Nutraceuticals in Brain Health and Beyond

Nutraceuticals in Brain Health and Beyond focuses on a variety of health disorders where intervention with nutritional supplements prove valuable, such as Alzheimer’s, Parkinson’s, autism, and attention-deficit disorder in children. In addition, Nutraceuticals in Brain Health and Beyond addresses "herb-nutra psychiatry" which is a field of research focused on developing a comprehensive, cohesive, and scientifically rigorous evidence base to shift conceptual thinking around the role of diet and nutrition in mental health.

Intended for nutrition researchers, nutritionists, dieticians, regulatory bodies, health professionals, and students studying related fields, Nutraceuticals in Brain Health and Beyond will be a useful reference in understanding the links between nutrition and brain health.

• Addresses nutritional psychiatry and cognitive health at all stages of the lifespan
• Contains extensive coverage of vitamins, minerals, botanicals, and other nutrients
• Offers novel insight into cognitive dysfunctions including depression and other neurodegenerative disorders
• Explores the role of genomics and epigenetics, including discussion of the gut–brain axis

• Language: English
• Publisher: Academic Press
• Release date: Nov 12, 2020
• ISBN: 9780128206102

Book preview

Nutraceuticals in Brain Health and Beyond

Editor

Dilip Ghosh

Nutriconnect, Sydney, NSW, Australia

Table of Contents

Cover image

Title page

Copyright

Contributors

Chapter 1. Introduction

Chapter 2. Role of food or food component in brain health

Introduction

Energy status and brain health

Neuroactive in foods

Omega-3 and phytochemicals: potential future therapeutic candidates

Cognition beyond foods: just diet or lifestyle pattern?

Food liking versus food wanting

Diet, aging, and neurodegenerative diseases

Diet, cognition, and epigenetics

Microbiota-targeted functional foods for brain health

Thinking outside the brain

Conclusion

Chapter 3. Bacopa monnieri for cognitive health—a review of molecular mechanisms of action

Cognition

Approved drugs as cognition enhancers

Nutraceuticals for cognitive performance

Bacopa monnieri for cognitive performance

Neuronal molecular mechanisms of cognitive benefits of BM in relation to signal transduction

Summary

Chapter 4. Indian medicinal plants as drug leads in neurodegenerative disorders

Abbreviations

Introduction

Methodology

Etiopathology of neurodegenerative disorders

Ayurvedic herbs: traditional usages in brain disorders

Role of Indian ayurvedic herbs in neurodegenerative brain disorders

Conclusion

Chapter 5. Role of nutraceuticals in the management of severe traumatic brain injury

Introduction

Traumatic brain injury

Nutritional management in TBI

Herbs and traditional medicines

Conclusions

Chapter 6. Understanding the relationship between oxidative stress and cognition in the elderly: targets for nutraceutical interventions

The aging population

What is cognitive aging?

What are the biological factors influencing cognitive aging?

Oxidative stress

Oxidative stress and cognition

Potential nutraceutical targets for improving cognition via reducing oxidative stress

Coenzyme Q10

Pycnogenol

Vitamins E and C

Carotenoids

Polyphenols

Conclusions

Chapter 7. Brain and mental health in Ayurveda

Ayurvedic principles of brain health

Brain diseases in Ayurveda - Manas roga

Ayurvedic drugs used in management of brain disorders

Ayurvedic herbs in brain health- medhya rasayan herbs

Chapter 8. 10 Persian herbal medicines used for brain health

Introduction

Herbal medicines for brain health

Polyherbal formulations and synergistic effects

Conclusion

Chapter 9. Beneficial effects of nutraceuticals in healthy brain aging

Introduction

Brain aging and associated neurodegenerative diseases

Conclusion

Chapter 10. Investigating the acute effect of pomegranate extract on indicators of cognitive function in human volunteers: a double-blind placebo-controlled crossover trial

Introduction

Potential mechanisms

Conclusions

Chapter 11. Glucosinolates: paradoxically beneficial in fighting both brain cell death and cancer

Introduction

Background and significance

Signaling apoptosis through the extrinsic pathway

Redox signaling

Effect on HDAC enzymes

ERK pathway

Activation of tumor suppressor genes: p53, p21, p27, and p73

Endoplasmic reticulum (ER) stress

The effect on cancer stem cells

The effect on SMYD3 genes

NrF2-ARE signaling pathway

AMPK and SFA toxicity and protection

Conclusion

Chapter 12. Efficacy of dietary polyphenols for neuroprotective effects and cognitive improvements

Introduction

Neuroprotective effects of curcumin

Neuroprotective effects of resveratrol

Neuroprotective effects of EGCG isolated from green tea

Application of other polyphenolic compounds in human central nervous system functions

Conclusion

Chapter 13. The gut microbiota–brain axis and role of probiotics

Introduction

Gut microbiota

Gut microbiome and the gut-brain axis

Impact of gut microbiota on CNS

Gut microbiota–brain communication

How does gut microbiota affect the brain?

Microbiota-gut-brain axis and depression

Microbiota-gut-brain axis and autism

Prebiotics and probiotics

Conclusion

Chapter 14. The gut microbiome: its role in brain health

Introduction

The human gut microbiome—a new frontier in medicine

The GI tract and its microbiome as an ecosystem

Shifting the therapeutic emphasis from the probiotic toward the host

How intestinal microbes communicate with the host

Other biochemical influences on neural function in the gut-brain axis

Nutrition-specific requirements of the host and its microbiota

How does nature maintain the gut-microbiome-brain axis?

Therapeutic interventions

Conclusion

Chapter 15. The psychopharmacology of saffron, a plant with putative antidepressant and neuroprotective properties

Introduction

Traditional and ethnomedicinal uses

Chemical constituents

Stigma

Flowers except stigma

Tepal

Stamen

Mode of action

Clinical applications

Conclusions

Chapter 16. Comprehensive review of Alzheimer’s disease drugs (conventional, newer, and plant-derived) with focus on Bacopa monnieri

Introduction

Alzheimer’s disease

Nutraceuticals in AD

Bacopa monnieri

Fundamental and clinical research in B. Monnieri in AD

Bacopa monnieri clinical practice

Conclusions

Chapter 17. Nutraceuticals in neurodegenerative diseases

Introduction

Alzheimer disease

Huntington disease

Parkinson disease

Amyotrophic lateral sclerosis

Conclusion

Chapter 18. Transforming curry extract-spice to liposome-based curcumin: lipocurc to restore and boost brain health in COVID-19 syndrome

COVID-19 pandemic

Curcumin pharmacology and COVID-19

Nanotechnology, epigenetics, and PK studies of liposome-curcumin

COVID-19 brain rehabilitation: role of epigenetics diet and exercise

Summary

Chapter 19. Cognitive health and nutrition: a millennial correlation

Molecular signaling of energy metabolism and synaptic plasticity

Oxidative damage and cognition

Nutrition and neurotransmitters

Nutrition and brain well-being

Correlation between metabolic diseases and psychiatric conditions

Diet and cognitive health

Cognitive enhancers

Active sports and cognitive performance: role of nutritional supplements

Diet and epigenetics

Nutraceuticals as key drivers for brain health

Future recommendations

Chapter 20. Mediterranean diet and its components: potential to optimize cognition across the lifespan

Diet, cognition, and dementia

Assessment of Mediterranean diet

Mediterranean diet and cognition across the lifespan

Mechanisms and food components

Olive oil

Fish

Nuts

Fruits and vegetables

Practical translation into Western countries

Chapter 21. Centella asiatica (Gotu kola) leaves: potential in neuropsychiatric conditions

Introduction

Psychological disorders

Cognitive disorders

Neurological disorders

Neurodegenerative and neuroinflammatory disorders

Recent advance: nasal delivery of CA extract

Chapter 22. Big data for clinical trials

Introduction

Role of big data in research

Technology of big data

Life cycle and management of data using technologies

Approach of regulatory agencies

Big healthcare data: security and privacy

Big data=big prospects

Chapter 23. The multifactorial contributions of Pycnogenol® for cognitive function improvement

Introduction

Pycnogenol® as a herbal medication

Deteriorating cognitive function in the aging brain

Mechanism of action of Pycnogenol®

Pycnogenol® as a cognitive enhancer

Chapter 24. Advancements in delivery of herbal drugs for cognitive disorders

Introduction

Herbal drugs in neurological health

Factors limiting brain delivery of herbal products

Advancements in the brain delivery technologies

Industrial applicability of these novel technologies and commercial viability

Regulatory challenges

Conclusion

Chapter 25. Impact of cardiometabolic disease on cognitive function

Introduction

Cardiometabolic disease

The impact of cardiometabolic disease on brain and cognitive health

The effect of nutritional medicine on cardiometabolic disease and cognitive function

Conclusion

Chapter 26. Vitamin B6, B9, and B-12: can these vitamins improve memory in Alzheimer’s disease?

