chair of ophthalmology, University of Texas Southwestern Medical Center, Dallas. Although humans evolved on a diet with an omega-6 to omega-3 acid of one, omega-6 consumption in the typical Western diet can outweigh omega-3 acids by 16 times, according to a study from the October 2002 issue of Biomedicine and Pharmacotherapy.
“We know our diet is relatively deficient in omega-3 fatty acids. It’s analogous to good and bad cholesterol, where the omega 6 is the bad cholesterol and the omega-3 is the good cholesterol. We need both, but we need the ratio to be appropriate,” Dr. McCulley said.
Omega-3 acids may benefit dry eye by reducing inflammatory activity in the body and by possibly altering the lipid profiles of the meibomian glands. Some components of the omega-3 acids are thought to stimulate aqueous tear secretion.
“Scientific research over the past decade has shown that specifically targeted nutritional supplements can restore function to the glands that provide lubrication to the eye. This includes both omega GLA as well as omega 3 EPA,” said Spencer P. Thornton, M.D., president of South Carolina-based Biosyntrx, which makes the dry-eye nutritional capsule BioTears.


Studies and anecdotal reports 

A study published last year in the American Journal of Clinical Nutrition, led by Biljana Miljanovic, M.D., Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, and fellow investigators further connected omega-3 acids to dry eye. Investigators used a food-frequency questionnaire with 32,470 women ages 45 to 84 participating in the Women’s Health Study, which is assessing risk factors related to cardiovascular disease and cancer.
After adjusting for demographics, hormone therapy, and total fat intake, investigators found different dietary patterns in the 1,546 women with clinically diagnosed dry eye versus the rest of the group. “Women with a higher intake of [omega-3 fatty acids] tended to have a lower risk of dry-eye syndrome than did women with a lower intake,” the investigators wrote. They also found the participants to be at a higher risk for dry-eye syndrome if they had a higher dietary consumption of omega-6 acids. Increased tuna consumption—at least five to six times a week—seemed to decrease the risk for dry eye in the study, compared with the participants who ate tuna only once a week or less frequently. Another study published in the February 2003 issue of theEuropean Journal of Clinical Nutrition found that patients with Sjögrens syndrome had a lower intake of omega-3 acids.
Those who treat dry eye find the results from the studies intriguing but want to see more information. “These studies need to be backed with clinical data, which is currently lacking,” said Colin C.K. Chan, M.D., F.R.A.N.Z.C.O., refractive and corneal surgeon, The Eye Institute, Chatswoodand Bondi JunctionAustralia.
Dr. Chan was involved with an omega-3-related study at the Boxer Wachler Vision Institute, Beverly Hills, which found that 3,000 mg a day of omega-3-rich flaxseed oil one week before and one week after LASIK was just as effective as doxycycline for dry eye when patients were seen three months post-op. He presented the study results at this year’s ASCRS•ASOA Symposium & Congress. “The study found that there was no difference in dry-eye outcomes between the 79 patients treated with flaxseed oil and the 73 patients treated with doxycycline. More importantly, no patient in the flaxseed oil group had anything more than mild dry eye at three months,” Dr. Chan said.
Results are also positive with 80% to 85% of patients who use BioTears, which contains omega-3 fatty acids from fish oils, as well as GLA from black currant seed oil and the necessary co-factors to push the metabolic process and other ingredients, Dr. Thornton said. Patients usually notice a difference in their dry-eye symptoms after two or three weeks, he said. Anecdotally, Dr. Latkany said some of his patients report good results from an omega-3-rich supplement that he developed called Dry Vites (Deep Blue See, New York). Patients can take the supplement, which is made from salmon oil and flaxseed oil, three times a day or less.
“I’ve had people come back and say their eyes feel better. They also say people tell them they’re glowing,” he said. Dr. McCulley is overseeing an omega-3-related study to examine aqueous tear characteristics, relative tear evaporation, and meibomian secretion in 36 patients with aqueous-deficient dry eye. Half of the patients will take the omega-3-rich supplement TheraTears (AdvancedVision Research, Woburn, Mass.), while the control group will not. Dr. Chan is involved with a new study that will examine the clinical use of fish oil to treat dry eye.


Ongoing research— and some cautions 

Physicians also are researching if omega-3 acids are best for dry-eye patients as part of their diet or in supplements. “The belief is that the supplements are purified,” Dr. Laktany said. Supplements that use fish oil as a source of omega-3 acids can use wild fish, a variety thought to have more nutritional benefits, he said.
“Two issues with fish oil are the contamination with heavy metals and rapid oxidation after processing. It is important to choose a fish oil product from a company that deals with those issues,” Dr. Chan said. Flaxseed oil and fish oil can increase clotting time; patients on blood thinners such as Coumadin (warfarin sodium, Bristol-Myers SquibbPrinceton, N.J.) should speak with their family physician before using the supplements, Dr. Chan said. He also said lactating and pregnant women should avoid supplements with the omega-3 acids and vitamins A, C, and E.

Editors’ note:). Dr. Chan has no financial interests related to this article. Dr. Latkany is the developer of Dry Vites supplements. Dr. McCulley is a consultant for Alcon (Fort Worth, Texas) and has affilations with Advanced Vision Research (Woburn, Mass.). Dr. Thornton is co-founder of Biosyntrx.

