Preface

This edited volume is a collection of reviewed and relevant research chapters concerning the developments within the malnutrition field of study.

This book covers a very relevant topic that not only proved a major disaster for developing economies but also caused problems in developed economies. Malnutrition causes severe structural and functional abnormalities that hinder the growth of the individual, but also society in general. This book provide complete insight into the problem, pathophysiology, impact and rectifying strategies.

Each contribution comes as a separate chapter complete in itself but directly related to the book's topics and objectives.

The book is composed of two sections: 1.) Introduction to Malnutrition, and 2.) Malnutrition and Global Determinants.

The "Introduction to Malnutrition" includes the following chapters: "Introductory Chapter: Malnutrition", "Biofortification of Crops Using Biotechnology to Alleviate Malnutrition", "Vitamins" and "Malnutrition: Current Challenges and Future Perspectives". The second section, "Malnutrition and Global Determinants", includes the following chapters: "Wernicke Encephalopathy in Elderly Related to Severe Malnutrition", "Global Prevalence of Malnutrition: Evidence from Literature" and "Detection of Nutrient-Related SNP to Reveal Individual Malnutrition Risk".

The target audience comprises scholars and specialists in the field. This book will provide deep insights into the problem, pathophysiology and tackling strategies.

> **Muhammad Imran** University of Lahore, Pakistan

**Ali Imran** Government College University, Pakistan

**1**

Section 1

Introduction to

Malnutrition

Section 1

Introduction to Malnutrition

**3**

**Chapter 1**

Malnutrition

well as stunting (low height for age) [2].

*and Ali Imran*

**1. Introduction**

Introductory Chapter:

*Farhan Saeed, Muhammad Imran, Tabussam Tufail* 

Malnutrition is defined as not having enough food to eat or more than feeling hungry. Insufficient intake of calories (a measure of energy the body needs), protein (necessary to build muscle and to keep the body healthy), iron (for appropriate blood cell function) as well as different types of nutrients can cause malnutrition [1]. In a person's intake of energy as well as nutrient imbalances, excesses or deficiencies are referred to as malnutrition. Two broad groups of conditions are covered by the term malnutrition. One is 'undernutrition' which comprises micronutrient deficiencies or insufficiencies (a lack of significant vitamins and minerals), underweight (low weight for age), wasting (low weight for height), as

Among the children fundamental cause of mortality and morbidity is malnutrition [3]. Approximately half of the mortality in children attributed to undernutrition around the globe [4]. In children's mental and physical development, it poses a risk as well that is result in deprived academic accomplishment [5]. To ensure in early childhood intellectual development, proper physical and a strong immune system adequate nutrition is indispensable [6, 7]. In the world under the age of five 110 million (19%) are moderately or severely underweight and 170 million (30%) of children are moderately or severely stunted [8]. In Asia reside approximately half of all stunned children, under five years of age children 51 million (8%) are wasted, as well as in Asia live two thirds of all wasted children [9]. The dynamic prospective of the society, socioeconomic development of children and future health affects by malnutrition. Prevalence of child malnutrition compared to other developing counties Pakistan has been reported to have one of the highest levels [10]. About 50% were anemic, 44% were stunted, 33% were anemic (iron deficiency), 33%of all children were underweight, 15% are wasted, According to the National Nutrition Survey. In Pakistan compared to other developing countries in the prevalence of child malnutrition there has been a little reduction, In the last two decades [11]. In less developed countries a major public health and social problem, childhood malnutrition still remains, despite economic and social development [12, 13]. In childhood malnutrition the contributing factors are infectious diseases, vaccination, poor sanitation, food insecurity, household socioeconomic status, birth spacing, parity, micronutrient intake, lack of proper knowledge of nutrition, maternal education, inappropriate complementary feeding, inadequate breast feeding and exclusive breastfeeding as well as low birth weight. In the world the Pakistan is among the countries with the highest rates of child malnutrition, as well as than in other South Asian

countries its progress and health in child nutrition remains slower.

#### **Chapter 1**

## Introductory Chapter: Malnutrition

*Farhan Saeed, Muhammad Imran, Tabussam Tufail and Ali Imran*

#### **1. Introduction**

Malnutrition is defined as not having enough food to eat or more than feeling hungry. Insufficient intake of calories (a measure of energy the body needs), protein (necessary to build muscle and to keep the body healthy), iron (for appropriate blood cell function) as well as different types of nutrients can cause malnutrition [1]. In a person's intake of energy as well as nutrient imbalances, excesses or deficiencies are referred to as malnutrition. Two broad groups of conditions are covered by the term malnutrition. One is 'undernutrition' which comprises micronutrient deficiencies or insufficiencies (a lack of significant vitamins and minerals), underweight (low weight for age), wasting (low weight for height), as well as stunting (low height for age) [2].

Among the children fundamental cause of mortality and morbidity is malnutrition [3]. Approximately half of the mortality in children attributed to undernutrition around the globe [4]. In children's mental and physical development, it poses a risk as well that is result in deprived academic accomplishment [5]. To ensure in early childhood intellectual development, proper physical and a strong immune system adequate nutrition is indispensable [6, 7]. In the world under the age of five 110 million (19%) are moderately or severely underweight and 170 million (30%) of children are moderately or severely stunted [8]. In Asia reside approximately half of all stunned children, under five years of age children 51 million (8%) are wasted, as well as in Asia live two thirds of all wasted children [9]. The dynamic prospective of the society, socioeconomic development of children and future health affects by malnutrition. Prevalence of child malnutrition compared to other developing counties Pakistan has been reported to have one of the highest levels [10]. About 50% were anemic, 44% were stunted, 33% were anemic (iron deficiency), 33%of all children were underweight, 15% are wasted, According to the National Nutrition Survey. In Pakistan compared to other developing countries in the prevalence of child malnutrition there has been a little reduction, In the last two decades [11]. In less developed countries a major public health and social problem, childhood malnutrition still remains, despite economic and social development [12, 13]. In childhood malnutrition the contributing factors are infectious diseases, vaccination, poor sanitation, food insecurity, household socioeconomic status, birth spacing, parity, micronutrient intake, lack of proper knowledge of nutrition, maternal education, inappropriate complementary feeding, inadequate breast feeding and exclusive breastfeeding as well as low birth weight. In the world the Pakistan is among the countries with the highest rates of child malnutrition, as well as than in other South Asian countries its progress and health in child nutrition remains slower.

#### **2. Undernutrition**

If undernutrition occurs before two years of age or during pregnancy, it may result in permanent problems with mental and physical development. Known as starvation, the extreme undernourishment, may have symptoms that comprise swollen legs and abdomen, very poor energy levels, thin body and a short height. Frequently cold and infections too often get people. On the micronutrient that is lacking depend the symptoms of micronutrient deficiencies. Not enough highquality food being available to eat most often undernourishment is because of it. Most often related to poverty as well as high food prices. Be short of breastfeeding might contribute as might a number of infectious diseases for instance measles, malaria, pneumonia as well as gastroenteritis which enhance nutrient requirements. Dietary deficiencies as well as protein-energy malnutrition, there are two main types of undernutrition. A lack of vitamin A, iron and iodine comprises common micronutrient deficiencies. Deficiencies may become more common, due to the body's increased need, during pregnancy. Two severe forms of Proteinenergy malnutrition are kwashiorkor (a lack of just protein) and marasmus (a lack of protein and calories). Within the same communities as undernutrition is beginning to present overnutrition in the form of obesity, in some developing countries. Malnutrition other causes comprise bariatric surgery and anorexia nervosa [14].

#### **3. Wasted and stunted**

In two major ways nutritionists have categorized undernutrition, Since the 1970s. If children have a small mid-upper arm circumference and low weight for-height, to signify acute undernutrition which is taken, they are defined as wasted and in need of treatment. If children have a low height-for-age, to signify chronic undernutrition which is taken they are defined as stunted. Low weightfor-age classified children as underweight, because of stunting or wasting or both thus, undernutrition index is composite. At the population level widely used these markers to assess child undernutrition as well as who are wasted or stunted a high prevalence of children is considered a public health problem [15]. At the level of interventions and programmatic design, however, the two categories of undernutrition were approached very differently.

Wasted children contain an elevated risk of dying that by nutritional therapy may often rapidly reduced [16]. To prevent deaths associated with child wasting, making therapy available is so considered essential. On the other hand, including fetal development, over long periods children have poor growth in height they are categorized as stunted. For rapid nutritional correction is not willing this growth faltering as well as consequently rather than treatment considered to require prevention, these outcomes in terms of policy leading to the separation, programmed interventions, guidance as well as financing: at the individual level, now viewed as separate conditions acute undernutrition as well as chronic undernutrition, and among policy makers as distinct outcomes are routinely reported [17].