Vitamin B6, B12, and folate

Cognitive decline, dementia, and the homocysteine hypothesis—what is the evidence showing?

Alzheimer’s disease and the effect of vitamin B6, folate, and B12

Clinical recommendations and application

Conclusions

Chapter 27. Sri Lankan medicinal herbs used for the management of neurodegenerative diseases of the brain

Introduction

Neurodegenerative diseases of the brain

Herbal medicines that could be recommended for the Neurodegenerative diseases of the brain

Review on medicinal herbs used for the management of neurodegenerative diseases of the brain

Chapter 28. Management of Alzheimer’s Disease with nutraceuticals

Introduction

Alzheimer’s disease: the leading cause of dementia

Understanding the origin of AD

Social and economic impact

Management and care of patients suffering with AD

Treatment and care

Nutraceuticals: an emerging trend in disease management

Dietary components of nutraceuticals

Conclusions

Chapter 29. Nutraceuticals in brain health

Introduction to nutraceuticals

Nutraceutical and overall brain health: Traditional versus modern outlook

Mechanistic insights into nutraceuticals functioning as protectors of brain health

Nutraceuticals from an evolutionary perspective

Conclusion

Chapter 30. Ayurveda and Brain health

Introduction - The brain and the nervous system

Ayurvedic perspective of the nervous system—Majja dhatu and Majjavaha srotas

Brain patterns and Dosha type

Brain aging—Modern and Ayurvedic perspective

Discussion and way forward

Index

Copyright

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Contributors

Emad A.S. Al-Dujaili,     Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom

Augustine Amalraj,     R&D Centre, Aurea Biolabs Pvt Ltd, Cochin, Kerala, India

Edward A. Armstrong,     University of Alberta, Department of Pediatrics, Division of Pediatric Neuroscience, Edmonton, AB, Canada

Zahra Ayati

Department of Traditional Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

NICM Heath Research Institute, Western Sydney University, Westmead, NSW, Australia

Vladimir Badmaev,     Medical Holdings Inc, New York, NY, United States

Arun Balakrishnan,     R&D | OmniActive Health Technologies, Mumbai, Maharashtra, India

Sharmistha Banerjee,     Division of Molecular Medicine, Bose Institute, Kolkata, West Bengal, India

Sarah Benson,     Centre for Human Psychopharmacology, Swinburne University, Melbourne, VIC Australia

Bharathi Bethapudi,     Research and Development Center, Natural Remedies Private Limited, Bengaluru, Karnataka, India

Yves Bureau,     Department of Psychology, University of Western Ontario London ON, Lawson Health Research Institute, London, ON, Canada

Autumn Carriere,     Faculty Applied Sciences, Nipissing University, North Bay, ON, Canada

Brendan Casola,     University of Guelph, Guelph, ON, Canada

Zack Cernovsky,     Department of Psychiatry, University of Western Ontario, London, ON, Canada

Nehru Sai Suresh Chalichem,     Research and Development Center, Natural Remedies Private Limited, Bengaluru, Karnataka, India

Divya Chandradhara,     BioAgile Therapeutics Pvt Ltd, Bangalore, Karnataka, India

Dennis Chang,     NICM Heath Research Institute, Western Sydney University, Westmead, NSW, Australia

Kaustubh S. Chaudhari

Department of Internal Medicine & Neurology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States

Department of Kayachikitsa, Smt. K.G. Mittal Punarvasu Ayurvedic College, Mumbai, Maharashtra, India

Department of Samhita Siddhanta, Smt. K.G. Mittal Punarvasu Ayurvedic College, Mumbai, Maharashtra, India

Simon S. Chiu

Lawson Health Research Institute, London, ON, Canada

Geriatric Mental Health Program, London Health Sciences Centre, London, ON, Canada

Department of Psychiatry, University of Western Ontario, London, ON, Canada

John Copen,     Department of Psychiatry, University of British Columbia, University of Victoria Medical Campus, Victoria, BC, Canada

Dezső Csupor

Department of Pharmacognosy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary

Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary

Hema Sharma Datta,     Interdisciplinary School of Health Sciences (ISHS), Savitribai Phule Pune University (SPPU), Pune, India

Anwar Siraj Daud,     Zim Laboratories Limited, Nagpur, Maharashtra, India

Preeticia Dkhar,     Department of Biochemistry, North Eastern Hill University, Shillong, Meghalaya, India

Sayanta Dutta,     Division of Molecular Medicine, Bose Institute, Kolkata, West Bengal, India

Seyed Ahmad Emami,     Department of Traditional Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Neha Garg,     Department of Medicinal Chemistry, Faculty of Ayurveda, Institute of Medical Sciences, BHU, Varanasi, Uttar Pradesh, India

Sarah Gauci,     Centre for Human Psychopharmacology, Swinburne University, Melbourne, VIC Australia

Dilip Ghosh,     Nutriconnect, Sydney, NSW, Australia

Rohit Ghosh,     Nutriconnect, Sydney, NSW, Australia

Souvik Ghosh,     Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, India

Sumit Ghosh,     Division of Molecular Medicine, Bose Institute, Kolkata, West Bengal, India

Sreeraj Gopi,     R&D Centre, Aurea Biolabs Pvt Ltd, Cochin, Kerala, India

Gilles J. Guillemin,     Department of Biomedical Sciences, Biomolecular Discovery and Design Research Centre, Macquarie University Centre for Motor Neuron Disease Research, NSW, Sydney, Australia

Swati Haldar,     Centre of Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, India

Marina Henein,     National University of Ireland Galway, Research Institution in Galway, Galway, Ireland

Christine A. Houghton

University of Queensland, St Lucia, QLD, Australia

Cell-Logic, Brisbane, QLD, Australia

3X4 Genetics, Seattle, A, United States

Mariwan Husni,     Department of Psychiatry, Northern Ontario Medical School, Thunderbay, ON, Canada

Satyajyoti Kanjilal,     Emami Limited, Research and Development Centre, Kolkata, West Bengal, India

Diana Karamacoska,     NICM Heath Research Institute, Western Sydney University, Westmead, NSW, Australia

Chandra Kant Katiyar,     Emami Limited, Research and Development Centre, Kolkata, West Bengal, India

Mostafa Khairy,     University of Alberta, Department of Pediatrics, Division of Pediatric Neuroscience, Edmonton, AB, Canada

Zahra Khazaeipool,     University of Western Ontario, London, ON, Canada

Kamil Kuca,     Department of Chemistry, Faculty of Science, University of Hradec Králové, Hradec Králové, Czech Republic

Viney Kumar,     Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, India

Zeenat Ladak,     University of Alberta, Department of Pediatrics, Division of Pediatric Neuroscience, Edmonton, AB, Canada

Debrupa Lahiri

Centre of Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, India

Department of Metallurgical and Materials Engineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, India

Ed Lui,     Department of Pharmacology, Schulich School of Medicine, University Western Ontario, London, ON, Canada

Helen Macpherson,     Institute for Physical Activity and Nutrition, Deakin University, Geelong, VIC Australia

Laura Martin,     Centre for Human Psychopharmacology, Swinburne University of Technology, Melbourne, Australia

Bradley J. McEwen,     School of Health and Human Sciences, Southern Cross University, Lismore, NSW, Australia

Abhijeet Morde,     R&D | OmniActive Health Technologies, Mumbai, Maharashtra, India

Javad Mottaghipisheh,     Department of Pharmacognosy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary

Deepak Mundkinajeddu,     Research and Development Center, Natural Remedies Private Limited, Bengaluru, Karnataka, India

Sasikumar Murugan,     Research and Development Center, Natural Remedies Private Limited, Bengaluru, Karnataka, India

Avinash Narwaria,     Emami Limited, Research and Development Centre, Kolkata, West Bengal, India

Ruchong Ou,     Centre for Human Psychopharmacology, Swinburne University of Technology, Melbourne, Australia

Muralidhara Padigaru,     R&D | OmniActive Health Technologies, Mumbai, Maharashtra, India

Bhushan Patwardhan,     Interdisciplinary School of Health Sciences (ISHS), Savitribai Phule Pune University (SPPU), Pune, India

Naomi Perry,     Centre for Human Psychopharmacology, Swinburne University of Technology, Melbourne, Australia

Andrew Pipingas,     Centre for Human Psychopharmacology, Swinburne University, Melbourne, VIC Australia

