[Discussion] hGH: Everyday vs. Every Other Day (ED vs EoD)
>***Alternate day hGH therapy prevents tolerance and yields improved long-term results***.
Everyday injections drastically lower the body's sensitivity to its own endogenous GH pulses.
In the attached clinical study, the dose was doubled on an every-other-day (EOD) schedule, resulting in the *same total dose per week* between the two subgroups. Desensitization occurred in response to everyday dosing, unlike with the EOD protocol.
GH itself has a short half-life when injected IV—the optimal route of administration—but injecting it IM or subQ leads to slow, sustained release and elevation above baseline levels for 12–24 hours, which is the same as continual administration from the perspective of your receptors. This leads to dramatic target tissue desensitization that persists for well over a year.
For enhanced benefits, hGH administration for bodybuilding, muscle growth, fat burning, and antiaging purposes should adhere to every-other-day dosing to maximize results and prevent tolerance in target tissue receptors.
EOD dosing for reduced tolerance—maintaining heightened sensitivity to both [exogenous hGH](https://www.alpco.com/role-igf-1-growth-hormoneigf-axis) and the body's own endogenous production—has been shown to yield far better long-term results than everyday administration.
## Prevention of Growth Deceleration after Withdrawal of Growth Hormone Therapy in Idiopathic Short Stature
Meir Lampit, Ze’ev Hochberg. *The Journal of Clinical Endocrinology & Metabolism*, Volume 87, Issue 8, 1 August 2002, Pages 3573–3577. Published [01 August 2002](https://doi.org/10.1210/jcem.87.8.8721).
## Abstract
>The treatment of children with idiopathic short stature by daily injections of human GH (hGH) is followed after its withdrawal by a growth deceleration with normal serum GH and IGF-I levels.
>
>The present study was designed to understand and prevent growth deceleration. We hypothesized that this phenomenon is due to tolerance at the target organ level, that tolerance develops in response to the unphysiological pharmacokinetics of daily-injected hGH, and that alternate day hGH therapy will prevent it.
>
>Thirty-eight prepubertal children with idiopathic short stature, aged 3.3–9.0 yr, were studied. Their heights were less than −2 SD score, growth rate was above the 10th percentile for age, bone age was less than 75% of chronological age, and the stimulated serum GH concentration was greater than 10 μg/liter.
>
>The children were matched for sex, height, and growth velocity SD score to receive daily or alternate day hGH at the same weekly dose of 6 mg/m^(2) for a period of 2 yr. The 1st and 2nd year mean growth velocities were 3.4 and 2.3 SD score for the daily therapy group and 3.0 and 2.0 SD score for the alternate day group, respectively (***P*** = NS).
>
>Over the initial 6 months after withdrawal of therapy, and growth velocity decelerated to a nadir of −3.9 SD score in the daily therapy group, whereas it decelerated in the alternate day group to only −0.2 SD score (***P*** < 0.01).
>
>Over the entire 2 yr off therapy the latter group maintained mean growth rates of −0.2 to −1.2 SD score, similar to their pretreatment velocities. The daily group recovered slowly to resume their mean pretreatment rate only on the fourth semiannual evaluation off therapy.
>
>The cumulative 4-yr growth velocity (2 yr on and 2 yr off therapy) of the alternate day group was greater than that of the daily therapy group (mean, 0.9 *vs.* 0.3 SD score; ***P*** < 0.002). At the end of the 4-yr therapy period, the adult height prediction of the alternate day group was greater than that of the daily group by a mean 6.5 cm (***P*** = 0.06).
## Discussion
*Posted by BMF2 on Qualitymuscle* — A very thorough, well-controlled four-year study published in *The Journal of Clinical Endocrinology & Metabolism* clearly shows **every other day** (EOD) **hGH injections** to be much **more beneficial** in the long run to everyday injections.
**Everyday** injections seem to drastically **lower your body's sensitivity** to its own GH secretion. The study included children with idiopathic short stature, but the results can be extrapolated at least loosely to normal, non-deficient hGH individuals who may use hGH periodically for antiaging, bodybuilding, sports and health purposes.
38 children were divided into two groups:
>***Group I*** *received daily hGH injections*
>
>***Group II*** *received alternate day hGH injections*
It is important to note that the *total weekly dosage of hGH was the same* for both groups. Both groups received the hGH therapy contiguously for two years. Their natural growth was followed for an additional two years after hGH therapy ended.
They were all measured at three-month intervals during the four-year period—two years with hGH therapy and two years thereafter. Serum GH was measured by double antibody RIA kit.
