Nutrition and the Physiology of Malnutrition Lia Fernald, Ph.D., M.B.A. Human Biology Lecture May 14, 2002

Male, 17, Oakland, weekly diet MonTuesWedSat Sausage, egg cheese burrito (McD) NothingFrosted FlakesHot link with mustard, ketchup, Coke Personal size pepperoni pizza Double cheese burger, fries, Coke (BK) Pepperoni pizza (PH) and french fries Nation’s cheeseburger, large fries, Coke Burrito from vending machine, Lays Banana nut muffin and carton of milk 2 ham & cheese sandwiches and can of soda 2 hot dogs, blueberry muffin Spaghetti, fried chicken, fruit punch Small round pizza Baked pork chops, mac & cheese, Pepsi Fries, BBQ bacon cheese burger (McD) 3,045 (38%) 2,400 (41%) 2,739 (33%) 3,163 (36%) B L S D

Overweight 9 th graders in the Bay Area “Overweight” defined as more than 25% body fat for boys and more than 32% for girls. Less than 1% of students are out of shape because they are too thin.

Today’s Class Overview of Nutritional Requirements Definition of Malnutrition Causes and correlates of Malnutrition Measurement and Types of Malnutrition Severe Malnutrition Mild/Moderate Malnutrition (Underweight and Stunting) Specific Nutritional Deficiencies (Iodine and Iron)

Nutritional requirements

Macro v. micro nutrients Macro-nutrients –Protein (amino acids) –Energy (carbohydrates) –Fat (fatty acids) Micro-nutrients –Water soluble vitamins (assist in energy-release of carbohydrates and red blood cell formation) –Fat soluble vitamins (development & metabolism) –Minerals

Macro-nutrients Energy –Necessary for all bodily function Protein –Necessary for structural development (muscle and bone) Fat –Necessary for cell membrane and skin cell development

Dietary Reference Intakes MacronutrientF (19-30 y.o.)M (19-30 y.o.) Energy (Kcal) Protein (g) 1940 – – – – 60 Fat15 – 33%

Water soluble vitamins Thiamin B –nervous system function, enzymatic energy release of carbohydrates (beef, pork, liver, legumes, breads) Riboflavin B2 –Participants in enzymatic energy release of carbs, fat & protein (milk, dairy, dark green vegetables, yogurt) Niacin –Participates in enzymatic energy release of energy nutrients (beef, pork, liver, breads, nuts) Folate –Red blood cell formation, new cell division (veg, seeds) Vitamin B12 (Cobalamin) –Red blood cell formation, nervous system maintainance (animal prod) Pantothenic Acid Biotin (Vitamin H, CoEnzyme R) Vitamin B6 (Pyridoxine) Vitamin C

Fat soluble vitamins Vitamin A –Essential to vision, fetal development, immune response –Found in dairy products, fish liver oils; as B-carotene found in many plants (e.g. carrots, mango) Vitamin D –Bone formation, calcium metabolism and absorption –Found in sunlight, egg yolk, dairy products and fish liver oil Vitamin E –Cell membrane construction and maintenance –In fats and oils, green leafy vegetables, poultry, fish Vitamin K –Blood clotting, protein synthesis –In green leafy vegetables, liver, cabbage

Minerals Major “Bone” MineralsTrace Minerals Calcium (bones)Iodine (thyroid function) Phosphorus (DNA)Iron (hemoglobin) Magnesium (bones)Zinc (enzyme, hormone) Sodium (nerve impulse)Copper (abs. of iron) Chloride (fluid balance)Flouride (bone & teeth) Potassium(prot. syn)Chromium (energy rel.) Sulfur (some a.a.’s)Molybdenum (enzymes) Manganese (enzymes) Selenium (antioxidant) Cobalt (part of B12)

Summary: Nutritional requirements In order to live and function, humans need macro- and micro- nutrients; Macro-nutrients are fat, protein and carbohydrates; Micro-nutrients are water-soluble vitamins, fat-soluble vitamins, and minerals (bone and trace); the most critical micro-nutrients are iron, iodine, zinc, vitamin A and vitamin D.

Today’s Class Overview of Nutritional Requirements Definition of Malnutrition Causes and correlates of Malnutrition Measurement and Types of Malnutrition Severe Malnutrition Mild/Moderate Malnutrition (Underweight and Stunting) Specific Nutritional Deficiencies (Iodine and Iron)

What is malnutrition? World Health Organization definition: The term is used to refer to a number of diseases, each with a specific cause related to one or more nutrients (for example, protein, iodine or iron) and each characterized by cellular imbalance between the supply of nutrients and energy on the one hand, and the body's demand for them to ensure growth, maintenance, and specific functions, on the other.

