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The retina is a highly vascularized tissue with a high metabolic and oxygen demand responsible for human vision. Considering that the polyphenolic flavanols and anthocyanins have been shown to be beneficial for endothelial function and cerebral blood-flow, an acute randomized and controlled crossover trial with two different sources of polyphenols, anthocyanins from red-berries and flavanols from cocoa, was designed to better understand the effect of polyphenols on visual acuity (VA) and cone-mediated dark adaptation (DA). Thirty-seven healthy subjects (22.1 ± 2.0 years old) participated in the acute intervention for three times (red-berries, cocoa or vehicle-control) with a washout period of two weeks in-between. VA under photopic and low luminance (mesopic) conditions, DA or dynamic of recovery of contrast threshold (CT) following near-total photopigment bleach for 5 min, urine total polyphenols, theobromine and antioxidant power were measured in the three study-arms after 2-hours ingestion of the study-food. 3-hours postprandial urine showed higher levels of total polyphenols after ingestion of cocoa flavanols or red-berries anthocyanins in comparison with the vehicle-control and higher levels of theobromine only for the cocoa group. There was an increase in photopic VA with cocoa flavanols that with red-berries anthocyanins did not reach statistical significance. Both, cocoa and red berries, failed to improve mesopic VA and the cone time constant for contrast recovery and final CT of DA.
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... The impression of humans toward chocolate products has gradually shifted from desserts to healthcare products, emphasizing the amount of bioactive substances found in cocoa beans. Polyphenols in cocoa beans not only bring out unique astringency and bitterness of chocolate flavor but also possess numerous benefits to human health, for instance, eyesight protection (Puell and de Pascual-Teres, 2021); prevention of Parkinson's and Alzheimer's diseases, improved recognition ability, prevention of obesity, increasing the amounts of adiponectin and glucose transporter, decreasing the production of lipid, and insulin resistance (Magrone et al., 2017). Moreover, Buijsse et al. (2010) discovered that polyphenols relax the smooth muscles, having the potential to reduce blood pressure. ...
Cocoa tree (Theobroma cacao L.) is a recently planted crop in Taiwan, a country located in East Asia. Taiwanese cocoa beans are appreciated globally because of their distinctive flavor and aroma. The effects of the water extracts of unfermented Taiwan cocoa beans (WUFCB) and fermented and roasted Taiwan cocoa beans (WFRCB) on the anti-oxidation, vascular protection, and variation in phytochemical components were investigated. Variations in the catechins components of WUFCB and WFRCB were examined by high performance liquid chromatography. The values of catechin compounds in WUFCB (epicatechin [EC]: 52.32 ± 0.56 mg/g, and catechin (C): 15.14 ± 0.26 mg/g) were approximately two times higher than those found in WFRCB (EC: 26.22 ± 0.48 mg/g, and C: 4.56 ± 0.10 mg/g), indicating that the fermentation and roasting steps caused decline in catechins compounds of WFRCB. In the range of 50–300 µg mL-1, both WUFCB and WFRCB depict noncytotoxicity in endothelial cells; they protect cells from H2O2-induced cytotoxicity as established by MTT assay. Meanwhile, nitric oxide (NO) levels in endothelial cells were elevated by WUFCB. In addition, WUFCB displayed radical scavenging in the acellular model and inhibited increase in reactive oxygen species (ROS) noted in endothelial cell induced by H2O2. Overall, the significant vascular protection of WUFCB is associated with increased NO formation. The decreased ROS generation against oxidative damage was attributed to abundant catechin compounds. This study establishes Taiwan cocoa polyphenol as an effective and complementary tool for preventing endothelial dysfunction and cardiovascular disease.
... While theobromine is currently not and nonselective adenosine receptor antagonists . While theobromine is currently not used as a prescription drug , it attracts the attention of researchers  since it possesses several beneficial properties related to human health, such as antioxidant , anti-inflammatory  or immunomodulatory  activities. A very important and widely explored property of theobromine is its anti-cancer activity . ...
The solubility of theobromine was studied both experimentally and theoretically. The solubility was determined spectrophotometrically at 25 °C in neat organic solvents, aqueous binary mixtures, Natural Deep Eutectic Solvents (NADES) and ternary NADES mixtures with water. It was found that addition of water in unimolar proportions with some organic solvents increases theobromine solubility compared to neat solvents. Additionally, using NADES results in a solubility increase of the studied compound not only in relation to water but also DMSO. The addition of water (0.2 molar fraction) to NADES is responsible for an even larger increase of solubility. The measured solubilities were interpreted in terms of three theoretical frameworks. The first one—belonging to the set of data reduction techniques—proved to be very efficient in quantitative back-computations of excess solubility of theobromine in all studied systems. The default approach utilizing the well-recognized COSMO-RS (Conductor-like Screening Model for Real Solvents) framework offered at most a qualitative solubility description. The extended search for possible contacts provided evidence for the existence of many intermolecular complexes that alter the electron density of the solute molecule, thus influencing solubility computations. Taking into account such intermolecular contacts by using the COSMO-RS-DARE (Conductor-like Screening Model for Realistic Solvation-Dimerization, Aggregation, and Reaction Extension) framework seriously increased the accuracy of solubility computations.
... A commercial freeze-dried red-berry mixture was kindly supplied by Salengei ® (Barcelona, Spain). The mixture contained a blend of red and black currant (16.7% and 33.3%, respectively), raspberry (33%) and blueberry (16.7%) and has been previously used in two human trials as one of the assayed foods (one unpublished and the other ). ...
Recommendations towards increased consumption of fresh fruit and vegetables are well supported by epidemiological and clinical trials. However, in some specific cases, it is difficult to follow these recommendations and the use of nutraceuticals or, in the present work, a freeze-dried fruits mixture can be recommended in order to afford the optimal consumption of dietary polyphenols naturally present in fruits and vegetables. In this work we have carefully characterized a red-berry mixture in terms of polyphenol composition, encountering mainly anthocyanins, which account for a total of 2.8 mg/g as cyanidin-3-glucoside equivalents. Additionally, we have assayed the red-berry blend in a cell model of neurological damage by differentiating the cells and measuring the effect of red-berry polyphenols on cell viability and redox state by flow cytometry. The berry-fruit extract showed an inhibitory effect on differentiated SH-SY5Y ROS formation at a concentration as low as 250 µg/mL (33% inhibition). The results show the potential of this berry-fruit blend for its nutraceutical use in the prevention of the neurodegeneration associated with age or environmental agents.
