n-3 fatty acids: role in neurogenesis and neuroplasticity.

Crupi R, Marino A, Cuzzocrea S.

Author information

Institute of Pharmacology, School of Medicine, University of Messina, Policlinico Universitario, Torre Biologica 98123 Messina, Italy.

Abstract

Omega-3 polyunsaturated fatty acids (PUFA) are essential unsaturated fatty acids with a double bond (C=C) starting after the third carbon atom from the end of the carbon chain. They are important nutrients but, unfortunately, mammals cannot synthesize them, whereby they must be obtained from food sources or from supplements. Amongst nutritionally important polyunsaturated n-3 fatty acids, -linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are highly concentrated in the brain and have anti-oxidative stress, anti-inflammatory and antiapoptotic effects. They are involved in many bodily processes and may reportedly lead to neuron protection in neurological diseases. aged or damaged neurons and in Alzheimer's disease. Their effect in cognitive and behavioral functions and in several neurological and psychiatric disorders has been also proven. The dentate gyrus (DG), a sub-region of hippocampus, is implicated in cognition and mood regulation. The hippocampus represents one of the two areas in the mammalian brain in which adult neurogenesis occurs. This process is associated with beneficial effects on cognition, mood and chronic pharmacological treatment. The exposure to n-3 fatty acids enhances adult hippocampal neurogenesis associated with cognitive and behavioral processes, promotes synaptic plasticity by increasing long-term potentiation and modulates synaptic protein expression to stimulate the dendritic arborization and new spines formation. On this basis we review the effect of n-3 fatty acids on adult hippocampal neurogenesis and neuroplasticity. Moreover their possible use as a new therapeutic approach for neurodegenerative diseases is pointed out.

- 3 : . R , , Cuzzocrea . , , , , 98123 , .- 3 () (C = C ), . , , , , . -3 , - ( ) , (EPA) ( DHA), , . , , . . . ( ) , , . , . , . - 3 , , . - 3 . , .

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

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

Bhargava R1, Kumar P2, Kumar M3, Mehra N1, Mishra A1.

Author information

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 65 y with MCI were randomized to receive a supplement richin the long-chain -3 PUFAs eicosapentaenoic acid (EPA; 1.67 g EPA + 0.16 g docosahexaenoic acid DHA/d; n = 12) or DHA (1.55 g DHA + 0.40 g EPA/d; n = 12), versus -6 PUFA linoleic acid (LA;2.2 g/d; n = 9) for 6 mo.

RESULTS:

The intervention did not show an increase in telomere length with treatment and there was a trend toward telomere shortening during the intervention period. Linear mixed modeling produced a robust model although statistically underpowered. Telomere shortening was greatest in the LA group (d = 0.21) than in the DHA (d = 0.12) and EPA groups (d = 0.06). Increased erythrocyte DHA levels were associated with reduced telomere shortening (r = -0.67; P = 0.02) in the DHA group.

CONCLUSION:

Telomeric shortening may be attenuated by -3 PUFA supplementation, requiring further investigation in larger samples.

- 3 : .' N1 , Parletta N2, Milte CM2 , Benassi - 3, M3 , PR4 .: . . - 3 ( - 3 ) (MCI) . : > 65 - 3 (EPA ; 1,67 + 0,16 DHA / ; = 12) DHA ( 1,55 DHA + EPA 0,40 / ; = 12) , -6 (LA ; 2,2 / , = 9) 6 .: . , . LA ( = 0,21 ) , DHA ( = 0,12 ) EPA (D = 0,06 ) . DHA ( = -0,67 , p = 0,02 ) DHA . : - 3 , .

Int J Geriatr Psychiatry. 2013 Dec 11. doi: 10.1002/gps.4058. [Epub ahead of print]

Omega-3 fatty acid biomarkers and subsequent depressive symptoms.

Persons JE, Robinson JG, Ammann EM, Coryell WH, Espeland MA, Harris WS, Manson JE, Fiedorowicz JG.

