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A randomized, phase 1, placebo-controlled trial of APG-157 in oral cancer demonstrates systemic absorption and an inhibitory effect on cytokines and tumor-associated microbes.
Basak, SK, Bera, A, Yoon, AJ, Morselli, M, Jeong, C, Tosevska, A, Dong, TS, Eklund, M, Russ, E, Nasser, H, et al
Cancer. 2020;126(8):1668-1682
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APG-157 is a botanical drug containing multiple polyphenols that delivers the active components to oromucosal tissues near the tumour target. APG-157 slowly disintegrates in the oral cavity over 15 to 20 minutes to release the drug substance. The drug substance is a precise, rational combination of multiple molecules derived from Curcuma longa wherein curcumin is the principal component. The main aim of this study was to determine the pharmacokinetics and safety of the orally delivered pastille (APG-157) when used by normal subjects and patients with cancer. This study is a randomised, double-blind, placebo-controlled trial. A total of 32 subjects were enrolled, and 25 completed the study (13 normal individuals and 12 patients with oral cancer). Results demonstrated that transoral APG-157 treatment leads to systemic absorption of curcumin and its analogs. There was a statistically significant concentration reduction in inflammatory cytokines and Bacteroides species noted in the salivary cells. Pre-treatment and post-treatment tumour samples from patients with cancer demonstrated T-cell recruitment to the tumour microenvironment. Authors conclude that APG-157 is absorbed well, reduces inflammation, and attracts T-cells to the tumour thus, it can be potentially used in combination with immunotherapy drugs. Furthermore, a long-term evaluation of immune checkpoint blockade with and without APG-157 could provide a clear understanding of the usefulness of APG-157 as either an adjuvant or neoadjuvant therapeutic agent for patients with advanced or recurrent head and neck cancer.
Abstract
BACKGROUND Although curcumin's effect on head and neck cancer has been studied in vitro and in vivo, to the authors' knowledge its efficacy is limited by poor systemic absorption from oral administration. APG-157 is a botanical drug containing multiple polyphenols, including curcumin, developed under the US Food and Drug Administration's Botanical Drug Development, that delivers the active components to oromucosal tissues near the tumor target. METHODS A double-blind, randomized, placebo-controlled, phase 1 clinical trial was conducted with APG-157 in 13 normal subjects and 12 patients with oral cancer. Two doses, 100 mg or 200 mg, were delivered transorally every hour for 3 hours. Blood and saliva were collected before and 1 hour, 2 hours, 3 hours, and 24 hours after treatment. Electrocardiograms and blood tests did not demonstrate any toxicity. RESULTS Treatment with APG-157 resulted in circulating concentrations of curcumin and analogs peaking at 3 hours with reduced IL-1β, IL-6, and IL-8 concentrations in the salivary supernatant fluid of patients with cancer. Salivary microbial flora analysis showed a reduction in Bacteroidetes species in cancer subjects. RNA and immunofluorescence analyses of tumor tissues of a subject demonstrated increased expression of genes associated with differentiation and T-cell recruitment to the tumor microenvironment. CONCLUSIONS The results of the current study suggested that APG-157 could serve as a therapeutic drug in combination with immunotherapy. LAY SUMMARY Curcumin has been shown to suppress tumor cells because of its antioxidant and anti-inflammatory properties. However, its effectiveness has been limited by poor absorption when delivered orally. Subjects with oral cancer were given oral APG-157, a botanical drug containing multiple polyphenols, including curcumin. Curcumin was found in the blood and in tumor tissues. Inflammatory markers and Bacteroides species were found to be decreased in the saliva, and immune T cells were increased in the tumor tissue. APG-157 is absorbed well, reduces inflammation, and attracts T cells to the tumor, suggesting its potential use in combination with immunotherapy drugs.
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Green tea (Camellia sinensis) for the prevention of cancer.
Filippini, T, Malavolti, M, Borrelli, F, Izzo, AA, Fairweather-Tait, SJ, Horneber, M, Vinceti, M
The Cochrane database of systematic reviews. 2020;3(3):CD005004
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Brewed tea is obtained from the infusion of leaves and buds of Camellia sinensis. The most consumed types of tea are green and black tea. Due to the high content of antioxidant compounds, a great deal of attention has been given to green tea regarding the possible prevention of chronic diseases and cancer, as well as possible beneficial effects on cardiovascular disease, insulin sensitivity and lipid profiles. The main aim of this review was to assess the association between green tea consumption and the risk of developing cancer in epidemiologic studies. This study is an update of a previously published Cochrane review based on studies in which participants consumed green tea orally, either as drinkable tea or as extracts. One hundred and forty-two epidemiological studies of experimental and nonexperimental design were included with a total of 1,100,000 participants. Findings yielded inconsistent results for the effect of green tea consumption on cancer risk, despite some indications of a beneficial effect of green tea on a few site-specific cancers. Authors conclude that the epidemiological evidence appears to be still inadequate to support a beneficial effect of green tea on cancer risk.