A new classification for malnutrition is established by John Conrad Water low. to show the stunting which results as of chronic malnutrition with height-for-age combines weight-for-height (representing acute episodes of malnutrition), rather than using just weight for age measurements, the classification established by Water low. Over the Gomez classification one advantage of the Water low classification is that even if ages are not known weight for height can be examined [18].

**5**

in India.

*Introductory Chapter: Malnutrition*

*DOI: http://dx.doi.org/10.5772/intechopen.93763*

modifications being commonly used.

**4. The effects of malnutrition**

alter then further suffer nutrition status [19].

obesity and overweight are on the rise.

**5. Effect of malnutrition on economy of a country**

**Degree of PEM Stunting (%) height for age Wasting (%) weight for height**

The above table shows the classifications of malnutrition by WHO, with some

More likely than others to be caught in the weakened immunity as well as downward spiral of malnutrition, people who restrict their food intakes, whether because of an eating disorder, illness, desire for weight loss, and lack of appetite. One or more of the following also susceptible: malnourished, poor, hospitalized and very young or old. When medical tests of a malnourished individual signify compromised immune system increase dramatically rate of death and sickness. When an individual becomes malnourished, often worsens disease by malnutrition that in turn gets worse malnutrition. For disease when impaired immunity opens the way often begins a destructive cycle: when impairs appetite by disease, interferes with absorption as well as digestion, excretion increases or metabolism

Malnutrition as well as global hunger remains big challenges in the last two decades, despite achieved significant progress. In the world about 805 million people continue to suffer as of chronic hunger and people suffer from micronutrient deficiencies more than 2 billion. Furthermore, in low and middle-income countries,

Huge economic and social costs are imposed by hunger and malnutrition that are able to be felt at societal, household, and individual levels. For instance, according to the FAO, the global economy per year US\$1.4–2.1 trillion cost for hunger and undernutrition or global gross domestic product 2–3%. To eliminate hunger and malnutrition, the economic returns are able to as well extremely elevate. From reducing child undernutrition, there are substantial, lifetime economic benefits demonstrated by evidence as of IFPRI-led research. For instance, every dollar spent on interventions in economic returns to reduce stunting is estimated to generate about US\$34,

Malnutrition as well as hunger is expensive. It is predictable that because of undernutrition (GDP) 2–3%, equivalent to per year US\$1.4–2.1 trillion is lost and because of overnutrition annual GDP another 2–3% is lost. Collectively, because of

Each dollar spent in economic benefits iodizing salt generates \$30; each dollar spent in economic benefits on iron supplements for children aged six to 24 months and for mothers generates \$24. Each dollar spent in economic benefits on vitamin A generates estimated to be \$40 or more. To reduce chronic undernutrition need bundling micronutrient interventions for instance, individuals that decrease iron, iodine and vitamin A deficiencies with the condition of other micronutrients (for

malnutrition global GDP 5% (per year US\$3.5 trillion) is lost [20].

Normal: Grade 0 >95% >90% Mild: Grade I 87.5–95% 80–90% Moderate: Grade II 80–87.5% 70–80% Severe: Grade III <80% <70%

*Introductory Chapter: Malnutrition DOI: http://dx.doi.org/10.5772/intechopen.93763*

*Malnutrition*

nervosa [14].

**3. Wasted and stunted**

tion were approached very differently.

**2. Undernutrition**

If undernutrition occurs before two years of age or during pregnancy, it may result in permanent problems with mental and physical development. Known as starvation, the extreme undernourishment, may have symptoms that comprise swollen legs and abdomen, very poor energy levels, thin body and a short height. Frequently cold and infections too often get people. On the micronutrient that is lacking depend the symptoms of micronutrient deficiencies. Not enough highquality food being available to eat most often undernourishment is because of it. Most often related to poverty as well as high food prices. Be short of breastfeeding might contribute as might a number of infectious diseases for instance measles, malaria, pneumonia as well as gastroenteritis which enhance nutrient requirements. Dietary deficiencies as well as protein-energy malnutrition, there are two main types of undernutrition. A lack of vitamin A, iron and iodine comprises common micronutrient deficiencies. Deficiencies may become more common, due to the body's increased need, during pregnancy. Two severe forms of Proteinenergy malnutrition are kwashiorkor (a lack of just protein) and marasmus (a lack of protein and calories). Within the same communities as undernutrition is beginning to present overnutrition in the form of obesity, in some developing countries. Malnutrition other causes comprise bariatric surgery and anorexia

In two major ways nutritionists have categorized undernutrition, Since the 1970s. If children have a small mid-upper arm circumference and low weight for-height, to signify acute undernutrition which is taken, they are defined as wasted and in need of treatment. If children have a low height-for-age, to signify chronic undernutrition which is taken they are defined as stunted. Low weightfor-age classified children as underweight, because of stunting or wasting or both thus, undernutrition index is composite. At the population level widely used these markers to assess child undernutrition as well as who are wasted or stunted a high prevalence of children is considered a public health problem [15]. At the level of interventions and programmatic design, however, the two categories of undernutri-

Wasted children contain an elevated risk of dying that by nutritional therapy may often rapidly reduced [16]. To prevent deaths associated with child wasting, making therapy available is so considered essential. On the other hand, including fetal development, over long periods children have poor growth in height they are categorized as stunted. For rapid nutritional correction is not willing this growth faltering as well as consequently rather than treatment considered to require prevention, these outcomes in terms of policy leading to the separation, programmed interventions, guidance as well as financing: at the individual level, now viewed as separate conditions acute undernutrition as well as chronic undernutrition, and among policy makers as distinct outcomes are routinely

A new classification for malnutrition is established by John Conrad Water low. to show the stunting which results as of chronic malnutrition with height-for-age combines weight-for-height (representing acute episodes of malnutrition), rather than using just weight for age measurements, the classification established by Water low. Over the Gomez classification one advantage of the Water low classification is

that even if ages are not known weight for height can be examined [18].

**4**

reported [17].


The above table shows the classifications of malnutrition by WHO, with some modifications being commonly used.

#### **4. The effects of malnutrition**

More likely than others to be caught in the weakened immunity as well as downward spiral of malnutrition, people who restrict their food intakes, whether because of an eating disorder, illness, desire for weight loss, and lack of appetite. One or more of the following also susceptible: malnourished, poor, hospitalized and very young or old. When medical tests of a malnourished individual signify compromised immune system increase dramatically rate of death and sickness.

When an individual becomes malnourished, often worsens disease by malnutrition that in turn gets worse malnutrition. For disease when impaired immunity opens the way often begins a destructive cycle: when impairs appetite by disease, interferes with absorption as well as digestion, excretion increases or metabolism alter then further suffer nutrition status [19].

#### **5. Effect of malnutrition on economy of a country**

Malnutrition as well as global hunger remains big challenges in the last two decades, despite achieved significant progress. In the world about 805 million people continue to suffer as of chronic hunger and people suffer from micronutrient deficiencies more than 2 billion. Furthermore, in low and middle-income countries, obesity and overweight are on the rise.

Huge economic and social costs are imposed by hunger and malnutrition that are able to be felt at societal, household, and individual levels. For instance, according to the FAO, the global economy per year US\$1.4–2.1 trillion cost for hunger and undernutrition or global gross domestic product 2–3%. To eliminate hunger and malnutrition, the economic returns are able to as well extremely elevate. From reducing child undernutrition, there are substantial, lifetime economic benefits demonstrated by evidence as of IFPRI-led research. For instance, every dollar spent on interventions in economic returns to reduce stunting is estimated to generate about US\$34, in India.

Malnutrition as well as hunger is expensive. It is predictable that because of undernutrition (GDP) 2–3%, equivalent to per year US\$1.4–2.1 trillion is lost and because of overnutrition annual GDP another 2–3% is lost. Collectively, because of malnutrition global GDP 5% (per year US\$3.5 trillion) is lost [20].

Each dollar spent in economic benefits iodizing salt generates \$30; each dollar spent in economic benefits on iron supplements for children aged six to 24 months and for mothers generates \$24. Each dollar spent in economic benefits on vitamin A generates estimated to be \$40 or more. To reduce chronic undernutrition need bundling micronutrient interventions for instance, individuals that decrease iron, iodine and vitamin A deficiencies with the condition of other micronutrients (for

example to reduce the duration and severity of diarrhea zinc powders needed) as well as energy-dense foods. About the importance of these for healthy child growth communication with caregivers and mother is also important. Across countries the costs related with doing so differ as do the benefits however in a typical developing country, each dollar spent in economic benefits on this bundle generates around \$18.