Countries at risk of malnutrition

Geneva Declaration 1924: Declaration of the Rights of the Child (also known as the Declaration of Geneva). Adopted after World War I by the League of Nations through the efforts of British child rights pioneer Marks the beginning of the international child rights movement and is also the first international affirmation of the right to nutrition. Affirms that "the child must be given the means needed for its normal development, both materially and spiritually" and states that "the hungry child should be fed."

Death from malnutrition Source: WHO, based on C.J.L. Murray and A.D. Lopez, The Global Burden of Disease, Harvard University Press, Cambridge (USA) 1996 and American Journal of Public Health * * * * * At least 70% of childhood diseases are related with one of these conditions *

Summary: Definition of malnutrition Malnutrition is having the inappropriate level of a micro- or macro- nutrient; In some cases (i.e. the US), malnutrition can be associated with being grossly overweight; In most of the world, malnutrition is defined as a LACK of nutrients; Malnutrition contributes to over 50% of deaths in children in the world.

Today’s Class Overview of Nutritional Requirements Definition of Malnutrition Causes and correlates of Malnutrition Measurement and Types of Malnutrition Severe Malnutrition Mild/Moderate Malnutrition (Underweight and Stunting) Specific Nutritional Deficiencies (Iodine and Iron)

Child malnutrition death and disability Inadequate Disease Diet Insufficient access to food Inadequate maternal and child care Poor water/ sanitation inadequate health services Causes of malnutrition

Baby Low Birth Weight Child Stunted Adolescent Stunted Woman Malnourished Pregnancy Low Weight Gain Elderly Malnourished Higher mortality rate Impaired mental development Increased risk of adult chronic disease Untimely/inadequate weaning Frequent Infections Inadequate catch up growth Inadequate food, health & care Reduced mental capacity Inadequate food, health & care Reduced mental capacity Inadequate fetal nutrition Inadequate food, health & care Inadequate food, health & care Higher maternal mortality Reduced capacity to care for baby Start here

Correlate: Unsafe Water Source for photos: Overseas Aid: Statistics, UNICEF State of the World’s Children 2000www.nat.uca.org.au 11% urban and 38% rural households do not have access to safe water

Correlate: Inadequate Sanitation Source for photos: Overseas Aid: Statistics, UNICEF State of the World’s Children 2000www.nat.uca.org.au 21% urban and 75% rural households do not have access to adequate sanitation

Correlate: Poor Education Source for photos: Overseas Aid: Statistics, UNICEF State of the World’s Children 2000www.nat.uca.org.au 25% of girls and 19% of boys do not enter primary school; 54% of girls and 45% of boys do not enter secondary school

Correlate: Poverty 28% of the population lives at below $1 per day Average GNP per capita is $1299 (compared with $29,080 in USA) Source for photos: Overseas Aid: Statistics, UNICEF State of the World’s Children 2000www.nat.uca.org.au

Correlate: Poor Stimulation Source for photos: Overseas Aid: Statistics, UNICEF State of the World’s Children 2000www.nat.uca.org.au 39% of females and 21% of males over the age of 15 cannot read or write 199 radios per 1000 population; 154 TV’s per 1000 population

Correlate: Poor Public Health About 30% of 1- year olds are not fully immunized for TB, DPT (Diptheria, Pertussis, and Tetanus), polio and measles Source for photos: Overseas Aid: Statistics, UNICEF State of the World’s Children 2000www.nat.uca.org.au

Correlate: No Breastfeeding Source: Children’s Hospital Islamabad Babies are twins (boy and girl) Mother was told that she wouldn’t have enough breast milk for both, so should bottle feed girl... girl died the day after this photo was taken 56% babies in developing countries are not breastfed from 0-3 months

Summary: Causes/correlates Malnutrition rarely exists in isolation, and many other factors contribute to its detrimental impact; –Poor physical resources, and overcrowded homes –Poor sanitation and water supply –Low income –Parents with little education –Minimal interaction/stimulation in the home Malnutrition has repercussions throughout the life cycle and is thus multi-generational (diagram with lots of arrows)

Today’s Class Overview of Nutritional Requirements Definition of Malnutrition Correlates of Malnutrition Measurement and Types of Malnutrition Severe Malnutrition Mild/Moderate Malnutrition (Underweight and Stunting) Specific Nutritional Deficiencies (Iodine and Iron)

Types of malnutrition Severe Protein-Energy Malnutrition (>3 S.D.) –Kwashiorkor (low protein) –Marasmus (low calories) Mild/moderate undernutrition (>2 S.D.) –Stunting –Underweight –Wasting Micro-nutrient deficiency –Iodine –Iron –Vitamin A –Vitamin D

Measurement of Malnutrition STUNTING: Height for age – height compared to a reference population of the same age. = represents long term growth retardation UNDERWEIGHT: Weight for age – weight compared to age in a reference population WASTING: Weight for height – weight compared to a reference population of the same height.

