Oral arginine-lysine does not increase growth hormone or insulin-like growth factor-I in old men.

BACKGROUND: Older adults tend to have reduced growth hormone (GH) secretion and insulin-like growth factor I (IGF-I) levels as well as changes in body composition which are partially reversed by GH injections. Arginine stimulates GH release, and lysine may amplify this response. We investigated whether oral arginine/lysine could be used to increase basal IGF-I and GH levels in non-obese old men (age 69 +/- 5 years; mean +/- SD) to values similar to those of untreated young men (age 26 +/- 4 years). METHODS: Two groups of 8 healthy old men were treated with 3 g of arginine plus 3 g of lysine or with placebo capsules twice daily for 14 days. Before and on day 14 of each treatment GH levels were determined in blood samples taken at 20-minute intervals from 2000-0800 h, IGF-I was measured at 0800 h, and a 1 microgram/kg GHRH stimulation test was done. RESULTS: At baseline, mean GH peak amplitude (p < .02) and serum IGF-I (p < .0001) were lower, whereas GHRH responses were similar, in old vs young men. Arginine/lysine did not significantly alter spontaneous or GHRH-stimulated GH levels, or serum IGF-I. Arginine absorption was age-independent. The correlation (p < .005) between measured increments in serum arginine and increases in serum GH after a single dose of arginine/lysine was similar in old and young groups. CONCLUSIONS: Our data suggest that oral arginine/lysine is not a practical means of chronically enhancing GH secretion in old men.

Human growth hormone and human aging.

In humans, both aging and GH deficiency are associated with reduced protein synthesis, decreased lean body and bone mass, and increased percent body fat. In healthy individuals, spontaneous and stimulated GH secretion, as well as circulating IGF-I and IGFBP-3 levels, are significantly decreased with advancing age. The extent to which these age-related changes in GH and IGF-I contribute to alterations in body composition and function remains to be elucidated. GH treatment of GH-deficient adults or old men with reduced IGF-I levels with exogenous GH increases plasma IGF-I, nitrogen retention, and lean body mass, decreases percent body fat, and exerts little effect on bone mineral density. Short-term adverse effects of GH therapy have been minimized by using low-dose regimens, but it is still uncertain whether long-term GH supplementation in adult life increases the risk of metabolic abnormalities or malignancy. Administration of GHRH, which has been shown to maintain the pattern of pulsatile GH secretion in old men, may represent another possible physiological approach to therapy. It may be justifiable initially to limit use of GH to certain elderly patients such as those suffering from catabolic illnesses, malnourishment, burns, cachexia, etc. A great deal more research will be necessary to determine whether normalization of GH and IGF-I levels in healthy older persons will lead to improvements in their physical and psychological functional capacity and quality of life.

Continuous subcutaneous infusions of growth hormone (GH) releasing hormone 1-44 for 14 days increase GH and insulin-like growth factor-I levels in old men.

Twice daily sc injections of GHRH increase serum GH and IGF-I levels in healthy old men to values like those of untreated young men by producing high amplitude GH peaks after the injections. In the present study, we measured baseline insulin-like growth factor-I (IGF-I) 24-h profiles of GH release, and responses to GHRH stimulation tests in healthy young and old men. Old men were then given, in random order, 1 and 2 mg continuous sc GHRH 1-44 infusions daily for 14 days with an intervening 14-day treatment-free period. The study protocol was repeated on day 14 of each treatment. At baseline, mean duration of GH peaks (P < 0.005) and IGF-I levels (P < 0.0001) were lower in old men. Both doses increased (vs. old basal) mean 24-h GH, integrated area under the GH curve, and GH peak number (P < 0.05), as well as serum IGF-I (P < 0.001). Interpeak GH levels also increased during low (P < 0.01) and high (P < 0.05) dose treatment. Significant increases in mean GH and integrated area under the GH curve occurred only during the day (0800-2000 h) during both low (P < 0.01) and high (P < 0.05) dose treatment. Treatment also decreased nocturnal peak GH amplitude and duration. GH responses to GHRH stimulation tests did not differ with age at baseline, or in old men after treatment. Thus, continuous, short-term sc administration of GHRH to healthy old men restores subnormal GH secretion and IGF-I levels by increasing GH peak frequency and interpeak secretion, particularly during the day.

Growth hormone (GH)-releasing hormone-(1-29) twice daily reverses the decreased GH and insulin-like growth factor-I levels in old men.

Aging is associated with decreased GH and insulin-like growth factor-I (IGF-I) levels and lean body mass, and increased body fat. Recombinant human GH treatment of old men partially reverses body composition changes. Administration of GH-releasing hormone (GHRH) to GH-deficient children and young adults increases GH and IGF-I levels while preserving physiological GH release. We investigated whether GHRH injections restore GH and IGF-I levels in old men to the levels in young men. Healthy young (n = 9; 26.2 +/- 4.1 yr; mean +/- SD) and old (n = 10; 68.0 +/- 6.2 yr) nonobese men underwent baseline blood sampling for measurements of IGF-I and 24-h profiles of GH release, followed by iv bolus GHRH stimulation tests. Old men then took, randomly, both low (0.5 mg) and high (1 mg) dose GHRH-(1-29) sc injections twice daily for 14 days, with an intervening 14-day nontreatment period. The study protocol was repeated on day 14 of each treatment. At baseline, the mean peak duration of spontaneous GH release (P less than 0.005) and IGF-I levels (P less than 0.0001) were lower in the old men. GHRH treatment evoked dose-related increases in all parameters, with significant differences (vs. old basal values) in mean 24-h GH (P less than 0.001), area under peaks (P less than 0.001), peak amplitude (P less than 0.05), and IGF-I (P less than 0.005) only at the high dose. After high dose treatment, there were no significant differences in these parameters between age groups. Peak and integrated responses to iv GHRH stimulation tests did not differ between young and old men either before or during GHRH treatment. Baseline serum levels of both testosterone (P less than 0.01) and phosphate (P less than 0.05) were lower in the older men. Phosphate levels increased (P less than 0.05) during GHRH treatment. GHRH treatment did not affect fasting glucose, urinary C-peptide, blood pressure, or chemistry and hematology profiles. Thus, short term sc administration of GHRH to healthy old men reverses age-related decreases in GH and IGF-I, suggesting that prolonged treatment could improve age-related alterations in body composition.