Polyphenols are a wide group of plant components that include a high number of individual compounds and are present in foods, dietary supplements and drugs. Many of them have shown pharmacological effects, are used in cardiovascular disease prevention, and not as many have been assayed in cancer treatment or co-treatment. In the last few years, however, the research on polyphenols implications in a healthy aging and especially in neurodegeneration and cognition improvement has increased dramatically. Most of the results found in this sense are again related with the capacity of some specific polyphenols to regulate the blood flow, but this time at the cerebral level, and to protect the endothelium at this same level. In this thorough review, we want to concentrate precisely on the effect of polyphenols on the cerebrovascular homeostasis, reviewing the mechanisms that underline this effect and the radiological methods and endogenous biomarkers that are used in human trials aimed at showing the beneficial effect of polyphenols or polyphenols rich foods on neuroprotection and cognition function.
Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus and is characterized by degeneration of retinal neurons and neoangiogenesis, causing a severe threat to vision. Nowadays, the principal treatment options for DR are laser photocoagulation, vitreoretinal surgery, or intravitreal injection of drugs targeting vascular endothelial growth factor. However, these treatments only act at advanced stages of DR, have short term efficacy, and cause side effects. Treatment with nutraceuticals (foods providing medical or health benefits) at early stages of DR may represent a reasonable alternative to act upstream of the disease, preventing its progression. In particular, in vitro and in vivo studies have revealed that a variety of nutraceuticals have significant antioxidant and anti-inflammatory properties that may inhibit the early diabetes-driven molecular mechanisms that induce DR, reducing both the neural and vascular damage typical of DR. Although most studies are limited to animal models and there is the problem of low bioavailability for many nutraceuticals, the use of these compounds may represent a natural alternative method to standard DR treatments.
In this study, we investigated how the acute physiological effects of cocoa flavanols might result in specific cognitive changes, in particular in temporal and spatial attention. To this end, we pre-registered and implemented a randomized, double-blind, placebo- and baseline-controlled crossover design. A sample of 48 university students participated in the study and each of them completed the experimental tasks in four conditions (baseline, placebo, low dose, and high-dose flavanol), administered in separate sessions with a 1-week washout interval. A rapid serial visual presentation task was used to test flavanol effects on temporal attention and integration, and a visual search task was similarly employed to investigate spatial attention. Results indicated that cocoa flavanols improved visual search efficiency, reflected by reduced reaction time. However, cocoa flavanols did not facilitate temporal attention nor integration, suggesting that flavanols may affect some aspects of attention, but not others. Potential underlying mechanisms are discussed.
Unblemished fully ripe fruit from five day-neutral strawberry cultivars were harvested on two separate dates and evaluated for ascorbic acid (AsA), fruit sugars, and phenolic composition. Individual phenolics were determined by HPLC, and total phenolics by Folin–Ciocalteu (F–C) and by a ‘new’ assay: Fast Blue BB (FBBB), which detects phenolics directly. FBBB reported an average 2.9-fold greater concentration of total phenolics than F–C, had a significant correlation (r = 0.80; P = 0.001) with total phenolics via HPLC and did not interact with AsA or sugars, whereas F–C, an indirect detection assay for total phenolics, appeared to under-report total phenolic concentrations, had no significant correlation (r = 0.20) with total phenolics via HPLC or with sugars, but had a significant correlation (r = 0.64; P = 0.05) with total AsA. Results from this study indicated that previous studies of strawberry fruit, using the standard indirect F–C assay, have greatly underestimated the total phenolics content and that this assay should be replaced in future studies by the FBBB assay.
Despite the large number of studies on the behavioural effects of caffeine, an unequivocal conclusion had not been reached. In this review, we seek to disentangle a number of questions.
Whereas there is a general consensus that caffeine can improve performance on simple tasks, it is not clear whether complex tasks are also affected, or if caffeine affects performance of the three attention networks (alerting, orienting and executive control). Other questions being raised in this review are whether effects are more pronounced for higher levels of caffeine, are influenced by habitual caffeine use and whether there effects are due to withdrawal reversal.
Literature review of double-blind placebo controlled studies that assessed acute effects of caffeine on attention tasks in healthy adult volunteers.
Caffeine improves performance on simple and complex attention tasks, and affects the alerting, and executive control networks. Furthermore, there is inconclusive evidence on dose-related performance effects of caffeine, or the influence of habitual caffeine consumption on the performance effects of caffeine. Finally, caffeine’s effects cannot be attributed to withdrawal reversal.
Evidence shows that caffeine has clear beneficial effects on attention, and that the effects are even more widespread than previously assumed.
The visual system is one of the most energetically demanding systems in the brain. The currency of energy is ATP, which is generated most efficiently from oxidative metabolism in the mitochondria. ATP supports multiple neuronal functions. Foremost is repolarization of the membrane potential after depolarization. Neuronal activity, ATP generation, blood flow, oxygen consumption, glucose utilization, and mitochondrial oxidative metabolism are all interrelated. In the retina, phototransduction, neurotransmitter utilization, and protein/organelle transport are energy-dependent, yet repolarization-after-depolarization consumes the bulk of the energy. Repolarization in photoreceptor inner segments maintains the dark current. Repolarization by all neurons along the visual pathway following depolarizing excitatory glutamatergic neurotransmission preserves cellular integrity and permits reactivation. The higher metabolic activity in the magno- versus the parvo-cellular pathway, the ON- versus the OFF-pathway in some (and the reverse in other) species, and in specialized functional representations in the visual cortex all reflect a greater emphasis on the processing of specific visual attributes. Neuronal activity and energy metabolism are tightly coupled processes at the cellular and even at the molecular levels. Deficiencies in energy metabolism, such as in diabetes, mitochondrial DNA mutation, mitochondrial protein malfunction, and oxidative stress can lead to retinopathy, visual deficits, neuronal degeneration, and eventual blindness.
The combination of theobromine and caffeine, methylxanthines found in chocolate, has previously been shown to improve mood and cognition. However, it is unknown whether these molecules act synergistically. This study tested the hypothesis that a combination of caffeine and theobromine has synergistic effects on cognition, mood and blood pressure in 24 healthy female subjects. The effects of theobromine (700 mg), caffeine (120 mg) or the combination of both, or placebo were tested on mood (the Bond-Lader visual analog scale), psychomotor performance (the Digit Symbol Substitution Test (DSST)) and blood pressure before and at 1, 2 and 3 h after administration. Theobromine alone decreased self-reported calmness 3h after ingestion and lowered blood pressure relative to placebo 1 h after ingestion. Caffeine increased self-reported alertness 1, 2 and 3h after ingestion and contentedness 1 and 2 h after ingestion, and increased blood pressure relative to placebo (at 1 h). The combination of caffeine+theobromine had similar effects as caffeine alone on mood, but with no effect on blood pressure. There was no treatment effect on DSST performance. Together these results suggest that theobromine and caffeine could have differential effects on mood and blood pressure. It was tentatively concluded that caffeine may have more CNS-mediated effects on alertness, while theobromine may be acting primarily via peripheral physiological changes.
