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Effects of dietary supplementation with a combination of fish oil, bilberry extract, and lutein on subjective symptoms of asthenopia in humans
Abstract
The aim of this study was to determine the effects of dietary supplementation with a combination of fish oil, bilberry extract, and lutein on subjective symptoms of asthenopia in humans by a double- blind, randomized, parallel-group, and placebo-controlled trial. In the Active group, eleven subjects ingested a supplement containing omega-3 fatty acid-rich fish oil (docosahexaenoic acid 783 mg/day, eicosapentaenoic acid 162 mg/day), bilberry extract (anthocyanidin 59 mg/day), and lutein (17.5 mg/day) in soft gel capsule form, every day for 4 weeks. In the Placebo group, nine subjects ingested placebo capsules. Before and after supplementation, subjects completed a questionnaire to determine their asthenopia symptoms and were also assessed for mental fatigue symptom by the visual analog scale (VAS) test. Asthenopia symptoms such as "stiff shoulder, low back pain", "frustration", "dry-eye", and "stuffy head" were improved in the Active group. Furthermore, a score of mental fatigue was improved after 4 weeks of supplementation, and no side effects were observed after the 4-week supplementation and a 2-week washout period in the Active group. These results suggest that dietary supplementation with the combination of omega-3 fatty acid-rich fish oil, bilberry extract, and lutein may safely improve subjective symptoms of asthenopia and mental fatigue in humans.
... Two randomized, placebo-controlled trials have reported that oral carotenoid supplements can reduce ocular symptoms associated with extended screen time, but neither evaluated ocular surface outcomes [581,582] Randomized controlled trials have also evaluated a range of 'combination' supplements for treating digital eye strain, including fish oil with bilberry extract and lutein [583], water chestnut extract and lutein [584], lutein, zeaxanthin and blackcurrant extract [585], anthocyanin, astaxanthin, and lutein [586], and lutein ester, zeaxanthin, and extracts of blackcurrant, chrysanthemum, and goji berry (at three doses) [587]. Of these studies, only two evaluated ocular surface parameters, showing no benefit with a lutein, zeaxanthin and blackcurrant extract supplement, relative to placebo, for tear film stability measures over six weeks [586], while another lutein-based supplement showed enhanced tear secretion, measured using the Schirmer test, relative to placebo after 90 days [587]. ...
... One hundred articles underwent full text screening and 65 (65%) were excluded (Appendix A2). Thirty-five articles were ultimately deemed eligible for inclusion and underwent data extraction [84,303,351,444,515,516,525,526,529,530,549,555,[572][573][574][575][576][577][578][579]583,586,587,590,591,593,595,[601][602][603][604][605][606][607][608]. Table 6 summarizes the characteristics of included studies. ...
... Four studies investigated a berry extract dose of 120-160 mg/day [574,578,579,586], three studies used a dose of 480-550 mg/day [303,575,576], and the remaining three studies used a berry extract dose of 1000 mg/day [577], a berry/botanical extract dose of 2, 800 mg/day [587] or 4.2 g/day of active hydrogen-producing ingredients [602]. One study additionally investigated a combination omega-3 and anti-oxidant supplement [583], but its data failed to meet the criteria for being approximately normally distributed and were not included in the meta-analysis (see Section 8.11.2.6). The results of the meta-analysis of secondary outcomes in studies using an anti-oxidant supplement intervention are shown in Fig. 9. Use of anti-oxidant supplements was not associated with a significant improvement in most secondary outcome symptoms, including ocular burning sensation (standardized mean differences = − 0.47 [favors intervention], 95% CI: − 1.03, 0.09), with the exception of foreign body sensation, for which treatment was associated with a modest improvement in symptoms. ...
Eye strain when performing tasks reliant on a digital environment can cause discomfort, affecting productivity and quality of life. Digital eye strain (the preferred terminology) was defined as "the development or exacerbation of recurrent ocular symptoms and/or signs related specifically to digital device screen viewing". Digital eye strain prevalence of up to 97% has, due to no previously agreed definition/diagnostic criteria and limitations of current questionnaires, failed to differentiate such symptoms from those arising from non-digital tasks. Objective signs such as blink rate or critical flicker frequency changes are not 'diagnostic' of digital eye strain nor validated as sensitive. The mechanisms attributed to ocular surface disease exacerbation are mainly reduced blink rate and completeness, partial/uncorrected refractive error and/or underlying binocular vision anomalies, together with the cognitive demand of the task and differences in position, size, brightness and glare compared to an equivalent non-digital task. In general, interventions are not well established; patients experiencing digital eye strain should be provided with a full refractive correction for the appropriate working distances. Improving blinking, optimizing the work environment and encouraging regular breaks may help. Based on current, best evidence, blue-light blocking interventions do not appear to be an effective management strategy. More and larger clinical trials are needed to assess artificial tear effectiveness for relieving digital eye strain, particularly comparing different constituents; a systematic review within the report identified use of secretagogues and warm compress/humidity goggles/ambient humidifiers as promising strategies, along with nutritional supplementation (such as omega-3 fatty acid supplementation and berry extracts).
... Prospective interventional studies containing anthocyanin extracts in formulation seem to demonstrate therapeutic protection against several asthenopic symptoms in patients with heavy screen time behaviors (Table 2) [193][194][195][196][197][198][199][200][201][202]. While the relationship between desktop computers and digital eye strain symptoms is clear, the putative implications of mobile smartphones and handheld devices on developing similar ocular discomforts and binocular vision stress are still under investigation [3,5,16,22,23,56]. ...
... While the scientific rationale for dietary strategies involving these nutraceuticals is quite clear, there is limited evidence pertaining to xanthophyll supplementation in treating digital eye strain available to date [200,201,206,267,268]. Traditionally, carotenoids by themselves did not appear to alleviate dry eye or signs of ocular fatigue so they were often combined with anthocyanins and other antioxidants in multivitamin formula to improve these symptoms [199][200][201]206,267]. ...
... While the scientific rationale for dietary strategies involving these nutraceuticals is quite clear, there is limited evidence pertaining to xanthophyll supplementation in treating digital eye strain available to date [200,201,206,267,268]. Traditionally, carotenoids by themselves did not appear to alleviate dry eye or signs of ocular fatigue so they were often combined with anthocyanins and other antioxidants in multivitamin formula to improve these symptoms [199][200][201]206,267]. However, alterations in macular pigment status have been posited as a surrogate for visual performance in both healthy and diseased states [231,269]. ...
Digital eye strain is a complex, multifactorial condition that can be caused by excessive screen time exposure to various electronic devices such as smartphones, tablets, e-readers, and computers. Current literature suggests oxidative damage concomitant with a chronic pro-inflammatory state represent significant etiopathogenic mechanisms. The present review aims to discuss the potential dietary role for micronutrients with nutraceutical properties to ameliorate various ocular and vision-related symptoms associated with digital eye strain. For ocular surface dysfunction, enhanced anti-inflammatory benefits with omega-3 polyunsaturated fatty acids have been well documented for treatment of dry eye disease. The anti-oxidative and immunosuppressive properties of anthocyanin phytochemicals may also confer protective effects against visually induced cognitive stress and digital asthenopia. Meanwhile, nutraceutical strategies involving xanthophyll macular carotenoids demonstrate enhanced cognitive functioning and overall visual performance that aids digital eye strain. Collectively, preliminary findings seem to offer a strong line of evidence to substantiate the need for additional randomized controlled trials aimed at treating digital eye strain with adjunctive nutraceutical strategies. Further RCT and comparisons on commercially available nutritional supplements are needed to quantify the clinical benefits.
... 82 Eleven trials did not report the study location. 53,54,57,58,63,67,75,76,78,79,83 Most RCTs (n ¼ 35) used a parallel arm design, 19,20,23e25,48e51,54e71,74,75,77,79e82,84 and 10 studies used a crossover design. 22,52,53,72,73,76,78,83,85,86 In total, 4497 participants were recruited across the included 45 RCTs; individual study sample sizes ranged from 10 to 522 participants. ...
... visual fatigue score. Four studies58,59,80,81 reported on visual fatigue; however, data were not pooled because the studies evaluated different supplement combinations(Table S4). Kan et al 81 reported reduced visual fatigue symptoms with a combination supplement of lutein ester, zeaxanthin, and extracts of blackcurrant, chrysanthemum, and goji berry after 4 weeks (303 participants; MD, e2.83 units; 95% CI, e3.56 to e2.10 units; P < 0.001) relative to placebo. ...
... Kan et al 81 reported reduced visual fatigue symptoms with a combination supplement of lutein ester, zeaxanthin, and extracts of blackcurrant, chrysanthemum, and goji berry after 4 weeks (303 participants; MD, e2.83 units; 95% CI, e3.56 to e2.10 units; P < 0.001) relative to placebo. Three studies58,59,80 reported no improvement in symptoms of visual fatigue with combination supplements compared with placebo(Table S6). The certainty of the evidence for this outcome was judged to be very low.2. ...
Topic
To evaluate the efficacy and safety of interventions for treating eye strain related to computer use relative to placebo or no treatment.
Clinical relevance
Computer use is pervasive and often associated with eye strain, referred to as “computer vision syndrome” (CVS). Currently, there are no clinical guidelines to help practitioners provide evidence-based advice about CVS treatments, many of which are directly marketed to patients. This systematic review and meta-analysis will help inform best practice for eye care providers.