Author information

Department of Epidemiology, College of Public Health, The University of Iowa, Iowa City, IA, USA.

Abstract

OBJECTIVE:

We sought to determine the relationship between the omega-3 fatty acid content of red blood cell membranes (RBC), in particular docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), and baseline and new-onset depressive symptoms in post-menopausal women. We secondarily sought to characterize the association between dietary omega-3 fatty acid intake and depressive symptomatology.

METHODS:

Study participants included 7086 members of the Women's Health Initiative Memory Study (aged 63-81years) who had an assessment of RBC omega-3 fatty acid concentrations at the baseline screening visit. Depressive symptoms at baseline and follow-up were characterized using the Burnam eight-item scale for depressive disorders (Center for Epidemiologic Studies Depression Scale/Diagnostic Interview Schedule short form) and secondarily additionally inferred by antidepressant medication use.

RESULTS:

In multivariable-adjusted models, our primary exposure, RBC DHA+EPA, was not related to depressive symptoms by any measure at baseline or follow-up, nor were RBC total omega-3, DHA, or EPA (all p>0.2). In contrast, dietary intake of omega-3 was positively associated with depressive symptoms at baseline (adjusted odds ratio 1.082, 95% confidence interval 1.004-1.166; p=0.04 for dietary DHA+EPA and Burnam score 0.06), although this generally did not persist at follow-up.

CONCLUSION:

No relationship between RBC omega-3 levels and subsequent depressive symptoms was evident, and associations between dietary omega-3 and depressive symptoms were variable. Biomarkers of omega-3 status do not appear to be related to risk of new depression in post-menopausal women. Copyright 2013 John Wiley & Sons, Ltd.

-3 ., JE , JG , Ammann .., WH , Espeland .., WS , JE , Fiedorowicz JG . , , , - , , .: -3 () , , ( DHA ) (EPA) . -3 . : 7086 , ( 63-81 ) , -3 . Burnam - ( / ) .: , , + , , -3 , DHA EPA ( > 0,2 ) . , -3 ( 1,082 , 95% 1.004-1.166 , = 0,04 + Burnam 0,06 ) , . : - 3- , -3 . -3 , , . Copyright 2013 John Wiley & Sons , Ltd

Lipids. 2013 Dec 14. [Epub ahead of print]

Lymphatic Transport of -Linolenic Acid and Its Conversion to Long Chain n-3 Fatty Acids in Rats Fed Microemulsions of Linseed Oil.

Sugasini D, Devaraj VC, Ramesh M, Lokesh BR.

Author information

Department of Lipid Science and Traditional Foods, CSIR-Central Food Technological Research Institute, Mysore, 570 020, India.

Abstract

In the present study we evaluated the uptake of ALA and its conversion to EPA+DHA in rats given linseed oil (LSO) in native form or as a microemulsion in whey protein or in lipoid. In a single oral dose study in which rats maintained on rodent pellets deficient in -3 fatty acids were intubated with 0.35g LSO in lipoid, the amount of ALA present in lymph was increased reaching a maximum concentration of 16.23mg/ml at 2.5h. The amount of ALA present in lymph was increased to a maximum level of 10.95mg/ml at 4h in rats given LSO as a microemulsion in whey protein. When LSO was given without emulsification, the amount of ALA present in lymph was found to reach a maximum level of 7.08mg/ml at 6h. A similar result was observed when weaning rats were intubated with 0.15g of LSO per day for a period of 60days. Higher levels of ALA by 41 and 103% were observed in lymph lipids of rats given microemulsions of LSO in whey protein and in lipoid respectively as compared to rats given LSO without pre-emulsification. Very little conversion of ALA to EPA and DHA was observed in lymph lipids but higher amounts of EPA+DHA was observed in liver and serum of rats given LSO in microemulsion form. This study indicated that ALA concentration in lymph lipids was increased when LSO was given in microemulsion form in lipoid and further conversion to EPA and DHA was facilitated in liver and serum.

