Evaluating Astaxanthin Bioavailability, and a New Technology for Improving it, Using Natural Food Materials Only

Clinical Evaluation of a New Encapsulation Technology for Improving Astaxanthin Bioavailability Based on Natural Food Ingredients Only

The purpose of this study was to develop a potato protein (PP)-based delivery system for increasing oral bioavailability of lipophilic bioactives (nutraceuticals and drugs), using astxanthin (AX) as a model, and to evaluate the system in vivo in a crossover clinical study in human volunteers. Three different formulations were prepared, encapsulating AX oleoresin (AXO) with (1) PP only, (2) PP+lecithin (LEC), and (3) PP+olive oil (OO). In a randomized, double-blind, crossover study in human subjects, the PP-OO-AX formulation had a 4.8-fold higher median plasma AX area under the concentration-over time curve (AUC; P<0.001) compared to the raw AXO formulation.

In conclusion, a non-allergenic, vegan, PP based delivery system made of "all-natural ingredients" offers a great promise for increasing oral bioavailability of lipophilic bioactives such as AX, for the enrichment of food and for dietary supplements, or oral delivery of lipophilic drugs.

Study Overview

• Status: Completed
• Conditions: Bioavailability
• Intervention / Treatment: Dietary supplement: AX-olive oil-PP emulsion

Detailed Description

Astaxanthin (AX) is a red xanthophyll carotenoid found mainly in algae (notably Haematococcus Pluvialis microalga) and marine animals. AX is a stronger antioxidant than vitamin E and β-carotene but has very low oral bioavailability. The purpose of this study was to develop a potato protein (PP)-based delivery system for increasing oral bioavailability of lipophilic bioactives (nutraceuticals and drugs), using AX as a model, and to evaluate the system in vitro and in vivo in a crossover clinical study in human volunteers. Three different formulations were prepared, encapsulating AX oleoresin (AXO) with (1) PP only, (2) PP+lecithin (LEC), and (3) PP+olive oil (OO). The average particle diameters after preparation were 0.29, 0.29, and 1.76 μm, and after freeze-drying and reconstitution 0.17, 0.07, and 6.93 μm, respectively. In vitro bioaccessibility was 33, 47, and 69%, respectively, versus 16% only for the raw AXO. In a randomized, double-blind, crossover study in human subjects, the PP-OO-AX formulation had a 4.8-fold higher median plasma AX area under the concentration-over time curve (AUC; P<0.001) compared to the raw AXO formulation. In conclusion, a non-allergenic, vegan, PP based delivery system made of "all-natural ingredients" offers a great promise for increasing oral bioavailability of lipophilic bioactives such as AX, for the enrichment of food and for dietary supplements, or oral delivery of lipophilic drugs.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Haifa, Israel
    • Rambam Health Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 26 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy volunteers
• Aged 18 - 26
• Normal physical examination
• Normal electrocardiogram (E.C.G.)
• Normal laboratory profile

Exclusion Criteria:

• Any active medical illness (e.g. liver disease, kidney disease, or diabetes, intestinal malabsorption, hypercalcemia)
• Lactose intolerance
• Food allergies
• Excessive alcohol use (over 40 ml/day)
• Pregnant or breast-feeding
• Hyperlipidemia (LDL>130, triglycerides>200)
• Regular medication use
• Obesity (BMI>30 kg/m2)
• Use of multivitamins, or carotenoid supplements during the past month prior to the study
• Current smoking

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: AX oleoresin; Raw AX oleoresin, 15 mg AX (in 4 pululan capsules)	Dietary supplement: AX-olive oil-PP emulsion; single dose and plasma samples; Other Names: (control- raw AXoleoresin)
EXPERIMENTAL: AX-olive oil-PP emulsion; Microencapsulated AX (1%:2%:3% (AXO:OO:PP, %w/v ratio) + 0.15% maltodextrin). 15 mg AX (in 4 pululan capsules)	Dietary supplement: AX-olive oil-PP emulsion; single dose and plasma samples; Other Names: (control- raw AXoleoresin)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma AX AUC	Plasma AX AUC of 13 participants after consuming either the microencapsulated AX or the reference AX oleoresin, measured during 72 hrs post-ingestion, in a cross over study.	1 year

Collaborators and Investigators

• Sponsor: Yoav D. Livney
• Collaborators: Israel Innovation Authority
• Investigators: Principal Investigator: Elena Segal, Doctor, Endocrine Institute, Rambam Health Care Campus

Publications and helpful links

General Publications

• Abuhassira-Cohen Y, Edelman R, Abbas R, Kurnik D, Shibel R, Livney YD, Enhancing the oral bioavailability of natural astaxanthin using plant-based micro- and nano-encapsulation materials: Results of an In vitro evaluation and a cross-over study in humans, Precision Nanomedicine 2020; 3 (4), 641-655.

Helpful Links

• The publication reporting the clinical study

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 15, 2018
• Primary Completion (ACTUAL): November 30, 2018
• Study Completion (ACTUAL): January 16, 2019

Study Registration Dates

• First Submitted: October 5, 2020
• First Submitted That Met QC Criteria: October 9, 2020
• First Posted (ACTUAL): October 12, 2020

Study Record Updates

• Last Update Posted (ACTUAL): April 1, 2021
• Last Update Submitted That Met QC Criteria: March 30, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Bioavailability; Encapsulation; Olive oil; Astaxanthin; Potato protein
• Other Study ID Numbers: 0048-18-RMB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No