The Potential of Dietary Antioxidants

Oxidative stress causes chronic diseases such as cardiovascular disease, cancer, Alzheimer, chronic obstructive pulmonary, and neurodegenerative pathologies. Antioxidant systems defend human cells from free radicals. They act by stopping free radicals, decreasing their development, and quenching the formed ROS and RNS. The antioxidant molecules are classified into primary and secondary defense molecules. The primary antioxidant molecules (i.e., vitamins C and E, ubiquinone, and glutathione) reduce oxidation effects by moving a proton to the free radical species or electron donors, or by terminating the chain reactions The secondary antioxidants (i.e., N-acetyl cysteine and lipoic acid) act as cofactors for some enzyme systems or neutralize the production of free radicals by transition metals. This work comprises original research papers and reviews on antioxidant molecules in food, the agricultural practices that maximize their levels in plants, the potential preventive effects of selected classes of antioxidant molecules, their potential use in functional foods, and the pharmaceutical delivery systems that maximize their potential activity when used as supplements

Factors affecting gut metabolism and bioavailabilty of orange juice flavanones in humans

Several studies have supported a beneficial role of dietary flavonoids in reducing the risk/progression of chronic diseases (including hypertension, cardiovascular disease, certain cancers, type-2-diabetes, cognitive dysfunction, age-related bone disease). Their beneficial properties are likely to be affected by their structure, distribution in foods, food matrix, life habits (physical activity). Most dietary polyphenols reach the colon where they are metabolized to phenolic acids by gut bacteria. Lack of knowledge of the factors affecting flavonoid metabolism and bioavailability hinders understanding of their health effects. Therefore, this thesis aimed to investigate the effect of factors on bioavailability and metabolism of dietary polyphenols from orange juices (OJ) in in vitro and in vivo studies. In chapter 3, the variability of orange juice polyphenolic content was assessed using in vitro models of the human gastrointestinal tract. Chapter 4 investigated the reduced urinary phenolic acids after OJ and yoghurt (Y) in humans compared to OJ alone using in vitro models of the human gut. In chapter 5, raftiline and glucose were tested for effects on metabolism of hesperidin (flavanone not OJ). In chapter 6, an intervention study of 4 weeks moderate intensity exercise determined whether exercise affected bioavailability and metabolism of OJ flavanones in healthy sedentary females. The studies in this thesis showed that food sources, food matrix and physical exercise may determine the significant variations in bioavailability and metabolism of flavonoids, seen in a number of studies. These factors could result in differences in bioactivity and bioefficacy of polyphenols, and need to be taken into account in further studies of the effects of flavanones on disease risk

Oxidative Stress and Exercise

Although regular moderate-intensity exercise can activate important cell adaptive properties, sporadic and strenuous bouts of exercise may induce oxidative stress due to an augmented production of reactive metabolites of oxygen (ROS) and nitrogen free radical species (RNS). Exercise-induced free radical formation may impair cell function by oxidatively modifying nucleic acids, where DNA damage and insufficient repair may lead to genomic instability. Likewise, lipid and protein damage are significant cellular events that can elicit potentially toxic perturbations in cellular homeostasis. This book focuses on aspects of exercise-induced oxidative stress while taking into consideration the basic mechanisms, consequences and function of ROS production, and whether antioxidants may either support or hinder these responses

Natural Products and Disease Prevention, Relief and Treatment

The consumption of fruits, vegetables, herbs, spices, etc., is thought to be associated with reduced risk for many human diseases, including cancers. Recently, significant advances have been made in evaluating the efficacy of natural products (compounds from natural sources) against human diseases. The purpose of this Special Issue, “Natural Products and Disease Prevention, Relief and Treatment", was to collect manuscripts concerning natural products for treating human diseases. Consequently, we have collected several high-quality manuscripts that focus on the molecular mechanisms of natural products, including their anti-inflammatory, antioxidative, neuroprotective, cardioprotective, antifibrotic, and anticancer effects, as well as other health beneficial effects across a wide range of human diseases. Overall, this Special Issue is an excellent source for information on promising natural products for future preclinical and clinical research into multiple diseases

