Improved Oral Bioavailability of Curcumin Incorporated Into Micelles

Novel Strategies for the Enhancement of the Potency of Nutraceuticals With Low Oral Bioavailability and Their Application in Novel Functional Foods for Optimum Protection of the Aging Brain

Curcumin, a lipophilic polyphenol derived from the plant curcuma longa possesses numerous health-promoting activities. The oral bioavailability of curcumin is low due to its poor aqueous solubility, limited gastrointestinal absorption, rapid metabolism and excretion. Therefore, we tested, in a randomized crossover study, simultaneous application of phytochemicals and micellar solubilisation, alone and together, as strategies to enhance the absorption of curcumin into the body. Furthermore, we investigated age and sex differences in curcumin pharmacokinetics.

Study Overview

• Status: Completed
• Conditions: Pharmacokinetics of New Curcumin Formulations; Safety of New Curcumin Formulations
• Intervention / Treatment: Dietary supplement: curcumin

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Germany
  • Baden-Württemberg
    • Stuttgart, Baden-Württemberg, Germany, 70599
      • University of Hohenheim

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• healthy volunteers with routine blood chemistry values within the normal ranges
• Age: 18-35 years or > 60 years

Exclusion Criteria:

• overweight (BMI >30 kg/m2)
• metabolic and endocrine diseases
• pregnancy
• lactation
• drug abuse
• use of dietary supplements or any form of medication (with the exception of oral contraceptives)
• smoking
• frequent alcohol consumption (>20 g ethanol/d)
• adherence to a restrictive dietary regimen
• physical activity of more than 5 h/wk

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Native curcumin; 80 mg curcumin as native powder	Dietary supplement: curcumin; 80 mg curcumin were given orally either as native powder, native powder plus phytochemicals,micelles or micelles plus phytochemicals
Experimental: Native curcumin plus phytochemicals; 80 mg curcumin as native powder plus 80 mg sesamin, 40 mg naringenin, 40 mg ferulic acid and 40 mg xanthohumol	Dietary supplement: curcumin; 80 mg curcumin were given orally either as native powder, native powder plus phytochemicals,micelles or micelles plus phytochemicals
Experimental: Curcumin micelles; 80 mg curcumin incorporated into liquid micelles	Dietary supplement: curcumin; 80 mg curcumin were given orally either as native powder, native powder plus phytochemicals,micelles or micelles plus phytochemicals
Experimental: Curcumin micelles plus phytochemicals; 80 mg curcumin incorporated into liquid micelles plus 80 mg sesamin, 40 mg naringenin, 40 mg ferulic acid, 40 mg xanthohumol incorporated into micelles	Dietary supplement: curcumin; 80 mg curcumin were given orally either as native powder, native powder plus phytochemicals,micelles or micelles plus phytochemicals

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration versus time curve (AUC) of total curcumin [nmol/L*h]	Total curcumin was determined after deconjugation with beta-glucuronidase/sulphatase	0, 0.5, 1, 2, 4, 6, 8 and 24 h post-dose
Area under the plasma concentration versus time curve (AUC) of total demethoxycurcumin [nmol/L*h]	Total demethoxycurcumin was determined after deconjugation with beta-glucuronidase/sulphatase	0, 0.5, 1, 2, 4, 6, 8 and 24 h post-dose
Area under the plasma concentration versus time curve (AUC) of total bisdemethoxycurcumin [nmol/L*h]	Total bisdemethoxycurcumin was determined after deconjugation with beta-glucuronidase/sulphatase	0, 0.5, 1, 2, 4, 6, 8 and 24 h post-dose
Maximum plasma concentration (Cmax) of total curcumin [nmol/L]	Total curcumin was determined after deconjugation with beta-glucuronidase/sulphatase	0, 0.5, 1, 2, 4, 6, 8 and 24 h post-dose
Maximum plasma concentration (Cmax) of total demethoxycurcumin [nmol/L]	Total demethoxycurcumin was determined after deconjugation with beta-glucuronidase/sulphatase	0, 0.5, 1, 2, 4, 6, 8 and 24 h post-dose
Maximum plasma concentration (Cmax) of total bisdemethoxycurcumin [nmol/L]	Total bisdemethoxycurcumin was determined after deconjugation with beta-glucuronidase/sulphatase	0, 0.5, 1, 2, 4, 6, 8 and 24 h post-dose
Time to reach maximum plasma concentration (Tmax) of total curcumin [h]	Total curcumin was determined after deconjugation with beta-glucuronidase/sulphatase	0, 0.5, 1, 2, 4, 6, 8 and 24 h post-dose
Time to reach maximum plasma concentration (Tmax) of total demethoxycurcumin [h]	Total demethoxycurcumin was determined after deconjugation with beta-glucuronidase/sulphatase	0, 0.5, 1, 2, 4, 6, 8 and 24 h post-dose
Time to reach maximum plasma concentration (Tmax) of total bisdemethoxycurcumin [h]	Total bisdemethoxycurcumin was determined after deconjugation with beta-glucuronidase/sulphatase	0, 0.5, 1, 2, 4, 6, 8 and 24 h post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Serum aspartate transaminase activity [U/L]	0, 4, 24h post-dose
Serum alanine transaminase activity [U/L]	0, 4, 24h post-dose
Serum gamma-glutamyl transferase activity [U/L]	0, 4, 24h post-dose
Serum alkaline phosphatase activity [U/L]	0, 4, 24h post-dose
Serum uric acid [mg/dL]	0, 4, 24h post-dose
Serum creatinine [mg/dL]	0, 4, 24h post-dose
Serum total cholesterol [mg/dL]	0, 4, 24h post-dose
Serum HDL cholesterol [mg/dL]	0, 4, 24h post-dose
Serum LDL cholesterol [mg/dL]	0, 4, 24h post-dose
Serum triacylglycerols [mg/dL]	0, 4, 24h post-dose
Serum bilirubin [mg/dL]	0, 4, 24h post-dose

Collaborators and Investigators

• Sponsor: University of Hohenheim
• Collaborators: German Federal Ministry of Education and Research

Publications and helpful links

General Publications

• Kocher, A., Schiborr, C., Behnam, D., & Frank, J. (2015). The oral bioavailability of curcuminoids in healthy humans is markedly enhanced by micellar solubilisation but not further improved by simultaneous ingestion of sesamin, ferulic acid, naringenin and xanthohumol. J Funct Foods 14: 183-19.

Helpful Links

• Website of the research group

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: November 5, 2013
• First Submitted That Met QC Criteria: November 5, 2013
• First Posted (Estimate): November 13, 2013

Study Record Updates

• Last Update Posted (Estimate): October 25, 2016
• Last Update Submitted That Met QC Criteria: October 24, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: sex differences; pharmacokinetic; bioavailability; curcumin; curcuma longa; age differences
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Curcumin
• Other Study ID Numbers: 051113-HS2