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Visual Function and Macular Carotenoid Changes in Eyes with Retinal Drusen-An Open Label Randomized Controlled Trial to Compare a Micronized Lipid-Based Carotenoid Liquid Supplementation and AREDS-2 Formula.
Davey, PG, Henderson, T, Lem, DW, Weis, R, Amonoo-Monney, S, Evans, DW
Nutrients. 2020;(11)
Abstract
PURPOSE To compare the changes in visual and ocular parameters in individuals with retinal drusen who were treated with two commercially available nutritional supplements. METHODS An open-label, single-center, randomized, parallel-treatment with an observational control group design was utilized. The treatment groups included individuals with fine retinal drusen sub-clinical age-related macular degeneration (AMD), while the control group consisted of ocular normal individuals. The treatment groups were randomly assigned to the micronized lipid-based carotenoid supplement, Lumega-Z (LM), or the PreserVision Age-Related Eye Disease Study 2 (AREDS-2) soft gel (PV). Visual performance was evaluated using the techniques of visual acuity, dark adaptation recovery and contrast sensitivity, at baseline, three months, and six months. Additionally, the macular pigment optical density (MPOD) was measured. The control group was not assigned any carotenoid supplement. The right eye and left eye results were analyzed separately. RESULTS Seventy-nine participants were recruited for this study, of which 68 qualified and 56 participants had useable reliable data. Of the individuals who completed this study, 25 participants belonged to the LM group, 16 belonged to the PV group, and 15 to the control group. The LM group demonstrated statistically significant improvements in contrast sensitivity function (CSF) in both eyes at six months (p < 0.001). The LM group displayed a positive linear trend with treatment time in CSF (p < 0.001), with benefits visible after just three months of supplementation. Although there was a trend showing improvement in CSF in the PV group, the change was not significant after a Bonferroni-corrected p-value of p < 0.00625. Visual acuity, dark adaptation recovery and MPOD did not significantly improve in either treatment groups. CONCLUSION The LM group demonstrated greater and faster benefits in visual performance as measured by CSF when compared to the PV group. This trial has been registered at clinicaltrials.gov (NCT03946085).
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Tomato Phytonutrients Balance UV Response: Results from a Double-Blind, Randomized, Placebo-Controlled Study.
Groten, K, Marini, A, Grether-Beck, S, Jaenicke, T, Ibbotson, SH, Moseley, H, Ferguson, J, Krutmann, J
Skin pharmacology and physiology. 2019;(2):101-108
Abstract
BACKGROUND Our previous double-blinded, placebo-controlled cross-over study indicated that a nutritional supplement named lycopene-rich tomato nutrient complex (TNC) can protect from UVA1-induced (340-400 nm) and UVA- (320-400 nm)/UVB-induced (280-320 nm) upregulation of molecular markers associated with oxidative stress, inflammation, and ageing. OBJECTIVES in the current double-blind, randomized, placebo-controlled multicenter study, we analyze whether a similar, synergistic carotenoid-rich TNC can protect from broadband UVB-induced threshold erythema formation assessed as increase in minimal erythemal dose (MED) reading, the intensity of erythema formation, and the upregulation of molecular markers associated with inflammation and immunosuppression, and whether this correlates with carotenoid blood levels. METHODS One hundred and forty-nine healthy volunteers were randomized to two groups and subjected to a 5-week washout phase, followed by a 12-week treatment phase receiving either 15 mg lycopene, 5.8 mg phytoene and phytofluene, 0.8 mg β-carotene, 5.6 mg tocopherols from tomato extract, and 4 mg carnosic acid from rosemary extract per day or placebo made from medium-chain triglycerides. At the end of each phase, MED determination, UVB irradiation, chromametry, biopsies, and blood samples were undertaken. RESULTS The active supplement was well tolerated. Interestingly, no significant difference was seen in the MED between the active-supplement and placebo groups, as determined by visual grading by expert assessors. Of note, the carotenoid-containing supplement significantly protected against UVB-induced erythema formation measured as Δa* after the intervention minus Δa* after the washout phase as compared to the placebo. Moreover, intake of the active supplement significantly protected against UVB-induced upregulation of IL6 and TNFα as compared with the intake of placebo. Lastly, carotenoid plasma levels were significantly increased. CONCLUSION This well-tolerated carotenoid-containing supplement significantly protected against UVB-induced erythema formation and upregulation of proinflammatory cytokines in healthy volunteers.
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Application of blood concentration biomarkers in nutritional epidemiology: example of carotenoid and tocopherol intake in relation to chronic disease risk.
