Nutrient Deficiencies

1. Nutrient Deficiencies Global Health Fellowship Nutrition Module Ramona Sunderwirth, MD MPH

2. Plan • Calcium & Vit D • Iodine • Zinc • Vit A • Thiamine (Vit 1) • Niacin • Vit C

3. Proteins • 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

4. Essential Fatty Acids • 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

5. Calcium • 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

6. Vit DCalciferols • 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

7. Rickets • ↓Sun exposure, ↓ Ca nutritional requirements • ↓serum Ca → induce ↑ PTH secretion → osteoclasts ↑ resorb bone → demineralization of bone & cartilage at sites of rapid growth & remodeling

8. Rickets Vit D deficiency, most common #Limited exposure to sun *limited sun exposure: poor air quality cultural, social habits, dress codes live > 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

9. Clinical Presentations • Early • Craniotabes, head asymmetry, frontal bossing, delayed closing ant fontanelle • Delayed tooth eruption, abnormal formation enamel, cavities • Rachitic rosary

10. Clinical Manifestations • 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

11. Rickets • Muscles • Delayed motor development • Tetany, carpopedal & laryngeal spasm • Convulsions • Pneumonia • 2ary defective immune function • Thorax deformity (restrictive airway) • Cor pulmonale

12. Rickets: Diagnosis • 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

13. Rickets: Treatment & Prognosis • 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

14. Rickets: Prevention • Community Health Education • Need for sunlight & animal foods (eggs) • Fish oil for children at risk: premies/infants/patients

15. Iodine Deficiency

16. IodineIDD • 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

17. Iodine deficiency Hypthyroidism • 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

18. IDD • 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

19. IDD • 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

20. Community investigation IDD • 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

21. Indicator/severity IDD 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%

22. IDD Prevention WHO/UNICEF/ICCIDD • 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

23. IDD Prevention Program

24. Zinc • 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

25. Zinc • 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

26. Vit A

27. Vit As Retinoic Acids: lipid soluble compounds • 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

28. Vit A (retinol) • 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

29. Vit A • 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

30. Clinical Manifestations • 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

31. Vit A Public Health Significance • 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

32. Vit A Treatment • 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

33. Vit A Supplementation

34. Thiamine (Vit B1)“anti beriberi factor” • 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)

35. Thiamine deficiency • Beriberi • Infantile • Adult • Wet or Dry • Wernicke-Korsakoff syndrome

36. Infantile Beriberi • 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

37. Adult Beriberi • 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

38. Wernicke-Korsakoff syndrome • 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

39. Thiamine Measurements & Requirements • 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

40. Niacin deficiency

41. Niacin(nicotinic acid & derivatives )deficiency: Pellagra • 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

42. Niacin • 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

43. Pellagra

44. Pellagra • 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)

45. Niacin deficiency • 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

46. Pellagra Treatment • Nicotinamide • 50mg TID PO • Chlorpromazine (for confusion) • 25-50 mg • Requirements • 14-18 NE (niacin equivalents) /day

48. Vit C (ascorbic acid) • 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

49. Scurvy • 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

50. Tests and Treatment • 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