Methods
Eligible randomized controlled trials (RCTs) were identified in Ovid MEDLINE, EMBASE, CENTRAL, and trial registries, searched from inception to November 23, 2021. Eligible studies were appraised for risk of bias, and synthesized. The certainty of the body of evidence was judged using GRADE. Standardized mean differences (SMD) were used when differently scaled measures were combined.
Results
Forty-five RCTs, involving 4497 participants, were included. Multifocal lenses did not improve visual fatigue scores compared to single-vision lenses (three RCTs, SMD: 0.11; 95% confidence interval (CI) -0.14 to 0.37; p=0.38). Visual fatigue symptoms were not reduced by blue-blocking spectacles (three RCTs), with evidence judged to be of low certainty. Relative to placebo, oral berry extract supplementation for 4 to 12 weeks did not improve visual fatigue (seven RCTs, SMD: -0.27; 95%CI -0.70 to 0.16; p=0.22), and dry eye symptoms (four RCTs, SMD: -0.10; 95%CI -0.54 to 0.33; p=0.65). Likewise, berry extract supplementation had no effect on critical flicker-fusion frequency (CFF) or accommodative amplitude. Oral omega-3 fatty acid supplementation for 45 days to 3 months improved dry eye symptoms (two RCTs, mean difference, MD: -3.36 units out of 18; 95%CI -3.63 to -3.10; p<0.00001) relative to placebo. Oral carotenoid supplementation improved CFF (two RCTs, MD: 1.55 Hz; 95%CI 0.42 to 2.67; p=0.007) relative to placebo, although the clinical significance of this finding is unclear.
Conclusions
We found no high certainty evidence supporting the use of any of the therapies analyzed. There was low certainty evidence that oral omega-3 supplementation reduces dry eye symptoms in symptomatic computer users.
... A large number of human trials have looked at the effectiveness of dietary supplementation with omega fatty acids and antioxidants alone or in combination with each other in subjects with dry eyes including Sjögren's syndrome, contact lens wear, meibomian gland dysfunction and following refractive surgery (Aragona et al., 2005;Barabino et al., 2003;Blades et al., 2001;Brignole-Baudouin et al., 2011;Creuzot-Garcher et al., 2011;Creuzot et al., 2006;Drouault-Holowacz et al., 2009;Horrobin et al., 1981;Jackson et al., 2011;Kangari et al., 2013;Kawabata and Tsuji, 2011;Kokke et al., 2008;Larmo et al., 2010;Macri et al., 2003;Macsai, 2008;Manthorpe et al., 1984;Mckendry, 1982;Oxholm et al., 1986;Pinazo-Duran et al., 2013;Pinna et al., 2007;Theander et al., 2002;Wojtowicz et al., 2010). Topical administration of these dietary compounds and their derivatives has also been investigated in animal models but this is not the subject of this review (Cortina et al., 2010;Esquenazi et al., 2005;Li et al., 2010;Rashid et al., 2008). ...
... Five RCT have investigated formulations of omega-3 alone or combined with antioxidants (Kangari et al., 2013;Kawabata and Tsuji, 2011;Macsai, 2008;Pinazo-Duran et al., 2013;Wojtowicz et al., 2010). In the first study, a supplement containing fish oil, bilberry extract and lutein (783mg DHA, 162mg EPA, 59mg anthocyanidin, 17.5 lutein) increased serum DHA/AA ratio and decreased serum DGLA after 4 weeks (Kawabata and Tsuji, 2011). ...
... Five RCT have investigated formulations of omega-3 alone or combined with antioxidants (Kangari et al., 2013;Kawabata and Tsuji, 2011;Macsai, 2008;Pinazo-Duran et al., 2013;Wojtowicz et al., 2010). In the first study, a supplement containing fish oil, bilberry extract and lutein (783mg DHA, 162mg EPA, 59mg anthocyanidin, 17.5 lutein) increased serum DHA/AA ratio and decreased serum DGLA after 4 weeks (Kawabata and Tsuji, 2011). The stated aim was to study the effectiveness of omega-3 supplementation on symptoms of asthenopia including those associated with visual display units and although reduced symptoms of dry eye were reported following supplementation, the trial suffered from many sources of bias (investigator employed by manufacturer of capsule, unsuccessful randomisation, placebo effect) (Kawabata and Tsuji, 2011). ...
Nutrition disorders and their correlates such as obesity are increasingly prevalent worldwide. A number of studies to date have suggested numerous potential associations between diet and tear film health; this paper will provide a summary of the available literature. The tear film is characterized through its protein and lipid content and through clinical measurements of characteristics such as osmolarity, volume and stability. Malnutrition, protein and vitamin-A deficiencies are extremely deleterious to tear film health and supplementation with oral vitamin A in this setting is of clear benefit. The relative impact of diet on tear film within what would be considered normal ranges of consumption is less clear. A number of population studies have suggested that hyperlipidemia and a diet low in omega-3 fatty acids are risks factor for dry eye disease. Numerous studies have investigated the effectiveness of oral supplementation with antioxidants, omega-3 (e.g. fish oil and linseed oil) and omega-6 (e.g. evening primrose oil) fatty acids in the last 10 years. Taken together, these suggest a small benefit of oral supplementation on tear film volume, stability and decreased ocular symptoms in patients previously diagnosed with diseases involving the ocular surface (e.g. Sjögren's syndrome, meibomian gland dysfunction, dry eye disease) and contact lens wearers suffering from dry eye. More research is required to determine the exact composition, dosage and indications for their use and to fully characterize how these nutraceuticals modulate the tear film.
... Therefore, effective nutritional intervention strategies should be proposed for improving or reducing the degree of damage to the fundus or ocular surface and balancing the health of the internal environment of the eye, thus playing an adjunctive role in relieving visual fatigue. In recent years, an increasing number of studies have found that optimal visual performance can be effectively promoted by supplementing the diet with appropriate foods or nutrients [22], such as anthocyanins [26], taurine [27], DHA-and eicosapentaenoic acid (EPA)-rich fish oils, lutein [28], astaxanthin [29], and lingonberry extracts [30], which can reduce or alleviate the onset of visual fatigue [31]. Among them, PUFAs, as essential nutrients, have a very important supporting role in alleviating visual fatigue [32]. ...
... Clinical studies have further confirmed that after a 30 d period of flaxseed oil soft gel supplementation administered to 101 visually fatigued individuals, visual fatigue symptoms were significantly reduced, with a 70.3% persistence of binocular vision and a 51% total effective rate, a significant difference, confirming that dietary supplementation with ω-3 PUFAs can effectively alleviate visual fatigue [106]. Fuminori et al. showed [28] that continuous supplementation with ω-3 PUFAs rich in ω-3 PUFAs, particularly a combination preparation of fish oil (DHA 783 mg/d and EPA 162 mg/d), lingonberry extract (containing anthocyanins 59 mg/d) and luteolin (17.5 mg/d), for 4 weeks significantly improved symptoms in people with visual fatigue. Thus, a growing body of research supports that increasing dietary levels of ω-3 PUFAs can promote human health. ...
When the eyes are exposed to the environment, they are easily affected by strong light stimulation and harmful substances. At the same time, prolonged use of the eyes or incorrect eye habits can cause visual fatigue, which mainly manifests as eye dryness, soreness, blurred vision, and various discomforts. The main reason for this is a decline in the function of the eye, especially the cornea and retina on the surface of the eye, which have the greatest impact on the normal function of the eye. Research has found that supplementation with appropriate foods or nutrients can effectively strengthen the eye against external and internal stimuli, thereby alleviating or avoiding visual fatigue. Among these, supplementation with polyunsaturated fatty acids has been found to be effective at protecting eye health and relieving visual fatigue. This article summarizes the sources of polyunsaturated fatty acids (including the main dietary sources and internal synthesis), the mechanisms of digestion and absorption of polyunsaturated fatty acids in the body and the safety of polyunsaturated fatty acid applications. It also reviews the mechanism of action of polyunsaturated fatty acids in aiding the relief of visual fatigue based on the mechanism of impaired function or structure of the ocular surface and fundus in the hope of providing some reference and insight into the development and application of polyunsaturated fatty acids in functional foods for the relief of visual fatigue.
... Lutein and zeaxanthin are well-known ingredients that have been shown to prevent age-related macular degeneration (AMD) due to their antioxidant properties and ability to absorb high-energy blue light produced by VDUs (12)(13)(14)(15). These 2 ingredients when used alone do not improve eye fatigue or dry eye, so they are always combined with other botanical ingredients with abundant anthocyanin to improve eye fatigue symptoms (16)(17)(18)(19). Blackcurrant (Ribes nigrum L.) can provide dietary anthocyanin, which can be beneficial to visual function by increasing retinal blood circulation to mitigate eye fatigue symptoms (20)(21)(22). ...
... It has been widely reported that supplementation of 10 mg of lutein and 2 mg of zeaxanthin could prevent AMD and improve visual performance (13-15, 47, 49-51). However, the information on eye fatigue in this regard is limited (16)(17)(18)(19). In this study, we tested different doses of lutein and zeaxanthin, namely, 6 mg lutein/1.2 ...
