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| ORIGINAL ARTICLE |
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| Year : 2023 | Volume
: 11
| Issue : 2 | Page : 92-96 |
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An open-label randomized clinical trial to evaluate the efficacy and tolerability of flax seed nutritional supplementation in comparison with omega-3 fatty acid capsule in mild dry eye disease
Meghana Patil1, Ravindra Banakar2, BH Manjunath2, Madhavi Gupta2
1 Department of Ophthalmology, JGMM Medical College, Hubli, Karnataka, India
2 Department of Ophthalmology, JJM Medical College, Davangere, Karnataka, India
| Date of Submission | 26-Feb-2023 |
| Date of Decision | 17-Mar-2023 |
| Date of Acceptance | 19-Mar-2023 |
| Date of Web Publication | 27-Apr-2023 |
Correspondence Address:
Meghana Patil
Department of Ophthalmology, JGMM Medical College, Hubli - 580 024, Karnataka
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/jcor.jcor_24_23
Background: Dry eye disease (DED) is a multifactorial disease commonly encountered in ophthalmology clinics. Omega-3 fatty acid has been proved to be effective in improving the symptoms of DED. Flax seed being the richest plant source of alpha-linolenic acid can be effective in DED. Aims: To evaluate the efficacy and tolerability of flax seed supplementation in comparison with omega-3 fatty acid capsules in DED. Setting and Design: Single-center randomized open-label clinical trial done at tertiary care hospital. Subjects and Methods: Two hundred sixty-eight subjects with clinically diagnosed mild dry eye received either flax seed supplementation daily for 3 months or omega-3 fatty acid capsule once daily for 3 months. Patients were evaluated at baseline, week 4, week 8, and week 12. On each visit subjects filled ocular surface disease index (OSDI) questionnaire and underwent Schirmer test, tear break up time (TBUT) and ocular staining. Results: One hundred thirty-three patients received flax seeds and 135 received omega-3 fatty acid. Schirmer test and TBUT showed increase in scores at each visit. OSDI scores reduced at subsequent visit and were statistically significant. Two factor repeated measures analyses of variances showed no statistically significant difference between the groups in terms of OSDI scores (P = 0.018). Conclusion: Our study demonstrated a rapid response to nutritional therapy (with flax seeds and omega-3 fatty acid capsules) in alleviating the signs and symptoms of dry eyes in both the groups. Flaxseeds supplementation is comparable to omega-3 fatty acid supplementation in DED and thus forms the cost-effective treatment for dry eyes and can be considered as an adjunctive therapy for the same.
Keywords: Dry eye disease, flax seeds, ocular surface disease index, omega-3 fatty acid, Schirmer test, tear break up time
How to cite this article:
Patil M, Banakar R, Manjunath B H, Gupta M. An open-label randomized clinical trial to evaluate the efficacy and tolerability of flax seed nutritional supplementation in comparison with omega-3 fatty acid capsule in mild dry eye disease. J Clin Ophthalmol Res 2023;11:92-6 |
How to cite this URL:
Patil M, Banakar R, Manjunath B H, Gupta M. An open-label randomized clinical trial to evaluate the efficacy and tolerability of flax seed nutritional supplementation in comparison with omega-3 fatty acid capsule in mild dry eye disease. J Clin Ophthalmol Res [serial online] 2023 [cited 2023 Jun 8];11:92-6. Available from: https://www.jcor.in/text.asp?2023/11/2/92/374870 |
Dry eye disease (DED) is a multifactorial disease (of the tears and ocular surface) with potential damage to the ocular surface.[1] DED is one of the most frequently encountered ocular morbidities. Twenty-five percent of the patients who visit ophthalmic clinic report symptoms of DED, making it a growing public health problem. It is associated with increased osmolarity of the tear film and inflammation of the ocular surface.[2] DED has physical, social, and psychological consequences due to impaired visual function and significantly affect the quality of life.[3] The prevalence of dry eye in computer vision syndrome has increased due to excessive use of visual display terminals causing alteration in tear film, which is a public health concern and economic challenge.[4]