Pradeep Kumar Prajapati,     Department of Rasa Shastra and Bhaishajya Kalpana, All India Institute of Ayurveda, Delhi, New Delhi, India

Divya Purusothaman,     Research and Development Center, Natural Remedies Private Limited, Bengaluru, Karnataka, India

Hana Raheb,     Lawson Health Research Institute, London, ON, Canada

Preeti Rathi,     School of Basic Sciences, IIT Mandi, Mandi, Himachal Pradesh, India

Frank Rosenfeldt,     Centre for Human Psychopharmacology, Swinburne University of Technology, Melbourne, Australia

Renee Rowsell,     Centre for Human Psychopharmacology, Swinburne University of Technology, Melbourne, Australia

Partha Roy

Centre of Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, India

Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, India

Saakshi Saini,     Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, India

Nidhi Prakash Sapkal

Department of Pharmaceutical Chemistry, Gurunanak College of Pharmacy, Nagpur, Maharashtra, India

Zim Laboratories Limited, Nagpur, Maharashtra, India

Frank Schoenlau,     Horphag Research (Europe) LTD, Limassol, Cyprus

Andrew Scholey,     Centre for Human Psychopharmacology, Swinburne University, Melbourne, VIC Australia

Mujeeb Shad,     Department of Psychiatry, Oregon Health Sciences University, Portland, OR, United States

Ramesh Sharma,     Department of Biochemistry, North Eastern Hill University, Shillong, Meghalaya, India

Rohit Sharma,     Department of Rasa Shastra and Bhaishajya Kalpana, Faculty of Ayurveda, Institute of Medical Sciences, BHU, Varanasi, Uttar Pradesh, India

Vineet Sharma,     Department of Rasa Shastra and Bhaishajya Kalpana, Faculty of Ayurveda, Institute of Medical Sciences, BHU, Varanasi, Uttar Pradesh, India

Siddhansh Shrivastava,     Avalon University School of Medicine, Sta. Rosaweg 122-124 WIllemstad, Curacao, Girard, OH, United States

Weam Sieffien,     University of Toronto Faculty of Medicine, Toronto, ON, Canada

Parames C. Sil,     Division of Molecular Medicine, Bose Institute, Kolkata, West Bengal, India

Ruby Sound,     Eatwise Nutrition and Wellness Clinic, Mumbai, Maharashtra, India

Angela V.E. Stockton,     Dietetics, Nutrition and Biological Sciences, Queen Margaret University, Edinburgh, United Kingdom

Con Stough,     Centre for Human Psychopharmacology, Swinburne University of Technology, Melbourne, Australia

Ramesh Teegala,     Department of Neurosurgery, Anu Institute of Neuro & Cardiac Sciences, Vijayawada, Andhra Pradesh, India

Kristen Terpstra,     Neurological Unit, St Michel's Hospital Affliliated with University Toronto, Toronto, ON, Canada

Prasad Arvind Thakurdesai,     Indus Biotech Private Limited, Pune, Maharashtra, India

Barbara Tóth

Department of Pharmacognosy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary

Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary

Josh Varghese,     Marian University College of Osteopathic Medicine, Indianapolis, IN, United States

Deepanshu Verma,     School of Basic Sciences, IIT Mandi, Mandi, Himachal Pradesh, India

Nikhil Verma,     THINQ Pharma-CRO Ltd., Mumbai, Maharashtra, India

W.A.L. Chandrasiri Waliwita,     Department of Cikitsa (Ayurveda Medicine), Gampaha Wickramarachchi Ayurveda Institute, University of Kelaniya, Yakkala, Heath Care Research Foundation and Ayurveda College of Physicians, Yakkala, Western Province, Sri Lanka

David J. White,     Centre for Human Psychopharmacology, Swinburne University, Melbourne, VIC Australia

Michel Woodbury-Farina,     Department of Psychiatry, School of Medicine, University of Puerto Rico, PR, United States

Jay Kant Yadav,     Department of Biotechnology, School of Life Sciences, Central University of Rajasthan, Ajmer, Rajasthan, India

Jerome Y. Yager,     University of Alberta, Department of Pediatrics, Division of Pediatric Neuroscience, Edmonton, AB, Canada

Lauren M. Young,     Centre for Human Psychopharmacology, Swinburne University, Melbourne, VIC Australia

Andrea Zangara

Euromed S.A., Barcelona, Spain

Centre for Human Psychopharmacology, Swinburne University, Melbourne, VIC, Australia

Chapter 1: Introduction

Dilip Ghosh     Nutriconnect, Sydney, NSW, Australia

References

The brain is a complex organ that neuroscientists are still attempting to understand. This is unique because of its high metabolism and high turnover of nutrients, and this makes it a high-maintenance device in terms of optimal nutrient intake. Moreover, the brain is highly prone to oxidative stress owing to high fatty acid content (especially polyunsaturated fatty acids, which contribute to 10% of total dry brain weight), high oxygen consumption and redox signaling (about 20% basal oxygen for ATP production), low antioxidant content with higher neurotransmitter auto-oxidation [2]. Due to the multifactorial nature, the role of nutrition and nutritional products in cognitive neuroscience is complex. The concern is not simply with the impact of a single chemical on the brain but with multiple nutrients, metabolites, and interacting factors. In addition, a myriad of nutrient-specific transport systems and physiological mechanisms add more complexities in the nutrient-gut-brain interaction.

As people live longer, dysfunction of the brain is becoming a predominant issue for the healthcare system. Cognitive decline, particularly in elderly people, often derives from the interaction between age-related changes and age-related diseases, and covers a wide spectrum of clinical manifestations, from intact cognition through mild cognitive impairment and dementia.

Chang et al. [1] classified 92 diseases as age related, meaning that the incidence rate of each disease increased quadratically with age. The disability-adjusted life-years (DALYs) from each disease among adults are used to calculate the age-related disease burden. Burden varied between countries, being lowest in Switzerland (104·9 DALYs per 1000 adults) and Singapore (108·3 DALYs) and highest in Papua New Guinea (506·6 DALYs) and Afghanistan (380·2 DALYs), with low socio-demographic index. The effect is quite pronounced for age groups 60–64 and above.

By 2050, the 85-year-old and above population in the United States will triple [3]. Other than cardiovascular diseases and cancer, brain-related disorders such as psychological and cognitive health-associated disorders, dementia-related neurodegenerative diseases, and depression are the leading causes of ill-health in the older population. Older people make up a considerable proportion of Australia's population—in 2017, over one in seven people were aged 65 and over. The increase in costs due to the 85+ age group ($2.9 billion) represents some 23% of the total increase in costs ($12.5 billion) but only about 8% of the total projected health costs ($35 billion).

Age-related changes in cognitive function vary considerably across individuals and lifecycle stages, with some cognitive functions appearing to be more susceptible than others to the effects of aging. The brain undergoes tremendous age-associated structural and functional changes as we age. Like age-related changes in brain structure and function, age-related changes in cognition are not uniform across all cognitive domains, or across all older individuals. The basic cognitive functions most affected by age are attention and memory. Older adults show significant impairments in attention tasks, particularly on multitasking platforms. General knowledge, vocabulary, and verbal ability do not significantly decline throughout the lifecycle.

In this book Nutraceuticals in Brain Health and beyond, the editor brings together contributions from experts in nutraceutical research to provide a contemporary overview of how evidence-based nutraceuticals can beneficially affect brain function at the molecular and clinical level. When we are talking about brain health, mostly we are focusing on cognition and memory. But there are many complex brain disorders beyond cognition and memory.

From the perspective of prehistoric medicine in the ancient world, plants have been used in the treatment of medical conditions throughout human history. Historically, all these terms, apothecary, herbalism, ethnopharmacology, phytotherapy, and alternative medicine, are linked to modern nutraceuticals. Nutraceutical-related research of molecular and clinical actions follows from the concept that traditional medicines or tribal practices offer neuroactive agents that cure brain-related diseases or disorders. The goal then is to elucidate how these neuroactive molecules from these sources might make the brain healthier and, in this book, we have several exciting basic studies that represent the prototype of how this field needs to evolve.

The neuroscience in the 21st century has shown tremendous growth, particularly in the identification of targets that provide therapeutic benefit in degenerative conditions, and neurodevelopmental, psychological, and psychiatric disorders through many randomized clinical trials. Since many natural products used in traditional medicine have long been known to exert beneficial actions on diverse brain functions and often the active principles have been identified, the prospect of future success in the field of neuro(nutra)ceuticals continues to capture the imagination of many neuroscientists and is also entering the developmental drug pipeline [4].