Abstract
BACKGROUND This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (2009, Issue 3).Tea is one of the most commonly consumed beverages worldwide. Teas from the plant Camellia sinensis can be grouped into green, black and oolong tea, and drinking habits vary cross-culturally. C sinensis contains polyphenols, one subgroup being catechins. Catechins are powerful antioxidants, and laboratory studies have suggested that these compounds may inhibit cancer cell proliferation. Some experimental and nonexperimental epidemiological studies have suggested that green tea may have cancer-preventative effects. OBJECTIVES To assess possible associations between green tea consumption and the risk of cancer incidence and mortality as primary outcomes, and safety data and quality of life as secondary outcomes. SEARCH METHODS We searched eligible studies up to January 2019 in CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and reference lists of previous reviews and included studies. SELECTION CRITERIA We included all epidemiological studies, experimental (i.e. randomised controlled trials (RCTs)) and nonexperimental (non-randomised studies, i.e. observational studies with both cohort and case-control design) that investigated the association of green tea consumption with cancer risk or quality of life, or both. DATA COLLECTION AND ANALYSIS Two or more review authors independently applied the study criteria, extracted data and assessed methodological quality of studies. We summarised the results according to diagnosis of cancer type. MAIN RESULTS In this review update, we included in total 142 completed studies (11 experimental and 131 nonexperimental) and two ongoing studies. This is an additional 10 experimental and 85 nonexperimental studies from those included in the previous version of the review. Eleven experimental studies allocated a total of 1795 participants to either green tea extract or placebo, all demonstrating an overall high methodological quality based on 'Risk of bias' assessment. For incident prostate cancer, the summary risk ratio (RR) in the green tea-supplemented participants was 0.50 (95% confidence interval (CI) 0.18 to 1.36), based on three studies and involving 201 participants (low-certainty evidence). The summary RR for gynaecological cancer was 1.50 (95% CI 0.41 to 5.48; 2 studies, 1157 participants; low-certainty evidence). No evidence of effect of non-melanoma skin cancer emerged (summary RR 1.00, 95% CI 0.06 to 15.92; 1 study, 1075 participants; low-certainty evidence). In addition, adverse effects of green tea extract intake were reported, including gastrointestinal disorders, elevation of liver enzymes, and, more rarely, insomnia, raised blood pressure and skin/subcutaneous reactions. Consumption of green tea extracts induced a slight improvement in quality of life, compared with placebo, based on three experimental studies. In nonexperimental studies, we included over 1,100,000 participants from 46 cohort studies and 85 case-control studies, which were on average of intermediate to high methodological quality based on Newcastle-Ottawa Scale 'Risk of bias' assessment. When comparing the highest intake of green tea with the lowest, we found a lower overall cancer incidence (summary RR 0.83, 95% CI 0.65 to 1.07), based on three studies, involving 52,479 participants (low-certainty evidence). Conversely, we found no association between green tea consumption and cancer-related mortality (summary RR 0.99, 95% CI 0.91 to 1.07), based on eight studies and 504,366 participants (low-certainty evidence). For most of the site-specific cancers we observed a decreased RR in the highest category of green tea consumption compared with the lowest one. After stratifying the analysis according to study design, we found strongly conflicting results for some cancer sites: oesophageal, prostate and urinary tract cancer, and leukaemia showed an increased RR in cohort studies and a decreased RR or no difference in case-control studies. AUTHORS' CONCLUSIONS Overall, findings from experimental and nonexperimental epidemiological studies yielded inconsistent results, thus providing limited evidence for the beneficial effect of green tea consumption on the overall risk of cancer or on specific cancer sites. Some evidence of a beneficial effect of green tea at some cancer sites emerged from the RCTs and from case-control studies, but their methodological limitations, such as the low number and size of the studies, and the inconsistencies with the results of cohort studies, limit the interpretability of the RR estimates. The studies also indicated the occurrence of several side effects associated with high intakes of green tea. In addition, the majority of included studies were carried out in Asian populations characterised by a high intake of green tea, thus limiting the generalisability of the findings to other populations. Well conducted and adequately powered RCTs would be needed to draw conclusions on the possible beneficial effects of green tea consumption on cancer risk.
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Probiotic fruit beverages with different polyphenol profiles attenuated early insulin response.