These are extraordinarily high benefit: cost ratios, by the standards of economics. Not merely that, trivially low the costs of these investments. Who are vitamin A deficient in the 95 million preschool children to eliminate vitamin A deficiency from every North American and western European less than two dollars would be enough, investment of about \$650 million dollars a year an additional annual, as well combating undernutrition spent to current expenditures. Nearly two billion people are affecting by iodine deficiencies and 80 million pregnant women are affecting by anemia. Needed to reduce chronic undernutrition – for the bundle of interventions a larger investment is needed, suggest by current estimates that in the 34 countries per year around nine and half billion dollars would reach 90% of children that in the developing world account for 90% of the burden of undernutrition [21].

### **Author details**

Farhan Saeed1 , Muhammad Imran2 , Tabussam Tufail1 and Ali Imran1 \*

1 Institute of Home and Food Sciences, Government College University Faisalabad, Pakistan

2 Faculty of Allied Health Sciences, University Institute of Diet and Nutritional Sciences, The University of Lahore, Lahore, Pakistan

\*Address all correspondence to: dr.aliimran@gcuf.edu.pk

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**7**

[PubMed]

*Introductory Chapter: Malnutrition*

[1] Torpy JM, Lynm C, Glass RM. Malnutrition in children. JAMA.

[2] Young E. Food and Development. Abingdon, Oxon: Routledge; 2012. pp. 36-38. ISBN: 978-1-135-99941-4

Shibuya K, Black RE. WHO child health epidemiology reference group. WHO estimates of the causes of death in children. Lancet. 2005;**365**:1147-1152.

**References**

[CrossRef]

2004;**292**(5):648-648

[3] Bryce J, Boschi-Pinto C,

[4] World Health Organization. Children: Reducing Mortality. 2017. Available from: http://www.who.int/ mediacentre/factsheets/fs178/en/ [Accessed: 03 March 2018]

Press; 2006. pp. 701-713

[5] Pelletier DL, Olson CM, Frongillo E Jr. Food insecurity, hunger, and under nutrition. In: Bowman BA, Russell RM, editors. Present Knowledge in Nutrition. 8th ed. Washington, DC, USA: ILSI

[6] Asad N, Mushtaq A. Malnutrition in Pakistani children, its causes, consequences and recommendations. The Journal of the Pakistan Medical Association. 2012;**62**:311. [PubMed]

[7] Ali SS, Karim N, Billoo AG, Haider SS. Association of literacy of mothers with malnutrition among children under three years of age in rural area of district Malir, Karachi. The Journal of the Pakistan Medical Association. 2005;**55**:550-553.

[8] Stevens GA, Finucane MM, Paciorek CJ, Flaxman SR, White RA, Donner AJ, et al. Nutrition impact model study group. Trends in mild, moderate, and severe stunting and underweight, and progress towards MDG 1 in 141 developing countries: A systematic analysis of population

*DOI: http://dx.doi.org/10.5772/intechopen.93763*

representative data. Lancet. 2012;**380**:824-834. [CrossRef]

[9] United Nation International Children's Emergency Fund (UNICEF). Levels and Trends in Child Malnutrition. 2014. Available from: http://www.unicef.org/media/ files/Levels\_and\_Trends\_in\_Child\_ Mortality\_2014.pdf [Accessed: 25

[10] Di Cesare M, Bhatti Z, Soofi SB, Fortunato L, Ezzati M, Bhutta ZA. Geographical and socioeconomic inequalities in women and children's nutritional status in Pakistan in 2011: An analysis of data from a nationally representative survey. The Lancet Global Health. 2015;**3**:e229-e239.

[11] Planning Commission, Government of Pakistan, Pakistan Institute of Development Economics. National Nutrition Survey. Islamabad, Pakistan: Planning Commission, Government of Pakistan, Pakistan Institute of Development Economics; 2011

[12] Masibo PK, Makoka D. Trends and determinants of undernutrition among young Kenyan children: Kenya Demographic and Health Survey; 1993, 1998, 2003 and 2008-2009. Public Health Nutrition. 2012;**15**:1715-1727.

[CrossRef] [PubMed]

[PubMed]

[13] Pasricha SR, Biggs BA.

Undernutrition among children in South and South-East Asia. Journal of Paediatrics and Child Health. 2010;**46**:497-503. [CrossRef ]

[14] World Health Organization. What is malnutrition? [Online]. 2020. Available from: https://www. who.int/features/qa/malnutrition/ en/#:~:text=Malnutrition%20

refers%20to%20deficiencies%2C%20

November 2015]

[CrossRef]

#### **References**

*Malnutrition*

around \$18.

undernutrition [21].

**6**

**Author details**

, Muhammad Imran2

Sciences, The University of Lahore, Lahore, Pakistan

provided the original work is properly cited.

\*Address all correspondence to: dr.aliimran@gcuf.edu.pk

, Tabussam Tufail1

1 Institute of Home and Food Sciences, Government College University Faisalabad,

example to reduce the duration and severity of diarrhea zinc powders needed) as well as energy-dense foods. About the importance of these for healthy child growth communication with caregivers and mother is also important. Across countries the costs related with doing so differ as do the benefits however in a typical developing country, each dollar spent in economic benefits on this bundle generates

These are extraordinarily high benefit: cost ratios, by the standards of economics. Not merely that, trivially low the costs of these investments. Who are vitamin A deficient in the 95 million preschool children to eliminate vitamin A deficiency from every North American and western European less than two dollars would be enough, investment of about \$650 million dollars a year an additional annual, as well combating undernutrition spent to current expenditures. Nearly two billion people are affecting by iodine deficiencies and 80 million pregnant women are affecting by anemia. Needed to reduce chronic undernutrition – for the bundle of interventions a larger investment is needed, suggest by current estimates that in the 34 countries per year around nine and half billion dollars would reach 90% of children that in the developing world account for 90% of the burden of

2 Faculty of Allied Health Sciences, University Institute of Diet and Nutritional

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

and Ali Imran1

\*

Farhan Saeed1

Pakistan

[1] Torpy JM, Lynm C, Glass RM. Malnutrition in children. JAMA. 2004;**292**(5):648-648

[2] Young E. Food and Development. Abingdon, Oxon: Routledge; 2012. pp. 36-38. ISBN: 978-1-135-99941-4

[3] Bryce J, Boschi-Pinto C, Shibuya K, Black RE. WHO child health epidemiology reference group. WHO estimates of the causes of death in children. Lancet. 2005;**365**:1147-1152. [CrossRef]

[4] World Health Organization. Children: Reducing Mortality. 2017. Available from: http://www.who.int/ mediacentre/factsheets/fs178/en/ [Accessed: 03 March 2018]

[5] Pelletier DL, Olson CM, Frongillo E Jr. Food insecurity, hunger, and under nutrition. In: Bowman BA, Russell RM, editors. Present Knowledge in Nutrition. 8th ed. Washington, DC, USA: ILSI Press; 2006. pp. 701-713

[6] Asad N, Mushtaq A. Malnutrition in Pakistani children, its causes, consequences and recommendations. The Journal of the Pakistan Medical Association. 2012;**62**:311. [PubMed]

[7] Ali SS, Karim N, Billoo AG, Haider SS. Association of literacy of mothers with malnutrition among children under three years of age in rural area of district Malir, Karachi. The Journal of the Pakistan Medical Association. 2005;**55**:550-553. [PubMed]

[8] Stevens GA, Finucane MM, Paciorek CJ, Flaxman SR, White RA, Donner AJ, et al. Nutrition impact model study group. Trends in mild, moderate, and severe stunting and underweight, and progress towards MDG 1 in 141 developing countries: A systematic analysis of population

representative data. Lancet. 2012;**380**:824-834. [CrossRef]

[9] United Nation International Children's Emergency Fund (UNICEF). Levels and Trends in Child Malnutrition. 2014. Available from: http://www.unicef.org/media/ files/Levels\_and\_Trends\_in\_Child\_ Mortality\_2014.pdf [Accessed: 25 November 2015]

[10] Di Cesare M, Bhatti Z, Soofi SB, Fortunato L, Ezzati M, Bhutta ZA. Geographical and socioeconomic inequalities in women and children's nutritional status in Pakistan in 2011: An analysis of data from a nationally representative survey. The Lancet Global Health. 2015;**3**:e229-e239. [CrossRef]

[11] Planning Commission, Government of Pakistan, Pakistan Institute of Development Economics. National Nutrition Survey. Islamabad, Pakistan: Planning Commission, Government of Pakistan, Pakistan Institute of Development Economics; 2011