This book presents the state-of-the-art scientific evidence, challenges, and potential applications within this exciting field, by providing insight into the treasures of Ayurvedic, Persian, and Western traditional medicines to treat neurodegenerative, neurodevelopmental, psychological, and psychiatric disorders of brain. Few important and upcoming issues such as brain epigenetics, gut-microbe-brain axis, and intelligent drug delivery mechanism are also discussed by eminent scientists. How Big Data is impacting clinical research is also discussed here. Well publicized and controversial role of vitamin B-6, B-9, and B-12 in Alzheimers disease is also discussed. The exciting fields of cardiometabolic impact on cognitive health and role of oxidative stress-antioxidant in elderly are also presented here. I believe our readers in the community, students, researchers, and industry R&D use the information, techniques, and insights of the book to support application of this research and teaching. It is also my belief that this book be used to promote a collaborative understanding of the field between industry and academia. More broadly, however, I hope that this book is accessible to nonspecialist readers, and so can also be utilized by those in the community with keen interest in understanding this research to learn more about (neuro)nutrients and dietary patterns which may provide cognitive protection or benefit, particularly to elderly people.

References

1. . Chang A.Y, Skirbekk V.F, Tyrovoras S, Kassebaum N.J, Dielman J.L. Measuring population ageing: an analysis of the global burden of disease study.  Lancet Public Health . 2019;4:e159–e167.

2. . Cobley J.N, Fiorello M.L, Bailey D.M. 13 reasons why the brain is susceptible to oxidative stress.  Redox biol . 2018;15:490–503.

3. . Jaul E, Barron J. Age-related diseases and clinical and public health implications for the 85 years old and over population.  Front Public Health . 2017;5:335. doi: 10.3389/fpubh.2017.00335.

4. . Williams R.J, Mohanakumar K.P, Beart P.M. Neuro-nutraceuticals: further insights into their promise for brain health.  Neurochem Int . 2016;95:1–3.

Chapter 2: Role of food or food component in brain health

Dilip Ghosh     Nutriconnect, Sydney, NSW, Australia

Abstract

Nutrients are bioactive molecules that are essential for human health and functioning. Most cannot be synthesized internally by human body (not at all, or not in sufficient amount) and need to be obtained from food. Nutrition plays a central role in hypotheses about human evolution, particularly the emergence of large-brained, anatomically modern Homo sapiens. The brain is a complex organ with high metabolism and high turnover of nutrients, and this makes it a high-maintenance device in terms of optimal nutrient intake. Indeed, a myriad of nutrient-specific transport systems and physiological mechanisms constantly work to replace the nutrients used by the brain. The roles of genomics, gut-brain axis, and epigenomics in modulating the effects of nutrition on the brain and mental health are very important directions and need to be included in our future healthcare strategies. In the long term, personalized nutrition, based on individual genetic variability and environmental susceptibility, should help to optimize brain function, and prevent or alleviate mental disorders.

Keywords

Brain health; Cognition; Functional foods; Microbiome; Neuroactive; Nutraceuticals; Nutrients; Omega-3; Polyphenols

Introduction

Energy status and brain health

Neuroactive in foods

Omega-3 and phytochemicals: potential future therapeutic candidates

Cognition beyond foods: just diet or lifestyle pattern?

Food liking versus food wanting

Diet, aging, and neurodegenerative diseases

Diet, cognition, and epigenetics

Microbiota-targeted functional foods for brain health

Thinking outside the brain

Conclusion

References

Introduction

With magnificent advancement in medical science over the last century, human life span has also increased significantly. However, with this advancement comes another potential challenge particularly, the people aged 70 years and more are become increasingly susceptible to chronic and extremely debilitating brain diseases, most notably Alzheimer’s and Parkinson’s disease.

There is growing concern that many existing drug treatments for neurodegenerative disorders are unable to prevent the underlying degeneration of neurons and consequently there is a strong market pull to develop alternative therapies capable of preventing progressive neurodegeneration. Conventional use of antioxidant therapies to combat neuronal damage is well accepted, but exploration of neuroprotective effects of a group of plant secondary metabolites known as flavonoids and other natural products is increasing. The potential beneficial effects of specific polyunsaturated fatty acids (PUFAs) have also been explored more than before. Increasing aging population and subsequent cognitive disability have now emerged as one of the greatest health threats globally. There is a common consumer belief that neurological diseases such as dementia, Alzheimer’s and Parkinson’s might be prevented or treated through personalized dietary intervention. However, there is limited evidence that such approaches are effective, and they might even be harmful in some cases.

Nutrition plays a central role in hypotheses about human evolution, particularly the emergence of large-brained, anatomically modern Homo sapiens in Africa ∼200 ka. Encephalization, increase in brain size that characterizes the human species, is supposed to be linked with the availability of food resources rich in energy as well as trace elements and fatty acids collectively referred to as brain-selective nutrients [1]. Neurodiversity has become a popular topic not only in medical science but also in business. The overlapping Venn diagram (Fig. 2.1, courtesy Dr. Nancy Doyle based on the work of Mary Colley) pictured shows how different conditions are often related and need to be explored for truly understanding the benefits of cognitive difference between people.

We are all aware about the recent controversies of the relationship of vitamin B with dementia [2] and vitamin D insufficiency in patients with Parkinson’s disease (PD) [3]. Indeed, there is convincing evidence that nutrients are essential for human health and physiological functioning. The human body cannot synthesize certain nutrients internally (not at all or not in sufficient amount) and they need to be complemented from food [4]. Particularly the brain with a high metabolism and high turnover of nutrients requires optimal nutrient intake.

Figure 2.1 Neurodiversity shows how interrelated conditions need to be explored for understanding the benefits of cognitive difference between people.

Energy status and brain health

Brain health has been defined as, a state of well-being in which the person can realize their potential, cope with normal stresses of life, work productively and fruitfully and contribute to the community. In addition to cultural, economic, social, and environmental factors, energy status has been identified as holding a critical role in brain health and well-being. The term energy status mentioned here includes energy intake, physical activity, and energy metabolism. Considerable evidence links physical activity and optimal energy intake with improved mood and cognitive function, while both underweight and obesity are associated with impaired cognitive performance. Suboptimal energy status, including undernutrition and overnutrition, is linked with mental and neurological disorders such as depression, schizophrenia, dementia, and Alzheimer’s disease (AD). Individual differences in genetic variability are related to the incidence of these disorders. Rather than considering an individual as having high or low energy status, the focus is on optimal compared with suboptimal energy status.

Neuroactive in foods

A neuroactive substance is defined as a chemical agent synthesized by a neuron, which affects the properties of other neurons and muscle cells. Many neuroactive compounds have significant roles as neurotransmitters, neuromodulators, and neurohormones [5]. These compounds have been not only synthesized by humans but also plants and microorganisms [6]. Therefore, the presence of neuroactive compounds in foods is inevitable. Most common neuroactive compounds in foods are gamma-aminobutyric acid (GABA), serotonin, melatonin, kynurenine, kynurenic acid, dopamine, norepinephrine, histamine, tryptamine, tyramine, and β-phenylethylamine. Fermented foods contain some of these compounds, which can affect human health and mood [7,8]. Neuroactive compounds present in certain raw and nonfermented foods are given in Table 2.1. Health effects of neuroactive compounds consumed with foods have no definite mechanism. Potential positive and negative health effects of neuroactive compounds are summarized in Table 2.2.

Table 2.1

Adapted and modified from Yılmaz C, Gökmen V. Neuroactive compounds in foods: occurrence, mechanism and potential health effects. Food Res Int 2020;128:108744.

It is now established that the composition of diet is significant for gut microbiota profile. There are a number of functional networks in the brain related to different mind states and mood, such as depression and anxiety, sleep, wakefulness, arousal, perception of pain, etc. Neuronal signaling is mediated by the release of neurotransmitters (NTs) at synapses between axons and dendrites. There are many types of NTs and other signaling substances in the brain: amino acids (glutamate, γ-aminobutyric acid (GABA), glycine), catecholamines (dopamine, norepinephrine), monoamines (serotonin, acetylcholine ACh), biogenic amines (histamine, tryptamine, tyramine, etc.), a number of peptides, purines such as adenosine as well as nitric oxide (NO) [9,10]. The delicate balance between synthesis, uptake, and regeneration of NTs can easily be disturbed, and this is one of the main targets when treating neuropsychiatric disorders. Many dietary components can affect the amount and effect of NTs [11]. The amino acid tryptophan is the precursor of serotonin, and dietary supply of tryptophan can influence serotonin levels in the brain [12]. The amino acid tyrosine is the precursor of the NTs dopamine and norepinephrine, and its supplementation seems to enhance cognitive performance, particularly in stressful situations [13]. The biogenic amines, histamine and tyramine, present in stored or fermented foods, are considered as active NTs in the brain [14,15]. There are more reports about the effects of carbohydrates, proteins, and polyphenols on the composition of the gut microbiota. Synthesis of neuroactive compounds can be affected by diet in three ways:

Table 2.2

Adapted and modified from Yılmaz C, Gökmen V. Neuroactive compounds in foods: occurrence, mechanism and potential health effects. Food Res Int 2020;128:108744.

