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Polycystic ovarian syndrome (PCOS) is related to pro‐apoptotic and pro‐inflammatory conditions generated by Endoplasmic reticulum (ER) stress. This study aimed to determine the effect of Astaxanthin (ASX), as carotenoid with potent antioxidant and anti‐inflammatory properties, on serum inflammatory markers, apoptotic factors and ER stress‐apoptotic genes in peripheral blood mononuclear cells (PBMCs) of women with PCOS. This randomized, double‐blind clinical trial included 56 PCOS patients aged 18–40. For 8 weeks, subjects were randomly assigned to one of two groups: either 12 mg ASX (n = 28) or placebo (n = 28). Real‐time PCR was used to quantify gene expression associated with ER stress‐apoptosis in PCOS women's PBMCs. The levels of TNF‐α, IL18, IL6 and CRP were determined by obtaining blood samples from all patients before and after the intervention using Enzyme‐linked immunosorbent assay (ELISA). Also, the levels of active caspase‐3 and caspase‐8 were detected in the PBMC by ELISA kit. Furthermore, we evaluated the efficacy of ASX on disease symptoms. Following the 8‐week intervention, ASX supplementation was able to reduce the expression of GRP78 (p = 0.051), CHOP (p = 0.008), XBP1 (p = 0.002), ATF4 (0.038), ATF6 (0.157) and DR5 (0.016) when compared to the placebo. However, this decrease was not statistically significant for ATF6 (p = 0.067) and marginally significant for GRP78 (p = 0.051). The levels of TNF‐α (p = 0.009), IL‐18 (p = 0.003), IL‐6 (p = 0.013) and active caspase‐3 (p = 0.012) were also statistically significant lower in the therapy group. However, there was no significant difference in CRP (p = 0.177) and caspase‐8 (p = 0.491) levels between the treatment and control groups. In our study, ASX had no significant positive effect on BMI, hirsutism, hair loss and regularity of the menstrual cycle. It appears that ASX may benefit PCOS by changing the ER stress‐apoptotic pathway and reducing serum inflammatory markers; however, additional research is required to determine this compound's potential relevance.

Astaxanthin (ASTX) is an antioxidant agent. Recently, its use has been focused on the prevention of diabetes and atherosclerosis. We examined the effects of astaxanthin supplementation for 12 weeks on glucose metabolism, glycemic control, insulin sensitivity, lipid profiles and anthropometric indices in healthy volunteers including subjects with prediabetes with a randomized, placebo-controlled trial. Methods: We enrolled 53 subjects who met our inclusion criteria and administered them with 12 mg astaxanthin or a placebo once daily for 12 weeks. Subsequently, their HbA1c levels, lipid profiles and biochemical parameters were determined. The participants also underwent a 75 g oral glucose tolerance test (OGTT), vascular endothelial function test and measurement of the visceral fat area. Results: After astaxanthin supplementation for 12 weeks, glucose levels after 120 min in a 75 g OGTT significantly decreased compared to those before supplementation. Furthermore, the levels of HbA1c (5.64 ± 0.33 vs. 5.57 ± 0.39%, p < 0.05), apo E (4.43 ± 1.29 vs. 4.13 ± 1.24 mg/dL, p < 0.05) and malondialdehyde-modified low-density lipoprotein (87.3 ± 28.6 vs. 76.3 ± 24.6 U/L, p < 0.05) were also reduced, whereas total cholesterol (TC), triglyceride (TG) and high-density lipoprotein-C (HDL-C) levels were unaltered. The Matuda index, which is one of the parameters of insulin resistance, was improved in the ASTX group compared to that before supplementation. Conclusions: our results suggest that ASTX may have preventive effects against diabetes and atherosclerosis and may be a novel complementary treatment option for the prevention of diabetes in healthy volunteers, including subjects with prediabetes, without adverse effects.