Plant polyphenols have been studied largely because of the possibility that they might underlie the protective effects afforded by fruit and vegetable intake against cancer and other chronic diseases. Measurement of polyphenol content excreted in urine as an indicator of polyphenol consumption may offer a routine screening method that could be used for these pathologies.
Thirty-six healthy volunteers each received 2 interventions, one with a polyphenol-rich food (cocoa beverage) and one with a polyphenol-free food (milk) as a control, in a randomized cross-over design with 1-week intervals. The total polyphenol content excreted in urine during the 6 h after consumption of the test meals was measured by a modified Folin-Ciocalteu assay after sample cleanup by solid-phase extraction.
The mean (SD) concentrations of polyphenols excreted in the urine 6 h after consumption of the test meals differed significantly: 140.95 (49.27) mg catechin/g of creatinine after the polyphenol-rich meal vs 90.43 (46.07) mg catechin/g of creatinine after the control meal (P <0.05).
This method allows analysis of a large number of samples per day, which is ideal for use in epidemiologic studies and may enable estimation of polyphenol consumption and determination of their possible role in preventing of certain pathologies, such as cancer, cardiovascular and degenerative diseases.
What are scientists, physicians, and the general public to make of the many null findings from randomized controlled trials (RCTs) of vitamin supplements? These trials are usually conducted on the basis of positive findings from prospective epidemiological studies and laboratory evidence of biological mechanisms. A common view is that the negative findings from the RCTs offer incontrovertible evidence that the nutrient is unrelated to disease and that the epidemiological studies are biased. An alternative explanation is that most RCTs of vitamin supplements are designed to test the hypothesis that supplementation, no matter the nutrient status, is protective. Vitamin treatment may not be effective in these trials because nutrient intake among the participants is already at optimum levels. To specify, examples are provided from the field of dementia and investigations of 3 dietary components: vitamin E, B vitamins, and docosahexaenoic acid.
Cocoa flavanols (CF) influence physiological processes in ways that suggest their consumption may improve aspects of neural function, and previous studies have found positive influences of CF on cognitive performance. In this preliminary study we investigated whether visual, as well as cognitive, function is influenced by an acute dose of CF in young adults. We employed a randomized, single-blinded, order counterbalanced, crossover design in which 30 healthy adults consumed both dark chocolate containing 720mg CF and a matched quantity of white chocolate, with a one week interval between testing sessions. Visual contrast sensitivity was assessed by reading numbers that became progressively more similar in luminance to their background. Motion sensitivity was assessed firstly by measuring the threshold proportion of coherently moving signal dots that could be detected against a background of random motion, and secondly by determining the minimum time required to detect motion direction in a display containing a high proportion of coherent motion. Cognitive performance was assessed using a visual spatial working memory for location task and a choice reaction time task designed to engage processes of sustained attention and inhibition. Relative to the control condition, CF improved visual contrast sensitivity and reduced the time required to detect motion direction, but had no statistically reliable effect on the minimum proportion of coherent motion that could be detected. In terms of cognitive performance, CF improved spatial memory and performance on some aspects of the choice reaction time task. As well as extending the range of cognitive tasks that are known to be influenced by CF consumption, this is the first report of acute effects of CF on the efficiency of visual function. These acute effects can be explained by increased cerebral blood flow caused by CF, although in the case of contrast sensitivity there may be an additional contribution from CF induced retinal blood flow changes.
Nowadays it is accepted that natural flavonoids present in fruits and plant-derived-foods are relevant, not only for technological reasons and organoleptic properties, but also because of their potential health-promoting effects, as suggested by the available experimental and epidemiological evidence. The beneficial biological effects of these food bioactives may be driven by two of their characteristic properties: their affinity for proteins and their antioxidant activity. Over the last 15 years, numerous publications have demonstrated that besides their in vitro antioxidant capacity, certain phenolic compounds, such as anthocyanins, catechins, proanthocyanidins, and other non coloured flavonoids, may regulate different signaling pathways involved in cell survival, growth and differentiation. In this review we will update the knowledge on the cardiovascular effects of anthocyanins, catechins and proanthocyanidins, as implied by the in vitro and clinical studies on these compounds. We also review the available information on the structure, distribution and bioavailability of flavanols (monomeric catechins and proanthocyanidins) and anthocyanins, data necessary in order to understand their role in reducing risk factors and preventing cardiovascular health problems through different aspects of their bioefficacy on vascular parameters (platelet agregation, atherosclerosis, blood pressure, antioxidant status, inflammation-related markers, etc.), myocardial conditions, and whole-body metabolism (serum biochemistry, lipid profile), highlighting the need for better-designed clinical studies to improve the current knowledge on the potential health benefits of these flavonoids to cardiovascular and metabolic health.
The purpose of this study was to investigate the effect of bilberry on night visual acuity (VA) and night contrast sensitivity (CS).
This study utilized a double-blind, placebo-controlled, crossover design. The subjects were young males with good vision; eight received placebo and seven received active capsules for three weeks. Active capsules contained 160 mg of bilberry extract (25-percent anthocyanosides), and the placebo capsules contained only inactive ingredients. Subjects ingested one active or placebo capsule three times daily for 21 days. After the three-week treatment period, a one-month washout period was employed to allow any effect of bilberry on night vision to dissipate. In the second three-week treatment period, the eight subjects who first received placebo were given active capsules, and the seven who first received active capsules were given placebo. Night VA and night CS was tested throughout the three-month experiment.
There was no difference in night VA during any of the measurement periods when examining the average night VA or the last night VA measurement during active and placebo treatments. In addition, there was no difference in night CS during any of the measurement periods when examining the average night CS or the last night CS measurement during active and placebo treatments.
The current study failed to find an effect of bilberry on night VA or night CS for a high dose of bilberry taken for a significant duration. Hence, the current study casts doubt on the proposition that bilberry supplementation, in the forms currently available and in the doses recommended, is an effective treatment for the improvement of night vision in this population.
Following exposure of our eye to very intense illumination, we experience a greatly elevated visual threshold, that takes tens of minutes to return completely to normal. The slowness of this phenomenon of "dark adaptation" has been studied for many decades, yet is still not fully understood. Here we review the biochemical and physical processes involved in eliminating the products of light absorption from the photoreceptor outer segment, in recycling the released retinoid to its original isomeric form as 11-cis retinal, and in regenerating the visual pigment rhodopsin. Then we analyse the time-course of three aspects of human dark adaptation: the recovery of psychophysical threshold, the recovery of rod photoreceptor circulating current, and the regeneration of rhodopsin. We begin with normal human subjects, and then analyse the recovery in several retinal disorders, including Oguchi disease, vitamin A deficiency, fundus albipunctatus, Bothnia dystrophy and Stargardt disease. We review a large body of evidence showing that the time-course of human dark adaptation and pigment regeneration is determined by the local concentration of 11-cis retinal, and that after a large bleach the recovery is limited by the rate at which 11-cis retinal is delivered to opsin in the bleached rod outer segments. We present a mathematical model that successfully describes a wide range of results in human and other mammals. The theoretical analysis provides a simple means of estimating the relative concentration of free 11-cis retinal in the retina/RPE, in disorders exhibiting slowed dark adaptation, from analysis of psychophysical measurements of threshold recovery or from analysis of pigment regeneration kinetics.
