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Effect of Fermented Bilberry Extracts on Visual Outcomes in Eyes with Myopia: A Prospective, Randomized, Placebo-Controlled Study
Abstract
Abstract Purpose: To investigate clinically the effects of yeast-fermented bilberry extract on visual outcomes in myopic eyes. Methods: In a prospective, randomized, placebo-controlled, cross-over study, we examined 30 eyes of 30 middle-aged healthy volunteers (mean age±standard deviation, 39.5±7.2 years) with myopia [manifest spherical equivalent, -2.40±1.88 diopters (D)], who were randomly assigned to 1 of 2 oral regimens: fermented bilberry extract (400 mg/day) or placebo. We quantitatively assessed visual acuity, refraction, pupil constriction rate, accommodation, and mesopic contrast sensitivity (CS), before and 1 month after treatment. Only the right eyes were tested. The amplitude of accommodation and CS were measured with an accommodometer (D'ACOMO; WOC) and a CS unit (VCTS-6500; Vistech), respectively. From the CS, the area under the log contrast sensitivity function (AULCSF) was calculated. Results: The mean amplitude of accommodation increased significantly, from 4.62±1.88 D before treatment, to 5.33±2.03 D after treatment in the study group (Wilcoxon signed-rank test, P=0.002). Moreover, the mesopic AULCSF was significantly increased, from 1.04±0.16 before, to 1.13±0.17 after, treatment (P=0.009). However, we found no significant changes in accommodation or AULCSF in the control group (P>0.05), or any significant changes in any other parameters in either group (P>0.05). Conclusions: The present data show that fermented bilberry extract is effective in causing increases in subjective accommodation and in mesopic CS in myopic eyes.
... Bilberry ingestion at the dose of 400 mg/d for 4 wk led to a significant elevation in the mesopic area under the log contrast sensitivity function (AULCSF) and the mean amplitude of accommodation compared with baseline. Nonetheless, other indices such as visual acuity, pupil constriction rate, refraction, and mesopic contrast sensitivity were not affected [88]. ...
... In most cases, plant-derived fermented products were considered to be superior to the unprocessed plant compounds for enhanced efficacy. Although studies on plant-fermented products demonstrated their promising abilities to improve various disease conditions clinically (Table 1) [17,18,38,43,45,49,52,53,[55][56][57][58][59][62][63][64][65][66][68][69][70][71][74][75][76][77][78][79][80][81][82][83][85][86][87][88][89][90][91][92], it is important to define the differences between pure extracts or fermented products in more controlled clinical studies. Despite the demonstrated efficacy of many fermented products, the exact mechanisms of action remain elusive and require further investigation. ...
The health benefits of fermenting plant-derived products remain an underexplored domain. Plants and other natural products serve as medicinal agents when consumed as part of our diets, and the role of microorganisms in fermentation garners significant scientific interest. The present narrative review investigates the effects of fermentation of substances such as plants, algae, and fungi on their therapeutic and related purposes. Among the microorganisms used in fermentation, lactic acid bacteria are often linked to fermented products, particularly dairy and animal-based ones, and take center stage. These microorganisms are adept at synthesizing vitamins, active peptides, minerals, proteinases, and enzymes. Plant-derived fermented products are a significant source of active peptides, phytochemicals, flavonoids, and bioactive molecules with a profound impact on human health. They exhibit anti-inflammatory, anticarcinogenic, antiatherosclerotic, antidiabetic, antimicrobial, and antioxidant properties, the effects being substantiated by experimental studies. Clinical investigations underscore their effectiveness in managing diverse health conditions. Various studies highlight a synergy between microorganisms and plant-based materials, with fermentation as an innovative method for daily food preparation or a treatment option for specific ailments. These promising findings highlight the need for continued scientific inquiry into the impact of fermentation-derived products in clinical settings. Clinical observations to date have offered valuable insights into health improvement for various disorders. This current narrative review explores the impact of natural and plant-originated fermented products on health and well-being.
... There have also been reports on the positive antioxidant effects of bilberry on cognitive functions (19) as well as cardiovascular disease (20). When administered in a purified high-dose anthocyanin form, it has shown improved visual functions of myopes suffering from asthenopia (21) as well as improved accommodation functions when taken in a yeastfermented bilberry extract form (22). So far, no major side effects have been reported on its use as a dietary supplement. ...
