Safety assessment of a highly bioavailable curcumin-galactomannoside complex (CurQfen) in healthy volunteers, with a special reference to the recent hepatotoxic reports of curcumin supplements: A 90-days prospective study.

Recently, there is a growing concern about the use of curcumin supplements owing to a few reported hepatotoxicity related adverse events among some of the long-term consumers. Even though no clear evidence was elucidated for the suspected toxicity, the addition of adjuvants that inhibits body's essential detoxification pathways, adulteration with synthetic curcumin, and presence of contaminants including heavy metals, chromate, illegal dyes, non-steroidal anti-inflammatory agents, and pyrrole alkaloids were suggested as plausible reasons. Considering these incidences and speculations, there is a need to critically evaluate the safety of curcumin supplements for prolonged intake. The present study is an evaluation of the safety of curcumin-galactomannoside complex (CGM), a highly bioavailable curcumin formulation with demonstrated high free curcuminoids delivery. Twenty healthy human volunteers were evaluated for toxic manifestations of CGM when supplemented with 1000 mg per day (∼380 mg curcuminoids) for 90-days. CGM supplementation did not cause any adverse effects or clinically significant variations in the vital signs, hematological parameters, lipid profile and renal function markers of the volunteers, indicating its safety. Liver function enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) and bilirubin were in the normal range after 90-day supplementation of CGM. In summary, no adverse effects were observed under the conditions of the study. CGM can be considered as a safe curcumin supplement for regular consumption and is devoid of any adulterants or contaminants.

Influence of a low-dose supplementation of curcumagalactomannoside complex (CurQfen) in knee osteoarthritis: A randomized, open-labeled, active-controlled clinical trial.

A 6-week, randomized, open-label, active-controlled clinical trial was conducted to evaluate the influence of a low-dose curcumagalactomannosides (CGM) (400 mg once daily) in OA subjects. The treatment was compared with a standard combination of 500 mg glucosamine hydrochloride (GLN) and 415 mg chondroitin sulphate (CHN), supplied as a single oral dose twice a day. Out of 84 subjects randomized, 72 subjects who have completed the study were evaluated for the safety and efficacy of the treatments at baseline and subsequent visits (day 28 and 42), by measuring walking performance, VAS, KPS, and WOMAC scores. CGM exhibited 47.02, 21.43, and 206% improvement in VAS, KPS, and walking performance, respectively, compared to the baseline. Similarly, there was 31.17, 32.93, 36.44, and 35% improvement in the pain, stiffness, physical function, and total WOMAC scores. CGM also caused a substantial reduction in the serum inflammatory marker levels. The results indicate that a short-term supplementation of a low dosage CGM exerted superior beneficial effects than a high-dosage CHN-GLN combination in alleviating the pain and symptoms of OA subjects. Further clinical trials of extended duration in a larger population is required to substantiate the efficacy of CGM in the long-term management of OA.

Curcumagalactomannoside/Glucosamine Combination Improved Joint Health Among Osteoarthritic Subjects as Compared to Chondroitin Sulfate/Glucosamine: Double-Blinded, Randomized Controlled Study.

Objective: A combination of curcumagalactomannosides (CGM) (400 mg) with glucosamine hydrochloride (GLN) (500 mg) was evaluated against a standard dietary supplement combination chondroitin sulfate (CHN) (415 mg)/GLN (500 mg) for their effectiveness in alleviating the pain and symptoms among osteoarthritic subjects. Design: Randomized, double-blinded and active-controlled study. Settings/Location: The study was conducted in a hospital-based research center in Vadodara, Gujarat, India. Subjects: Eighty subjects (38 males and 42 females), with confirmed osteoarthritis (OA) (Class I-III), were randomized into two parallel groups designated as Group I (CGM-GLN) and Group II (CHN-GLN). Interventions: All the study subjects were supplemented with their corresponding intervention capsules (ether CGM along with GLN or CHN along with GLN), as a single oral dose twice a day, once in the morning 10-15 min before breakfast and again in the evening before dinner, for 84 days. Outcome measures: A validated treadmill uphill walking protocol was used for the study, and the efficiency of supplementation was evaluated using visual analogue scale (VAS) score, Karnofsky Performance Scale (KPS) score, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire at the baseline, 28th, and 84th day following the treatment. Mechanism of action of CGM-GLN combination was analyzed by measuring the levels of serum inflammatory markers interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), and soluble vascular cell adhesion molecule-1 (sVCAM) at the baseline and 84th day. Results: CGM-GLN was found to offer significant beneficial effects to pain, stiffness, and physical function of OA subjects compared with CHN-GLN, which was evident from the improvement in walking performance, VAS score, KPS score, and WOMAC score. The efficiency of CGM-GLN was almost double compared with the CHN-GLN by the end of the study (84th day). A significant reduction of inflammatory serum marker levels was observed among CGM-GLN subjects compared with CHN-GLN subjects. Compared with the baseline, CGM-GLN produced 54.52%, 59.08%, and 22.03% reduction in IL-1ß, IL-6, and sVCAM levels, respectively. Whereas CHN-GLN group of subjects expressed only 23.17%, 21.38%, and 6.82% reduction in IL-1ß, IL-6, and sVCAM levels, respectively. Conclusions: In conclusion, the present study demonstrated the potential benefits of CGM-GLN supplements in alleviating the symptoms and function of OA subjects compared with the standard CHN-GLN treatment. The augmented efficacy of CGM-GLN combination could be attributed to the enhanced anti-inflammatory effect of CGM.

The Inflammatory Response to Alcohol Consumption and Its Role in the Pathology of Alcohol Hangover.

An increasing number of studies are focusing on the inflammatory response to alcohol as a potentially important determinant of hangover severity. In this article, data from two studies were re-evaluated to investigate the relationship between hangover severity and relevant biomarkers of alcohol metabolism, oxidative stress and the inflammatory response to alcohol. Hangover severity was significantly and positively correlated with blood concentrations of biomarkers of the inflammatory response to alcohol, in particular, Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and C-reactive protein (CRP). At 4 h after alcohol consumption, blood ethanol concentration (but not acetaldehyde) was significantly and positively associated with elevated levels of IL-6, suggesting a direct inflammatory effect of ethanol. In addition, biomarkers of oxidative stress, i.e., malondialdehyde and 8-isoprostrane, were significantly correlated with hangover severity, suggesting that oxidative stress also contributes to the inflammatory response. The timing of the assessments suggests initial slow elimination of ethanol in the first hours after alcohol consumption. As a consequence, more ethanol is present in the second half of the night and the next morning, which will elicit more oxidative stress and a more profound inflammatory response. Together, these processes result in more severe hangovers.