Liking, cravings and addiction for chocolate ("chocoholism") are often explained through the presence of pharmacologically active compounds. However, mere "presence" does not guarantee psycho-activity.
Two double-blind, placebo-controlled studies measured the effects on cognitive performance and mood of the amounts of cocoa powder and methylxanthines found in a 50 g bar of dark chocolate.
In study 1, participants ( n=20) completed a test battery once before and twice after treatment administration. Treatments included 11.6 g cocoa powder and a caffeine and theobromine combination (19 and 250 mg, respectively). Study 2 ( n=22) comprised three post-treatment test batteries and investigated the effects of "milk" and "dark" chocolate levels of these methylxanthines. The test battery consisted of a long duration simple reaction time task, a rapid visual information processing task, and a mood questionnaire.
Identical improvements on the mood construct "energetic arousal" and cognitive function were found for cocoa powder and the caffeine+theobromine combination versus placebo. In chocolate, both "milk chocolate" and "dark chocolate" methylxanthine doses improved cognitive function compared with "white chocolate". The effects of white chocolate did not differ significantly from those of water.
A normal portion of chocolate exhibits psychopharmacological activity. The identical profile of effects exerted by cocoa powder and its methylxanthine constituents shows this activity to be confined to the combination of caffeine and theobromine. Methylxanthines may contribute to the popularity of chocolate; however, other attributes are probably much more important in determining chocolate's special appeal and in explaining related self-reports of chocolate cravings and "chocoholism".
A cathode-ray-tube (CRT) monitor-based technique was used to isolate clinically significant components of dark adaptation. The utility of the technique in identifying adaptation abnormalities in eyes with age-related maculopathy (ARM) is described.
A CRT dark adaptometer was developed to assess cone and rod recovery after photopigment bleach. The following measures were obtained: cone recovery rate (R(c); in decades per minute) and absolute threshold (Tf(c); log candelas per square meter), rod recovery rate (R(r); decades per minute), and rod-cone transition (rod-cone break [RCB], in minutes). These components were isolated by appropriately selecting stimulus size, stimulus location, pigment bleach, and test duration and by coupling the CRT with judiciously selected neutral-density (ND) filters. The protocol was developed by using 5 young observers and was tested on 27 subjects with ARM in the study eye and 22 age-matched control subjects.
The parameters necessary for effective isolation of cone and early phase rod dark adaptation were a 2.6 ND filter (for a standard CRT monitor, 0.08-80 cd . m(-2) luminance output); a 4 degrees foveated, 200-ms, achromatic spot; approximately 30% pigment bleaching; and a 30-minute test duration. These settings returned obvious rod and cone recovery curves in control and ARM eyes that were compatible with conventional test methods and identified 93% of participants with ARM as having delayed dynamics in at least one of the parameters. Cone recovery dynamics were significantly slower in the ARM group when compared with age-matched control subjects (R(c), 0.99 +/- 0.35 vs. 2.63 +/- 0.61 decades . min(-1), P < 0.0001). Three of the 27 eyes with ARM did not achieve RCB during the allowed duration (30 minutes). The remaining eyes with ARM (n = 24) exhibited a significant delay in rod recovery (R(r)(,) ARM, 0.16 +/- 0.03 vs. controls, 0.22 +/- 0.02 decades . min(-1), P < 0.0001) and the average time to RCB (+/-SD) in the ARM group was significantly longer than in the control subjects (19.12 +/- 5.17 minutes vs. 10.40 +/- 2.49 minutes, P < 0.0001).
The CRT dark-adaptation technique described in this article is an effective test for identifying abnormalities in cone and rod recovery. Slowed cone and rod recovery and a delayed RCB were evident in the eyes with ARM. The test method is potentially useful for clinical intervention trials in which ARM progression is monitored.
A recently reported randomized clinical trial suggested beneficial effects of vasodilating flavanols in dark chocolate on visual function without objective quantification of retinal perfusion.
To assess the effects of dark chocolate flavanols on subjective visual function and retinal perfusion objectively quantified on optical coherence tomography (OCT) angiography.
Design, Setting, and Participants
This randomized, masked double-blind crossover clinical trial analyzed 22 healthy participants at the Department of Ophthalmology, Ludwig Maximilians-University Munich, Germany, in July 2018. Analysis was intention to treat. Analysis began in July 2018.
Participants were randomized to consume 20 g of dark chocolate containing 400 mg of flavanols or 7.5 g of milk chocolate. Two hours later, visual function and retinal perfusion on OCT angiography were evaluated. Systemic blood pressure was measured to rule out artifacts on OCT angiography.
Main Outcomes and Measures
The primary end point was macular retinal perfusion quantified as vessel density on OCT angiography. The secondary end point was subjective visual function (Early Treatment Diabetic Retinopathy Study visual acuity, Pelli-Robson chart, and Mars chart contrast sensitivity).
All 22 participants (13 women [59.1%]; mean [SD] age, 27.3 [11.1] years) completed the trial. No relevant differences in baseline parameters between groups were identified. No change in the primary outcome measure, retinal perfusion, could be detected after consumption of dark vs milk chocolate (superficial plexus 48.0% vs 47.5%, treatment effect: −0.59 [95% CI, −2.68 to 1.50], P = .56; deep plexus 54.1% vs 54.0%, treatment effect: −1.14 [95% CI, −4.01 to 1.73], P = .42). No differences in changes in the secondary outcome parameters Early Treatment Diabetic Retinopathy Study visual acuity, Pelli-Robson chart, or Mars chart contrast sensitivity could be detected. Potentially confounding effects of changes in blood pressure were excluded.
Conclusions and Relevance
In contrast to a previous similarly sized randomized clinical trial reporting beneficial effects on visual function, no short-term effects of flavanol-rich dark chocolate on automatically assessed retinal blood flow on OCT angiography or subjective visual function were observed in this study. As this small trial does not rule out the possibility of benefits, further trials with larger sample sizes would be needed to rule in or out possible long-term benefits confidently.
