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Author ORCID Identifier

https://orcid.org/0000-0002-5988-5961

AccessType

Campus-Only Access for Five (5) Years

Document Type

dissertation

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Food Science

Year Degree Awarded

2022

Month Degree Awarded

May

First Advisor

Hang Xiao

Subject Categories

Food Chemistry | Food Processing | Human and Clinical Nutrition

Abstract

Lipophilic nutraceuticals such as curcumin and carotenoids are health-promoting beneficial compounds found in various fruits and vegetables. However, the human utilization of lipophilic nutraceuticals was limited due to their poor oral bioavailability. We aimed to improve oral bioavailability by designing excipient emulsion food system. Initially, we determined the effects of different oil types of excipient emulsion on the bioavailability of curcumin. In this study, curcumin was incorporated in the excipient emulsions based on different carrier oil types, including corn oil, olive oil, and medium chain triglyceride (MCT). These emulsions were submitted to in vitro digestion model. The obtained micelle layer was applied on a Caco-2 cell model to evaluate the effects of oil type on the absorption and metabolism of curcumin. Results demonstrated that micelles from all groups improved the transportation rate of curcumin across Caco-2 cell monolayer. Among them, olive oil group exhibited the highest efficacy in the first 2 h. In addition, micelles, especially olive oil group, can protect curcumin from metabolism to produce both phase I and phase II metabolites. While most of curcumin metabolites are hexahydro-curcumin (HHC) and its conjugates, micelles facilitated producing a small portion of tetrahydro-curcumin (THC). These results have important implications in the rational design of lipid nanoparticle-based excipient systems to control the fate of nutraceuticals like curcumin.

Dietary lipid and black pepper have been shown to increase lipophilic nutraceuticals bioavailability by different mechanisms. However, their combined effects on bioavailability of lipophilic nutraceuticals remained unknown. We aimed to develop an innovative excipient system that utilized the combination of dietary lipid-based emulsion and black pepper to synergistically enhance oral bioavailability of carotenoids. In a randomized crossover design, healthy young adults consumed (1) vegetable salad (control), (2) salad with canola oil emulsion (COE), (3) salad with black pepper (BP), and (4) salad with canola oil emulsion and black pepper (COE + BP). COE + BP led to a higher AUC0–10h of total plasma carotenoids (p < 0.0005) than the control (6.1-fold), BP (2.1-fold), and COE (3.0-fold). COE + BP increased AUC0–10h of plasma lutein, α-carotene, β-carotene, and lycopene by 4.8, 9.7, 7.6, and 5.5- fold than the control, respectively (p < 0.0001). COE + BP produced a significant synergy in increasing both Cmax and AUC0–10h of total carotenoids, α-carotene, β-carotene, and lycopene. Moreover, COE + BP produced a stronger enhancement on AUC0–10h of total carotenoids, α-carotene, β-carotene, and lycopene in females than in males.

Our previous study demonstrated the canola oil emulsion significantly increased the bioavailability of carotenoids in vegetable salads. Moreover, the impact of different particle size of emulsion on the bioavailability of carotenoids in human is still unknown. Thus, this study aimed to evaluate the bioavailability of carotenoids with large particle size emulsion to compare with our previous study. Our results showed that the combination of canola oil coarse emulsion (COCE) and black pepper (BP) significantly increased the AUC0-10h of total carotenoids than control (3.9-fold), BP (1.9-fold), and COCE (1.7-fold), whereas the combination of canola oil emulsion (COE) and black pepper with smaller particle size showed significant higher bioavailability of carotenoids than COCE and BP. While the COCE and BP (AUC0-10h) led a stronger enhancement on bioavailability of lutein, α-carotene, β-carotene, and lycopene by 3.5, 5.9, 4.4, 3.4-fold than control, respectively.

We obtained results that 0.5g black pepper significantly improved the bioavailability of carotenoids. However, people have different preference on the amount of black pepper used in a meal. Therefore, the aim of the following study was to determine the efficacy of different dose of black pepper when combined with nanoemulsion in producing synergistic enhancement on carotenoid bioavailability under different dosing strategies of black pepper that are relevant to dietary pattern of Americans. In the randomized crossover design study, healthy adults (8 males and 8 females) consumed (1) vegetable salad (control); (2) vegetable salad with 0.1 g of black pepper and 40 g of canola oil emulsion pepper (COE + 0.1g BP); (3) vegetable salad with 0.3 g of black pepper and 40 g of canola oil emulsion (COE + 0.3g BP); (4) vegetable salad with 0.5 g of black pepper and 40 g of canola oil emulsion (COE + 0.5g BP); (5) mixed vegetable salad with 0.1 g of black pepper and 40 g of canola oil emulsion (COE + 0.1g×3 BP) (and 0.1 gram of BP added to the controlled lunch and dinner on the day before the test day). The results showed that COE+0.1g BP, COE+0.1g×3 BP, COE+0.3g BP, and COE+0.5g BP increased AUC0-10h by 3.4-fold, 3.6-fold, 4.4-fold, and 6.1-fold when compared with control, respectively. Overall, the bioavailability of carotenoids from vegetable salad was increasing with the increasing dose of black pepper.

Dietary lipids containing different composition of fatty acids may also contribute to the different bioavailability of lipophilic nutraceuticals. Thus, the following study aimed to determine the influence of different type of oils excipient emulsion including olive oil, canola oil, corn oil, sunflower oil, and flaxseed oil on bioavailability of carotenoids from vegetable salad in human. In the randomized crossover design study, healthy adults (8 males and 8 females) consumed (1) raw, mixed vegetable salad (control), (2) the salad with olive oil emulsion and 0.5 gram of black pepper (OE + BP), (2) the salad with canola oil emulsion and 0.5 gram of black pepper (COE + BP), (2) the salad with corn oil emulsion and 0.5 gram of black pepper (CE + BP), (2) the salad with sunflower oil emulsion and 0.5 gram of black pepper (SE + BP), and (2) the salad with flaxseed oil emulsion and 0.5 gram of black pepper (FE + BP). The newly absorbed carotenoids were quantified in the blood by high performance liquid chromatography. In summary, OE+BP, COE+BP, CE+BP, SE+BP, and FE+BP increased the CMAX by 5.9-fold, 5.7-fold, 5.4-fold, 5.2-fold, and 4.5-fold, and increased AUC0-10h by 6.5-fold, 6.1-fold, 5.7-fold, 5.2-fold, and 4.5-fold when compared with CTL, respectively. Overall, the oil containing more monounsaturated fatty acids produced higher bioavailability of carotenoids.

DOI

https://doi.org/10.7275/28345319

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Available for download on Saturday, May 13, 2023

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