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Objective: Curcuminoids, the major component of which is curcumin, are natural polyphenolic compounds from the rhizome of Curcuma longa Linn. and possess extensive biopharmacological properties that are limited in humans due to poor bioavailability. Currently, most commercial bioavailable turmeric extracts use synthetic excipients or the addition of piperine to enhance bioavailability, and are needed in multiple daily doses to achieve clinical efficacy. This study was conducted to compare the bioavailability of a natural, water-dispersible turmeric extract containing 60% natural curcuminoids, the test product, WDTE60N (1 × 250 mg per day), with the reference product, turmeric extract capsules (500 mg curcuminoids and 5 mg piperine, CPC; 3 × 500 mg per day). Methods: Sixteen healthy adult male subjects fasted overnight for 10 hours and then were dosed with either one capsule of the test product WDTE60N or three capsules of reference product CPC orally (One capsule administered at every 6 hours interval i.e. at 0.00 hrs, 6.00 hrs and at 12.00 hrs) in each study period. Blood sampling before and after dosing was carried out at defined time points at -12.00, -02.00, 00.00 (within 10 minutes prior to dosing) hours in morning before dosing and post-dose (First dose) at 00.50, 01.00, 02.00, 03.00, 04.00, 05.00, 06.50, 07.00, 08.00, 09.00, 10.00, 11.00, 12.50, 13.00, 14.00, 16.00, 18.00, 20.00 and 24.00 hours in each period. Plasma concentration of curcuminoids was determined using a validated liquid chromatography with tandem mass spectrometry bioanalytical method. Results: The Cmax (GLSM) for the test product WDTE60N was observed to be 74.56 ng/mL; and same for the reference CPC was 22.75 ng/mL. AUC0-t (GLSM) for test WDTE60N was 419.00 hâng/mL; and for reference CPC it was 359.86 hâng/mL for total curcuminoids. Conclusion: The test formulation WDTE60N showed improved relative absorption and equivalent exposure at a 10-fold-lower dose of actives than the reference formulation CPC.
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Alcaloides , Benzodioxoles , Estudios Cruzados , Curcuma , Curcumina , Piperidinas , Extractos Vegetales , Humanos , Masculino , Extractos Vegetales/farmacología , Extractos Vegetales/farmacocinética , Curcuma/química , Adulto , Alcaloides/farmacocinética , Alcaloides/farmacología , Benzodioxoles/farmacocinética , Benzodioxoles/farmacología , Curcumina/farmacocinética , Curcumina/farmacología , Piperidinas/farmacocinética , Piperidinas/farmacología , Disponibilidad Biológica , Adulto Joven , Alcamidas Poliinsaturadas/farmacología , Alcamidas Poliinsaturadas/farmacocinéticaRESUMEN
Context: Turmeric is a well-known herb that has been used in many traditional medicinal systems since ancient times. Turmeric roots contain hydrophobic polyphenols called curcuminoids, which have proven anti-inflammatory and antioxidant effects and are shown to be beneficial for the management of musculoskeletal health. Various products containing curcumin or turmeric extract are commercially available. Objective: This systematic review and meta-analysis of randomized clinical trials (RCTs) is intended to evaluate the effective dose, safety, and efficacy of commercial turmeric extract and curcumin supplements in musculoskeletal health. Design: The research team performed a systematic literature search of PubMed, Google Scholar, and Cochrane Library databases and conducted a meta-analysis according to PRISMA guidelines. Setting: Authors from India and USA contributed to this systematic review and meta-analysis. Results: The research team analyzed 21 prospective, randomized clinical studies, of which seven studies were focused on skeletal muscle health and fourteen on joint health. Statistical heterogeneity was established based on the results of heterogeneity analysis of a Chi-square (χ2) value for Cochran's Q statistic of 29.3765 for musculoskeletal and 3666.80 for joint health studies (P < .0001 for both analyses). Therefore, the random effects model was used. The χ2 value of the random effects model was 216.5545 for skeletal muscle health studies and 1400.65 for joint health studies, which was statistically significant with P < .0001 for both analyses. Conclusions: Turmeric extract and curcumin supplements can be effective adjuvants for the management of musculoskeletal health, with a low incidence of AEs. The water-dispersible turmeric extract, WDTE60N, at a dose of 250 mg per day, was found to be more effective than other curcumin products. However, the studies included in the analysis were conducted using diverse doses and treatment durations. Further evaluation using comparisons in future clinical trials can establish the appropriate effective dose of curcumin supplements for the overall maintenance of musculoskeletal health.
