Dose escalation of a Curcuminoid formulation
BMC Complement Altern Med. 006; 6:10
|Curcumin in animal models has shown to reduce the levels of oxidative DNA adduct M1G and expression of COX-2 enzyme.|
In previous studies on animal models, Curcumin was found to be safe, but for humans, few studies regarding its pharmacology and toxicology are available. Minimal toxicity of doses up to 8000 mg have been described in humans and before this publication no maximum tolerated dose had been defined.
To perform a dose escalation study for determining the maximum tolerated dose, safety profile, and resultant serum concentration of a single dose of standardized powdered extract (Curcumin C3 Complex®) obtained from Alleppey finger turmeric.
24 subjects with mean age of 34 years were assessed in this dose escalation study. Subjects were administered escalating doses from 500 to 12,000 mg of standardized Curcumin extract with 8 fl. Oz. of water followed by a standard meal containing dietary fat. Safety was assessed for 72 hours following the Curcumin dose. Blood specimens from all subjects on the escalation phase were obtained just prior to dosing, and 1, 2 and 4 hours after completing dosing at each dose level was tested. The primary endpoints in this clinical study will be to measure safety and tolerability of the FOLFOX-Curcumin combination.
This will be the first clinical trial to investigate the outcomes from the combination of oral Curcumin with standard care oxaliplatin-based chemotherapy. This clinical trial is a first randomized trial of its kind and results of this trial can provide early evidence of clinical efficacy of Curcumin within the chemotherapeutic setting.
For successful chemopreventive action of Curcumin, information regarding its highest dose with minimal toxicity is important. In this study it was found that even the high dose up to 12,000 mg/day produced minimal toxicity, concluding excellent tolerance of Curcumin in humans. In other words, no maximum tolerated dose has been identified in humans, although successful administration may be affected by difference in drug formulation. Given that achieving systemic bioavailability of Curcumin or its metabolite may not be essential for colorectal cancer prevention, these findings warrant further investigation for its utility as a long-term chemopreventive agent.