[12] Masibo PK, Makoka D. Trends and determinants of undernutrition among young Kenyan children: Kenya Demographic and Health Survey; 1993, 1998, 2003 and 2008-2009. Public Health Nutrition. 2012;**15**:1715-1727. [CrossRef] [PubMed]

[13] Pasricha SR, Biggs BA. Undernutrition among children in South and South-East Asia. Journal of Paediatrics and Child Health. 2010;**46**:497-503. [CrossRef ] [PubMed]

[14] World Health Organization. What is malnutrition? [Online]. 2020. Available from: https://www. who.int/features/qa/malnutrition/ en/#:~:text=Malnutrition%20 refers%20to%20deficiencies%2C%20

#### *Malnutrition*

excesses,of%20energy%20 and%2For%20nutrients [Accessed: 26 July 2020]

[15] Bergeron G, Castleman T. Program responses to acute and chronic malnutrition: Divergences and convergences. Advances in Nutrition. 2012;**3**:242-249

[16] Bhutta ZA, Berkley JA, Bandsma RHJ, et al. Severe childhood malnutrition. Nature Reviews. Disease Primers. 2017;**3**:17067

[17] Development Initiatives. 2018 Global Nutrition Report: Shining a Light to Spur Action. London: WCRF International

[18] Waterlow JC. Classification and definition of protein-calorie malnutrition. British Medical Journal. 1972;**3**(5826):566-569

[19] Finch CE. The Biology of Human Longevity: Inflammation, Nutrition, and Aging in the Evolution of Lifespans. London: Academic Press; 2007

[20] FAO. The State of Food and Agriculture. Rome: Food and Agriculture Organization of the United Nations; 2013

[21] Hoddinott J. The economic cost of malnutrition. In: The Road to Good Nutrition. India: Karger Publishers; 2013. pp. 64-73

**9**

**Chapter 2**

**Abstract**

**1. Introduction**

Malnutrition

*Kathleen Hefferon*

Biofortification of Crops Using

Malnutrition affects millions of people around the world, and the vast majority are found in developing countries. Malnutrition increases childhood mortality, amplifies poor outcomes during pregnancy, and is responsible for a variety of health disorders ranging from anemia to blindness. Biofortification of crops using biotechnological approaches such as genetic modification and genome editing holds promise as a powerful tool to combat malnutrition. This chapter describes progress that has been made in the development of biofortified staple crops to address malnutrition.

**Keywords:** malnutrition, biofortification, biotechnology, transgenic plant

Micronutrients play a variety of roles in metabolism and homeostasis. Micronutrient deficiency, also known as malnutrition, can result in the increased incidence of many diseases and metabolic disorders. To improve nutritional status through a balanced and enriched diet, the quantification and bioavailability of vitamins and minerals must be determined. The analysis of micronutrient content

The level and composition of micronutrients vary significantly among crop varieties. Globally, cereals, roots, and tubers represent major staple food staples. While these crops are rich in carbohydrates, they may have very low quantity or poor-quality proteins and micronutrients [2]. In Asia, people who depend on rice are more prone to vitamin A deficiencies due to the lack of this micronutrient. This in turn makes them more susceptible to a number of health problems such as blindness [3]. Similarly, over 20 different dietary minerals are considered essential for human health. Global-level deficiencies in iron (Fe), zinc (Zn), and iodine (I) are

can enhance nutritional quality and improve nutritional status [1].

most common as they have a significant negative impact on public health. Since the concentrations of most vitamins in the edible parts of the plants are frequently low, one research goal has been to identify biochemical pathways involved in the synthesis, translocation, and accumulation of micronutrients in plant tissues [4]. Further understanding of these mechanisms would enable us to manipulate these pathways and improve their micronutrient content through metabolic engineering [5]. Although these strategies have demonstrated some degree of success, issues such as appropriate nutrient levels, bioavailability, ready adaptation

by farmers, and acceptance by consumers must be addressed [6].

Biotechnology to Alleviate

#### **Chapter 2**

*Malnutrition*

26 July 2020]

2012;**3**:242-249

International

Nations; 2013

2013. pp. 64-73

excesses,of%20energy%20

and%2For%20nutrients [Accessed:

responses to acute and chronic malnutrition: Divergences and convergences. Advances in Nutrition.

[16] Bhutta ZA, Berkley JA,

Primers. 2017;**3**:17067

1972;**3**(5826):566-569

[15] Bergeron G, Castleman T. Program

Bandsma RHJ, et al. Severe childhood malnutrition. Nature Reviews. Disease

[17] Development Initiatives. 2018 Global Nutrition Report: Shining a Light to Spur Action. London: WCRF

[18] Waterlow JC. Classification and definition of protein-calorie malnutrition. British Medical Journal.

London: Academic Press; 2007

[20] FAO. The State of Food and Agriculture. Rome: Food and

Agriculture Organization of the United

[21] Hoddinott J. The economic cost of malnutrition. In: The Road to Good Nutrition. India: Karger Publishers;

[19] Finch CE. The Biology of Human Longevity: Inflammation, Nutrition, and Aging in the Evolution of Lifespans.

**8**

## Biofortification of Crops Using Biotechnology to Alleviate Malnutrition

*Kathleen Hefferon*

#### **Abstract**

Malnutrition affects millions of people around the world, and the vast majority are found in developing countries. Malnutrition increases childhood mortality, amplifies poor outcomes during pregnancy, and is responsible for a variety of health disorders ranging from anemia to blindness. Biofortification of crops using biotechnological approaches such as genetic modification and genome editing holds promise as a powerful tool to combat malnutrition. This chapter describes progress that has been made in the development of biofortified staple crops to address malnutrition.

**Keywords:** malnutrition, biofortification, biotechnology, transgenic plant

#### **1. Introduction**

Micronutrients play a variety of roles in metabolism and homeostasis. Micronutrient deficiency, also known as malnutrition, can result in the increased incidence of many diseases and metabolic disorders. To improve nutritional status through a balanced and enriched diet, the quantification and bioavailability of vitamins and minerals must be determined. The analysis of micronutrient content can enhance nutritional quality and improve nutritional status [1].

The level and composition of micronutrients vary significantly among crop varieties. Globally, cereals, roots, and tubers represent major staple food staples. While these crops are rich in carbohydrates, they may have very low quantity or poor-quality proteins and micronutrients [2]. In Asia, people who depend on rice are more prone to vitamin A deficiencies due to the lack of this micronutrient. This in turn makes them more susceptible to a number of health problems such as blindness [3]. Similarly, over 20 different dietary minerals are considered essential for human health. Global-level deficiencies in iron (Fe), zinc (Zn), and iodine (I) are most common as they have a significant negative impact on public health.

Since the concentrations of most vitamins in the edible parts of the plants are frequently low, one research goal has been to identify biochemical pathways involved in the synthesis, translocation, and accumulation of micronutrients in plant tissues [4]. Further understanding of these mechanisms would enable us to manipulate these pathways and improve their micronutrient content through metabolic engineering [5]. Although these strategies have demonstrated some degree of success, issues such as appropriate nutrient levels, bioavailability, ready adaptation by farmers, and acceptance by consumers must be addressed [6].

#### *Malnutrition*

For the past several years, food supplementation has been the main strategy used for vitamin and mineral fortification. This strategy has a number of weaknesses, such as the decreased bioavailability of micronutrients after food processing. Biofortification has been considered an alternative solution and can be achieved via (i) an agronomic approach, (ii) conventional plant breeding, and (iii) genetic engineering [2, 7–10]. In the following chapter, the micronutrient biofortification of edible crops by genetic engineering will be examined.

#### **2. Uptake and bioaccumulation of minerals by plants**

Minerals can accumulate in various ways and are stored in different compartments/organelles by plants species. These in turn can be affected by growing conditions as well as through interactions with other mineral nutrients [11, 12]. For example, iron is an essential element for plant metabolism, growth, and development [13]. Iron can be absorbed by the roots in the form of Fe2+, then becomes oxidized to Fe3+, is chelated by citrate, and then is transported to the top of the plant [14]. Zinc, another essential nutrient for plant growth and development, accumulates preferably in the vacuoles of the epidermal leaf cells as electron-dense deposits [15, 16].

#### **3. Mineral biofortification using transgenic plants**

Biofortification of crops using modern biotechnology techniques has been under exploration. Transgenic crops with increased accumulation of important minerals such as iron, zinc, and calcium within edible tissue are under development. Simultaneously, research into transgenic crops with reduced concentrations of antinutrients such as phytate has been developed. Antinutrients reduce the bioavailability of minerals by interfering with their absorption in the gut [9].

