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A Hot Water Extract of Curcuma longa L. Improves Fasting Serum Glucose Levels in Participants with Low-Grade Inflammation: Reanalysis of Data from Two Randomized, Double-Blind, Placebo-Controlled Trials.
Uchio, R, Okuda-Hanafusa, C, Saji, R, Kawasaki, K, Muroyama, K, Murosaki, S, Yamamoto, Y, Hirose, Y
Nutrients. 2022;14(18)
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Chronic low-grade inflammation plays a significant role in the development of type 2 diabetes. The hot water extract of turmeric (Curcuma longa L.) has been shown to have anti-inflammatory and antioxidant properties, as well as the ability to lower blood glucose levels in animal models. Curcuma longa L. extract may improve systemic glucose levels by reducing insulin resistance and pancreatic β-cell dysfunction. In this study, the results from two randomised, double-blind, placebo-controlled trials were reanalysed to assess the effects of hot water extract of C. longa on serum glucose levels in overweight individuals with low-grade inflammation. When compared to the placebo group, participants in the Curcuma longa L. group with high hs-CRP levels showed significant improvements in serum hs-CRP levels and fasting blood glucose levels. Healthcare professionals can use the results of this study to understand the potential beneficial effects of Curcuma longa L. extract on systemic glucose regulation in overweight individuals with low-grade inflammation. Further robust research is needed to investigate the effect of Curcuma longa L. extract on reducing proinflammatory cytokines and suppressing the activation of the NF-kB signalling pathway.
Abstract
The dietary spice Curcuma longa L. (C. longa), also known as turmeric, has various biological effects. A hot water extract of C. longa was shown to have anti-inflammatory activities in preclinical and clinical studies. Chronic low-grade inflammation is associated with the disruption of glucose homeostasis, but the effect of C. longa extract on glucose metabolism in humans is poorly understood. Therefore, we investigated the effect of C. longa extracts on serum glucose levels in the presence of low-grade inflammation. We reanalyzed our published data from two randomized, double-blind, placebo-controlled trials in overweight participants aged 50 to 69 years and performed a stratified analysis using the inflammatory marker high-sensitivity C-reactive protein (hsCRP). In both studies, participants took a test food with a hot water extract of C. longa (C. longa extract group, n = 45 per study) or without C. longa extract (placebo group, n = 45 per study) daily for 12 weeks, and we measured the levels of serum hsCRP and fasting serum glucose. The mean baseline hsCRP value was used to stratify participants into two subgroups: a low-hsCRP subgroup (baseline mean hsCRP < 0.098 mg/dL) and a high-hsCRP subgroup (baseline mean hsCRP ≥ 0.098 mg/dL). In the low-hsCRP subgroup, we found no significant difference in fasting serum glucose levels between the two groups in either study, but in the high-hsCRP subgroup, the C. longa extract group had significantly lower levels of serum hsCRP (p < 0.05) and fasting serum glucose (p < 0.05) than the placebo group in both studies. In conclusion, a hot water extract of C. longa may help to improve systemic glucose metabolism in people with chronic low-grade inflammation.
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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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Tolerability of curcumin in pediatric inflammatory bowel disease: a forced-dose titration study.
Suskind, DL, Wahbeh, G, Burpee, T, Cohen, M, Christie, D, Weber, W
Journal of pediatric gastroenterology and nutrition. 2013;56(3):277-9
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Inflammatory bowel disease (IBD) is characterised by chronic intestinal inflammation. Conventional drug treatment is effective, but may cause adverse effects. The beneficial effects of turmeric on intestinal inflammation have been shown in animal and adult human studies. The aim of this pilot study was to test the tolerability of curcumin extract in children with IBD at different doses. The doses of curcumin extract tested were 500mg twice a day for two weeks, increasing to 1g twice a day for three weeks, increasing to 2g twice a day for three weeks. These doses was taken in addition to patients standard drug treatment. The curcumin was well tolerated at all three of these doses by patients who completed the study (nine children aged 11-18 years with IBD (Crohn's or UC)) in remission or with mild disease. Some symptoms were reported by the majority of patients during the study but these were mild, not clearly related to curcumin and did not require the dose of curcumin to be reduced. Two patients reported ‘gassiness’ at all three doses. Two patients with UC went into remission. Disease activity improved in patients with Crohn's. No participants experienced a relapse or worsening of symptoms during the study. This pilot study suggests that curcumin extract may be taken in combination with conventional medicine without clinically significant side- or adverse-effects, though larger studies are needed to fully assess the safety and efficacy of curcumin in children with IBD.
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation in the absence of a recognized etiology. The primary therapies are medications that possess anti-inflammatory or immunosuppressive effects. Given the high use of complementary alternative medicines in pediatric IBD, a prospective tolerability study of curcumin, an herbal therapy with known anti-inflammatory effects, was conducted to assess possible dosage in children with IBD. METHODS Prospectively, patients with Crohn disease or ulcerative colitis in remission or with mild disease (Pediatric Crohn's Disease Activity Index [PCDAI] <30 or Pediatric Ulcerative Colitis Activity Index [PUCAI] score <34) were enrolled in a tolerability study. All patients received curcumin in addition to their standard therapy. Patients initially received 500 mg twice per day for 3 weeks. Using the forced-dose titration design, doses were increased up to 1 g twice per day at week 3 for a total of 3 weeks and then titrated again to 2 g twice per day at week 6 for 3 weeks. Validated measures of disease activity, using the PUCAI and PCDAI, and the Monitoring of Side Effect System score were obtained at weeks 3, 6, and 9. RESULTS All patients tolerated curcumin well, with the only symptom that was consistently reported during all 3 visits being an increase in gassiness, which occurred in only 2 patients. Three patients saw improvement in PUCAI/PCDAI score. CONCLUSIONS This pilot study suggests that curcumin may be used as an adjunctive therapy for individuals seeking a combination of conventional medicine and alternative medicine.