Global Health FellowshipNutrition Module

Ramona Sunderwirth, MD MPH

Calcium & Vit D Iodine Zinc Vit A Thiamine (Vit 1) Niacin Vit C

Evidence shows that energy deficits more general than protein deficit in community & hospitals

1ary protein deficiency: Staple food cassava or plantain Mothers feed inappropriate foods (sugar water) A major precipitating factor in Kwashiorkor

Sufficient carbs in diet spares protein from being used as substrate for glucose

Varied diet, proteins from plants & animal sources increases NPU

Variety & balance

Long chain PUFAs alfa-linolenic & linoleic acids only available in diets

Requirements EFA small gross deficiencies in bowel resection s/p weaning in many communities: cognitive

impairment , (-) impact on community development

Good intake of LC-PUFAs beneficial to health

Breast milk critical source on LC-PUFAs Major influence on brain development

Absorption Aided by Vit D, regulated Parathyroid hormone

Dietary Non dairy diets in Africa: low Ca Rural African mothers: low Ca in breast milk

Deficiency Stunting in children Ca deficient Rickets rare

Sources Milk, dairy products, fish (bones), beans, peas, dark green

leaves, nuts, millet

Function Fat soluble vit, stimulates intestinal Ca absorption

Sources Fortified food products richest source Vit D Fish oils, egg yolks, mushrooms Animal products (fatty parts, liver) Vit D in diet: cholecalciferol or ergocalficerol Converted to active form 1,25-dihydroxyvit D3 in skin,

liver & kidney Requires ultraviolet light

Deficiency Interaction of low dietary sources + lack exposure sunlight Rickets

↓Sun exposure, ↓ Ca nutritional requirements

↓serum Ca → induce ↑ PTH secretion → osteoclasts ↑ resorb bone → demineralization of bone & cartilage at sites of rapid growth & remodeling

#Limited exposure to sun*limited sun exposure: poor air quality cultural, social habits, dress codeslive > 37TH parallel darkly pigmented skin

#Nutritional deficiencies*breast milk low in Vit D, weaning diets (low in fats/oils) * inadequate intake Ca (↑consumption polished rice), Phosphate* diets w/ ↑ content phytate (wheat - binds Ca in gut)* ↓ energy supplies, growth outstrips Ca availability

#Genetic causes *Vit D-dependent rickets type 1&2

#Malabsorption (repeated GI infections)#Chronic renal, liver disease

Early

Craniotabes, head asymmetry, frontal bossing, delayed closing ant

fontanelle Delayed tooth eruption, abnormal

formation enamel, cavities Rachitic rosary

Late Pigeon chest irregularity, Harrison groove Motor delays, hypotonia (muscle weakness) Classic limb abnormalities

Genu varum, genu valgum, windswept deformities Fraying, widening, cupping metaphysis long bones, fxs Lordosis, kyphosis, scoliosis Narrow pelvis: obstructed labor

Muscles Delayed motor development Tetany, carpopedal & laryngeal spasm Convulsions

Pneumonia 2ary defective immune function Thorax deformity (restrictive airway) Cor pulmonale

Biochemistry Serum Ca: Nl or ↓ Serum Ph: ↓ Alkaline Phosphatase: ↑ Hydryxyproline excretion: ↑

Radiology Radius/ulna: widened, cupped, frayed ends Costochondral junctions: widened Osteopenia

Bone biopsy Inadequate mineralization Excessive volume of osteoid tissue

Sunlight or ultraviolet light Calciferol

PO or IM Vit D2: 150K i.u. once PO calciferol: 3K i.u. (75mg) QD x 1 mo Cod liver oil (75 i.u./ml or 1.8mg/ml) QD x 1mo

Tetany IV Ca Gluconate 10%solution ( 5-10ml) PO Ca Chloride 1g q 6 h ( in milk)

Ca supplements Milk or Ca lactate tab 5g TID

Healing 6 wks Vit D treatment biochemical changes reverses Bones heal more slowly, may never become normal

Community Health Education

Need for sunlight & animal foods (eggs)

Fish oil for children at risk: premies/infants/patients

Iodine > thyroid hormones

Regulation of growth, development & metabolism Commonest thyroid disease is goiter, response to

insufficient I intake

All body systems vulnerable to I deficiency CNS (fetal life & infancy-3yr age) Milder degrees of MR affect whole populations

Hypothyroidism → Goiter

Subclinical I deficiency Loss energy Brain damage Iodine deficiency in pregnancy → cretinism infants (MR +

stunted growth)