#### **4. Transgenic crops biofortified with iron and zinc**

Rice is one of the most well-studied cereals for mineral biofortification. Rice (*Oryza sativa*) is a staple of a large proportion of the world's poor and is deficient in several essential micronutrients. Transgenic rice plants have provided a model system to enhance the amount of bioavailable iron and zinc that is found in the edible seed (endosperm) of cereals. Plant scientists discovered that metal transporter proteins found in many crop species can be used for multiple metal substrates, including iron, zinc, and even cadmium. These metal substrates can be taken up from the soil and into the roots. Researchers found that loss of function mutants of these transporter proteins creates a loss of uptake of all three of these metals into plant cells [17]. Ferritin, the iron storage protein, can assist in metal accumulation in plant tissue. Masuda et al. demonstrated an increase in accumulation of ferritin as well as an increase in iron translocation via the overexpression of the iron (II)-nicotianamine transporter OsYSL2 within rice endosperm. Transgenic lines generated higher levels of both iron (6-fold in the greenhouse and 4.4-fold in the paddy) and zinc (1.6-times), demonstrating that introduction of multiple genes involved in iron and zinc homeostasis could improve iron biofortification more than the introduction of a single gene. Later, Masuda et al. [18] increased iron and zinc accumulation through increased iron uptake and transport using the ferric iron chelator, mugineic acid. Transgenic plants that were generated expressed the ferritin gene from soybean (SoyferH2), and are driven by two endosperm-specific

**11**

*Biofortification of Crops Using Biotechnology to Alleviate Malnutrition*

promoters, in addition to the barley nicotianamine synthase gene (HvNAS1), two nicotianamine aminotransferase genes (HvNAAT-A and HvNAAT-B), and a mugineic acid synthase gene (IDS3) (to increase mugineic acid production in rice plants). These transgenic plants were tolerant of iron-deficient soil and displayed increased iron accumulation by 2.5-fold. Under iron-sufficient conditions, transgenic rice lines increased iron accumulation by 4-fold as much as lines that had been cultivated in either commercially supplied soil (iron-sufficient conditions) or calcareous soil (iron-deficient conditions). Transgenic lines expressing both ferritin and mugineic acid biosynthetic genes displayed signs of iron-deficiency tolerance in calcareous soil, and the iron concentration in polished T3 seeds increased by 4 and 2.5 times, respectively, compared to nontransgenic lines grown in normal and calcareous soil. Recently, Li et al. [19] have identified a zinc transporter protein family (ZIP) for taking up divalent cations in plants. The researchers found that by overexpressing the ZmZIP5 protein, iron and zinc levels were increased in seeds of rice plants. Similarly, Beasley et al. [20] constitutively expressed the rice (*Oryza sativa* L.) nicotianamine synthase 2 (OsNAS2) gene in bread wheat. This brought about the upregulation of nicotianamine (NA) and 2′-deoxymugineic acid (DMA), which are important for iron and zinc transport and nutrition. Transgenic plants accumulated higher concentrations of Fe and Zn in wheat grain endosperm and iron bioavailabil-

ity was increased in white flour milled from field-grown CE-OsNAS2 grain.

used as a tool to biofortify cereal grains with micronutrients.

levels of cadmium to reduce toxicity in the rice seed.

There are other ways for iron deficiency to be addressed using transgenic plants. For example, Sharma and Yeh [21] used an ethyl methanesulfonate (EMS) mutant in *Arabidopsis* that is tolerant of iron-deficient soil and demonstrated the accumulation of 4–7 times higher amounts of iron than wild type in roots, shoots, and seeds. This mutant presented a dominant "Metina" phenotype that constitutively activates the Fe regulatory pathway by optimizing Fe homeostasis and thus may be useful in Fe biofortification. Similarly, Qiao et al. [22] found that the wheat gene encoding the cell number regulator (CNR) protein showed enhanced tolerance to Zn, and overexpression of *TaCNR5* in *Arabidopsis* increased Cd, Zn, and Mn translocation from roots to shoots. This indicates that heavy metal tolerance characteristics can be

Since the same molecular machinery is utilized for transporting iron and zinc into plants, increasing iron content in rice also brings about increased zinc accumulation. As an example, Aung et al. [23] generated a transgenic line of rice commonly eaten by consumers in Myanmar, where approximately 70% of the populace is iron deficient. This line overexpressed the nicotianamine synthase gene HvNAS1 to enhance iron transport, the Fe(II)-nicotianamine transporter gene OsYSL2 to transport iron to the endosperm and the Fe storage protein gene SoyferH2 to increase iron accumulation in the endosperm. The rice plants were shown to accumulate over 3.4-fold higher iron concentrations, in addition to 1.3-fold higher zinc concentrations compared to conventional, nontransgenic rice. The results of this study indicate that transgenic rice biofortified for increased iron content could address both iron as well as zinc micronutrient deficiency in the Myanmar population.

Paul et al. [24] generated transgenic high-yielding indica rice that expressed the soybean-derived ferritin gene. Transgenic plants produced over 2.6-fold higher levels of ferritin than their nontransgenic counterparts, even in the fourth generation of rice plants. Upon milling, transgenic rice grains provided 2.54-fold and 1.54-fold increases in iron and zinc content, respectively. Similarly, the iron transporter gene MxIRT1 taken from apple trees was utilized by Tan et al. (2015) to generate transgenic rice plants that exhibited an increase in iron and zinc of threefold, in addition to a decrease in cadmium concentration. Cadmium is thought to compete with iron and zinc for transport and accumulation in the rice endosperm and, thus, lower

*DOI: http://dx.doi.org/10.5772/intechopen.92390*

#### *Biofortification of Crops Using Biotechnology to Alleviate Malnutrition DOI: http://dx.doi.org/10.5772/intechopen.92390*

*Malnutrition*

For the past several years, food supplementation has been the main strategy used for vitamin and mineral fortification. This strategy has a number of weaknesses, such as the decreased bioavailability of micronutrients after food processing. Biofortification has been considered an alternative solution and can be achieved via (i) an agronomic approach, (ii) conventional plant breeding, and (iii) genetic engineering [2, 7–10]. In the following chapter, the micronutrient biofortification

Minerals can accumulate in various ways and are stored in different compartments/organelles by plants species. These in turn can be affected by growing conditions as well as through interactions with other mineral nutrients [11, 12]. For example, iron is an essential element for plant metabolism, growth, and development [13]. Iron can be absorbed by the roots in the form of Fe2+, then becomes oxidized to Fe3+, is chelated by citrate, and then is transported to the top of the plant [14]. Zinc, another essential nutrient for plant growth and development, accumulates preferably

in the vacuoles of the epidermal leaf cells as electron-dense deposits [15, 16].

ability of minerals by interfering with their absorption in the gut [9].

Biofortification of crops using modern biotechnology techniques has been under exploration. Transgenic crops with increased accumulation of important minerals such as iron, zinc, and calcium within edible tissue are under development. Simultaneously, research into transgenic crops with reduced concentrations of antinutrients such as phytate has been developed. Antinutrients reduce the bioavail-

Rice is one of the most well-studied cereals for mineral biofortification. Rice (*Oryza sativa*) is a staple of a large proportion of the world's poor and is deficient in several essential micronutrients. Transgenic rice plants have provided a model system to enhance the amount of bioavailable iron and zinc that is found in the edible seed (endosperm) of cereals. Plant scientists discovered that metal transporter proteins found in many crop species can be used for multiple metal substrates, including iron, zinc, and even cadmium. These metal substrates can be taken up from the soil and into the roots. Researchers found that loss of function mutants of these transporter proteins creates a loss of uptake of all three of these metals into plant cells [17]. Ferritin, the iron storage protein, can assist in metal accumulation in plant tissue. Masuda et al. demonstrated an increase in accumulation of ferritin as well as an increase in iron translocation via the overexpression of the iron (II)-nicotianamine transporter OsYSL2 within rice endosperm. Transgenic lines generated higher levels of both iron (6-fold in the greenhouse and 4.4-fold in the paddy) and zinc (1.6-times), demonstrating that introduction of multiple genes involved in iron and zinc homeostasis could improve iron biofortification more than the introduction of a single gene. Later, Masuda et al. [18] increased iron and zinc accumulation through increased iron uptake and transport using the ferric iron chelator, mugineic acid. Transgenic plants that were generated expressed the ferritin gene from soybean (SoyferH2), and are driven by two endosperm-specific

of edible crops by genetic engineering will be examined.

