Boosting growth hormone levels has become all the rage for anti-aging (slowing or reversing the aging process), boosting vitality, enhancing recovery, etc.
There are a couple of ways of doing this, with the first being using human growth hormone (HGH) directly.
Alternatively, you can stimulate your pituitary to release more GH, with something like ipamorelin.
What I’ll be covering
- How ipamorelin and HGH work
- Benefits of ipamorelin and HGH
- Fat loss
- Lean body mass
- IGF-1 levels
- Energy levels
- Cognitive function
- Exercise performance
- Sleep quality
- Potential side effects
- How to use ipamorelin
- Ipamorelin supercharge stack
- What lowers GH
- 👇Ipamorelin vs HGH explained👇
How ipamorelin and HGH work
How ipamorelin works
Ipamorelin (a synthetic peptide consisting of 5 amino acids), similar to MK-677, GHRP-2 and GHRP-6, is a growth hormone secretagogue that stimulates the ghrelin receptor.
Ghrelin is produced by the oxyntic glands of the stomach. Here is a good way to remember it: when your stomach is growling, it’s ghrelin.
Ghrelin is released when you’re fasted and stimulation of the ghrelin receptors in the pituitary promotes growth hormone release.
Ipamorelin was originally developed to improve gastric motility in the setting of postoperative ileus, but it seems to be ineffective (R). Meaning, after that surgery, you don’t have enough ghrelin to stimulate bowel movements. Agonizing the ghrelin receptor can thus help. However, it was discontinued for use in this area as it was deemed ineffective.
Despite its failure at stimulating bowel movements, it’s still great for boosting GH, and most clinics add it to their peptide therapy combos.
How GH works
Injecting GH is like injecting testosterone. It’s a direct replacement for what you make.
Ipamorelin is like HCG. Ipamorelin stimulates the pituitary to release GH and HCG stimulates the testes to produce testosterone. They don’t cause shutdown.
Taking GH directly will shut you down.
HGH therapy is mainly prescribed for growth deficiency (due to growth hormone deficiency), HIV patients with muscle wasting and burn victims. That’s about it.
Growth hormone release in the pituitary is controlled by GH-releasing hormone (GHRH) and somatostatin. GHRH promotes GH release whereas somatostatin inhibits it.
The duration of action of growth hormone (GH) can vary depending on the specific type of GH used and your metabolism. The circulating half-life of GH is a relatively short half-life (20-30 minutes), while its biological half-life is much longer (9-17 hours) due to its indirect effects.
After injection, GH levels in the blood peak within 1-3 hours and then decline rapidly over the next several hours. Typically, the effects of GH injections last for several hours, up to a day or two, depending on the dose administered and individual factors.
Once GH is released into the bloodstream, it travels to the liver where it’s converted to IGF-1 (insulin-like growth factor). IGF-1 is then bound to many IGF-binding proteins (IGFBPs) to be transported in the body.
Research has shown that it’s not IGF-1 that’s the problem in disease, but instead the dysregulation of the IGFBPs, thus increasing free IGF-1 too much.
Benefits of ipamorelin and HGH
Ipamorelin and HGH benefits
Since both increase GH, they have the same benefits, such as.
- Reduces body fat
- Potentially help to increase energy levels
- Increases collagen production and skin thickness
- Increases lean body mass
- Improves sleep quality
- Increases bone density
- Supports the repair of cartilage and nerves
- Increases IGF-1
- Might help with erections
- Reduces colonic hypersensitivity to pain and somatic allodynia (R)
- Increases long bone growth in rats in a dose-dependent manner (R)
- Prevents bone loss induced by glucocorticoid medication (R)
- Improves the immune system
In this retrospective survey, extended testosterone and/or GH supplementation did not adversely affect metabolic markers or clinical outcomes (R).
Additionally, GH treatment stops fatty liver disease and inflammation (R).
Lastly, ipamorelin doesn’t increase cortisol or prolactin to the same extent as GHRP-2 and GHRP-6 (R).
Both ipamorelin and HGH have been shown to help with weight loss.
