Nutritional Management of Diarrhea

Agenda

What is diarrhea and what are different types?

Intestinal mucosal damage and impact on nutrition

Secondary Lactase Deficiency during diarrhea

Nutritional interventions in diarrhea

Acutewatery

diarrhoea

• Severe fluid loss and rapid dehydration in infected patients which last for few hours or days(<14days)

• Common etiologic pathogens: V. cholera, or E. coli, and rotavirus

Bloodydiarrhoea

• Intestinal damage and nutrient losses in infected patients with blood in the stools

• It is also termed as dysentery

• Common etiologic pathogen : Shigella bacteria

Persistent diarrhoea

• Continuous episode of diarrhea, with or without blood loss, lasting for a minimum of 14 days

• Commonly affected: Malnourished children and those with illnesses such as AIDS

UNICEF/WHO. Diarrhoea: Why children are still dying and what can be done? WHO 2009

DiarrheaPassage of unusually loose or watery stools at least 3 times in 24 hours; stool consistency rather than frequency is most important

for infants

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Childhood diarrhea is a major public health burden in India1

Diarrhea is third most common cause of death in children under five years of age in India2

1.Shah D, Choudhury P, Gupta P, et al. Promoting appropriate management of diarrhea: a systematic review of literature for advocacy and action: UNICEF-PHFI series on newborn and

child health, India. Indian Pediatr. 2012;49(8):627-49.

2. Bajait C, Thawani V. Role of zinc in pediatric diarrhea. Indian J Pharmacol. 2011 May;43(3):232-5.

3. International Institute for Population Sciences (IIPS) and Macro International. 2007. National Family Health Survey (NFHS-3), 2005–06: India: Volume I. Chapter 9. Child health page

no 223-266

Highest incidence of 18%

among children between 6-11

months2

Approximately 13.8 % in

children between 12-23

months2

Rotavirus is the leading cause of severe diarrhea in Indian children under five years1

15-30% of diarrheal episodes in hospitalized children, 7-15% in

community infections are caused due to rotavirus

Shigella infection accounts for 10-20% of diarrheal episodes

Infection with Vibrio cholerae can lead to cholera outbreaks and

commonly affected children are 2-5 year of age

1. Shah D, Choudhury P, Gupta P, et al. Promoting appropriate management of diarrhea: a systematic review of literature for advocacy and action:

UNICEF-PHFI series on newborn and child health, India. Indian Pediatr. 2012;49(8):627-49.

2. Kahn G,Fitzwater S, Tate J et al. Epidemiology and Prospects for Prevention of Rotavirus Disease in India. Indian Pediatr 2012;49: 467-474

Most Rotaviral infection occurs in children under 2 years of age2

Prevalence of rotavirus diarrhea is high in neonates (22%-73%), in India2

Vicious circle of diarrhoea-malnutrition

Infection (viral, bacterial etc.)

DiarrhoeaIntestinal Mucosa damage

/ Villous atrophy

Nutrient Loss (Macro & micro)

Malnutrition

Loss of fluid & electrolytes

Decreased Immunity

Reduced Lactase enzyme Secondary Lactose

Intolerance

Impact of diarrhea on nutritional status

Increased metabolic needs1

Increased protein and nutrient loss1

Reduction in micronutrient levels (E.g. zinc and copper1,2)

1. Guerrant RL, Oria RB, Moore SR et al. Malnutrition as an enteric infectious disease with long-term effects on child development. Nutr Rev. 2008;66(9):487-509

2. Zinc and copper wastage during acute diarrhea. Nutr Rev. 1990;48(1):19-22

Decreased nutrient absorption during diarrheal episodes

Diarrheal episodes result in villous atrophy and intestinal epithelial cell

damage resulting in

Decrease in absorption of micronutrients1

Decrease in absorption of macronutrients1

1.DeBoer MD, Lima AA, Oría RB et al. Early childhood growth failure and the developmental origins of adult disease: do enteric infections and malnutrition increase risk

for the metabolic syndrome? Nutr Rev.2012;70(11):642-53.

