oral bioavailability of curcumin from micronized powder and liquid micelles is significantly increased in healthy humans and differs between sexes

SCOPE: Curcumin revealed various health‐beneficial properties in numerous studies. However its bioavailability is low due to its limited intestinal uptake and rapid metabolism. The aim of our project was to develop novel curcumin formulations with improved oral bioavailability and to study their saf...

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Veröffentlicht in:Molecular nutrition & food research Jg. 58; H. 3; S. 516 - 527
Hauptverfasser: Schiborr, Christina, Kocher, Alexa, Behnam, Dariush, Jandasek, Josef, Toelstede, Simone, Frank, Jan
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Weinheim Blackwell Publishing Ltd 01.03.2014
Wiley
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ISSN:1613-4125, 1613-4133, 1613-4133
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Abstract SCOPE: Curcumin revealed various health‐beneficial properties in numerous studies. However its bioavailability is low due to its limited intestinal uptake and rapid metabolism. The aim of our project was to develop novel curcumin formulations with improved oral bioavailability and to study their safety as well as potential sex‐differences. METHODS AND RESULTS: In this crossover study, healthy subjects (13 women, 10 men) took, in random order, a single oral dose of 500 mg curcuminoids as native powder, micronized powder, or liquid micelles. Blood and urine samples were collected for 24 h and total curcuminoids and safety parameters were quantified. Based on the area under the plasma concentration–time curve (AUC), the micronized curcumin was 14‐, 5‐, and 9‐fold and micellar curcumin 277‐, 114‐, and 185‐fold better bioavailable than native curcumin in women, men, and all subjects, respectively. Thus, women absorbed curcumin more efficiently than men. All safety parameters remained within the reference ranges following the consumption of all formulations. CONCLUSION: Both, the micronized powder and in particular the liquid micellar formulation of curcumin significantly improved its oral bioavailability without altering safety parameters and may thus be ideally suited to deliver curcumin in human intervention trials. The observed sex differences in curcumin absorption warrant further investigation.
AbstractList Curcumin revealed various health-beneficial properties in numerous studies. However its bioavailability is low due to its limited intestinal uptake and rapid metabolism. The aim of our project was to develop novel curcumin formulations with improved oral bioavailability and to study their safety as well as potential sex-differences. In this crossover study, healthy subjects (13 women, 10 men) took, in random order, a single oral dose of 500 mg curcuminoids as native powder, micronized powder, or liquid micelles. Blood and urine samples were collected for 24 h and total curcuminoids and safety parameters were quantified. Based on the area under the plasma concentration-time curve (AUC), the micronized curcumin was 14-, 5-, and 9-fold and micellar curcumin 277-, 114-, and 185-fold better bioavailable than native curcumin in women, men, and all subjects, respectively. Thus, women absorbed curcumin more efficiently than men. All safety parameters remained within the reference ranges following the consumption of all formulations. Both, the micronized powder and in particular the liquid micellar formulation of curcumin significantly improved its oral bioavailability without altering safety parameters and may thus be ideally suited to deliver curcumin in human intervention trials. The observed sex differences in curcumin absorption warrant further investigation.
SCOPE: Curcumin revealed various health‐beneficial properties in numerous studies. However its bioavailability is low due to its limited intestinal uptake and rapid metabolism. The aim of our project was to develop novel curcumin formulations with improved oral bioavailability and to study their safety as well as potential sex‐differences. METHODS AND RESULTS: In this crossover study, healthy subjects (13 women, 10 men) took, in random order, a single oral dose of 500 mg curcuminoids as native powder, micronized powder, or liquid micelles. Blood and urine samples were collected for 24 h and total curcuminoids and safety parameters were quantified. Based on the area under the plasma concentration–time curve (AUC), the micronized curcumin was 14‐, 5‐, and 9‐fold and micellar curcumin 277‐, 114‐, and 185‐fold better bioavailable than native curcumin in women, men, and all subjects, respectively. Thus, women absorbed curcumin more efficiently than men. All safety parameters remained within the reference ranges following the consumption of all formulations. CONCLUSION: Both, the micronized powder and in particular the liquid micellar formulation of curcumin significantly improved its oral bioavailability without altering safety parameters and may thus be ideally suited to deliver curcumin in human intervention trials. The observed sex differences in curcumin absorption warrant further investigation.