Dietary Habits, Beneficial Exercise and Chronic Diseases

Several lines of evidence indicate that healthy diet and exercise can prevent cardiovascular diseases, stroke, diabetes, and some types of cancer such as colon cancer, and smoking-related cancers. Dietary patterns defined as the quantities, proportions, variety, or combination of different foods and drinks, and the frequency with which they are habitually consumed are also associated with an increased or decreased incidence of chronic diseases. Lately, an association has been found between eating habits, exercise, and psychological and/or mental disorders. This Special Issue of Nutrients, entitled “Dietary Habits, Beneficial Exercise, and Chronic Diseases: Latest Advances and Prospects”, contains 20 manuscripts, either describing original research or reviewing the scientific literature, focused on the relationship between dietary habits (macronutrients, micronutrients, etc.) and/or exercise with metabolic, cardiovascular, neurological, mental, rheumatic, inflammatory, gastrointestinal, odontostomatological, and other chronic diseases

Antioxidants in Health and Disease

Antioxidants in Health and Disease discusses the effects of dietary antioxidants and antioxidant supplementation in humans. It reviews the latest evidence-based research in the area, principally through prospective cohort studies and randomized controlled trials. The book assesses major dietary antioxidants and discusses their use in diseases such as cancer, diabetes, stroke, coronary heart disease, HIV/AIDS, and neurodegenerative and immune diseases. The use of antioxidants in health is also discussed along with common adverse effects associated with antioxidant use. Separating myth from fact, this book gives you insight into the true role of antioxidants in health and disease

Background and Management of Muscular Atrophy

A healthy skeletal musculature is necessary for a good quality of life and is important in sports. The loss of skeletal muscle mass leads to severe clinical complications and alters daily functioning. The aim of this book is to give an overview of skeletal muscle atrophy including pathomechanism, clinical characters, and the tools for prevention and treatment. Skeletal muscle atrophy can develop due to neurogenic or myogenic reasons, and frequently appears as an age-dependent disorder (sarcopenia). The studies of theoretical background give promising perspectives to prevent and treat muscle atrophy. The book is recommended to scientists, practitioners, students, sportsmen, and everybody who is interested in the normal and impaired function of the skeletal muscle

Phenolic Compounds

Phenolics are commonly available compounds in foods, beverages, and spices. They have great importance in all aspects of daily life including industry, health, and research. As such, this book presents a comprehensive overview of phenolic compounds and their potential applications in industry, environment, and public health. Chapters cover such topics as the production of these compounds and their uses in environmental sustainability, climate change, green industry, and treatment of human disease

Stopping the progression towards type 2 diabetes mellitus : investigating the hypoglycaemic (glucose-lowering) potential of antioxidant-rich plant extracts : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Nutritional Science, Massey University, Albany, New Zealand