Background:
With the frequent use of video display units, eye fatigue is becoming more common globally. An alternative nutritional strategy is needed to prevent the aggravation of eye fatigue symptoms.
Objectives:
The objective was to evaluate the protective effect of a novel botanical combination of lutein ester, zeaxanthin, and extracts of blackcurrant, chrysanthemum, and goji berry on adults with eye fatigue in a randomized, double-blind, placebo-controlled clinical trial.
Methods:
We randomly allocated 360 participants into 4 groups to receive placebo and 3 doses of our formula (chewable tablets, containing 6 mg, 10 mg, or 14 mg of lutein) once daily for 90 d. Each participant had 3 visits at baseline (V1), 45 d (V2), and 90 d (V3) during the study.
Results:
Intervention with the formula improved individual scores of eye fatigue symptoms, including eye soreness, blurred vision, dry eye, foreign body sensation, and tearing. Compared with placebo, the formula at all 3 doses significantly decreased the total score of eye fatigue symptoms and increased the visuognosis persistence time at both V2 and V3. According to the Schirmer test, both 10-mg and 14-mg lutein formula groups had improved tear secretion at V3 compared with the placebo. The keratography results indicated that the first tear break-up time, average tear break-up time, and tear meniscus height were significantly increased after formula intervention. The formula at all 3 doses significantly increased the macular pigment optical density at V2 and V3 compared with the placebo, whereas optical coherence tomography showed no significant difference in retinal thickness and retinal volume across all groups at both visits.
Conclusions:
Our botanical formula improves eye fatigue, dry eye, and macular function without changing the retinal structure, and thus it could serve as an effective nutritional strategy in improving eye fatigue without causing serious side effects.Clinical Trial Registry: chictr.org.cn (ChiCTR1800018987).
... An eight-week bilberry extract supplementation, in contrast to placebo group, alleviated the subjective symptoms of eye fatigue (including ocular pain, eye heaviness, uncomfortable sensation, and foreign body sensation) and reduction in critical flicker fusion which were induced by an acute video display terminal (VDT) load [17] . Another double-blind, randomized, and placebo-controlled trial showed that asthenopia symptoms (such as stiff shoulder, low back pain, frustration, dry-eye and stuffy head) and a score of mental fatigue were improved in subjects after a dietary intervention containing omega-3 fatty acid-rich fish oil, bilberry extract, and lutein [18] . However, evidence of habitual dietary factors in relation to the asthenopia risk remains sparse, especially among college students. ...
... Several prior studies have reported an inverse association of fruit and vegetable intake with certain types of age-related eye diseases, including AMD and cataract [19][20] , which provided appreciable evidence for the potential benefits of fruit and vegetable intake in eye health. In accordance with previous research [17][18][19][20] , our results showed that highest category of dark-green leafy vegetable intake (≥4 servings/wk) was associated with a lower risk of asthenopia, compared with the lowest category (≤1 serving/wk). The mechanisms by which dark-green leafy vegetable intake may alter asthenopia risk are speculative. ...
Aim:
To investigate the associations between fruit and vegetable consumption and risk of asthenopia among Chinese college students.
Methods:
A total of 1022 students were selected from five universities by a multi-stage stratified cluster sampling method. They were surveyed via a self-administered questionnaire including socio-demographic features, dietary and lifestyle habits, eye-related symptoms, eye care habits and history of diseases. Ascertainment of asthenopia was based on participants' subjectively reported symptoms. The associations between fruit and vegetable intake with asthenopia risk were assessed using multivariate logistic regression analysis.
Results:
There were no significant associations between total fruit and vegetable, total vegetable, or fruit and the risk of asthenopia. Higher intake of dark-green leafy vegetable was likely to be inversely associated with asthenopia risk [odd ratio (OR): 0.60; 95%CI: 0.37-0.97; Ptrend=0.21] after controlling for nondietary and dietary risk factors. Stratified analysis showed that the inverse association between dark-green leafy vegetable intake and asthenopia risk was limited to participants with suboptimal eyesight (OR: 0.45; 95%CI: 0.25-0.82; Ptrend=0.05), wearing glasses (OR: 0.35; 95%CI: 0.17-0.72; Ptrend=0.03) or using computer ≥3h/d (OR: 0.48; 95%CI: 0.25-0.93; Ptrend=0.08).
Conclusion:
A higher consumption of dark-green leafy vegetable is associated with a lower asthenopia risk among college students with suboptimal eyesight and poor eye care habits.
... The aim of the present study was to investigate whether PFA exerts ameliorating effects on visual fatigue. Several studies have demonstrated that certain food ingredients, such as docosahexaenoic acid [35], eicosapentaenoic acid [35], omega-3 fatty acids [36], lutein [37], zeaxanthin [37], astaxanthin [9], bilberry extract [2], black soybean hull extract [9], and anthocyanin [19,38] can improve visual fatigue. ...
... The aim of the present study was to investigate whether PFA exerts ameliorating effects on visual fatigue. Several studies have demonstrated that certain food ingredients, such as docosahexaenoic acid [35], eicosapentaenoic acid [35], omega-3 fatty acids [36], lutein [37], zeaxanthin [37], astaxanthin [9], bilberry extract [2], black soybean hull extract [9], and anthocyanin [19,38] can improve visual fatigue. ...
... When an article reported results for more than one pain-PUFA relationship (i.e., different supplements), we considered each one as a separate study unit. When necessary, we contacted authors for further information (9,10,18). The studies retrieved were divided into 2 groups, according to their preventive or curative purpose. ...
... Our search brought 47 articles which provided data on 51 studies: 5 observational studies (10,11,(24)(25)(26) and 46 intervention studies (8,9,18,. The complete search strategy and exclusion motives are shown in Fig. 1. ...
Background:
Chronic pain is one of the most frequent disease symptoms and represents a global health problem with a considerable economic burden. The role of polyunsaturated fatty acids (PUFA) in chronic pain conditions was debated during the last decade with conflicting results.
Objective:
To assess whether polyunsaturated fatty acids intake is useful as a preventive or curative tool in chronic pain.
Study design:
Systematic review and meta-analysis.
Setting:
This study examined all published studies, either preventive or curative, on PUFA supplementation and chronic pain.
Methods:
We retrieved studies published in any language by searching systematically Medline, Embase, Conference Proceedings Citation Index, dissertations databases, and the 5 regional bibliographic databases of the World Health Organization until May 2015. We included both observational and intervention studies reporting effect measures and their confidence intervals of polyunsaturated fatty acids intake in the regular diet or supplementation and pain. Two investigators selected studies; extracted data independently on baseline characteristics, exposure, and outcomes; and rated the quality of interventional studies using Jadad score. We calculated pooled standardized mean differences (SMDs) of pain indexes such as the Visual Analogue Score. We further carried out subgroup analyses by disease, type of PUFA, outcome scale, quality index, dose, and time of supplementation.
Results:
We retrieved 5 observational and 46 intervention studies. Only one observational study showed a protective effect of PUFA. On the contrary, the interventional studies yielded a pooled random effects SMD of -0.40 (95% CI -0.58, -0.22), which indicates improvement, as 0 is the value that indicates absence of effect. The largest effect was found for dysmenorrhea (SMD -0.82, 95% CI -1.21, -0.43), Ω-3 supplementation (-0.47, 95% CI -0.68, -0.26) and composite scores (-0.58, 95% CI -1.07, -0.09). Mitigation of pain was stronger for low doses (-0.55, 95% CI -0.79, -0.30) and short supplementation periods (-0.56, 95% CI -0.86, -0.25).
Limitations:
While the number of curative studies was large, that of preventive studies available was limited.
Conclusion:
Our results suggest that Ω-3 PUFA supplementation moderately improves chronic pain, mainly that due to dysmenorrhea. Further investigation on the preventive potential of PUFA supplementation is needed, as the amount of evidence is scarce. Key words: Meta-analysis, systematic review, chronic pain, PUFA, supplementation, Ω-3, dysmenorrhea.
... Many studies have suggested that plant-derived components, including lutein, zeaxanthin, and blackcurrant extract, might have positive effects on visual fatigue recovery in animals. These previous studies thoroughly investigated lutein and visual fatigue and confirmed the beneficial effects of lutein supplementation on visual function [15,17]. However, there are few clinical trials that directly demonstrate that lutein can alleviate visual fatigue. ...
Asthenopia is a syndrome based on the symptoms of eye discomfort that has become a chronic disease that interferes with and harms people’s physical and mental health. Lutein is an internationally recognized “eye nutrient”, and studies have shown that it can protect the retina and relieve visual fatigue. In this study, lutein was extracted from marigold (Tagetes erecta L.) and saponified. The purified lutein concentration measured by HPLC was 50.12 mg/100 g. Then, purified lutein was modified to be water-soluble by nanoscale modification and microencapsulation technology. Water-soluble lutein was then mixed with a leaching solution of Chinese wolfberry and chrysanthemum to make a functional beverage. The effects of this beverage on hepatic antioxidant enzymes and the alleviation of visual fatigue in a rat model of diabetes were investigated for 4 weeks. Lutein intake of 0.72 (medium-lutein beverage group) and 1.44 mg/mL (high-lutein beverage group) relieved visual fatigue, ameliorated turbidity symptoms of impaired crystalline lenses, reduced hepatic MDA concentration, increased hepatic GSH concentration, and significantly increased the activities of the hepatic antioxidant enzymes SOD, CAT, GSH-Px, and GR in rats. These data suggest that a lutein-rich beverage is an effective and harmless way to increase the total anti-oxidation capacity of lenses and alleviate visual fatigue.