Prentice, RL, Pettinger, M, Neuhouser, ML, Tinker, LF, Huang, Y, Zheng, C, Manson, JE, Mossavar-Rahmani, Y, Anderson, GL, Lampe, JW
The American journal of clinical nutrition. 2019;(4):1189-1196
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BACKGROUND Biomarkers provide potential to objectively measure the intake of nutrients and foods, and thereby to strengthen nutritional epidemiology association studies. However, there are only a few established intake biomarkers, mostly based on recovery of nutrients or their metabolites in urine. Blood concentration measures provide a potential biomarker source for many additional nutritional variables, but their use in disease-association studies requires further development. OBJECTIVE The aim of this study was to apply recently proposed serum-based carotenoid and tocopherol intake biomarkers and to examine their association with the incidence of major cardiovascular diseases, cancers, and diabetes in a subset of Women's Health Initiative (WHI) cohorts. METHODS Serum concentrations of α- and β-carotene, lutein plus zeaxanthin (L + Z), and α-tocopherol were routinely measured at baseline in a subset of 5488 enrollees in WHI cohorts. Intake biomarkers for these 4 micronutrients, obtained by combining serum concentrations with participant characteristics, were recently proposed using a 153-woman feeding study within WHI. These biomarker equations are augmented here to include pertinent disease risk factors and are associated with subsequent chronic disease incidence in this WHI subset. RESULTS HRs for a doubling of micronutrient intake differed only moderately from the null for the outcomes considered. However, somewhat lower risks of specific cardiovascular outcomes, breast cancer, and diabetes were associated with a higher intake of α- and β-carotene, lower risk of diabetes was associated with higher L + Z intake, and elevated risks of certain cardiovascular outcomes were associated with a higher intake of α-tocopherol. These patterns remained following the exclusion of baseline users of dietary supplements. CONCLUSIONS Concentration biomarkers can be calculated from blood specimens obtained in large epidemiologic cohorts and applied directly in disease-association analyses, without relying on self-reported dietary data. Observed associations between carotenoid and tocopherol biomarkers and chronic disease risk could be usefully evaluated further using stored serum specimens on the entire WHI cohort. This study was registered at www.clinicaltrials.gov as NCT00000611.
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No CFH or ARMS2 Interaction with Omega-3 Fatty Acids, Low versus High Zinc, or β-Carotene versus Lutein and Zeaxanthin on Progression of Age-Related Macular Degeneration in the Age-Related Eye Disease Study 2: Age-Related Eye Disease Study 2 Report No. 18.
van Asten, F, Chiu, CY, Agrón, E, Clemons, TE, Ratnapriya, R, Swaroop, A, Klein, ML, Fan, R, Chew, EY, ,
Ophthalmology. 2019;(11):1541-1548
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PURPOSE To assess whether genotypes at 2 major loci associated with age-related macular degeneration (AMD), complement factor H (CFH), or age-related maculopathy susceptibility 2 (ARMS2), modify the response to oral nutrients for the treatment of AMD in the Age-Related Eye Disease Study 2 (AREDS2). DESIGN Post hoc analysis of a randomized trial. PARTICIPANTS White AREDS2 participants. METHODS AREDS2 participants (n = 4203) with bilateral large drusen or late AMD in 1 eye were assigned randomly to lutein and zeaxanthin, omega-3 fatty acids, both, or placebo, and most also received the AREDS supplements. A secondary randomization assessed modified AREDS supplements in 4 treatment arms: lower zinc dosage, omission of β-carotene, both, or no modification. To evaluate the progression to late AMD, fundus photographs were obtained at baseline and annual study visits, and history of treatment for late AMD was obtained at study visits and 6-month interim telephone calls. Participants were genotyped for the single-nucleotide polymorphisms rs1061170 in CFH and rs10490924 in ARMS2. Bivariate frailty models using both eyes were conducted, including a gene-supplement interaction term and adjusting for age, gender, level of education, and smoking status. The main treatment effects, as well as the direct comparison between lutein plus zeaxanthin and β-carotene, were assessed for genotype interaction. MAIN OUTCOME MEASURES The interaction between genotype and the response to AREDS2 supplements regarding progression to late AMD, any geographic atrophy (GA), and neovascular AMD. RESULTS Complete data were available for 2775 eyes without baseline late AMD (1684 participants). The participants (mean age ± standard deviation, 72.1±7.7 years; 58.5% female) were followed up for a median of 5 years. The ARMS2 risk allele was associated significantly with progression to late AMD and neovascular AMD (P = 2.40 × 10-5 and P = 0.002, respectively), but not any GA (P = 0.097). The CFH risk allele was not associated with AMD progression. Genotype did not modify significantly the response to any of the AREDS2 supplements. CONCLUSIONS CFH and ARMS2 risk alleles do not modify the response to the AREDS2 nutrient supplements with respect to the progression to late AMD (GA and neovascular AMD).