Contact Information

Chancolin.chan@vghnet.com

Latkany: 212-832-2020, relief@dryeyedoctor.com

McCulley: 214-648-3407, james.mcculley@utsouthwestern.edu

Thornton: 615-373-1236, thornton@eyecareusa.org


———————————————————–
REFERENCES: 


1. This is the best study I could find to date. It is the first meta-analysis published to my knowledge that demonstrates the effect of omega-3 fatty acid in the treatment of dry eye, encompassing a total of 7 studies. Note: no publication bias was detected by Begg’s funnel plot or Egger’s tests.


Study characteristics of included studies.
Author Year Site Patients Age Gender (female/male) Source Case group Control group
Wojtowicz JC 2011 USA 21/15 61 (29–84) 20/16 Fish oil 450 mg of eicosapentaenoic acid, 300 mg of docosahexaenoic acid 1000 mg of flaxseed oil Wheat germ oil
Barabino S 2003 Italy 13/13 63.4±8.2/54.3±11.3 9:4/8:5 Drug LA (28.5 mg) and GLA (15 mg) twice daily Preservative-free substitute tears
Manuel Neuzimar Pinheiro Jr 2007 Brazil 25/13 NA Women Flax seed Flaxseed oil capsules Basal oleic acid
Haleh Kangari 2013 Iran 33/31 61.8±8/60.6±8.8 38/26 Drug 180 mg of EPA and 120 mg DHA Medium-chain triglycerides
Nikki Heidi Ong 2013 USA 9/9 31.1±6.2/32.1±10.6 12/6 Drug 750 mg of omega-3 EFAs both eicosapentaenoic (EPA) docosahexaenoic acid (DHA), 1000 mg offlaxseed oil about 183 IU of vitamin E per day Same medical regimen
Andrea Oleñik 2013 Spain 33/31 58/54 22: 9/24: 9 Drug DHA 350 mg, EPA 42.5 mg Placebo oral agent
Kawakita T 2013 Japan 15/11 52.5±2.5/51.9±2.2 15/12 Fish oil EPA 1245 mg; DHA 540 mg Placebo supplement without EPA and DHA





 2014 Sep 6;20:1583-9. doi: 10.12659/MSM.891364.

Omega-3 essential fatty acids therapy for dry eye syndrome: a meta-analysis of randomized controlled studies.

Abstract

BACKGROUND:

Dry eye is a common, complex condition that can reduce ocular comfort and visual performance. The impact on quality of life has been rated as similar to the effect of moderate angina and, in more severe cases, dialysis and severe angina. This study aimed to use meta-analysis to compare omega-3 fatty acid and placebo fatty acid in the management of dry eye syndrome.

MATERIAL AND METHODS:

Comparative studies published until 1 June 2014 were searched through a comprehensive search of the Medline, Embase, Web of Science, and the Cochrane Library electronic databases. A systematic review and cumulative analysis of comparative studies reporting the effect of omega-3 fatty acid on dry eye syndrome was conducted. All analyses were performed using the Review Manager (RevMan) v.5 software (Nordic Cochrane Centre, Copenhagen, Denmark).

RESULTS:

The trials involved a total of 790 participants in 7 independent studies. All the studies are published between 2007 and 2013. Meta-analysis of the 5 studies that reported data in mean SD values revealed that the tear break-up time (TBUT) was significantly greater by 1.58 s (WMD=1.58, 95% CI=0.60 to 2.55; P=0.007). Combination of all the Schirmer’s test data showed that omega-3 fatty acid supplementation could significantly improve the Schirmer’s test (WMD=0.74, 95% CI=0.29 to 1.19; P=0.001). However, the combination of all the OSDI test data showed that omega-3 fatty acid supplementation did not significantly improve the OSDI test results (WMD=-4.54, 95% CI=-9.85 to 0.78; P=0.09).

CONCLUSIONS:

Based on the data included in our meta-analysis, omega-3 fatty acid was associated with better TBUT and Schirmer’s. No significant differences were detected in OSDI test results. Consequently, our findings suggest that omega-3 fatty acid offers is an effective therapy for dry eye syndrome.
PMID:

 

25193932

 

[PubMed – in process] 
PMCID:

 

PMC4165511

 

Free PMC ArticleMed Sci Monit. 2014; 20: 1583–1589.

Published online Sep 6, 2014. doi:  10.12659/MSM.891364
PMCID: PMC4165511

Omega-3 Essential Fatty Acids Therapy for Dry Eye Syndrome: A Meta-Analysis of Randomized Controlled Studies