German Clinical Trials Register identifier: DRKS0001506
Obesity has been associated with abnormal lipid metabolism and with tissue hypoxia. Human Bruch's membrane (BrM) lipid deposits have been proposed to create a diffusion barrier to metabolic exchange between the choroid and photoreceptors, delaying the regeneration of photopigments. The speed of retinal dark adaptation (DA) is dependent on the regeneration of these photopigments. While the retina is extremely sensitive to hypoxia, the inner retina, which encodes visual contrast, is more affected by hypoxia than the outer retina. This study examines the association between adiposity measures and the time course of DA measured psychophysically through contrast detection to test the functionality of both the outer and inner retina. Cone-mediated DA recovery of contrast threshold (CT) was measured following near-total photopigment bleach for 6 min in 52 healthy eyes of 52 individuals (42.6 ± 18.3 years). Stimuli were sine-wave gratings of low-spatial frequency (1 cycle-per-degree (cpd)) and low luminance (1 cd/m ² ) generated at the centre of a CRT monitor. CT recovery functions were fitted to an exponential decay model to determine the time constant (τ, seconds) of cone sensitivity recovery, final cone CT (CT f ) and CT elevation (CT 0 ). Weight, height and waist circumference (WC) were measured and body mass index (BMI) and waist-to-height ratio (WHtR) calculated. Relationships were examined through Spearman correlation and through multiple linear regression using age, optical and adiposity measures as independent variables. The repeatability of cone time constant measurements was estimated by the Bland-Altman method and reported as the coefficient of repeatability (CoR). Mean ± SD of time constant and CT f were 57.3 ± 27.7 s and −1.78 ± 0.20 log 10 units respectively. Cone time constant showed positive Spearman correlation with WC (p = 0.008) and WHtR (p = 0.023) but not with BMI (p = 0.058). Only WHtR emerged as an independent predictor of time constant (p = 0.001). CT f was not correlated with any adiposity measures. Mean cone time constant was 41 s slower in subjects (25%, n = 13) with abdominal obesity (WHtR≥0.5). Mean CT f was not significantly different in subjects with or without abdominal obesity. CoR for cone time constant was ±16 s. In adult subjects, greater abdominal obesity (WHtR) was related to a longer contrast recovery time for cone-mediated DA (time to dark-adapt) suggesting outer retinal dysfunction. Final contrast threshold, preferentially processed by inner retinal cells, was unaffected by abdominal obesity.
Caffeine, a popular psychostimulant that acts as an adenosine receptor antagonist, is the most widely used drug in history, consumed daily by people worldwide. Knowledge of the physiological and pathological effects of caffeine is crucial in improving public health because of its widespread use. We provide a summary of the current evidence on the effect of caffeine on the eye. Most of the research conducted to date is in relation to cataract and glaucoma, two of the most common eye diseases among the elderly.
Consumption of dark chocolate can improve blood flow, mood, and cognition in the short term, but little is known about the possible effects of dark chocolate on visual performance.
To compare the short-term effects of consumption of dark chocolate with those of milk chocolate on visual acuity and large- and small-letter contrast sensitivity.
A randomized, single-masked crossover design was used to assess short-term visual performance after consumption of a dark or a milk chocolate bar. Thirty participants without pathologic eye disease each consumed dark and milk chocolate in separate sessions, and within-participant paired comparisons were used to assess outcomes. Testing was conducted at the Rosenberg School of Optometry from June 25 to August 15, 2017.
Main Outcomes and Measures
Visual acuity (in logMAR units) and large- and small-letter contrast sensitivity (in the log of the inverse of the minimum detectable contrast [logCS units]) were measured 1.75 hours after consumption of dark and milk chocolate bars.
Among the 30 participants (9 men and 21 women; mean [SD] age, 26  years), small-letter contrast sensitivity was significantly higher after consumption of dark chocolate (mean [SE], 1.45 [0.04] logCS) vs milk chocolate (mean [SE], 1.30 [0.05] logCS; mean improvement, 0.15 logCS [95% CI, 0.08-0.22 logCS]; P < .001). Large-letter contrast sensitivity was slightly higher after consumption of dark chocolate (mean [SE], 2.05 [0.02] logCS) vs milk chocolate (mean [SE], 2.00 [0.02] logCS; mean improvement, 0.05 logCS [95% CI, 0.00-0.10 logCS]; P = .07). Visual acuity improved slightly after consumption of dark chocolate (mean [SE], −0.22 [0.01] logMAR; visual acuity, approximately 20/12) and milk chocolate (mean [SE], −0.18 [0.01] logMAR; visual acuity, approximately 20/15; mean improvement, 0.04 logMAR [95% CI, 0.02-0.06 logMAR]; P = .05). Composite scores combining results from all tests showed significant improvement after consumption of dark compared with milk chocolate (mean improvement, 0.20 log U [95% CI, 0.10-0.30 log U]; P < .001).
Conclusions and Relevance
Contrast sensitivity and visual acuity were significantly higher 2 hours after consumption of a dark chocolate bar compared with a milk chocolate bar, but the duration of these effects and their influence in real-world performance await further testing.
clinicaltrials.gov Identifier: NCT03326934
Whether all dietary polyphenols nourishes the eyes via oral supplementation is controversial. Given that passage of dietary polyphenols across the blood-retina barrier (BRB) is the precondition for polyphenols to exhibit ocular benefits, the BRB permeability of polyphenols was assessed in this study. Being common dietary polyphenols in fruits and vegetables, non-anthocyanin flavonoids, anthocyanins, and phenolic acids were investigated. BRB was simulated in vitro by using a differentiated retinal pigment epithelial cell monolayer cultivated on a Transwell culture system. Penetration rate was calculated by quantitatively analyzing the polyphenols in basolateral media. BRB permeability of different polyphenols obviously (p<0.05) differed, as follows: phenolic acids > non-anthocyanin flavonoids > anthocyanins. Glycosylation and methylation improved the BRB permeability of non-anthocyanin flavonoids and anthocyanins. However, instability and carbonylation at C-4 position severely suppressed the BRB permeability of anthocyanins and non-anthocyanin flavonoids. Moreover, a new metabolite was discovered during penetration of anthocyanins into the BRB. However, hydrophilic phenolic acids exhibited better BRB permeability than hydrophobic ones. Data demonstrate that BRB permeability of polyphenols was determined based on structural characteristics, hydrophilicity, stability, and metabolic changes.