Endemic Goitre Soil deficient Marginal I deficient areas, precipitated by consumptions of

goitrogenic agents in food: poorly cooked roots (cassava)/leaves

Fetus Abortions, stillbirths,

congenital malformations ↑PNM, neurological & myxoedematous cretinism

Neonate NN hypothyroidism

Child & adolescent Retarded mental &

physical development

Adult Goitre I-induced hyperthy

(IIH) All ages

Goitre, Hypothy Impaired mental

function ↑ susceptibility

nuclear radiation

I content water & food reflects levels in soil & groundwater

I sources: animal>fruits/vegetables Goitergens

Thiocyanate ( from cassava) Selenium deficiency, high levels fluoride

Soil erosion Inland, mountainous areas w/ poor soils & hi

rainfall + coastal areas, large cities Public Health Problem

Reduces potential of whole community Low achievement, poor quality life, blunted ambition

Urinary iodine Most useful/reliable indicator I status 24hr or random (30 samples) urine collection Related to recent dietary I intake 100mico gm/l satisfactory

Thyroid size (goitre surveys) Palpation, ultrsound (more reliable) “Total Goitre Rate”, schoolchildren

TSH NN screening programs For early detection of congenital NN hypothyroidism Useful epi information severity of I deficiency, not cost

effective to monitor IDD programs

Mild Moderate Severe

Goitre 5-19% 20-29% >30%

Median Urinary I 50-99 20-49 <20

TSH > 5mU/L 3-19% 20-39% >40%

Consumption of adequate amounts I (150microgm/d) Sea fish, kelp

Supplementation programs Iodization of water or salt Direct administration I oil: IM or PO Iodine solutions (Lugol’s iodine): regular PO dose

Iodization of all salt for human consumption Sustainable , costs borne by consumer K iodate recommended (more stable) 20-40mg I/kg salt Monitoring essential

Function Cell replication & growth Stabilizing fct in organic compounds (cell

membranes) Bone & muscle (total body content: 2-3gm) No known correlation btw intakes & plasma levels

Sources Animal products, seafood, cereals (outer layers) Absorption impaired by phytates, protein acts as

anti-phytate, aids absorption

Deficiency Growth retardation (IUGR) cell mediated immunity wound healing

Replacement Strong evidence supports low dose supplementation

Reducing diarrhea Reducing mortality Children in several areas of developing world

Careful in administration in early recovery phases severe malnutrition w/ chronic diarrhea

Retinols Retinol: preformed Vit A

Most active form Found in animal sources

Beta-carotenes Provitamin A (converted to Vit A in intestines) Plant source of retinol from which mammals make

2/3 of their Vit A

Carotenoids Largest group

Functions Cell differentiation (eye, mouth, gut, respiratory tract,

immune cells, reproduction & growth) Vision (retinal rod & cone cells) & maintenance of

integrity of conjunctiva & cornea

Sources Retinol: animal products, liver Carotenoids: yellow, red fruits/vegetables & leaves

Deficiency Syndromes 3rd most common nutritional deficiency in world S. & SE Asia, Africa & S. America

Night, complete blindness & Xerophthalmia in malnourished adults & children

500K preschool school children/yr blind Chronic illnesses can deplete tissue Vit A Disorders w/ fat malabsorption

CF, celiac disease, cholestatic liver disease, Crohn’s, pancreatic insufficiency

Xerophthalmia Inadequate fct of lacrimal glands Night blindness Bitot’s spots →corneal xerosis →keratomalacia

Poor bone growth

Dermatological problems Hyperkeratosis, follicular hyperkeratosis, destruction of

hair follicles and replacement w/ mucus secreting glands

Impairment of humoral & cellular immune system Effects on phagocytes & T cells

Community wide administration of Vit A WHO recommended: beneficial effects on immunity ↓ U5MR by 25%

Replacement : q4-6 mos Infants 50K IU PO Infants 6-12mo: 100K IU PO Mothers: 200K IU PO w/in 8 wks delivery Pregnant or women of reproductive age: small doses 10K IU/d

or 25K IU wkly

Hi dose supplementation Children at hi risk Vit A deficiency: *measles, diarrhea, respiratory diseases, severe

malnutrition (single dose if no supplement in 1-4 mo) Reduces complications & mortality

Treatment Xerophthalmia 3 doses at age specific doses 1st immediately on diagnosis, 2nd the next day, 3rd dose 2 weeks later

Functions Co factor for many reactions: amino acid & carbohydrate

metabolism, requirements of Vit related to carbohydrate intake Catalyst in pyruvate → acetyl CoA Role in initiation nerve impulse propagation Transketolation of pentose phosphate pathway (WE, WKS) Found in skeletal muscle, liver, heart, kidney, brain ½ life 10-20d, cont. supplementation required