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Limited appearance of apocarotenoids is observed in plasma after consumption of tomato juices: a randomized human clinical trial.
Cooperstone, JL, Novotny, JA, Riedl, KM, Cichon, MJ, Francis, DM, Curley, RW, Schwartz, SJ, Harrison, EH
The American journal of clinical nutrition. 2018;(4):784-792
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BACKGROUND Nonvitamin A apocarotenoids occur in foods. Some function as retinoic acid receptor antagonists in vitro, though it is unclear if apocarotenoids are absorbed or accumulate to levels needed to elicit biological function. OBJECTIVE The aim of this study was to quantify carotenoids and apocarotenoids (β-apo-8'-, -10'-, -12'-, and -14'-carotenal, apo-6'-, -8'-, -10'-, -12'-, and -14'-lycopenal, retinal, acycloretinal, β-apo-13-carotenone, and apo-13-lycopenone) in human plasma after controlled consumption of carotenoid-rich tomato juices. DESIGN Healthy subjects (n = 35) consumed a low-carotenoid diet for 2 wk, then consumed 360 mL of high-β-carotene tomato juice (30.4 mg of β-carotene, 34.5 μg total β-apocarotenoids/d), high-lycopene tomato juice (42.5 mg of lycopene, 119.2 μg total apolycopenoids/d), or a carotenoid-free control (cucumber juice) per day for 4 wk. Plasma was sampled at baseline (after washout) and after 2 and 4 wk, and analyzed for carotenoids and apocarotenoids using high-pressure liquid chromatography (HPLC) and HPLC-tandem mass spectrometry, respectively. The methods used to analyze the apocarotenoids had limits of detection of ∼ 100 pmol/L. RESULTS Apocarotenoids are present in tomato juices at 0.1-0.5% of the parent carotenoids. Plasma lycopene and β-carotene increased (P < 0.001) after consuming high-lycopene and β-carotene tomato juices, respectively, while retinol remained unchanged. β-Apo-13-carotenone was found in the blood of all subjects at every visit, although elevated (P < 0.001) after consuming β-carotene tomato juice for 4 wk (1.01 ± 0.27 nmol/L) compared with both baseline (0.37 ± 0.17 nmol/L) and control (0.46 ± 0.11 nmol/L). Apo-6'-lycopenal was detected or quantifiable in 29 subjects, while β-apo-10'- and 12'-carotenal were detected in 6 and 2 subjects, respectively. No other apolycopenoids or apocarotenoids were detected. CONCLUSIONS β-Apo-13-carotenone was the only apocarotenoid that was quantifiable in all subjects, and was elevated in those consuming high-β-carotene tomato juice. Levels were similar to previous reports of all-trans-retinoic acid. Other apocarotenoids are either poorly absorbed or rapidly metabolized or cleared, and so are absent or limited in blood. β-Apo-13-carotenone may form from vitamin A and its presence warrants further investigation. This trial was registered at clinicaltrials.gov as NCT02550483.
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Colonic Mucosal Bacteria Are Associated with Inter-Individual Variability in Serum Carotenoid Concentrations.
Djuric, Z, Bassis, CM, Plegue, MA, Ren, J, Chan, R, Sidahmed, E, Turgeon, DK, Ruffin, MT, Kato, I, Sen, A
Journal of the Academy of Nutrition and Dietetics. 2018;(4):606-616.e3
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BACKGROUND Relatively high serum carotenoid levels are associated with reduced risks of chronic diseases, but inter-individual variability in serum carotenoid concentrations is modestly explained by diet. The bacterial community in the colon could contribute to the bioaccessibility of carotenoids by completing digestion of plant cells walls and by modulating intestinal permeability. OBJECTIVE To evaluate whether colonic bacterial composition is associated with serum and colon carotenoid concentrations. DESIGN The study was a randomized dietary intervention trial in healthy individuals who were at increased risk of colon cancer. Colon mucosal biopsy samples were obtained before and after 6 months of intervention without prior preparation of the bowels. PARTICIPANTS/SETTING Participants were recruited from Ann Arbor, MI, and nearby areas from July 2007 to November 2010. Biopsy data were available from 88 participants at baseline and 82 participants after 6 months. METHODS Study participants were randomized to counseling for either a Mediterranean diet or a Healthy Eating diet for 6 months. RESULTS At baseline, bacterial communities in biopsy samples from study participants in the highest vs the lowest tertile of total serum carotenoid levels differed by several parameters. Linear discriminant analysis effect size identified 11 operational taxonomic units that were significantly associated with higher serum carotenoid levels. In linear regression analyses, three of these accounted for an additional 12% of the variance in serum total carotenoid concentrations after including body mass index, smoking, and dietary intakes in the model. These factors together explained 36% of the inter-individual variance in serum total carotenoid concentrations. The bacterial community in the colonic mucosa, however, was resistant to change after dietary intervention with either a Mediterranean diet or Healthy Eating diet, each of which doubled fruit and vegetable intakes. CONCLUSIONS The colonic mucosal bacterial community was associated with serum carotenoid concentrations at baseline but was not appreciably changed by dietary intervention.
