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Nutraceuticals

A Holistic Approach to Disease Prevention

Edited by
Hammad Ullah, Abdur Rauf, and Maria Daglia
Editors
Hammad Ullah, PhD
Department of Pharmacy
University of Napoli Federico II
Via D. Montesano
80131 Naples
e-mail: [email protected]

Abdur Rauf, PhD

Department of Chemistry
University of Swabi
94640 Khyber Pakhtunkhwa Swabi
Pakistan
e-mail: [email protected]

Maria Daglia, PhD

Department of Pharmacy
University of Napoli Federico II
Via D. Montesano
80131 Naples
And
International Research Center for Food Nutrition and Safety
Jiangsu University
Zhenjiang 212013
China
e-mail: [email protected]

ISBN 978-3-11-131730-4
e-ISBN (PDF) 978-3-11-131760-1
e-ISBN (EPUB) 978-3-11-131787-8

Library of Congress Control Number: 2023952308

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Preface
In the dynamic landscape of healthcare and wellness, the pursuit of optimal health
has taken center stage, prompting individuals to explore diverse avenues for main-
taining and enhancing their well-being. Among the myriad approaches, nutraceuticals
have emerged as a fascinating intersection between nutrition and pharmaceuticals,
offering a unique blend of science and nature to support health.
This book entitled Nutraceuticals: A Holistic Approach to Disease Prevention
endeavors to unravel the intricate tapestry of nutraceuticals, providing readers with
a comprehensive understanding of these compounds and their potential impact on
health and disease. As we delve into this realm, we embark on a journey that tran-
scends conventional boundaries, where food becomes medicine and science merges
seamlessly with holistic well-being.
The term “nutraceutical” itself embodies the fusion of “nutrition” and “pharma-
ceuticals,” encapsulating a diverse array of bioactive compounds found in foods and
dietary supplements. From antioxidants to probiotics, omega-3 fatty acids to herbal
extracts, each nutraceutical harbors the promise of promoting health and preventing
illness. This book aims to demystify these compounds, shedding light on their origins,
mechanisms of action, and evidence-based benefits.
As we navigate the chapters ahead, we will examine the cutting-edge research
that underpins their efficacy, offering readers a glimpse into the exciting advance-
ments that continue to shape this field. Moreover, practical insights on incorporating
nutraceuticals into daily life, alongside considerations of safety and potential risks,
will empower readers to make informed decisions about their health and wellness.
It is important to note that this book does not replace professional medical advice.
Instead, it serves as a valuable resource, equipping readers with knowledge to engage
in informed discussions with healthcare professionals and make personalized choices
aligned with their unique health goals.
We extend our gratitude to the experts and researchers whose work has paved
the way for this exploration, and to the readers who embark on this journey with cu-
riosity and a commitment to their well-being. May this book serve as a beacon, guid-
ing you through the vast landscape of nutraceuticals and empowering you to make
choices that nurture a healthier, more vibrant life.

December, 2023 Hammad Ullah

University of Naples Federico II, Italy

Abdur Rauf
University of Swabi, Pakistan

Maria Daglia
University of Naples Federico II, Italy

https://doi.org/10.1515/9783111317601-202
Contents
Preface V

About the editors XI

Hammad Ullah, Maria Daglia

Chapter 1
Nutraceuticals and food supplements: basic concepts and
regulatory aspects 1

Imad Ahmad
Chapter 2
Nutraceutical properties of bioactive peptides 17

Munazza Kiran, Almas Jahan, Sammina Mahmood, Hammad Ullah

Chapter 3
Nutraceutical properties of dietary lipids 43

Arif Ali, Mac Dionys Rodrigues da Costa, Emanuel Paula Magalhães,

Alice Maria Costa Martins
Chapter 4
Biological importance of vitamins and minerals 63

Thadiyan Parambil Ijinu, Maheswari Priya Rani,

Sreejith Pongillyathundiyil Sasidharan, Santny Shanmugarama,
Raghavan Govindarajan, Varughese George and Palpu Pushpangadan
Chapter 5
Clinical significance of herb–drug interactions 103