Intestinal mucosal damage and its effect on lactase secretion

Lactase enzyme is located in the internal lining (Brush border (microvilli) of the small intestine (Enterocyte).1

Reduction in the surface area of the microvilli caused by infections is associated with reduced levels of enzymes (including lactase) that are vital for digestion and absorption of sugars.2,3

1. Swagerty DL. Lactose Intolerance. Am Fam Physician. 2002 May 1;65(9):1845-1851.

2. Vesa TH, Marteau P, Korpela R, et al. Lactose Intolerance. J Am Coll Nutrition. 2000;19:165S–175S.

3. Mohammadi SS, Singer SM. Regulation of intestinal epithelial cell cytoskeletal remodeling by cellular immunity following gut infection. Mucosal

Immunology 2013; 6:369–378

4. Guidance on the management of lactose intolerance and cow’s milk protein allergy and the prescription of specialized infant formula. NHS

5. Evidence-Based Research in Pediatric Nutrition. edited by H. Szajewska, R. Shami World Review of Nutrition and Dietetics 2013. Karger Publications

Secondary lactose intolerance lasts for 6 to 8 weeks4

Lactase activity returns to normal following healing of damaged epithelium5

Congenital

Type of lactase deficiency

Definition Characteristics

Complete absence of lactase from birth

• Very rare

There are several types of lactase deficiency

Heymann MB for the Committee on Nutrition, American Academy of Pediatrics Lactose intolerance in infants, children and adolescents. Pediatrics 2006; 118(3):1279-86.

Primary

Decline in lactase levels after birth to clinical lactose intolerance

Affects:• 2% of adults in Northern Europe and North

America• Nearly 100% of adults in Asia and American

Indian• 60-80% of Africans and Ashkenazi Jew• 50-80% of Latin Americans

Secondary (transitory)

Temporary deficiency resulting from an injury of the intestinal mucosa

• Can follow gastrointestinal illness that damages intestinal epithelial cells

• Young children with severe diarrhea are at risk

• Up to 77% of children hospitalized with acute diarrhea have lactose intolerance

Carbohydrate Intolerance inIndian children with Acute Diarrhea

30.3

39.5

55.7

0

10

20

30

40

50

60

Incidence ofCarbohydrate intolerance

Well-nourished

Under-nourished

Marasmic

40.6% (110 infants) with carbohydrate intolerance.

Incidence of carbohydrate intolerance increased with the degree of malnourishment.

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f in

fan

ts

1. Chandrasekaran R, Kumar V, Walia BN, Moorthy B. Carbohydrate intolerance in infants with acute diarrhoea and its complications. Acta Paediatr Scand. 1975

;64(3):483-8.

Secondary Lactose Intolerance in acute diarrhea

0

0

0

1

1

1

14

6

90Lactose-intolerant

Multiple Disaccharideintolerance

Monosaccharide intolerance

Out of 110 infants with carbohydrate intolerance, 90 infants had lactose intolerance.

Proportion of carbohydrate

intolerant infants

Chandrasekaran R, Kumar V, Walia BN, Moorthy B. Carbohydrate intolerance in infants with acute diarrhoea and its complications. Acta Paediatr Scand. 1975 ;64(3):483-8.

Nutritional Interventions for diarrhea

Current Nutritional advices in Nutritional Management of Diarrhea

• Breast feeding

• ORS

• Stop milk completely

• Low lactose diet (Curd etc.)

• Banana

• Diluted cow’s milk/formula

• Fruit Juice

• Glucose beverages

• Coconut water

• Khichdi (Rice Lentils)

• Lactose Free formula

• Early reintroduction offeeds after acutegastroenteritis riskedexacerbating theillness, causingprotracted diarrhea

• Starvation for 24hours or even longer

1. Murphy MS. Guidelines for managing acute gastroenteritis based on a systematic review of published research. Arch Dis Child. 1998;79(3):279-84.