Scope Curcumin revealed various health‐beneficial properties in numerous studies. However its bioavailability is low due to its limited intestinal uptake and rapid metabolism. The aim of our project was to develop novel curcumin formulations with improved oral bioavailability and to study their safety as well as potential sex‐differences. Methods and results In this crossover study, healthy subjects (13 women, 10 men) took, in random order, a single oral dose of 500 mg curcuminoids as native powder, micronized powder, or liquid micelles. Blood and urine samples were collected for 24 h and total curcuminoids and safety parameters were quantified. Based on the area under the plasma concentration–time curve (AUC), the micronized curcumin was 14‐, 5‐, and 9‐fold and micellar curcumin 277‐, 114‐, and 185‐fold better bioavailable than native curcumin in women, men, and all subjects, respectively. Thus, women absorbed curcumin more efficiently than men. All safety parameters remained within the reference ranges following the consumption of all formulations. Conclusion Both, the micronized powder and in particular the liquid micellar formulation of curcumin significantly improved its oral bioavailability without altering safety parameters and may thus be ideally suited to deliver curcumin in human intervention trials. The observed sex differences in curcumin absorption warrant further investigation.
Curcumin revealed various health-beneficial properties in numerous studies. However its bioavailability is low due to its limited intestinal uptake and rapid metabolism. The aim of our project was to develop novel curcumin formulations with improved oral bioavailability and to study their safety as well as potential sex-differences.SCOPECurcumin revealed various health-beneficial properties in numerous studies. However its bioavailability is low due to its limited intestinal uptake and rapid metabolism. The aim of our project was to develop novel curcumin formulations with improved oral bioavailability and to study their safety as well as potential sex-differences.In this crossover study, healthy subjects (13 women, 10 men) took, in random order, a single oral dose of 500 mg curcuminoids as native powder, micronized powder, or liquid micelles. Blood and urine samples were collected for 24 h and total curcuminoids and safety parameters were quantified. Based on the area under the plasma concentration-time curve (AUC), the micronized curcumin was 14-, 5-, and 9-fold and micellar curcumin 277-, 114-, and 185-fold better bioavailable than native curcumin in women, men, and all subjects, respectively. Thus, women absorbed curcumin more efficiently than men. All safety parameters remained within the reference ranges following the consumption of all formulations.METHODS AND RESULTSIn this crossover study, healthy subjects (13 women, 10 men) took, in random order, a single oral dose of 500 mg curcuminoids as native powder, micronized powder, or liquid micelles. Blood and urine samples were collected for 24 h and total curcuminoids and safety parameters were quantified. Based on the area under the plasma concentration-time curve (AUC), the micronized curcumin was 14-, 5-, and 9-fold and micellar curcumin 277-, 114-, and 185-fold better bioavailable than native curcumin in women, men, and all subjects, respectively. Thus, women absorbed curcumin more efficiently than men. All safety parameters remained within the reference ranges following the consumption of all formulations.Both, the micronized powder and in particular the liquid micellar formulation of curcumin significantly improved its oral bioavailability without altering safety parameters and may thus be ideally suited to deliver curcumin in human intervention trials. The observed sex differences in curcumin absorption warrant further investigation.CONCLUSIONBoth, the micronized powder and in particular the liquid micellar formulation of curcumin significantly improved its oral bioavailability without altering safety parameters and may thus be ideally suited to deliver curcumin in human intervention trials. The observed sex differences in curcumin absorption warrant further investigation.
Author Behnam, Dariush
Jandasek, Josef
Frank, Jan
Kocher, Alexa
Toelstede, Simone
Schiborr, Christina
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  fullname: Toelstede, Simone
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  fullname: Frank, Jan
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https://www.ncbi.nlm.nih.gov/pubmed/24402825$$D View this record in MEDLINE/PubMed
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Issue 3
Keywords Human
Monocotyledones
Curcuma longal
Nutrition
Tyrosine kinase inhibitor
Toxicity
Sex
Oral administration
Micelle
Sex differences
Healthy humans
Bioavailability
Powder
Liquid
Angiospermae
Spermatophyta
Curcumin
Curcuma
Safety
Pharmacokinetics
Zingiberaceae
Curcuma longa
Language English
License Attribution-NonCommercial-NoDerivs
http://creativecommons.org/licenses/by-nc-nd/3.0
CC BY 4.0
2014 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
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PublicationTitle Molecular nutrition & food research
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Garcea, G., Berry, D. P., Jones, D. J., Singh, R. et al., Consumption of the putative chemopreventive agent curcumin by cancer patients: assessment of curcumin levels in the colorectum and their pharmacodynamic consequences. Cancer Epidemiol. Biomarkers Prev. 2005, 14, 120-125.