Aihua LiuA,B,C,D,E,F,G and Jian JiA,B,C,D,E,F,G

Background

Dry eye is a common, complex condition that can reduce ocular comfort and visual performance. The impact on quality of life has been rated as similar to the effect of moderate angina and, in more severe cases, dialysis and severe angina []. Dry eye is reported to be a complex condition involving the lacrimal glands, eyelids, and tear film, as well as a variety of ocular surface tissues, including epithelial, inflammatory, immune, and goblet cells []. Dry eyes usually affect people aged over 65 years []; moreover, dry eyes affect women selectively, as emphasized by several large studies [,], with an estimated 3.23 million American women suffering from dry eyes. There are 2 types of dry eye, although clinically they are frequently encountered together: 1) aqueous insufficiency, in which the aqueous secretion from the lacrimal glands is reduced; and 2) evaporative dry eye, in which a deficient lipid layer results in an unstable tear film []. The term “dry eye disorder” (DED) has recently been introduced to better define the ocular surface dysfunction that leads to tear film impairment and dry eye.
Omega-3 essential fatty acids have been reported to be associated with several kinds of diseases, such as cancers, cardiovascular diseases, and autoimmune disease []. In animal models, daily supplementation with omega-3 fatty acid has shown great potential to produce significant therapeutic effectiveness in dry eye treatment []. Another study was conducted to investigate the efficacy of the topical application of omega-3 essential fatty acids and hyaluronic acid mixtures in a mouse model of experimental dry eye. The results showed that a mixture of topical omega-3 essential fatty acids and hyaluronic acid may have a greater therapeutic effect on clinical signs and inflammation of dry eye compared with hyaluronic acid mixture artificial tears []. Observational studies have reported that consumption of fish oil, which is known to be rich in omega-3, is positively associated with reduced risk of dry eye []. The Women’s Health Study (WHS), which included 39876 female health professionals, reported that a higher ratio of omega-3 to omega-6 fatty acid consumption was associated with a significantly reduced risk of dry eye. In addition, tuna consumption was inversely associated with dry eye []. However, such observational studies are unable to establish causality because of the difficulty in adjusting for complex confounding factors that also influence the development of dry eye. For this reason, randomized controlled trials (RCTs) are necessary to determine whether an omega-3 fatty acid supplementation is effective in treatment of dry eye. Such trials are considered important because omega-3 fatty acid supplementation may be a low-risk and cost-effective strategy to treat dry eye syndromes. RCTs of omega-3 fatty acid are increasingly being reported, with varying results, and quite discordant conclusions were reported. Accordingly, a comprehensive systematic review of RCTs conducted according to the Cochrane handbook is required to reach a credible conclusion on the effect of omega-3 fatty acid therapy for dry eye.

Material and Methods

Study selection

We systematically searched the following electronic databases: Medline, Embase, Web of Science, and Cochrane Library, for articles addressing the effect omega-3 fatty acid on the treatment of dry eye. The following key words were used: “ophthalmoxerosis”, “xerophthalmia”“dry eye”, “xeroma”, “dry eye syndrome”, “keratoconjunctivitis sicca”, and combined with “fatty acid”, “omega-3”, and “n-3”. In addition, reference lists were scanned to identify any additional studies. No language restrictions were set in the literature search. All the reports were published before 1 June 2014. We sought randomized controlled trials (RCTs) involving the effect of omega-3 on dry eye. Letters, review articles, animal or laboratory studies, and conference abstracts were not included.

Data extraction

Two reviewers (AL and JJ) independently extracted the following data from each study: first author, year of publication, study population characteristics, study design, content of case and control groups, and the tear film break up time (TBUT), Schirmer’s test result, and Ocular Surface Disease Index (OSDI) change in both groups.

Inclusion criteria

To be included, studies had to:
  1. Report the effect of omega-3 fatty acid supplementation on the management of dry eye.
  2. Compare omega-3 and placebo drugs.
  3. Report on at least 1 of the outcome measures mentioned (TBUT, Schirmer’s test, and OSDI).
  4. Contain a previously unreported patient group (if patient material was reported more than once, we chose the most informative and recent article).
  5. When 2 studies were reported by the same institution, our analysis included either the one of better quality, or the most recent publication.

Exclusion criteria

The following criteria were used to exclude studies from our analysis:
  1. Studies in which the outcomes of interest (mentioned below) were not reported for omega-3 fatty acid or it was impossible to calculate these from the published results.
  2. Only oral omega-3 fatty acid was considered in this study and other routes of administration were excluded.
  3. Studies in which the standard deviation of the mean for continuous outcomes of interest (length of stay and operative time) were not reported.

Quality of the comparative studies

Assessment of quality characteristics used the following criteria: 1) Random sequence generation; 2) Allocation concealment; 3) Blinding of participants; 4) Blinding of outcome assessment; 5) Follow-up ≥80%; 6) Free of selective reporting; and 7) Free of other bias. The adequate (low risk of bias); unclear (unknown risk of bias) and inadequate (high risk of bias) items were marked for each study. More adequate item demonstrated better quality of the included studies.

Statistical analyses

Continuous parameters were analyzed by using the estimated weighted mean differences. However, different outcomes were reported in different studies and the number of included studies for each parameter was different. All the data were measured as the change from baseline and required calculation was conducted. Interstudy heterogeneity was measured using the Q-test. Heterogeneity was also quantified with the I2 metric, which is independent of the number of studies included in the cumulative analysis. The scale of I2 values ranges between 0% and 100%, with higher values denoting a greater degree of heterogeneity. Data were pooled using fixed-effects or random-effects models according to the heterogeneity. The random-effects model incorporates an estimate of the interstudy variance and tends to provide wider CIs; it was used when heterogeneity was present. The Begg funnel plot and Egger’s test were conducted to identify potential publication bias. The significance of the intercept was determined by the t test.. All analyses were performed using the Review Manager (RevMan) v.5 software package (Nordic Cochrane Centre, Copenhagen, Denmark; http://www.cc-ims.net/revman/download). All p values were calculated using the 2-tailed t test, and p values were considered statistically significant at p<0.05.