1. Firstly, since amino acids are precursors of neuroactive compounds, proteins or peptides, in the diet which reach the colon, it can lead to the formation of neuroactive compounds by gut microbiota.

2. Secondly, some metabolites (short-chain fatty acids, etc.) formed because of fermentation of carbohydrates and proteins in the gut can trigger the synthesis of neurotransmitters in the human gut.

3. Thirdly, carbohydrates, proteins, lipids, and polyphenols can alter the composition and count of microorganisms which have the ability to produce neuroactive compounds.

Omega-3 and phytochemicals: potential future therapeutic candidates

The brain is one of the most metabolically active organs and, as such, utilizes a large proportion of the dietary intake of carbohydrates to function effectively. The dietary lipids, such as PUFAs, are also thought to play a much important role in supporting optimum brain function by maintaining the optimal function of cholinergic neurons arising from the basal forebrain and terminating in the cortex and hippocampus [16]. This information is leading the way to develop a strategy to prevent the cognitive decline that occurs during normal aging and in AD. The well-characterized and demonstrated effects of both dietary phytochemicals and lipids on endothelial function and peripheral blood flow may also enter into the list of future candidate molecules for brain health. Phenolic compounds are secondary metabolites of plants and include flavonoids, lignans, stilbenes, coumarins, and tannins [17]. Please refer Table 2.3 for more information on food components that have ability to ameliorate brain function. Despite this list, components derived from Vitis vinifera (grape), Camellia sinensis (tea), Theobroma cacao (cocoa), and Vaccinium spp (blueberry) have demonstrated beneficial effects on human vascular function and on improving memory and learning. The PAQUID Study was one of the first epidemiological studies to suggest that flavonoids play a protective role against cognitive decline and AD [18,19,20]. More recent findings from the SU.VI.MAX studies confirm earlier results, showing an association between polyphenols intake and better performance in language and verbal memory tasks [21].

PUFAs could be involved in the maintenance of cognitive function and have a preventive effect against dementia through their antithrombotic and antiinflammatory properties, in addition to their specific effect on neural functions [22]. Indeed, DHA is a key component of membrane phospholipids in the brain, and adequate n-3 PUFA status may help maintain neuronal integrity and function via a range of potential mechanisms. DHA may modify the expression of genes that regulate a variety of biological functions potentially important for cognitive health, including neurogenesis and neuronal function [23]. Fatty fish is the primary dietary source of EPA and DHA, the longer-chain n-3 fatty acids. A growing body of evidence suggests that monounsaturated fatty acids (MUFA), and oleic acid may also have antiinflammatory effects [24]. Recent longitudinal studies support the hypothesis that MUFA may play a protective role toward the development of cognitive decline and dementia [25,26].

Table 2.3

Adapted from Gomez-Pinilla, F., Tyagi, E., Diet and cognition: interplay between cell metabolism and neuronal plasticity. Cur Opin Clin Nutr Metab Care 2013;16:726–733.

Table 2.4 demonstrated the associations of fish consumption with dementia risk to populations in low and middle-income countries. Kyriacou et al. [27] study confirmed that marine animals and, especially, intertidal shellfish indigenous to the region contain relatively large amounts of omega-6 and omega-3 PUFAs, as well as iron, copper, and zinc. The collection and consumption of abundant, accessible and reliable marine mollusks would have been beneficial to early modern humans visiting the Atlantic west coast, particularly in the case of pregnant and lactating mothers. The relatively high EPA and DHA content of intertidal mussels and limpets suggests that small numbers of these marine foods would be needed to fulfill even the highest requirements for these PUFAs. Their inclusion in the diet of early modern humans may have conferred an evolutionary advantage on their consumers by providing sufficient PUFAs for optimal neurological development during gestation and infancy.

Table 2.4

a  Modest increased risk of dementia due to higher meat consumption.

Adapted from Albanese E, Dangour AD, Uauy R, Acosta D, Guerra M, Guerra SSG. Dietary fish and meat intake and dementia in Latin America, China, and India: a 10/66 dementia research group population-based study. Am J Clin Nutr 2009;90(2):392–400.

Cognition beyond foods: just diet or lifestyle pattern?

Mediterranean diet is a term always closely association with cognitive health. This concept is supported by many observational studies. But some lifestyle behaviors, beyond diet, have an evidence-based synergistic association-effect with cognitive health, although not well studied by robust clinical setup. In the lines of the concept of food synergy, several nutritional experts propose a lifestyle behavior synergy to investigate the link between food and cognitive decline. Other factors such as socialization, physical activity, leisure activities, and appropriate rest could be expanded by studying all these in concert, or/and as an independent factor also. This approach may help to develop even more comprehensive dietary intervention strategies on cognitive health.

It is well accepted that diet and lifestyle have been shown to play an important role in halting the progression of neurodegenerative diseases and impaired cognitive function through the enhancement of structural and functional plasticity in the hippocampus, increased expression of neurotrophic factors, maintenance of synaptic function, and adult neurogenesis [28]. Dietary interventions have emerged as potential inducers of brain plasticity, e.g., calorie restriction and intermittent fasting [29,30]. There is a long-term positive effect on cerebral blood flow in response to lifestyle interventions with restricted diet, weight loss, and increased physical activity [31]. In order to provide the brain with all components necessary to support the synthesis of new synapses and maintenance of existing neuronal connections, thereby possibly reducing the consequences of AD, specially designed multicomponent (DHA, EPA, UMP, choline, folic acid, vitamins B6, B12, C E, selenium and phospholipids) diets have been proposed, e.g., Souvenaid (Fortasyn Connect) [32,33].

Food liking versus food wanting

We need a better understanding of how humans evaluate foods and make choices about them, particularly if associated with objective brain markers underlying decision-making processes. This is of great interest because eating-related disorders and especially obesity incidences are still increasing world-wide. In daily life, decisions of food eating are determined by hunger (homeostatic needs), and also by hedonic drives that can even override homeostatic needs [34]. In human food choice behavior science, a prominent concept dominates a dissociation of processes related to food liking as opposed to wanting, as well as how liking and wanting impact food choices and intake [35]. Behaviorally, Bielser et al. showed (unsurprisingly) that strongly liked food items were more frequently chosen than dismissed, and that disliked items were more frequently dismissed than chosen. In this study, participants rated how much they liked each food item (valuation) and subsequently chose between the two alternative food images. The findings [34] show that the spatiotemporal brain dynamics to food viewing are immediately influenced both by how much foods are liked and by choices taken on them. Because food intake is influenced by neurosensory stimulation and memory cues, personalized food images may be useful in prompting appropriate affective responses to food intake, which may subsequently lead to healthier eating behaviors. Whole brain analyses suggested [36] that the visualization of personal images of diet evoked greater brain activation in memory regions (e.g., superior frontal gyrus). This also generates mediating emotion (e.g., thalamus, putamen, anterior cingulate cortex), imagery, and executive functions (e.g., inferior orbitofrontal gyrus, fusiform, and parietal lobe) compared to a written dietary record.

Diet, aging, and neurodegenerative diseases

Aging is commonly associated with a decline in cognitive functioning, which ranges from mild cognitive impairment to dementia. Up to 50% of individuals with mild cognitive impairment will develop dementia within 5 years [37]. AD, the most prevalent cause of dementia, is a progressive neurodegenerative disorder characterized by global cognitive impairment affecting memory, language, and other behavioral functions [38,39]. Although old age is the main risk factor for dementia, other prominent factors have been shown to be diet-related [40]. These include obesity, hypertension, and unbalanced diets [41]. Dietary components have been demonstrated to modulate cerebral structure and connectivity, cognition and emotion, and to induce changes in brain and behavioral functions [42]. Nutritional approaches to manage AD include healthy dietary patterns (e.g., Mediterranean diet) with individual components that may produce positive effects on pathophysiological processes of AD [43]. Ketogenic dietary approaches target energetic deficits and reduce glucose utilization in AD [44], and medical foods also meeting specific nutritional needs of individuals with AD [45].