Phaeodactylum tricornutum (PT) is a microalgae extract that contains fucoxanthin and has been shown to enhance cognitive function in younger populations. The present study assessed if PT supplementation affects cognition in healthy, young-old, physically active adults with self-perceptions of cognitive and memory decline. Methods: Forty-three males and females (64.3 ± 6.0 years, 79.8 ± 16.0 kg, 27.0 ± 4.0 kg/m2) with perceptions of cognitive and memory decline completed the double-blind, randomized, parallel-arm, placebo-controlled intervention clinical trial. Participants were counterbalanced by sex and BMI and randomly allocated to their respective 12-week supplementation interventions, which were either the placebo (PL) or 1100 mg/day of PT containing 8.8 mg of fucoxanthin (FX). Fasting blood samples were collected, and cognitive assessments were performed during the testing session at 0, 4, and 12 weeks of intervention. The data were analyzed by multivariate and univariate general linear model (GLM) analyses with repeated measures, pairwise comparisons, and mean changes from baseline analysis with 95% confidence intervals (CIs) to assess the clinical significance of the findings. Results: FX supplementation significantly affected (p < 0.05) or exhibited tendencies toward significance (p > 0.05 to p < 0.10 with effect sizes ranging from medium to large) for word recall, picture recognition reaction time, Stroop color–word test, choice reaction time, and digit vigilance test variables. Additionally, FX supplementation promoted a more consistent clinical improvement from baseline values when examining mean changes with 95% CIs, although most differences were seen over time rather than between groups. Conclusions: The results demonstrate some evidence that FX supplementation can improve working and secondary memory, vigilance, attention, accuracy, and executive function. There was also evidence that FX promoted more positive effects on insulin sensitivity and perceptions about sleep quality with no negative effects on clinical blood panels or perceived side effects. Additional research should investigate how FX may affect cognition in individuals perceiving memory and cognitive decline. Registered clinical trial #NCT05759910.

Background and Objective Astaxanthin is a naturally occurring carotenoid with high anti-oxidant properties, but it is a very lipophilic compound with low oral bioavailability. This study was conducted to compare the pharmacokinetic parameters of a novel astaxanthin preparation based on micellar solubilization technology, NovaSOL ® 400-mg capsules (Test product), and those of astaxanthin 400-mg capsules (reference product), after single oral dose administration to healthy male adults. Methods A single oral dose (400 mg equivalent to 8 mg astaxanthin) of test and reference astaxanthin were administered with 240 mL of water to 12 volunteers according to crossover design, in two phases, with a washout period of 1 week in between. Blood samples were collected at hourly intervals for the first 12 h, then at 24.0, 48.0, and 72.0 h after administration. Aliquots of plasma were centrifuged and the clear supernatant was injected into the high performance liquid chromatography–diode array detection (HPLC-DAD) system. Plasma concentration of astaxanthin versus time profiles were constructed, and the primary pharmacokinetic parameters, maximum concentration ( C max ), area under concentration time curve from time of administration (0) to time (t) [AUC 0-t ] or to infinity ∞, [AUC 0-∞ ],  half-life ( T ½ ) and time to reach C max ( T max ) were calculated. Results The test micellar astaxanthin reached a C max of 7.21 µg/ml after 3.67 h compared to only 3.86 µg/ml after 8.5 h for the reference native astaxanthin. Conclusion Micellar formulation of astaxanthin is capable of producing a high concentration of astaxanthin in plasma in a shorter time, thereby expected to provide faster potential therapeutic efficacy.

This study aimed to investigate whether supplementation with 12 mg⋅day−1 astaxanthin for 7 days can improve exercise performance and metabolism during a 40 km cycling time trial. A randomised, double-blind, crossover design was employed. Twelve recreationally trained male cyclists (VO2peak: 56.5 ± 5.5 mL⋅kg−1⋅min−1, Wmax: 346.8  ± 38.4 W) were recruited. Prior to each experimental trial, participants were supplemented with either 12 mg⋅day−1 astaxanthin or an appearance-matched placebo for 7 days (separated by 14 days of washout). On day 7 of supplementation, participants completed a 40 km cycling time trial on a cycle ergometer, with indices of exercise metabolism measured throughout. Time to complete the 40 km cycling time trial was improved by 1.2 ± 1.7% following astaxanthin supplementation, from 70.76 ± 3.93 min in the placebo condition to 69.90 ± 3.78 min in the astaxanthin condition (mean improvement = 51 ± 71 s, p = 0.029, g = 0.21). Whole-body fat oxidation rates were also greater (+0.09 ± 0.13 g⋅min−1, p = 0.044, g = 0.52), and the respiratory exchange ratio lower (−0.03 ± 0.04, p = 0.024, g = 0.60) between 39–40 km in the astaxanthin condition. Supplementation with 12 mg⋅day−1 astaxanthin for 7 days provided an ergogenic benefit to 40 km cycling time trial performance in recreationally trained male cyclists and enhanced whole-body fat oxidation rates in the final stages of this endurance-type performance event.

