Growth Retardation in Children Receiving Long‐Term Total Parenteral Nutrition: Effects of Ornithine α‐Ketoglutarate A A MOUKARZEL, O GOULET, J S SALAS, ET AL: Am J Clin Nutr 60: 408–413, 1994
Authors: Ziegler Thomas R. 
Published: May 2008

The authors evaluated the effect of supplementing parenteral nutrition (PN) with ornithine‐α‐ketoglutarate (OAK) on linear growth and biochemical parameters in a small group of prepubertal children requiring long‐term PN because of short bowel syndrome. Six study patients (5 male, 1 female) were selected from a group of 62 children receiving long‐term PN followed at a pediatric hospital in Paris, France. All of the patients had demonstrated significant growth retardation at entry (1 to 4 standard deviations below expected 50th percentile for height), and were prepubertal as evidenced by Stage I Tanner scores and prepubertal blood levels of testosterone, estradiol, and insulin‐like growth factor‐I (IGF‐1). The patients were determined to be normally nourished, as they received adequate doses of energy and nitrogen in PN prior to the study and demonstrated appropriate weight‐for‐height ratios, skinfold measurements and normal serum protein concentrations. The subjects had received constant dietary energy and nitrogen intakes for at least 8 months prior to study (primarily via PN).

The usual PN prescription was continued during the entire 10 month experimental period. PN provided mean (± SD) energy and nitrogen doses of 242 ± 33 kJ/kg/d (~ 50 kcal/kg/d) and 324 ± 87 mg N/kg/d (~ 2.0 g protein/kg/ day) respectively, during each of two consecutive 5 month study periods. During the first 5 months of study, 15 g OAK was added to the daily PN solution bag immediately before the weekly home delivery of PN. During the second 5 months of study (control period), no OAK was added to the PN solution. Linear growth (height) velocities, body weight and plasma concentrations of amino acids, transferrin, retinol‐binding protein, prealbumin, albumin, total IGF‐1, testosterone and estradiol were measured monthly.

During the 5‐month period of OAK supplementation of PN, linear growth velocity significantly increased to a median of 156% (range 126 to 186%) of baseline in five of the six subjects. During the subsequent 5 month control period (when OAK was not administered), three of these subjects demonstrated decreased height velocity (60%, 64% and 94% of baseline). The remaining two OAK responders evidently entered puberty during the post‐OAK control period, as their height velocities accelerated to 219% and 238% of baseline, their Tanner scores increased to stage 11, and their plasma IGF‐I and testosterone levels markedly rose. Overall, during OAK treatment, height velocity increased from a median of 3.80 cm/y to 6.45 cm/y (p <.05) and decreased to a median of 3.65 cm/y in the subsequent OAK‐free period (p <.05). Plasma IGF‐I concentrations rose significantly from a median of 200 U/L to 945 U/ L during OAK (p <.05); IGF‐I levels fell after OAK in 3 of the 5 responders, but continued to rise in the two patients entering puberty.

The change in IGF‐I level were positively correlated with the change in height velocity. No change in circulating proteins was observed. Although testosterone levels tended to rise in the 5 males studied during the OAK+ and OAK‐periods, levels remained prepubertal and no clear effect of OAK was discerned. No increase in plasma ornithine or other amino acid levels occurred during OAK, with the exception of plasma glutamine + glutamate, which rose by ~ 15% (from a mean of 621 to 715 mmol/L). The one subject who exhibited no increase in height response or IGF‐I levels during OAK had hepatic cirrhosis, and died of liver failure a few months after completion of study.