Pauline Donn, Sepidar Seyyedi-Mansour, Ana Perez-Vazquez, Paula Barciela,

Maria Fraga-Corral, Franklin Chamorro, Lucia Cassani, Jesus Simal-Gandara,
Miguel A. Prieto
Chapter 6
Nutraceuticals and oxidative stress 125

Hammad Ullah, Tokpam Reshma Chanu, Sivaa Arumugam Ramakrishnan,

Rajan Logesh
Chapter 7
Nutraceuticals and inflammation 145
VIII Contents

Imad Ahmad, Fazle Rabbi, Fiaz Alam

Chapter 8
Metabolic disorders 167

Galvina Pereira, Saasha Vinoo, Pranali Yadhav

Chapter 9
Multiple gastrointestinal tract disorders 193

Zubair Ahmad, Musarat Riaz, Abdur Rauf, Hassan Zeb, Taghrid S. Alomar
Chapter 10
Bone health 223

Hemanth Kumar Manikyam

Chapter 11
Medicinal plants and alternative therapies for reproductive system
health 237

Besma Sehili
Chapter 12
Infectious disorders 267

Mostafa Pirali Hamedani, Saied Goodarzi

Chapter 13
Medicinal plants for urinary tract problems 293

Nusrat K. Shaikh
Chapter 14
Ocular health 315

Ebrahim Alinia-Ahandani, Zahra Alizadeh-Tarpoei, Farjad Rafeie, Zeliha Selamoglu,

Seyed Sara Heidari-Bazardehy, Chonoor Mohammadi,
Elifsena Canan Alp Arici
Chapter 15
Medicinal plants and pregnancy sickness 333
 Contents IX

Paula Barciela, Ana Perez-Vazquez, Sepidar Mansour, Pauline Donn,

P. Garcia-Perez, Maria Carpena, Maria Fraga-Corral,
Jesus Simal-Gandara and Miguel A. Prieto
Chapter 16
Toxicity and safety of nutraceuticals 345

Index 365
About the editors
Hammad Ullah obtained his PhD in “Nutraceuticals, Functional Foods, and Human Health” at the
Department of Pharmacy, University of Naples Federico II in liaison with the Department of Analytical and
Food Chemistry, University of Vigo, Spain. The research activity focuses mainly on the comprehensive
investigation of natural products, with the final aim of the development of new food supplement and
functional food ingredients. The scientific activity is documented by more than 50 peer-reviewed articles,
4 book chapters, and 20 communications to national and international congresses. He is currently an
editorial board member of BMC Complementary Medicine and Therapies and Journal of Medicinal Food. His
scientific contributions are recognized by several research awards including MEDWELL Award for Best PhD
Thesis (2023), PSE Dra. Mariola Macías Award (2023), and Young Researcher Award at MONASH INITIATE
2022. In addition, he is a regular member of American Chemical Society, Society for Medicinal Plant and
Natural Product Research (GA), Royal Society of Chemistry (MRSC), International Natural Product Sciences
Taskforce (INPST), Phytochemical Society of Europe (PSE), and IUPHAR Mediterranean Group of Natural
Products Pharmacology.

Abdur Rauf works at the Department of Chemistry, University of Swabi, Khyber Pakhtunkhwa, Pakistan. He
completed his PhD at the Institute of Chemical Sciences, University of Peshawar, Pakistan, in 2015. His
research work focuses on phytochemistry, pharmacology, and nanotechnology. Abdur Rauf is the author
and coauthor of more than 366 research papers published in peer-reviewed journals. He has edited 2 books
and contributed 33 book chapters for international publishers. He also published one US patent, and
submitted one national and three international patents for the discovery of novel drugs. Furthermore, he is
the Associate Editor/Editorial Board Member of several journals including Frontier in Pharmacology, Medicinal
Chemistry; Green Processing and Synthesis; Open Chemistry; and Medicinal Chemistry, among others. Abdur Rauf
won the Young Scientist Award from the Directorate of Science and Technology in 2018 and the Research
Productivity Award for 2016–17, from the Pakistan Science Foundation. His name is also in World’s Top 1%
Highly Cited Researchers 2022 list released by Clarivate. He has won 9 national and 10 international projects.
As a scientist in the past few years, he contributed a lot to the fields of medicinal chemistry, pharmacology,
and nanotechnology. His research interests also include exploring the local natural resources (i.e., Pakistani
flora) for efficient treatment of different health disorders, which in turn would significantly impact the
national economy.