Results

Results of the literature search

The method used to select the studies is shown in Figure 1. The initial search identified 666 reports (255 from Medline, 310 from Embase, 54 from Web of Science, 25 from Cochrane Library and 22 studies identified from reference lists), of which 212 duplicates were excluded. The title and abstract of the remaining 454 reported were identified and 438 studies were excluded. A total of 16 full-text articles were then assessed for eligibility. The studies were excluded in the full-text assessment and in which 3 articles combined omega-3 fatty acid with other interventions and 5 articles without available data. Finally, a total of 8 relevant randomized controlled studies were included in this study [].
Figure 1

Flow chart of the literature search. The literature search was conducted in Medline, EMBASE, Web of Science, and Cochrane Library. The reference lists of the relevant studies were reviewed as well.

Study characteristics

The trials involved a total of 790 participants in 7 independent studies. All the studies are published between 2007 and 2013. The data are from the USA, Italy, Brazil, Iran, Spain, and Japan. In most studies, both females and males are included in the analyses. Most studies were based on a relatively older group (50 years and older). The sources of omega-3 fatty acid were fish oil, flax seed, and synthetic. In the control group, the placebo group was wheat germ oil or other placebo oral agents. The follow-up durations of all the included studies are from 1 month to 6 month and the most frequent duration was 3 months in 4 studies.

Methods of included trials

All trials reported a randomized design. Two trials generated the randomization sequence with colored marbles to represent trial groups and 5 did not clearly report how the randomization sequence was generated. Concealed allocation was performed in 3 studies. Blinding of participants was undertaken in all the included studies and the blinding of outcome assessment in 4 studies. All the studies had a follow-up rate of over 80%. A total of 3 studies were free of selective reporting and 5 studies were free of other bias.

Quantitative analyses

TBUT

Five of the included studies reported the TBUT in omega-3 and placebo groups. Moreover, meta-analysis of the 5 studies that reported data in mean SD values revealed that the TBUT was significantly greater by 1.58 s (WMD=1.58, 95% CI=0.60 to 2.55; P=0.007, Figure 2)
Figure 2

Forest plot of the tear film break-up time for omega-3 fatty acid on dry eye syndrome. The size of the shaded square is proportional to the percent weight of each study. The horizontal lines represent 95% CIs. The diamond data markers indicate pooled 

Schirmer’s test

In 3 of all the included studies, the results of Schirmer’s test were reported. Through the meta-analysis, the combination of all the Schirmer’s test data showed that omega-3 fatty acid supplementation significantly improved the Schirmer’s test result (WMD=0.74, 95% CI=0.29 to 1.19; P=0.001, Figure 3)
Figure 3

Forest plot of the Schirmer’s test results for omega-3 fatty acid effect on dry eye syndrome. The size of the shaded square is proportional to the percent weight of each study. The horizontal lines represent 95% CIs. The diamond data markers indicate 

OSDI

In 3 of the included studies, the OSDI test results were reported. Through the meta-analysis, the combination of all the OSDI test data showed that omega-3 fatty acid supplementation did not significantly improve the OSDI test result (WMD=−4.54, 95% CI=−9.85 to 0.78; P=0.09, Figure 4)
Figure 4

Forest plot of the Ocular Surface Disease Index for the effect of omega-3 fatty acid on dry eye syndrome. The size of the shaded square is proportional to the percent weight of each study. The horizontal lines represent 95% CIs. The diamond data markers 

Heterogeneity and sensitivity analysis

In the TBUT test, a significant heterogeneity was detected (heterogeneity: P<0.0001); I2=91%). To find the source of heterogeneity, the included studies were excluded one by one and we found no significant changes in the heterogeneity or the results. The sensitivity analysis showed that no significant change was detected after excluding the studies with lower methodological quality.

Publication bias

Funnel plots (Figure 5) and Egger’s regression asymmetry test results of the included studies suggested no significant publication bias (Egger’s test P=0.513) over the effects of omega-3 fatty acid supplementation on dry eye syndrome.
Figure 5

Funnel plot of all the included studies.