Eckert, G. P., Schiborr, C., Hagl, S., Abdel-Kader, R. et al., Curcumin prevents mitochondrial dysfunction in the brain of the senescence-accelerated mouse-prone 8. Neurochem. Int. 2013, 62, 595-602.
Pan, M. H., Huang, T. M., Lin, J. K., Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metab. Dispos. 1999, 27, 486-494.
Sugawara, J., Akazawa, N., Miyaki, A., Choi, Y. et al., Effect of endurance exercise training and curcumin intake on central arterial hemodynamics in postmenopausal women: pilot study. Am. J. Hypertens. 2012, 25, 651-656.
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Lao, C. D., Ruffin, M. T., Normolle, D., Heath, D. D. et al., Dose escalation of a curcuminoid formulation. BMC Complement. Alter. Med. 2006, 6, 10. doi:10.1186/1472-6882-6-10.
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Anand, K., Sarkar, A., Kumar, A., Ambasta, R. K. et al., Combinatorial antitumor effect of naringenin and curcumin elicit angioinhibitory activities in vivo. Nutr. Cancer 2012, 64, 714-724.
Jurenka, J. S., Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Altern. Med. Rev. 2009, 14, 141-153.
Thayyullathil, F., Chathoth, S., Hago, A., Patel, M. et al., Rapid reactive oxygen species (ROS) generation induced by curcumin leads to caspase-dependent and -independent apoptosis in L929 cells. Free Radic. Biol. Med. 2008, 45, 1403-1412.
Kuo, C. L., Wu, S. Y., Ip, S. W., Wu, P. P. et al., Apoptotic death in curcumin-treated NPC-TW 076 human nasopharyngeal carcinoma cells is mediated through the ROS, mitochondrial depolarization and caspase-3-dependent signaling responses. Int. J. Oncol. 2011, 39, 319-328.
Antony, B., Merina, B., Iyer, V. S., Judy, N. et al., A pilot cross-over study to evaluate human oral bioavailability of BCM-95CG (Biocurcumax), a novel bioenhanced preparation of curcumin. Indian J. Pharm. Sci. 2008, 70, 445-449.
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Gota, V. S., Maru, G. B., Soni, T. G., Gandhi, T. R. et al., Safety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy volunteers. J. Agric. Food Chem. 2010, 58, 2095-2099.
Chandran, B., Goel, A., A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis. Phytother. Res. 2012, 26, 1719-1725.
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Carroll, R. E., Benya, R. V., Turgeon, D. K., Vareed, S. et al., Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev. Res. (Phila) 2011, 4, 354-364.
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Ringman, J. M., Frautschy, S. A., Teng, E., Begum, A. N. et al., Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study. Alzheimers Res. Ther. 2012, 4, 43. doi:10.1186/alzrt146.
Cheng, A. L., Hsu, C. H., Lin, J. K., Hsu, M. M. et al., Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 2001, 21, 2895-2900.
Vareed, S. K., Kakarala, M., Ruffin, M. T., Crowell, J. A. et al., Pharmacokinetics of curcumin conjugate metabolites in healthy human subjects. Cancer Epidemiol. Biomarkers Prev. 2008, 17, 1411-1417.
Heath, D. D., Pruitt, M. A., Brenner, D. E., Rock, C. L., Curcumin in plasma and urine: quantitation by high-performance liquid chromatography. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2003, 783, 287-295.
2011; 652
2012; 2012
2005; 273
2010; 58
2010; 17
2013; 62
1999; 27
2008; 17
2011; 74
2009; 652
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1998; 433
2011; 34
2011; 14
2011; 39
2011; 4
2012; 35
2008; 70
1998; 64
2012; 11
2012; 32
2011; 8
2001; 21
2004; 10
2009; 14
2004; 75
2010; 1
2013; 33
2001; 7
2002; 41
2002; 23
2007; 595
2011; 50
2008; 45
2012; 26
2010; 70
2012; 25
2012; 69
2008; 40
2012; 7
2012; 4
2012; 22
2003; 783
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Mol Nutr Food Res. 2014 Mar;58(3):647
References_xml – reference: Dal Piaz F, B. A., Belisario, M. A., De Tommasi, N., Thioredoxin system modulation by plant and fungal secondary metabolites. Curr. Med. Chem. 2010, 17, 479-494.