**2. Uptake and bioaccumulation of minerals by plants**

**3. Mineral biofortification using transgenic plants**

**4. Transgenic crops biofortified with iron and zinc**

**10**

promoters, in addition to the barley nicotianamine synthase gene (HvNAS1), two nicotianamine aminotransferase genes (HvNAAT-A and HvNAAT-B), and a mugineic acid synthase gene (IDS3) (to increase mugineic acid production in rice plants). These transgenic plants were tolerant of iron-deficient soil and displayed increased iron accumulation by 2.5-fold. Under iron-sufficient conditions, transgenic rice lines increased iron accumulation by 4-fold as much as lines that had been cultivated in either commercially supplied soil (iron-sufficient conditions) or calcareous soil (iron-deficient conditions). Transgenic lines expressing both ferritin and mugineic acid biosynthetic genes displayed signs of iron-deficiency tolerance in calcareous soil, and the iron concentration in polished T3 seeds increased by 4 and 2.5 times, respectively, compared to nontransgenic lines grown in normal and calcareous soil. Recently, Li et al. [19] have identified a zinc transporter protein family (ZIP) for taking up divalent cations in plants. The researchers found that by overexpressing the ZmZIP5 protein, iron and zinc levels were increased in seeds of rice plants. Similarly, Beasley et al. [20] constitutively expressed the rice (*Oryza sativa* L.) nicotianamine synthase 2 (OsNAS2) gene in bread wheat. This brought about the upregulation of nicotianamine (NA) and 2′-deoxymugineic acid (DMA), which are important for iron and zinc transport and nutrition. Transgenic plants accumulated higher concentrations of Fe and Zn in wheat grain endosperm and iron bioavailability was increased in white flour milled from field-grown CE-OsNAS2 grain.

There are other ways for iron deficiency to be addressed using transgenic plants. For example, Sharma and Yeh [21] used an ethyl methanesulfonate (EMS) mutant in *Arabidopsis* that is tolerant of iron-deficient soil and demonstrated the accumulation of 4–7 times higher amounts of iron than wild type in roots, shoots, and seeds. This mutant presented a dominant "Metina" phenotype that constitutively activates the Fe regulatory pathway by optimizing Fe homeostasis and thus may be useful in Fe biofortification. Similarly, Qiao et al. [22] found that the wheat gene encoding the cell number regulator (CNR) protein showed enhanced tolerance to Zn, and overexpression of *TaCNR5* in *Arabidopsis* increased Cd, Zn, and Mn translocation from roots to shoots. This indicates that heavy metal tolerance characteristics can be used as a tool to biofortify cereal grains with micronutrients.

Since the same molecular machinery is utilized for transporting iron and zinc into plants, increasing iron content in rice also brings about increased zinc accumulation. As an example, Aung et al. [23] generated a transgenic line of rice commonly eaten by consumers in Myanmar, where approximately 70% of the populace is iron deficient. This line overexpressed the nicotianamine synthase gene HvNAS1 to enhance iron transport, the Fe(II)-nicotianamine transporter gene OsYSL2 to transport iron to the endosperm and the Fe storage protein gene SoyferH2 to increase iron accumulation in the endosperm. The rice plants were shown to accumulate over 3.4-fold higher iron concentrations, in addition to 1.3-fold higher zinc concentrations compared to conventional, nontransgenic rice. The results of this study indicate that transgenic rice biofortified for increased iron content could address both iron as well as zinc micronutrient deficiency in the Myanmar population.

Paul et al. [24] generated transgenic high-yielding indica rice that expressed the soybean-derived ferritin gene. Transgenic plants produced over 2.6-fold higher levels of ferritin than their nontransgenic counterparts, even in the fourth generation of rice plants. Upon milling, transgenic rice grains provided 2.54-fold and 1.54-fold increases in iron and zinc content, respectively. Similarly, the iron transporter gene MxIRT1 taken from apple trees was utilized by Tan et al. (2015) to generate transgenic rice plants that exhibited an increase in iron and zinc of threefold, in addition to a decrease in cadmium concentration. Cadmium is thought to compete with iron and zinc for transport and accumulation in the rice endosperm and, thus, lower levels of cadmium to reduce toxicity in the rice seed.

Improvements in iron and zinc biofortification have also taken place using other approaches. Trijatmiko et al. [25] demonstrated that plants expressing rice nicotianamine synthase (OsNAS2) and soybean ferritin (SferH-1) genes possessed enriched endosperm Fe and Zn content. A Caco-2 cellular assay illustrated that increased iron and zinc levels found in these rice plants were bioavailable. Transgenic plants generated by Banakar et al. [26] expressed high levels of nicotianamine and 2′-deoxymugenic acid (DMA). These plants were able to accumulate up to 4-fold more iron and 2-fold more zinc in rice endosperm, in addition to lower levels of cadmium compared to wild-type plants.

Other crop species have also been studied for iron and zinc biofortification using biotechnology. Tan et al. [27] improved iron levels in the pulse crop chickpea (*Cicer arietinum* L.) by increasing iron transport and storage through a combination of chickpea nicotianamine synthase 2 (CaNAS2) and soybean (*Glycine max*) ferritin (GmFER) genes. Transgenic chickpea plants that overexpressed these genes illustrated a doubling of NA concentration, suggesting an increase in iron bioavailability. Pearl millet was examined by Manwaring et al. [28] for iron and zinc biofortification by improving the currently available gene pool. High iron and zinc-biofortified pearl millet would be advantageous for poor regions of the world where soil management or supplementation programs are ineffectual. Narayanan et al. [29] have expressed the iron sequestering Arabidopsis AtVIT1 gene in cassava plants to increase iron storage in the crop's roots. Iron concentration also increased in stem tissues and accumulated in plant cellular vacuoles.

#### **5. Calcium-biofortified transgenic plants**

The calcium content of crops can also be increased using biotechnology. These advances hinge on improved knowledge of how soluble calcium ions found in the soil are transported and accumulate in plant tissue [30]. Calcium plays a significant role in general cell signaling; how calcium transporters are expressed can thus influence a plant's ability to withstand stress, ward off pathogens, and can influence the nutritional status of animals and humans. Park et al. [31] have generated transgenic tomato, potato, lettuce, and carrots expressing high levels of calcium transporters. One of these calcium transporters, known as a short cation exchanger (sCAX1), can increase calcium transport into plant cell vacuoles [32]. Enhanced calcium absorption has been demonstrated in animal models that were fed transgenic carrots. Similarly, Sharma et al. have examined the potential of finger millet, an orphan crop with high calcium content, by studying the mechanisms behind calcium uptake, transport, and accumulation in grain. It has been reported that climate change may act detrimentally on mineral accumulation in different crop species; this could limit their further availability from food crops for both humans and animals [33].

#### **6. Bioaccumulation of vitamins in plants**

Vitamins such as β-carotene and folic acid are critical for human health. The development of microbial biochemistry facilitated the understanding of the biosynthetic pathways involved in vitamin production in plants. All vitamins that are required in the diet are synthesized by plants with the exception of ascorbic acid (vitamin C), which is specifically synthesized by eukaryotic cells [5, 34, 35]. Often biosynthesis is compartmentalized within various organelles. With greater comprehension of the metabolic pathways involved in vitamin production, plants can be developed with high levels of vitamin accumulation.

**13**

transgenes.

*Biofortification of Crops Using Biotechnology to Alleviate Malnutrition*

**7. Vitamins and transgenic biofortification strategies of edible crops**

GM technology also has the potential to reduce the global burden of malnutrition and hidden hunger. Vitamin- or mineral-enriched GM foods (GM biofortified foods) are considered to be the next generation of GMOs. Non-GM biofortified crops have been widely developed and commercialized, but the applied conventional breeding techniques may be inadequate for crops with a low level or absence of a certain micronutrient [36]. A recent review has summarized successful R&D efforts in the field of GMOs with increased micronutrient

The well-known example of GM vitamin biofortification is Golden Rice, enriched with pro-vitamin A (β-carotene) [38, 39], followed by vitamin B9 (folate)-enhanced rice [40, 41]. Conventional breeding techniques could not be applied due to the absence/low content of vitamin A in rice grain. For Golden Rice, daffodil, and Pantoea genes were used to increase pro-vitamin A levels within rice endosperm [39]. The most recent version of Golden Rice has been improved further for a 23-fold increase in carotenoids [38]. Similarly, folate-biofortified rice has been generated by overexpressing Arabidopsis genes in rice endosperm. A fourfold increase in folate concentrations in rice was accomplished using this strategy [41] and in the process, folate stability for long-term storage was improved (Blancquaert

Fifteen simulation analyses confirmed the positive impact of GM biofortified crop consumption on dietary intake and nutritional outcomes in humans [42]. The vast majority of these studies also confirmed that a regular portion of the targeted biofortified crop would provide the daily micronutrient requirements. For example, the recent simulation analysis of Golden Rice in Asia [43] indicated that it could reduce the prevalence of dietary vitamin A inadequacy by up to 30% (children) and 55–60% (women) in Indonesia and the Philippines, and up to 71% (children) and

A randomized trial on Golden Rice performed in the United States resulted in a high bio-conversion factor of β-carotene (3.8:1), by which 100 g of uncooked Golden Rice would provide about 80–100% of the estimated average requirement and 55–70% of the recommended dietary allowance (RDA) for adult men and women [44]. Currently, Golden Rice has been approved in an increasing number of countries, including the Philippines. Golden Rice and other GM biofortified crops [16, 42] would be highly cost-effective investments to reduce target micronutrient

Recently, Endo et al. [46] devised a genome editing approach to produce β-carotene rice that is fast and direct, by making use of splicing variants in the Orange (Or) gene that cause β-carotene accumulation in cauliflower. The authors genome edited the orthologue of the cauliflower or gene in rice using CRISPR/ Cas9 and were able to accumulate β-carotene, without having to introduce

Bananas are the world's most important fruit crop and a major staple in many African countries. Banana grows in tropical climates, where vitamin A deficiency is

**9. "Golden" bananas to combat vitamin A deficiency**

*DOI: http://dx.doi.org/10.5772/intechopen.92390*

content in staple crops [37].