Background/Objective: Paprika xanthophylls (PXs) have potent antioxidant properties and are believed to improve oxygen delivery (DO2) efficiency by enhancing red blood cell (RBC) deformability. This study investigated whether PX ingestion improves endurance performance and subsequently enhances cognitive function by improving brain microcirculation. Methods: A crossover design was used to compare the effects of PX ingestion and a control condition in 21 healthy college students (18 males, 3 females). Each participant served as their own control, completing both conditions in a randomized order with a one-month washout period to eliminate any carryover effects. The participants underwent an incremental load test, a constant load test, the Trail Making Test Type B (TMT-B), and the Stroop test (ST). Results: In the incremental tests, the PX group showed a significantly lower heart rate (p = 0.032) and higher exercise efficiency (EE) (p = 0.004). In the constant load test, heart rate was lower (p = 0.020), and EE was higher (p = 0.030). No significant between-group differences were found in the cognitive tests; however, the PX group showed significant improvements in the TMT-B (p = 0.034) and ST interference rate I (p = 0.040). Conclusions: It is speculated that PX intake may improve DO2 efficiency, which could contribute to the observed enhancements in endurance performance and, in turn, positively affect cognitive function by optimizing the brain’s oxygenation state. However, due to the absence of a placebo control group and unmeasured RBC deformability and cerebral blood flow, as well as a significant male predominance, this study’s results should be interpreted with caution.

Firefighters are at risk for cardiovascular disease due to occupational-related inflammation, oxidative stress, and lifestyle practices. Astaxanthin (AX) possesses anti-inflammatory/antioxidant and purported ergogenic properties. This study examined the impact of supplementing the diet with 12 mg/d AX for four weeks on markers of inflammation, oxidative stress, cardiometabolic health, exercise capacity, and occupation-related performance in career firefighters. In a randomized, double-blinded, placebo-controlled, crossover fashion, 15 male career firefighters (34.5 ± 7.4 years; 177.7 ± 7.0 cm; 95.6 ± 12.0 kg; 30.1 ± 2.9 kg/m ; 11.03 ± 6.85 years of service) ingested 12 mg/d of AX (AstaReal®, AstaReal AB, Nacka, SWE) or placebo (PLA) for four weeks while following a standardized resistance training program. After each treatment, testing sessions were completed to assess inflammatory markers, oxidative stress markers, cardiopulmonary exercise capacity, and performance to a fire ground test (FGT) consisting of nine fire suppressive activities. Data were analyzed using general linear model (GLM) analysis with repeated measures. Clinical significance was assessed via mean changes from baseline with 95% confidence intervals. Analysis of mean percent changes from baseline revealed that AX supplementation lessened the inflammatory response to to performing an incremental maximal exercise test and attenuated increases in interleukin-1β, cortisol, and uric acid in response to performing fire suppressive activities compared to when they ingested PLA. However, most of these effects were within groups rather than between groups. Additionally, there was evidence that AX ingestion increased the ventilatory anaerobic threshold. Four weeks of AX supplementation did not significantly affect fasting markers of oxidative stress, blood lipids, performance during the FGT, general clinical chemistry panels, or self-reported side effects. Results provide some evidence that AX supplementation may help mediate occupation-related inflammation in response to high-intensity, short-duration exercise in firefighters. More research is warranted to determine if long-term supplementation can improve cardiometabolic risk in this population. ISRCTN10901752.

