Comprehensive Reviews In Food Science And Food Safety

Bioavailability of nutraceuticals: Role of the food matrix, processing conditions, the gastrointestinal tract, and nanodelivery systems

Cristian Dima,  Elham Assadpour,  Stefan Dima,  Seid Mahdi Jafari
First published: 04 March 2020


Nowadays, many consumers prefer foods with a high content of nutraceuticals that contribute to the prevention or healing of chronic diseases. Therefore, in recent years, more and more researchers have studied the bioefficiency, safety, and toxicity of nutraceutical‐enriched foods. The key stage of nutraceutical bioefficiency is oral bioavailability, which involves the following processes: the release of nutraceuticals from food matrices or nanocarriers in gastrointestinal fluids, the solubilization of nutraceuticals and their interaction with other components of gastrointestinal fluids, the absorption of nutraceuticals by the epithelial layer, and the chemical and biochemical transformations into epithelial cells. These processes are endogenous factors that greatly influence the bioavailability of nutraceuticals. In addition to endogenous factors, the bioavailability of nutraceuticals is also affected by exogenous factors, such as: physicochemical properties of nutraceuticals, food matrix, food processing and storage, and so forth. Both the endogenous and exogenous factors are comprehensively analyzed in this review. Thus, the physicochemical and enzymatic processes involved in food digestion are described, highlighting the role of each stage of gastrointestinal tract (mouth, stomach, and intestine) in nutraceuticals bioaccessibility. The structure and functions of the mucus and epithelial layers, the mechanisms involved in the active and passive transport of nutraceuticals through the cell membrane, and phase I and phase II metabolism reactions are also discussed. Finally, this review focuses on several types of bioactive‐loaded nanocarriers such as lipid‐based, surfactant‐based, and biopolymeric nanocarriers that improve the bioavailability of nutraceuticals.


Consumers have lately been more and more inclined to prefer foods able to provide not only the nutritional needs for the biological functions of the human body, but also long‐term health benefits (Assadpour & Jafari, 2019a,2019b; Jafari, Vakili, & Dehnad, 2019). With this in mind, preferences go toward foods rich in bioactive compounds/nutraceuticals that have the potential to minimize the risk of acute and chronic illnesses, such as cardiovascular diseases, immunodeficiencies, neurodegenerative diseases, cancer, obesity, and so forth (Chow, 2014). In order to define bioactive compounds with the nutritive and physiological effects, De Felice (1995) coined the term “nutraceutical,” by combining “nutrition” and “pharmaceutical” words (De Felice, 1995). According to De Felice’s definition, nutraceuticals are “foods or parts of food offering health benefits, including the prevention and treatment of diseases.” The term “nutraceutical” was defined and accepted in various countries in a different manner. For instance, in China, nutraceuticals are regulated by law and allowed as an alternative and complementary method of treating and preventing some diseases (Gupta, 2016). In the United States and European Union, nutraceuticals are regulated as food supplements. Thus, according to the Dietary Supplement and Health Education Act (DSHEA), a dietary supplement is a product “intended to supplement the diet” that contains one or more of the following: a vitamin, mineral, herb, or botanical, amino acid, or “a dietary substance for consumption by man to supplement the diet by increasing the total dietary intake” or a “concentrate, metabolite, constituent, extract, or combination of the above.” (, January 23, 2019, DSHEA).

According to the definition above, nutraceuticals also include substances that are not traditionally acknowledged as nutrients (e.g., vitamins and minerals) or are not synthesized by the human body but are known to be beneficial to human health. From a chemical point of view, nutraceuticals are compounds belonging to different classes, such as polyphenols, polyunsaturated omega‐3 fatty acids (PUFA omega 3), conjugated linoleic acids (CLAs), terpenoids, alkaloids, carotenoids, and so forth (Mudila, Prasher, Kumar, & Punetha, 2018).

