Astaxanthin Formulation Bioavailability

Bioavailability Testing of Astaxanthin Formulations

Human crossover pharmacokinetic study involving 12 subjects to determine the relative bioavailability of astaxanthin in six commercially available oral formulations.

Study Overview

• Status: Completed
• Conditions: Bioavailability of Astaxanthin Formulations
• Intervention / Treatment: Dietary supplement: Enteric Coated Softgels; Dietary supplement: Liposomal astaxanthin; Dietary supplement: Standard Softgel; Dietary supplement: Astaxanthin Water Soluble Emulsion; Dietary supplement: Astaxanthin Water Dispersible Powder; Dietary supplement: Standard Softgel with Astaxanthin Gel

Detailed Description

Astaxanthin is commercially available through several vendors. As a highly-lipophilic compound, its oral bioavailability is likely limited by its solubility in the gut. Pre-formulation strategies for addressing limited solubility include pre-dissolving the astaxanthin in fatty solvents and encapsulating in gelatin capsules. This study will evaluate the oral bioavailability of six different formulations of astaxanthin (12mg) in a double blind crossover study involving 12 subjects.

All subjects will be asked to abstain from consuming any salmon 48hrs before and consuming any food or alcoholic beverages 10 hours before reporting to the blood draw center at 8 AM. They will be fed a standardized breakfast by choosing one of two Jimmy Dean brand breakfast sandwiches (EGG, RED PEPPERS, ONIONS AND PEPPER JACK CHEESE CROISSANT or BACON, EGG & CHEESE BISCUIT. Immediately following the standardized meal, they will take one of six different formulations each containing 12 mg of astaxanthin. Bottled water (Zephyrhills® Brand 100% Natural Spring Water) will be available to each subject ad lib. Blood will be collected immediately before consuming the standardized meal and formulation (0 hr) and then again at 4, 8, 10, and 24 hours post dose by a licensed phlebotomist. In between blood draws, the subjects will be allowed to leave the clinic and allowed to resume their normal diet and lifestyle. However, they will be asked to abstain from consuming any alcoholic beverages or salmon until after completion of the last blood draw at 24hrs. As a measure of quality control, each subject will receive a breathalyzer test for alcohol prior to the 0 and 24 hr blood draws. For each time point, blood will be collected in one 10ml Vacutainer Tube (BD 16x100 containing K2 EDTA) labeled using the randomization scheme to blind the samples. Because 3 of the formulations are powders and the remaining 3 formulations are capsules, which differ slightly size and appearance, neither the subjects nor investigators will be blind to the formulation being tested on any given day. However, each subject will receive separate random assignment to each of the 6 formulations tested over the course of the study and all blood samples will be blinded to the quantitative analysis of astaxanthin plasma levels. This process will be repeated six times for the entire subject population (with-in subject design) with two-week washout periods between each pharmacokinetic (pK) run. The blinded blood samples will be kept refrigerated and will be transported to the Center for Excellence and Brain Repair (CEABR) lab within 24 hours, where it will be processed and subjected to the High pressure liquid chromatograph (HPLC) analysis to quantify the astaxanthin.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • USF Health: College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:Subjects who have signed an informed consent form and who meet all of the following entrance criteria may be enrolled in this clinical trial: Generally healthy men and women who are 21 to 65 years of age, inclusive, at the baseline visit.

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Exclusion Criteria:Subjects who meet any of the following exclusion criteria are not eligible for participation in this clinical trial:

1. Are unwilling to follow the procedures of the trial, such as making visits or having their blood drawn.
2. Have unintentionally lost or gained 10 or more pounds of body weight in the last 3 months;
3. Have an acute illness (such as a severe cold or flu) or have been hospitalized within the past month for certain conditions;
4. Have severe co-morbid disease including cardiac, pulmonary, renal, hepatic, carotid, peripheral vascular disease, stroke, neurological, clotting disorders or active cancer;
5. Consume alcohol at an elevated level (Defined as consumption of more than 10 standard alcoholic drinks per week. A standard alcoholic drink is defined as one bottle/can of beer (12 ounces) equals one glass of wine (4 ounces) equals one ounce of hard liquor).
6. Have a Body Mass Index (BMI) of less than 15 or greater than 55 m/kg2;
7. Have participated in a clinical trial in the past 4 weeks;
8. Have any disease or condition that in the investigator's opinion compromises the integrity of the clinical trial or the safety of the subject;
9. Severe co-morbid disease is defined as any condition that would cause severe limitations or inability to carry out usual activities of daily living.