Discussion

In this study, by pooling the results of the available randomized controlled trials, we found that omega-3 fatty acid supplementation improved the TBUT and Schirmer’s test results of the patients with dry eye syndrome. Previous studies indicated that omega-3 fatty intake was associated with a reduced risk of dry eye, and the results of our study demonstrated that oral omega-3 fatty acid supplementation improved TBUT and Schirmer’s test results, indicating that it may be an important mechanism underlying the therapeutic effect of omega-3 fatty acid. However, omega-3 fatty acid did not improve the OSDI scale results.
The Women’s Health Study is a randomized, double-blind, placebo-controlled trial among 39 876 female health professionals to assess the benefits and risks of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer. The baseline and follow-up data showed that for the highestvs. the lowest fifth of omega-3 fatty acid intake, the odds ratio was 0.83 with a CI=0.70 to 0.98 []. A series of randomized controlled studies showed that omega-3 fatty helped in the treatment of dry eye syndrome. In this study, the combination of 7 studies showed that omega-3 fatty acid improved TBUT and Schirmer’s test results but not OSDI test results. In general, omega-3 fatty acid helps in tear secretion and tear film stability. However, omega-3 fatty acid does not improve the degree of comfort of patients with dry eye syndrome. This is particularly relevant in the context of intervention decisions for therapeutic strategies, thus more advanced studies are required to detect whether the intervention should be used for the primary prevention of dry eye.
In a mouse model, topical application of the n-3 fatty acid linoleic acid (18: 3n-3; ALA) produces a significant decrease in epithelial damage, expression of inflammatory cytokines, and macrophage infiltration []. The beneficial effects could be due to the action of ALA, to the elongation and desaturation products, EPA and DHA, or to new derivatives of these fatty acids, such as resolvins and neuroprotectins. Several studies showed omega-3 fatty acids and their derivatives, resolvins and neuroprotectins, decrease inflammation and increase tear production, and the combination of NGF and PEDF with DHA improves nerve regeneration after injury []. Although DHA is a minute component of lipids in the cornea, this tissue can synthesize NPD1 when treated with a combination of DHA and PEDF. Therefore, this docosanoid could have therapeutic value in preventing serious consequences of nerve damage, such as DE, epithelial erosions, and corneal ulcerations [].
Inflammation is now understood to be a key process in development of dry eye syndrome. A previous study showed that a significant decrease in the levels of IL-1β, -17, and IP-10 were observed in the 0.2% essential fatty acids mixture-treated group compared with the other groups. In the mice treated with the mixture containing 0.2% omega-3 fatty acids, the concentration of 4-hydroxynonenal was also lower than in the other groups. Although the 0.2% omega-3 essential fatty acids alone group also had significant improvement in corneal irregularity scores and IL-17, IL-10, and 4-hydroxynonenal levels compared with the other groups, the efficacy was lower than in the 0.2% omega-3 mixture group []. Thus, we suspect that the therapeutic effect of omega-3 fatty on dry eye syndrome might be through suppressing inflammatory reactions in ocular tissues.
In this study, we only evaluated the effect of oral omega-3 fatty acid on the treatment of dry eye syndrome. However, eye drops containing omega-3 fatty acid might be an option for the management of dry eye. Omega-3 fatty acid can also be combined with other anti-inflammatory agents during treatment. When combined with an anti-inflammatory agent, cyclosporine A, omega-3 fatty acid preferably improves the TBUT compared with the omega-3 fatty acid supplement only group [].
As previously reported, meta-analysis has been used in the past to assess the treatment of dry eye. Ng et al. studies the effect of omega-3 and omega-6 polyunsaturated fatty acids for dry eye syndrome, using a combination of different kinds of polyunsaturated fatty acids. However, the combination of different fatty acids might be able to demonstrate the effect of omega-3 fatty acid. This study has investigated the possible benefits of omega-3 fatty acid in the management of dry eye syndrome. The strengths of this study are that, to the best of our knowledge, this research is the first meta-analysis detecting the effect of omega-3 fatty acid in the treatment of dry eye, encompassing a total of 7 studies, and that no publication bias was detected by Begg’s funnel plot or Egger’s tests. The overall results did not change remarkably after sensitivity analyses were performed. Our analysis combined the data from all studies that passed our predefined criteria; therefore, we are confident of the validity of our findings. It is important, however, to address the limitations of the meta-analysis, which are as follows: First, the longest follow-up duration of the included studies was 6 months. Considering that omega-3 fatty acid is an essential nutrient, longer duration of treatment and follow-up are required. Second, the data of the included studies were insufficient to conduct a dose-response meta-analysis. There points all indicate the need for additional well-designed studies in the future. Third, it is important to bear in mind non-publication bias, particularly in meta-analytic research based on published studies.

Conclusions

Based on the data included in our meta-analysis, omega-3 fatty acid appears to be associated with better TBUT and Schirmer’s test results. No significant differences were detected in the OSDI test. Consequently, our results suggest that omega-3 fatty acid is effective in treatment of dry eye syndrome. Accordingly, oral omega-3 fatty acid might be a potential therapy for patients with dry eye syndrome. Larger, well-designed, multicenter RCTs with more extensive follow-up are needed to confirm our findings.

Table 1

Study characteristics of included studies.
Table 2

The study quality of the included studies assessed by the Cochrane collaboration tool.

Footnotes

Source of support: The study was funded by Tianjin Municipal Education Committee Foundation (Project No. 20110132)

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2.
 2014 Sep;39(9):871-8. doi: 10.3109/02713683.2014.884595. Epub 2014 Feb 21.

Effects of eye drops containing a mixture of omega-3 essential fatty acids and hyaluronic acid on the ocular surface in desiccating stress-induced murine dry eye.

Abstract

PURPOSE:

To investigate the efficacy of the topical application of omega-3 essential fatty acids (EFAs) and hyaluronic acid (HA) mixtures in a mouse model of experimental dry eye (EDE).

METHODS:

Eye drops consisting of 0.1% HA, 0.02%, or 0.2% omega-3 EFAs alone and mixture of 0.02%, or 0.2% omega-3 EFAs and 0.1% HA were applied in desiccating stress-induced murine dry eye. Corneal irregularity scores and fluorescein staining scores were measured 5 and 10 days after treatment. Levels of interleukin (IL)-1β, -17, and interferon gamma-induced protein (IP)-10 were measured in the conjunctiva at 10 days using a multiplex immunobead assay. The concentrations of hexanoyl-lys (HEL) and 4-hydroxynonenal (4-HNE) in conjunctiva tissue were measured with enzyme-linked immunosorbent assays.

RESULTS:

Mice treated with the mixture containing 0.2% omega-3 EFAs showed a significant improvement in corneal irregularity scores and corneal fluorescein staining scores compared with EDE, HA, 0.02% or 0.2% omega-3 EFAs alone, and 0.02% omega-3 EFAs mixture-treated mice. A significant decrease in the levels of IL-1β, -17, and IP-10 were observed in the 0.2% EFAs mixture-treated group, compared with the other groups. In the mice treated with the mixture containing 0.2% omega-3 EFAs, the concentration of 4-HNE was also lower than the other groups. Although 0.2% omega-3 EFAs alone group also had a significant improvement in corneal irregularity scores and IL-17, IL-10, and 4 HNE levels compared with the other groups, the efficacy was lower than 0.2% omega-3 mixture group.