- - 3 , .Sugasini D , VC , , . , CSIR - , , 570 020 , . ALA + , ( ) . , , -3 0,35 LSO , ALA , 16,23 / 2,5 . ALA , 10,95 / 4 , LSO . LSO , ALA , 7,08 / 6 . 0,15 LSO 60 . 41 103% , LSO , LSO . , + , LSO . , , EPA DHA .

Nutr Clin Pract. 2013 Dec 14. [Epub ahead of print]

Biomarkers of Fish Oil Omega-3 Polyunsaturated Fatty Acids Intake in Humans.

Silva V, Barazzoni R, Singer P.

Author information

1Institute for Nutrition Research, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel.

Abstract

A biomarker is a measured characteristic that may be used as an indicator of some biological state or condition. In health and disease, biomarkers have been used not only for clinical diagnosis purposes but also as tools to assess effectiveness of a nutrition or drug intervention. When considering nutrition studies, evaluating the appropriate biomarker is a useful tool to assess compliance and incidence of a particular dietary component in the biochemistry of the organism. Fish oil is rich in -3 fatty acids that have well-known beneficial effects on human health mainly through its anti-inflammatory properties. It has been widely use to improve health and as a nutrition supplement in different pathological conditions such as cardiovascular, neurological, and critically ill related diseases. Eicosapentaenoic acid and docosahexaenoic acid levels present in different biological moieties (plasma, cellular membranes, adipose tissue, etc) are the best biomarkers of fish oil intake. Each biological source of fatty acids has its own advantages and disadvantages, thus which biomarker to choose and where to measure it requires a comprehension of the objectives of the investigation. In this article we will review key facts about fish oil intake biomarkers to evaluate how components of a specific diet could be monitored and identified in biological samples. Having an accurate assessment of nutrition patterns could provide effective targets for intervention aimed at modifying eating habits and lifestyle towards the improvement of health.

-3 . V, Barazzoni R, .1 , , " ", -, .- , . , , . , . -3- , , , . , , -, , , . , (, , .) . , , . , . , , .

Prog Lipid Res. 2013 Oct 24;53C:1-17. doi: 10.1016/j.plipres.2013.10.002. [Epub ahead of print]

Long-chain polyunsaturated fatty acids (LCPUFA) from genesis to senescence: The influence of LCPUFA on neural development, aging, and neurodegeneration.

Janssen CI1, Kiliaan AJ2.

Author information

1Department of Anatomy, Radboud University Medical Center, Donders Institute for Brain, Cognition, and Behaviour, PO Box 9101, 6500 HB Nijmegen, The Netherlands. Electronic address: Carola.Janssen@radboudumc.nl.

2Department of Anatomy, Radboud University Medical Center, Donders Institute for Brain, Cognition, and Behaviour, PO Box 9101, 6500 HB Nijmegen, The Netherlands. Electronic address: Amanda.Kiliaan@radboudumc.nl.

Abstract

Many clinical and animal studies demonstrate the importance of long-chain polyunsaturated fatty acids (LCPUFA) in neural development and neurodegeneration. This review will focus on involvement of LCPUFA from genesis to senescence. The LCPUFA docosahexaenoic acid and arachidonic acid are important components of neuronal membranes, while eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid also affect cardiovascular health and inflammation. In neural development, LCPUFA deficiency can lead to severe disorders like schizophrenia and attention deficit hyperactivity disorder. Perinatal LCPUFA supplementation demonstrated beneficial effects in neural development in humans and rodents resulting in improved cognition and sensorimotor integration. In normal aging, the effect of LCPUFA on prevention of cognitive impairment will be discussed. LCPUFA are important for neuronal membrane integrity and function, and also contribute in prevention of brain hypoperfusion. Cerebral perfusion can be compromised as result of obesity, cerebrovascular disease, hypertension, or diabetes mellitus type 2. Last, we will focus on the role of LCPUFA in most common neurodegenerative diseases like Alzheimer's disease and Parkinson's disease. These disorders are characterized by impaired cognition and connectivity and both clinical and animal supplementation studies have shown the potential of LCPUFA to decrease neurodegeneration and inflammation. This review shows that LCPUFA are essential throughout life.