]The ocular surface is almost constantly exposed to sunlight (high wavelength ultraviolet light) which increases the oxidative stress. Dry eye is also seen in patients of glaucoma taking antiglaucoma medications and the prevalence is reported between 48% and 59%.[5] Omega-3 fatty acids are known to reduce inflammation, primarily through resolvins that are derived from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and through anti-inflammatory mediators.[6] Omega-3 polyunsaturated fatty acids (PUFAs) are fundamental structural components of cell membranes and biological fluids. The main omega-3 fatty acids include alpha-linoleic acid, EPA and DHA.[7] These fatty acids are released into the tear film from the ocular surface epithelium in response to injury from desiccating stress. Omega-3 fatty acids block the synthesis of interleukin-1 and tumor necrosis factor alpha (TNF-α) thereby reducing inflammation and decreasing oxidative stress.[8] Oral supplementation with omega-3 fatty acids could improve inflammation on the ocular surface and relieve symptoms of dry eyes.[9] Flaxseed is an edible grain or seed oil which is emerging as an attractive functional food with the richest plant source of alpha-linolenic acid (ALA) (50%–62% of flaxseed oil or 22% of whole flaxseed).[10] Flaxseeds given at 10 gram/day to human subjects over 4 weeks has anti-inflammatory activity by decreasing the levels of TNF-α interleukin-6, and cytokines.[11] The Academy of Nutrition and Dietetics recommends getting between 1.3 g and 2.7 g of ALA each day and 1 tablespoon of flax seeds provides 2.4 g of ALA.[12] Most of these organizations recommend a min of 250–500 mg combined EPA and DHA each day for healthy adults.[13] The management of dry eye includes lid hygiene, tear substitutes, tear stimulation, anti-inflammatory and immunomodulatory agents. Recently, omega-3 fatty acids have been used in dry eye for altering the inflammatory status and improving the fatty acid content of meibomian secretions.[14] Oral supplementation with omega-3 fatty acids for 45 days resulted in improvements in dry eye symptoms, ocular surface inflammation and corneal staining in patients with inflammatory DED.[15] Hence, the aim of the study was to compare the efficacy and tolerability of flax seed supplementation with omega-3 fatty acid capsules in mild DED.
| Subjects and Methods | |  |
This study was an open-label, randomized, active controlled trial conducted in the Ophthalmology outpatient department in a tertiary care hospital for 12 months on subjects with mild DED. The study adheres to the tenets of the Declaration of Helsinki. The study was approved by Institutional Ethics Committee.
Selection of participants
Patients attending ophthalmology outpatient department for routine eye checkup underwent complete ophthalmic examination including visual acuity, anterior segment, posterior segment evaluation and Intra ocular pressure (IOP) measurement. The study subjects were subjected to Schirmer test for tear volume assessment and graded as mild, moderate, and severe. Only patients with mild dry eye without any dry eye symptoms were included in the study. The sample size of the study was calculated to be 300 patients and 150 in each group.
Inclusion criteria
- Patients of either sex above 18 years and patients diagnosed clinically with mild DED.
Exclusion criteria
- Moderate to severe dry eyes
- Pregnant and lactating women
- Active ocular infections
- Use of topical medications within 2 weeks
- Patients on treatment for DED within 2 months, ocular surgery in the past 2 months
- Patients on hormonal replacement therapy
- Patients with associated systemic conditions – diabetes mellitus, Hypertension, Tuberculosis, rheumatoid arthritis, connective tissue disorders, Systemic lupus erythematosus, thyroid disorders etc.