CONCLUSIONS:

Topically applied eye drops containing a mixture of omega-3 EFAs and HA could improve corneal irregularity and corneal epithelial barrier disruption, and decrease inflammatory cytokines and oxidative stress markers on the ocular surface. Topical omega-3 EFAs and HA mixture may have a greater therapeutic effect on clinical signs and inflammation of dry eye compared with HA artificial tears.

KEYWORDS:

Dry eyeeye drops; hyaluronic acid; mixtures; omega-3 essential fatty acids

3. Do they authors imply 3 capsules of 1.5g of Omega 3 or a total of 1.5g? The paper seems to imply a total of 4500mg.

 2014;8:169-76. doi: 10.2147/OPTH.S54658. Epub 2014 Jan 6.

Effectiveness and tolerability of dietary supplementation with a combination of omega-3 polyunsaturated fattyacids and antioxidants in the treatment of dry eye symptoms: results of a prospective study.

Abstract

BACKGROUND:

We assessed the effectiveness and tolerability of a dietary supplement based on the combination of omega-3 essential fatty acids and antioxidants on dry eye-related symptoms.

METHODS:

A total of 905 patients (72% women, median age 60 years) with dry eye syndrome and using artificial tears to relieve symptoms participated in an open-label prospective intervention study. They were recruited during a routine ophthalmological appointment. Patients were instructed to take three capsules/day of the nutraceutical formulation (Brudysec® 1.5 g) for 12 weeks. Dry eye symptoms (categorized as 0, none; 1, mild; 2, moderate; and 3, severe) included scratchy and stinging sensation in the eyes, eye redness, grittiness, painful eyes, tired eyes, grating sensation, and blurry vision.

RESULTS:

The mean intensity of dry eye symptoms varied from 1.1 (± standard deviation [SD] 0.9) for painful eyes to 2.0 (0.9) for grittiness, with a mean value of 11.9 (4.8) for all symptoms together. At week 12, all individual symptoms improved significantly (P<0.001). The mean value for all symptoms together decreased from a mean value of 11.9 (± SD 4.8) at baseline to 6.8 (± SD 4.5) after 12 weeks of treatment (P<0.001). There was a decrease in the percentage of patients in which dry eye symptoms predominated nearly all the time (53.5% versus 34.1%). A total of 68.1% of patients reported better tolerance to contact lenses after treatment. The mean number of daily instillations of artificial tears also decreased significantly (3.8 [± SD 1.6] versus 3.3 [± SD 1.6], P<0.001). A total of 634 patients (70.1%) did not report any adverse events. In the remaining patients with adverse events, the most frequent was fish-tasting regurgitation in 13.5% of cases, followed by nausea in 4.9%, diarrhea in 1.3%, and vomiting in 0.3%.

CONCLUSION:

Dietary supplementation with a combination of omega-3 essential fatty acids and antioxidants was an effective treatment for dry eye.

KEYWORDS:

Brudysec 1.5 g; antioxidants; dry eye symptoms; nutraceutics; omega-3; polyunsaturated fatty acids

4. This article below seems to indicate 3 capsules of 1.5g of Omega 3 is needed per day to notice an improvement on dry eye symptoms. 

 2014;8:169-76. doi: 10.2147/OPTH.S54658. Epub 2014 Jan 6.

Effectiveness and tolerability of dietary supplementation with a combination of omega-3 polyunsaturated fattyacids and antioxidants in the treatment of dry eye symptoms: results of a prospective study.

Abstract

BACKGROUND:

We assessed the effectiveness and tolerability of a dietary supplement based on the combination of omega-3 essential fatty acidsand antioxidants on dry eye-related symptoms.

METHODS:

A total of 905 patients (72% women, median age 60 years) with dry eye syndrome and using artificial tears to relieve symptoms participated in an open-label prospective intervention study. They were recruited during a routine ophthalmological appointment. Patients were instructed to take three capsules/day of the nutraceutical formulation (Brudysec® 1.5 g) for 12 weeks. Dry eye symptoms (categorized as 0, none; 1, mild; 2, moderate; and 3, severe) included scratchy and stinging sensation in the eyes, eye redness, grittiness, painful eyes, tired eyes, grating sensation, and blurry vision.

RESULTS:

The mean intensity of dry eye symptoms varied from 1.1 (± standard deviation [SD] 0.9) for painful eyes to 2.0 (0.9) for grittiness, with a mean value of 11.9 (4.8) for all symptoms together. At week 12, all individual symptoms improved significantly (P<0.001). The mean value for all symptoms together decreased from a mean value of 11.9 (± SD 4.8) at baseline to 6.8 (± SD 4.5) after 12 weeks of treatment (P<0.001). There was a decrease in the percentage of patients in which dry eye symptoms predominated nearly all the time (53.5% versus 34.1%). A total of 68.1% of patients reported better tolerance to contact lenses after treatment. The mean number of daily instillations of artificial tears also decreased significantly (3.8 [± SD 1.6] versus 3.3 [± SD 1.6], P<0.001). A total of 634 patients (70.1%) did not report any adverse events. In the remaining patients with adverse events, the most frequent was fish-tasting regurgitation in 13.5% of cases, followed by nausea in 4.9%, diarrhea in 1.3%, and vomiting in 0.3%.