... 桑葚有养肝明目作用，研究表明，桑葚不仅 含丰富的胡萝卜素、维生素、矿物质、纤维素等 营养成分，且含花青素等生物活性物质，常食桑 葚可缓解眼睛疲劳干涩的症状 [3][4] 。越橘富含花 青素，许多研究表明越橘可通过保护毛细血管， 促进视紫红质再生发挥缓解视疲劳作用 [5] 。叶黄 素是蔬菜水果中常见的色素成分之一，能预防蓝 光导致的视网膜损伤，具有保护视网膜，缓解视 疲劳的作用 [6][7] [6] 、万寿菊提取物(41.2 %) [13] 、 越橘提取物和叶黄素复方(18.0 %) [12] 。本研究 的复合营养素提高明视持久度的幅度为11.5 %， 高于万寿菊提取物(5.36 %) [13] 、越橘提取物和 叶黄素复方(11.0 ...
Objective To study the function of compound nutrients mainly composed of mulberry extract, bilberry extract and lutein on asthenopia. Methods 108 subjects with eye-fatigue were selected and divided into trial group or control group by the randomized double-blind method. The functional and safety indices were measured after taking compound nutrients or placebo respectively for 60 days. Results The symptom score of the trial group after experiment was significantly alleviated compared with that of the trial group before experiment and the control group (P<0.001, respectively). Symptoms of 23 subjects in the trial group were improved, and the total effective rate in the trial group was 42.6 %, which was significantly higher than that of the control group. Visuognosis persistence of the trial group after experiment were significantly improved compared with that of the trial group before experiment and the control group (P<0.001, respectively). Both intra-group comparison and intergroup comparison before and after the experiment showed no significant difference in visual acuity and eye using time. The safety indicators of the subjects were normal. Conclusion The compound nutrients can obviously relieve the symptoms of asthenopia without side effect.
... One cup of lentil contains 73.3 mg of omega-3 and 271 mg of omega-6, so it can be considered as a plant omega-3 supplier. Previous studies have shown that consumption of omega-3 in food and supplements may improve dry eye symptoms [24]. In the present tripleblind clinical trial, the efficacy of lentil compared to the placebo was studied in the treatment of mild to moderate dry eye. ...
Objective
To evaluate the safety and efficacy of dietary lentil capsules in patients suffering from dry eye symptoms.
Methods
A randomized, triple-blind, interventional, placebo-controlled study was done. Sixty patients were randomized in two groups to receive either one capsule containing 500 mg of lentil powder or placebo daily for 3 months. UCVA, tear film breakup time (TBUT), Schirmer’s test, tear film osmolarity, and OSDI score were recorded at baseline and 3 months after intervention. Data analysis was performed using IBM SPSS for Windows version 20 (SPSS, Chicago, IL, USA).
Results
In the lentil group, at baseline, the mean UCVA (LogMAR), OSDI, TBUT (S), tear film osmolarity (mOsm/L), and Schirmer (mm) scores were 0.104 (0.026), 22.66 (19.40), 10.31 (5.32), 301.07 (15.57), and 8.22 (6.87), respectively. These values were 0.101 (0.026), 20.85 (19.44), 13.04 (7.11), 299.81 (11.60), and 9.87 (10.11). In the placebo group, these values were 0.084 (0.027), 25.35 (20.08), 10.56 (4.95), 299.77 (15.09), and 9.35 (8.06) at baseline and 3 months later were 0.077 (0.027), 23.32 (22.90), 13.62 (6.30), 297.54 (12.08), and 8.64 (9.60), respectively. Three patients (one in the lentil group and two in the placebo group) experienced severe gastrointestinal symptoms.
Conclusion
Although consumption of 500 mg of lentil is safe, this amount is not sufficient for reduction of dry eye syndrome in 3 months. For more validation, a clinical study with increased dosage of lentil is proposed.
... The effectiveness of antioxidative supplements in preventing the progression of AMD [2,3], a blinding disease, have been previously reported; however, these effects were assessed and observed only in patients who already had signs of AMD, and were thus defined as high-risk patients. In contrast, the effects in the eyes of general participants with no serious diseases were reported regarding fatigue or accommodation disorders such as visual display terminal syndrome [6,32,33], dry eye disorders [34], and asthenopia [35]. Therefore, the effects were generally thought to be on mitigating the uncomfortableness rather than affecting visual acuity. ...
Randomized controlled studies have shown that antioxidative supplements are effective in suppressing the progression of age-related macular degeneration and visual display terminal syndrome. However, effects of their general use in the real-world and by young and healthy individuals have not been well documented. We analyzed 27 participants who were under 35 years of age and had no diagnosed diseases. Mean functional visual acuity (FVA) score and visual maintenance ratio, which represent quick recognition of a target, both measured using FVA system, were better (both p < 0.01) in subjects who had had regular antioxidative supplement intake for more than 2 months (11 participants) compared with those who had not. Systemic data, i.e., total cholesterol, hemoglobin A1c (HbA1c), and high-sensitivity C-reactive protein (hs-CRP) levels, which correspond to chronic low-grade inflammation, were lower (all p < 0.05) in the former. Overall, hs-CRP levels had a correlation with total cholesterol (p < 0.05) and a trend of correlation with HbA1c (p = 0.054) levels. Thus, current real-world data showed that young, healthy participants who had a regular intake of antioxidative supplements had better visual acuity and systemic levels of metabolic and low-grade inflammation markers. This study will help promote future research into the effects of general antioxidative supplement use.
... We evaluated the primary endpoint; high-frequency component 1 (HFC1) as an objective eyestrain parameter, measured by AA-2 accommodometer (Nidec Corp., Tokyo, Japan) according to the manufacturer's instructions [13]. We also evaluated the secondary endpoint; subjective symptoms of eyestrain, dry eye, and sleep, stiffness of the neck and shoulder, and waist stiffness using a visual analog scale (VAS) questionnaire [14], with the left side of VAS showing worse feelings and the right side showing better feelings. The VAS score was calculated as a distance from the left (worst) side. ...
Background
Eyestrain is a serious quality of life problem, especially in the workplace. In particular, work at visual display terminals (VDTs) is a common cause of eyestrain. Currently, there are many workers who work at VDTs and tend to feel eyestrain. Rutin, derived from various food plants such as the Japanese pagoda tree (Styphnolobium japonicum), is a known polyphenol compound. Monoglucosyl rutin (MGR) is a highly water-soluble α-glucose adduct of rutin. Previous studies have demonstrated that rutin improved dry eye and also affected the microvascular blood flow in animal experiments. Based on these findings, we hypothesized that MGR could alleviate eyestrain caused by work at VDTs. In this clinical study, we evaluated whether MGR could improve eyestrain in healthy adults.
Methods
This study was designed as a randomized, placebo-controlled, double-blind, crossover study. Twenty healthy Japanese adults who tended to feel eyestrain were recruited to participate. During the first test period, the participants were asked to drink either a test food containing 377 mg of MGR or a placebo food without MGR. After the food intake, the participants did personal computer work at VDT for 30 min and then relaxed for 20 min. We evaluated the participants’ eyestrain using an objective parameter (high-frequency component 1, HFC1) and subjective parameters (visual analog scale). After 7 days, for the second test period, the participants consumed an alternate food following the same protocol as during the first test period.
Results
The objective parameter of eyestrain (HFC1) was significantly lower in the MGR group than that in the placebo group. The subjective parameters of eyestrain and waist stiffness were improved in the MGR group in comparison with those in the placebo group.
Conclusions
MGR supplementation has the potential to objectively and subjectively improve eyestrain symptoms due to VDT use.
... Omega-3 vitamins and bilberry extract have been found to reduce eye discomfort and ocular fatigue. 23,24 This may be through improving the tear film or may reflect a previously suboptimal diet. ...
... We used a form with a scale of 0, I have no fatigue to 100, I feel extremely fatigued marked on the extreme ends of a 100-mm line. [12] We used the modified questionnaire of Ames et al. [13] to evaluate the CVS score. The questionnaires included five questions on the severity of fatigue, burning, dryness, blurred vision, and dullness associated with subjective asthenopia; each question was graded on a numerical scale of 0-6, with 0 defined as none and 6 as most severe. ...
Purpose
To investigate the influences of smartphone use on ocular symptoms, status of the tear film, and oxidative stress indices in the tears and at the ocular surface.
Methods
Eighty healthy volunteers were enrolled in the study. Subjective symptoms and asthenopia were evaluated using the ocular surface disease index (OSDI), visual analogue scale (VAS), and computer vision syndrome (CVS) score before and after smartphone or computer display (control) use. The status of the tear film was evaluated using fluorescein film break-up time (FBUT), non-invasive keratograph break up time (NIKBUT), Schirmer score, keratoepitheliopathy (KEP), and tear meniscus height (TMH). Oxidative stress markers in the tear film including hexanoyl lysine (HEL), 4-hydroxy-2-nonenal (4-HNE), malondialdehyde (MDA), and 8-oxo-2’-deoxyguanosine (8-OHdG) in the tear film were measured using ELISA. Reactive oxygen species (ROS) at the ocular surface were measured through 2’,7’-dichloro-dihydrofluorescein diacetate. All measurements were conducted at baseline, and after use for 1 and 4 h.