A written informed consent was obtained from the subjects who fulfilled the inclusion and exclusion criteria. Participant's demographic data, relevant medical and ocular history was taken and ophthalmological tests were done. The study subjects were randomized into two groups using computer generated random number table. One hundred and fifty subjects in Group A received 15 g (one table spoon) of whole flax seeds per day for 3 months. One hundred and fifty subjects in Group B received one omega-3 fatty acid soft gel capsule (OSMEGA-500, Allergan) per day for 3 months. Further patient evaluations were done at visit 1 (2 weeks), visit 2 (4 weeks), visit 3 (6 weeks), visit 4 (8 weeks), visit 5 (10 weeks), and visit 6 (12 weeks). These frequent visits at 15 days interval were required to know the compliance of the participant to the oral supplements. At each visit flax seeds and omega-3 fatty acid capsules were given to the subjects according to their groups. All the subjects answered an ocular surface disease index (OSDI) questionnaire at base line, visit 2, visit 4, and visit 6 and graded. The dry eye evaluation was done by assessing the tear break up time (TBUT), Schirmer test and ocular staining at base line, visit 2, visit 4 and visit 6. After 2 weeks of supplementation if the subjects had no improvement in ocular signs, they were put on topical medications and were excluded from the study. The participants were enquired about the adverse effects and compliance to the supplementations during each study visit. Three hundred subjects were included in the study and 32 subjects were lost to follow up within visit 2 and were excluded from the analysis.
Outcome measures
- Primary outcome measure was the change in mean scores for symptoms quantified using OSDI questionnaire from baseline to visit 6
- Secondary outcome measures were the changes in mean scores of TBUT, Schirmer test, and ocular surface staining from baseline to visit 6.
Statistical analysis: Descriptive data was analyzed by frequency and percentage. Categorical variables were analyzed using Chi-square test and continuous variables were analyzed using analyses of variances (ANOVA). The association between continuous variables was investigated with Pearson's correlation. For all statistical tests, P < 0.05 was taken significant.
| Results | | |
Two hundred sixty-eight patients with clinically diagnosed mild dry eye completed the study. Among 268 patients, 133 patients received flax seeds and 135 received omega-3 fatty acid. The mean age of patients in Group 1 and Group 2 was 40.42 and 43.98 years, respectively. There was no statistically significant difference between the two groups (P = 0.062) and were comparable in terms of age distribution. There were 76 (57.1%) males and 57 (42.9%) females in Group 1 and 89 (65.9%) males and (34.1%) females in Group 2. Gender distribution was equal in both the groups.
Schirmer test and tear break up time
Schirmer test and TBUT showed increase in scores at each visit which was highly significant statistically (P = 0.00) [Figure 1] and [Figure 2]. Two factor repeated measures ANOVA test was done to compare the mean scores of two groups. There was no statistically significant difference between the 2 groups in the mean scores of Schirmer test and TBUT. Thus, patients receiving flax seed and omega-3FA showed improvement in the scores of dry eye and both these groups are comparable in terms of improvement of dry eye symptoms. | Figure 1: Comparison of mean scores of Schirmer test at each visit in both the groups
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 | Figure 2: Comparison of mean scores of TBUT at each visit in both the groups. TBUT: Tear break up time
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Ocular staining: Staining was present in 73 (54.8%) subjects in Group A and 75 (55.5%) subjects in Group B at baseline visit which was comparable statistically. At week 12, the staining was present in 2 (1.5%) and 0 subjects in Group A and B respectively. There was disappearance of dry spots in both the groups.
Ocular surface disease index
OSDI scores reduced at subsequent visit and were statistically significant. Two-factor repeated measures ANOVA showed that there was a statistically significant difference between the groups in terms of OSDI scores (P = 0.018) [Table 1]. | Table 1: Comparison of Schirmer, tear break up time and ocular surface disease index scores among groups
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Post-hoc analysis was done using Bonferroni test which showed that there was significant difference between the groups in the mean difference of OSDI scores between baseline visit and Visit 2 (P = 0.0314) [Table 2]. Thus omega-3 FA showed better results at week 4 compared to flax seeds in terms of OSDI scores. | Table 2: Post hoc analysis of ocular surface disease index score among groups using Bonferroni test
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| Discussion | | |
Oral supplementation with both flax seed nutritional supplementation and omega-3 fatty acid capsules improved the signs and symptoms of dry eyes over a 12-week period in this study.