CONCLUSION:

Dietary supplementation with a combination of omega-3 essential fatty acids and antioxidants was an effective treatment for dry eye.

KEYWORDS:

Brudysec 1.5 g; antioxidants; dry eye symptoms; nutraceutics; omega-3; polyunsaturated fatty acids





5. This article seems to indicate 1000mg (1.0g) of Omega 3 (formulation below) is enough to improve dry eye symptoms.


 2013 Dec 18;6(6):811-6. doi: 10.3980/j.issn.2222-3959.2013.06.13. eCollection 2013.

A randomized controlled trial of omega-3 fatty acids in dry eye syndrome.

Abstract

AIM:

To evaluate the role of dietary supplementation of omega-3 fatty acids in dry eye syndrome.

METHODS:

A prospective, interventional, placebo controlled, double blind randomized trial was done at two referral eye centers. Two hundred and sixty-four eyes of patients with dry eye were randomized to receive one capsule (500mg) two times a day containing 325mg EPA and 175mg DHA for 3 months (omega-3 group). The omega-3 group was compared to a group of patients (n=254) who received a placebo (placebo group). There were 4 patient visits (at baseline, 1 month, 2 months and 3 months). On each visit, recording of corrected distance visual acuity (CDVA), slit lamp examination and questionnaire based symptom evaluation and scoring was done. A symptomatic score of 0-6 was mild, 6.1-12 moderate and 12.1-18 severe dry eye. Response to intervention was monitored by routine tear function tests like Schirmer I test, tear film break-up time (TBUT), Rose Bengal staining and most notably, conjunctival impression cytology.

RESULTS:

Sixty-five percent of patients in the omega-3 group and 33% of patients in placebo group had significant improvement in symptoms at 3 months (P=0.005). There was a significant change in both Schirmer’s test value and TBUT values in the omega-3 group (P<0.001), both comparisons. However, there was a larger drift in TBUT values in omega-3 than the placebo group, in comparison to Schirmer’s test values. The mean TBUT score was 2.54±2.34 in the omega-3 group and 0.13±0.16 in placebo group, respectively. The mean reduction in symptom score inomega-3 group was 2.02±0.96 as compared to 0.48±0.22 in placebo group (P<0.001). Despite a slight increase mean score, the Schirmer scores did not correlate well with symptomatic improvement.

CONCLUSION:

Omega-3 fatty acids have a definite role for dry eye syndrome. The benefit seems to be more marked in conditions such as blepharitis and meibomian gland disease. The role of omega fatty acids in tear production and secretion needs further evaluation.

KEYWORDS:

conjunctival impression cytology; dry eye syndrome; meibomian gland disease; omega-3 fatty acids



Other:



Saudi J Ophthalmol. Jul 2014; 28(3): 195–197.
Published online Jun 24, 2014. doi:  10.1016/j.sjopt.2014.06.004
PMCID: PMC4181435

Essential fatty acids in the treatment of dry eye syndrome: A myth or reality?

Ammar M. Al Mahmood, MD, FRCS(Glasg.)a and Samar A. Al-Swailem, MDb,[low asterisk]

Introduction

Dry eye syndrome (DES) is a frequent cause of office visits due to ocular discomfort and commonly leads to problems with sustained visual activities. These include problems during reading, using a computer, driving at night and carrying out professional work. DES manifests more in elderly people. Moreover, it affects women more selectively.
DES is a complex condition involving the lacrimal glands, eyelids, and tear film, as well as a variety of ocular surface tissues including epithelial, inflammatory, immune, and goblet cells.
Essential fatty acids (EFAs) have been of interest in the area of dry eye disease treatment. Both topical and systemic EFAs have been evaluated in regard to alleviation of DES manifestations. In this paper we try to review the literature in regard to efficacy of using EFAs to treat DES.

Source of EFAs

EFAs are fatty acids that humans and other animals must ingest because the body requires them for good health but cannot synthesize them. These are polyunsaturated fats.
The EFAs omega-3 and omega-6 play pivotal functions and display a wide spectrum of positive effects in the body, such as: helping to lower cholesterol and triglyceride levels; giving energy to the body; helping to reduce acute and chronic inflammation; reducing respiratory and asthma-like symptoms; enhancing appropriate pre- and postnatal development mainly of the central and peripheral nervous systems; helping in the regulation of blood pressure; reducing the odds of developing cancer, heart disease, and stroke; managing emotional distress and depression; and benefiting patients with neurodegenerative disorders.
Some of the food sources of omega-3 and omega-6 fatty acids are fish and shellfish, flaxseed (linseed, (hemp oil, soya oil, canola (rapeseed) oil, chia seeds, pumpkin seeds, sunflower seeds, leafy vegetables and walnuts.

Role of EFAs in the management of DES – pathogenesis

Many hypothesize that the cause of dry eye is inflammatory. The omega-3 fatty acid eicosapentaenoic acid (EPA) and the omega-6 fatty acid arachidonic acid (AA) act competitively as substrate for both enzymes cyclooxygenase and 5-lipoxygenase. The anti-inflammatory action is believed to result from the synthesis of prostaglandin E3 (PGE3) and of leukotriene B5 (LTB5(from EPA that inhibits the conversion of AA to potentially harmful inflammatory mediators prostaglandin E2 (PGE2) and leukotriene B4 (LTB4).

