Current Nutrition & Food Science - Volume 6, Issue 1, 2010

Nutrition is an important factor determining quality of life and health. In recent years, nutritional strategies have received much attention with respect to the prevention of a number of chronic diseases, including diabetes, cancer, cardiovascular diseases, osteoporosis, and many more. Next to the macro-constituents of the diet such as proteins and dietary fiber, micronutrients and phytochemicals such as polyphenols, carotenoids, phytosterols, and phytoestrogens have been discussed for their potential in chronic disease prevention. Despite a number of promising features of some of these phytochemicals, controversial discussions about their safety, dosing, bioavailability, metabolism, synergistic effects, actions on the cellular level and effectiveness are ongoing, emphasizing existing gaps in our understanding of their way of action. For example, knowledge on factors impacting polyphenol uptake from the gut and further metabolism is still marginal, and their ways of action, such as on gene transcription via e.g. histone modification, is poorly understood. However, nutritional strategies including dietary intervention with food-originating bioactive compounds have, as opposed to medical treatment alone, the potential of being sustainable, cost-effective, and truly preventive in nature, given that their safety can be evaluated and warranted. In addition to a number of already described health beneficial properties, such as the anti-oxidative and anti-inflammatory characteristics of several polyphenols, new possible ways of their employment with respect to chronic diseases are just emerging, such as the use of carotenoids to reduce photo-oxidative stress, or the utilization of polyphenols as anxiolytics or antidepressants. This special issue is based on presentations and discussions of the first Luxembourgish Food and Nutrition Conference, aiming to highlight the importance of selected phytochemicals within human nutrition, with a focus on polyphenols and carotenoids, presenting current knowledge and gaps in our understanding with respect to determining their bioavailability and further metabolism in humans, and their way of action and potential health beneficial effects. We can be very grateful for the insightful results gained based on this Conference, partly presented in this special issue, and I would like to express my gratitude toward all authors for their valuable contributions.

Plants have evolved antioxidant molecules to help them withstand environmental stresses. Humans may also benefit from these defense molecules through their consumption in fruits and vegetables. Dietary antioxidants are indeed believed to play a very important role in the human body defense system, protecting, as in plants, against oxidative damage induced by Reactive Oxygen Species (ROS), which are known to be involved in the pathogenesis of aging and many degenerative diseases such as cardiovascular diseases and cancers. In this review, we compare the systems involved in ROS production and scavenging in humans and in plants. We focus mainly on the description of the best-known dietary antioxidants: ascorbate (vitamin C), tocopherols (vitamin E), carotenoids, and phenolic compounds. Their redox properties, metabolism and functions are discussed from both a human and a plant perspective.

Following recent evidence that disturbances in oxidative metabolism are involved in anxiety disorders, high anxiety levels and depression, the use of antioxidants has been proposed as a novel approach for the prevention or treatment of these conditions. Polyphenols are naturally-occurring antioxidant substances which can have pharmacological actions on the central nervous system. This mini-review aims to examine the current evidence for the potential use of dietary polyphenols as neuroprotective agents to reduce anxiety and to manage depression. I will outline recent findings which demonstrate that polyphenols have anti-anxiety effects at higher doses (300/60/30/20 mg/kg body weight) as well as at lower doses (2-4 mg/kg); this can be compared to conventional anxiolytics, which only have anxiolytic effects at lower doses (1-5 mg/kg). To circumvent problems associated with polyphenols (e.g., quercetin) having difficulty crossing the blood-brain barrier and to effectively reduce the active dose, intranasal administration in the form of liposomes could be an interesting approach. I also suggest that dietary polyphenols could be a new alternative approach to treat depression, because they exhibit antidepressant activity with relatively lower doses (0.3-2 mg/kg) than commonlyused antidepressants such as imipramine (10 mg/kg). The polyphenols discussed in this mini-review are found in vegetables and fruits such as apples, plums, cherries, onions and tea. Therefore, a varied diet that is rich in naturallyoccurring polyphenols could be an effective means to prevent (or delay) anxiety, depression and other diseases linked to oxidative stress.

Apples (Malus spp., Rosaceae) and their products contain significant concentrations of polyphenols, which have diverse biological activities and may have important beneficial effects on human health. The main polyphenols in apples are hydroxycinnamic acids, dihydrochalcones, flavonols, catechins and oligomeric procyanidins, although triterpenoids are also present in apple peel and anthocyanins in red apples. Human intervention studies have provided clear evidence that dietary polyphenols are at least partially absorbed following ingestion. They undergo extensive metabolism during the absorption process and subsequent distribution in the body. Hence, plasma and tissues are not generally exposed to polyphenols in their ingested form in vivo, and knowledge about their bioavailability, metabolism and concentrations in target tissues is of great importance when evaluating their biological effects and for ensuring that in vitro studies have physiological relevance. Metabolites, such as glucuronides, sulfates and methylated derivatives have been investigated in vivo. In addition, activities of colonic microbiota have been shown to generate other metabolites, including phenolic and short chain fatty acids. It has also been shown that deconjugations catalyzed by intracellular enzymes can occur during gastrointestinal absorption, thereby releasing aglycones. The present review summarizes current knowledge of the bioavailability and metabolism of apple-derived polyphenols in humans.