Antioxidant and ω−3 supplementation improve tear film parameters and decrease ocular surface inflammation.[16],[17] Dietary supplementation with PUFAs yields positive results in the improvement of dry eye signs and symptoms, and it seems that DHA and EPA may constitute the most effective treatment.[18] Harvard women's Study demonstrated a dose-dependent incidence of protection from dry eyes associated with fish consumption.[19] A study by Sheppard et al. has shown an improvement in DED and a reduction in inflammation with omega-3 fatty acid consumption.[20]
In our study, Schirmer and TBUT test scores improved in both the groups at each visit which was highly significant statistically but there was no difference between the groups. Thus, there was improvement in dry eye symptoms after taking supplements. A study by Epitropoulos et al. demonstrated that the Schirmer and TBUT scores increased with omega-3 supplementation but there was no improvement in symptoms of dry eye.[15] In our study, OSDI scores quantifying symptoms of DED showed that both omega-3 fatty acid and flax seed supplementation showed improvement in symptoms whereas, the post-hoc analysis showed that there was significant difference between the groups in the mean difference of OSDI scores between baseline and 2 weeks which concludes that omega-3 fattyacid shows faster improvement compared to flax seeds. However, there was no significant difference in the mean difference in further visits between the groups. Several studies have demonstrated that omega-3 supplements improve the OSDI symptom score.[21],[22],[23] This was the first ever study which compared the omega-3 fatty acid supplementation with flax seed nutritional supplementation and because of which we are not able to compare the results with other studies.
Deinema et al. concluded that moderate daily dose of both omega-3 fatty acid for 3 months, resulted in reduced tear osmolarity and increased tear stability in people with DED.[14]
A study by Downie et al. used novel preservative free nano-emulsion ophthalmic solution containing trehalose and flax seed oil for treating dry eyes and concluded that flax seed oil nano-emulsion improved TBUT and OSDI scores. There was significant improvement in dry eye symptoms. No adverse drug reaction were found to flax seed nano-emulsion in their study.[24]
A study by Rodriguez-Leyva et al. concluded that dietary flax seeds decrease both systolic and diastolic blood pressure in patients with peripheral arterial disease.[25]
A study by Arjmandi et al. compared whole flax seeds and sunflower seeds in hypercholesteraemic postmenopausal women and concluded that whole flax seeds markedly reduced total cholesterol and low density lipoproteins better than sunflower seeds.[26]
The direct cost of interventions in the two groups are as follows: flax seeds used in the treatment of DED costs 2.36 rupees per day (1 kg flax seed cost 236 rupees, 10 g is used per day) and omega-3 capsules in DED costs 16.4 rupees per day (Lacriguard capsules, 10 capsules cost 164 rupees) which is 8 times more than flax seeds.[27],[28] Thereby, flax seeds form the cost-effective modality in treating DED in developing countries.
Limitations
This was a single-center study and included subjects who had only mild DED, moderate, and severe dry eyes were excluded. Thus, we cannot generalize the results to all the dry eye patients with different disease severity. In future, multicentric trials with larger sample size with patients with different disease severity are recommended.
| Conclusion | | |
Our study demonstrated a significant improvement in dry eye signs and symptoms from baseline with the oral ingestion of flax seed and omega-3 fatty acid supplements for 12 weeks. The improvement of majority of the signs was seen as early as 4 weeks, suggesting a rapid response to nutritional therapy. Flax seeds are locally available and form the cost-effective treatment for DED. The improvement in signs and symptoms for dry eyes in both the groups supports the recommendation that dietary supplementation of flax seeds should be included as an adjunctive therapy for dry eyes.
Financial support and sponsorship
This study was financially supported by the RGUHS advanced research grant, RGUHS University, Bengaluru, Karnataka, India. The funders had no role in the preparation, review, or approval of the manuscript.
Conflicts of interest
There are no conflicts of interest.
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| 28. | |
[Figure 1], [Figure 2]
[Table 1], [Table 2]
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