Increased exposure to solar ultraviolet B (UVB) radiation produce oxidative damage that may promote age related macular degeneration (AMD) and other ocular pathologies. This study aimed to demonstrate protective effects of some anthocyanins and xanthophylls against UVB-induced oxidative damage to retinal epithelial cells (RPE). ARPE-19 cells were treated with 5 μM delphinidin, cyanidin, lutein, zeaxanthin or a mix of cyanidin-zeaxanthin prior to UVB exposure (500 J/m2). Cell viability and mitogen-activated protein kinases (MAPKs) phosphorylation were determined by MTT and western blot analysis, respectively. Oxidative damage was evaluated by measuring intracellular reactive oxygen species (ROS). The data showed that UVB irradiation reduce the cell viability to 46% with increasing of intracellular ROS levels and phosphorylation of MAPKs. However, pre-treatment (60 min) with 5 μM cyanidin, lutein or zeaxanthin significantly reduced cellular ROS levels and phosphorylation of MAPKs (JNK1/2 and p38) mediated by UVB irradiation and subsequently increased cell viability. Thus, results show that UVB irradiation is able to induce apoptosis in ARPE19 cells through oxidative stress; however anthocyanins and xanthophylls pre-treatment can attenuate this damage. This suggests that cyanidin, lutein and zeaxanthin are effective in preventing UVB-induced damage in RPE cells and may be suitable for further developments as a chemoprotective factors for the primary prevention of ocular damage. Finally, the use of natural antioxidants may be useful in reducing the ocular oxidative damage mediated by UVB radiation.
Clinical evidence for anthocyanin benefits in night vision is controversial. We present two human trials investigating blueberry anthocyanin effects on dark adaptation, functional night vision, and vision recovery after retinal photo-bleaching. One trial, S2 (n=72) employed a 3-week intervention and 3-week washout, two anthocyanin doses (271 and 7.11 mg cyanidin 3-glucoside (C3G)) and placebo. The other trial, L1 (n=59) employed a 12-week intervention and 8-week washout and tested one dose (346 mg C3g) and placebo. In both S2 and L1 dark adaptation was not improved by anthocyanin intake. However in both trials anthocyanin consumption hastened the recovery of visual acuity after photo-bleaching. In S2 the two anthocyanin doses were effective (P=0.014) and in L1 photo-bleaching recovery was improved at 8 weeks (P=0.027) and 12 weeks (P= 0.030). While photo-bleaching recovery was hastened by anthocyanin intake, it is not known whether this improvement would have an impact on everyday vision.
Theobromine, a methylxanthine related to caffeine and present in high levels in cocoa, may contribute to the appeal of chocolate. However, current evidence for this is limited.
We conducted a within-subjects placebo-controlled study of a wide range of oral theobromine doses (250, 500, and 1,000 mg) using an active control dose of caffeine (200 mg) in 80 healthy participants.
Caffeine had the expected effects on mood including feelings of alertness and cardiovascular parameters. Theobromine responses differed according to dose; it showed limited subjective effects at 250 mg and negative mood effects at higher doses. It also dose-dependently increased heart rate. In secondary analyses, we also examined individual differences in the drug's effects in relation to genes related to their target receptors, but few associations were detected.
This study represents the highest dose of theobromine studied in humans. We conclude that theobromine at normal intake ranges may contribute to the positive effects of chocolate, but at higher intakes, effects become negative.
To determine photopic and mesopic distance high-contrast visual acuity (HC-VA) and low-contrast visual acuity (LC-VA) in eyes with early age-related macular degeneration (AMD).
Measurements were made in 22 subjects with early AMD and 28 healthy control subjects. Inclusion criteria included a photopic HC-VA of 20/25 or better. Distance VA was measured using HC (96%) and LC (10%) Bailey-Lovie logMAR letter charts under photopic (85 cd/m(2)) and mesopic (0.1-0.2 cd/m(2)) luminance conditions.
Mean mesopic distance HC-VA and LC-VA were significantly worse (0.1 logMAR and 0.28 logMAR, respectively) in the early AMD group than in the control group. Under mesopic conditions, the mean difference between LC-VA and HC-VA was significantly greater in the early AMD (0.45 logMAR) than the control group (0.27 logMAR). Mean differences between mesopic versus photopic HC-VA and mesopic versus photopic LC-VA were significantly greater in the early AMD than the control group (0.13 and 0.32 logMAR of difference between the means, respectively). Sensitivity and specificity were significantly greater for mesopic LC-VA than for mesopic HC-VA (Receiver Operating Characteristics, area under the curve [AUC], 0.94 ± 0.030 and 0.76 ± 0.067, respectively). AUC values for photopic HC-VA and LC-VA were below 0.70.
Visual acuity testing under low luminance conditions emerged as an optimal quantitative measure of retinal function in early AMD.
To determine the effect of diabetes on inner and outer retinal function in persons with diabetes and no clinically detectable retinopathy or with non-proliferative diabetic retinopathy (NPDR).
Visual function was assessed in 18 adults with normal retinal health, 23 adults with diabetes and 35 adults with NPDR and normal visual acuity. Contrast sensitivity and frequency doubling technology (FDT) sensitivity were used to assess ganglion cell function. Acuity, dark adaptation, light-adapted visual sensitivity and dark-adapted visual sensitivity were measured to evaluate cone and rod photoreceptor visual function. The presence and severity of diabetic retinopathy was determined by grading of 7-field stereoscopic fundus photographs using the Early Treatment Diabetic Retinopathy Study grading system.
Participants with NPDR exhibited impairment of all measured visual functions in comparison with the normal participants. Inner retinal function measured by FDT perimetry was the most impaired visual function for patients with NPDR, with 83% of patients exhibiting clinically significant impairment. Rod photoreceptor function was grossly impaired, with almost half of the patients with NPDR exhibiting significantly impaired dark-adapted visual sensitivity.
Both inner retinal and outer retinal functions exhibited impairment related to NPDR. FDT perimetry and other visual function tests reveal an expanded range of diabetes induced retinal damage even in patients with good visual acuity.
The main cell systems of the retina that provide input to the striate cortex are now well described, although certain aspects of their anatomy and physiology remain contentious. Under simple stimulus conditions and in a threshold context psychophysical performance can often be assigned to one or other of these systems, and an identification of psychophysical channels with afferent pathways is justifiable. However, results from psychophysical studies using more complex stimulus conditions are more difficult to relate to 'front end' channels, and it is more difficult to separate the physiological contributions of afferent pathways from those of cortical mechanisms, in particular the separation of dorsal and ventral streams.
A long-standing yet controversial bioactivity attributed to polyphenols is their beneficial effects in vision. Although anecdotal case reports and in vitro research studies provide evidence for the visual benefits of anthocyanin-rich berries, rigorous clinical evidence of their benefits is still lacking. Recent in vitro studies demonstrate that anthocyanins and other flavonoids interact directly with rhodopsin and modulate visual pigment function. Additional in vitro studies show flavonoids protect a variety of retinal cell types from oxidative stress-induced cell death, a neuroprotective property of significance because the retina has the highest metabolic rate of any tissue and is particularly vulnerable to oxidative injury. However, more information is needed on the bioactivity of in vivo conjugates and the accumulation of flavonoids in ocular tissues. The direct and indirect costs of age-related vision impairment provide a powerful incentive to explore the potential for improved vision health through the intake of dietary polyphenolics.