(LCPUFA) : LCPUFA , . CI1, Kiliaan AJ2.1 , Radboud University Medical Center, Donders , , PO Box 9101, 6500 HB (). : Carola.Janssen@radboudumc.nl.2 , Radboud University Medical Center, Donders , , PO Box 9101, 6500 HB (). : Amanda.Kiliaan@radboudumc.nl. , (LCPUFA) . LCPUFA . LCPUFA , , , - . , LCPUFA , . LCPUFA , , . , LCPUFA . LCPUFA , . , , 2 . , LCPUFA , . , LCPUFA . , LCPUFA .

Neurobiol Aging. 2013 Nov 21. pii: S0197-4580(13)00579-4. doi: 10.1016/j.neurobiolaging.2013.11.011. [Epub ahead of print]

Blood markers of fatty acids and vitamin D, cardiovascular measures, body mass index, and physical activity relate to longitudinal cortical thinning in normal aging.

Walhovd KB1, Storsve AB2, Westlye LT3, Drevon CA4, Fjell AM5.

Author information

1Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway; Department of Physical Medicine and Rehabilitation, Unit of Neuropsychology, Oslo University Hospital, Oslo, Norway. Electronic address: k.b.walhovd@psykologi.uio.no.

2Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway.

3Department of Psychology, University of Oslo, Oslo, Norway.

4Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.

5Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway; Department of Physical Medicine and Rehabilitation, Unit of Neuropsychology, Oslo University Hospital, Oslo, Norway.

Abstract

We hypothesized that higher levels of omega-3 fatty acids, vitamin D, and physical activity relate to cortical sparing, whereas higher levels of cholesterol, systolic blood pressure, and body mass index (BMI) relate to increased atrophy in the adult lifespan. Longitudinal measures of cortical thickness were derived from magnetic resonance imaging scans acquired (mean interval 3.6 years) from 203 healthy persons aged 23-87 years. At follow-up, measures of BMI, blood pressure, and physical activity were obtained. Blood levels of docosahexaenoic acid, eicosapentaenoic acid, vitamin D, and cholesterol were measured in a subsample (n= 92). Effects were tested in cortical surface-based analyses, with sex, age, follow-up interval, and the interactions between each included as covariates. Higher levels of docosahexaenoic acid, vitamin D, and physical activity related to cortical sparing. Higher cholesterol and BMI related to increased cortical thinning. Effects were independent, did not interact with age, and the cholesterol effect was restricted to males. Eicosapentaenoic acid and blood pressure showed no effects. The observed effects show promise for potential factors to reduce cortical atrophy in normal aging.

D, - , .Walhovd KB1, Storsve AB2, Westlye LT3, Drevon CA4, -5.1 , , , , , ; , , Oslo University Hospital, , . : k.b.walhovd@psykologi.uio.no.2- , , , , .3Department , , .4 Department of Nutrition, , , , , .5Research , , , , , ; , , Oslo University Hospital, , . , -3 , D , , , () . - , ( 3,6 ) 203 23-87 . , , . , , D, (n = 92). , , , . , D, , . , . , , . . .

J Clin Psychiatry. 2013 Nov;74(11):e1037-45. doi: 10.4088/JCP.13m08453.

Effects of 1-year treatment with highly purified omega-3 fatty acids on depression after myocardial infarction: results from the OMEGA trial.

Zimmer R, Riemer T, Rauch B, Schneider S, Schiele R, Gohlke H, Diller F, Steinbeck G, Katus H, Senges J.

Author information

Department of Psychiatry, Klinikum rechts der Isar, Technical University of Munich, Meisenweg 7, DE-82237 Wrthsee, Germany reinhilde.zimmer@lrz.tu-muenchen.de.