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Effects of Mixed Carotenoids on Adipokines and Abdominal Adiposity in Children: A Pilot Study.
Canas, JA, Lochrie, A, McGowan, AG, Hossain, J, Schettino, C, Balagopal, PB
The Journal of clinical endocrinology and metabolism. 2017;(6):1983-1990
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CONTEXT Carotenoids have been implicated in the regulation of adipocyte metabolism. OBJECTIVE To compare the effects of mixed-carotenoid supplementation (MCS) versus placebo on adipokines and the accrual of abdominal adiposity in children with obesity. DESIGN AND SETTING Randomized (1:1), double-blind, placebo-controlled intervention trial to evaluate the effects of MCS over 6 months in a subspecialty clinic. PARTICIPANTS Twenty (6 male and 14 female) children with simple obesity [body mass index (BMI) > 90%], a mean age (± standard deviation) of 10.5 ± 0.4 years, and Tanner stage I to V were enrolled; 17 participants completed the trial. INTERVENTION MCS (which contains β-carotene, α-carotene, lutein, zeaxanthin, lycopene, astaxanthin, and γ-tocopherol) or placebo was administered daily. MAIN OUTCOME MEASURES Primary outcomes were change in β-carotene, abdominal fat accrual (according to magnetic resonance imaging), and BMI z-score; secondary outcomes were adipokines and markers of insulin resistance. RESULTS Cross-sectional analysis of β-carotene showed inverse correlation with BMI z-score, waist-to-height ratio, visceral adipose tissue, and subcutaneous adipose tissue (SAT) at baseline. MCS increased β-carotene, total adiponectin, and high-molecular-weight adiponectin compared with placebo. MCS led to a greater reduction in BMI z-score, waist-to-height ratio, and SAT compared with placebo. The percentage change in β-carotene directly correlated with the percentage change in SAT. CONCLUSIONS The decrease in BMI z-score, waist-to-height ratio, and SAT and the concomitant increase in the concentration of β-carotene and high-molecular-weight adiponectin by MCS suggest the putative beneficial role of MCS in children with obesity.
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The effects of crocin on the symptoms of depression in subjects with metabolic syndrome.
Jam, IN, Sahebkar, AH, Eslami, S, Mokhber, N, Nosrati, M, Khademi, M, Foroutan-Tanha, M, Ghayour-Mobarhan, M, Hadizadeh, F, Ferns, G, et al
Advances in clinical and experimental medicine : official organ Wroclaw Medical University. 2017;(6):925-930
Abstract
BACKGROUND Studies have suggested that metabolic syndrome (MetS) is associated with increased depressive symptoms, and reducing depression in subjects with MetS is important. Crocin, an active component of saffron, has useful properties for subjects with MetS, including antidepressant properties. OBJECTIVES The aim of the study was to assess the effect of a preparation of crocin on the symptoms of depression in subjects with MetS, and the relationship between changes in those symptoms and the serum pro-oxidant/anti-oxidant balance (PAB). MATERIAL AND METHODS This sub-study was carried out on 34 subjects with MetS from the authors' previous randomized double-blind controlled clinical trial (RCT), all of whom met the inclusion criteria for this study. The subjects were randomly assigned to treatment and placebo groups (n = 17 in each group) and received each 30 mg of crocin (2 tablets of 15 mg) or placebo for 8 weeks. Depressive symptoms were assessed using the Beck Depression Inventory (BDI). The BDI questionnaire was completed for each subject at the baseline and at the end of the 8th week of treatment. Blood samples were taken from the subjects before and after the intervention period. Statistical analyses were performed using the SPSS for Windows, v. 16 (SPSS Inc., Chicago, USA). RESULTS Out of the 34 participants enrolled, 33 completed the trial. The degree of depression decreased significantly in the crocin group (p = 0.005), but not in the placebo group (p > 0.05), and the difference between the 2 groups was statistically significant (p = 0.013). No significant relationship was observed between changes in depression symptoms and changes in the serum PAB (p > 0.05). CONCLUSIONS This study demonstrates that at a dose of 30 mg per day for 8 weeks, crocin reduced the symptoms of depression in subjects with MetS compared to the control group, and this effect was independent of its effect on the serum PAB.