Caffeine (1,3,7-trimethylxanthine), theobromine (3,7-dimethylxanthine) and theophylline (1,3-dimethylxanthine) are the most important naturally occurring methylxanthines. Caffeine is a constituent of coffee and other beverage and included in many medicines. Theobromine and theophylline are formed as metabolites of caffeine in humans, and are also present in tea, cocoa and chocolate products. In order to improve the chromatographic resolution (R(s)) with a good analysis time, experimental designs were applied for multivariate optimisation of the experimental conditions of an isocratic reversed-phase high-performance liquid chromatographic (RP-HPLC) method used for the simultaneous determination of caffeine, theobromine and theophylline. The optimisation process was carried out in two steps using full three-level factorial designs. The factors optimised were: flow rate and mobile phase composition. Optimal conditions for the separation of the three methylxanthines were obtained using a mixture of water/ethanol/acetic acid (75:24:1%, v/v/v) as mobile phase and a flow rate of 1.0mLmin(-1). The RP-HPLC/UV method was validated in terms of limit of detection (LOD), limit of quantitation (LOQ), linearity, recovery and the precision, calculated as relative standard deviation (R.S.D.). In these conditions, the LOD was 0.10mugL(-1) for caffeine, 0.07mugL(-1) for theobromine and 0.06mugL(-1) for theophylline. The proposed method is fast, requires no extraction step or derivatization and was suitable for quantification of these methylxanthines in coffee, tea and human urine samples.
Light vision is a major element of the visual function. However, it varies from one subject to another. Many factors may modify it in the absence of amy retinal pathology (âge, fatigue, stress). A lower resistance to glare and an alteration of scotopic vision are often mentioned during medical visits. We endeavored to obtain a protection with Endotelon in subjects presenting no major retinal or ophthalmological pathology. Endotelon comes in tablets of 50 mg of procyanidolic oligomers. This compound of vegetal origin (from grape seeds) belongs to the chemical class of flavones which selectively fix on collagen and elastin fibers, thus reinforcing the structure of the vascular connective tissue. The drug efficiency on the resistance to glare and on the night morphoscopic vision was demonstrated by means of three tests: Comberg's nyctometer, Beyne's lantern and ergovision. One hundred subjects were tested in two center. In both center, a treated group received 4 tablets of Endotelon a day for five weeks and a control group received no treatment. Two patients stopped the experiment. Nyctometer: the improvement in the visual performances after glare as well as the rapidity with which these results were obtained is very significant compared to the results obtained by the control group. Visual adaptation to low luminances is also improved under treatment. Ergovision tests were performed in two light environments: a standard one and glare. These results support the previous ones. There is a narrow correlation between the decrease in visual performances after a quick retinal glare and the increase in the environmental luminance at the time of inclusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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.
Older adults have serious difficulty seeing under low illumination and at night, even in the absence of ocular disease. Optical changes in the aged eye, such as pupillary miosis and increased lens density, cannot account for the severity of this problem, and little is known about its neural basis. Dark adaptation functions were measured on 94 adults ranging in age from the 20s to the 80s to assess the rate of rod-mediated sensitivity recovery after exposure to a 98% bleach. Fundus photography and a grading scale were used to characterize macular health in subjects over age 49 in order to control for macular disease. Thresholds for each subject were corrected for lens density based on individual estimates, and pupil diameter was controlled. Results indicated that during human aging there is a dramatic slowing in rod-mediated dark adaptation that can be attributed to delayed rhodopsin regeneration. During the second component of the rod-mediated phase of dark adaptation, the rate of sensitivity recovery decreased 0.02 log unit/min per decade, and the time constant of rhodopsin regeneration increased 8.4 s/decade. The amount of time to reach within 0.3 log units of baseline scotopic sensitivity increased 2.76 min/decade. These aging-related changes in rod-mediated dark adaptation may contribute to night vision problems commonly experienced by the elderly.
An HPLC method, using detection after postcolumn derivatization with p-dimethylaminocynnamaldehyde (DMACA), was developed for the quantitative analysis of individual flavanols in food. This method was applied to flavanol determination in 56 different kinds of Spanish food products, including fruit, vegetables, legumes, beverages (cider, coffee, beer, tea, and wine), and chocolate. The determined compounds corresponded to the catechins and proanthocyanidin dimers and trimers usually present in food and, therefore, they were representative of the flavanols of low degree of polymerization consumed with the diet. The data generated could be used for calculation of the dietary intake of either individual or total flavanols, which would allow the further establishment of epidemiological correlations with the incidence of chronic diseases. Similar flavanol profiles were found in the different samples of a similar type of product, even though important variations could exist in the concentrations of total and individual flavanols among them. This was attributed to factors such as sample origin, stage of ripeness, post-harvesting conservation, and processing. Total flavanol contents varied from nondetectable in most of the vegetables to 184 mg/100 g found in a sample of broad bean. Substantial amounts were also found in some fruits, such as plum and apple, as well as in tea and red wine. Epicatechin was the most abundant flavanol, followed by catechin and procyanidin B2. In general, catechins were found in all the flavanol-containing products, but the presence of gallocatechins was only relevant in pomegranate, broad bean, lentil, grape, wine, beer, and tea, and most of the berries. Galloyled flavanols were only detected in strawberry, medlar, grape, and tea.
To determine whether there are disturbances in the rod-mediated kinetics of dark adaptation in early age-related maculopathy (ARM).
Comparative, observational case series.
Twenty older adults with early ARM as defined by one or more large (> 63 microm) drusen, focal hyperpigmentation, or both, but no choroidal neovascularization or geographic atrophy, and 16 adults in the same age range with none of these fundus features. All participants had 20/25 visual acuity or better in the tested eye.
Dark adaptation functions were measured using a modified Humphrey Field Analyzer (Zeiss Humphrey Systems, Dublin, CA) to assess the rate of rod-mediated sensitivity recovery at 12 degrees on the vertical meridian in the inferior visual field after exposure to the equivalent of a 98% bleach. Baseline (prebleach) scotopic sensitivity, visual acuity, contrast sensitivity, and photopic sensitivity were also measured.
Rod-cone break; second and third components of rod-mediated dark adaptation; time to baseline sensitivity; and baseline (prebleach) scotopic sensitivity.
Although their visual acuity was at least 20/25, patients with early ARM on average exhibited deficits in almost all rod-mediated parameters of dark adaptation as compared with age-similar healthy participants. For example, the rod-cone break was delayed approximately 10 minutes in early ARM patients as compared with healthy participants. Age-related maculopathy patients were more likely to fall outside the normal reference range for variables representing dark adaptation kinetics than for steady-state visual functions such as scotopic sensitivity. For example, 85% of ARM patients fell outside the normal reference range in at least one dark adaptation kinetic parameter, whereas only 25% of ARM patients fell outside the normal reference range for steady-state scotopic sensitivity.