Early refeeding is

beneficial in

diarrhea

Early feeding helps in:• Reducing the abnormal increase in intestinal permeability• Enhancing enterocyte regeneration and promote recovery of

brush border membrane disaccharidases

Early Refeeding during diarrhea

ESPGHAN Recommendations on Early RefeedingChildren who require rehydration should continue to befed. Food should not be withdrawn for longer than 4 to 6hours after the onset of rehydration.

Management of feeding in

Gastroenteritis

1. Guarino A, Albano F, Ashkenazi S, et al; European Society for Paediatric Gastroenterology, Hepatology, and Nutrition; European Society for Paediatric Infectious

Diseases. European Society for Paediatric Gastroenterology, Hepatology, and Nutrition/European Society for Paediatric Infectious Diseases evidence-based guidelines for

the management of acute gastroenteritis in children in Europe. J Pediatr Gastroenterol Nutr. 2008 ;46 Suppl 2:S81-122

ESPHAGN: European Society of Paediatric Gastroenterology, Hepatology and Nutrition.

Early Refeeding during diarrhea

Role of milk in the diet of the child with diarrhea

Milk is the main source of nutrients for the young child

According to UNICEF survey, ~29% of children were not eating anything

during diarrhea2

Limiting milk intake among young children can promote nutritional deficiency

if substitute sources of protein and energy are not consumed sufficiently1

1. Gaffey MF, Wazny K, Bassani DG, et al. Dietary management of childhood diarrhea in low- and middle-income countries: a systematic review. BMC Public Health.

2013;13 Suppl 3:S17.

2. Management Practices for Childhood Diarrhea in India. Survey of 10 districts. New Delhi: UNICEF; 2009

3. World Health Organization. Clinical management of acute diarrhea. Available at: http://www.childinfo.org/files/ENAcute_Diarrhoea_reprint.pdf accessed on 15 July

2014.

Decrease in diarrheal

frequency

Reduction in diarrheal

stool volume

Faster recovery from

diarrhea

Advantages of Breast-feeding during diarrhea3

World Health Organisation/UNICEF Joint statement recommends

continued breastfeeding during acute diarrhea in children3

Impact of High Lactose content (Cow’s Milk/Regular Formula) in diarrhea

Infection1 DiarrheaDamage to the

intestinal mucosa

Secondary transient lactase

deficiency

Regular Lactose

formula/Cow’s milk2,3

1. Heyman MB. Lactose intolerance in infants, children, and adolescents. Pediatrics 2006; 118: 1279 -1286

2. Penny ME, Paredes P, Brown KH. Clinical and nutritional consequences of lactose feeding during persistent postenteritis diarrhea. Pediatrics. 1989;84(5):835-44.

3. MacGillivray S, Fahey T, McGuire W. Lactose avoidance for young children with acute diarrhoea. Cochrane Database of Systematic Reviews. 2013, Issue 10. Art. No.: CD005433.

DOI: 10.1002/14651858.CD005433.pub2.

Undigested/unabsorbed lactose

Osmotically Increased fluid secretion in gut and gas in bowel

Altered bowel movements (persitalsis)

Feeding Infants with Secondary Lactose-Intolerance

A lactose restricted diet should be given during the period of secondary lactose intolerance.

Lactase deficiency resolves once the diarrhoea gradually diminishes with the disappearance of underlying inflammation.

Secondary lactase intolerance is transient

1. Tomar BS. Lactose Intolerance and Other Disaccharidase Deficiency. Ind J Peadiatrics. 2014 Mar 6. [Epub ahead of print]

Reviewing the current options

Breast Milk

The Gold Standard

• Provides important

immune factors

Diluted Cow’s Milk/Regular formula

Not suitable for infants

with diarrhea

• Compromises adequate

nutrition to the baby

• High osmolality

Lactose Free formula

Limited indications

• Very severe diarrhea and

hospitalized children

• If trial with Low Lactose fails

• Congenital/Primary Lactose

Intolerance

Curd

• Good source of reduced lactose content.