Role of systemic EFAs in the management of DES – clinical trials

Multiple trials looked at the effect of oral supplement of omega-3 and omega-6 in the treatment of DES. A large cross sectional study by Miljanović et al. has suggested that a higher dietary intake of omega-3 fatty acids is associated with a decreased presence of DES in women.
Barabino et al. evaluated the effect of linoleic acid and gammalinolenic acid, on chronic ocular inflammation in 26 patients with aqueous-deficient keratoconjunctivitis sicca. Statistically significant changes in symptoms (P < 0.005), lissamine green staining (P < 0.005), and ocular surface inflammation (P < 0.05) occurred in the study group compared with controls.
Aragona et al. evaluated the effect of oral omega-6 essential fatty acids on PGE(1) tear content and signs and symptoms of ocular discomfort in patients with Sjögren’s syndrome(SS). This was a randomized, double-masked, controlled, clinical trial involving 40 patients with primary SS. Twenty patients received omega-6 supplements while controls received placebo. In omga-6 treatment group significant changes were noted in the following: increased tear PGE1 levels, reduction of DES symptom score, and improved corneal fluorescein stain.
Wojtowicz et al. investigated the potential effect of dietary supplementation with omega-3 fatty acid on lipid composition of meibum, aqueous tear evaporation, and tear volume in patients with dry eye. Thirty-six patients were included in this case-control trial whom received a daily dose of fish oil, containing 450 mg of eicosapentaenoic acid, 300 mg of docosahexaenoic acid, and 1000 mg of flaxseed oil for 90 days. At the end of the study, 70% of the patients treated with omega-3 supplements became asymptomatic and Schirmer testing together with fluorophotometry suggested that the omega-3 supplement increased tear secretion. A similar improvement was reported by Kokke et al. in 76 patients with contact lens related DES following treatment with omega-6 supplements.
Tear film hyperosmolarity is a focal factor in dry eye. Larmo et al. evaluated in a double-blind, randomized, parallel trial, effect of consumption of 2 g of sea buckthorn (SB) oil, containing omega-3 and omega-6 fatty acids and anti-oxidants daily for 3 months to improve dry eye symptoms. There was a general increase in the osmolarity from baseline to the end of the intervention. Compared with the placebo group, the increase was significantly less in the SB group when all participants were included (P = 0.04) and when only participants consuming the study products for at least 80% of the intervention days were included. This positively affected the dry eye symptoms.
Some reports tried to evaluate the effect of omega-3 deficiency on severity of DES. Viau et al. evaluated whether a dietary deficiency in omega-3 may increase the severity of the pathology in a scopolamine-induced model of dry eye in the rat. Rats of three consecutive generations were bred under a balanced diet or a diet deprived of omega-3. Dry eye was experimentally induced by continuous scopolamine delivery in female animals from the third generation of both groups. Dryness was evaluated in vivo using fluorescein staining. Deficiency in omega-3 supplement does not increase the severity of dry eye in a rat model of dry eye.
Jackson et al. evaluate the effect of a prescription-only medical food supplement containing omega-3 and omega-6 essential fatty acids on dry eye signs and symptoms, with or without concomitant topical cyclosporine. A proper balance of omega-3 and omega-6 essential fatty acids improved tear break up time and relieved patient symptoms. The addition of topical cyclosporine did not show any extra benefit.

Role of systemic EFAs in the reducing inflammation of DES – clinical trials

Pinazo-Durán et al. in a prospective case control study have evaluated clinical outcomes, and expression levels of inflammation and immune response mediators in human reflex tear samples in patients diagnosed with nonsevere DEDs whom received a combination of antioxidants and omega-3 essential fatty acids for three months. Levels of interleukin (IL)-1β, IL6, and IL10 in tears were significantly lower in the treatment versus control group. Subjective symptoms of dry eye significantly improved in the treatment group.
Brignole-Baudouin et al. in a multicentre, double-masked, randomized, controlled trial demonstrated that supplementation with omega-3 and omega-6 fatty acids can reduce expression of HLA-DR conjunctival inflammatory marker and may help improve DES symptoms.

Role of topical EFAs in the management of DES – clinical trials

Rashid et al. used topical drops of ALA and linoleic acid EFAs in different formulations in a mouse model in which dry eye was both pharmacologically and environmentally induced.
Treatment with ALA significantly decreased corneal fluorescein staining compared with both vehicle and untreated controls. Additionally, ALA treatment was associated with a significant decrease in CD11b+ cell number, expression of corneal Interleukin-1α and Tumor necrosis factor (TNF) and conjunctival TNF. All these are important inflammatory mediators that are raised in DES patients.

Conclusion

A clear answer exists to our concern: “Essential Fatty Acids in the treatment of Dry Eye Syndrome: A myth or reality?”, as most of the studies suggest a beneficial role of omega-3 and omega-6 supplement in reducing inflammation and improving DES symptoms. We therefore find it a reasonable practice to encourage higher consumption of foods rich with those EFAs initially followed by prescribing oral supplements in patients not satisfied with topical medications alone. Although it should be kept in mind that these supplements need some time to work and commitment from patients to achieve its desired goal. More studies are required in order to consider these supplements as part of an established protocol to treat DES.

Financial disclosure

The authors have no proprietary or commercial interest in any material discussed in this article. No financial support was received.

Conflict of interest

The authors declared that there is no conflict of interest

Footnotes

Peer review under responsibility of Saudi Ophthalmological Society, King Saud University.

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