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.
... Thirty healthy individuals with myopic eyes have undergone treatment with either 400 mg of yeast-fermented bilberry fruit extract or placebo. After 4 weeks of treatment, there was an improvement in accommodation and mesopic contrast sensitivity, but not in other measured parameters (Kamiya et al., 2013). ...
Bilberry (Vaccinium myrtillus L.) fruits are an important part of local diets in many countries and are used as a medicinal herb to treat various disorders. Extracts from fruits are often a part of eye health-promoting supplements, whereas extracts from leaves are advertised for type 2 diabetes mellitus and glycemic control. This review provides an overview of the current knowledge of the phytochemical contents of bilberry fruits and leaves and their bioactivities, critically summarizes origins of the health claims and the outcome of clinical trials, with special attention towards those published in the past 10 years. Overall, the three most referenced indications, which are type 2 diabetes mellitus, vision disorders and circulatory diseases, all include contradictory results with no clear conclusion as to the benefits and recommended dosages. Moreover, the indications for vision disorders and diabetes originate from unproven or false claims that have been repeated in research since the 20th century without consistent fact-checking. Beneficial clinical results have been attested for the treatment of dyslipidemia and chronic inflammatory disorders when applied as dietary supplementation of fresh bilberries or as anthocyanin-rich bilberry fruit extracts. However, there is a general lack of double-blinded controlled research with larger sample sizes.
... An improvement in capillary retinal blood circulation and perfusion might also improve visual functions [50]. In fact, a treatment for 30 days with anthocyanins resulted in a significant improvement of the VA and CS of adult myopic subjects, thus implicating also an effect on the ciliary muscle, lens pliability and accommodation [51]. ...
The rationale of this study stems from the consideration that vision is a dynamic process, during which photopigments of photoreceptor cells (rods and cones) are continuously consumed and regenerated by retinal pigmented epithelial (RPE) cells. The whole process of vision triggered by light radiation generates free radicals which are potentially toxic to the cells in the central retina (macula), which is the main player in vision. Therefore, the central retina contains carotenoid pigments (mainly lutein and zeaxanthin) with the double function of shielding the cells from light radiation and providing free radical-scavenging action due to their antioxidant power. Nonetheless, visual performance (including visual acuity, contrast sensitivity and stereoscopic perception) can be hampered by bright light and by sudden changes in illumination conditions, such as during the transit from the dark to intense light. Therefore, objective of this study has been to investigate whether the treatment with a food supplement regimen containing different antioxidant and protective elements shown to protect from photo-oxidative damage retinal pigment epithelial (RPE) cells, might also improve retina functions during challenging light conditions. We present here our findings, showing the protective effects on human RPE cells in vitro of lutein and cyanidin-3-glucoside (C3G) against photo-oxidative stress. Accordingly, the results of a retrospective analysis of a case series show that sport motorcycle test pilots (who need for their profession an optimal visual performance) taking a commercially available food supplement containing a blend of antioxidant and protective molecules (lutein, C3G, verbascoside and zinc), improved their visual abilities and reduced their sensibility to glaring lights in a dose/time-dependent fashion. In conclusion, these results suggest that a food supplement may increase the antioxidant defense of the retina, thus improving the visual performance also during challenging illumination conditions, hence increasing the safety of individuals finding themselves in such situations.
... For example, administration of AO improves subjective symptoms and objective contrast sensitivity in myopic subjects with asthenopia (Lee et al., 2005). In addition, fermented bilberry extract containing AO is effective in increasing the subjective accommodation and in mesopic contrast sensitivity of myopic eyes (Kamiya, Kobashi, Fujiwara, Ando, & Shimizu, 2013). ...