Ipamorelin and fat loss
There are no human studies on ipamorelin and fat loss, but there is 1 animal study. Since ipamorelin increases GH, it can help with fat loss.
However, due to the increase in hunger, if someone eats more, they are more likely to experience weight gain than lose weight.
In this animal study, they compared GH with ipamorelin on body composition.
Ipamorelin caused an increase in fat mass (total body fat percentages).
The main reason for this is because the animals ate more food initially, but that effect stabilized over time. So as long as you can control your hunger initially, ipamorelin should help with fat loss (R).
Additionally, according to the study ipamorelin promoted lipogenesis (the creation of fat from glucose), which can increase circulating lipids and fat storage.
You can see in the image below that the rats given the ipamorelin injections had the most body fat (white patches).
HGH on fat loss
One of the big reasons people use GH is because they think it’s magical for fat loss. But it’s not as magical as you think, especially when used at “low” doses of 1-2IU daily.
This meta-analysis looked at 24 well-done studies using GH for fat loss. They found that the dose of HGH dose used in many studies was clearly supraphysiological at an average of 31.1 IU per week (10.4 mg/wk) (R).
Using such as large dose per week only resulted in a:
- 0.9kg loss in fat mass
- 1% loss in body fat
- 22.8cm2 loss in visceral adipose area.
Not so great honestly.
This study found that 8mg of HGH per week (2.67mg x3 week) promoted fat loss in trained individuals (R).
Although HGH promotes lipolysis (which mobilizes fat from fat stores), it doesn’t also promote fat oxidation, thus the fat balance remains the same.
Lean body mass
Another common reason why people use growth hormone, is because they’re under the assumption that growth hormone will promote muscle growth.
I should point out that growth hormone does promote water retention in the muscle, which is most likely responsible for the increase in muscle mass, as seen in various studies. This is likely true since no other markers of muscle function (strength, power, and aerobic exercise capacity) are enhanced by growth hormone.
HGH and muscle mass gains
The same meta-analysis that looked at fat mass loss also looked at lean body mass. They found that using 31.1 IU per week (10.4 mg/wk) resulted in an increase in lean body mass of 1.8 kg (R). Maybe if these individuals combined it with exercise and insulin, the effects would have been better, who knows?
The problem with all measuring tools (e.g. DEXA) is that it can’t tell the difference between actual new muscle fibers or just more water in the muscle.
This study found that 4 weeks of 0.1 IU/kg per day combined with endurance exercise didn’t affect muscle mass (R). It’s likely that the study was too short to see proper results. But it just points out that GH has a very small anabolic effect (not anywhere close to anabolic steroids).
The evidence suggests that muscle strength, power, and aerobic exercise capacity are not enhanced by GH administration, however GH may improve anaerobic exercise capacity (R).
The main area where GH might shine is by sparing muscle tissue by increasing muscle protein synthesis during a catabolic state, such as a caloric deficit.
This study found that 0.18 IU/kg of ideal BW/week (2IU daily for an 80kg man) of GH created a positive nitrogen balance. In the placebo group, there was a loss in lean body mass (-2.62 +/- 1.51 kg) and a negative nitrogen balance (-4.52 +/- 3.51 g/day). By contrast, the GH group increased in lean body mass (1.13 +/- 1.04 kg) and had a positive nitrogen balance (1.81 +/- 2.06 g/day) (R).
Additionally, GH injections caused a 1.6-fold increase in IGF-I, despite the caloric restriction.
Ipamorelin and muscle mass gain
In animals, ipamorelin therapy has been shown to prevent muscle loss during a highly catabolic state induced by glucocorticoids by keeping IGF-1 high (R).
In this animal study, GH was better at promoting growth than ipamorelin.
As a bonus, ipamorelin didn’t increase organ weight, whereas growth hormone increased liver weight. This suggests that patients treated with ipamorelin may not experience the same organomegaly as that seen in patients treated with GH itself. (R)
Ipamorelin on IGF-1 levels
Ipamorelin is just as effective as GHRP-6 at increasing GH, without affecting LH, FSH, TSH, ACTH and cortisol (R).
An ipamorelin injection can spike GH by 20-30-fold (R).