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Influences of Orally Taken Carotenoid-Rich Curly Kale Extract on Collagen I/Elastin Index of the Skin.
Meinke, MC, Nowbary, CK, Schanzer, S, Vollert, H, Lademann, J, Darvin, ME
Nutrients. 2017;(7)
Abstract
Two differently designed, spatially resolved reflectance spectroscopy-based scanners and two-photon tomography were used for noninvasive in vivo determination of cutaneous carotenoids, and collagen I/elastin aging index of dermis, respectively, in the skin of 29 healthy female volunteers between 40 and 56 years of age. The volunteers received a supplement in the form of a carotenoid-rich natural curly kale extract containing 1650 µg of carotenoids in total (three capsules of 550 µg), once a day. Measurements were taken before, after 5 months and after 10 months of daily supplementation. The results showed significantly increased values for the cutaneous carotenoids and the collagen I/elastin aging index of dermis 5 and 10 months after the beginning of the study. The obtained results show that a natural carotenoid-rich extract could prevent the aging-related collagen I degradation in the dermis and improve the extracellular matrix.
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A randomized double-blind placebo controlled phase I-II study on clinical and molecular effects of dietary supplements in men with precancerous prostatic lesions. Chemoprevention or "chemopromotion"?
Gontero, P, Marra, G, Soria, F, Oderda, M, Zitella, A, Baratta, F, Chiorino, G, Gregnanin, I, Daniele, L, Cattel, L, et al
The Prostate. 2015;(11):1177-86
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BACKGROUND Antioxidants effectiveness in prostate cancer (PCa) chemoprevention has been severely questioned, especially after the recent results of the Selenium and Vitamin E Cancer Prevention Trial. We present the results of a double-blind randomized controlled trial (dbRCT) on the pharmacokinetic, clinical, and molecular activity of dietary supplements containing lycopene, selenium, and green tea catechins (GTCs) in men with multifocal high grade prostatic intraepithelial neoplasia (mHGPIN) and/or atypical small acinar proliferation (ASAP). METHODS From 2009 to 2014, we conducted a dbRCT including 60 patients with primary mHGPIN and/or ASAP receiving daily lycopene 35 mg, selenium 55 µg, and GTCs 600 mg, or placebo for 6 months. Pharmacokinetic analysis were performed with UV-Visible spectrophotometric assay under standard (SC) and accelerated (AC) conditions. Upon plasma lycopene concentrations falling within the expected range (1.2-90 mcg/l) and no side-effects of grade >1, study proceeded to phase II (n = 50). After unblinding of results, eight men (4 per arm, 2 without and 2 with PCa, respectively) were randomly selected and totRNA extracted from "non-pathological" tissues. MicroRNA profiling was performed with the Agilent platform. Raw data processing used R-statistical language and linear models for microarray analysis. RESULTS Samples were stable except for lycopene, showing significant degradation (SC = 56%, AC = 59%) and consequently stabilized under vacuum in a dark packaging. Mean plasmatic lycopene concentration was 1,45 ± 0,4 μM. At 6 months, 53 men underwent re-biopsy and 13 (24.5%) were diagnosed with PCa (supplementation n = 10, placebo n = 3 [P = 0.053]). At a mean 37 months follow-up, 3 additional PCa were found in the placebo group. No significant variations in PSA, IPSS, and PR25 questionnaires were observed. Stronger modulation of miRNAs was present on re-biopsy in the supplementation group compared to the placebo, including: (i) overexpression of miRNAs present in PCa versus non-cancer tissue; (ii) underexpression of miRNAs suppressing PCa proliferation; (iii) detection of 35 miRNAs in PCa patients versus disease-free men, including androgen-regulated miR-125b-5p and PTEN-targeting miR-92a-3p (both upregulated). CONCLUSION Administration of high doses of lycopene, GTCs, and selenium in men harboring HGPIN and/or ASAP was associated with a higher incidence of PCa at re-biopsy and expression of microRNAs implicated in PCa progression at molecular analysis. The use of these supplements should be avoided.