PD is the second-most common neurodegenerative disease after AD and is hallmarked by damage to the dopaminergic neurons of the substantia nigra and by alpha synuclein containing inclusion bodies (Lewy pathology; LP) in the surviving neurons, resulting in the characteristic motor impairment. Although PD is generally considered as a movement disorder, it has long been recognized that the symptoms go beyond motor dysfunction, since PD patients very often develop nonmotor symptoms, including cognitive impairment [46], depression [47], and others. Levodopa is the most commonly used drug in the treatment of PD. No current therapeutic strategies have a favorable influence on PD progression and they have shown to develop several side effects [48]. Current treatment does not prevent dopaminergic neuron degeneration and has no effect on nonmotor symptoms [49]. Nutritional interventions including phospholipid membrane precursors and/or microbiota-directed therapy like prebiotics and probiotics might provide opportunities to complement the traditional PD therapies and overcome some of their shortcomings including lack of efficacy for GI symptoms/dysfunction. Dietary interventions might have some positive effect on the gut-brain axis by altering microbiota composition (and therefore altering PD pathogenesis) [50,51]; or by affecting neuronal functioning in both the ENS and the central nervous system. Specific nutrient combination containing neuronal precursors and cofactors may counteract synaptic loss and reduce membrane-related pathology in the CNS and the ENS of PD patients. Uridine (as uridine monophosphate, UMP), the omega-3 fatty acid docosahexaenoic acid (DHA), and choline are phospholipid precursors needed for the formation and maintenance of neuronal membranes [52]. Various studies have reported the beneficial effects of probiotics such as representatives of Lactobacilli, Enterococci, Bifidobacteria, yeasts by enhancing intestinal epithelial integrity, protecting from barrier disruption, stimulating a healthy homeostasis of the mucosal immune system and suppressing pathogenic bacterial growth [53,54]. Ingestion of selected probiotics also exhibited beneficial effects on brain function in humans. The administration of Lactobacillus casei strain Shirota in chronic fatigue syndrome patients significantly decreased anxiety symptoms [55].

The insulin Insert ’-’ in-between ’Insulin’ & ’like’like growth factor 1 (IGF-1) plays an essential role in energy metabolism in the brain. The metabolic capacity of the mitochondria is dependent on the IGF-1 signaling pathway [56]. The degradative product of IGF-1, cyclic glycine-proline (cGP), is a key factor in the brain that normalizes IGF-1 signaling, essential for cognitive function [57]. Several clinical trials in which patients suffering from PD received supplementation of blackcurrant anthocyanins extract have demonstrated increased levels of cGP [58].

Diet, cognition, and epigenetics

Several recent groundbreaking studies have highlighted the potential possibility of extending the effects of diet on cognitive health across generations. The outcomes of these studies have great impact on the development of future strategies for combating several diseases. Overall these studies indicate the importance of dietary components in influencing epigenetic events i.e., nongenetic events, such as DNA methylation, transcriptional activation, translational control, and posttranslational modifications that cause a potentially heritable phenotypic change and, thus, their potential for disease modulation. Although the exact molecular mechanisms for the epigenetics influence of diet are not properly known, it is understood that the brain-derived neurotrophic factor system is particularly susceptible to epigenetic modifications that influence cognitive function. For instance, the serotonergic system is influenced by early nutrition and stress, causing epigenetic modifications that affect expression and are linked to bipolar disorders and depression in later stage of life [59]. A number of additional direct connections between nutrition and epigenetics have been identified [60]. As for example, methionine, folic acid, vitamins B6 and B12, choline, and glycine betaine are all important for the one-carbon metabolism which can affect DNA methylation. Genistein from soy and tea catechins affect DNA demethylation and histone modification, whereas resveratrol from red wine, sulforaphane from broccoli, butyrate, diallyl sulfide (garlic), and curcumin (turmeric) all affect histone acetylation, and retinoic acid is affecting miRNA transcription. Oleuropein, tyrosol, and hydroxytyrosol from olive tree (Olea europaea) demonstrate neuroprotective effects, partly via epigenetic modifications [61].

These studies clearly demonstrating the intracellular signaling pathways triggered by lifestyle factors can promote long-lasting changes in DNA function in the brain and in cognitive capacity. For an example, a diet that is high in saturated fat reduces the expression of Silent information regulator 2 (SIRT2) in the rat hippocampus, whereas a diet that is high in omega-3 fatty acids has the opposite effect. This is just an early warning on stable and heritable association of our own bad lifestyle and cognitive decline for generations.

Microbiota-targeted functional foods for brain health

The etiology of most neuropsychiatric disorders is likely multifactorial, based on both genetic and environmental factors (Fig. 2.2 [62]), particularly, the environmental factors can directly affect the gut microbiome that, in turn, can affect host physiology. In recent years accumulating body of evidence indicates a bidirectional communication between the gastrointestinal tract and the brain, an interaction termed as the gut-brain axis [63]. This interaction relates to the gut microbiota and the physiology and pathology of the mammalian brain. During homeostasis, we have a symbiotic relationship with our gut microbes that ensure a regulated and healthy brain development. However, dysbiosis (i.e., an imbalanced population of gut microbes), can lead to pathological states, including brain pathologies. Normal gut microbiota has been shown to lead to proper brain development and behavior. Gut dysbiosis has been shown to be associated with neurological disorders, such as psychiatric disorders—depression and anxiety, as well as autism and neurodegenerative diseases [64,65]. The gut microbiota has been shown to impact CNS neurogenesis. In addition, the gut microbiota was shown to impact neuronal excitability and communicate with the host via neurochemicals.

Figure 2.2 Interaction of gut microbiota with brain development, physiology, and pathology± (a) Healthy gut microbiota in normal brain development, fetal neuro proliferation, and adult neurogenesis. (b) Altered gut microbiota (dysbiosis) affects neurodegenerative diseases (e.g., AD, amyotrophic lateral sclerosis, and PD). (c) Altered gut microbiota affects host behavior and neuropsychiatric diseases. (d) Altered gut microbiota affects brain pathologies (e.g., stroke, autoimmune diseases) and related-immune response. 

Adapted and modified from Hajjo H, Geva-Zatorsky N. Gut microbiota – host interactions now also brain-immune axis. Curr Opin Neurobiol 2020;62:53–59.

Considering all study outcomes in recent years, modulation of the gut microbiota using dietary intervention, in particular with prebiotics and probiotics, is a promising strategy in promoting normal brain function and mental health. Prebiotics may exert a beneficial brain effect through improving host immunity, enhancing SCFA production, reducing potentially pathogenic microbes, and improving gut barrier function [66]. Lactobacillus spp. and Bifidobacterium spp. are the most used probiotics and may act via a number of mechanisms to alter the gut microbiota of the host in order to improve brain health. This intervention may help in production of antimicrobial compounds, reduction of the luminal pH through the production of SCFA, competitive exclusion of other microbes from adhering to epithelial cells, production of growth substrates, enhancing barrier function, and modulation of immune responses [67].

As discussed previously, polyphenols are a large group of compounds naturally occurring in plants and a variety of foods, including citrus fruits, cocoa, red wine, tea, and coffee. Large-scale epidemiological investigations suggest that a diet rich in polyphenols may help maintain normal brain function and mental health [19]. Interventional studies in humans provide some supportive evidence for this epidemiological data (see Table 2.3).

Antiinflammatory and antioxidant properties and modulation of enzyme activity have been proposed to be responsible for the positive CNS effects of polyphenols [19], but due to the poor bioavailability of most of the polyphenols [68], approx. 90%–95% of total dietary polyphenols accumulate in the large intestine where they are broken down into less complex metabolites by the gut microbiota [69]. For example, black and green tea (epigallocatechin, epicatechin, catechin) have been shown to affect the growth of Helicobacter pylori, Staphylococcus aureus, Salmonella typhimurium, Listeria monocytogenes, while other polyphenols have been shown to promote the growth of beneficial bacteria, such as Bifidobacterium spp. [70].

It is likely that the beneficial CNS effects of polyphenol compounds are mediated, at least in part, by interactions with the gut microbiota [71]. So it is imperative that when food scientists and technologists are developing polyphenol-based brain function enhancing products, they should consider the large interindividual variation in gut microbiota composition, which may significantly affect polyphenol bioefficacy [69].

Thinking outside the brain

The brain is traditionally known to play an essential role in governing and coordinating our systemic homeostasis. In recent years, it is also becoming clear that the conditions of brain health are intimately associated with other physiological systems. Therefore, a much more complex picture has emerged concerning the exact pathophysiological basis of cognitive deficits and many other neuropsychological disorders [72]. Despite much conceptual progress made so far, disappointment exists for the CNS drug discovery mode that solely focuses on the brain but ignores peripheral mediators. To achieve this holistic goal, it will be imperative to look beyond the brain and integrate an interdisciplinary approach to the research pipeline. These emerging findings have shed novel insights into cognitive dysfunctions and also raised a number of interesting questions on future preventive and therapeutic strategies.