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Curcumina , Humanos , Curcumina/uso terapéutico , Curcuma/química , Extractos Vegetales/uso terapéutico , Antiinflamatorios/uso terapéuticoRESUMEN
Background: Stress is the psychological, physiological, and behavioral response of an individual's body when they perceive a lack of equilibrium between the demands placed upon them and their ability to meet those demands. Adaptogens are herbs that help with stress management, and Ashwagandha is one such safe and effective adaptogen. Objective: We evaluated the anti-neuroinflammatory potential of Ashwagandha sustained-release formulation (AshwaSR) by estimating the in vitro expression of pro-inflammatory cytokines, and its efficacy on anxiety and depression in an in vivo study. Methods: Our in vitro study investigated the anti-inflammatory potential of AshwaSR by estimating the expression of tumour necrosis factor [TNF]-α and interleukin [IL]-1ß levels in LPS-induced THP-1 human monocytes, and the antioxidant effects by its potential to inhibit the superoxide [SO] generation in PMA-induced HL-60 human monocytic cells. The in vivo study assessed the efficacy of AshwaSR on chronic unpredictable stress (CUS)-induced comorbid anxiety and depression in Sprague Dawley rats. Antidepressant and anxiolytic effects of AshwaSR were evaluated by open field test (OFT), elevated plus maze (EPM), forced swim test (FST), and Morris water maze (MWM) test. Results: AshwaSR inhibited TNF-α, IL-1ß and superoxide production in a dose-dependent manner in the in vitro study. The in vivo CUS model induced depression-like and anxiety-like behaviour. Treatments with AshwaSR and escitalopram showed improvement in the EPM and MWM models compared to the CUS-group. Conclusion: In vitro study demonstrated that AshwaSR inhibits expressions of pro-inflammatory cytokines, IL-1ß and TNF-α, and superoxide production. Further, the in vivo study confirmed its anxiolytic and stress-relieving effects in the CUS model that confirmed AshwaSR's potential in managing stress and stress-related symptoms.
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Background: Delayed onset of muscle soreness (DOMS) and its physiological consequences influenced an individual's adherence to an exercise routine. Objective: This study aimed to evaluate the efficacy, safety, and tolerability of TurmXTRA® 60N (WDTE60N) on DOMS compared to placebo in recreationally active healthy subjects. Methods: This randomized, double-blind, placebo-controlled parallel-group study enrolled 30 healthy and recreationally active subjects (average age: 28.23 ± 4.20 years) and randomized them to receive WDTE60N (WDTE60N group; n = 15) or placebo (placebo group; n = 15). Study treatments were initiated 29 days before the eccentric exercise and were continued for 4 days after the exercise. The primary endpoint was the change in pain intensity measured by the visual analog scale (VAS) at the end of study treatment (at 96 hours after eccentric exercise) from baseline (measured immediately after exercise). Results: The VAS score indicated that subjects from the WDTE60N group reported significantly less pain after eccentric exercise compared to the placebo group (AUC0-96h: 286.8 ± 46.7 vs. 460 ± 40.5, respectively; p < 0.0001). Well-being status was assessed using the adapted version of the Hooper and MacKinnon questionnaire and was calculated as individual and cumulative scores of the domains (fatigue, mood, general muscle soreness, sleep quality, and stress) that demonstrated improvement in all domains and in overall well-being in the WDTE60N group compared to the placebo group (p < 0.0001). Serum lactate dehydrogenase (LDH) was significantly lower in the WDTE60N group compared to the placebo group (AUC0-96h: 23623.7 ± 2532.0 vs. 26138.6 ± 3669.5, respectively; p=0.0446). Conclusion: Intake of WDTE60N before and after eccentric exercise significantly reduced subjective perception of muscle soreness and serum LDH activity and increased the psychological well-being in recreationally active subjects.