Carotenoids are secondary plant constituents and more than 700 different compounds have been identified. They are synthesized by plants, where they serve as colorants for fruits and leaves, bacteria, fungi and algae. In nature carotenoids are important biological compounds due to their provitamin A activity, antioxidant properties and accessory functions in the light harvesting system of plants. Considerable amounts of carotenoids are ingested with the diet and accumulate in the human organism. α- and β- carotene, β- cryptoxanthin, lutein, zeaxanthin and lycopene are the major carotenoids in human blood and tissues. Based on their structural features carotenoids are suitable compounds for photoprotection in humans. They may act as ultraviolet (UV) absorbers and dietary antioxidants capable of scavenging reactive intermediates generated under the condition of photooxidative stress. Photooxidative stress is involved in processes of photoageing, photocarcinogenesis and plays a major role in the pathogenesis of photodermatoses. Intervention studies with β- carotene and lycopene supplements or diets rich in those carotenoids have shown that these molecules contribute to systemic photoprotection ameliorating UVinduced erythema. In- vitro data provide evidence that also other carotenoids are efficient photoprotectors, for example lutein and the structurally unusual phenolic polyene 3,3'- dihydroxyisorenieratene.

Carotenoids are a group of C-40 isoprenoid-based molecules with >600 representatives in nature, of which approximately 30 are of importance within our daily diet. This class of phytochemicals has recently attracted much attention due to potential health beneficial effects associated with carotenoid consumption, including reduction of cardiovascular diseases, protection from age-related macular degeneration, various types of cancer, and perhaps, bone health. Therefore, an increasing number of studies have been carried out, focusing on carotenoid bioavailability from the diet, which is typically low, in the magnitude of 1-50%, successive metabolization and measuring carotenoid status. However, up to date, there is no clear consensus on how to measure carotenoid bioavailability and status. A number of methods have been developed to measure certain aspects of bioavailability, including in vitro studies assessing matrix release and micellarization, i.e. bioaccessibility, uptake or transport into cells simulating the human small intestine (e.g. Caco-2 cells), animal experiments, and also human studies. However, these techniques do not necessarily yield wellcorrelated results. In living beings, carotenoids may be determined in different tissues, including plasma, plasma triacylrich lipoprotein fraction reflecting newly absorbed carotenoids, or various target tissues where carotenoids do accumulate to some degree, including the retina, liver, or adipose tissue. Isotopic methods employing stable or radioactive labeled carotenoids have been developed to differentiate between endogenous and exogenous carotenoids and to estimate utilization from single meals. The relation between carotenoid intake, uptake, absorption, distribution, metabolization/ excretion, and status demand a good understanding of the existing methods to assess these various aspects of bioavailability across different models.

Food may be either contaminated with a range of industrial chemicals or contain naturally produced toxic compounds. Even the most sophisticated chemical analyses are not able to perform or contribute to an effect assessment of food constituents. While in environmental research the application of “effect directed analysis” (EDA) and “toxicity identification and evaluation” (TIE) has been widely accepted and applied, these concepts had been hardly applied for toxicity characterization to food matrices. It has been nevertheless used in the areas of botanical chemistry, pharmacology and ethno-pharmacology, focusing on new drug discovery and in the search for new ingredients. Within this review a scheme for EDA application to food items is formulated based on experiences from environmental toxicology, the few experiences of in vitro effect-directed analysis of food items with a related epidemiological risk are described and discussed. A wider use of EDA for food toxicity characterization is strongly emphasized.

Acetylation and deacetylation of lysine residues on histones, which are catalyzed by histone acetyltransferases (HATs) and histone deacetylases (HDACs), are epigenetic modifications that play a very important role in the regulation of gene transcription. Perturbation of the balance between histone acetylation and deacetylation leads to a myriad of diseases, including cancer, AIDS, malaria, neurodegenerative diseases, and diabetes. HATs and HDACs have recently been recognized as key targets for chemoprevention and drug discovery, and numerous natural and synthetic compounds have been screened in order to identify promising regulators of subtle balance between histone acetylation and deacetylation. Here, we present dietary compounds and other natural products that have emerged as potent HAT or HDAC activity modulators, and we discuss their current and future applications as chemopreventive or therapeutic agents.