Chapter 4 was published under a Creative Commons Attribution 4.0 license (CC BY 4.0) as: Lim, W X J, Chepulis, L, von Hurst, P, Gammon, C S, & Page, R A. (2020). An acute, placebo-controlled, single-blind, crossover, dose-response, exploratory study to assess the effects of New Zealand pine bark extract (Enzogenol ®) on glycaemic responses in healthy participants. Nutrients,12(2):497. https://doi.org/10.3390/nu12020497Background: Prediabetes is a condition where the blood glucose levels are high but not high enough to be classified as having type 2 diabetes mellitus (T2DM). It is also considered a high risk for developing T2DM. There is increasing evidence that demonstrates antioxidant-rich plant extracts exhibiting hypoglycaemic effects in humans. Therefore the extracts may improve glycaemic control in individuals with prediabetes and help prevent or delay the progression of prediabetes towards T2DM. Overall Aim: To examine the acute hypoglycaemic potential of four antioxidant-rich plant extracts, namely the New Zealand pine bark, grape seed, rooibos tea and olive leaf extracts in humans. Methods/Design: The hypoglycaemic effects of the New Zealand pine bark was examined in healthy participants (n=25) in an acute, placebo-controlled, single-blind, crossover, dose-response (50 and 400 mg), exploratory study (Pine Bark study). Blood samples were collected via finger pricking using disposable lancet to measure glucose levels at -20, 0, 15, 30, 45, 60, 90 and 120 min during an oral glucose tolerance test (OGTT) with 75 g of glucose. The hypoglycaemic effects of grape seed, rooibos tea and olive leaf extracts matched for antioxidant capacity were examined in an acute, placebo-controlled, crossover study (GLARE study) in participants with prediabetes (n=19). Blood samples were collected via cannulating the antecubital fossa region of the arm at -10, 0, 15, 30, 45, 60, 90 and 120 min during the OGTT with 75 g of glucose. Outcome glycaemic measures were analysed in both clinical studies (Pine Bark study and GLARE study). An in vitro mechanistic study investigating the potential inhibitory action of all four plant extracts (grape seed, rooibos tea, olive leaf and New Zealand pine bark) on digestive enzyme α-amylase and the dipeptidyl peptidase-4 (DPP4) enzyme were carried out using appropriate enzymatic assays of inhibition. Results: Prior to secondary analysis in the Pine Bark study, a significant reduction in the primary outcome mean glucose incremental area under the curve (iAUC) was only observed for the 400 mg dose of pine bark (21.3% reduction, p=0.016) compared to control. After stratification in the monophasic glucose curve shape group (n=12), 50 and 400 mg of pine bark significantly reduced the mean glucose iAUC compared to control (28.1% reduction, p=0.034 and 29.5% reduction, p=0.012), respectively. In contrast, mean glucose iAUC was not significantly different in the complex glucose curve shape group (n=13). In the monophasic group, 400 mg dose further improved glycaemic indices by reducing mean percentage increment of postprandial glucose (%PG) (33.9% reduction, p=0.010), mean glucose peak (11.2% reduction, p=0.025), and mean 2h postprandial glucose (2hPG) (8.9% reduction, p=0.027) compared to control. Within the complex group, there were no other significant changes except for reductions in mean %PG after 50 mg and 400 mg dose (33.8% reduction, p=0.012 and 41.4% reduction, p=0.025) compared to control, respectively. There were no significant differences between treatments in both subgroups (p>0.05). In the GLARE study, there were no overall significant changes in glucose and insulin responses between the extracts and control, or amongst the plant extracts (p>0.05). After secondary analysis, the less healthy subgroup (n=9), grape seed consumption showed significant reduction in mean glucose iAUC (21.9% reduction, p=0.016), mean 2hPG (14.7% reduction, p=0.034) and mean 2h postprandial insulin (2hPI) (22.4% reduction, p=0.029), whilst there was significant improvement in mean overall insulin sensitivity (ISIoverall) (15.0% increase, p=0.028) and mean glucose metabolic clearance rate (MCR) (16.7% increase, p=0.016) compared to control. Rooibos tea extract was shown to improve β-cell function measured by the mean oral disposition index (DI) (32.4% increase, p=0.031) in the less healthy subgroup compared to control. This was coupled with a non-significant improvement in insulin sensitivity measured by mean insulin-secretion-sensitivity-index-2 (ISSI-2) (18.3% increase, p=0.074). Olive leaf exhibited improved mean insulin sensitivity indices of insulinogenic index (IGI₃₀) (27.8% increase, p=0.078), Stumvoll first phase insulin sensitivity (ISIfirst) (17.8% increase, p=0.075) and Stumvoll second phase insulin sensitivity (ISIsecond) (15.6% increase, p=0.062) in the less healthy subgroup compared to control, although significance was not reached. Olive leaf extract was also consistently shown to elevate insulin levels in the study, with a higher mean 2hPI in the healthier subgroup (49.5% increase, p=0.030) and an elevated mean insulin iAUC in the less healthy (16.7% increase, p=0.040) subgroups. There were no significant changes in glucose and insulin responses in the healthier subgroup (n=10) compared to control nor between treatments in both subgroups (p>0.05). The mechanistic study demonstrated that the New Zealand pine bark extract exhibited the greatest inhibitory effects against digestive enzyme α-amylase (IC₅₀ 3.98 ± 0.11 mg/mL) and DPP4 enzyme (IC₅₀ 2.51 ± 0.04 mg/mL) compared to the other extracts (p<0.001). Both grape seed and rooibos tea extracts showed good inhibition of both enzymes tested. Rooibos tea was able to inhibit DPP4 enzyme to a greater extent than grape seed (p=0.018). In contrast, olive leaf extract showed minimal inhibition on α-amylase and no inhibition action against DPP4 enzyme. Conclusions: All four plant extracts (New Zealand pine bark, grape seed, rooibos tea and olive leaf) have shown acute hypoglycaemic potential in the Pine Bark study and the GLARE study by improving various indices of glucose and insulin responses in humans. The inhibitory action of the New Zealand pine bark, grape seed and rooibos tea extracts on DPP4 enzyme might have contributed to the hypoglycaemic effects observed in the clinical studies conducted. Whereas for olive leaf extract other underlying mechanisms on glycaemia remain to be elucidated. Our acute studies have indicated the need to investigate the chronic impact of these plant extracts in longer-term studies. Future studies in the prediabetes cohort should also look to target different metabolic profiles of varying degrees of dysglycaemia, as this may provide more meaningful results