Abstract

OBJECTIVE:

The effects of supplementation of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on prevalence and severity of depression were evaluated in patients after a myocardial infarction.

METHOD:

A cross-sectional evaluation (posttest-only design) within the prospective, randomized, controlled, multicenter OMEGA trial was performed in patients after myocardial infarction at 12 months' follow-up (N = 2,081; age, mean = 64 years; men, 76.7%; women, 21.8%) from April 2005 to June 2007. Patients received supplementation with ethyl esters 90 (460-mg EPA and 380-mg DHA) or placebo for 12 months. Depression was assessed with the Beck Depression Inventory-II (BDI-II); a BDI-II cutoff score of 14 was used as diagnosis of depression.

RESULTS:

When the total population was evaluated, no effects of EPA/DHA supplementation on depressive symptoms according to BDI-II score (mean [SD]) could be demonstrated: EPA/DHA (n = 1,046), 7.1 (6.9); placebo (n = 1,035), 7.1 (7.0); P = .7. The post hoc analyses of depressed patients with and without antidepressants revealed a tendency toward an antidepressant effect in patients with EPA/DHA supplementation as monotherapy: EPA/DHA (n = 125), 19.4 (5.8); placebo (n = 113), 19.9 (5.1); P = .07. However, in depressed patients with EPA/DHA supplementation as adjunctive to conventional antidepressants, a clinically relevant antidepressant effect was demonstrated: EPA/DHA (n = 33), 20.9 (7.1); placebo (n = 29), 24.9 (8.5); P < .05.

CONCLUSIONS:

EPA/DHA supplementation in the total sample of patients after myocardial infarction had no effect on depressive symptoms. The clinically relevant antidepressant effect in the subgroup of depressed patients with EPA/DHA supplementation as adjunctive to conventional antidepressants that was revealed in the post hoc analysis might provide a basis for a controlled, prospective trial of omega-3 augmentation of antidepressants in patients after myocardial infarction.

1 , -3 : OMEGA .Zimmer R, T, B, Schneider S, R, Gohlke , Diller F, G, Katus , Senges . , Klinikum rechts der Isar, , Meisenweg 7, -82237 Wrthsee, reinhilde.zimmer@lrz.tu-muenchen.de.: -3 () (DHA) .: ( - ) , , , OMEGA , 12 (N = 2,081; , = 64 ; , 76.7%; , 21,8%), 2005 2007 . 90 (460 380 ) 12 . -II (BDI-II); BDI-II 14 .: , EPA/DHA , BDI-II ( [SD]) : EPA/DHA (n = 1,046), 7.1 (6.9); (n = 1,035), 7.1 (7.0); P = .7. Post hoc EPA/DHA : EPA/DHA (n = 125), 19.4 (5.8); (n = 113), 19,9 (5.1); P = .07. , EPA/DHA , : EPA/DHA (n = 33), 20.9 (7.1); (n = 29), 24.9 (8.5); P < .05.:EPA/DHA , . EPA/DHA , post hoc , -3 , .

J Vis Exp. 2013 Nov 29;(81). doi: 10.3791/50879.

Dietary Supplementation of Polyunsaturated Fatty Acids in Caenorhabditis elegans.

Deline ML, Vrablik TL, Watts JL.

Author information

School of Molecular Biosciences, Washington State University.

Abstract

Fatty acids are essential for numerous cellular functions. They serve as efficient energy storage molecules, make up the hydrophobic core of membranes, and participate in various signaling pathways. Caenorhabditis elegans synthesizes all of the enzymes necessary to produce a range of omega-6 and omega-3 fatty acids. This, combined with the simple anatomy and range of available genetic tools, make it an attractive model to study fatty acid function. In order to investigate the genetic pathways that mediate the physiological effects of dietary fatty acids, we have developed a method to supplement the C. elegans diet with unsaturated fatty acids. Supplementation is an effective means to alter the fatty acid composition of worms and can also be used to rescue defects in fatty acid-deficient mutants. Our method uses nematode growth medium agar (NGM) supplemented with fatty acidsodium salts. The fatty acids in the supplemented plates become incorporated into the membranes of the bacterial food source, which is then taken up by the C. elegans that feed on the supplemented bacteria. We also describe a gas chromatography protocol to monitor the changes in fatty acid composition that occur in supplemented worms. This is an efficient way to supplement the diets of both large and small populations of C. elegans, allowing for a range of applications for this method.