Major pathways outside brain in cognitive regulation are:

• Neuroimmune signaling and cognition

• Endocrinal signaling and cognition

• Metabolic signaling and cognition

• The blood-brain barrier

Conclusion

Although food has traditionally been perceived as a supplier of energy and building material to the body, its ability to prevent and protect against diseases is starting to be recognized by consumers, industries, and regulators. There is a tendency to think of nutritional supplements as harmless at worst and beneficial at best. However, at the same time several recent trials warn about this hypothesis. Due to the encouraging results of clinical and preclinical studies, the topic has attracted substantial global media attention in recent years. The downside of this hype is scientific understanding of perceived benefits and actual cause-benefit relationships of such supplementation.

The roles of genomics and epigenomics in modulating the effects of nutrition on the brain and mental health are very important directions and need to be included in our future healthcare strategies. In the long term, personalized nutrition, based on individual genetic variability and environmental susceptibility, should help to optimize brain function, and prevent or alleviate mental disorders.

Finally, one important issue to be determined under strict clinical environment is that whether the functional foods (prebiotics, probiotics, omega-3 PUFAs, and polyphenols) can be employed as stand-alone nutritional solutions to promote normal brain function and mental health, or will be most effective as adjunct to current therapeutic approaches.

Brain health is one of the rapidly developing fields, new findings are continually emerging which bolster our knowledge of how the gut microbiota influence brain function and behavior. Despite significant gains over the past decade in understanding the mechanisms underlying the development and manifestation of most major psychiatric disorders, few advances have been made in the discovery of novel CNS acting agents. As a result, Psychobiotic’ interventions, which target pathways of microbiota-gut-brain axis, represent a new era in psychotropic therapies and hold great promise in promoting normal brain function and mental health across the lifespan.

References

1. . Kuipers E, Onwumere J, Bebbington P. Cognitive model of caregiving in psychosis.  Br J Psychiatry . 2010;196(4):259–265.

2. . Garrard P, Jacoby R. B-vitamin trials meta-analysis: less than meets the eye.  Am J Clin Nutr . 2015;101(2):414–415.

3. . Hiller A.M, Murchison C.F, Lobb B, O'Connor S. A randomized, controlled pilot study of the effects of vitamin D supplementation on balance in Parkinson's disease: does age matter?  PLoS One . 2018;13(9):e0203637. .

4. . Morris M.C. Nutritional determinants of cognitive aging and dementia.  Proc Nutr Soc . 2012;71:1–13.

5. . Zieger E, Schubert M. New insights into the roles of retinoic acid signaling in nervous system development and the establishment of neurotransmitter systems. In: Galluzzi L, ed.  Int. Rev. Cell Molec. Biol. . Academic Press; 2017:1–84.

6. . Roshchina V.V. Evolutionary considerations of neurotransmitters in microbial, plant, and animal cells. In: Lyte M, Freestone P.P.E, eds.  Microbial endocrinology: interkingdom signaling in infectious disease and health . New York, NY: Springer; 2010:17–52.

7. . Yılmaz C, Gökmen V. Formation of tyramine in yoghurt during fermentation –Interaction between yoghurt starter bacteria and Lactobacillus plantarum.  Food Res Int . 2017;97:288–295.

8. . Yılmaz C, Gökmen V. Kinetic evaluation of the formation of tryptophan derivatives in the kynurenine pathway during wort fermentation using Saccharomyces pastorianus and Saccharomyces cerevisiae.  Food Chem . 2019;297:124975.

9. . Calabrese V, Mancuso C, Calvani M, Rizzarelli E, Butterfield D.A, Stella A.M.Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity.  Nat Rev Neurosci . 2007;8(10):766–775.

10. . Lovinger D.M. Communication networks in the brain: neurons, receptors, neurotransmitters, and alcohol.  Alcohol Res Health . 2008;31(3):196–214.

11. . Briguglio M, Dell'Osso B, Panzica G, Malgaroli A, Banfi G, Zanaboni Dina C, et al. Dietary neurotransmitters: a narrative review on current knowledge.  Nutrients . 2018;10(5) doi: 10.3390/nu10050591.

12. . Young S.N. How to increase serotonin in the human brain without drugs.  J Psychiatry Neurosci . 2007;32(6):394–399.

13. . Jongkees B.J, Hommel B, Kuhn S, Colzato L.S. Effect of tyrosine supplementation on clinical and healthy populations under stress or cognitive demands-a review.  J Psychiatr Res . 2015;70:50–57.

14. . Ladero V, Calles-Enriquez M, Fernandez M.A, Alvarez M. Toxicological effects of dietary biogenic amines.  Curr Nutr Food Sci . 2010;6(2):145–156.

15. . Passani M.B, Panula P, Lin J.S. Histamine in the brain.  Front Syst Neurosci . 2014;8:64.

16. . Caracciolo B, Xu W, Collins S, Fratiglioni L. Cognitive decline, dietary factors and gut–brain interactions.  Mech Ageing Dev . 2014;136–137:59–69.

17. . Ghosh D, Scheepens A. Vascular action of polyphenols.  Mol Nutr Food Res . 2009;53:322–331.

18. . Commenges D, Scotet V, Renaud S, Jacqmin-Gadda H, Barberger-Gateau P, Dartigues J.F.Intake of flavonoids and risk of dementia.  Eur J Epidemiol . 2000;16:357–363.

19. . Letenneur L, Proust-Lima C, Le Gouge A, Dartigues J.F, Barberger-Gateau P. Flavonoid intake and cognitive decline over a 10-year period.  Am J Epidemiol . 2007;165:1364–1371.

20. . Schaffer S, Asseburg H, Kuntz S, Muller W.E, Eckert G.P. Effects of polyphenols on brain ageing and Alzheimer's disease: focus on mitochondria.  Mol Neurobiol . 2012;46:161–178.

21. . Kesse-Guyot E, Fezeu L, Andreeva V.A, Touvier M, Scalbert A, Hercberg S, et al. Total and specific polyphenol intakes in midlife are associated with cognitive function measured 13 years later.  J Nutr . 2012;142:76–83.

22. . Gillette-Guyonnet S, Secher M, Vellas B. Nutrition and neurodegeneration: epidemiological evidence and challenges for future research.  Br J Clin Pharmacol . 2013;75:738–755.

23. . Sydenham E, Dangour A.D, Lim W.S. Omega 3 fatty acid for the prevention of cognitive decline and dementia.  Cochrane Database Syst Rev . 2012;6:CD005379.

24. . Galland L. Diet and inflammation.  Nutr Clin Pract . 2010:25.

25. . Naqvi A.Z, Harty B, Mukamal K.J, Stoddard A.M, Vitolins M, Dunn J.E. Monounsaturated, trans, and saturated fatty acids and cognitive decline in women.  J Am Geriatr Soc . 2011;59:837–843.

26. . Vercambre M.N, Grodstein F, Kang J.H. Dietary fat intake in relation to cognitive change in high-risk women with cardiovascular disease or vascular factors.  Eur J Clin Nutr . 2010;64:1134–1140.

27. . Kyriacou K, Blackhurst D.M, Parkington J.E, Marais A.D. Marine and terrestrial foods as a source of brain-selective nutrients for early modern humans in the southwestern Cape, South Africa.  J Hum Evol . 2016;97:86–96.

28. . Murphy T, Dias G.P, Thuret S. Effects of diet on brain plasticity in animal and human studies: mind the gap.  Neural Plasticity . 2014;2014:563160.

29. . Guo J, Bakshi V, Lin A.L. Early shifts of brain metabolism by caloric restriction preserve white matter integrity and long-term memory in aging mice.  Front Aging Neurosci . 2015;7:213.

30. . Martin B, Mattson M.P, Maudsley S. Caloric restriction and intermittent fasting: two potential diets for successful brain aging.  Ageing Res Rev . 2006;5(3):332–353.

31. . Espeland M.A, Luchsinger J.A, Neiberg R.H, Carmichael O, Laurienti P.J, Pi-Sunyer X, et al. Long term effect of intensive lifestyle intervention on cerebral blood flow.  J Am Geriatr Soc . 2018;66(1):120–126.

32. . Cummings J, Scheltens P, McKeith I, Blesa R, Harrison J.E, Bertolucci P./, et al. Effect size analyses of Souvenaid in patients with Alzheimer's disease.  J Alzheim Dis . 2017;55(3):1131–1139.