More GH usually means more IGF-1.
There isn’t much on ipamorelin and IGF-1 at all. However, as GH goes up, so will IGF-1
The following study found that in diabetic animals, the increase in IGF-1 from ipamorelin was non-existent.
When diabetic animals were injected with ipamorelin, GH spiked much higher compared to non-diabetic animals, but there was no increase in IGF-1 (R).
On the graph, C/IPA is the healthy animals that got ipamorelin and D/IPA is the diabetic animals that got ipamorelin.
HGH on IGF-1
In general, a single injection of GH can increase IGF-1 levels by approximately 20-30%, with peak levels occurring within 12-24 hours after the injection.
According to this study, 0.03 mg/kg/BW (0.09IU/kg/BW) x3 week of GH increases IGF-1 from 118 to 237ng/mL (R). That’s 7.2IU x3 week for an 80kg individual.
This study found that a 10mg (30IU) injection increased IGF-1 almost 4 fold (R).
This study found that GH therapy increased IGF-1 from 60.5 to 150 and 120ng/ml from baseline to 3 and 12 months respectively (R). The dose they used was 5 μg/kg 3 times per week, which would equate to 0.5mg (1.5IU) for 100kg guy. Additionally, lean mass increased by 3kg and fat mass decreased by 2kg after 1 year.
In summary, long-term GH becomes less effective (IGF-1 starts to drop) and small doses of 1-2IU 2-3 times per week will likely have a minor effect on IGF-1 (going up to between 120-150ng/ml). Nothing pathological about this.
Also, the loss in fat mass was a meager 2kg after 1 year. Nothing to write home about.
There are no studies looking at GH or ipamorelin on energy levels, but in general, people with low GH tend to have poor sleep and daytime fatigue (R).
Boosting their GH with GH injections or ipamorelin will increase sleep quality and reduce daytime sleepiness.
GH has also been shown to promote the conversion of T4 into T3 (R). Thus optimizing your GH levels will help to keep your T3 high, which will help with energy.
GH and IGF-1 have many beneficial effects on the brain.
GH and IGF-1:
- Have potent neurotrophic and neuroprotective actions
- Stimulate neurite outgrowth
- Promote neuronal survival
- Promote vascular growth and blood flow
- Regulate tau phosphorylation
- Protect from the neurotoxic effects of Aβ (thus protecting against Alzheimer’s disease).
- Protect and reverse cerebellar ataxia caused by neurotoxins (R)
- increased GABA in the brain (R)
Compounds that promote GH release, such as tesamorelin (in the case of this study), had a beneficial effect on cognitive function in healthy older men. Particularly on tasks of executive function including selective attention, problem-solving, working memory, and planning/organization (R).
Boosting GH improves memory, alertness, motivation, and working capacities (R).
In animals, GH restored the cognitive capacity of older animals to that of younger animals (R).
It’s unlikely that GH or ipamorelin will give you a cognitive boost if you’re healthy, but if you’re fatigued and inflamed, it will likely help.
Ipamorelin hasn’t been studied for exercise performance yet, but GH has.
A recent meta-analysis reviewed 44 randomized trials compared GH treatment to placebo to see the effects on exercise performance in healthy adults. While GH increased lean body mass (most likely water retention), strength, power, and aerobic exercise capacity weren’t increased. Exercise capacity might actually worsen, and adverse events, such as edema and fatigue, were more common with the use of exogenous GH (R).
One way how GH might help with exercise performance is by speeding up recovery. Faster recovery plus fewer injuries can mean more volume over time and better exercise performance gains.
Ipamorelin hasn’t been studied for sleep quality yet, but GH has.
GH injections reduced excessive sleep duration and delta sleep. People with low GH tend to sleep for longer with higher intensities of SWS (slow wave sleep) (R). However, this doesn’t mean that they are more refreshed from more SWS. Usually, it’s the opposite.
As you can see in the graph below, GH reduced delta activity, without really affecting the other brain wave states.
Potential side effects
Few compounds are without side effects and ipamorelin and GH are no exception.