Microbial fermentation of grape‐skin extracts is found to synthesize anthocyanin oligomers (AO), which are more active than the monomeric anthocyanins that are effective for some metabolic diseases such as diabetes and obesity. This study investigated the functional role of AO in 3T3‐L1 white adipocyte metabolism, with a focus on inducing browning. To achieve this, we determined the expressions of core genes and protein markers responsible for browning and lipid metabolism in response to AO treatment of 3T3‐L1 white adipocytes. AO exposure significantly increases the expressions of beige‐specific genes (Cidea, Cited1, Ppargc1α, Prdm16, Tbx1, Tmem26, and Ucp1) and brown‐fat signature proteins (UCP1, PRDM16, and PGC‐1α), and suppresses the expressions of lipogenic marker proteins while enhancing the protein levels of lipolysis in white adipocytes. The mechanistic study revealed stimulation of white fat browning via activation of the β3‐AR/PKA/p38 axis and ERK/CREB signaling pathway subsequent to AO treatment. In conclusion, our current findings indicate the beneficial effects of AO for the treatment of obesity with interesting properties such as regulating the browning of adipocytes and increasing thermogenic activity. Although further research based on animal models or clinical trials remains, AO treatment can bring more insights into the treatment of obesity and metabolic syndrome.
... Антоцианозиды способны оказать воздействие на функциональные показатели глаза при миопии как у детей, так и у взрослых. Месячный прием экстракта черники у пациентов молодого и среднего возраста (средний возраст 39,5 ± 7,2 года) с миопией слабой и средней степени привел к достоверному повышению мезопической контрастной чувствительности и объема аккомодации [48]. ...
The ophthalmologist often raises the issues about using of various vitamins, trace elements and other nutrients for the prevention and treatment of the different ocular diseases at their practice. The significance of this problem is caused by the importance of the vision for the socialization of modern person, as well as the high intensity of the visual analyzer using both in the process of performing professional occupation and in the usual indoor/outdoor activities. The issues of the supplemental support in pediatric ophthalmology are especially important, as today formation of the visual organ in children develops under increased visual stress. For the total population, including children, of the industrialized countries the most typical form of vitamin deficiency is subnormal vitamin supply, which occurs among almost healthy children of different ages. The supplemental support issues should be considered in relation to certain types of ocular pathology in children. The most common problem today among children is myopia with projected high increase of this refraction anomaly magnitude in the future. The oxidative stress is the main pathogenesis factor of many degenerative diseases development, including myopia. It is considered as the oxidative stress is realized due to both endogenous processes and various external factors impact, including ultraviolet radiation. Not only vitamins with antioxidant properties (A, C, E), but the trace elements (zinc and copper), bioflavonoids (anthocyanoides) and xanthophilic pigments (lutein, zeaxanthin) are necessary to stabilize myopia and to prevent the development of degenerative diseases in adulthood. These substances are involved in the most important physiological and biosynthetic processes in the sclera, retina and other eye structures and render an influence on its microvessels and hemodynamics in general. All these substances are not synthesized in the human body, and in order to maintain metabolism and homeostasis the sufficient alimentary intake should be provided beginning with early age. The complex drugs, which include multipotential and synergistic active substances, are of particular interest.
The aim of this study was a qualitative and quantitative analysis of macro- and (ultra)trace elements, the main groups of biologically active substances (BAS) of organic nature in the shoots of bilberry (Vaccinium myrtillus L., family Ericaceae), collected after fruit harvesting in the Tomsk region (Tomsk and Zyryansky districts). The study of the elemental composition was carried out after ashing using the methods of emission spectral and instrumental neutron activation analysis with irradiation with thermal neutrons. Determination of classes of BAS of organic nature and their representatives was carried out using chemical reactions, chromatography (sorbents: silica gel, cellulose) using reliable samples, spectroscopy in the UV, visible and IR rangles of the spectrum. As a result of applying the method of emission spectrometry, 45 elements were determined, among which 18 are (conditionally) essential. The macroelements K, Ca, P, Na, Si, Mg and the trace element Mn dominate in the composition of the ash of bilberry shoots after harvesting the fruits. Using the method of neutron activation analysis, the presence of 27 elements was established, nine of which are classified as (conditionally) essential. The data indicate the predominance of Ca, Fe, Na, as well as Ba, Rb, Sr in the ashes of the shoots of the plant after harvesting the fruits. The results of the study show that the Tomsk and Zyryansk districts of the region belong to the background territories. The specificity of bilberry shoots after harvesting the fruits of the Tomsk region is reflected in the highest concentration of the characteristic group of elements (Ba, Sr, Sb, Hf, Fe, Rb), which follows from the formation of chelate complexes and strong organometallic compounds. In the composition of bilberry shoots after harvesting the fruits, the main groups of BAS of a phenolic nature are: simple phenols, flavonoids, phenolcarboxylic acids, coumarins and tannins; triterpene compounds, sterols, water-soluble polysaccharides, carotenoids, amino acids are also present. The research results show the possibility of using plant shoots after harvesting fruits as pharmaceutical raw materials for the development of medicines based on them, including for correcting disorders of higher integrative functions of the brain.