During hGH therapy, both groups accelerated their growth substantially:
>***Group I*** *receiving the daily hGH injections first and second year velocity was 3.4 and 2.3 SD.*
>
>***Group II*** *receiving the alternate hGH inj. had 3.0 and 2.0 SD for first and second year, respectively.*
Over the initial six months after withdrawal of therapy, growth velocity decelerated to a low nadir –3.9 SD score for the daily therapy group, whereas it decelerated in the alternate day group to only –0.2 SD score.
During the 2 years off therapy, the latter group taking EOD injections maintained growth rates of –0.2 to –1.2 SD score, which is similar to their SD score prior to the hGH treatment. The daily group also recovered but very slowly, on the fourth semiannual evaluation off therapy. The cumulative 4-year growth velocity—2 yrs on and 2 yrs off therapy—of the alternate day group was greater than that of the daily therapy group: mean, 0.9 vs. 0.3 SD score.
>***At the end of the 4-yr therapy period, the adult height prediction of the alternate day group was greater than that of the daily group by a mean of 6.5 cm—which is over 2.5****"* ***in height.***
In even simpler English, to translate what it may mean to us is that using hGH everyday will only negligibly give better short-term results. Yet using **alternate day** hGH will give radically **better long-term results** and **much better recovery**. As the body may get back to homeostasis much faster.
The two groups got the same weekly total hGH dosage, so every other day hGH injections would be twice as many IU as if you used it every day. The researchers said the dose was of less importance than the schedule of the injections. Daily hGH therapy for 3 years caused subnormal growth persisting for 1.5 years (***very bad***).
It may be that the problem is not related to the levels of hGH or IGF-1 secretion but rather the body's decreased sensitivity to it. The interesting part is that the serum GH levels and serum IGF-I and IGF-binding protein remained unaffected, or relatively mutely affected.
>***Your body's endogenous secretion of GH resumes within days, even after long-term hGH therapy***.
The researcher’s hypothesis is that the tolerance may be in the “GH signal transduction in selective target organs in response to the disappearance of the unique pulsatile pattern of serum GH during GH therapy. This is due to the fact that GH taken via SubQ injections does not match your body's own GH release schedule."
>*Daily SubQ administration of GH results in an unphysiological serum GH profile, with peak levels at 4h and a slow decline over the course of the following 12–24 h. This pattern can be regarded as continuous administration, rather than the body's natural physiological GH pulses with a frequency of about eight pulses per day.*
Assuming that the withdrawal syndrome is related to tolerance that might have developed toward hGH or IGF-I, we tried to prevent it by alternate day treatment. Moreover, hGH doses used in therapy often stimulate IGF-I to supraphysiological serum levels, suggesting that target tissues IGF-I may also be higher than normal. The mechanism seems, therefore, to rest with hGH and IGF-I action at their target tissues. We now show that alternate day therapy with hGH in children with an intact GH-IGF-I axis prevents the withdrawal syndrome.”
Researchers link the analogy to another endocrine tolerance and withdrawal syndrome: “alternate day therapy with glucocorticosteroids prevents tolerance to that hormone to a substantial degree. Interestingly, glucocorticoid withdrawal syndrome can also occur while the hypothalamic-pituitary-adrenal axis is intact, indicating that tolerance to glucocorticoids has developed at the target organ level.”
**An example of a good protocol could be**:
>hGH taken for 16 weeks or more at **8 IU every other day**, split to **4 IU fasted immediately after waking** and another **4 IU taken eight hours later**. This approach is quite conservative, and may be optimal. The dose may be further split if desired to reduce the total IU injected at any one point in time.
Obviously, you may extend past four months, and take more IU per day. This approach goes with 8 IU EOD, so it is equivalent to those who would otherwise go with 4 IU ED, which is what most do. There is some controversy as to how many of these IU the body can utilize at once. There are many opinions and doctrines in endocrinology, bodybuilding, etc. Older individuals on hGH for life would not mind, as no rebound would affect them. Professional bodybuilders probably wouldn't mind as well.
This study targeted *height* in adolescents—not *lean body mass* in adult bodybuilders, or *antiaging effects* in middle-aged adults—so it's still a matter of extrapolation as to whether or not the results can be applied to these user subgroups. Bodybuilders aren't children, nor idiopathic hGH deficient and not aGHD.
Since the weekly dosages remain the same, as well as the duration of the hGH usage, just changing to the EOD protocol from the previous standard everyday injection protocol is worth it, and seems statistically a better bet than the everyday protocol.
>**TL;DR**: *Alternate day hGH therapy prevents tolerance and yields improved long-term results with the same weekly total IU administration*.
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I’d say so brother, lots can be said for everything that gos into staying lean and on-point with nutrition right 