Results
All parameters showed no significant group-wise differences at baseline. Scores of OSDI, VAS, fatigue, burning sensation, and dryness showed significant increases after 1 and 4 h of smartphone use compared with those at baseline (all P < 0.05). The smartphone group showed higher OSDI, fatigue, burning, and dryness scores than the control group at 4 h. Smartphone use showed significantly decreased FBUT and NIBUT at 4 h than those at baseline (P < 0.01). In the smartphone group, the concentration of HEL significantly increased at 4 h compared with that at baseline and 1 h (P < 0.01). Both groups showed increased ROS with higher value in the smartphone group versus the control group at 4 h (P < 0.01).
Conclusions
Smartphone use could not only aggravate subjective symptom indices such as the OSDI, VAS, and CVS but also induce tear film instability and oxidative stress indices in the tears and at the ocular surface.
... However, xanthophylls and anthocyanins are often included, together or independently, in commercially available food supplements to improve ocular health. On the other hand, there are few studies in the scientific literature that have shown an effect of their combined consumption, and the few studies available are not conclusive [25][26][27]. Therefore, there is still a need for intervention studies in well-defined population groups, mainly in those who could benefit from a higher intake of lutein, e.g., older subjects, as MPOD decreases with age [19], which increases the risk of age-related ocular diseases. ...
Xanthophylls (lutein, L; zeaxanthin, Z) and anthocyanins are often included in food supplements to improve ocular health. There are no dietary reference intakes for them. The aim was to assess the effects of L, Z and anthocyanin supplementation on short and long-term lutein status markers (serum concentration and macular pigment optical density (MPOD)). Seventy-two postmenopausal women were randomized into a parallel study of 8 months: Group A—anthocyanines (60 mg/day); Group X—xanthophylls (6 mg L + 2 mg Z/day); Group X+A—anthocyanines (60 mg/day) + xanthophylls (6 mg L + 2 mg Z/day). At the beginning of the study, 4 and 8 month serum L and Z concentrations were determined (HPLC), as well as L, Z and anthocyanine dietary intake and MPOD (heterochromic flicker photometry). Baseline concentrations of L (0.35 ± 0.19 μmol/L), Z (0.11 ± 0.05 μmol/L), L+Z/cholesterol/triglycerides (0.07 ± 0.04 μmol/mmol) increased in Group X (2.8- and 1.6-fold in L and Z concentrations) and in group XA (2- and 1.4-fold in L and Z concentrations). MPOD (baseline: 0.32 ± 0.13 du) was not modified in any of the groups at the end of the study. There were no differences in the dietary intake of L+Z and anthocyanin at any point in time in any group. Supplementation of L and Z at a dietary level provoked an increase in their serum concentration that was not modified by simultaneous supplementation with anthocyanins.
... Among supplement foods, bilberry, a type of shrub in Ericaceae family, which grows in Northern and Central Europe, is currently investigated for its antioxidant properties, capillary vessels protection and treatment of ocular disorders 11 . In particular, dietary supplementation with bilberry extract alone or combined with other ingredients safely improved subjective symptoms of computer eye strain 12 or asthenopia 13 . So far, no direct evaluation has been made on the effect of bilberry in alleviating DED symptoms. ...
Objective:
Dry eye, a chronic disease of lachrymal fluid and corneo-conjunctival epithelium, could significantly impact visual function, affects quality of life and work productivity. Beside several conventional treatments, nutritional supplements based on bilberry extract have been identified as effective contributors to eye health. Here, we aim at investigating the bioavailability of a standardized bilberry extract, its ability to alleviate dry eye symptoms and its antioxidant potential.
Materials and methods:
Either bilberry dried standardized extract derived from Vaccinium myrtillus L. fresh frozen fruits (Mirtoselect®) or a highly purified anthocyanin-rich extract, devoid of the non anthocyanin component and supported on maltodextrins, were each orally administrated to 5 male rats. Blood samples were collected at 5, 10, 15, 20, 30, 45, 60, 90, 120 minutes after treatment, processed and analyzed by UV spectrophotometric method. In a parallel analysis, 22 otherwise healthy subjects suffering from dry eye symptoms were enrolled randomly assigned to receive the more bioavailable bilberry extract or placebo. Ophthalmological and clinical examinations including Schirmer's test, pupil constriction, diacron-reactive oxygen metabolites (d-ROMs) test and biological antioxidant potential (BAP) test were performed at inclusion and after the 4-week study period.
Results:
The area under the curve of plasmatic levels of anthocyanosides in rats resulted 202.34±24.23 µg·min/ml for Mirtoselect® and 130.93±4.93 µg·min/ml for the highly purified anthocyanin-rich bilberry extract, notwithstanding the fact that the highly purified anthocyanin-rich extract group received an anthocyanins dosage much higher than the Mirtoselect® group (354 mg/Kg in anthocyanosides vs. 136 mg/Kg in anthocyanosides). 21 subjects, 11 subjects in the bilberry extract (Mirtoselect®) group and 10 subjects in the placebo group completed the clinical study. Schirmer's test values indicating the volume of tear secretion were significantly improved in the bilberry extract group (p=0.019), whereas no significant changes were observed in the placebo group. A subset analysis revealed that Mirtoselect® could be more effective in subjects with higher tendency of dry eye. In terms of antioxidant potential, the bilberry extract produced significant improvement of BAP (p=0.003) and an increase of modified BAP/d-ROMs ratio, an indicator of overall balance between antioxidant potential and oxidative stress.
Conclusions:
Our results suggested that natural, standardized bilberry extract (Mirtoselect®) is a natural more bioavailable delivery form anthocyanins, suggesting a strong matrix effect exerted by the non-anthocyanin component. Furthermore, it can improve tear secretion and plasmatic antioxidant potential in subjects suffering from DED symptoms.
... The recent data have evidenced that dietary supplements with a combination of omega-3 fatty acid, bilberry extract, and lutein reduce asthenopia symptoms [20] and eight week consumption improves some objective and subjective symptoms of eye fatigue induced by visual loads [21]. ...
Background. Asthenopia is a key point in information fatigue syndrome. The incidence of asthenopia syndromes (one or several) among students is 57-89.9%. The recent data have evidenced that dietary supplements with a combination of omega-3 fatty acid, bilberry extract and lutein reduce asthenopia symptoms. Purpose. The purpose was to assess the efficacy of a course of laser stimulation of the retina with a subsequent nutrient supplementation in students with asthenopia. Material and Methods. We performed comprehensive examination of 36 students (72 eyes), aged 18 to 25, with asthenopia signs. There were two groups: group 1, 19 students (38 eyes); group 2, 17 students (34 eyes). All study eyes underwent 10 every-day sessions of diode laser stimulation of the retina (LSR) (wavelength, 650 nm; irradiance, 0.4 mW/sm²; treatment timing, 300 s). On completion of a course of LSR, the students of group 2 were recommended a Nutrof®Total vitaminous antioxidant complex, one capsule daily for 6 months. Results. A course of laser stimulation of the retina and a 6 month nutrient supplementation for asthenopia students made it possible to improve visual acuity by 12% in 91 % of the students, to recover the reserves of accommodation over 3 D in 73% of the students, to improve the vascular tone by 34% in 59% of the students and light sensitivity of retinal cones by 25% in 82% of the students; asthenopia graded from moderate to mild in 91% of the students; the overall emotional state was normalized in all students by 37% according to a HADS scale. Conclusions. A course of LSR and a 6 month nutrient supplementation enables to improve students' overall health and professional activity while reduced asthenopia creates conditions for health improvement, better quality of studying and open career opportunities.
... Among supplement foods, bilberry, a type of shrub in Ericaceae family, which grows in Northern and Central Europe, is currently investigated for its antioxidant properties, capillary vessels protection and treatment of ocular disorders 11 . In particular, dietary supplementation with bilberry extract alone or combined with other ingredients safely improved subjective symptoms of computer eye strain 12 or asthenopia 13 . So far, no direct evaluation has been made on the effect of bilberry in alleviating DED symptoms. ...
OBJECTIVE:
Dry eye, a chronic disease of lachrymal fluid and corneo-conjunctival epithelium, could significantly impact visual function, affects quality of life and work productivity. Beside several conventional treatments, nutritional supplements based on bilberry extract have been identified as effective contributors to eye health. Here, we aim at investigating the bioavailability of a standardized bilberry extract, its ability to alleviate dry eye symptoms and its antioxidant potential.
MATERIALS AND METHODS:
Either bilberry dried standardized extract derived from Vaccinium myrtillus L. fresh frozen fruits (Mirtoselect®) or a highly purified anthocyanin-rich extract, devoid of the non anthocyanin component and supported on maltodextrins, were each orally administrated to 5 male rats. Blood samples were collected at 5, 10, 15, 20, 30, 45, 60, 90, 120 minutes after treatment, processed and analyzed by UV spectrophotometric method. In a parallel analysis, 22 otherwise healthy subjects suffering from dry eye symptoms were enrolled randomly assigned to receive the more bioavailable bilberry extract or placebo. Ophthalmological and clinical examinations including Schirmer's test, pupil constriction, diacron-reactive oxygen metabolites (d-ROMs) test and biological antioxidant potential (BAP) test were performed at inclusion and after the 4-week study period.