33. . Mi W, van Wijk N, Cansev M, Sijben J.W, Kamphuis P.J. Nutritional approaches in the risk reduction and management of Alzheimer's disease.  Nutrition . 2013;29(9):1080–1089.

34. . Bielser M, Crézé C, Murray M.M, Toepel U. Does my brain want what my eyes like? – how food liking and choice influence spatio-temporal brain dynamics of food viewing.  Brain Cognit . 2016;110:64–73.

35. . Berridge K.C. Liking and wanting food rewards: brain substrates and roles in eating disorders.  Physiol Behav . 2009;97:537–550.

36. . Dodd S.L, Long J.D, Hou J, Kahathuduwa C.N, O'Boyle M.W. Brain activation and affective judgements in response to personal dietary images: an fMRI preliminary study.  Appetite . 2020;148:104561.

37. . Gauthier S, Reisberg B, Zaudig M, Petersen R.C, Broich R.K, Belleville S, et al. Mild cognitive impairment.  Lancet . 2006;367:1262–1270.

38. . Lange K.W, Sahakian B.J, Quinn N.P, Marsden C.D, Robbins T.W. Comparison of executive and visuospatial memory function in Huntington's disease and dementia of the Alzheimer-type matched for degrees of dementia.  J Neurol Neurosurg Psychiatry . 1995;58:598–606.

39. . Scheltens P, Blennow K, Breteler M.M, Strooper B.de, Frisoni G.B, Salloway S, et al. Alzheimer's disease.  Lancet . 2016;388:505–517.

40. . Moore K, Hughes C.F, Ward M, Hoey L, McNulty H. Diet, nutrition and the ageing brain: current evidence and new directions.  Proc Nutr Soc . 2018;77:152–163.

41. . World Health Organization.  Towards a dementia plan: a WHO guide . Geneva: World Health Organization; 2018.

42. . Gustafson D.R, Morris M.C, Scarmeas N, Shah R.C, Sijben J, Yaffe K, et al. New perspectives on Alzheimer's disease and nutrition.  J. Alzheimers Dis.  2015;46:1111–1127. .

43. . Petersson S.D, Philippou E. Mediterranean diet, cognitive function, and dementia: a systematic review of the evidence.  Adv Nutr . 2016;7:889–904.

44. . Lange K.W, Lange K.M, Makulska-Gertruda E, Nakamura Y, Reissmann A, Kanaya S, et al. Ketogenic diets and Alzheimer's disease.  Food Sci Hum Wellness . 2017;6:1–9.

45. . Shah R.C. Medical foods for Alzheimer's disease.  Drugs Aging . 2011;28:421–428.

46. . Aarsland D, Creese B, Politis M, Chaudhuri K.R, Ffytche D.H, Weintraub D, et al. Cognitive decline in Parkinson disease.  Nat Rev Neurol . 2017;13:217–231.

47. . Remy P, Doder M, Lees A, Turjanski N, Brooks D. Depression in Parkinson's disease: loss of dopamine and noradrenaline innervation in the limbic system.  Brain J Neurol . 2005;128:1314–1322.

48. . Schrag A, Quinn N. Dyskinesias and motor fluctuations in Parkinson's disease. A community-based study.  Brain J Neurol.  2000;123:2297–2305.

49. . Lee H.M, Koh S.B. Many faces of Parkinson's disease: non-motor symptoms of Parkinson's disease.  J Mov Disord . 2015;8:92–97.

50. . Clemente J.C, Ursell L.K, Parfrey L.W, Knight R. The impact of the gut microbiota on human health: an integrative view.  Cell . 2012;148:1258–1270.

51. . Maslowski K.M, Mackay C.R. Diet, gut microbiota and immune responses.  Nat Immunol . 2011;12:5–9.

52. . Wurtman R.J. A nutrient combination that can affect synapse formation.  Nutrients . 2014;6:1701–1710.

53. . Corridoni D, Pastorelli L, Mattioli B, Locovei S, Ishikawa D, Arseneau K.O, et al. Probiotic bacteria regulate intestinal epithelial permeability in experimental ileitis by a TNF-dependent mechanism.  PLoS One . 2012;7:e42067.

54. . Patel R.M, Myers L.S, Kurundkar A.R, Maheshwari A, Nusrat A, Lin P.W. Probiotic bacteria induce maturation of intestinal claudin 3 expression and barrier function.  Am J Pathol . 2012;180:626–635.

55. . Rao A.V, Bested A.C, Beaulne T.M, Katzman M.A, Iorio C, Berardi J.M, et al. A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome.  Gut Pathog . 2009;1:6.

56. . Yin F, Jiang T, Cadenas E. Metabolic triad in brain aging: mitochondria, insulin/IGF-1 signalling and JNK signalling.  Biochem Soc Trans . 2013;41(1):101–105.

57. . Guan J, Gluckman P, Yang P.Z, Krissansen G, Sun X, Zhou Y, et al. Cyclic glycine-proline regulates IGF-1 homeostasis by altering the binding of IGFBP-3 to IGF-1.  Sci Rep . 2014;4:4388. doi: 10.1038/srep04388.

58. . Fan D, Alamri Y, Liu K, MacAskill M, Harris P, Brimble M, et al. Supplementation of blackcurrant anthocyanins increased cyclic glycine-proline in the cerebrospinal fluid of Parkinson patients: potential treatment to improve insulin-like growth factor-1 function.  Nutrients . 2018;10(6) doi: 10.3390/nu10060714.

59. . Dauncey M.J. Genomic and epigenomic insights into nutrition and brain disorders.  Nutrients . 2013;5(3):887–914.

60. . Choi S.W, Friso S. Epigenetics: a new bridge between nutrition and health.  Advan. Nutr. (Bethesda, Md) . 2010;1(1):8–16.

61. . St-Laurent-Thibault C, Arseneault M, Longpre F, Ramassamy C. Tyrosol and hydroxytyrosol, two main components of olive oil, protect N2a cells against amyloid-beta-induced toxicity. Involvement of the NF-kappaB signaling.  Curr Alzheimer Res . 2011;8(5):543–551.

62. . Hajjo H, Geva-Zatorsky N. Gut microbiota – host interactions now also brain-immune axis.  Curr Opin Neurobiol . 2020;62:53–59.

63. . Khanna S, Tosh P.K. A clinician's primer on the role of the microbiome in human health and disease.  Mayo Clin Proc . 2014;89:107–114.

64. . Lurie I, Yang Y.X, Haynes K, Mamtani R, Boursi B. Antibiotic exposure and the risk for depression, anxiety, or psychosis.  J Clin Psychiatr . 2015;76:1522–1528.

65. . Rogers G.B, Keating D.J, Young R.L, Wong M.L, Licinio J, Wesselingh S. From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways.  Mol Psychiatr . 2016;21:738–748.

66. . Slavin J. Fiber and prebiotics: mechanisms and health benefits.  Nutrients . 2013;5:1417–1435.

67. . Power S.E, O'Toole P.W, Stanton C, Ross R.P, Fitzgerald G.F. Intestinal microbiota, diet and health.  Br J Nutr . 2014;111:387–402.

68. . Yılmaz C, Gökmen V. Neuroactive compounds in foods: occurrence, mechanism and potential health effects.  Food Res Int . 2020;128:23 108744.

69. . Crozier A, Jaganath I.B, Clifford M.N. Dietary phenolics: chemistry, bioavailability and effects on health.  Nat Prod Rep . 2009;26:1001–1043.

70. . Selma M.V, Espin J.C, Tomas-Barberan F.A. Interaction between phenolics and gut microbiota: role in human health.  J Agric Food Chem . 2009;57:6485–6501.

71. . Duda-Chodak A, Tarko T, Satora P, Sroka P. Interaction of dietary compounds, especially polyphenols, with the intestinal microbiota: a review.  Eur J Nutr . 2009;54(3):325–341.

72. . Schaffer S, Halliwell B. Do polyphenols enter the brain and does it matter? Some theoretical and practical considerations.  Genes Nutr . 2012;7:99–109.

74. . Zheng X, Zhang X, Kang A, Ran C, Wang G, Hao H. Thinking outside the brain for cognitive improvement: is peripheral immunomodulation on the way?  Neuropharmacology . 2015;96:94–104.

Chapter 3: Bacopa monnieri for cognitive health—a review of molecular mechanisms of action

Divya Purusothaman, Nehru Sai Suresh Chalichem, Bharathi Bethapudi, Sasikumar Murugan, and Deepak Mundkinajeddu     Research and Development Center, Natural Remedies Private Limited, Bengaluru, Karnataka, India

Abstract

The chapter reviews the overall neuronal molecular mechanisms of Bacopa monnieri