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Amelioration of anxiety, depression, and chemotherapy related toxicity after crocin administration during chemotherapy of breast cancer: A double blind, randomized clinical trial.
Salek, R, Dehghani, M, Mohajeri, SA, Talaei, A, Fanipakdel, A, Javadinia, SA
Phytotherapy research : PTR. 2021;(9):5143-5153
Abstract
The effects of saffron (Crocus sativus L.) on mood disorders have already been established. More recently, its anti-neoplastic effects have provoked a great attention. This study aims to assess the effects of crocin administration during doxorubicin-based chemotherapy of breast cancer on anxiety, depression, and chemotherapy toxicity profile. Seventy-two patients with non-metastatic Her2/neu positive or triple negative breast cancer were enrolled and randomly assigned to receive either 30 mg/day of crocin or placebo during chemotherapy [2:2]. Beck's Depression and Anxiety Inventories were used at baseline and end of the trial. In addition, the ECOG Common Toxicity Criteria were applied to assess chemotherapy side-effects. After the intervention, the degree of anxiety and depression decreased significantly in the crocin group (p = .001 for both) and increased significantly in the placebo-group (p = .006 and p = .036, respectively). There were significantly higher grade II-IV leukopenia (47.2% vs. 19.4%, p = .012) in the crocin group, and grade II-IV hypersensitivity-reaction (30.6% vs. 5.6%, p = .006) in addition to neurological disorders (66.7% vs. 41.7%, p = .03) in the placebo-group. The results indicate that using crocin during chemotherapy in patients with breast cancer has ameliorated anxiety and depression. Moreover, leucopenia increased whereas hypersensitivity reaction and neurological disorders decreased in the crocin group. In addition, a trend toward survival improvement was observed, which is going to be investigated on longer follow up.
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Inflammatory markers response to crocin supplementation in patients with type 2 diabetes mellitus: A randomized controlled trial.
Behrouz, V, Sohrab, G, Hedayati, M, Sedaghat, M
Phytotherapy research : PTR. 2021;(7):4022-4031
Abstract
Inflammation and oxidative stress is a risk factor for the development of long-term consequences in patients with type 2 diabetes mellitus (T2DM). This study was designed to investigate the effects of crocin consumption on oxidative stress and inflammatory markers in patients with T2DM. In this clinical trial with a parallel-group design, 50 patients with T2DM were randomly assigned to either the crocin or the placebo group. The crocin group received 15 mg crocin twice daily, whereas the placebo group received corresponding placebos. At baseline and the end of week 12, serum high sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-ɑ (TNF-ɑ), nuclear factor-κB (NF-κB), and malondialdehyde (MDA) were measured. Compared with placebo group, crocin reduced hs-CRP (-1.03 vs. 1.42, p = .007), TNF-ɑ (-0.8 vs. 0.28, p = .009), and NF-κB (-0.39 vs. 0.01, p = .047) after 12 weeks intervention; these improvements were also significant in comparison with the baseline values. Plasma IL-6 decreased significantly in the crocin group at the end of week 12 compared to baseline (p = .037), whereas no significant change was observed in the placebo group. Plasma concentration of MDA did not change within and between groups after intervention. This study indicates that daily administration of 30 mg crocin supplement to patients with T2DM reduces the concentrations of hs-CRP, TNF-ɑ, and NF-κB which are involved in the pathogenesis of complications of T2DM.
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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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Effects of crocin and saffron aqueous extract on gene expression of SIRT1, AMPK, LOX1, NF-κB, and MCP-1 in patients with coronary artery disease: A randomized placebo-controlled clinical trial.
Abedimanesh, N, Motlagh, B, Abedimanesh, S, Bathaie, SZ, Separham, A, Ostadrahimi, A
Phytotherapy research : PTR. 2020;(5):1114-1122
Abstract
This trial evaluated the potential impacts of saffron aqueous extract (SAE) and its main carotenoid on some of the atherosclerosis-related gene expression and serum levels of oxidized low-density cholesterol (ox-LDL) and Monocyte chemoattractant protein 1 (MCP-1) in patients with coronary artery disease (CAD). Participants of this randomized controlled trial included 84 CAD patients who categorized into three groups: Group 1 received crocin (30 mg/day), Group 2 SAE (30 mg/day), and Group 3 placebo for 8 weeks. Gene expression of Sirtuin 1 (SIRT1), 5'-adenosine monophosphate-activated protein kinase (AMPK), Lectin-like oxidized LDL receptor 1 (LOX1), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and MCP-1 in peripheral blood mononuclear cells assessed by real-time PCR. Furthermore, serum ox-LDL and MCP-1 levels measured at the beginning and end of the intervention. Compared with the placebo group, gene expression of SIRT1 and AMPK increased significantly in the crocin group (p = .001), and the expression of LOX1 and NF-κB decreased significantly (p = .016 and .004, respectively). Serum ox-LDL levels decreased significantly in the crocin group after the intervention (p = .002) while MCP-1 levels decreased both in crocin and SAE groups (p = .001). Crocin may have beneficial effects on CAD patients by increasing the gene expression of SIRT1 and AMPK and decreasing the expression of LOX1 and NF-κB.
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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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Abstract
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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Abstract
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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Changes in dietary intake, plasma carotenoids and erythrocyte membrane fatty acids in breast cancer survivors after a lifestyle intervention: results from a single-arm trial.
