Oral Bioavailability of Curcumin From Micronized Powder and Liquid Micelles in Healthy Young Women and Men

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

Background: The oral bioavailability of curcumin is low due to its limited intestinal uptake, rapid metabolism and excretion from the body. Considering its potent reported health-beneficial properties, researchers have tried to increase its bioavailability as a means to enhance its biological activities.

Objective: The aim of the project was to develop novel curcumin formulations with enhanced oral bioavailability and to study the safety of the formulations and potential sex-differences in humans.

Design: In this single-blind crossover study with three arms separated by ≥1-week washout periods, healthy subjects (13 women, 10 men) were provided standardized meals and took, in random order, a single oral dose of 500 mg curcumin as native powder, micronized powder, or liquid micelles. Blood and urine samples were collected in intervals for 24 h and total curcumin, demethoxycurcumin, and bis-demethoxycurcumin were quantified.

Study Overview

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

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

Contacts and Locations

Study Locations

• Germany
  • Stuttgart, Germany, 70599
    • University of Hohenheim

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• healthy volunteers with routine blood chemistry values within the normal ranges

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
• participation in a clinical trial within the past 3 months prior to recruitment
• known intolerance against curcuma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Native curcumin powder; 500 mg curcumin as native powder	Dietary supplement: curcumin; 500 mg curcumin were given orally either as native powder, micronized powder, or liquid micelles
EXPERIMENTAL: Micronized curcumin powder; 500 mg curcumin as micronized powder	Dietary supplement: curcumin; 500 mg curcumin were given orally either as native powder, micronized powder, or liquid micelles
EXPERIMENTAL: Curcumin micelles; 500 mg curcumin incorporated into liquid micelles	Dietary supplement: curcumin; 500 mg curcumin were given orally either as native powder, micronized powder, or liquid micelles

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, 1.5, 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, 1.5, 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, 1.5, 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, 1.5, 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, 1.5, 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, 1.5, 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, 1.5, 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, 1.5, 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, 1.5, 2, 4, 6, 8 and 24 h post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Serum aspartate transaminase activity [U/L]	Baseline
Serum aspartate transaminase activity [U/L]	4 h post-dose
Serum aspartate transaminase activity [U/L]	24 h post-dose
Serum alanine transaminase activity [U/L]	Baseline
Serum alanine transaminase activity [U/L]	4 h post-dose
Serum alanine transaminase activity [U/L]	24 h post-dose
Serum gamma-glutamyl transferase activity [U/L]	Baseline
Serum gamma-glutamyl transferase activity [U/L]	4 h post-dose
Serum gamma-glutamyl transferase activity [U/L]	24 h post-dose
Serum alkaline phosphatase activity [U/L]	Baseline
Serum alkaline phosphatase activity [U/L]	4 h post-dose
Serum alkaline phosphatase activity [U/L]	24 h post-dose
Serum bilirubin [mg/dL]	Baseline
Serum bilirubin [mg/dL]	4 h post-dose
Serum bilirubin [mg/dL]	24 h post-dose
Serum uric acid [mg/dL]	Baseline
Serum uric acid [mg/dL]	4 h post-dose
Serum uric acid [mg/dL]	24 h post-dose
Serum cystatin C [mg/L]	Baseline
Serum cystatin C [mg/L]	4 h post-dose
Serum cystatin C [mg/L]	24 h post-dose
Glomerular filtration rate [mL/min]	Baseline
Glomerular filtration rate [mL/min]	4 h post-dose
Glomerular filtration rate [mL/min]	24 h post-dose
Serum creatinine [mg/dL]	Baseline
Serum creatinine [mg/dL]	4 h post-dose
Serum creatinine [mg/dL]	24 h post-dose
Serum total cholesterol [mg/dL]	Baseline
Serum total cholesterol [mg/dL]	4 h post-dose
Serum total cholesterol [mg/dL]	24 h post-dose
Serum HDL cholesterol [mg/dL]	Baseline
Serum HDL cholesterol [mg/dL]	4 h post-dose
Serum HDL cholesterol [mg/dL]	24 h post-dose
Serum LDL cholesterol [mg/dL]	Baseline
Serum LDL cholesterol [mg/dL]	4 h post-dose
Serum LDL cholesterol [mg/dL]	24 h post-dose
Serum triacylglycerols [mg/dL]	Baseline
Serum triacylglycerols [mg/dL]	4 h post-dose
Serum triacylglycerols [mg/dL]	24 h post-dose

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Schiborr C, Kocher A, Behnam D, Jandasek J, Toelstede S, Frank J. The oral bioavailability of curcumin from micronized powder and liquid micelles is significantly increased in healthy humans and differs between sexes. Mol Nutr Food Res. 2014 Mar;58(3):516-27. doi: 10.1002/mnfr.201300724. Epub 2014 Jan 9. Erratum In: Mol Nutr Food Res. 2014 Mar;58(3):647. Dosage error in article text.

Helpful Links

• Website of the research group

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (ACTUAL): July 1, 2013
• Study Completion (ACTUAL): July 1, 2013

Study Registration Dates

• First Submitted: August 13, 2013
• First Submitted That Met QC Criteria: August 15, 2013
• First Posted (ESTIMATE): August 19, 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: safety; sex differences; bioavailability; curcumin; healthy humans; curcuma longa
• 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: 01EA1334AHS1