Abstract
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.
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