Low plasma ghrelin levels in children with severe protein energy malnutrition

Harikrishnan V., Rakesh Kumar, Naresh Sachdeva, Devi Dayal


Background: Children with primary protein energy malnutrition (PEM) have significant loss of appetite which makes their nutritional rehabilitation difficult. Trials in patients with anorexia nervosa and cancer cachexia have shown short term efficacy of supplementing ghrelin to increase appetite. However, literature on ghrelin hormone status in children with PEM is scarce. We planned to study plasma ghrelin hormone levels in children with PEM and difference in plasma ghrelin levels among children having PEM of different grades.

Methods: Cross-sectional observational study was conducted over one year period. All hospitalised children during the study period and fulfilling the inclusion criteria for primary PEM (WHO criteria for malnutrition) were enrolled as cases. The cases (59 children) were divided into 2 groups – (Group 1 -severe PEM, group 2 - mild to moderate PEM) and were compared with 19 healthy children as controls (Group 3). Plasma fasting ghrelin levels were measured using enzyme immunoassay. The results were analysed using Mann-Whitney U Test.

Results: Median plasma ghrelin level among severe PEM group was 1.942ng/ml (interquartile range (IQR): 0.064, 9.506), mild to moderate PEM - 17.662 ng/ml (IQR: 1.658, 40.129) and controls - 17.525 ng/ml (IQR: 0.626, 27.361). Median ghrelin value was significantly lower in severe PEM group as compared to mild to moderate PEM (p value- 0.027).

Conclusions: Plasma ghrelin levels are significantly reduced in children with severe PEM as compared with mild to moderate PEM and healthy controls.


Children, Ghrelin, Protein energy malnutrition (PEM)

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Ghosh S. National Family health Survey-3 (2007). Indian Pediatr. 2007;44:619-20.

Kilic M, Taskin E, Ustundag B, Aygun AD. The evaluation of serum leptin level and other hormonal parameters in children with severe malnutrition. Clin Biochem. 2004;37:382-7.

Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999;402:656.

Kojima M, Kangawa K. Ghrelin: structure and function. Physiol Rev. 2005; 85:495-522.

El-Hodhod MA, Emam EK, Zeitoun YA, El-Araby AM. Serum Ghrelin in infants with protein-energy malnutrition. Clin Nutr. 2009;28:173-7.

Das UN. Relationship between gut and sepsis: Role of Ghrelin. World J Diabetes. 2011;2:1-7.

Tuca A, Jimenez-Fonseca P, Gascon P. Clinical evaluation and optimal management of cancer cachexia. Crit Rev Oncol Hematol. 2013;88:625-36.

Shintani M, Ogawa Y, Ebihara K, Aizawa-Abe M, Miyanaga F, Takaya K, et al. Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway. Diabetes. 2001;50:227-32.

Hosoda H, Kojima M, Kangawa K. Biological, physiological, and pharmacological aspects of Ghrelin. J Pharmacol Sci. 2006; 100:398-410.

Altinkaynak S, Selimoglu MA, Ertekin V, Kilicarslan B. Serum Ghrelin levels in children with primary protein-energy malnutrition. Pediatr Int. 2008;50:429-31.

Mohsen MA, Halwa MS, Saleh MT, Oraby FS, Wafay HA. Plasma Ghrelin in Marasmic Infants. Aust J Basic Appl Sci. 2008; 2:1315-9.

WHO child growth standards and the identification of severe acute malnutrition in infants and children - A Joint Statement by the World Health Organization and the United Nations Children’s Fund. Geneva, Switzerland: World Health Organization and UNICEF; 2009; Available at

WHO Multicentre Growth Reference Study Group: WHO Child Growth Standards: Length/height-for-age, weight-for-age, weight-for-length, weight-for-height and body mass index-for-age: Methods and development. Geneva: World Health Organization; 2006; Available at

Bairwa M, Rajput M, Sachdeva S. Modified Kuppuswamy's Socioeconomic Scale: Social Researcher Should Include Updated Income Criteria, 2012. Indian J Community Med. 2013;38:185-6.

Gernaat HB, Voorhoeve HW. A new classification of acute protein-energy malnutrition. J Trop Pediatr. 2000;46:97-106.

Bellone S, Castellino N, Broglio F, Rapa A, Vivenza D, Radetti G, et al. Ghrelin secretion in childhood is refractory to the inhibitory effect of feeding. J Clin Endocrinol Metab. 2004;89:1662-5.

Tannenbaum GS, Ramsay M, Martel C, Samia M, Zygmuntowicz C, Porporino M et al. Elevated circulating acylated and total Ghrelin concentrations along with reduced appetite scores in infants with failure to thrive. Pediatr Res. 2009 May;65:569-73.

Wali P, King J, He Z, Tonb D, Horvath K. Ghrelin and obestatin levels in children with failure to thrive and obesity. J Pediatr Gastroenterol Nutr. 2014;58:376-81.

Prodam F, Monzani A, Ricotti R, Marolda A, Bellone S, Aimaretti G et al. Systematic review of Ghrelin response to food intake in pediatric age, from neonates to adolescents. J Clin Endocrinol Metab. 2014;99:1556-68.

Fazeli PK, Lawson EA, Faje AT, Eddy KT, Lee H, Fiedorek FT et al. Treatment with a Ghrelin agonist in outpatient women with Anorexia Nervosa: A Randomized Clinical Trial. J Clin Psychiatry. 2018 Jan 2;79(1)pii:17m11585.

Rocha NN, de Oliveira MV, Braga CL, Guimarães G, Maia LA, Padilha GA et al. Ghrelin therapy improves lung and cardiovascular function in experimental emphysema. Respir Res. 2017 Nov 3;18:185.

Garcia JM, Polvino WJ. Effect on body weight and safety of RC-1291, a novel, orally available Ghrelin mimetic and growth hormone secretagogue: results of a phase I, randomized, placebo-controlled, multiple-dose study in healthy volunteers. Oncologist. 2007;12:594-600.