• Not suitable for as a sole source of

nutrition as infant with diarrhea may

depend predominantly on milk for their

nutritional needs.

Clinical Evidence with Low Lactose Formulae

Recovery of lactose tolerance after acute diarrhea

% of infants able to tolerate lactose after acute diarrhea

1. Gabr M, Maraghi S, Morsi S. Management of lactose intolerance secondary to acute diarrhea with a soy based formula. Clin Ther 1979; 2: 271-6.

Low Lactose Formula Improves Early Weight Gain in Infants with Acute Diarrhea

Group A – Lactose free corn syrup formula

Group B - Low-lactose milk formula,

Group C – Standard formula

Efficacy of refeeding after rehydration in 135 infants with gastroenteritis indicated that

1. Wall CR, Webster J, Quirk P, et al. The nutritional management of acute diarrhea in young infants: effect of carbohydrate ingested. J

Pediatr Gastroenterol Nutr. 1994;19(2):170-4.

Comparison of Four Feeding Regimens in Well Nourished Infants with Acute Gastroenteritis (1/2)

Assessed for

a. Weight change among the four treatment

groups at two and five days

b. Duration of diarrhoea

c. Failure of treatment

Infants (aged 6 weeks to 12 months) with acute gastroenteritis (n=200)

previously fed with formula

Group A – ORS followed by gradual standard cows' milk formula Group B - A low lactose formula (followed by standard formula)Group C – Standard formulaGroup D - Soya based milk

1. Conway SP, Iresont A. Acute gastroenteritis in well nourished infants: comparison of four feeding regimens. Archives of Disease in Childhood 1989, 64, 87-91

Comparison of Four Feeding Regimens in Well Nourished Infants with Acute Gastroenteritis (2/2)

Early Weight Gain with Low Lactose Formula

1. Conway SP, Iresont A. Acute gastroenteritis in well nourished infants: comparison of four feeding regimens. Archives of Disease in Childhood 1989, 64, 87-91

Weight gain (p=0.01)

Group A (ORS followed by standard formula) babies lost weight initially

Group B babies (Low Lactose formula) gained weight significantly during initial days

There was no

significant difference

in the duration of

diarrhea or failure of

treatment between the

regimens.

Low Lactose diet in Persistent Diarrhea

A double-blind prospective trial, which included 64 children, (3-36 months of age) with diarrhoea for at least 14 days compared the effects of a milk-based diet containing lactose or the same diet with

95% prehydrolysed lactose

Treatment failure due to excessive purging with or without refusal to accept the diet in 12.1% of children fed lactose containing diet vs. 3.2% in hydrolysed group (p=0.20)

A greater purge of a mean 74.4 g/kg per day in the lactose group vs. 42.0 g/kg per day in the hydrolysed lactose group (p<0.01)

Stoppage of diarrhoea within 30 hours of hospital admission in 35.5% of children in the hydrolysed lactose group vs. 3.3% of those in the lactose group (p<0.001)

Lactose containing milk formula caused greater purging and an increased risk of dehydration in

children with persistent diarrhea.1. Penny ME, Paredes P, Brown KH. Clinical and nutritional consequences of lactose feeding during persistent postenteritis diarrhea.

Pediatrics. 1989;84(5):835-44.

The study results indicated

Low Lactose diet in Persistent Diarrhea

1. Penny ME, Paredes P, Brown KH. Clinical and nutritional consequences of lactose feeding during persistent postenteritis diarrhea.

Pediatrics. 1989;84(5):835-44.

Fecal wet weight by dietary group and day of study for successfully treated boys

only.

IAP recommendations

Persistent Diarrhea:• Low Osmolarity and Low Lactose diet are recommended for

children with persistent diarrhea.