Growth Curves (0-3 years) Weight Length/ Height Age

Summary: Measurement There are several types of malnutrition, micro- and macro-malnutrition; Measurement of severe malnutrition (>3 S.D.) and micro-nutrient deficiency usually occurs due to presence of critical signs (to be discussed); Measurement of mild/moderate malnutrition (>2 S.D.) occurs with growth charts.

Today’s Class Overview of Nutritional Requirements Definition of Malnutrition Correlates of Malnutrition Measurement and Types of Malnutrition Severe Malnutrition Mild/Moderate Malnutrition (Underweight and Stunting) Specific Nutritional Deficiencies (Iodine and Iron)

Severe malnutrition % <5 y.o. Developing Countries12% Least Developed Countries13% (India 21%, Bangladesh 21%, Cambodia 18%) Data for , UNICEF State of the World’s Children 2000

Severe PEM: Real Numbers Example: India 21% of all children under 5 # children under 5 is 115,615,000 24M children severely malnourished (Bigger than population of Texas 20M) Example: All developing countries Total # <5 in developing countries: 536,105,000 and 12% of that is: 64M children under 5y.o. severely malnourished (California & New York & Florida) Example: World (total number is 603,449,000) 11% = 66M (France or England)

Kwashiorkor Swollen belly Pellagra Decreased muscle mass Sparse hair Infection Apathy

Kwashiorkor (low protein) Decreased muscle mass (failure to gain weight and of linear growth) Swollen belly (edema and lipid build-up around the liver) Changes in skin pigment (pellagra); may lose pigment where the skin has peeled away (desquamated) and the skin may darken where it has been irritated or traumatized Hair lightens and thins, or becomes reddish and brittle. Increased infections and increased severity of normally mild infection, diarrhea Apathy, lethargy, irritability  Death does not occur from actual starvation but from secondary infection

Kwashiorkor – mechanisms Occurs in reaction to emergency situations (famine) Kwashiorkor more likely in areas where cassava, yam, plantain, rice and maize are staples, not wheat Increased carbohydrate intake with decreased protein intake eventually leads to edema (water) and fatty liver

Marasmus (low calories) Ravenously hungry Gross weight loss & no fat

Marasmus Deficit in calories – “marasmus” comes from Greek origin of word “to waste” Gross weight loss Hyper-alert and ravenously hungry Children have no subcutaneous fat or muscle  eventually starve to death (immediate cause often is pneumonia)

Marasmus – mechanism Energy intake is insufficient for body’s requirements – body must draw on own stores Liver glycogen exhausted in a few hours – skeletal muscle protein used via gluconeogenesis to maintain adequate plasma glucose When near starvation is prolonged, fatty acids are incompletely oxidized to ketone bodies, which can be used by brain and other organs for energy High cortisol and growth hormone levels  Mechanism is same as anorexia

Mental development –Lower IQ levels –Poorer school performance Behaviors of recovered severely malnourished children –shy, isolated, withdrawn –decreased attention span –immature, emotionally unstable –fewer peer relationships/reduced social skills –played less/stayed nearer to mothers Severe Malnutrition: Consequences

Summary: Severe malnutrition Severe malnutrition is defined as > 3 s.d. away from median reference standards; 66M children under the age of 5 are severely malnourished (64M of these in developing countries); Key types of severe malnutrition are kwashiorkor (low protein) and marasmus (low calories); Severe malnutrition results in severe deficits for children

Today’s Class Overview of Nutritional Requirements Definition of Malnutrition Correlates of Malnutrition Measurement and Types of Malnutrition Severe Malnutrition Mild/Moderate Malnutrition (Underweight and Stunting) Specific Nutritional Deficiencies (Iodine and Iron)

Stunting – Height for Age Height for age reflects pre- and post- natal linear growth “Stunting” refers to shortness that is not genetic, but due to poor health or nutrition Most standard definition < 2 S.D. Stunting is good cumulative measure of “well-being” for populations of children (because not affected by weight recovery)

Stunting These girls are: From same school and the same neighborhood Both have the same birthday

Stunting % <5 y.o. Developing Countries39% Least Developed Countries47% Data for , UNICEF State of the World’s Children 2000 (India 52%, Bangladesh 55%, Cambodia 56%)

Stunting: Real Numbers India where 52% of all children under 5 (total <5 is 115,615,000) are stunted 60M children in India are stunted (as many people live in the MidWest) Example all developing countries, where 39% of all children under 5 (536,105,000) 209M children in dev world In world, the total # of children <5 is 603,449,000 and 37% of that is 223M children in world (US popn 272M US minus California and Texas)