Rod-mediated kinetic parameters of dark adaptation, which reflect the sensitivity recovery of the visual cycle, are disrupted early in ARM pathogenesis.
We have systematically reviewed placebo-controlled trials of V. myrtillus-extracted anthocyanosides for evidence of positive effects on night vision. Searches of computerized databases and citations in retrieved articles identified 30 trials with outcome measures relevant to vision in reduced light. Of these, 12 were placebo-controlled. The 4 most recent trials were all randomized controlled trials (RCTs) and were negative in outcome. A fifth RCT and 7 non-randomized controlled trials reported positive effects on outcome measures relevant to night vision. Negative outcome was associated with more rigorous methodology but also with lower dose level and extracts from geographically distinct sources that may differ in anthocyanoside composition. Healthy subjects with normal or above average eyesight were tested in 11 of the 12 trials. The hypothesis that V. myrtillus anthocyanosides improves normal night vision is not supported by evidence from rigorous clinical studies. There is a complete absence of rigorous research into the effects of the extract on subjects suffering impaired night vision due to pathological eye conditions. Evidence from methodologically weaker trials and auxiliary evidence from animal studies, trials of synthetic anthocyanosides, and a recent randomized controlled trial of Ribes nigrum (black currant) anthocyanosides may warrant further trials of V. myrtillus anthocyanosides in subjects with impaired night vision.
Flavonoids with two to five hydroxy groups, with or without sugar, and/or methoxy groups were studied on their effects to affect ocular blood flow.
Colored microsphere technique was used to determine the ocular blood flow in rabbit eyes.
Flavonoids with three free hydroxy (OH) groups seemed to produce the optimal effects in increasing ocular blood flow (naringenin and hesperitin, Pfalts and Bauer, Waterbury, CT). Whether the OH groups are below three (naringenin, hesperitin, Pfalts and Bauer, Waterbury, CT) or above four (Quercetin, Pfalts and Bauer, Waterbury, CT), they produced no effects on the ocular blood flow. When OH groups are four (rutin, Aldrich, Milwaukee, WI), it produced mixed effects on ocular blood flow. The attachment of rutinose and/or methoxy group in the structure did not affect the ocular blood flow one way or the other.
The ocular blood flow is increased significantly by the number of OH group in the molecule, with three the best to increase the ocular blood flow.
The aim of the present study was to determine the effect of purified high-dose anthocyanoside oligomer administration on nocturnal visual function and clinical symptoms in low-to-moderate myopia subjects. The study was a randomized, double-blind, placebo-controlled trial and involved sixty subjects with asthenopia and refractive errors between -1.00 and -8.00 diopters in both eyes. Thirty subjects were administered a purified high-dose anthocyanoside oligomer (100 mg tablet comprising 85 % anthocyanoside oligomer), and thirty were given a placebo in tablet form twice daily for 4 weeks. Prior to the treatment, the placebo and anthocyanoside groups were similar in terms of age and contrast sensitivity. Before and after treatment, subjects completed a questionnaire to determine their clinical symptoms and were also assessed for nocturnal visual function using contrast sensitivity testing. Questionnaire data analysis showed that, following treatment, twenty-two (73.3 %) anthocyanoside subjects showed improved symptoms, whereas only one placebo subject showed an improvement (Fisher's exact test, P<0.0001). Contrast sensitivity levels according to each cycle per degree significantly improved in the anthocyanoside group and remained stable in the placebo group. The mean contrast sensitivity change in the anthocyanoside group was 2.41 (SD) 1.91, compared with -0.66 (SD) 2.66 dB for the placebo group (unpaired Student's t test, P<0.0001). At all cycle per degree levels, contrast sensitivity changes in the anthocyanoside group were better than in the placebo group (unpaired Student's t test, P<0.05). The present data show that the administration of anthocyanoside oligomer appears to improve subjective symptoms and objective contrast sensitivity in myopia subjects with asthenopia.
Anthocyanins (ACs) are phenolic compounds that are distributed widely in fruits and vegetables. Although consumption of these compounds has been shown to improve visual function, the distribution of ACs in ocular tissue has not been examined in detail. The aim of this study was therefore to evaluate the ocular distribution of blackcurrant anthocyanins (BCAs) in rats and rabbits after oral, intravenous (i.v.) and intraperitoneal (i.p.) administration. Identification and quantification of ACs were carried out using high-performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-ESI-MS) and high-performance liquid chromatography (HPLC) with UV-visible detection, respectively. BCAs were identified in the plasma and whole eye after oral and i.p. administration in rats. No other peaks were detected in either plasma or ocular tissues after administration when the absorbance of the eluate was monitored at 520 nm. This finding indicates that intact forms of ACs were present in rats after administration of BCA. In rats given i.p. administration, the concentration of total ACs in the whole eye and some ocular tissues was higher than that measured in plasma. These results suggested that ACs detected in the ocular tissues were not due to residual blood. Following i.v. administration in rabbits, four ACs were identified in the plasma and several ocular tissues including the aqueous humor, cornea, sclera, choroid, ciliary body, iris and retina. A small amount of ACs was also detected in the vitreous and lens. In conclusion, this study demonstrated that BCAs were absorbed and distributed in ocular tissues as intact forms. Our data show clearly that intact forms of BCAs pass thorough the blood-aqueous barrier and blood-retinal barrier in both rats and rabbits.
The oxygen distribution in the retina of six anesthetized macaques was investigated as a model for retinal oxygenation in the human retina in and adjacent to the fovea. P(O2) was measured as a function of retinal depth under normal physiological conditions in light and dark adaptation with O(2) microelectrodes. Oxygen consumption (Q(O2)) of the photoreceptors was extracted by fitting a steady-state diffusion model to P(O2) measurements. In the perifovea, the P(O2) was 48 +/- 13 mmHg (mean and SD) at the choroid and fell to a minimum of 3.8 +/- 1.9 mmHg around the photoreceptor inner segments in dark adaptation, rising again toward the inner retina. The P(O2) in the inner half of the retina in darkness was 17.9 +/- 7.8 mmHg. When averaged over the outer retina, photoreceptor Q(O2) (called Q(av)) was 4.6 +/- 2.3 ml O(2).100 g(-1).min(-1) under dark-adapted conditions. Illumination sufficient to saturate the rods reduced Q(av) to 72 +/- 11% of the dark-adapted value. Both perifoveal and foveal photoreceptors received most of their O(2) from the choroidal circulation. While foveal photoreceptors have more mitochondria, the Q(O2) of photoreceptors in the fovea was 68% of that in the perifovea. Oxygenation in macaque retina was similar to that previously found in cats and other mammals, reinforcing the relevance of nonprimate animal models for the study of retinal oxygenation, but there was a smaller reduction in Q(O2) with light than observed in cats, which may have implications for understanding the influence of light under some clinical conditions.