With regard to the fundamental changes in the lifestyle of people in developed countries, consumption of the nutraceuticals and food supplements has increased tremendously. It is estimated that by 2021, the nutraceuticals market will reach 278.96 billion US$, as compared to 2014 when it was 165.62 billion US$ (Mudila et al., 2018). In this context, it is imperative to provide clear and complete regulations on the efficiency, safety, and toxicity of nutraceuticals and food supplements, respectively. Therefore, over the last decade, academic and industrial research has focused on assessing the biological efficiency of nutraceuticals consumed directly from natural sources, or from functional foods and/or dietary supplements (McClements & Xiao, 2014). In this respect, according to data from the literature, researchers in the food, pharmaceutical, and medical fields have the following common research topics: in vitro and in vivo testing of the physiological effects of nutraceuticals; developing and standardizing in vitro and in vivo investigation methods for evaluation of the mechanisms involved in nutraceutical bioavailability; and diversifying the food matrices and nutraceutical delivery systems for improving oral bioavailability.

Many research teams have investigated various methods and techniques for improving the oral bioavailability of bioactive compounds. One of these techniques is encapsulation within different types of nanocarriers (Katouzian & Jafari, 2016; Koshani & Jafari, 2019; Rezaei, Fathi, & Jafari, 2019). Most studies have shown that enhancing the bioavailability of encapsulated bioactives is due to increased solubility, avoidance of their chemical and biochemical degradation at pH variation or in the presence of enzymes and other components of gastrointestinal tract (GIT) fluids, controlled release of bioactives, and increased absorption through the epithelial membrane (Faridi Esfanjani, Assadpour, & Jafari, 2018; Garavand, Rahaee, Vahedikia, & Jafari, 2019; Rafiee, Nejatian, Daeihamed, & Jafari, 2019).

The present revision summarizes the results of literature in the last decade regarding the oral bioavailability of nutraceuticals in food matrix and nanocarriers. The work comprises two parts. The first part describes the main steps and mechanisms involved in the oral bioavailability of nutraceuticals, and the second part reviews the most important types of nanocarriers that contribute to the improvement of oral bioavailability of nutraceuticals.


The efficiency of bioactive compounds in drugs, foods, and food supplements is assessed by means of the concepts such as bioavailability, bioaccessibility, bioactivity, bioconversion, and bioequivalence (Parada & Aguilera, 2007). Sometimes these concepts have been erroneously defined and used, creating confusion in characterizing bioactive compounds. For instance, no distinction is made among the bioavailability of a medicine that is administered parenterally (intravenously or intra‐arterially), when the biocomponent is directly introduced into the systemic circulation, and the bioavailability of an orally administered medicine, when it has to go through the GIT stages. That is why pharmacology uses the term “absolute bioavailability of a medicine,” defined as the fraction of a dosage form administered on a certain pathway, which is completely absorbed into the systemic circulation. Absolute bioavailability is calculated in comparison to the amount of bioactive substance integrally absorbed into the systemic circulation through intravenous administration. If the bioactive substance cannot be administered intravenously, the relative bioavailability is calculated instead (Sinko, 2006).

It is no rare occurrence for the concept of oral bioavailability to be reduced only to absorbing, distributing, metabolizing, and eliminating bioactive compounds or metabolites, without taking into account the release of nutraceuticals and their transformations at the level of GIT. Thus, the concept of oral bioavailability should not be reduced to only the release of nutraceuticals from the food matrix, or only their absorption in the intestine or even less the stomach. Oral bioavailability is a unitary concept integrating all the stages a bioactive compound (nutraceutical or pharmaceutical) goes through, from swallowing to excretion. Extended to foods, “bioavailability” is the fraction from the ingested nutraceutical that becomes accessible to absorption at the level of GIT, is metabolized, and distributed to the organs and tissues (Parada & Aguilera, 2007).

The studies on the bioavailability of nutraceuticals (BA) highlight three main stages: bioaccessibility (B*), absorption (A*), and transformation (T*), as shown in Figure 1 (McClements, Li, & Xiao, 2015).


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