– reference: Schaffer, M., Schaffer, P. M., Zidan, J., Bar Sela, G., Curcuma as a functional food in the control of cancer and inflammation. Curr. Opin. Clin. Nutr. Metab. Care 2011, 14, 588-597.
– reference: Liu, H., Liang, Y., Wang, L., Tian, L. et al., In vivo and in vitro suppression of hepatocellular carcinoma by EF24, a curcumin analog. PLoS One 2012, 7, e48075.
– reference: Eckert, G. P., Schiborr, C., Hagl, S., Abdel-Kader, R. et al., Curcumin prevents mitochondrial dysfunction in the brain of the senescence-accelerated mouse-prone 8. Neurochem. Int. 2013, 62, 595-602.
– reference: Garcea, G., Berry, D. P., Jones, D. J., Singh, R. et al., Consumption of the putative chemopreventive agent curcumin by cancer patients: assessment of curcumin levels in the colorectum and their pharmacodynamic consequences. Cancer Epidemiol. Biomarkers Prev. 2005, 14, 120-125.
– reference: Savjani, K. T., Gajjar, A. K., Savjani, J. K., Drug solubility: importance and enhancement techniques. ISRN Pharm. 2012, 2012, 195727. doi:10.5402/2012/195727.
– reference: Sugawara, J., Akazawa, N., Miyaki, A., Choi, Y. et al., Effect of endurance exercise training and curcumin intake on central arterial hemodynamics in postmenopausal women: pilot study. Am. J. Hypertens. 2012, 25, 651-656.
– reference: Lao, C. D., Ruffin, M. T., Normolle, D., Heath, D. D. et al., Dose escalation of a curcuminoid formulation. BMC Complement. Alter. Med. 2006, 6, 10. doi:10.1186/1472-6882-6-10.
– reference: Heath, D. D., Pruitt, M. A., Brenner, D. E., Rock, C. L., Curcumin in plasma and urine: quantitation by high-performance liquid chromatography. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2003, 783, 287-295.
– reference: Belakavadi, M., Salimath, B. P., Mechanism of inhibition of ascites tumor growth in mice by curcumin is mediated by NF-kB and caspase activated DNase. Mol. Cell Biochem. 2005, 273, 57-67.
– reference: Gota, V. S., Maru, G. B., Soni, T. G., Gandhi, T. R. et al., Safety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy volunteers. J. Agric. Food Chem. 2010, 58, 2095-2099.
– reference: Cuomo, J., Appendino, G., Dern, A. S., Schneider, E. et al., Comparative absorption of a standardized curcuminoid mixture and its lecithin formulation. J. Nat. Prod. 2011, 74, 664-669.
– reference: Alwi, I., Santoso, T., Suyono, S., Sutrisna, B. et al., The effect of curcumin on lipid level in patients with acute coronary syndrome. Acta. Med. Indones 2008, 40, 201-210.
– reference: Sharma, R. A., Euden, S. A., Platton, S. L., Cooke, D. N. et al., Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin Cancer Res. 2004, 10, 6847-6854.
– reference: Lim, G. P., Chu, T., Yang, F., Beech, W. et al., The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J. Neurosci. 2001, 21, 8370-8377.
– reference: Kuo, C. L., Wu, S. Y., Ip, S. W., Wu, P. P. et al., Apoptotic death in curcumin-treated NPC-TW 076 human nasopharyngeal carcinoma cells is mediated through the ROS, mitochondrial depolarization and caspase-3-dependent signaling responses. Int. J. Oncol. 2011, 39, 319-328.
– reference: Kurita, T., Makino, Y., Novel curcumin oral delivery systems. Anticancer Res. 2013, 33, 2807-2821.
– reference: Anand, K., Sarkar, A., Kumar, A., Ambasta, R. K. et al., Combinatorial antitumor effect of naringenin and curcumin elicit angioinhibitory activities in vivo. Nutr. Cancer 2012, 64, 714-724.