• Children with persistent diarrhea, who continue to have diarrhea on the low lactose diets, should be given lactose (milk) free diets.

Severe Malnutrition (Hospital Based Management):Start feeding as soon as possible with a diet, which has:• Osmolarity less than < 350 mosm/L.• Lactose not more than 2-3 g/kg/day.

High osmolality foods can aggravate diarrhea

• Hyperosmolar foods include

– Cow’s milk

– Boiled skim milk

– Hypertonic (10 to 20%) glucose solution

– Tinned milk formulas (Regular/High lactose content)

– Commercial glucose-electrolyte solutions containing dextrose polymers in high concentration (10%)

1. Hirschhorn N. The treatment of acute diarrhea in children An historical and physiological perspective. Am. J. Clin. Nutr. 1980;33: 637-663

Low osmolarity oral rehydration therapy is recommended

Advantages: Decreased need for unscheduled IV therapy, Less stool output and lesser risk of

hypernatraemia and less vomiting.1

Modified low osmolarity ORS has a total osmolarity of 245 mmol/l and

reduced levels of glucose and sodium (WHO, 2004).

1. Acute diarrhea in adults and children: a global perspective. World Gastroenterology Organization Global Guidelines, February 2012.

Constituents of low osmolarity ORS solution1

ORS: oral rehydration salts, WHO: World Health Organization

Maltodextrin

A polysaccharide used in place of glucose in standard ORS

Compared to standard ORS, maltodextrin when hydrolysedmay yield more glucose without

increasing intraluminalosmolarity

The increased glucose may

promote higher absorption of sodium and

water

May reduce the stool output

Glucose

• 20g/L; total osmolarity311 mmol/L

Maltodextrin

• (30-80g/L; total osmolarity about 230mmol/L)

Suggested

mechanis

m of

action

1. EB-Mougi M, Hendawi A, Koura H, et al. Efficacy of standard glucose-based and reduced osmolarity maltodextrin-based oral rehydration

solutions: Effect of sugar malabsorption. Bulletin of the World Health Organization. 1996;74(5): 471–477.

Medium Chain Triglycerides

• The WHO recommends feeding of fats or oils during diarrhea:– To enhance the nutrient density of foods

– To provide maximum energy when there is limited absorptive capacity

• Medium-chain triglycerides can be used as a supportive nutritional therapy as they: – Increase the calorie value

– Improve the palatability, digestibility, absorption and transport of a diet indicated for diseases with maldigestion/malabsorption

1. Tanchoco CC, Cruz AJ, Rogaccion JM, et al. Diet supplemented with MCT oil in the management of childhood diarrhea. Asia Pac J Clin Nutr. 2007;16

(2):286-292.

• Easily hydrolysed and rapidly absorbed

• Can be absorbed even before hydrolysis

• Do not enter the lymph system and they pass through the portal venous system as albumin-bound free fatty acids

• Do not require lipoprotein lipase for oxidation as they are incorporated into chylomicrons

Medium Chain Triglycerides (MCTs)

1. Tanchoco CC, Cruz AJ, Rogaccion JM, et al. Diet supplemented with MCT oil in the management of childhood diarrhea. Asia Pac J Clin Nutr. 2007;16

(2):286-292.

Clinical Evidence

MCT: Medium chain triglycerides

1. Tanchoco CC, Cruz AJ, Rogaccion JM, et al. Diet supplemented with MCT oil in the management of childhood diarrhea. Asia Pac J Clin Nutr. 2007;16

(2):286-292.

*3 tsp MCT oil equally divided and incorporated in

formula/daily meals given during the diahrreal episode.