Significance:
The ethnic differences in myopia rates, ocular dimensions, and risk factors between Han and non-Han schoolchildren observed in this study may help fill the knowledge gap about ethnic minorities and are important for China and other countries to address vision-related health inequalities among different ethnic groups.
Purpose:
This study aimed to investigate the risk factors of juvenile myopia and elucidate the disparities of risk factors among Han and non-Han school students in Xinjiang, China.
Methods:
A population-based cross-sectional study of 876 schoolchildren from grades 1 to 9 was conducted in the Anjihai Middle School in Shawan, Xinjiang Uygur Autonomous Region, China. Visual acuity and ocular biometry were assessed, and personal information, including behavior, birth status, and familial factors, was collected using self-made standardized questionnaires.
Results:
The myopia rate among students of Han ethnicity (50.5%) was the highest, followed by Hui (41.3%) and Uygur et al. (32.0%, P < .001). Similar patterns were observed for mean axial length. The mean axial lengths are 23.7, 23.4, and 23.3 mm, respectively ( P = .01). Overall, performing high-quality eye exercises, longer sleep duration, being born in summer, parental smoking, and consuming more food containing anthocyanins were all associated with a lower incidence of myopia. Meanwhile, Han ethnicity, intensive near task, bad eye habits, and myopic mothers were associated with higher odds of myopia. After adjusting for environmental influences pertaining to myopia, the variation in myopia prevalence between Han and Uygur et al. remained significant, whereas it changed to not significant between Han and Hui ethnicities.
Conclusions:
Significant disparities were found in the prevalence of myopia among various ethnic groups in Shawan, Xinjiang. Life habits, birth status, and familial factors may contribute to such variance and play different roles in the occurrence of juvenile myopia among various ethnicities.
This chapter reviews the properties and pharmacological effects of anthocyanins, as well as the latest research progress in major eye diseases such as relief of eye fatigue, myopia, cataracts, retinal degeneration, and dry eye disease. It is suggested that anthocyanins possess protective effect on many eye diseases due to its antioxidant and free radical scavenging ability.
Awareness of the human health benefits of blueberries is underpinned by a growing body of positive scientific evidence from human observational and clinical research, plus mechanistic research using animal and in vitro models. Blueberries contain a large number of phytochemicals, including abundant anthocyanin pigments. Of their various phytochemicals, anthocyanins probably make the greatest impact on blueberry health functionality. Epidemiological studies associate regular, moderate intake of blueberries and/or anthocyanins with reduced risk of cardiovascular disease, death, and type 2 diabetes, and with improved weight maintenance and neuroprotection. These findings are supported by biomarker-based evidence from human clinical studies. Among the more important healthful aspects of blueberries are their anti-inflammatory and antioxidant actions and their beneficial effects on vascular and glucoregulatory function. Blueberry phytochemicals may affect gastrointestinal microflora and contribute to host health. These aspects have implications in degenerative diseases and conditions as well as the aging process. More evidence, and particularly human clinical evidence, is needed to better understand the potential for anthocyanin-rich blueberries to benefit public health. However, it is widely agreed that the regular consumption of tasty, ripe blueberries can be unconditionally recommended.
Previous studies have demonstrated that the intake of berry foods was associated with a reduced risk of cardiovascular diseases. The aim of the present study was to evaluate the effects of two bilberry extracts, one rich in anthocyanins extracted from untreated bilberries (BE) and a second one extracted from yeast-fermented bilberries (FBE), on the development of atherosclerosis in apolipoprotein E-deficient mice (apo E(-/-)). Apo E(-/-) mice received for 16 weeks a diet supplemented with 0.02% of either BE or FBE. Atherosclerotic plaque area was measured in the aortic sinus. Supplementation of the diet with both bilberry extracts led to a significant inhibition of plaque development, whereas no effect on oxidative stress parameters or lipid profiles could be observed, suggesting the implication of other mechanisms of action. In addition, a better protection was observed with FBE, suggesting that the fermentation generates new bioactive compounds more effective in attenuating progression of the atherosclerotic lesions.