**8. Vitamin-biofortified rice**

78% (women) in Bangladesh.

deficiencies such as vitamin A [45].

et al., 2015).

#### **7. Vitamins and transgenic biofortification strategies of edible crops**

GM technology also has the potential to reduce the global burden of malnutrition and hidden hunger. Vitamin- or mineral-enriched GM foods (GM biofortified foods) are considered to be the next generation of GMOs. Non-GM biofortified crops have been widely developed and commercialized, but the applied conventional breeding techniques may be inadequate for crops with a low level or absence of a certain micronutrient [36]. A recent review has summarized successful R&D efforts in the field of GMOs with increased micronutrient content in staple crops [37].

#### **8. Vitamin-biofortified rice**

*Malnutrition*

Improvements in iron and zinc biofortification have also taken place using other approaches. Trijatmiko et al. [25] demonstrated that plants expressing rice nicotianamine synthase (OsNAS2) and soybean ferritin (SferH-1) genes possessed enriched endosperm Fe and Zn content. A Caco-2 cellular assay illustrated that increased iron and zinc levels found in these rice plants were bioavailable. Transgenic plants generated by Banakar et al. [26] expressed high levels of nicotianamine and 2′-deoxymugenic acid (DMA). These plants were able to accumulate up to 4-fold more iron and 2-fold more zinc in rice endosperm, in addition to lower

Other crop species have also been studied for iron and zinc biofortification using biotechnology. Tan et al. [27] improved iron levels in the pulse crop chickpea (*Cicer arietinum* L.) by increasing iron transport and storage through a combination of chickpea nicotianamine synthase 2 (CaNAS2) and soybean (*Glycine max*) ferritin (GmFER) genes. Transgenic chickpea plants that overexpressed these genes illustrated a doubling of NA concentration, suggesting an increase in iron bioavailability. Pearl millet was examined by Manwaring et al. [28] for iron and zinc biofortification by improving the currently available gene pool. High iron and zinc-biofortified pearl millet would be advantageous for poor regions of the world where soil management or supplementation programs are ineffectual. Narayanan et al. [29] have expressed the iron sequestering Arabidopsis AtVIT1 gene in cassava plants to increase iron storage in the crop's roots. Iron concentration also increased

The calcium content of crops can also be increased using biotechnology. These advances hinge on improved knowledge of how soluble calcium ions found in the soil are transported and accumulate in plant tissue [30]. Calcium plays a significant role in general cell signaling; how calcium transporters are expressed can thus influence a plant's ability to withstand stress, ward off pathogens, and can influence the nutritional status of animals and humans. Park et al. [31] have generated transgenic tomato, potato, lettuce, and carrots expressing high levels of calcium transporters. One of these calcium transporters, known as a short cation exchanger (sCAX1), can increase calcium transport into plant cell vacuoles [32]. Enhanced calcium absorption has been demonstrated in animal models that were fed transgenic carrots. Similarly, Sharma et al. have examined the potential of finger millet, an orphan crop with high calcium content, by studying the mechanisms behind calcium uptake, transport, and accumulation in grain. It has been reported that climate change may act detrimentally on mineral accumulation in different crop species; this could limit

their further availability from food crops for both humans and animals [33].

Vitamins such as β-carotene and folic acid are critical for human health. The development of microbial biochemistry facilitated the understanding of the biosynthetic pathways involved in vitamin production in plants. All vitamins that are required in the diet are synthesized by plants with the exception of ascorbic acid (vitamin C), which is specifically synthesized by eukaryotic cells [5, 34, 35]. Often biosynthesis is compartmentalized within various organelles. With greater comprehension of the metabolic pathways involved in vitamin production, plants can be

levels of cadmium compared to wild-type plants.

in stem tissues and accumulated in plant cellular vacuoles.

**5. Calcium-biofortified transgenic plants**

**6. Bioaccumulation of vitamins in plants**

developed with high levels of vitamin accumulation.

**12**

The well-known example of GM vitamin biofortification is Golden Rice, enriched with pro-vitamin A (β-carotene) [38, 39], followed by vitamin B9 (folate)-enhanced rice [40, 41]. Conventional breeding techniques could not be applied due to the absence/low content of vitamin A in rice grain. For Golden Rice, daffodil, and Pantoea genes were used to increase pro-vitamin A levels within rice endosperm [39]. The most recent version of Golden Rice has been improved further for a 23-fold increase in carotenoids [38]. Similarly, folate-biofortified rice has been generated by overexpressing Arabidopsis genes in rice endosperm. A fourfold increase in folate concentrations in rice was accomplished using this strategy [41] and in the process, folate stability for long-term storage was improved (Blancquaert et al., 2015).

Fifteen simulation analyses confirmed the positive impact of GM biofortified crop consumption on dietary intake and nutritional outcomes in humans [42]. The vast majority of these studies also confirmed that a regular portion of the targeted biofortified crop would provide the daily micronutrient requirements. For example, the recent simulation analysis of Golden Rice in Asia [43] indicated that it could reduce the prevalence of dietary vitamin A inadequacy by up to 30% (children) and 55–60% (women) in Indonesia and the Philippines, and up to 71% (children) and 78% (women) in Bangladesh.

A randomized trial on Golden Rice performed in the United States resulted in a high bio-conversion factor of β-carotene (3.8:1), by which 100 g of uncooked Golden Rice would provide about 80–100% of the estimated average requirement and 55–70% of the recommended dietary allowance (RDA) for adult men and women [44]. Currently, Golden Rice has been approved in an increasing number of countries, including the Philippines. Golden Rice and other GM biofortified crops [16, 42] would be highly cost-effective investments to reduce target micronutrient deficiencies such as vitamin A [45].

Recently, Endo et al. [46] devised a genome editing approach to produce β-carotene rice that is fast and direct, by making use of splicing variants in the Orange (Or) gene that cause β-carotene accumulation in cauliflower. The authors genome edited the orthologue of the cauliflower or gene in rice using CRISPR/ Cas9 and were able to accumulate β-carotene, without having to introduce transgenes.

#### **9. "Golden" bananas to combat vitamin A deficiency**

Bananas are the world's most important fruit crop and a major staple in many African countries. Banana grows in tropical climates, where vitamin A deficiency is most prevalent [47]. The vast number of different banana varieties and the highly variable distribution of vitamin A levels make them amenable for biofortification using biotechnology. Unfortunately, the cooking banana East African highland banana (EAHB) consumed in Uganda as a staple for tens of millions of people has low vitamin A levels.

As bananas are difficult to breed, genetic engineering of bananas with increased vitamin A content has been critical to improving vitamin A levels. The bulk of the research has been performed on the Cavendish banana, most popular in the Western Hemisphere. As a result, the Cavendish has been used as a model system for the EAHB. High levels of vitamin A (20 lg/g dry weight) were found in transgenic banana lines expressing phytoene synthase (derived from the fruit of the Fe'I banana found in Papa New Guinea, which only grows in small bunches) under the control of the banana ubiquitone promoter (Ubi). These transgenic lines appear as dark yellow-orange in color and can provide improved nutrition to some of the poorest subsistence farmers in Africa. Consumption of 300 g of transgenic banana could provide as much as 50% of vitamin A required per person per day. Although there is no existing regulatory framework for biotechnology that is currently set up in Uganda, early release is hoped for [48]. More recently, Kaur et al. [49] demonstrated the capability of genome editing to increase β-carotene accumulation in Cavendish banana. The authors created indels in the lycopene epsilon-cyclase (LCYε) gene to increase β-carotene content.