• Higher rate of weight gain in MCT supplemented children (0.22 ± 0.22 kg/day) compared to the non-supplemented children (-0.048 ± .26 kg/day; p=0.042)

• Decreased trend towards reduction in the duration of intervention

• Safe; no vomiting, dehydration, or fat intolerance

• No increase in the serum cholesterol and triglyceride levels

Therapeutic effects and safety of MCT oil supplementation* in children (aged 6 months to 47 months, n=17) with diarrhea:

Zinc Supplementation

1. Khan WU, Sellen DW, University of Toronto, Toronto, Canada. April 2011. Zinc supplementation in the management of diarrhoea.Available at:

http://www.who.int/elena/titles/bbc/zinc_diarrhoea/en/ Accessed on: 03 Apr 2014.

2. Galvao TF, Thees MFRS, Pontes RF, et al. Zinc supplementation for treating diarrhea in children: a systematic review and meta-analysis. Rev Panam Salud Publica.

2013;33(5):372–377.

Zinc aids in protein synthesis, cell growth and differentiation, immune function, and intestinal transport

of water and electrolytes.1

Zinc supplementation along with ORS has

shown:1

Reduction in the duration and severity of diarrheal

episodes

Reduction in the possibility of subsequent infections

over 2–3 months

A 2013 systematic review and metaanalysis of 18 randomized

clinical trials has also confirmed that oral zinc supplementation in

children <5 years significantly reduces duration of the diarrhea.

This effect is more prominent in malnourished children.2

Mechanism of Action of Zinc

Inhibits cAMP-induced, chloride-dependent fluid secretion by obstructing basolateral potassium channels

Enhances the absorption of water and electrolytes

Improves restoration of the intestinal epithelium and boosts the levels of brush border enzymes

Enhances the immune response and thereby promotes better clearance of the pathogens

1. Baiait C, Thawani V. Role of zinc in pediatric diarrhea. Indian J Pharmacol. 2011;43(3):232–235.

Based on the WHO/UNICEF/IAP recommendations, Government of India recommends:1

• Supplementation to be started as soon as diarrhea starts

• Children >6 months: 20 mg/day of elemental zinc for 14 days

• Children aged 2-6 months: 10 mg/day of elemental zinc for 14 days

1. Shah D, Choudhury P, Gupta P, et al. Promoting appropriate management of diarrhea: a systematic review of literature for advocacy and action: UNICEF-PHFI series on

newborn and child health, India. Indian Pediatr. 2012;49(8):627-49 7

Recommendation by Government of India

Nucleotides

• Non-protein nitrogenous compounds1

• Supports Immunity: Increased Serum IgA concentrations

• Favourable effects on the fecal microbial composition (increase in bifidobacteria)1

• Exert trophic effect on GI epithelium3

1. Singhal A, Macfarlane G, Macfarlane S, et al. Dietary nucleotides and fecal microbiota in formula-fed infants: a randomized controlled trial. Am J Clin

Nutr. 2008 ;87(6):1785-92.

2. Yau KI, Huang CB, Chen W, et al. Effect of nucleotides on diarrhea and immune responses in healthy term infants in Taiwan. J Pediatr Gastroenterol Nutr.

2003;36(1):37-43.

3. http://www.ncbi.nlm.nih.gov/books/NBK54100/

Nucleotide supplementation has beneficial effects on

the growth of the intestinal epithelium.3

Summary and Conclusion

In India, childhood diarrhea accounts for third most common cause of death in under five age group

Diarrhea results in villous atrophy and decreased absorption of micro-and macro-nutrients. The lactase-containing epithelial cells may be lost , leading to secondary lactase deficiency.

There is increased nutritional requirement during diarrheal episode and energy dense foods are recommended.

Presence of lactose intolerance can lead to prolongation of diarrhea and milk containing products may worsen diarrhea.

Summary and Conclusion

Use of a low lactose diet enables milk consumption even during diarrhea which constitutes a major portion of an Infant’s diet.

Lactose free formulations should be reserved for severe lactose intolerance where the trial with low lactose diet has failed

Use of Zinc, Medium-chain triglycerides (MCTs), Maltodextrinsand Nucleotides along with early refeeding is a novel approach in the nutritional management of diarrhea.

Thank you