No. People over think protocols. You'll get results regardless of timing.
If you want natural HGH secretion while sleeping then take your HGH upon waking in a fasted state (If you take it subcutaneously it will keep HGH elevated for at least 12 hours, 7 hours if taken intramuscularly), then take a ghrp/GHRH combo before bed for elevated natural HGH secretion, like GHRP2 with cjc no DAC. Or, take mk677 before bed.
Guys are finding excellent value in adding the oral HGH sexretagogue, mk677 at 25mg before bed. Mk677 has its largest GH pulse 12 hours after administration with additional GH pulses every hour or two. It increases the amplitude of all HGH pulses for its 25 hour half-life.
In this study, single sc administration of recombinant 20K-hGH in normal men induced significant elevations in spontaneous serum FFA and IGF-I levels associated with a marked reduction in the serum 22K-hGH level in a different time-dependent manner. hGH secretion is mainly controlled by hypothalamic hormones, GHRH, and somatostatin (18), and also controlled negatively by hGH itself (19, 20, 21) or hGH-dependent substances: IGF-I (21), FFA (23, 24), glucose (18), and so on. The increases in the main hGH-dependent substances (FFA and IGF-I) after 20K-hGH administration suggested that 20K-hGH has direct GH actions on adipose tissue or the liver through hGH receptors similarly to 22K-hGH. Therefore, 20K-hGH is expected to exert GH actions (growth-promoting activity and lipolytic activity) in humans. Furthermore, the suppression of endogenous 22K-hGH secretion could be a result of so-called “GH-induced negative feedback mechanisms.”
We found that the 24-h profile of 20K-hGH secretion in the placebo group was similar to that of 22K-hGH and that the proportion of 20K- to 22K-hGH was fairly constant. These observations suggested that regulation of 20K-hGH secretion is physiologically the same as that of 22K-hGH. Baumann and Stolar (25) suggested that 20K- and 22K-hGH may be stored together in secretory granules in the somatotroph and, hence, released together in response to various stimuli. Our observations support this hypothesis. Furthermore, these results suggested that the endogenous kinetics of 20K-hGH may be comparable with those of 22K-hGH. Interestingly, the pharmaco-kinetics after sc injection of recombinant 20K-hGH were nearly comparable with those of recombinant 22K-hGH (26, 27). In 20K-hGH-treated groups, the serum 20K-hGH levels contained both exogenously administered and endogenously secreted 20K-hGH, but the endogenous 20K-hGH levels were ignored in this study because the mean secreted 20K-hGH levels in the placebo group were fairly low (0.13 ± 0.12 ng/mL). It has been reported that 20K-hGH is cleared more slowly than 22K-hGH in rats (28, 29), but this observation has not been confirmed in guinea pigs (30). These discrepancies may be related to the differences in the species studied (rat, guinea pig, human) and/or assay methods used.
We have demonstrated the time course of the suppressive effect induced by exogenous 20K-hGH on endogenous 22K-hGH secretion in humans. The reduction of serum 22K-hGH level after 20K-hGH administration required a period of ca. 4 h, and the level tended to recover by 24 h. However, the delay in suppression of endogenous 22K-hGH by exogenous 20K-hGH is difficult to define precisely because of the intermittent nature of hGH secretion. Additional studies are required to clarify the time lag between 20K-hGH exposure and suppression of endogenous 22K-hGH. In previous studies (31, 32), single intramuscularly or sc administration of hGH (with monitoring of the resulting plasma profiles) showed a delayed and prolonged suppressive effect on rat GH secretion. The time course of endogenous GH suppression in rats was similar to but faster than that in humans reported here. The fast time course in rats was probably due to the rapid absorption of hGH in this species (14, 33). Willoughby et al. (31) suggested that suppression is achieved through metabolic or other intermediary processes, rather than acutely by a direct membrane effect of the hGH molecule.
The marked suppression of endogenous 22K-hGH secretion occurred in parallel with the FFA elevation; serum FFA levels increased with maximum levels at 4–8 h and recovered by 24 h after 20K-hGH administration. In contrast, serum IGF-I levels increased after 8 h and were prolonged up to 24 h or more, and no increase in circulating glucose levels was observed for 24 h. Our data are consistent with those of Rosenthal et al. (34), who found that 6-h methionyl 22K-hGH infusion raised plasma FFA levels but not IGF-I or glucose levels and blunted GHRH-induced GH secretion in normal men. Of the main hGH-dependent substances, elevation of FFA rather than IGF-I levels may play a leading role at least in the marked 22K-hGH suppression at AUC6–12 h after a single sc administration of 20K-hGH. Administration of FFA markedly reduced the basal GH secretion and blocked GH secretion induced by pharmacological and physiological stimuli in humans (23, 35). Recently, Briard et al. (36) reported that FFA acts both at the hypothalamic level, through increased somatostatin secretion, and at the pituitary level in sheep.
The suppression of 22K-hGH secretion was observed even at the lowest dose of 20K-hGH administered (0.01 mg/kg), with a Cmax of 8.1 ± 4.1 ng/mL. Rosenthal et al. (34) reported that the GHRH-induced GH response in humans was significantly inhibited during 6-h methionyl 22K-hGH infusion, whereas the plasma GH level remained constant (9–13 ng/mL). Therefore, the effect of 20K-hGH on negative feedback may be as potent as that of 22K-hGH.
There are experimental limitations to differentiating between exogenous and endogenous hGH in humans. The time course of GH-induced negative feedback in humans can only be studied indirectly by using the peripheral GH response to GH provocation (21, 34, 37, 38) or the amplitude of sleep-related GH secretion (20) as an indicator of suppression of GH secretion. Our observations extended these studies and indicated that an exogenously administered GH isoform could suppress the other endogenously secreted GH isoform in a time-dependent manner. The proportion of 20K- to 22K-hGH is fairly constant under physiological conditions. Therefore, by measuring the serum 20K- and 22K-hGH levels and using the other hGH isoform as an indicator of the endogenous hGH, it may be possible to monitor the internal behavior of exogenously administered hGH in clinical application of 20K-hGH and, especially, 22K-hGH. Measurement of serum 20K- and 22K-hGH may be useful in evaluating the effects of circulating GH isoforms on their own release from the pituitary.
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Acknowledgments
We thank Drs. Kohei Yazawa, Fumiaki Ikeda, and Masaru Honjo for advice and encouragement during these studies. We also thank Ms. Noriko Takayama, Ms. Keiko Kawano, and Ms. Hiromi Takeda for technical assistance.
Received August 3, 1999.
Revision received October 12, 1999.
Accepted October 20, 1999.
Previous Section
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