Sources Yeast, legumes, pork, rice, cereals Hi cooking temperatures, canning, pasteurization can destroy

thiamine (denatured at hi pH/temperature)

Beriberi Infantile Adult

Wet or Dry

Wernicke-Korsakoff syndrome

Apparent between ages 2-3 mos

Fulminant cardiac syndrome Cardiomegaly, tachycardia, cyanosis, dyspnea Loud piercing cry, vomiting

Aseptic meningitis Vomiting, nystagmus, purposeless movements Seizures, normal CSF

Dry Symmetrical peripheral neuropathy Sensory & motor distal extremities Acidotic, often w/ chronic diarrhea

Wet Neuropathy Cardiac: cardiomegaly, cardiomyopathy, CHF (hi

output), peripheral edema & tachycardia

Complication of Bariatric surgery & TPN Polyneuropathy w/ burning sensation extremities,

weakness, falls

Wernicke’s encephalopathy (WE) Acute syndrome, emergent treatment required Nystagmus, ophthalmoplegia, ataxia, confusion Chronic alcoholics w/ thiamine deficiency

Wernicke’s Korsakoff syndrome (WKS) Chronic neurological condition, consequence of WE Impaired short term memory & confabulation Otherwise grossly normal cognition

Blood thiamine concentration ITKA erythrocyte thiamine tranketolase Transketolase urinary thiamine excretion

Requirements: RDA 1.2-1.4mg/d

Treatment Beriberi Bed rest IV or IM 50-100mg/d x 7-14 d PO of 10mg/d till full recovery

Epi: Endemic in maize eating populations Central & S.

Africa Subsist on maize (deficient in tryptophan) & lots alcohol Prisoners, refugees, poor urban/rural

Functions Niacinamide & nicotinamide: incorporated into NAD

& NADP Function in many reactions : glycolysis, fatty acid/

carbohydrate/protein synthesis & metabolism, respiration & detoxification

Sources Plant & animal foods: yeast, meats,

cereals, legumes, seeds, dairy products Any hi protein diet of 100g/d (tryptophan → niacin)

Deficiency Common in poorer countries w/ local diet cereal,

corn, sorghum Alcoholics, complication bariatric surgery/anorexia

3 D’s Dermatitis

Photosensitive, hyperpigmentation/roughening skin Forearms, & around neck (“Casal’s Collar)

Diarrhea Smooth red & painful tongue, esophagitis, vomiting

Dementia Insomnia, anxiety, confusion, disorientation, delusions,

hallucinations (like DT) Dementia, encephalopathy, Acute, precipitated by acute infection (typhoid)

Carcinoid syndrome Tryptophan → 5-OH tryptophan & serotonin (rather

than nicotinic acid) INH prolonged use

Isoniazid depletes stores of pyridoxal phosphate, which ↑production tryptophan, precursor niacin

Hartnup Disease Autosomal recessive congenital disorder Defect of membrane transport in intestinal & renal

cells responsible for absorption tryptophan

Nicotinamide 50mg TID PO

Chlorpromazine (for confusion) 25-50 mg

Requirements 14-18 NE (niacin equivalents) /day

Epi Laborers in S. Africa, S. Sudanese migrants Prisoners, constant threat to refugees Patients w/ severe malabsorption, alcoholics, drug addicts Scurvy develops > 6mo severe deficient diet

Functions Cofactor, enzyme complement, co substrate, antioxidant

in many reactions & metabolic processes (copper, iron, folic acid, Vit E)

Collagen synthesis Fatty acid transport (mitochondial membrane w/ carnitine) Neurotransmitters (synthesis of norepi & dopamine) Prostaglandin metabolism, attenuating inflammatory response

Sources: Vegetable & fruit

Marginal deficiency Bleeding gums, retarded wound healing

Signs Peri follicular hemorrhage (early) Bruises, petechiae, coiled hairs, hyperkeratosis Subperiosteal hemorrhages (very painful) Arthralgias, Sjogren’s syndrome

Generalized systemic symptoms Weakness, malaise, joint swelling, edema, Depression, neuropathy Vasomotor instability

Leukocyte ascorbic test Best test to prove deficiency

Plasma concentration <0.2mg/dL

Xrays in infants Knees: atrophic b ones, white line (calcified cartilage at

metaphysis & epiphysis)

Treatment Children: 100mg ascorbic acid TID x 1 week, the QD x several

weeks till full recovery Adults: 300-1000mg QD x 1mo Improvement constitutional symptoms 24 hr, skin in wks

Principles of Medicine in Africa, Ed E. Parry, R. Godfrey. 3rd Ed. Cambridge 2004

Clinical Manifestations of malnutrition in children, Overview of water soluble vitamins Up to Date