10. The exclusion criteria identified above are based upon general safety concerns identified by the study supervisor with input from medical director, or confounders identified by the biostatistician.

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Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Enteric Coated Softgels; Enteric coated softgel capsule containing 4 mg astaxanthin, 3 softgels per dose	Dietary supplement: Enteric Coated Softgels; Enteric coated softgel capsule containing 4 mg astaxanthin, 3 softgels per dose; Other Names: BioAstin
Experimental: Liposomal Astaxanthin; Liposomal astaxanthin containing 4.5 mg astaxanthin per gram. 2.66 grams per dose	Dietary supplement: Liposomal astaxanthin; Liposomal astaxanthin containing 4.5 mg astaxanthin per gram. 3.66 grams per dose; Other Names: BioAstin
Experimental: Standard Softgel; Standard softgel containing 4 mg per softgel. 3 softgels per dose	Dietary supplement: Standard Softgel; Standard softgel containing 4 mg astaxanthin per softgel. 3 softgels per dose; Other Names: BoAstin
Experimental: Astaxanthin Water Soluble Emulsion; Astaxanthin water soluble emulsion containing 1% astaxanthin. 1.2 grams per dose	Dietary supplement: Astaxanthin Water Soluble Emulsion; Astaxanthin water soluble emulsion containing 1% astaxanthin. 1.2 grams per dose; Other Names: BioAstin
Experimental: Astaxanthin Water Dispersible Powder; Astaxanthin water dispersible powder containing 3% astaxanthin. 0.4 grams per dose	Dietary supplement: Astaxanthin Water Dispersible Powder; Astaxanthin water dispersible powder containing 3% astaxanthin. 0.4 grams per dose; Other Names: BioAstin
Experimental: Standard Softgel with Astaxanthin Gel; Statndard softgel with astaxanthin gel containing 4 mg astaxanthin. 3 softgels per dose	Dietary supplement: Standard Softgel with Astaxanthin Gel; Standard softgel with astaxanthin gel containing 4 mg astaxanthin. 3 soft gels per dose; Other Names: BioAstin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Peak Plasma Concentration Cmax) of astaxanthin	24 hurs
Area under the plasma concentration versus time curve (AUC) of astaxanthin	24 hours

Collaborators and Investigators

• Sponsor: Cyanotech Corporation
• Collaborators: University of South Florida

Publications and helpful links

General Publications

• Baralic I, Djordjevic B, Dikic N, Kotur-Stevuljevic J, Spasic S, Jelic-Ivanovic Z, Radivojevic N, Andjelkovic M, Pejic S. Effect of astaxanthin supplementation on paraoxonase 1 activities and oxidative stress status in young soccer players. Phytother Res. 2013 Oct;27(10):1536-42. doi: 10.1002/ptr.4898. Epub 2012 Nov 28.
• Barros MP, Marin DP, Bolin AP, de Cassia Santos Macedo R, Campoio TR, Fineto C Jr, Guerra BA, Polotow TG, Vardaris C, Mattei R, Otton R. Combined astaxanthin and fish oil supplementation improves glutathione-based redox balance in rat plasma and neutrophils. Chem Biol Interact. 2012 Apr 15;197(1):58-67. doi: 10.1016/j.cbi.2012.03.005. Epub 2012 Mar 21.
• Bolin AP, Macedo RC, Marin DP, Barros MP, Otton R. Astaxanthin prevents in vitro auto-oxidative injury in human lymphocytes. Cell Biol Toxicol. 2010 Oct;26(5):457-67. doi: 10.1007/s10565-010-9156-4. Epub 2010 Mar 14.
• Smith AJ, Kavuru P, Wojtas L, Zaworotko MJ, Shytle RD. Cocrystals of quercetin with improved solubility and oral bioavailability. Mol Pharm. 2011 Oct 3;8(5):1867-76. doi: 10.1021/mp200209j. Epub 2011 Aug 25.
• Smith AJ, Kavuru P, Arora KK, Kesani S, Tan J, Zaworotko MJ, Shytle RD. Crystal engineering of green tea epigallocatechin-3-gallate (EGCg) cocrystals and pharmacokinetic modulation in rats. Mol Pharm. 2013 Aug 5;10(8):2948-61. doi: 10.1021/mp4000794. Epub 2013 Jun 26.

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: March 20, 2015
• First Submitted That Met QC Criteria: March 20, 2015
• First Posted (Estimate): March 25, 2015

Study Record Updates

• Last Update Posted (Estimate): August 9, 2016
• Last Update Submitted That Met QC Criteria: August 5, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Other Study ID Numbers: Pro00019850