Research question In a randomized, triple-blind, placebo-controlled clinical trial (RCT), we investigated the effect of astaxanthin (AST) on pro-inflammatory cytokines, oxidative stress (OS) markers, and assisted reproductive technology (ART) outcomes in 44 infertile Polycystic Ovary Syndrome (PCOS) patients. Design Patients with PCOS were randomly divided into two groups. The intervention group received 6 mg AST, and the control group received placebo daily for 8 weeks. Blood samples were obtained from all patients before and after intervention and follicular fluid (FF) was collected during the ART procedure. Interleukin (IL) ‐6, IL‐1β were evaluated from serum samples and FF and OS markers (malondialdehyde [MDA], catalase [CAT], superoxide dismutase [SOD], and reactive oxygen species [ROS]) were measured from FF. The groups were compared for ART outcomes as well. Results A significant decrease in IL-6 and IL-1β concentrations (both, P = < 0.01) serum levels was found following AST treatment. FF cytokine levels and OS markers did not differ significantly between the groups. Reproductive outcomes, including the number of oocytes retrieved (P = 0.01), the MII oocyte count (P = 0.007), oocyte maturity rate (MII %) (P = 0.02) and number of frozen embryos (P = 0.03) significantly improved after intervention. No significant differences were found in chemical, clinical and multiple pregnancies between the groups. Conclusions AST pretreatment may modify inflammation and improve ART outcomes in PCOS infertile patients. Further investigations are recommended to verify these findings.

The macular carotenoids lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ) accumulate at the macula, where they are collectively referred to as macular pigment (MP). Augmentation of this pigment, typically achieved through diet and supplementation, enhances visual function and protects against progression of age-related macular degeneration. However, it is known that eggs are a rich dietary source of L and Z, in a highly bioavailable matrix. In this single-blind placebo-controlled study, L- and MZ-enriched eggs and control non-enriched eggs were fed to human subjects (mean age 41 and 35 years, respectively) over an 8-week period, and outcome measures included MP, visual function and serum concentrations of carotenoids and cholesterol. Serum carotenoid concentrations increased significantly in control and enriched egg groups, but to a significantly greater extent in the enriched egg group (P<0·001 for L, Z and MZ). There was no significant increase in MP in either study group post intervention, and we saw no significant improvement in visual performance in either group. Total cholesterol increased significantly in each group, but it did not exceed the upper limit of the normative range (6·5 mmol/l). Therefore, carotenoid-enriched eggs may represent an effective dietary source of L, Z and MZ, reflected in significantly raised serum concentrations of these carotenoids, and consequentially improved bioavailability for capture by target tissues. However, benefits in terms of MP augmentation and /or improved visual performance were not realised over the 8-week study period, and a study of greater duration will be required to address these questions.

BackgroundDiabetes is known to affect visual function before onset of retinopathy (diabetic retinopathy (DR)). Protection of visual function may signal disruption of mechanisms underlying DR.MethodsThis was a 6-month randomised, controlled clinical trial of patients with type 1 and type 2 diabetes with no retinopathy or mild to moderate non-proliferative retinopathy assigned to twice daily consumption of placebo or a novel, multi-component formula containing xanthophyll pigments, antioxidants and selected botanical extracts. Measurement of contrast sensitivity, macular pigment optical density, colour discrimination, 5-2 macular threshold perimetry, Diabetic Peripheral Neuropathy Symptoms, foveal and retinal nerve fibre layer thickness, glycohaemoglobin (HbA1c), serum lipids, 25-OH-vitamin D, tumour necrosis factor α (TNF-a) and high-sensitivity C reactive protein (hsCRP) were taken at baseline and 6 months. Outcomes were assessed by differences between and within groups at baseline and at study conclusion using meand ± SDs and t tests (p<0.05) for continuous variables.ResultsThere were no significant intergroup differences at baseline. At 6 months, subjects on active supplement compared with placebo had significantly better visual function on all measures (p values ranging from 0.008 to <0.0001), significant improvements in most serum lipids (p values ranging from 0.01 to 0.0004), hsCRP (p=0.01) and diabetic peripheral neuropathy (Fisher's exact test, p=0.0024) No significant changes in retinal thickness, HbA1c, total cholesterol or TNF-α were found between the groups.ConclusionsThis study provides strong evidence of clinically meaningful improvements in visual function, hsCRP and peripheral neuropathy in patients with diabetes, both with and without retinopathy, and without affecting glycaemic control.Trial registration numberwww.ClinicalTrials.gov Identifier: NCT01646047