European Journal of Nutrition

, Volume 56, Issue 2, pp 613–620 | Cite as

Role of selected amino acids on plasma IGF-I concentration in infants

  • Manja Fleddermann
  • Hans Demmelmair
  • Veit Grote
  • Martin Bidlingmaier
  • Philipp Grimminger
  • Maximilian Bielohuby
  • Berthold Koletzko
Original Contribution



Insulin-like growth factor-I (IGF-I) is related to growth and its secretion is modified by protein intake in early infancy. We examined the relationship of dietary protein and circulating amino acids on plasma IGF-I levels and early growth.


Healthy formula-fed infants (n = 213) were randomly assigned to receive either a protein-reduced infant formula with alpha-lactalbumin-enriched whey and free tryptophan and phenylalanine (IF) or an isocaloric standard formula without free amino acids (CF) for the first 120 days of life. A group of breastfed (BF) infants was studied as a non-randomized reference cohort. Biochemical variables were measured shortly after birth (subpopulation) and at an age of 120 days. A path analysis was used to explore the relationship between IGF-I, insulin and amino acids. Results are derived from secondary analyses of a randomized controlled trial.


Plasma concentrations of IGF-I at 120 days were significantly higher in IF than in CF infants [58.5 (15.0) vs. 53.7 (9.95) ng/mL; p = 0.020]. BF infants showed lower IGF-I concentrations of 41.6 (10.7) ng/mL. All amino acids but Thr and Cit had a more marked effect on insulin than on IGF-I level. Considering weight, sex and feeding group, Trp explained an equal percentage of variance of IGF-I and insulin (total R 2 12.5 % of IGF-I and 12.3 % of insulin), while branched-chain AA explained an up to twofold higher variance of insulin than IGF-I. Compared to CF, IF explained 18.9 % of the IGF-I level (p = 0.03), while for insulin no direct effect was detectable.


Higher IGF-I concentrations and growth velocities in infants receiving protein-reduced IF indicate that the protein concentration of an infant formula alone does not control IGF-I levels and growth. Other components (e.g., selected amino acids) of infant formulae might control directly or indirectly via insulin influence IGF-I.


Infant formula Growth regulation Alpha-lactalbumin Insulin-like growth factor-I Human milk 



Amino acid




Control formula




Intervention formula


Insulin-like growth factor-I


Long-chain polyunsaturated fatty acids


Glucose-dependent insulinotropic peptide



We are very grateful for the wonderful support of the study by Tatjana Nikolic and Dr. Branka Trisic during the preparation, recruitment and performance of the study in Belgrade, Serbia.

Source of funding

The clinical trial was financially supported by HiPP GmbH and Co Vertrieb KG (Pfaffenhofen, Germany). Work reported herein is carried out with partial financial support from the European Research Council Advanced Grant ERC-2012-AdG-No. 322605 META-GROWTH.

Author contribution

MB, PG and MB were responsible for IGF-I and insulin analysis; MF was responsible for amino acid analysis; VG and MF were responsible for statistical analyses; MF, HD, VG and BK undertook data interpretation; MF and HD were responsible for writing the manuscript. Finally, all authors critically revised the manuscript.

Compliance with ethical standards

Conflict of interest

All authors have made substantial contributions to the conception and design of the study, or acquisition of data, or analysis and interpretation of data, drafting the article or revising it critically for important intellectual content. Each author has seen and approved the contents of the submitted manuscript. None of the authors had any personal or financial conflict of interest.

Ethical standards

Manuscripts submitted for publication include data of the BeMIM study Fleddermann et al. (2013). The study was conducted according to the guidelines laid down in the Declaration of Helsinki 1964 and all procedures involving human subjects were approved by the ethical committee of the Clinical Center Serbia Ethical Committee. Written informed consent was obtained from all parents prior to study start after the experimental protocol had been explained to them in detail. The ethical approval to do further analyses with anonymized data and blood samples was obtained by the Ethical Committee of the Medical Faculty of Ludwig Maximilians University of Munich, Germany.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Manja Fleddermann
    • 1
  • Hans Demmelmair
    • 1
  • Veit Grote
    • 1
  • Martin Bidlingmaier
    • 2
  • Philipp Grimminger
    • 2
  • Maximilian Bielohuby
    • 2
  • Berthold Koletzko
    • 1
  1. 1.Dr. von Hauner Children’s HospitalLudwig Maximilians University of MunichMunichGermany
  2. 2.Endocrine Research Unit, Medizinische Klinik und Poliklinik IVLudwig Maximilians University of MunichMunichGermany

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