#### **10. Biofortified maize, cassava, and sweet potato**

Maize also produces β-carotene, and concentrations vary greatly between different varieties. Although β-carotene content can be increased using conventional breeding, genetic engineering strategies have also been implemented. Consumption of transgenic maize biofortified with β-carotene improved volunteer's health in clinical trials held in Africa and North America [50, 51]. Moreover, chickens fed transgenic biofortified maize produced eggs that exhibited increased carotenoid content [52]. The deep orange color of biofortified maize challenges public perception for some African populaces, as orange maize is often associated with animal feed, whereas white maize is traditionally considered to be for human consumption.

The BioCassava Plus project specifically targets cassava, a staple crop in Africa that is nutritionally deficient yet is consumed by a quarter of a million sub-Saharan Africans [53]. Transgenic cassava expressing high levels of β-carotene have been demonstrated to increase vitamin A levels and improve nutritional status in feeding studies [54]. Programs such as the BioCassava Project could therefore generate cassava crops with lasting nutritional benefits.

β-Carotene biofortified sweet potato has become a priority for sub-Saharan Africa [55]. White-fleshed sweet potato was transformed with the Orange (Or) gene responsible for carotenoid accumulation, so that β-carotene and total carotenoids levels in the IbOr-Ins transgenic sweet potato were 10-fold higher compared to that of white-fleshed sweet potato [56, 57].

#### **11. Conclusions**

This chapter illustrates the ability of biofortification using genetic engineering to address micronutrient deficiencies in a variety of crops found in resource-poor nations. The current regulatory climate and anti-GMO lobbying efforts have retarded the release of GM crops that address highly prevalent vitamin and mineral

**15**

**Author details**

Kathleen Hefferon

Department of Microbiology, Cornell University, Ithaca, NY, USA

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

\*Address all correspondence to: klh22@cornell.edu

provided the original work is properly cited.

*Biofortification of Crops Using Biotechnology to Alleviate Malnutrition*

deficiencies [58, 59]. Nevertheless, the proof of concept has been realized for various nutritionally enhanced GMOs [37, 60]. This has triggered an increase in the number of nutritional traits in the global GM crops pipeline over the last two decades and is expected to be further reinforced in the near future [61]. Consumer opinion on nutritious crops is hardly affected by the type of technology used to generate them [45, 62]. It is unfortunate that a significant effect of lobbying polarizes public opinion, regardless of the scientific basis of given arguments [63]. The current environment is showing signs of turning around with the approval of Golden Rice in several countries. It is anticipated that other biofortified crops will soon follow regulatory approval, and thus help to alleviate malnutrition worldwide.

*DOI: http://dx.doi.org/10.5772/intechopen.92390*

#### *Biofortification of Crops Using Biotechnology to Alleviate Malnutrition DOI: http://dx.doi.org/10.5772/intechopen.92390*

*Malnutrition*

low vitamin A levels.

(LCYε) gene to increase β-carotene content.

cassava crops with lasting nutritional benefits.

of white-fleshed sweet potato [56, 57].

**11. Conclusions**

**10. Biofortified maize, cassava, and sweet potato**

most prevalent [47]. The vast number of different banana varieties and the highly variable distribution of vitamin A levels make them amenable for biofortification using biotechnology. Unfortunately, the cooking banana East African highland banana (EAHB) consumed in Uganda as a staple for tens of millions of people has

vitamin A content has been critical to improving vitamin A levels. The bulk of the research has been performed on the Cavendish banana, most popular in the Western Hemisphere. As a result, the Cavendish has been used as a model system for the EAHB. High levels of vitamin A (20 lg/g dry weight) were found in transgenic banana lines expressing phytoene synthase (derived from the fruit of the Fe'I banana found in Papa New Guinea, which only grows in small bunches) under the control of the banana ubiquitone promoter (Ubi). These transgenic lines appear as dark yellow-orange in color and can provide improved nutrition to some of the poorest subsistence farmers in Africa. Consumption of 300 g of transgenic banana could provide as much as 50% of vitamin A required per person per day. Although there is no existing regulatory framework for biotechnology that is currently set up in Uganda, early release is hoped for [48]. More recently, Kaur et al. [49] demonstrated the capability of genome editing to increase β-carotene accumulation in Cavendish banana. The authors created indels in the lycopene epsilon-cyclase

As bananas are difficult to breed, genetic engineering of bananas with increased

Maize also produces β-carotene, and concentrations vary greatly between different varieties. Although β-carotene content can be increased using conventional breeding, genetic engineering strategies have also been implemented. Consumption of transgenic maize biofortified with β-carotene improved volunteer's health in clinical trials held in Africa and North America [50, 51]. Moreover, chickens fed transgenic biofortified maize produced eggs that exhibited increased carotenoid content [52]. The deep orange color of biofortified maize challenges public perception for some African populaces, as orange maize is often associated with animal feed, whereas white maize is traditionally considered to be for human consumption. The BioCassava Plus project specifically targets cassava, a staple crop in Africa that is nutritionally deficient yet is consumed by a quarter of a million sub-Saharan Africans [53]. Transgenic cassava expressing high levels of β-carotene have been demonstrated to increase vitamin A levels and improve nutritional status in feeding studies [54]. Programs such as the BioCassava Project could therefore generate

β-Carotene biofortified sweet potato has become a priority for sub-Saharan Africa [55]. White-fleshed sweet potato was transformed with the Orange (Or) gene responsible for carotenoid accumulation, so that β-carotene and total carotenoids levels in the IbOr-Ins transgenic sweet potato were 10-fold higher compared to that

This chapter illustrates the ability of biofortification using genetic engineering to address micronutrient deficiencies in a variety of crops found in resource-poor nations. The current regulatory climate and anti-GMO lobbying efforts have retarded the release of GM crops that address highly prevalent vitamin and mineral

**14**

deficiencies [58, 59]. Nevertheless, the proof of concept has been realized for various nutritionally enhanced GMOs [37, 60]. This has triggered an increase in the number of nutritional traits in the global GM crops pipeline over the last two decades and is expected to be further reinforced in the near future [61]. Consumer opinion on nutritious crops is hardly affected by the type of technology used to generate them [45, 62]. It is unfortunate that a significant effect of lobbying polarizes public opinion, regardless of the scientific basis of given arguments [63]. The current environment is showing signs of turning around with the approval of Golden Rice in several countries. It is anticipated that other biofortified crops will soon follow regulatory approval, and thus help to alleviate malnutrition worldwide.

### **Author details**

Kathleen Hefferon Department of Microbiology, Cornell University, Ithaca, NY, USA

\*Address all correspondence to: klh22@cornell.edu

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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*Malnutrition*

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**18**

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**21**

**Chapter 3**

**Abstract**

benefits, dosage

**1. Introduction**

**2. Fat-soluble vitamins**

**2.1 Vitamin A**

out from the body through urine [8–10].

Vitamins

*Mohanad Mousa Kareem and Majid S. Jabir*

for health, growth, replica, and other crucial metabolism.

This chapter is going to explain a part of the nutrients the human body needs. They are organic compounds called vitamins. Those compounds will be clarified, as well as their benefits, deficiencies, chemical structure, and why the body needs them crucially. Vitamins is an exceptionally vital recognized name required in certain amounts in the body, some of them exist as a complicated natural compounds found in herbal meals. It plays a key function in regular metabolism, the absence of which in the diet causes deficiency and several diseases. Vitamins are differentiated from the trace elements, also found in the weight-reduction plan in small quantities

**Keywords:** vitamins, water-soluble vitamins, fat-soluble vitamins, deficiency,

The human body is a magnificent machine, and to function well, the body needs certain supplements. Vitamins are one of the most essential elements for the body. There are nutrients that the body can make on its own, and there are others that the body is not able to make. Vitamins are one of the nutrients that the body is unable to make, so they must be consumed from aliments. Vitamins are an organic molecule, which is an essential micronutrient that an organism needs for its metabolism to function. They are divided into two groups, fat-soluble vitamins and water-soluble vitamins. The first group contains vitamins A, D, E, and K, while the second consists of thiamin (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), pyridoxal, pyridoxamine, pyridoxine (B6), biotin-cobalamin (B12), folic acid, and ascorbic acid [1–10].

They are a type that is absorbed well into the blood stream via fatty nourishments and are stored in limited amounts; they can be easy to separate and disposed

Vitamin A is a yellow viscous liquid alicyclic alcohol C20H30O that contains one more double bond in a molecule than vitamin A1 and is less active biologically in mammals and that occurs especially in the liver oil of freshwater fish. It consists of three biologically active molecules, retinol, retinal (retinaldehyde), and retinoic acid, all derived from the plant precursor molecule, β-carotene (**Figure 1**) [11, 12].