Xu, J, Jönsson, T, Plaza, M, Håkansson, Å, Antonsson, M, Ahrén, IL, Turner, C, Spégel, P, Granfeldt, Y
Nutrition journal. 2018;17(1):34
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Elevated levels of blood glucose after eating, known as postprandial hyperglycaemia, contribute to the development of cardiovascular disease and type 2 diabetes. Postprandial hyperglycaemia is a condition that can be improved through lifestyle and diet modifications. The aim of the study was to investigate and compare the postprandial glycaemic and insulin responses after consuming five different probiotic fruit or vegetable beverages. A secondary aim was to analyse beverages for their polyphenol content and antioxidative capacity. The study is a randomised, controlled, crossover study which included twelve healthy young adults (6 men and 6 women) with a BMI of 24.3 +/- 2.4kg/m2. Results indicate that Bilberry showed the most profound insulin lowering effect, followed by Rose hip. The analysis also showed that Bilberry had the highest values of the total phenolic compounds and flavonols, whereas Mango had the lowest. The highest values of antioxidative capacity were found in Bilberry and Beetroot. Authors conclude that consumption of food products that induce a lower insulin response may enhance insulin sensitivity.
Abstract
BACKGROUND Consumption of polyphenol-rich fruits and vegetables may improve postprandial glucose and insulin levels and hence promote well-being. Previously it has been observed that consumption of bilberry decreases the postprandial insulin demand. The intention with the present study was to compare the impact of different supplements with various polyphenol profiles, on the postprandial glucose and insulin responses in healthy young adults. METHODS In a randomized, controlled, crossover study the postprandial glycemic and insulin responses were observed in eleven healthy adults after intake of five different beverages containing bilberry (European blueberry), blackcurrant, beetroot, mango and rose hip, respectively; all drinks were enriched with the same composition of fermented oatmeal and probiotics. The control was a glucose drink. The profile and content of the polyphenols in the different beverages were determined by HPLC-DAD analysis. The antioxidative capacity of the different beverages were measured by TEAC and DPPH assays. RESULTS Beverages containing bilberry, blackcurrant, mango or rose hip significantly attenuated the early postprandial insulin response (0-90 min), but showed no effect on glucose response. Drinks with bilberry or rose hip reduced the insulin response from the very early phase (0-30 min), and had significantly lower insulin index compared with the control. The efficiency of the bilberry and rose hip to decrease early postprandial insulin responses correlated with higher phenolic contents. CONCLUSIONS Supplements with bilberry, blackcurrant, mango or rose hip in the tested probiotic and oatmeal enriched beverage attenuated early-phase insulin response, but had no effect on the postprandial glycemic response. The improved ability of bilberry and rose hip to lower the very early phase of insulin response seems to be due to a higher phenolic content. TRIAL REGISTRATION The study was retrospectively registered at ClinicalTrials.gov with number NCT03159065 .
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The effect of green tea extract supplementation on exercise-induced oxidative stress parameters in male sprinters.
Jówko, E, Długołęcka, B, Makaruk, B, Cieśliński, I
European journal of nutrition. 2015;54(5):783-91
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High intensity exercise generates reactive oxygen species (ROS), which help with muscle recovery. However, when produced in excess, ROSs cause oxidative stress and cellular damage. Antioxidants produced in the body or taken in through the diet are able to make ROSs inactive. This double blind, randomised controlled trial aimed to evaluate the effects of Green tea extract supplementation on oxidative stress in 16 male sprinters. The study found no significant difference between the group given the supplement and the placebo group in terms of muscle damage recovery and exercise performance. However, an increased levels of polyphenols were observed in the supplement group post-exercise in comparison to the placebo group.
Abstract
BACKGROUND Although research suggests that antioxidant supplementation can protect against exercise-induced muscle damage and oxidative stress, also delayed post-exercise muscle recovery and hindered adaptation to training were reported in the supplemented athletes. PURPOSE The purpose of the study was to evaluate the effects of green tea extract (GTE) supplementation on selected blood markers of oxidative stress and muscle damage in sprinters during preparatory phase of their training cycle. METHODS Sixteen sprinters participated in a double-blind, randomized, placebo (PL)-controlled crossover study, including two 4-week treatment periods with PL and GTE (980 mg polyphenols daily). The sprinters performed two repeated cycle sprint tests (RST; 4 × 15 s, with 1-min rest intervals), after PL and GTE supplementation. Blood was sampled before (at rest), 5 min after RST, and after the 24-h recovery. The activities of superoxide dismutase (SOD) and glutathione peroxidase were measured in erythrocytes, and total polyphenols, total antioxidant capacity (TAC), uric acid (UA), albumin (AL), malondialdehyde (MDA), and creatine kinase (CK) were determined in blood plasma. RESULTS Repeated cycle sprint test performed after PL induced an increase in MDA, TAC, and SOD. Moreover, an increase in UA, AL, and CK was observed after RST irrespective of experimental conditions (PL, GTE). Supplementation with GTE caused an increase in total polyphenols and TAC at rest, and a decrease in MDA and SOD after RST. No significant changes in sprint performance were noted after GTE, as compared to PL. CONCLUSIONS Supplementation with GTE prevents oxidative stress induced by RST in sprinters. Furthermore, GTE supplementation does not seem to hinder training adaptation in antioxidant enzyme system. On the other hand, neither prevention of exercise-induced muscle damage, nor an improvement in sprint performance is noted after GTE administration.