RESULTS:
The area under the curve of plasmatic levels of anthocyanosides in rats resulted 202.34±24.23 µg·min/ml for Mirtoselect® and 130.93±4.93 µg·min/ml for the highly purified anthocyanin-rich bilberry extract, notwithstanding the fact that the highly purified anthocyanin-rich extract group received an anthocyanins dosage much higher than the Mirtoselect® group (354 mg/Kg in anthocyanosides vs. 136 mg/Kg in anthocyanosides). 21 subjects, 11 subjects in the bilberry extract (Mirtoselect®) group and 10 subjects in the placebo group completed the clinical study. Schirmer's test values indicating the volume of tear secretion were significantly improved in the bilberry extract group (p=0.019), whereas no significant changes were observed in the placebo group. A subset analysis revealed that Mirtoselect® could be more effective in subjects with higher tendency of dry eye. In terms of antioxidant potential, the bilberry extract produced significant improvement of BAP (p=0.003) and an increase of modified BAP/d-ROMs ratio, an indicator of overall balance between antioxidant potential and oxidative stress.
CONCLUSIONS:
Our results suggested that natural, standardized bilberry extract (Mirtoselect®) is a natural more bioavailable delivery form anthocyanins, suggesting a strong matrix effect exerted by the non-anthocyanin component. Furthermore, it can improve tear secretion and plasmatic antioxidant potential in subjects suffering from DED symptoms.
... Multiple dietary supplements containing several functional ingredients as mentioned above in order to improve asthenopia are currently on the market. Also, effects of multiple dietary supplements containing several functional ingredients on subjective symptoms of asthenopia have been verified [13,19,20]. On the other hand, there are few dietary supplements and foods designed focusing on the effect on accommodative ability. ...
Objective
The study aimed to verify that ingestion of multiple dietary supplement containing lutein, astaxanthin, cyanidin-3-glucoside and docosahexaenoic acid (DHA) would improve accommodative ability of aged and older subjects who were aware of eye strain on a daily basis.
Methods
A randomized double-blind placebo-controlled parallel group comparison study was conducted for 48 participants aged 45 to 64 years who complained of eye strain. The subjects took multiple dietary supplement containing 10 mg of lutein, 20 mg of bilberry extract and 26.5 mg of black soybean hull extract (a total of 2.3 mg of cyanidin-3-glucoside in both extracts), 4 mg of astaxanthin, and 50 mg of DHA (test supplement) or placebo for four consecutive weeks. Near-point accommodation (NPA) and subjective symptoms were evaluated both before and after four weeks’ intake.
Results
The variation of the NPA of both eyes from baseline to 4 weeks’ post-intake in the test supplement group was significantly higher than in the placebo group (1.321±0.394 diopter (D) in the test supplement group and 0.108±0.336 D in the placebo group, p=0.023). The multiple dietary supplement group showed improvement in the NPA. Regarding subjective symptoms, significant improvement of “stiff shoulders or neck” and “blurred vision” was also found in the test supplement group compared to the placebo group (p<0.05). There were no safety concerns in this study.
Conclusion
This study shows that multiple dietary supplement containing lutein, astaxanthin, cyanidin-3-glucoside, and DHA has effect to improve accommodative ability and subjective symptoms related to eye fatigue.
... Of these dietary ingredients, anthocyanins and berry extracts rich in anthocyanins have been most intensively studied in humans with regard to their effect on vision, including many early studies carried out in several European countries in the 1960s (22). These early studies suggesting the ability of anthocyanins to prevent visual disturbance and/or eye fatigue have led to more recent clinical trials using dietary supplementation with anthocyanins, alone (18)(19)(20) or in combination with fish oil and lutein (23). However, VDT load-related eye fatigue may involve multiple signs or symptoms; thus, further information is required to determine whether anthocyanins constitute a useful supplement for the preservation of ocular health in those working with VDTs. ...
To examine the effect of a dietary supplement containing bilberry extract (BE) on eye fatigue induced by acute video display terminal (VDT) loads.
A prospective, randomized, double-blind, placebo-controlled study was performed from August 2012 to February 2013 in the Medical Corporation Jico-kai Yagi Hospital, and the Shinyokohama Shinoharaguchi Orthopedic Surgery and Dermatology Clinic, in Japan.
Two hundred eighty-one office workers aged 20-40 years that used VDTs were screened by critical flicker fusion (CFF) and near point accommodation (NPA).
The participants were randomized to either a BE (480 mg/day) or placebo (vehicle) group, and took allocated capsule, daily, for 8 weeks.
The CFF, NPA, contrast visual acuity, functional visual acuity, keratoconjunctival epithelial damage, and fluorescein tear film break-up time were examined, and 18 subjective symptoms of eye fatigue were evaluated by questionnaire. Adverse events were reported via medical interviews. Data were collected both before and after VDT load at baseline, and 4, and 8 weeks after daily supplementation with either BE or placebo.
Of 281 participants screened, 88 having relatively lower levels of CFF and NPA were enrolled in the study. Of these, 37 control and 43 BE group subjects completed the study. The VDT load-induced reduction in CFF was alleviated after 8 weeks of BE supplementation (95% confidence interval, 0.10-1.60; p=0.023), in contrast to placebo supplementation, while NPA variation was not. Of the subjective symptoms of eye fatigue, VDT load-induced ocular fatigue sensation, ocular pain, eye heaviness, uncomfortable sensation, and foreign body sensation were mitigated more in the BE group than in the control group, at week 8 (p<0.05). There were no severe adverse events in either group.
BE supplementation improved some of the objective and subjective parameters of eye fatigue induced by VDT loads.
Purpose
To explore the effect of bilberry and fish oil combination supplement on a small clinical sample patient-base with severe dry eyes.
Methods
Twenty-four subjects were recruited with twelve randomly assigned to the intervention and control groups, respectively. Inclusion criteria included severe dry eye symptoms determined by scores >33 from the Ocular Surface Disease Index (OSDI) questionnaire. The intervention group was instructed to take an oral supplement with key ingredients of 600 mg bilberry extract and 240 mg docosahexaenoic acid-refined fish oil once daily for 3 months. The control group did not take any supplements. Mean changes in OSDI score, non-invasive tear break-up time (NITBUT), phenol red thread test (PRT), and percentage of meibomian gland openings were used as outcome measures. Testing was done at baseline, 1-month, and 3-month follow-up. Comparison between the treatment and control groups, and the younger adult and middle-age groups were performed.
Results
The mean baseline values for the treatment and control groups were not clinically different. The OSDI score, NITBUT, PRT, and percentage of meibomian gland openings improved after taking the supplements for 3 months. The OSDI score, NITBUT, and PRT showed clinical improvements between the intervention and control groups. These improvements were consistent between the two age groups.
Conclusion
This study suggested preliminary improvements in signs and symptoms of severe dry eyes that were independent of age after taking dietary supplementation of bilberry extract and fish oil for 3 months. Further studies using more device-based measures and a placebo supplement are warranted.
Background:
Polyunsaturated fatty acid (PUFA) supplements, involving omega-3 and/or omega-6 components, have been proposed as a therapy for dry eye. Omega-3 PUFAs exist in both short- (alpha-linolenic acid [ALA]) and long-chain (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) forms, which largely derive from certain plant- and marine-based foods respectively. Omega-6 PUFAs are present in some vegetable oils, meats, and other animal products.
Objectives:
To assess the effects of omega-3 and omega-6 polyunsaturated fatty acid (PUFA) supplements on dry eye signs and symptoms.
Search methods:
CENTRAL, Medline, Embase, two other databases and three trial registries were searched in February 2018, together with reference checking. A top-up search was conducted in October 2019, but the results have not yet been incorporated.
Selection criteria:
We included randomized controlled trials (RCTs) involving dry eye participants, in which omega-3 and/or omega-6 supplements were compared with a placebo/control supplement, artificial tears, or no treatment. We included head-to-head trials comparing different forms or doses of PUFAs.
Data collection and analysis:
We followed standard Cochrane methods and assessed the certainty of the evidence using GRADE.