Buckland, G, Travier, N, Arribas, L, Del Barco, S, Pernas, S, Zamora, E, Bellet, M, Cirauqui, B, Margelí, M, Muñoz, M, et al
Journal of human nutrition and dietetics : the official journal of the British Dietetic Association. 2019;(4):468-479
Abstract
BACKGROUND The influence of nutrition on breast cancer prognosis is still inconclusive and therefore dietary interventions incorporating dietary biomarkers are needed to confirm compliance with dietary goals and clarify biological mechanisms. The present study assessed whether a lifestyle intervention in breast cancer survivors could affect dietary biomarkers of fruit and vegetables and fatty acids. METHODS In this phase II single-arm trial, 37 overweight/obese early stage breast cancer patients completed a 12-week diet and exercise intervention. The intervention involved 1-h weekly diet sessions delivered by a dietician and 75-min bi-weekly physical activity sessions of moderate-to-high intensity led by trained monitors. Before and after the intervention, three 24-h dietary recalls were carried out to calculate nutrient intakes and, in addition, blood samples were taken to measure plasma carotenoids, vitamin E and retinol concentrations and erythrocyte membrane fatty acid (EFA) composition. Wilcoxon signed rank tests were used to assess changes in dietary and biomarkers measurements over the intervention period. RESULTS After the intervention, there was a significant increase in the intake of dietary carotenoids (+15.1% compared to baseline) but not plasma carotenoids levels (+6.3%). Regarding the EFA levels, we observed a significant decrease in percentage of saturated fatty acids (-1.4%) and n-6 polyunsaturated fatty acids (-2.9%) and an increase in monounsaturated fatty acids (1.7%) and total and long-chain n-3 polyunsaturated fatty acids (by 13.1% and 13.7%, respectively). A favourable decrease in the ratio of long-chain n-6 to n-3 polyunsaturated fatty acids (-9.1%) was also observed. CONCLUSIONS After a short-term diet and exercise intervention in overweight/obese breast cancer survivors, we observed significant changes in dietary nutrients and fatty acid biomarkers, suggesting positive dietary changes that could be relevant for breast cancer prognosis.
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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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Compared to an Oatmeal Breakfast, Two Eggs/Day Increased Plasma Carotenoids and Choline without Increasing Trimethyl Amine N-Oxide Concentrations.
Missimer, A, Fernandez, ML, DiMarco, DM, Norris, GH, Blesso, CN, Murillo, AG, Vergara-Jimenez, M, Lemos, BS, Medina-Vera, I, Malysheva, OV, et al
Journal of the American College of Nutrition. 2018;(2):140-148
Abstract
BACKGROUND Habitual consumption of eggs has been hypothesized to positively modify biomarkers of cardiovascular disease risk through proposed antioxidant properties. OBJECTIVES To examine this relationship, 50 young, healthy men and women were enrolled into a randomized crossover clinical intervention. METHODS Participants consumed either 2 eggs per day or one packet of oatmeal a day for 4 weeks, followed by a 3-week wash-out and crossed over to the alternate breakfast. Fasting blood samples and peripheral blood mononuclear cells (PBMCs) were collected at the end of each intervention period. RESULTS Increases in plasma large high-density lipoprotein (HDL) and large low-density lipoprotein (LDL) particle concentrations as measured by nuclear magnetic resonance were found following egg consumption (p < 0.001, p < 0.05), respectively, with increases in apolipoprotein concentration as well (p < 0.05). Though there was no difference in the intake of antioxidants lutein and zeaxanthin, a significant increase in plasma concentrations of these carotenoids was observed (p < 0.001) after egg consumption. There was no change in lecithin-cholesterol acyl transferase, cholesteryl ester transfer protein, or paroxanase-1 arylesterase activities between breakfast interventions. Dietary and plasma choline were both higher following egg consumption compared to oatmeal consumption (p < 0.001); however, there was no change in plasma trimethylamine N-oxide (TMAO) concentrations. Two eggs per day had no impact on PBMC gene expression related to cholesterol metabolism, oxidation, or TMAO production. CONCLUSIONS These results suggest that compared to oatmeal, consumption of 2 eggs for breakfast provided increased plasma carotenoids and improved biomarkers of cardiovascular disease (CVD) risk while not affecting TMAO levels in this population.
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Supplementation with macular carotenoids reduces psychological stress, serum cortisol, and sub-optimal symptoms of physical and emotional health in young adults.
Stringham, NT, Holmes, PV, Stringham, JM
Nutritional neuroscience. 2018;(4):286-296
Abstract
PURPOSE Oxidative stress and systemic inflammation are the root cause of several deleterious effects of chronic psychological stress. We hypothesize that the antioxidant and anti-inflammatory capabilities of the macular carotenoids (MCs) lutein, zeaxanthin, and meso-zeaxanthin could, via daily supplementation, provide a dietary means of benefit. METHODS A total of 59 young healthy subjects participated in a 12-month, double-blind, placebo-controlled trial to evaluate the effects of MC supplementation on blood cortisol, psychological stress ratings, behavioural measures of mood, and symptoms of sub-optimal health. Subjects were randomly assigned to one of three groups: placebo, 13 mg, or 27 mg / day total MCs. All parameters were assessed at baseline, 6 months, and 12 months. Serum MCs were determined via HPLC, serum cortisol via ELISA, and macular pigment optical density (MPOD) via customized heterochromatic flicker photometry. Behavioural data were obtained via questionnaire. RESULTS Significant baseline correlations were found between MPOD and Beck anxiety scores (r = -0.28; P = 0.032), MPOD and Brief Symptom Inventory scores (r = 0.27; P = 0.037), and serum cortisol and psychological stress scores (r = 0.46; P < 0.001). Supplementation for 6 months improved psychological stress, serum cortisol, and measures of emotional and physical health (P < 0.05 for all), versus placebo. These outcomes were either maintained or improved further at 12 months. CONCLUSIONS Supplementation with the MCs significantly reduces stress, cortisol, and symptoms of sub-optimal emotional and physical health. Determining the basis for these effects, whether systemic or a more central (i.e. brain) is a question that warrants further study.