Pharmacokinetics of Curcumin Conjugate Metabolites in Healthy Human Subjects

Department of Internal Medicine, University of Michigan Medical School and Veterans Affairs Medical Center, Ann Arbor, Michigan, USA.
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.13). 07/2008; 17(6):1411-7. DOI: 10.1158/1055-9965.EPI-07-2693
Source: PubMed


Curcumin is a polyphenol, found in the spice turmeric, that has promising anticancer properties, but previous studies suggest that absorption of curcumin may be limited.
This study examined the pharmacokinetics of a curcumin preparation in healthy human volunteers 0.25 to 72 h after a single oral dose. Curcumin was administered at doses of 10 g (n = 6) and 12 g (n = 6). Subjects were randomly allocated to dose level for a total of six subjects at each dose level. Serum samples were assayed for free curcumin, for its glucuronide, and for its sulfate conjugate. The data were fit to a one-compartment absorption and elimination model.
Using a high-performance liquid chromatography assay with a limit of detection of 50 ng/mL, only one subject had detectable free curcumin at any of the 14 time points assayed, but curcumin glucuronides and sulfates were detected in all subjects. Based on the pharmacokinetic model, the area under the curve for the 10 and 12 g doses was estimated (mean +/- SE) to be 35.33 +/- 3.78 and 26.57 +/- 2.97 mug/mL x h, respectively, whereas C(max) was 2.30 +/- 0.26 and 1.73 +/- 0.19 mug/mL. The T(max) and t(1/2) were estimated to be 3.29 +/- 0.43 and 6.77 +/- 0.83 h. The ratio of glucuronide to sulfate was 1.92:1. The curcumin conjugates were present as either glucuronide or sulfate, not mixed conjugates.
Curcumin is absorbed after oral dosing in humans and can be detected as glucuronide and sulfate conjugates in plasma.

  • Source
    • "Oral administration of 500ppm and 2000ppm curcumin in chow for four months resulted in 1.276µM and 1.428µM concentrations, respectively, in the brain [130]. It has been shown that curcumin is metabolised (glucuronidated) to a higher extent in humans compared to rodent intestine, leaving the bioavailability in humans critically low [131] [132]. However, optimised formulations of lipidated curcumin reached brain concentrations of 5.79µM in mice after two weeks of oral administration of 500ppm in chow [130]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Alzheimer's disease (AD) is a progressive neurodegenerative disorder, characterized by deposition of amyloid beta, neurofibrillary tangles, astrogliosis and microgliosis, leading to neuronal dysfunction and loss in the brain. Bio- and histochemical evidence suggests a pivotal role of central and peripheral inflammation in its aetiopathology, linked to the production of free radicals. Numerous epidemiological studies support that the long-term use of non-steroidal anti-inflammatory drugs is preventive against AD, but these medications do not slow down the progression of the disease in already diagnosed patients. There are a number of studies focusing on traditional herbal medicines and small molecules (usually plant secondary metabolites) as potential anti-inflammatory drugs, particulary in respect to cytokine suppression. For instance, ω-3 polyunsaturated fatty acids and a number of polyphenolic phytochemicals have been shown to be effective against inflammation in animal and cell models. Some of these plant secondary metabolites have also been shown to possess antioxidant, anti-inflammatory, anti-amyloidogenic, neuroprotective, and cognition-enhancing effects. This review will overview the the effects of catechins/proanthocyanidins from green tea, curcumin from turmeric, extracts enriched in bacosides from Brahmi, Ginkgo flavone glycosides, and ω-3 polyunsaturated fatty acids not only counteract one pathophysiological aspect of AD in numerous in vitro and in vivo studies of models of AD, but also ameliorate several of the above mentioned pathologies. The evidence suggests that increased consumption of these compounds might lead to a safe strategy to delay the onset of AD. The continuing investigation of the potential of these substances is necessary as they are promising to yield a possible remedy for this pervasive disease.
    Full-text · Article · Sep 2014 · CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders)
  • Source
    • "In humans, due to its fast metabolic turnover in the liver and intestinal wall, blood concentrations of curcumin are low and tissue distribution is limited following oral dosing [28] [29] [30] [31] [32] [33] [34] [35] [36]. Maximum plasma curcumin concentrations in humans, even upon intake of doses as high as 10 or 12 g curcumin, remain in the low nanomolar range (<160 nmol/L) [30]. "

    Full-text · Article · Sep 2013 · Free Radical Biology and Medicine
  • Source
    • "It was suggested that the low systematic bioavailability of curcumin may be due to the hydrophobic nature of the molecule, poor absorption and the metabolic biotransformation in intestine and liver [23]. These conjugates are detectable in plasma at greater concentrations than free curcumin with a peak at 4 h after oral dosing [24]. This may be explained by the fact that curcumin constitutes about 5% of turmeric root; the remainder is made up of carbohydrates, proteins and essential oils [10]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The idiopathic pulmonary arterial hypertension is a complex disease that mainly affects pulmonary arterial circulation. This undergoes a remodeling with subsequent reduction of flow in the small pulmonary arteries. Because of this damage an increased vascular resistance gradually develops, and over time it carries out in heart failure. The inflammatory process is a key element in this condition, mediated by various cytokines. The inflammatory signal induces activation of NF-κB, and prompts TGF-β-related signaling pathway. Clinical evolution leads to progressive debilitation, greatly affecting the patient quality of life. The actual therapeutic approaches, are few and expensive, and include systemic drugs such as prostanoids, phosphodiesterase inhibitors and antagonists of endothelin-1 (ERBs). Some researchers have long investigated the anti-inflammatory effects of curcumin. It shows a role for inactivation of NF-κB-mediated inflammation. On the basis of these findings we propose a potential role of curcumin and its pharmacologically fit derivatives for treatment of idiopathic pulmonary arterial hypertension.
    Full-text · Article · Aug 2013 · Medical Hypotheses
Show more