Eto et al. investigated highly trained cyclists ages 18 to 22 ingesting 20 g of glutamate-ARG (AG) salt per day and found that although AG had no effect on resting plasma levels of hGH, the AG subjects had marked reduction in cortisol and hGH compared to the placebo group during and after exercise. Those results suggest that AG may modify energy metabolism during endurance exercise.
A study published by Hellman et al.298 investigated an AA blend called Growlean 15® that contained 200 mg of L-glutamine, 200 mg of ornithine, 200 mg of L-ARG, 500 mg of glycine, 200 mg of lysine, 200 mg of tyrosine, and 600 mg of miscellaneous glandulars. The supplement was taken immediately before bed on an empty stomach and was touted to increase the body's natural production of GH. They found no differences between the placebo and experimental groups in plasma GH levels either before or after exercise challenge and no change in body composition. The amounts of AAs provided by the product were much lower than levels known to stimulate GH, which readily explains the lack of GH increase. As most other studies have discovered, the results of this study indicated that supplementing AAs will not raise GH beyond the level produced by exercise.
Fricker et al.299 had found the same result in male and female strength athletes. Ingesting an AA mixture of 1.8 g of ARG, 1.2 g of ornithine, 0.48 g of methionine, and 0.12 mg of phenylalanine following an overnight fast, and before exercise (presumably to take advantage of a primed pituitary), did not raise GH levels beyond the exercise-induced increase.
Four well-controlled trials associated with exercise and fitness that investigated oral ingestion of AA blends are summarized in Table 15.5.166-170 For comparison, the table also includes results of the studies by Isidori et al.300 and Corpas et al.,166 since they are so frequently cited in literature regarding AA supplementation and GH release. Isidori et al.'s research also appears in connection with the first noted sport-related use of specific AA combinations to boost GH. That research demonstrated a tenfold increase in plasma levels of GH at 90 min after oral ingestion of 1200 mg each of lysine and ARG in nonexercising subjects.300 The prospect of athletes being able to enhance GH production with oral ingestion of relatively small doses of AAs was probably the spark that ignited the marketing and widespread use of these supplements as supposed secretagogues for GH release.
Natural GH production declines with age,301-308 and paradoxically, GH secretagogues appear to be more effective on normal subjects in younger age brackets.166,168,300 Tanaka et al.,309 using an AA infusion to stimulate GH release, demonstrated an inverse relationship between age and responsiveness to AA GH stimulus. Corpas et al.166 reported that healthy male subjects over 60 years of age absorbed ARG as well as young men, but 3 g each of ARG and lysine, given twice daily, had no effect on GH or insulin-like growth factor-I (IGF-I) secretion.166 This result was in stark contrast to Isidori's findings300 that administration of 1200 mg of the same two AAs to 15- to 20-year-old males elicited up to a tenfold increase in GH. Suminski's subjects were 20 to 25 years of age, and in the absence of exercise, oral ingestion of 1200 mg each of ARG and lysine caused a 2.4-fold increase. Collectively, these three studies appear to support the theory of age-related decline in GH response to oral administration of an ARG/lysine mixture (Arg/Lys).168
Exercise amount and intensity are strongly related to GH release.310-317 Research incorporating high-intensity cycling and resistance training demonstrates up to a tenfold increase in GH concentration when blood is sampled immediately following exercise.312,318
The young bodybuilders used in Lambert's study exercised 5 to 10 h/week, maintained their normal diet (1.2 to 2.2 g of protein/day), and ingested the Arg/Lys supplement after an 8-h overnight fast (to take advantage of the anterior pituitary being naturally primed to secrete GH). Blood GH was measured in increments up to 180 min after ingestion. The mean increase of serum GH in the ARG and lysine group doubled that of the placebo group (Table 15.6). However, no firm conclusions should be drawn from these results because of the small group size (n = 7) and the dramatic variations among subjects.167
Exercise appears to have a significantly greater effect on GH release than ingestion of Arg/Lys. Consequently, exercise may overwhelm and obviate any simultaneous effects of supplementation.
Suminski et al.,168 using 1500 mg of Arg/Lys, measured GH levels in subjects before exercise and in a separate group without exercise. In the exercise group, they measured GH levels before training and in 30- to 90-min intervals after exercise. GH levels were measured in the nonexercise subjects at the same times. In the two exercise groups (placebo and Arg/Lys), the GH levels were elevated equally (not altered by supplementation) and exercise performances were not improved. In the nonexercise groups (placebo and Arg/Lys), the GH level in the supplemented group was 2.4 times higher than in the placebo group. These results suggest that AA supplementation can raise GH in the absence of exercise, but there is no additive effect to the GH stimulation resulting from exercise, at least when protein intake is already adequate. The smaller increase in GH in the nonexercise group compared to Isidori's results may be partly attributed to the age differences, since Suminski's participants were 20 to 25 years old, whereas Isidori's 1982 study participants were 15 to 20 years old.168,300 In addition, the dosages used by the exercisers may have been too small because of the obligatory tissue uptake of AAs in response to exercise. That tissue uptake diverts a significant portion of the Arg/Lys to muscle and the splanchnic bed, and likely renders the remaining supplemental AAs ineffective in stimulating the anterior pituitary.256,319
Lambert and Fogelholm also studied experienced weight lifters and found no significant increases in GH release using 1.2 g each of Arg/Lys once daily, and 1 g each of ARG, ornithine, and lysine twice daily. In contrast to the findings of Suminski et al.,168 they were unable to demonstrate an acute basal increase in GH in their similar subjects — a result that might be attributed to differences in protein intake.
As discussed in the introduction to this section, exercisers typically have adequate protein intake, and the timing of ingestion can play a role in enhancing the anabolic environment following exercise.262'279320321 The protein requirements for exercisers may be twice those of sedentary counterparts.322 This fact offers a possible explanation for results of the Lambert et al.167 and Fogelhom et al.169 studies, which contradict results reported by Suminski relative to basal GH stimulation through Arg/Lys supplementation. Lambert and Fogelholm's subjects ingested between 1.5 and 2.0 times the amount of protein during the trials as did Suminski's participants, and diets high in protein, compared to "normal" balanced diets, are associated with higher basal GH.323 These results suggest that high-protein intake throughout the day may exhaust the GH-releasing potential that Arg/Lys supplementation might otherwise tap.
The only other study showing a significant increase in GH levels from Arg/Lys oral supplementation was Isidori's. That study did not report protein intake, but the subjects were nonexercisers, and we may assume they consumed the typical Italian diet of the times, in which protein intake was probably not relatively high.300
Finally, in the absence of exercise (based on the effects of the cellular compart-mentalization of circulating AAs from any source [see Section 18.104.22.168.1]), high
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