Maria Daglia obtained her PhD degree in pharmaceutical chemistry and technology at the University of
Pavia, Italy, and is currently Full Professor of Food Chemistry at the University of Naples Federico II, Italy,
and a visiting professor at the International Research Center for Food Nutrition and Safety, Jiangsu
University, Zhenjiang China. The scientific activity has developed along two lines of research: (i) the study of
biological properties of components that are either naturally present or induced following thermo/
technological treatments in foods useful in food and pharmaceutical fields; (ii) the development of
analytical spectrophotometric and chromatographic methods useful in the identification and determination
of biological active compounds occurring in foods. More recently, further research has been carried out,
including (i) the investigation of the mechanism at the molecular level through which foods with
nutraceutical activity and/or their components perform beneficial effects in humans, with particular
reference to polyphenols, secondary metabolites of plants widely distributed in all categories of foods,
from current foods to food supplements and (ii) the study of components with nutraceutical activity to be
used in the health product industry, with in vitro, in vivo model systems and clinical studies. Her research
activity is documented by more than 270 scientific papers, 2 books, 4 book chapters, and more than 120
communications to national and international congresses. As per Clarivate analytics, Prof. Daglia remained
a highly cited researcher in the field of agricultural sciences in 2021. She is currently Editor-in-Chief of Food
Safety and Health (Wiley), and editorial board member of Phytomedicine (Elsevier) and Food Frontiers (Wiley).

https://doi.org/10.1515/9783111317601-204
Hammad Ullah, Maria Daglia✶
Chapter 1
Nutraceuticals and food supplements: basic
concepts and regulatory aspects
Abstract: Nutraceuticals, a hybrid term of nutrient and pharmaceutical, are derived
from food sources providing health effects beyond nutrition. Food supplements are
manufactured products intended to supplement the human diet, whereas functional
foods refer to foods containing bioactive components (in addition to basic nutrients)
with potential health benefits. Nutraceuticals can be further classified based on their
dietary sources. Dietary fibers are one of the critical components of food supplies that
may promote human health via regulation of gastrointestinal digestion and gut micro-
biota. Prebiotics support the growth and activity of the gut flora. Probiotics are live
microorganisms, providing benefits to host health via regulation of gut microbiota.
Polyunsaturated fatty acids (PUFAs) possess potential to ameliorate systemic inflam-
mation and the pathogenesis of chronic disorders (mainly of cardiac and metabolic
origin). Vitamins and minerals are abundantly found in food sources, fighting against
oxidative stress and regulate the cellular and biochemical processes of the body. Die-
tary polyphenols including flavonoids and nonflavonoids are one of the potent antiox-
idants with a wide array of biological effects. Dietary spices, known for their use as
food additives and traditional medicine, possess a great impact on human health
when consumed regularly in adequate amount. This chapter is focusing on the basic
definitions and classification, efficacy, safety and regulation of nutraceuticals, func-
tional foods, and food supplements.

