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      No effect of the turmeric root phenol curcumin on prednisolone-induced glucometabolic perturbations in men with overweight or obesity

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          Abstract

          Objectives

          Preclinically, curcumin has been shown to protect against glucocorticoid-induced insulin resistance. We evaluated the effect of curcumin administered with prednisolone in healthy overweight or obese men.

          Methods

          In a double-blind, parallel-group trial, 24 overweight/obese non-diabetic men were randomised to one of three intervention groups (A) prednisolone placebo+curcumin placebo, (B) prednisolone (50 mg/day)+curcumin placebo or (C) prednisolone and curcumin (400 mg/day). Curcumin or curcumin placebo treatment started 1 day prior to 10-day prednisolone or prednisolone placebo treatment. The primary endpoint was change in prednisolone-induced insulin resistance assessed by homeostatic model assessment of insulin resistance (HOMA2-IR). Other endpoints included anthropometric measurements, magnetic resonance spectroscopy-assessed hepatic fat content, blood pressure, circulating metabolic markers and continuous glucose monitoring measures.

          Results

          Baseline characteristics (mean ± s.d): age 44.2 ± 13.7 years, BMI 30.1 ± 3.5 kg/m 2, HbAlc 33.3 ± 3.2 mmol/mol, HOMA2-IR 1.10 ± 0.45 and fasting plasma glucose 5.2 ± 0.4 mmol/L. Prednisolone significantly increased HOMA2-IR (estimated treatment difference 0.36 (95% CI 0.16; 0.57)). Co-treatment with curcumin had no effect on HOMA2-IR (estimated treatment difference 0.08 (95% CI −0.13; 0.39)). Prednisolone increased HbAlc, insulin, C-peptide, glucagon, blood pressure, mean interstitial glucose, time spent in hyperglycaemia and glucose variability, but no protective effect of curcumin on any of these measures was observed.

          Conclusions

          In this double-blind, placebo-controlled parallel-group study involving 24 overweight or obese men randomised to one of three treatment arms, curcumin treatment had no protective effect on prednisolone-induced insulin resistance or other glucometabolic perturbations.

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          Most cited references52

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          Curcumin: Biological, Pharmaceutical, Nutraceutical, and Analytical Aspects

          Turmeric is a curry spice that originated from India, which has attracted great interest in recent decades because it contains bioactive curcuminoids (curcumin, demethoxycurcumin, and bisdemethoxycurcumin). Curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl)-hepta-1,6-diene-3,5-dione), a lipophilic polyphenol may work as an anticancer, antibiotic, anti-inflammatory, and anti-aging agent as suggested by several in vitro, in vivo studies and clinical trials. However, poor aqueous solubility, bioavailability, and pharmacokinetic profiles limit curcumin’s therapeutic usage. To address these issues, several curcumin formulations have been developed. However, suboptimal sample preparation and analysis methodologies often hamper the accurate evaluation of bioactivities and their clinical efficacy. This review summarizes recent research on biological, pharmaceutical, and analytical aspects of the curcumin. Various formulation techniques and corresponding clinical trials and in vivo outcomes are discussed. A detailed comparison of different sample preparation (ultrasonic, pressurized liquid extraction, microwave, reflux) and analytical (FT-IR, FT-NIR, FT-Raman, UV, NMR, HPTLC, HPLC, and LC-MS/MS) methodologies used for the extraction and quantification of curcuminoids in different matrices, is presented. Application of optimal sample preparation, chromatographic separation, and detection methodologies will significantly improve the assessment of different formulations and biological activities of curcuminoids.
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            Dose escalation of a curcuminoid formulation

            Background Curcumin is the major yellow pigment extracted from turmeric, a commonly-used spice in India and Southeast Asia that has broad anticarcinogenic and cancer chemopreventive potential. However, few systematic studies of curcumin's pharmacology and toxicology in humans have been performed. Methods A dose escalation study was conducted to determine the maximum tolerated dose and safety of a single dose of standardized powder extract, uniformly milled curcumin (C 3 Complex™, Sabinsa Corporation). Healthy volunteers were administered escalating doses from 500 to 12,000 mg. Results Seven of twenty-four subjects (30%) experienced only minimal toxicity that did not appear to be dose-related. No curcumin was detected in the serum of subjects administered 500, 1,000, 2,000, 4,000, 6,000 or 8,000 mg. Low levels of curcumin were detected in two subjects administered 10,000 or 12,000 mg. Conclusion The tolerance of curcumin in high single oral doses appears to be excellent. Given that achieving systemic bioavailability of curcumin or its metabolites may not be essential for colorectal cancer chemoprevention, these findings warrant further investigation for its utility as a long-term chemopreventive agent.
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              Curcumin Extract for Prevention of Type 2 Diabetes

              OBJECTIVE To assess the efficacy of curcumin in delaying development of type 2 diabetes mellitus (T2DM) in the prediabetic population. RESEARCH DESIGN AND METHODS This randomized, double-blinded, placebo- controlled trial included subjects (n = 240) with criteria of prediabetes. All subjects were randomly assigned to receive either curcumin or placebo capsules for 9 months. To assess the T2DM progression after curcumin treatments and to determine the number of subjects progressing to T2DM, changes in β-cell functions (homeostasis model assessment [HOMA]-β, C-peptide, and proinsulin/insulin), insulin resistance (HOMA-IR), anti-inflammatory cytokine (adiponectin), and other parameters were monitored at the baseline and at 3-, 6-, and 9-month visits during the course of intervention. RESULTS After 9 months of treatment, 16.4% of subjects in the placebo group were diagnosed with T2DM, whereas none were diagnosed with T2DM in the curcumin-treated group. In addition, the curcumin-treated group showed a better overall function of β-cells, with higher HOMA-β (61.58 vs. 48.72; P < 0.01) and lower C-peptide (1.7 vs. 2.17; P < 0.05). The curcumin-treated group showed a lower level of HOMA-IR (3.22 vs. 4.04; P < 0.001) and higher adiponectin (22.46 vs. 18.45; P < 0.05) when compared with the placebo group. CONCLUSIONS A 9-month curcumin intervention in a prediabetic population significantly lowered the number of prediabetic individuals who eventually developed T2DM. In addition, the curcumin treatment appeared to improve overall function of β-cells, with very minor adverse effects. Therefore, this study demonstrated that the curcumin intervention in a prediabetic population may be beneficial.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                17 February 2023
                17 February 2023
                01 April 2023
                : 12
                : 4
                : e220334
                Affiliations
                [1 ]Center for Clinical Metabolic Research , Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
                [2 ]Department of Clinical Medicine , Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
                [3 ]Clinical Research , Steno Diabetes Center Copenhagen, Herlev, Denmark
                [4 ]Section of Biostatistics , Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
                [5 ]Department of Radiology , Herlev Hospital, University of Copenhagen, Herlev, Denmark
                [6 ]Department of Biomedical Sciences , Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
                [7 ]Novo Nordisk Foundation Center for Basic Metabolic Research , Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
                Author notes
                Correspondence should be addressed to F K Knop: filip.krag.knop.01@ 123456regionh.dk
                Author information
                http://orcid.org/0000-0002-2495-5034
                Article
                EC-22-0334
                10.1530/EC-22-0334
                10083679
                36800259
                3479cf08-309c-4d8b-840a-b1554f933d02
                © the author(s)

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 22 January 2023
                : 17 February 2023
                Categories
                Research

                prednisolone,glucose,insulin resistance,continuous glucose monitoring,curcumin

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