A controlled, clinical trial, comparing cyaninoside chloride and Heleniene , was conducted on 31 out-patients suffering from functional disturbances of vision in low-luminance conditions. The evolution of photopic and mesopic visual acuities, electro- oculograms and adapto -electroretinograms was assessed for both treatment groups and controls. Both agents significantly improved photopic visual acuity (p less than 0.05). Only cyaninoside chloride treatment improved visual functions related to mesopic and scotopic vision (p less than 0.01). There were also significant differences between the two treatment groups regarding the velocity of visual adaptation in adapto -electroretinography. This study thus demonstrates the therapeutic value of cyaninoside chloride for the treatment of functional disturbances of mesopic and scotopic vision, especially in night blindness and myopia.
Refractive surgery and videokeratography have allowed us to study the effects on visual performance of relatively large changes in corneal aberration structure induced by surgical changes in corneal shape.
We quantified in one eye of nine normal and 23 radial keratotomy patients, the area under the log contrast sensitivity function (AULCSF) and corneal first surface wavefront variance for two artificial pupil sizes (3 and 7 mm). Contrast sensitivity was measured with sine-wave gratings at six spacial frequencies. Wavefront variance was derived from videokeratographs using Zernike polynomials.
For normals eyes there were no significant changes over time. For eyes that had radial keratotomy, there were significant pupil size-dependent changes. For the 3 mm pupil, there were significant surgery-induced changes in the corneal wavefront variance which became large (approximately 30 times preoperative values) at 7 mm. Significant correlated changes in AULCSF for the 7 mm pupil but not for the 3 mm pupil occurred immediately following surgery and remained.
Radial keratotomy, like photorefractive keratectomy, shifts the distribution of aberrations from third order dominance (coma-like aberrations) to fourth order dominance (spherical-like aberrations). Radial keratotomy-induced aberrations and loss in contrast sensitivity are reduced with increasing clear zone diameter. Radial keratotomy induces an increase in the optical aberrations of the eye and the increase for large pupils (7 mm) but not small (3 mm) is correlated to a decrease in contrast sensitivity.
In view of research demonstrating the ability of anthocyanosides in a single oral dose to improve night vision in normal individuals, it was decided to evaluate their effect on three night vision tests: full-field scotopic retinal threshold (SRT), dark adaptation rate (DAR) and mesopic contrast sensitivity (MCS).
In a double-masked, placebo-controlled, cross-over study, 16 young normal volunteers were randomly assigned to one of four different regimens of single oral administrations of 12, 24 and 36 mg of anthocyanosides, and a placebo, with a 2 week washout period between doses. SRT, DAR and MCS were measured immediately before, and 4, 8 and 24 h after treatment.
No significant effect was found on any of the three night vision tests during the 24 h following a single oral administration of 12, 24 or 36 mg anthocyanosides. The study had a power of 0.95 to detect a 0.1 log unit improvement in SRT and 0.5 log unit improvement in MCS.
Single oral administration of 12-36 mg of anthocyanosides appears to lack significant effect on militarily relevant night vision tests.
In view of research demonstrating the ability of anthocyanosides in a multiple oral dose to improve night vision in normal individuals, we assessed their effect on three night vision tests: full-field absolute scotopic retinal threshold (SRT), dark adaptation rate (DAR) and mesopic contrast sensitivity (MCS).
In a double-masked, placebo-controlled, cross-over study, 18 young normal volunteers were randomly assigned to one of three different regimens of multiple oral administrations of 12 and 24 mg anthocyanosides, and a placebo, given twice daily for 4 days. A 2 week washout period was allowed between each 4 day treatment period. SRT, DAR and MCS was tested 1 day before and at days 1, 2, 3 and 4 during the treatment period.
No significant effect was found on any of the three above-mentioned night vision tests. The study had a power of 0.95 to detect a 0.1 log unit improvement in SRT and 0.5 log unit improvement in MCS.
Multiple oral administrations of 12 and 24 mg anthocyanosides twice a day appear to lack significant effect on night vision tests.