1 Nutraceuticals: definition and classification

Foods contain various dietary factors with a range of biological effects, offering an
opportunity to improve human health, while providing a protection against chronic
diseases [1, 2]. The medicinal benefits of foods were recognized in 500 BC by a Greek
physician Hippocrates, who quoted “Let food be thy medicine and medicine be thy
food.” Stephen DeFelice used the term “nutraceutical” in 1989 for the first time as a
hybrid of “nutrition” and “pharmaceutical” to describe the health-promoting products

✶
Corresponding author: Maria Daglia, Department of Pharmacy, University of Napoli Federico II,
Via D. Montesano 49, 80131 Naples, NA, Italy; International Research Center for Food Nutrition and
Safety, Jiangsu University, Zhenjiang 212013, China, e-mail: [email protected]
Hammad Ullah, Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49,
80131 Naples, NA, Italy

https://doi.org/10.1515/9783111317601-001
2 Hammad Ullah, Maria Daglia

based on food-derived nutritional factors. DeFelice defined it as “a food (or part of a

food) that provides medical or health benefits, including the prevention and/or treat-
ment of a disease.” Nutraceuticals may include whole food, isolated nutrients, food
supplements, herbal products, or processed foods (i.e., beverages, cereals, and soups)
that can also be used as medicine other than nutrition. In other words, nutraceuticals
are food-derived products that possess physiological benefits and/or provide protec-
tion against chronic disorders. They may be used to delay the aging processes, en-
hance the life expectancy, prevent the chronic ailments, and support the anatomy or
physiology of the body [3].
Functional foods refer to foods, containing bioactive components beyond basic
nutrition. The Food and Agriculture Organization (FAO) defines functional foods as “a
foodstuff containing other components, in addition to the basic nutrients, that may
possess specific health effects, such as preventing and/or treating disease” [4]. How-
ever, there are certain issues with the commonly used definition such as (i) inclusion
of commonly used healthy foods, that contain phytochemicals with a potential to en-
hance health and prevent disease, that is, peanuts, beetroot, strawberries, pomegran-
ate juice, and sweet potato; (ii) many foods are contributing to healthy life, and it is
not clear which food components (beyond basic nutrients) possess health-enhancing
and disease-preventing potential. To address these issues, new definition for func-
tional foods was proposed as “the novel foods, formulated to contain substances or
live microorganisms, which may possess a potential health-improving or disease-
preventing value. The added ingredients will be at safe and effective concentration to
achieve the desired biological effects, and that may include nutrients, phytochemicals,
dietary fiber, other components or probiotics” [5]. Some of the key examples of func-
tional foods include margarine with enhanced omega-3 fatty acid levels, orange juice
with added calcium, fermented foods containing probiotic strains, prebiotics supple-
mented foods, and margarine with added phytosterols and stanols. The subclasses of
functional foods including fortified products, altered products, enriched products,
and enhanced commodities are summarized in Figure 1.
In scientific community, the terms “nutraceuticals” and “functional foods” are usu-
ally used interchangeably, as both the definitions often overlap. Kalra (2003) proposed
to redefine these terms as “a food being cooked or prepared using a scientific intelli-
gence, with or without having knowledge of how and why it is being used is known as
functional food” while “nutraceuticals can be defined as the functional foods with a
potential to prevent and/or treat diseases’ [6]. Other related products include dietary
supplements, fortified foods, and herbal medicine. Dietary supplements refer to the
pharmaceutical formulations containing food-derived components, indented to pre-
vent or treat a deficiency, for example, micronutrients, amino acids, dietary fibers,
and plant extract. Herbal medicines are defined by World Health Organization (WHO)
as ”herbs, herbal materials, herbal preparations and finished herbal products that con-
tain as active ingredients parts of plants, or other plant materials, or combinations.”
 Fortified products
Increasing the contents of existing nutrients.
Example: folic acid fortified grain products.

Altered products
Enhanced commodities
Replace existing components with beneficial
Changes in the raw commodities that have
components.
altered nutrient composition.
Example: use of high fiber fat replacer produced
Example: high lysine corn.
from grain products.

Functional Foods

Enriched products
Adding new nutrients or components.
Example: orange juice with added calcium.

Figure 1: Subclasses of functional foods and their examples.

Chapter 1 Nutraceuticals and food supplements: basic concepts and regulatory aspects
3