Improved Oral Bioavailability of Curcumin Incorporated Into Micelles

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Pharmacokinetics of New Curcumin Formulations, Safety of New Curcumin Formulations

Intervention / Treatment
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* Dietary Supplement: curcumin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | Measure Description | 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 bilirubin [mg/dL] |  | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bioavailability, curcumin, pharmacokinetic, curcuma longa, age differences, sex differences