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BACKGROUND: The global prevalence of stress is increasing. Stress adversely affects cognitive ability, sleep quality, and overall psychological well-being. Ashwagandha (Withania somnifera (L.) Dunal), an essential medicine in Ayurveda, is reportedly beneficial in reducing stress and improving memory. This double-blind, randomized, placebo-controlled clinical study evaluated the effect of Ashwagandha root extract sustained-release capsule 300 mg (Prolanza™; hereafter Ashwagandha SR) on cognitive functions, stress levels, sleep quality, overall well-being, and safety in stressed subjects. METHODS: Subjects (130 healthy cognitively sound adults [20-55 years, body mass index:18-29 kg/m2]) having a Perceived Stress Scale (PSS) score of 14-24 were randomized to receive either Ashwagandha SR or placebo. Subjects took one capsule of Ashwagandha SR or placebo daily for 90 consecutive days. This study was registered on Clinical Trials Registry-India (CTRI) on 13/11/2019 [number: CTRI/2019/11/021990]. The primary endpoint was the change in cognitive function as measured by CANTAB from baseline to the end of the study period (90 ± 7 days). The secondary outcomes included the change in PSS-10 score, serum cortisol level (9-11 am), the OHQ score, the PSQI, and serum BDNF levels. RESULTS: Only 125 completed the study and were evaluated. The Cambridge Neuropsychological Test Automated Battery (CANTAB) reported significantly improved recall memory, and the total error rate in recalling patterns significantly decreased at visit 4 in the Ashwagandha SR group vs. the placebo group (first attempt memory score:12.9 ± 6.7 vs. 10.1 ± 6.3; total errors:17.5 ± 23.3 vs. 27.7 ± 23.6). At visit 4, lower PSS-10 score (13.0 ± 5.0 vs. 18.7 ± 4.6; p < .0001), serum cortisol levels (p=0.0443), and Pittsburgh Sleep Quality Index (PSQI) score (p < .0001) but higher Oxford Happiness Questionnaire (OHQ) scores (p < .0001) were seen in Ashwagandha SR vs. the placebo group, suggesting significantly lower stress levels and significantly better psychological well-being and sleep quality in the former. No adverse events were reported. CONCLUSIONS: This is the first clinical study assessing Ashwagandha SR for its safety and efficacy. Treatment with one Ashwagandha SR capsule once daily for 90 days improved memory and focus, psychological well-being, and sleep quality, reduced stress levels, and was safe and well-tolerated.
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BACKGROUND: Knee pain causes functional limitations, eventually compromising the quality of life. We evaluated the efficacy of our water-dispersible turmeric formulation (60% natural curcuminoids, TurmXTRA 60N®-WDTE60N), which exhibited better PK profile at low dose (250 mg) than standard turmeric extract, in alleviating symptoms of chronic knee pain. METHODS: In this randomized, double-blind, placebo-controlled trial, subjects received either 250 mg WDTE60N capsule (150 mg curcuminoids; n = 53) or appearance-matched placebo capsule (n = 53) once daily for 90 days. Primary endpoint was change in pain score on the visual analogue scale (VAS) after 80-m fast-paced walk test. RESULTS: A total of 96 subjects completed the study. WDTE60N reduced VAS score from baseline (5.4 ± 0.9) to day 90 (3.8 ± 0.8) with greater mean reduction than placebo (-1.5 ± 0.7 vs -0.6 ± 0.8, p < 0.0001; 2.5 times). It also significantly improved the time taken for 80-m fast-paced walk test and 9-step stair-climb test; and improved all biomarkers compared to placebo (p > 0.05). Three adverse events occurred but were unrelated to study products. CONCLUSION: WDTE60N 250 mg administered once daily for 3 months, alleviated knee pain, improved joint function in healthy subjects with chronic knee pain, was well tolerated and safe.
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OBJECTIVES: The therapeutic utility of turmeric (Curcuma longa L., Zingiberaceae) is limited due to low bioavailability of its active principal curcuminoids. This study evaluates the pharmacokinetic characteristics of a natural, water-dispersible turmeric extract containing 60% curcuminoids (TurmXtra 60N), referred to as WDTE60N, compared to standard turmeric extract 95% (STE95). METHODS: This open-label, two-way crossover, single oral dose, comparative pharmacokinetic study, randomized 14 subjects to receive one capsule of WDTE60N (150 mg curcuminoids) or three capsules of STE95 (500 mg curcuminoids each). The resulting dose ratio of actives for WDTE60N:STE95 was 1:10. KEY FINDINGS: Peak plasma levels of free curcumin, total curcuminoids, tetrahydrocurcumin and demethoxycurcumin were similar (P > 0.05). Cmax of total curcumin was higher (P = 0.0253) for WDTE60N at a 10-fold lower dose compared to STE95 (43.5 ± 28.5 vs. 21.3 ± 10.7 ng/ml). Mean AUC0-t was higher (P < 0.001) for free curcumin and comparable for total curcumin and total curcuminoids with WDTE60N than with STE95. Five adverse events were reported in three subjects (mild in severity) and were unrelated to study products. CONCLUSION: WDTE60N showed higher absorption and comparable exposure for free curcumin, total curcumin and total curcuminoids at a 10-fold lower dose than STE95.