Caenorhabditis elegans. , Vrablik TL, JL. - , . . , , . Caenorhabditis elegans , -6 -3 . , , . , , C. elegans . - , - . (NGM) acidsodium . , C. elegans, . , , . , C. elegans, .

J Clin Lipidol. 2013 Nov-Dec;7(6):615-25. doi: 10.1016/j.jacl.2013.09.002. Epub 2013 Sep 18.

Long-term safety and efficacy of TAK-085 in Japanese subjects with hypertriglyceridemia undergoing lifestyle modification: The omega-3 fatty acids randomized long-term (ORL) study.

Tatsuno I, Saito Y, Kudou K, Ootake J.

Author information

Center for Diabetes, Metabolism and Endocrinology, Toho University Sakura Medical Center, Chiba 285-8741, Japan. Electronic address: ichiro.tatsuno@med.toho-u.ac.jp.

Abstract

BACKGROUND:

TAK-085 is an omega-3 preparation that contains eicosapentaenoic acid ethyl-ester (EPA-E) and docosahexaenoic acid-ethyl ester used in the management of hypertriglyceridemia.

OBJECTIVE:

The aim of the study was to evaluate the long-term safety (adverse events [AEs], laboratory parameters, vital signs, weight, and electrocardiograms) and effects on lipid profiles, especially triglyceride levels, of TAK-085 in Japanese patients with hypertriglyceridemia (triglyceride levels 150 mg/dL and 0.05). In addition, while MDA increased 18% in the placebo group (P = 0.009), it did not change in the EPA or DHA group (P > 0.05).

CONCLUSIONS:

Twelve weeks of supplementation with 1gr/d EPA or DHA prevent increasing oxidative stress without changing marker of inflammation. This study is the first report demonstrating that neither EPA nor DHA have effects on body fat mass in type 2 diabetic patients.

, 2 .- F, Jazayeri S, Eghtesadi S, , -, - , , , .:N-3 - . , , , 2 , , , , -3 . () (), -3, , , 2 .: II 1 EPA 1 DHA, 12 , - . , , , , .: , ( SD) 54,9 8.2 27,6 4,1 /(2) 96.0 16.2 / . EPA DHA FBS, C- , , , (P > 0,05). , MDA 18% (P = 0.009), EPA DHA (P > 0,05).: 1gr/d DHA EPA . , , EPA DHA), 2 .

Clin Interv Aging. 2013;8:1133-8. doi: 10.2147/CIA.S48955. Epub 2013 Aug 30.

A randomized, double-masked study to evaluate the effect of omega-3 fatty acids supplementation in meibomian gland dysfunction.

Oleik A, Jimnez-Alfaro I, Alejandre-Alba N, Mahillo-Fernndez I.

Author information

Department of Ophthalmology, Jimnez Daz Foundation, Madrid, Spain.

Abstract

BACKGROUND:

Dysfunction of the meibomian gland (MG) is among the most frequent causes of ophthalmological symptoms. The inflammation seen in meibomian gland dysfunction (MGD) is part of its pathogenesis, and evidence of the antioxidant-inflammatory properties of omega-3 fatty acids suggests this to be an appropriate treatment for MGD.

OBJECTIVE:

We aimed to assess the effectiveness of omega-3 fatty acids versus placebo, in improving the symptoms and signs of MGD.

METHODS:

We conducted a randomized and double-mask trial of 3 months duration. We enrolled 61 patients who presented with symptomatic MGD and no tear instability (defined as tear breakup time [TBUT]