– reference: Khajehdehi, P., Zanjaninejad, B., Aflaki, E., Nazarinia, M. et al., Oral supplementation of turmeric decreases proteinuria, hematuria, and systolic blood pressure in patients suffering from relapsing or refractory lupus nephritis: a randomized and placebo-controlled study. J. Ren. Nutr. 2012, 22, 50-57.
– reference: Pareyson, D., Marchesi, C., Natural history and treatment of peripheral inherited neuropathies. Adv. Exp. Med. Biol. 2009, 652, 207-224.
– reference: Shoba, G., Joy, D., Joseph, T., Majeed, M. et al., Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med. 1998, 64, 353-356.
– reference: Vareed, S. K., Kakarala, M., Ruffin, M. T., Crowell, J. A. et al., Pharmacokinetics of curcumin conjugate metabolites in healthy human subjects. Cancer Epidemiol. Biomarkers Prev. 2008, 17, 1411-1417.
– reference: Carroll, R. E., Benya, R. V., Turgeon, D. K., Vareed, S. et al., Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev. Res. (Phila) 2011, 4, 354-364.
– reference: Karlstetter, M., Lippe, E., Walczak, Y., Moehle, C. et al., Curcumin is a potent modulator of microglial gene expression and migration. J. Neuroinflammat. 2011, 8, 125. doi:10.1186/1742-2094-8-125.
– reference: Meibohm, B., Beierle, I., Derendorf, H., How important are gender differences in pharmacokinetics? Clin. Pharmacokinet. 2002, 41, 329-342.
– reference: Jemal, A., Murray, T., Ward, E., Samuels, A. et al., Cancer statistics, 2005. CA Cancer. J. Clin. 2005, 55, 10-30.
– reference: Sharma, R. A., Steward, W. P., Gescher, A. J., Pharmacokinetics and pharmacodynamics of curcumin. Adv. Exp. Med. Biol. 2007, 595, 453-470.
– reference: Pan, M. H., Huang, T. M., Lin, J. K., Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metab. Dispos. 1999, 27, 486-494.
– reference: Sasaki, H., Sunagawa, Y., Takahashi, K., Imaizumi, A. et al., Innovative preparation of curcumin for improved oral bioavailability. Biol. Pharm. Bull. 2011, 34, 660-665.
– reference: Kanai, M., Imaizumi, A., Otsuka, Y., Sasaki, H. et al., Dose-escalation and pharmacokinetic study of nanoparticle curcumin, a potential anticancer agent with improved bioavailability, in healthy human volunteers. Cancer Chemother. Pharmacol. 2012, 69, 65-70.
– reference: Chandran, B., Goel, A., A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis. Phytother. Res. 2012, 26, 1719-1725.
– reference: Akazawa, N., Choi, Y., Miyaki, A., Tanabe, Y. et al., Curcumin ingestion and exercise training improve vascular endothelial function in postmenopausal women. Nutr. Res. 2012, 32, 795-799.
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Snippet SCOPE: Curcumin revealed various health‐beneficial properties in numerous studies. However its bioavailability is low due to its limited intestinal uptake and...
Scope Curcumin revealed various health‐beneficial properties in numerous studies. However its bioavailability is low due to its limited intestinal uptake and...
Curcumin revealed various health-beneficial properties in numerous studies. However its bioavailability is low due to its limited intestinal uptake and rapid...
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StartPage 516
SubjectTerms absorption
Administration, Oral
Bioavailability
Biological and medical sciences
Biological Availability
blood
Cross-Over Studies
Curcuma longa
Curcumin
Curcumin - adverse effects
Curcumin - analogs & derivatives
Curcumin - analysis
Curcumin - metabolism
Curcumin - pharmacokinetics
Diarylheptanoids
Feeding. Feeding behavior
Female
Fundamental and applied biological sciences. Psychology
gender differences
Healthy humans
Humans
Male
men
Micelles
Powders
Safety
Sex differences
Sex Factors
urine
Vertebrates: anatomy and physiology, studies on body, several organs or systems
women
Young Adult
Title oral bioavailability of curcumin from micronized powder and liquid micelles is significantly increased in healthy humans and differs between sexes
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https://www.proquest.com/docview/1539444485
Volume 58
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