Stunting: Causes Poor nutrition plays major role Role of environment: improvements in average height shown by populations over last century (impact of genetic influence subsumed by level of socio-economic development)  In 1833, British children were as tall as children today from India and Guatemala  All immigrant populations have same height after 3 generations in US

Stunting: Timing Age of onset varies, but usually in first 2-3 years of life First few months, infants in developing countries grow just as quickly as children in reference populations –Growth retardation starts from 2-6 month of life (often associated with weaning) –Infants at risk during this time because of high nutritional requirements and high rates of infections (breast fed infants often protected)

Stunting: Consequences Cross-sectional associations – Low height for age associated with: –Reduced cognitive development –Poor motor skills –Poor neuro-sensory integration –Quiet, reserved, withdrawn, timid, passive –Difficulty making decisions –Decreased involvement with environment, toys, tasks –Less able to deal with stressor such as hunger or parasites

poor nutrition poor mental development & behavior alterations in development of CNS “functional isolation” emotional reactivity, impaired stress response Hypothesized Mechanisms

Summary: Mild/moderate maln. Stunting refers to growth retardation (>2 S.D.) secondary to malnutrition; Almost 40% (223M) of children <5 in the developing world are stunted; Children are most at risk for stunting in the first 2-3 years of life; Stunting is associated with poor mental development and altered behavior.

Today’s Class Overview of Nutritional Requirements Definition of Malnutrition Correlates of Malnutrition Measurement and Types of Malnutrition Severe Malnutrition Mild/Moderate Malnutrition (Underweight and Stunting) Specific Nutritional Deficiencies (Iodine, Iron, Vitamin A, Vitamin D)

Specific Nutritional Deficiencies Iodine Deficiency Iron Deficiency Vitamin A Vitamin D

Iodine deficiency - thyroid “Simple goiter is the easiest of all known diseases to prevent... It may be excluded from the list of human diseases as soon as society determines to make the effort” David Marine 1923

Iodine Deficiency Disorders Source: State of the World’s Children, 1998

Causes of Iodine Deficiency Mountainous areas at risk (soils leached by high rainfall, melting snow, flooding) Culturally induced behavioral change –Tasmanian Aboriginals migrated every season until European invasion, became sedentary and had incidence of thyroid problems

Iodine Deficiency: Severe Goiter: most commonly recognized consequence (enlarged thyroid) –Occurs when thyroid gland is unable to meet the metabolic demands of the body through sufficient hormone production – thyroid compensates by enlarging (works in short term) Cretenism: proximal pyramidal signs, intellectual impairment, primitive reflexes –Only occurs with severe fetal iodine deficiency

Iodine Deficiency: Moderate Studies comparing 2 Villages –Consistent results: meta-analysis showed 13.5 IQ point difference between groups Intervention Studies –Prenatal supplementation (esp. 1 st trimester): clear impact – prevents cretenism, and affects mental development in children –Childhood supplementation: many mediocre studies, but positive impact

Source:UN ACC-SCN-IFPRI - 4th Report on World Nutrition Situation Iron deficiency - anemia % Source: UN-ACC-SCN-IFPRI-4 Report on World Nutrition Situation

Iron Deficiency Iron is critical for body: –Carries oxygen to tissues from lungs –Transports electrons within cells –Integral part of important enzyme reactions Anemia is caused most commonly by iron deficiency (anemia is found in 40-60% of women and children in developing countries)

Iron Deficiency Consequences Iron deficiency results in: –Decreased work capacity and work productivity –Permanently impaired development Psychomotor development of anemic children will be reduced by 5-10 IQ points –Increased morbidity and mortality from infections –Decreased growth

Vitamin A Deficiency Vitamin A is important because it is essential to vision, fetal development, immune response 250 million children of pre-school age lack sufficient Vitamin A in their diet. 350,000 become blind each year, and half of them die within a year of becoming blind….

Vitamin A Deficiency Associated with blindness and increased severity of infections such as measles and diarrhoeal disease WHO estimates that 2.8 million children under 5 years old have signs of clinical xerophthalmia (childhood blindness) WHO estimates that 14 million pre-school children already have some eye damage from Vitamin A deficiency

Vitamin D Deficiency: Rickets

Summary: Micronutrient deficiency Iodine is critical for thyroid function – deficiency results in cretinism & goiter Iron is critical for blood and muscles – deficiency results in anemia Vitamin A is critical for visual development – deficiency results in blindness Vitamin D is critical for bone development – deficiency results in rickets

From UNICEF, State of the World’s Children: Adapted from Stuart Gillespie, John Mason and Reynaldo Martorell, How nutrition improves, ACC/SCN, Geneva Where do we go from here? Improved child nutrition Increased productivity Enhanced human capital Poverty reduction Economic growth Social sector investments