Main results:
We included 34 RCTs, involving 4314 adult participants from 13 countries with dry eye of variable severity and etiology. Follow-up ranged from one to 12 months. Nine (26.5%) studies had published protocols and/or were registered. Over half of studies had high risk of bias in one or more domains. Long-chain omega-3 (EPA and DHA) versus placebo or no treatment (10 RCTs) We found low certainty evidence that there may be little to no reduction in dry eye symptoms with long-chain omega-3 versus placebo (four studies, 677 participants; mean difference [MD] -2.47, 95% confidence interval [CI] -5.14 to 0.19 units). We found moderate certainty evidence for a probable benefit of long-chain omega-3 supplements in increasing aqueous tear production relative to placebo (six studies, 1704 participants; MD 0.68, 95% CI 0.26 to 1.09 mm/5 min using the Schirmer test), although we did not judge this difference to be clinically meaningful. We found low certainty evidence for a possible reduction in tear osmolarity (one study, 54 participants; MD -17.71, 95% CI -28.07 to -7.35 mOsmol/L). Heterogeneity was too substantial to pool data on tear break-up time (TBUT) and adverse effects. Combined omega-3 and omega-6 versus placebo (four RCTs) For symptoms (low certainty) and ocular surface staining (moderate certainty), data from the four included trials could not be meta-analyzed, and thus effects on these outcomes were unclear. For the Schirmer test, we found moderate certainty evidence that there was no intergroup difference (four studies, 455 participants; MD: 0.66, 95% CI -0.45 to 1.77 mm/5 min). There was moderate certainty for a probable improvement in TBUT with the PUFA intervention relative to placebo (four studies, 455 participants; MD 0.55, 95% CI 0.04 to 1.07 seconds). Effects on tear osmolarity and adverse events were unclear, with data only available from a single small study for each outcome. Omega-3 plus conventional therapy versus conventional therapy alone (two RCTs) For omega-3 plus conventional therapy versus conventional therapy alone, we found low certainty evidence suggesting an intergroup difference in symptoms favoring the omega-3 group (two studies, 70 participants; MD -7.16, 95% CI -13.97 to -0.34 OSDI units). Data could not be combined for all other outcomes. Long-chain omega-3 (EPA and DHA) versus omega-6 (five RCTs) For long-chain omega-3 versus omega-6 supplementation, we found moderate certainty evidence for a probable improvement in dry eye symptoms (two studies, 130 participants; MD -11.88, 95% CI -18.85 to -4.92 OSDI units). Meta-analysis was not possible for outcomes relating to ocular surface staining, Schirmer test or TBUT. We found low certainty evidence for a potential improvement in tear osmolarity (one study, 105 participants; MD -11.10, 95% CI -12.15 to -10.05 mOsmol/L). There was low level certainty regarding any potential effect on gastrointestinal side effects (two studies, 91 participants; RR 2.34, 95% CI 0.35 to 15.54).
Authors' conclusions:
Overall, the findings in this review suggest a possible role for long-chain omega-3 supplementation in managing dry eye disease, although the evidence is uncertain and inconsistent. A core outcome set would work toward improving the consistency of reporting and the capacity to synthesize evidence.
Increasing the solubility of poorly water-soluble bioactives is essential to enhancing their bioavailability. The objective of this study was to evaluate the impact of phytoglycogen (PG) on water solubility of lutein and its transepithelial permeation across Caco-2 cell monolayers. Solid PG-LT complexes were prepared by combining an acetone solution of LT with an aqueous solution of PG under sonication, followed by centrifugation and vacuum drying of the supernatant as well as a further purification procedure. X-ray powder diffraction and differential scanning calorimetry showed negligible crystalline structure of LT in the PG-LT complex tested. The maximal water solubility of LT (130.65 μg/mL) occurred at the PG/LT combination ratio of 53.3/1, which was significantly higher than that of LT alone (0.56 μg/mL). Remarkably, LT, when complexed with PG, exhibited much-enhanced permeation through Caco-2 monolayer than LT alone, suggesting a potential role of PG to improve LT bioavailability. This study indicated that PG could be applied for the delivery of LT and possibly other hydrophobic ingredients.
ABSTRACT An evidence-based systematic review of lutein by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated, reproducible grading rationale. This article includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.
Dry eye syndrome (DES) is a prevalent condition, but information on risk or protective factors is lacking.
We aimed to determine the association between the dietary intake and ratio of n-3 and n-6 fatty acids (FAs) and DES occurrence.
Of the 39876 female health professionals in the Women's Health Study (WHS), 32470 women aged 45-84 y who provided information on diet and DES were cross-sectionally studied. We assessed FA intakes by using a validated food-frequency questionnaire and assessed DES by using self-reports of clinically diagnosed cases. Of the sample, 1546 (4.7%) subjects reported DES. We used logistic regression models to estimate the odds ratios (ORs) and 95% CIs to describe the relation of FA intake with DES.
After adjustment for demographic factors, hormone therapy, and total fat intake, the OR for the highest versus the lowest quintile of n-3 FAs was 0.83 (95% CI: 0.70, 0.98; P for trend = 0.05). A higher ratio of n-6 to n-3 FA consumption was associated with a significantly increased risk of DES (OR: 2.51; 95% CI: 1.13, 5.58) for >15:1 versus <4:1 (P for trend = 0.01). In addition, tuna consumption [1 serving was 113 g (4 oz)] was inversely associated with DES (OR: 0.81; 95% CI: 0.66, 0.99 for 2-4 servings/wk; OR: 0.32; 95% CI: 0.13, 0.79 for 5-6 servings/wk versus < or =1 serving/wk; P for trend = 0.005).
These results suggest that a higher dietary intake of n-3 FAs is associated with a decreased incidence of DES in women. These findings are consistent with anecdotal clinical observations and postulated biological mechanisms.
To investigate the role of eicosapentaenoic acid (EPA), the major omega-3 polyunsaturated fatty acid (PUFA), in the development of choroidal neovascularization (CNV), together with underlying molecular mechanisms.
Six-week-old C57BL/6 mice were fed with laboratory chow with 5% EPA or the omega-6 PUFA linoleic acid (LA) for 4 weeks. Laser photocoagulation was performed to induce CNV, and the volume of CNV tissue was evaluated by volumetric measurements. The expression and production of intercellular adhesion molecule (ICAM)-1, monocyte chemotactic protein (MCP)-1, vascular endothelial growth factor (VEGF) and interleukin (IL)-6 in the retinal pigment epithelium (RPE)-choroid in vivo, and stimulated b-End3 endothelial cells and RAW264.7 macrophages in vitro were evaluated by RT-PCR and ELISA. Fatty acid composition in the serum and the RPE-choroid was analyzed by gas chromatography and high-performance liquid chromatography, respectively. Serum levels of C-reactive protein (CRP), IL-6, VEGF, MCP-1, and soluble ICAM-1 were examined by ELISA.
The CNV volume in EPA-fed animals was significantly suppressed compared with that in control mice, whereas the LA-rich diet did not affect CNV. The mRNA expression and protein levels of ICAM-1, MCP-1, VEGF, and IL-6 after CNV induction were significantly reduced in EPA-supplemented mice. In vitro, EPA application led to significant inhibition of mRNA and protein levels of ICAM-1 and MCP-1 in endothelial cells and VEGF and IL-6 in macrophages. EPA-fed mice exhibited significantly higher levels of EPA and lower levels of the omega-6 PUFA arachidonic acid in the serum and the RPE-choroid than control animals. EPA supplementation also led to significant reduction of serum levels of IL-6 and CRP after CNV induction.
The present study demonstrates for the first time that an EPA-rich diet results in significant suppression of CNV and CNV-related inflammatory molecules in vivo and in vitro. These results suggest that frequent consumption of omega-3 PUFAs may prevent CNV and lower the risk of blindness due to age-related macular degeneration.
The omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are orthomolecular, conditionally essential nutrients that enhance quality of life and lower the risk of premature death. They function exclusively via cell membranes, in which they are anchored by phospholipid molecules. DHA is proven essential to pre- and postnatal brain development, whereas EPA seems more influential on behavior and mood. Both DHA and EPA generate neuroprotective metabolites. In double-blind, randomized, controlled trials, DHA and EPA combinations have been shown to benefit attention deficit/hyperactivity disorder (AD/HD), autism, dyspraxia, dyslexia, and aggression. For the affective disorders, meta-analyses confirm benefits in major depressive disorder (MDD) and bipolar disorder, with promising results in schizophrenia and initial benefit for borderline personality disorder. Accelerated cognitive decline and mild cognitive impairment (MCI) correlate with lowered tissue levels of DHA/EPA, and supplementation has improved cognitive function. Huntington disease has responded to EPA. Omega-3 phospholipid supplements that combine DHA/EPA and phospholipids into the same molecule have shown marked promise in early clinical trials. Phosphatidylserine with DHA/EPA attached (Omega-3 PS) has been shown to alleviate AD/HD symptoms. Krill omega-3 phospholipids, containing mostly phosphatidylcholine (PC) with DHA/EPA attached, markedly outperformed conventional fish oil DHA/EPA triglycerides in double-blind trials for premenstrual syndrome/dysmenorrhea and for normalizing blood lipid profiles. Krill omega-3 phospholipids demonstrated anti-inflammatory activity, lowering C-reactive protein (CRP) levels in a double-blind trial. Utilizing DHA and EPA together with phospholipids and membrane antioxidants to achieve a triple cell membrane synergy may further diversify their currently wide range of clinical applications.
Background: Lutein and docosahexaenoic acid (DHA) may protect against age-related macular degeneration (AMD). Lutein is a component of macular pigment. DHA is in the retina.
Objective: The objective of this 4-mo study was to determine the effects of lutein (12 mg/d) and DHA (800 mg/d) on their serum concentrations and macular pigment optical density (MPOD).
Design: Forty-nine women (60–80 y) were randomly assigned to placebo, DHA, lutein, or lutein + DHA supplement. Serum was analyzed for lutein and DHA (0, 2, and 4 mo). MPOD was determined (0 and 4 mo) at 0.4, 1.5, 3, and 5° temporal retinal eccentricities. Serum was analyzed for lipoproteins (4 mo).