The most common side effects of GH are (R):
- Joint pain
- Water retention
- Paresthesias (burning or prickling sensation)
- Increased fasting glucose
- Increased fasting insulin (a marker of insulin resistance)
The other significant side effect of GH use is shut down. Mark Gordan said that after using GH for just 28 days, your natural production can shut down for 1+ years.
The most common side effects of Ipamorelin are:
- Increased hunger initially
- Potential water retention
- Potential for worsening insulin resistance
- Having to take it frequently.
- Once a day for longevity
- x2 daily for fat loss
- x3 daily for building muscle and losing fat
The effect of GH on tumor growth and cancers seems to be neutral. However, a small number of studies reported that childhood cancer survivors who receive GH treatment have a small increased risk of developing de novo cancer and secondary malignant neoplasm (R).
A 2022 study discussed that both high and low levels of IGF‐1 increase mortality risk, with a specific 120–160 ng/ml range being associated with the lowest mortality (R).
In order to minimize the rate of side effects, a retrospective analysis of 28 studies of GH replacement therapy in adults indicates that the maintenance dose should usually not exceed 1.5-2.0 IU/day in GH-deficient patients (R).
How to use ipamorelin
Ipamorelin is recommended to use for 3-6 weeks only.
In terms of dosing, 100 mcg seems to be a low-end dose, and 500 mcg is an average dose. The low average is around 250-300 mcg, which is a good starting dose.
For longevity, take 300-500mcg before bed
For fat loss, take 300-500mcg 2 times daily (e.g. 8am and 8pm)
For building muscle and more aggressive fat loss, take 500mcg 3 times daily.
Here are the half-life durations of ipamorelin.
5 different doses were tested, ranging from 0.003, 0.01, 0.03, 0.06, 0.1 mg/kg. For a 100mg guy, that would be 300mcg, 1mg, 3mg, 6mg and 10mg. Quite big doses.
The elimination half-life ranged for the 3 lowest doses was 2.4 to 3.1 hours and for the higher doses, it was 6.4 and 5.5 hours (R).
Since most people will be taking between 0.3 and 1mg, it will roughly stay 2-3 hours in your system. That’s why it’s recommended to take it multiple times a day.
Ipamorelin supercharge stack
Most clinics and experts use a combination of these growth hormone secretagogues. Combining a ghrelin receptor agonist and a synthetic analogue of growth hormone-releasing hormone would give you a synergistic boost in GH, more than either one alone (R).
An example would be ipamorelin (a ghrelin receptor agonist) and CJC-1295 (a synthetic analog of GHRH).
Another example would be MK-677 (a ghrelin receptor agonist) and Sermorelin (a synthetic analog of GHRH).
There is no need to combine multiple ghrelin agonists, such as MK-677, ipamorelin, GHRP-2 or GHRP-6, as they work on the same receptor.
What lowers GH
We want to keep GH normal as best as possible. We start running into problems when GH drops as we get older and/or more unhealthy.
A few things that lower GH (lead to suboptimal GH) include:
- Insulin (overeating is a sure way to crush GH. Insulin resistance as well.)
- Free fatty acids, due to insulin resistance (R).
- Leptin resistance
- Inflammation (due to gut dysbiosis, nutrient deficiencies, etc.)
- Glucocorticoids (high-stress or glucocorticoid medication)
- Excess estradiol (causes GH resistance)
👇Ipamorelin vs HGH explained👇
Ipamorelin is a safe peptide to use to boost your natural GH. It works best in conjunction with a GHRH analog, such as CJC-1295.
The only downside is the frequent injection requirement, which is best taken as a subcutaneous injection.
Both ipamorelin and GH have their downsides, but ipamorelin is very effective at boosting GH without increasing prolactin or cortisol or insulin resistance and is much cheaper than GH. The main downside of GH is likely its high cost, but also that it can cause more significant suppression which requires a longer recovery time.
I prefer to optimize GH naturally. If you have low GH, find out why instead of just patching it. Low GH is a symptom that is caused by something. That missing link isn’t just causing low GH, but problems elsewhere in the body as well. That’s why it’s important to find the root cause.