Results: There was no interaction between lutein and DHA supplementations for serum lutein and MPOD. The lutein supplementation × DHA supplementation × month interaction was significant for serum DHA response (P < 0.05). In the lutein group, serum lutein increased from baseline at 2 and 4 mo (P < 0.001), and MPOD increased at 3.0° (P < 0.01). In the DHA group, serum DHA increased at 2 and 4 mo (P < 0.0001), and MPOD increased at 0.4° (P < 0.05). In the lutein + DHA group, serum lutein and DHA increased at 2 and 4 mo (P < 0.01), and MPOD increased at 0.4, 1.5, and 3° (P = 0.06, 0.08, and 0.09, respectively). Differences from placebo in lipoprotein subfractions were greatest for the lutein + DHA group (4 mo).
Conclusions: Lutein supplementation increased MPOD eccentrically. DHA resulted in central increases. These results may be due to changes in lipoproteins. Lutein and DHA may aid in prevention of age-related macular degeneration.
This study was designed to assess whether macular pigment optical density (MPOD) is associated with visual performance. One hundred and forty-two young healthy subjects were recruited. Macular pigment optical density and visual performance were assessed by psychophysical tests including best corrected visual acuity (BCVA), mesopic and photopic contrast sensitivity, glare sensitivity, photostress recovery time (PRT). Measures of central visual function, including BCVA and contrast sensitivity, were positively associated with MPOD (p<0.05, for all). Photostress recovery and glare sensitivity were unrelated to MPOD (p>0.05). A longitudinal, placebo-controlled and randomized supplementation trial will be required to ascertain whether augmentation of MPOD can influence visual performance.
Two of the circa 600 naturally occurring carotenoids, zeaxanthin and lutein, the major carotenoids of maize and melon respectively, are the constituents of the macula lutea, the yellow spot in the macula, the central part of the retina in primates and humans. Of the circa ten carotenoids found in the blood these two are specifically concentrated in this area, which is responsible for sharp and detailed vision. This paper reviews the ideas that this concentration of dietary carotenoids in the macula is not accidental, but that their presence may prevent or limit damage due to their physicochemical properties and their capability to quench oxygen free radicals and singlet oxygen, which are generated in the retina as a consequence of the simultaneous presence of light and oxygen. Additionally, in vitro and in vivo animal experiments are reviewed as well as observational and epidemiological data in humans. These show that there is enough circumstantial evidence for a protective role of carotenoids in the retina to justify further research. Some emphasis will be put on age-related macular degeneration (AMD), a multifactorial degenerative retinal disease for which the exposure to light and thus photochemical damage has been suggested as one of the etiological factors. Recent attempts at nutritional intervention in this condition will also be reviewed.
Carotenoid pigments, including hydrocarbons such as beta-carotene or xanthophylls such as lutein and zeaxanthin, are very widely distributed in nature, where they play an important role in protecting cells and organisms against the harmful effects of light, air, and sensitizer pigments. This process has been demonstrated in bacteria, algae, plants, animals, and even in humans in the light-sensitive disease, erythropoietic protoporphyria. The primary mechanism of action of this phenomenon appears to be the ability of carotenoids to quench excited sensitizer molecules as well as quench 1O2. In addition to this protection, and potentially of even greater biological importance, is the fact that carotenoids can also serve as antioxidants under conditions other than photosensitization. This review presents the data available indicating the extent of this important function. Antioxidant action can be documented in both enzymic and nonenzymic systems, and has been reported in subcellular, cellular, and animal studies. In fact, the many reports indicating that carotenoids may possess some anticarcinogenic properties may well be related to their ability to interact with and quench various radical species that can be generated within cells.
The carotenoid pigments in the whole human retina and in the macular region were measured quantitatively by high pressure liquid chromatography (HPLC). Approximately a five-fold larger amount of carotenoids was found in the human macula (35-120 ng) than in previously reported work. The dominant carotenoids in the whole retina are lutein and zeaxanthin. Zeaxanthin is concentrated in the macular region, whereas lutein is dispersed throughout the entire retina. Contrary to prior reports, substantial quantities of both carotenoids are present in the infant retina. Increasing variability is observed in carotenoid levels between individuals with advancing age, and some older individuals show very high whole retina carotenoid levels. These quantitative studies were made possible by synthesis of a new, stable carotenoid internal standard. Carotenoids have been proposed to be potent antioxidants, protecting membrane lipids from toxic peroxidation reactions. The method presented in this study will facilitate quantitative investigations of the association between carotenoid levels and health and disease of the retina.
In vitro enzymatic and non-enzymatic polyunsaturated fatty acid peroxidation was significantly inhibited in a dose dependent manner by purified anthocyanin, a deep-red colour pigment from carrot cell culture. The kinetics showed that anthocyanin is a non-competitive inhibitor of lipid peroxidation. Anthocyanin has been found to be a potent antioxidant compared to classical antioxidants such as butylated hydroxy anisole (BHA), butylated hydroxy toulene (BHT) and alpha tocopherol. This natural agent, in addition to imparting colour to the food, might prevent autooxidation of lipids as well as lipid peroxidation in biological systems.
Recent evidence supports differential effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the 2 major omega3 fatty acids of marine origin, on blood pressure in humans and vascular reactivity in adult spontaneously hypertensive rats. We investigated possible differences in the effects of purified EPA or DHA on forearm vascular reactivity in overweight hyperlipidemic men that might contribute to the blood pressure-lowering effects of fish oils.
With a double-blind, placebo-controlled trial of parallel design, 59 overweight, mildly hyperlipidemic men were randomized to receive 4 g/d purified EPA, DHA, or olive oil (placebo) capsules while continuing their usual diets for 6 weeks. Forearm blood flow (FBF) was measured with venous occlusion, strain-gauge plethysmography during the sequential intra-arterial administration of acetylcholine (7.5, 15, and 30 microg/min), sodium nitroprusside (1.5, 3, and 10 microg/min), norepinephrine (10, 20, and 40 ng/min), a single-dose infusion of N:(G)-monomethyl-L-arginine (L-NMMA) (1 mg/min), and coinfusion of acetylcholine (7.5, 15, and 30 microg/min) and L-NMMA. Forty of the 56 subjects who completed the study underwent FBF measurements. Plasma phospholipid EPA levels increased significantly (P:<0.0001) after supplementation with EPA, and DHA composition increased with DHA supplementation (P:<0.0001). Relative to placebo, DHA, but not EPA, supplementation significantly improved FBF in response to acetylcholine infusion (P:=0.040) and coinfusion of acetylcholine with L-NMMA (P:=0.040). Infusion of L-NMMA alone showed no group differences. DHA significantly enhanced dilatory responses to sodium nitroprusside (P:<0.0001) and attenuated constrictor responses to norepinephrine (P:=0.017).
Relative to placebo, DHA, but not EPA, enhances vasodilator mechanisms and attenuates constrictor responses in the forearm microcirculation. Improvements in endothelium-independent mechanisms appear to be predominant and may contribute to the selective blood pressure-lowering effect observed with DHA compared with EPA in humans.
Anthocyanins have been suggested to improve visual functions. This study examined the effect of four anthocyanins in black currant fruits on the regeneration of rhodopsin using frog rod outer segment (ROS) membranes. Cyanidin 3-glycosides, glucoside and rutinoside, stimulated the regeneration, but the corresponding delphinidins showed no significant effect. The formation of a regeneration intermediate was suggested to be accelerated by cyanidin 3-rutinoside. Their effects on the cGMP-phosphodiesterase activity in the ROS membranes were also investigated but found to be negligible. It was concluded that the major effect of anthocyanins in rod photoreceptors is on the regeneration of rhodopsin.
Dementia and age-related macular degeneration (AMD) are major causes of disability in the elderly. n-3 Fatty acids, particularly docosahexaenoic acid (DHA), are highly concentrated in brain and retinal tissue and may prevent or delay the progression of dementia and AMD. Low dietary intakes and plasma concentrations have been reported to be associated with dementia, cognitive decline, and AMD risk. The major dietary sources of DHA are fish and fish oils, although dietary supplements are available. At this point, it is not possible to make firm recommendations regarding n-3 fatty acids and the prevention of dementia and AMD. Our own unpublished observations from the Framingham Heart Study suggest that > or =180 mg/d of dietary DHA (approximately 2.7 fish servings/wk) is associated with an approximately 50% reduction in dementia risk. At least this amount of DHA is generally found in one commercially available 1-g fish oil capsule given daily.
Clinical evaluation of oral blueberry extract in mental fatigue and asthenopia
- O Kajimoto
- H Ohtani
- K Kogasa
- R Takahashi
Kajimoto O, Ohtani H, Kogasa K and Takahashi R (1998)
Clinical evaluation of oral blueberry extract in mental fatigue
and asthenopia. Food Industry 41, 29-35. (in Japanese)
Study of evaluation methods among asthenopia of VDTs
- H Nakamura
- T Suehiro
- S Oishi
- T Koyama
- T Omoto
- T Nakao
- I Takemoto
- N Mishima
Nakamura H, Suehiro T, Oishi S, Koyama T, Omoto T,
Nakao T, Takemoto I and Mishima N (1994) Study of evaluation methods among asthenopia of VDTs. JJOMT 42, 617-620. (in Japanese with English abstract)